1 00:00:07,069 --> 00:00:08,404 >> GOOD AFTERNOON, EVERYONE, AND 2 00:00:08,404 --> 00:00:10,606 WELCOME TO THE EIGHTH ANNUAL 3 00:00:10,606 --> 00:00:12,775 VIVIAN PINN SYMPOSIUM. 4 00:00:12,775 --> 00:00:15,110 I'M DR. JANINE CLAYTON, THE 5 00:00:15,110 --> 00:00:16,512 ASSOCIATE DIRECTOR FOR RESEARCH 6 00:00:16,512 --> 00:00:17,713 ON WOMEN'S HEALTH AND IN THAT 7 00:00:17,713 --> 00:00:18,781 CAPACITY I DIRECT THE OFFICE OF 8 00:00:18,781 --> 00:00:20,082 RESEARCH ON WOMEN'S HEALTH AND 9 00:00:20,082 --> 00:00:20,716 WE'RE DELIGHTED TO HAVE YOU 10 00:00:20,716 --> 00:00:22,518 HERE. 11 00:00:22,518 --> 00:00:25,254 WE HAVE A FULL LINEUP FOR YOU 12 00:00:25,254 --> 00:00:26,989 SCHEDULED, AND AN AWESOME 13 00:00:26,989 --> 00:00:28,090 AGENDA, AND SO PLEASE DO STAY 14 00:00:28,090 --> 00:00:29,725 WITH US FOR THE FULL AFTERNOON 15 00:00:29,725 --> 00:00:32,695 FOR THIS FANTASTIC PROGRAM. 16 00:00:32,695 --> 00:00:34,763 IF SOMEBODY COULD PULL UP THE 17 00:00:34,763 --> 00:00:37,499 AGENDA VERY BRIEFLY THERE AND 18 00:00:37,499 --> 00:00:39,034 THEN MY SLIDES, THAT WOULD BE 19 00:00:39,034 --> 00:00:46,775 FANTASTIC. 20 00:00:46,775 --> 00:00:47,209 GREAT. 21 00:00:47,209 --> 00:00:51,480 AND NEXT? 22 00:00:51,480 --> 00:00:51,981 WONDERFUL. 23 00:00:51,981 --> 00:00:53,249 I'M GOING TO JUST GIVE SOME 24 00:00:53,249 --> 00:00:55,217 BRIEF OPENING REMARKS ABOUT HOW 25 00:00:55,217 --> 00:00:56,752 IMPORTANT IT IS TO BRIDGE THE 26 00:00:56,752 --> 00:00:59,021 GAP AND CHART THE PATH FOR 27 00:00:59,021 --> 00:01:00,889 WOMEN'S AUTOIMMUNE DISEASE 28 00:01:00,889 --> 00:01:04,927 RESEARCH. 29 00:01:04,927 --> 00:01:07,363 THIS IS SOME AMAZING SCIENCE, SO 30 00:01:07,363 --> 00:01:08,764 I ALWAYS LOVE TO BEGIN WITH THE 31 00:01:08,764 --> 00:01:10,199 DATA AND THE SCIENCE THAT WAS 32 00:01:10,199 --> 00:01:12,468 RECENTLY IN THE LITERATURE. 33 00:01:12,468 --> 00:01:15,537 WE KNOW THAT FOUR OUT OF FIVE 34 00:01:15,537 --> 00:01:16,639 PATIENTS WITH AUTOIMMUNE DISEASE 35 00:01:16,639 --> 00:01:18,374 ARE FEMALE. 36 00:01:18,374 --> 00:01:20,576 WORK DONE BY DIANA DU AND HER 37 00:01:20,576 --> 00:01:22,444 COLLEAGUES RECENTLY PUBLISHED IN 38 00:01:22,444 --> 00:01:23,312 SELF HIGHLIGHTED WHAT THEY 39 00:01:23,312 --> 00:01:25,180 BELIEVE IS ONE OF THE MAJOR 40 00:01:25,180 --> 00:01:28,684 REASONS WHY WE SEE THAT SEX BI 41 00:01:28,684 --> 00:01:30,419 BIAS. 42 00:01:30,419 --> 00:01:31,954 XIST IS A LONG CODING RNA 43 00:01:31,954 --> 00:01:33,589 EXPRESSED ONLY IN FEMALES TO 44 00:01:33,589 --> 00:01:35,924 RANDOMLY INACTIVATE ONE OF THE 45 00:01:35,924 --> 00:01:39,295 2X CHROMOSOMES TO ACHIEVE GENE 46 00:01:39,295 --> 00:01:39,728 DOSAGE COMPENSATION. 47 00:01:39,728 --> 00:01:43,766 IN THIS STUDY, THEY POSITED THAT 48 00:01:43,766 --> 00:01:44,867 XIST RIBONUCLEAR PROTEIN 49 00:01:44,867 --> 00:01:48,037 COMPLEXES COULD ACT AS ANTIGENIC 50 00:01:48,037 --> 00:01:50,039 TRIGGERS, AND THAT THIS 51 00:01:50,039 --> 00:01:51,407 UNDERLIES THE GREATER PREVALENCE 52 00:01:51,407 --> 00:01:52,408 OF AUTOIMMUNE DISEASES IN 53 00:01:52,408 --> 00:01:53,709 FEMALES. 54 00:01:53,709 --> 00:01:55,811 THEY CONDUCTED ELEGANT STUDIES 55 00:01:55,811 --> 00:01:57,446 WITH TRANSGENIC MOUSE MODELS 56 00:01:57,446 --> 00:01:59,415 INDUCING EXPRESSION OF XIST IN 57 00:01:59,415 --> 00:02:01,150 MALE ANIMALS AND THAT EXPRESSION 58 00:02:01,150 --> 00:02:03,252 IN MALES AND THROUGH TRANSGENIC 59 00:02:03,252 --> 00:02:06,188 EXPRESSION INDUCED 60 00:02:06,188 --> 00:02:07,156 AUTOANTIBODIES AS WELL AS 61 00:02:07,156 --> 00:02:08,257 AUTOIMMUNE PATHOLOGY IN THOSE 62 00:02:08,257 --> 00:02:10,592 MALE MICE. 63 00:02:10,592 --> 00:02:13,195 FURTHER, THAT XIST EXPRESSION 64 00:02:13,195 --> 00:02:15,597 REPROGRAMMED T AND B CELL 65 00:02:15,597 --> 00:02:16,999 POPULATIONS TO LOOK MORE LIKE 66 00:02:16,999 --> 00:02:18,534 FEMALE POPULATIONS. 67 00:02:18,534 --> 00:02:21,870 SO CLEARLY, XIST IS PLAYING A 68 00:02:21,870 --> 00:02:22,805 CRITICAL ROLE. 69 00:02:22,805 --> 00:02:25,007 AND ONCE AGAIN, DR. MONICA 70 00:02:25,007 --> 00:02:26,842 BERTAGNOLLI, THE NEW NIH 71 00:02:26,842 --> 00:02:29,311 DIRECTOR, FEATURED THIS STUDY IN 72 00:02:29,311 --> 00:02:30,312 HER BLOG. 73 00:02:30,312 --> 00:02:34,750 SHE'S BEEN VERY -- SHE HAS 74 00:02:34,750 --> 00:02:35,818 FOCUSED A LOT ON WOMEN'S HEALTH 75 00:02:35,818 --> 00:02:37,052 IN HER SHORT TIME WITH US, AND 76 00:02:37,052 --> 00:02:38,687 SHE FEATURED IN THIS BLOG THIS 77 00:02:38,687 --> 00:02:45,894 NEW RESEARCH. 78 00:02:45,894 --> 00:02:47,996 SO AT NIH, AUTOIMMUNE DISEASE 79 00:02:47,996 --> 00:02:49,231 RESEARCH HAS BEEN SOMETHING THAT 80 00:02:49,231 --> 00:02:50,165 HAS BEEN IMPORTANT TO US FOR 81 00:02:50,165 --> 00:02:51,700 MANY, MANY YEARS. 82 00:02:51,700 --> 00:02:53,936 AND I WANT TO HIGHLIGHT THAT IN 83 00:02:53,936 --> 00:02:56,071 FISCAL YEAR 2021 AND 2022, WHICH 84 00:02:56,071 --> 00:02:58,907 ARE THE MOST RECENT YEARS FOR 85 00:02:58,907 --> 00:03:00,809 FULL INFORMATION AVAILABLE, NIH 86 00:03:00,809 --> 00:03:03,712 SUPPORTED OVER 1400 GRANTS AND 87 00:03:03,712 --> 00:03:04,780 ADMINISTRATIVE SUPPLEMENTS THAT 88 00:03:04,780 --> 00:03:06,782 WERE CODED AS AUTOIMMUNE DISEASE 89 00:03:06,782 --> 00:03:07,783 RESEARCH. 90 00:03:07,783 --> 00:03:10,285 AND IN TERMS OF THE AMOUNT OF 91 00:03:10,285 --> 00:03:11,687 FUNDING, THE AMOUNT OF FUNDING 92 00:03:11,687 --> 00:03:12,788 FOR AUTOIMMUNE DISEASE RESEARCH 93 00:03:12,788 --> 00:03:14,423 HAS INCREASED AND HAS REACHED 94 00:03:14,423 --> 00:03:18,827 NEARLY A BILLION DOLLARS IN FY 95 00:03:18,827 --> 00:03:18,994 21. 96 00:03:18,994 --> 00:03:20,696 THE OFFICE OF AUTOIMMUNE DISEASE 97 00:03:20,696 --> 00:03:23,832 RESEARCH WITHIN ORWH HAS 98 00:03:23,832 --> 00:03:24,500 UNDERTAKEN A PORTFOLIO ANALYSIS 99 00:03:24,500 --> 00:03:27,336 TO BE ABLE TO ESTABLISH A 100 00:03:27,336 --> 00:03:28,871 BASELINE, AND FOR THE PURPOSES 101 00:03:28,871 --> 00:03:30,739 OF THAT PORTFOLIO ANALYSIS, WE 102 00:03:30,739 --> 00:03:33,842 ARE LOOKING AT THE 144 DISEASES 103 00:03:33,842 --> 00:03:35,244 AND CONDITIONS THAT WERE LISTED 104 00:03:35,244 --> 00:03:36,945 IN THE NATIONAL ACADEMIES OF 105 00:03:36,945 --> 00:03:38,714 SCIENCE, ENGINEERING AND 106 00:03:38,714 --> 00:03:40,682 MEDICINE REPORT ENTITLED 107 00:03:40,682 --> 00:03:42,651 "ENHANCING NIH RESEARCH ON 108 00:03:42,651 --> 00:03:44,420 AUTOIMMUNE DISEASE" AS EITHER 109 00:03:44,420 --> 00:03:45,954 CONSIDERED AUTOIMMUNE OR 110 00:03:45,954 --> 00:03:46,989 CO-EXISTING WITH OTHER 111 00:03:46,989 --> 00:03:49,158 AUTOIMMUNE DISEASES SUGGESTING 112 00:03:49,158 --> 00:03:50,626 POTENTIAL COMMONALITIES IN 113 00:03:50,626 --> 00:03:51,960 PATHOGENESIS. 114 00:03:51,960 --> 00:03:53,729 IT'S VERY IMPORTANT FOR US TO 115 00:03:53,729 --> 00:03:54,696 UNDERSTAND OUR AUTOIMMUNE 116 00:03:54,696 --> 00:03:56,432 DISEASE RESEARCH PORTFOLIO AT 117 00:03:56,432 --> 00:03:57,766 THIS TIME BECAUSE THAT'S GOING 118 00:03:57,766 --> 00:03:59,835 TO INFORM THE DEVELOPMENT OF THE 119 00:03:59,835 --> 00:04:02,237 FIRST NIH-WIDE STRATEGIC PLAN 120 00:04:02,237 --> 00:04:10,212 FOR AUTOIMMUNE DISEASE RESEARCH. 121 00:04:10,212 --> 00:04:13,182 AS I MENTIONED, AUTOIMMUNE 122 00:04:13,182 --> 00:04:17,786 DISEASE HAS BEEN IMPORTANT -- 123 00:04:17,786 --> 00:04:24,660 1SEC. 124 00:04:24,660 --> 00:04:30,666 I LOST VIEW OF THE SLIDE THERE. 125 00:04:30,666 --> 00:04:31,967 ARE THEY STILL SHOWING FOR YOU 126 00:04:31,967 --> 00:04:36,805 ALL? 127 00:04:36,805 --> 00:04:40,075 >> YES. 128 00:04:40,075 --> 00:04:41,477 >> I'M NOT ABLE TO SEE THEM. 129 00:04:41,477 --> 00:04:42,778 CAN YOU LET ME KNOW WHICH SLIDE 130 00:04:42,778 --> 00:04:46,415 WE'RE ON? 131 00:04:46,415 --> 00:04:48,417 >> OMNIBUS LANGUAGE. 132 00:04:48,417 --> 00:04:48,917 >> GREAT. 133 00:04:48,917 --> 00:04:49,384 OKAY. 134 00:04:49,384 --> 00:04:51,753 THANKS SO MUCH. 135 00:04:51,753 --> 00:04:53,622 SO IN FISCAL YEAR '23, CONGRESS 136 00:04:53,622 --> 00:04:55,390 CREATED THE OFFICE OF AUTOIMMUNE 137 00:04:55,390 --> 00:04:57,993 DISEASE RESEARCH WITHIN ORWH BY 138 00:04:57,993 --> 00:05:00,929 THIS CONGRESSIONAL DIRECTIVE. 139 00:05:00,929 --> 00:05:04,666 THEY APPROPRIATED $10 BILLION IN 140 00:05:04,666 --> 00:05:08,170 FUNDS TO COORDINATE A MULTI-IC 141 00:05:08,170 --> 00:05:09,705 STRATEGIC RESEARCH PLAN TO 142 00:05:09,705 --> 00:05:11,640 IDENTIFY EMERGING AREAS OF 143 00:05:11,640 --> 00:05:12,875 INNOVATION AND RESEARCH 144 00:05:12,875 --> 00:05:14,510 OPPORTUNITY, COORDINATING AND 145 00:05:14,510 --> 00:05:15,811 EVALUATING THE PORTFOLIO, 146 00:05:15,811 --> 00:05:17,679 PROVIDING RESOURCES TO SUPPORT 147 00:05:17,679 --> 00:05:18,680 PLANNING, COLLABORATION AND I 148 00:05:18,680 --> 00:05:20,516 OVATION AND TO DEVELOP PUBLICLY 149 00:05:20,516 --> 00:05:21,817 ACCESSIBLE CENTRAL REPOSITORY 150 00:05:21,817 --> 00:05:24,786 FOR AUTOIMMUNE DISEASE RESEARCH. 151 00:05:24,786 --> 00:05:26,655 I AM THRILLED TO TELL YOU IN OUR 152 00:05:26,655 --> 00:05:28,824 VERY FIRST YEAR OF EXISTENCE, 153 00:05:28,824 --> 00:05:30,993 THE AUTOIMMUNE DISEASE RESEARCH 154 00:05:30,993 --> 00:05:32,661 OFFICE FUNDED 41 APPLICATIONS 155 00:05:32,661 --> 00:05:33,529 FROM 12 INSTITUTES AND CENTERS 156 00:05:33,529 --> 00:05:35,097 AND WE WERE ABLE TO COVER 17 157 00:05:35,097 --> 00:05:36,031 DISEASES IN THAT VERY FIRST 158 00:05:36,031 --> 00:05:42,070 YEAR. 159 00:05:42,070 --> 00:05:44,039 THE VERY FIRST FUNDING 160 00:05:44,039 --> 00:05:45,774 OPPORTUNITY THAT WE'RE ABLE TO 161 00:05:45,774 --> 00:05:48,210 DELIVER IS THE EXACT PLAN, 162 00:05:48,210 --> 00:05:50,279 STANDS FOR EXPOSOME IN 163 00:05:50,279 --> 00:05:51,246 AUTOIMMUNE DISEASE COLLABORATING 164 00:05:51,246 --> 00:05:53,448 TEAMS PLANNING AWARDS. 165 00:05:53,448 --> 00:05:55,417 IN COLLABORATION WITH THE 166 00:05:55,417 --> 00:05:57,819 NATIONAL INSTITUTE OF ARTHRITIS, 167 00:05:57,819 --> 00:05:58,487 MUSCULOSKELETAL AND SKIN 168 00:05:58,487 --> 00:06:01,223 DISEASES AS WELL AS THE NATIONAL 169 00:06:01,223 --> 00:06:01,857 INSTITUTE OF ENVIRONMENTAL 170 00:06:01,857 --> 00:06:04,693 HEALTH SCIENCES, THE EXACT PLAN 171 00:06:04,693 --> 00:06:06,361 NOTICE OF SPECIAL INTEREST WAS 172 00:06:06,361 --> 00:06:09,364 ISSUED AND HERE ARE THE SIX 173 00:06:09,364 --> 00:06:11,066 FIRST COMPACT-PLAN AWARDEE 174 00:06:11,066 --> 00:06:11,500 REACCEPT YENTS. 175 00:06:11,500 --> 00:06:13,035 YOU'RE GOING TO HEAR FROM 176 00:06:13,035 --> 00:06:14,770 DR. BUCKNER SHORTLY, BUT THE 177 00:06:14,770 --> 00:06:16,738 EXACT NETWORK IS DESIGNED TO BE 178 00:06:16,738 --> 00:06:17,606 A NATIONAL RESEARCH 179 00:06:17,606 --> 00:06:18,941 COLLABORATIVE TEAM TO CONDUCT 180 00:06:18,941 --> 00:06:20,676 RESEARCH TO DISCOVER THE 181 00:06:20,676 --> 00:06:22,744 ENVIRONMENTAL EXPOSURES THAT 182 00:06:22,744 --> 00:06:24,613 INFLUENCE AUTOIMMUNE DISEASE 183 00:06:24,613 --> 00:06:26,915 SUSCEPTIBILITY, ONSET AND 184 00:06:26,915 --> 00:06:28,483 OUTCOMES, AND WILL DEVELOP A 185 00:06:28,483 --> 00:06:29,318 SYSTEMS-LEVEL APPROACH TO 186 00:06:29,318 --> 00:06:32,154 UNDERSTANDING THE MECHANISMS 187 00:06:32,154 --> 00:06:34,356 RELATED TO PERTURBATIONS THAT 188 00:06:34,356 --> 00:06:40,128 CROSS AUTOIMMUNE DISEASES. 189 00:06:40,128 --> 00:06:42,764 WE WORKED ALSO WITH DR. LINDSAY 190 00:06:42,764 --> 00:06:45,400 CRISWELL, DR. BOB CARTER, THE 191 00:06:45,400 --> 00:06:47,736 LEADERSHIP OF THE NATIONAL 192 00:06:47,736 --> 00:06:49,338 INSTITUTE OF ARTHRITIS, 193 00:06:49,338 --> 00:06:50,305 MUSCULOSKELETAL AND SKIN 194 00:06:50,305 --> 00:06:51,139 DISEASES TO CREATE A NEW PROGRAM 195 00:06:51,139 --> 00:06:53,275 ALONG WITH THE OFFICE OF DAY A 196 00:06:53,275 --> 00:06:54,476 SCIENCE STRATEGY. 197 00:06:54,476 --> 00:06:56,211 THIS PROGRAM IS FOCUSED ON 198 00:06:56,211 --> 00:06:57,546 LEADERSHIP DEVELOPMENT AND TEAM 199 00:06:57,546 --> 00:06:59,815 SCIENCE IN THE AREAS OF WOMEN'S 200 00:06:59,815 --> 00:07:00,482 HEALTH SPECIFICALLY AUTOIMMUNE 201 00:07:00,482 --> 00:07:04,019 AND IMMUNE MEDIATED DISEASES. 202 00:07:04,019 --> 00:07:06,555 THROUGH THIS LEADERSHIP SCHOLAR 203 00:07:06,555 --> 00:07:08,290 PROGRAM OR LSP, WE ARE 204 00:07:08,290 --> 00:07:09,458 SUPPORTING MID CAREER SCIENTISTS 205 00:07:09,458 --> 00:07:10,692 WHO ARE WORKING IN THE WOMEN'S 206 00:07:10,692 --> 00:07:11,994 HEALTH SPACE AND THEY HAVE THE 207 00:07:11,994 --> 00:07:14,096 OPPORTUNITY TO WORK WITH THE 208 00:07:14,096 --> 00:07:16,398 ACCELERATING MEDICINES 209 00:07:16,398 --> 00:07:18,367 PARTNERSHIP, AUTOIMMUNE AND 210 00:07:18,367 --> 00:07:20,535 IMMUNE-MEDIATED DISEASES 211 00:07:20,535 --> 00:07:21,837 PUBLIC-PRIVATE PARTNERSHIP OR 212 00:07:21,837 --> 00:07:22,838 AMP AIM. 213 00:07:22,838 --> 00:07:24,039 THROUGH THAT LARGE 214 00:07:24,039 --> 00:07:24,706 PUBLIC-PRIVATE PARTNERSHIP WITH 215 00:07:24,706 --> 00:07:26,441 THE FOUNDATION FOR NIH, THESE 216 00:07:26,441 --> 00:07:29,945 SIX INVESTIGATORS ARE WORKING ON 217 00:07:29,945 --> 00:07:31,246 TOPICS THAT RANGE FROM 218 00:07:31,246 --> 00:07:32,781 MULTI-OMIC APPROACHES TO EARLY 219 00:07:32,781 --> 00:07:39,888 DISEASE PATHOGENESIS IN LUPUS 220 00:07:39,888 --> 00:07:42,524 NEPHRITIS, AT THE 221 00:07:42,524 --> 00:07:43,825 TRANSCRIPTIONAL AND EPIGENETIC 222 00:07:43,825 --> 00:07:45,293 LEVELS AND TO A TOPIC NEAR AND 223 00:07:45,293 --> 00:07:50,832 DEAR TO MY HEART, PERSONALIZED 224 00:07:50,832 --> 00:07:56,972 USE OF METHOTREXATE FOR THE 225 00:07:56,972 --> 00:08:00,776 TREATMENT OF JUVENILE IDIOPATHIC 226 00:08:00,776 --> 00:08:05,180 ARTHRITIS-ASSOCIATED UVEITIS. 227 00:08:05,180 --> 00:08:07,049 ORWH WAS ASKED BY CONGRESS TO 228 00:08:07,049 --> 00:08:08,216 EXAMINE THE NIH PORTFOLIO AROUND 229 00:08:08,216 --> 00:08:09,418 THREE AREAS. 230 00:08:09,418 --> 00:08:13,155 MATERNAL MO MORBIDITY AND 231 00:08:13,155 --> 00:08:14,556 MORTALITY, STALLED CERVICAL 232 00:08:14,556 --> 00:08:15,824 CANCER SURVIVAL RATES IN THE 233 00:08:15,824 --> 00:08:16,858 UNITED STATES AND RISING RATES 234 00:08:16,858 --> 00:08:17,793 OF CHRONIC DISEASES IN WOMEN IN 235 00:08:17,793 --> 00:08:19,494 THE U.S. 236 00:08:19,494 --> 00:08:21,897 AS A RESULT OF THAT REQUEST, WE 237 00:08:21,897 --> 00:08:26,835 HOSTED AN NIH-WIDE ADVISORY 238 00:08:26,835 --> 00:08:27,703 COMMITTEE LED CONFERENCE ON 239 00:08:27,703 --> 00:08:29,137 WOMEN'S HEALTH RELATED TO THOSE 240 00:08:29,137 --> 00:08:30,672 TOPICS, AND WE IDENTIFIED 241 00:08:30,672 --> 00:08:32,841 CHRONIC CONDITIONS UNDER WOMEN 242 00:08:32,841 --> 00:08:34,910 AS A RESEARCH GAP. 243 00:08:34,910 --> 00:08:36,211 WE PARTNERED WITH FIVE 244 00:08:36,211 --> 00:08:37,145 INSTITUTES AND CENTERS 245 00:08:37,145 --> 00:08:38,613 IDENTIFIED HERE ON THE SLIDE TO 246 00:08:38,613 --> 00:08:41,349 CREATE THESE TWO RFAs FOCUSING 247 00:08:41,349 --> 00:08:42,684 ON UNDERSTUDIED CHRONIC 248 00:08:42,684 --> 00:08:46,288 CONDITIONS IN WOMEN, AN R01 AND 249 00:08:46,288 --> 00:08:47,589 AN R21. 250 00:08:47,589 --> 00:08:49,891 HERE OUR SPECIAL AREAS OF 251 00:08:49,891 --> 00:08:51,860 INTEREST WERE IDENTIFIED AS 252 00:08:51,860 --> 00:08:52,427 FEMALE-SPECIFIC CONDITIONS, 253 00:08:52,427 --> 00:08:53,395 CONDITIONS MORE COMMON IN WOMEN. 254 00:08:53,395 --> 00:08:55,597 HERE'S WHERE WE CALLED OUT 255 00:08:55,597 --> 00:08:57,132 SPECIFICALLY AUTOIMMUNE 256 00:08:57,132 --> 00:08:57,999 DISEASES, POSITIONS POTENTIALLY 257 00:08:57,999 --> 00:08:59,434 UNDERSTUDIED IN WOMEN AND THOSE 258 00:08:59,434 --> 00:09:05,207 WITH HIGH MORBIDITY IN WOMEN. 259 00:09:05,207 --> 00:09:06,541 THE NEXT ROUND OF APPLICATIONS 260 00:09:06,541 --> 00:09:08,043 WILL CLOSE ON JUNE 20TH AND 261 00:09:08,043 --> 00:09:09,377 WE'RE LOOKING FORWARD TO SHARING 262 00:09:09,377 --> 00:09:11,446 NEWS WITH YOU THOSE FUNDING 263 00:09:11,446 --> 00:09:14,082 APPLICATIONS IN THE FUTURE. 264 00:09:14,082 --> 00:09:16,685 ON NOVEMBER 13TH, I WAS 265 00:09:16,685 --> 00:09:19,121 ABSOLUTELY HONORED TO BE ABLE TO 266 00:09:19,121 --> 00:09:20,288 JOIN THE PRESIDENT AND FIRST 267 00:09:20,288 --> 00:09:21,957 LADY ALONG WITH DR. MONICA 268 00:09:21,957 --> 00:09:23,592 BERTAGNOLLI, WHO HAD JUST BEEN 269 00:09:23,592 --> 00:09:26,194 NAMED NIH DIRECTOR, SECRETARY 270 00:09:26,194 --> 00:09:28,597 BECERRA AND OTHERS IN THE OVAL 271 00:09:28,597 --> 00:09:30,365 OFFICE FOR THE SIGNING OF THE 272 00:09:30,365 --> 00:09:31,466 HISTORIC WHITE HOUSE INITIATIVE 273 00:09:31,466 --> 00:09:33,869 ON WOMEN'S HEALTH RESEARCH. 274 00:09:33,869 --> 00:09:35,871 IN THAT INITIATIVE, THE 275 00:09:35,871 --> 00:09:36,838 PRESIDENT AND THE FIRST LADY 276 00:09:36,838 --> 00:09:38,173 TALKED ABOUT HOW IMPORTANT 277 00:09:38,173 --> 00:09:40,742 WOMEN'S HEALTH RESEARCH IS TO 278 00:09:40,742 --> 00:09:42,277 THEM AND CHALLENGED ALL THE 279 00:09:42,277 --> 00:09:44,146 AGENCIES INVOLVED TO IDENTIFY 280 00:09:44,146 --> 00:09:47,115 CONCRETE ACTIONS THAT WE COULD 281 00:09:47,115 --> 00:09:48,850 TAKE WITHIN 45 DAYS TO MAXIMIZE 282 00:09:48,850 --> 00:09:50,719 THE ADMINISTRATION'S INVESTMENTS 283 00:09:50,719 --> 00:09:52,454 IN WOMEN'S HEALTH RESEARCH, 284 00:09:52,454 --> 00:09:53,655 INCLUDING ADDRESSING HEALTH 285 00:09:53,655 --> 00:09:54,656 DISPARITIES AND HEALTH 286 00:09:54,656 --> 00:09:58,360 INEQUITIES. 287 00:09:58,360 --> 00:10:00,061 THE INITIATIVE IS DESIGNED TO 288 00:10:00,061 --> 00:10:01,196 FUNDAMENTALLY CHANGE THE WAY WE 289 00:10:01,196 --> 00:10:03,732 DO WOMEN'S HEALTH RESEARCH. 290 00:10:03,732 --> 00:10:04,699 WHETHER THAT'S IDENTIFYING 291 00:10:04,699 --> 00:10:06,735 OPPORTUNITIES FOR ADDITIONAL 292 00:10:06,735 --> 00:10:08,203 INVESTMENTS, INTEGRATING 293 00:10:08,203 --> 00:10:10,071 RESEARCH EFFORTS AND 294 00:10:10,071 --> 00:10:11,072 FACILITATING INTERDISCIPLINARY 295 00:10:11,072 --> 00:10:12,574 RESEARCH, DEVELOPING 296 00:10:12,574 --> 00:10:17,078 PUBLIC-PRIVATE PARTNERSHIPS, AND 297 00:10:17,078 --> 00:10:17,946 INCREASING PUBLIC AWARENESS OF 298 00:10:17,946 --> 00:10:19,114 THE NEED FOR GREATER INVESTMENT 299 00:10:19,114 --> 00:10:21,449 AND ATTENTION TO WOMEN'S HEALTH 300 00:10:21,449 --> 00:10:22,784 RESEARCH. 301 00:10:22,784 --> 00:10:24,052 YOU'RE GOING TO NEED TO CLICK 302 00:10:24,052 --> 00:10:25,253 NEXT A COUPLE TIMES UNTIL THREE 303 00:10:25,253 --> 00:10:28,223 RED BARS ARE UP. 304 00:10:28,223 --> 00:10:28,590 OKAY. 305 00:10:28,590 --> 00:10:29,558 AND THEN PLEASE GO FORWARD TO 306 00:10:29,558 --> 00:10:32,494 THE NEXT SLIDE, WHERE I AM 307 00:10:32,494 --> 00:10:35,230 TALKING ABOUT THIS AMAZING 308 00:10:35,230 --> 00:10:39,367 EXECUTIVE ORDER 14120. 309 00:10:39,367 --> 00:10:40,268 THIS EXECUTIVE ORDER IS 310 00:10:40,268 --> 00:10:41,469 HIGHLIGHTING THE IMPORTANCE OF 311 00:10:41,469 --> 00:10:42,237 ADVANCING WOMEN'S HEALTH 312 00:10:42,237 --> 00:10:43,371 RESEARCH. 313 00:10:43,371 --> 00:10:44,206 SO FIRST THE PRESIDENT SIGNED A 314 00:10:44,206 --> 00:10:45,707 PRESIDENTIAL MEMO AND THEN THIS 315 00:10:45,707 --> 00:10:47,475 WAS FILED WITH AN EXECUTIVE 316 00:10:47,475 --> 00:10:49,778 ORDER THAT HIGHLIGHTS FOUR 317 00:10:49,778 --> 00:10:50,979 AREAS: THE IMPORTANCE OF 318 00:10:50,979 --> 00:10:51,947 PRIORITIZING INVESTMENT IN 319 00:10:51,947 --> 00:10:53,481 WOMEN'S HEALTH RESEARCH, 320 00:10:53,481 --> 00:10:54,683 INTEGRATING WOMEN'S HEALTH 321 00:10:54,683 --> 00:10:56,651 ACROSS THE FEDERAL RESEARCH 322 00:10:56,651 --> 00:10:58,753 PORTFOLIO, IN MULTIPLE AGENCIES 323 00:10:58,753 --> 00:11:01,056 AND DEPARTMENTS, GALVANIZING NEW 324 00:11:01,056 --> 00:11:02,891 RESEARCH ON WOMEN'S MID LIFE 325 00:11:02,891 --> 00:11:04,960 HEALTH, AND THEN ASSESSING UNMET 326 00:11:04,960 --> 00:11:06,628 NEEDS TO SUPPORT WOMEN'S HEALTH 327 00:11:06,628 --> 00:11:07,062 RESEARCH. 328 00:11:07,062 --> 00:11:08,697 AND I'M LOOKING FORWARD TO 329 00:11:08,697 --> 00:11:10,432 SHARING NEWS WITH YOU ABOUT ALL 330 00:11:10,432 --> 00:11:12,200 OF THE AMAZING STEPS WE ARE 331 00:11:12,200 --> 00:11:14,936 TAKING TO ALIGN WITH THIS 332 00:11:14,936 --> 00:11:17,239 EXECUTIVE ORDER. 333 00:11:17,239 --> 00:11:18,773 THE NEXT SLIDE HIGHLIGHTS A 334 00:11:18,773 --> 00:11:19,741 NOTICE OF SPECIAL INTEREST WHICH 335 00:11:19,741 --> 00:11:21,743 IS ONE OF NIH'S VERY FIRST STEPS 336 00:11:21,743 --> 00:11:23,445 WE ARE TAKING TO ADDRESS AND 337 00:11:23,445 --> 00:11:25,881 ALIGN WITH THE EXECUTIVE ORDER. 338 00:11:25,881 --> 00:11:27,382 WE HAVE ISSUED A NOTICE OF 339 00:11:27,382 --> 00:11:28,583 SPECIAL INTEREST RELATED TO 340 00:11:28,583 --> 00:11:31,786 WOMEN'S HEALTH RESEARCH EVERY 341 00:11:31,786 --> 00:11:32,754 SINGLE INSTITUTE AND CENTER 342 00:11:32,754 --> 00:11:34,489 SIGNED ON TO THIS NOSI. 343 00:11:34,489 --> 00:11:37,225 IT IS LINKED TO ALL OF THE NIH 344 00:11:37,225 --> 00:11:39,861 PARENT FUNDING OPPORTUNITIES 345 00:11:39,861 --> 00:11:42,264 REGARDLESS OF MECHANISM OR 346 00:11:42,264 --> 00:11:44,833 INSTITUTE, SO ALL THE PARENT 347 00:11:44,833 --> 00:11:46,735 FUNDING OPPORTUNITIES, THE 348 00:11:46,735 --> 00:11:48,904 RPGs, THE Ts, THE Ks, THE 349 00:11:48,904 --> 00:11:50,538 Fs, THE SMALL BUSINESS 350 00:11:50,538 --> 00:11:52,307 INNOVATION, THE TECH TRANSFER, 351 00:11:52,307 --> 00:11:53,074 EVERYBODY SINGLE FUNDING 352 00:11:53,074 --> 00:11:54,409 OPPORTUNITY THAT'S APPARENT IS 353 00:11:54,409 --> 00:11:54,843 LINKED TO THIS. 354 00:11:54,843 --> 00:11:58,213 AND WHAT THAT DOES IS THAT GIVES 355 00:11:58,213 --> 00:11:59,414 APPLICANTS MANY PATHWAYS TO 356 00:11:59,414 --> 00:12:01,016 WOMEN'S HEALTH RESEARCH. 357 00:12:01,016 --> 00:12:03,084 IT INDICATES OUR INTEREST IN 358 00:12:03,084 --> 00:12:04,786 RECEIVING APPLICATIONS ON 359 00:12:04,786 --> 00:12:06,855 WOMEN'S HEALTH RESEARCH ACROSS A 360 00:12:06,855 --> 00:12:09,057 WIDE RANGE OF TOPICS. 361 00:12:09,057 --> 00:12:10,592 CERTAINLY CONDITIONS THAT 362 00:12:10,592 --> 00:12:11,993 PREDOMINANTLY AFFECT WOMEN AND, 363 00:12:11,993 --> 00:12:14,396 AGAIN, AUTOIMMUNE DISEASES WERE 364 00:12:14,396 --> 00:12:16,164 EXPRESSLY CALLED OUT HERE ALONG 365 00:12:16,164 --> 00:12:18,433 WITH DEPRESSIVE DISORDERS, 366 00:12:18,433 --> 00:12:19,968 ALZHEIMER'S DISEASE AND OTHER 367 00:12:19,968 --> 00:12:21,503 DISEASES THAT PRESENT OR 368 00:12:21,503 --> 00:12:22,270 PROGRESS DIFFERENTLY IN WOMEN 369 00:12:22,270 --> 00:12:25,006 AND THEN THOSE THAT ARE 370 00:12:25,006 --> 00:12:26,107 FEMALE-SPECIFIC. 371 00:12:26,107 --> 00:12:27,409 SO WE ARE VERY EXCITED ABOUT 372 00:12:27,409 --> 00:12:33,882 THIS NEW OPPORTUNITY. 373 00:12:33,882 --> 00:12:35,717 TODAY WE LAUNCHED THE NEW 374 00:12:35,717 --> 00:12:36,718 NIH-WIDE STRATEGIC PLAN FOR 375 00:12:36,718 --> 00:12:38,353 RESEARCH ON THE HEALTH OF WOMEN 376 00:12:38,353 --> 00:12:41,623 FOR 2024 TO 2028, A ROAD MAP TO 377 00:12:41,623 --> 00:12:42,290 THE FUTURE. 378 00:12:42,290 --> 00:12:44,492 I AM DELIGHTED TO BE HERE TODAY 379 00:12:44,492 --> 00:12:46,895 WITH YOU TO ANNOUNCE THIS 380 00:12:46,895 --> 00:12:48,630 NIH-WIDE STRATEGIC PLAN THAT 381 00:12:48,630 --> 00:12:52,133 WILL SET OUT OUR GOALS FOR THE 382 00:12:52,133 --> 00:12:53,234 NEXT FIVE YEARS AND WILL BE THE 383 00:12:53,234 --> 00:12:55,103 ROAD MAP THAT ALL OF US WILL 384 00:12:55,103 --> 00:12:56,838 FOLLOW ACROSS THE 27 INSTITUTES 385 00:12:56,838 --> 00:12:59,841 AND CENTERS HERE AT NIH TO 386 00:12:59,841 --> 00:13:01,977 ADDRESS WHAT WAS IDENTIFIED 387 00:13:01,977 --> 00:13:03,712 COLLECTIVELY WITH KEY INTERESTED 388 00:13:03,712 --> 00:13:05,246 PARTNERS, FEDERAL PARTNERS, OUR 389 00:13:05,246 --> 00:13:07,449 ADVISORY COMMITTEE AND OTHERS, 390 00:13:07,449 --> 00:13:09,317 SCIENTISTS, CLINICIANS IN THE 391 00:13:09,317 --> 00:13:10,385 FIELD, WHO'VE IDENTIFIED 392 00:13:10,385 --> 00:13:11,886 RESEARCH GAPS AND WE HAVE 393 00:13:11,886 --> 00:13:13,688 ARTICULATED GOALS AND OBJECTIVES 394 00:13:13,688 --> 00:13:15,223 TO ADDRESS THOSE GAPS. 395 00:13:15,223 --> 00:13:17,625 WE HAVE TAKEN A DATA-DRIVEN 396 00:13:17,625 --> 00:13:19,260 ITERATIVE APPROACH AND WE ARE 397 00:13:19,260 --> 00:13:21,329 COMMITTED TO HEARING FROM THE 398 00:13:21,329 --> 00:13:23,531 INDIVIDUALS AFFECTED BY THE 399 00:13:23,531 --> 00:13:28,737 DISEASES UNDER STUDY WOMEN IN 400 00:13:28,737 --> 00:13:29,537 OUR COMMUNITY AND FROM THE 401 00:13:29,537 --> 00:13:30,305 PUBLIC IN GENERAL. 402 00:13:30,305 --> 00:13:31,639 SO I'M DELIGHTED TO BE ABLE TO 403 00:13:31,639 --> 00:13:33,108 ANNOUNCE THAT TO YOU AND WE'LL 404 00:13:33,108 --> 00:13:34,242 REFER YOU TO A VIDEO THAT HAS 405 00:13:34,242 --> 00:13:36,211 BEEN LAUNCHED TODAY WHERE THE 406 00:13:36,211 --> 00:13:39,247 NIH DIRECTOR, DR. MONICA 407 00:13:39,247 --> 00:13:39,814 BERTAGNOLLI, ARTICULATES HER 408 00:13:39,814 --> 00:13:40,582 VISION FOR WOMEN'S HEALTH 409 00:13:40,582 --> 00:13:44,652 RESEARCH IN THE FUTURE. 410 00:13:44,652 --> 00:13:46,388 THIS SLIDE IS A THANK YOU SLIDE. 411 00:13:46,388 --> 00:13:51,559 I WANTED TO ARTICULATE ON THIS 412 00:13:51,559 --> 00:13:52,894 SLIDE SO MANY THINGS WE ARE 413 00:13:52,894 --> 00:13:55,363 GRATEFUL FOR TO DR. PINN, BUT I 414 00:13:55,363 --> 00:13:57,332 DECIDED JUST TO SAY THAT WE ARE 415 00:13:57,332 --> 00:13:58,233 THANKFUL FOR EVERYTHING THAT 416 00:13:58,233 --> 00:13:59,300 SHE'S DONE IN TERMS OF CREATING 417 00:13:59,300 --> 00:14:01,169 THE VERY FIRST NIH-WIDE 418 00:14:01,169 --> 00:14:02,037 STRATEGIC PLAN FOR WOMEN'S 419 00:14:02,037 --> 00:14:04,873 HEALTH RESEARCH, TO CREATING THE 420 00:14:04,873 --> 00:14:05,673 BIRCH PROGRAM AND THE SCORE 421 00:14:05,673 --> 00:14:07,842 PROGRAM AND THE RE-ENTRY 422 00:14:07,842 --> 00:14:10,678 SUPPLEMENT PROGRAM AND ADVANCING 423 00:14:10,678 --> 00:14:12,447 INCLUSION POLICY AND OTHER 424 00:14:12,447 --> 00:14:15,517 PROGRAMS FOR THE RECRUITMENT 425 00:14:15,517 --> 00:14:17,786 RE-ENTRY AND SUSTAINED 426 00:14:17,786 --> 00:14:18,887 ADVANCEMENT OF WOMEN IN SCIENCE 427 00:14:18,887 --> 00:14:19,220 CAREERS. 428 00:14:19,220 --> 00:14:20,622 WE REALLY WANT TO ACKNOWLEDGE 429 00:14:20,622 --> 00:14:23,358 YOU, DR. PINN, FOR ALL OF YOUR 430 00:14:23,358 --> 00:14:24,459 EFFORTS THAT HAVE HELPED US GET 431 00:14:24,459 --> 00:14:25,660 TO WHERE WE ARE TODAY, AND THAT 432 00:14:25,660 --> 00:14:27,295 IS WHY THIS SYMPOSIUM IS NAMED 433 00:14:27,295 --> 00:14:33,601 IN YOUR HONOR, SO THANK YOU, DR. 434 00:14:33,601 --> 00:14:36,805 I ALSO WANT TO THANK DR 435 00:14:36,805 --> 00:14:37,639 DR. SHANMUGAM AND THE TEAM FOR 436 00:14:37,639 --> 00:14:40,175 PLANNING THIS EVENT, THE OFFICE 437 00:14:40,175 --> 00:14:41,910 OF AUTOIMMUNE DISEASE RESEARCH, 438 00:14:41,910 --> 00:14:44,212 THEIR VERY FIRST NIH-WIDE VIVIAN 439 00:14:44,212 --> 00:14:47,048 PINN SYMPOSIUM TYPE OF EVENT, 440 00:14:47,048 --> 00:14:48,950 THE ORWT COMMUNICATIONS TEAM, 441 00:14:48,950 --> 00:14:50,318 OUR PARTNERS AND THE NIH 442 00:14:50,318 --> 00:14:51,619 INSTITUTES AND CENTERS, 443 00:14:51,619 --> 00:14:52,187 CONTRACTORS AND COLLEAGUES 444 00:14:52,187 --> 00:14:53,555 ACROSS THE ICs WHO WORKED ON 445 00:14:53,555 --> 00:14:54,923 THE PROGRAM, ALL OF THE 446 00:14:54,923 --> 00:14:57,225 SPEAKERS, ALL OF THE MODERATORS, 447 00:14:57,225 --> 00:14:58,293 FOR PARTICIPATING TODAY, AND I 448 00:14:58,293 --> 00:15:00,161 ALSO WANT TO ACKNOWLEDGE ALL OF 449 00:15:00,161 --> 00:15:02,030 THE WOMEN AND INDIVIDUALS WHO 450 00:15:02,030 --> 00:15:05,200 HAVE PARTICIPATED IN THE 451 00:15:05,200 --> 00:15:06,768 RESEARCH THAT WE'RE ABLE TO 452 00:15:06,768 --> 00:15:08,269 PRESENT TO YOU TODAY. 453 00:15:08,269 --> 00:15:09,804 YOU ARE THE REASON WHY WE ARE 454 00:15:09,804 --> 00:15:11,773 DOING THIS AND WE LOOK FORWARD 455 00:15:11,773 --> 00:15:12,974 TO CONTINUED EFFORTS IN THIS 456 00:15:12,974 --> 00:15:16,478 REGARD. 457 00:15:16,478 --> 00:15:18,313 IF YOU GO TO THE NEXT SLIDE, YOU 458 00:15:18,313 --> 00:15:20,181 WILL SEE THE SPEAKERS WE WILL BE 459 00:15:20,181 --> 00:15:22,250 HAVING, OUR TWO KEY NOTES. 460 00:15:22,250 --> 00:15:24,552 TODAY'S SYMPOSIUM IS ENTITLED 461 00:15:24,552 --> 00:15:26,955 SYNERGY IN SCIENCE, INNOVATIONS 462 00:15:26,955 --> 00:15:27,856 IN AUTOIMMUNE DISEASE RESEARCH 463 00:15:27,856 --> 00:15:28,256 AND CARE. 464 00:15:28,256 --> 00:15:33,461 FIRST YOU'LL BE HEARING FROM DRL 465 00:15:33,461 --> 00:15:35,263 HEAR AT THE END FROM OUR 466 00:15:35,263 --> 00:15:38,433 CAPSTONE SPEAKER, DR. GAIL KARR. 467 00:15:38,433 --> 00:15:39,534 SO PLEASE STAY WITH US FOR THIS 468 00:15:39,534 --> 00:15:39,968 FULL EVENT. 469 00:15:39,968 --> 00:15:42,270 I'M GOING TO WELCOME OUR KEYNOTE 470 00:15:42,270 --> 00:15:44,105 SPEAKER, DR. JANE BUCKNER. 471 00:15:44,105 --> 00:15:46,307 DR. BUCKNER IS THE PRESIDENT OF 472 00:15:46,307 --> 00:15:47,609 THE BENAROYA RESEARCH INSTITUTE 473 00:15:47,609 --> 00:15:48,510 IN SEATTLE, WASHINGTON. 474 00:15:48,510 --> 00:15:52,347 SHE ALSO SERVES AS AFFILIATE 475 00:15:52,347 --> 00:15:54,749 PROFESSOR IN THE DEPARTMENT OF 476 00:15:54,749 --> 00:15:56,918 MEDICINE, DEPARTMENT OF 477 00:15:56,918 --> 00:15:59,320 RHEUMATOLOGY AND DEPARTMENT OF 478 00:15:59,320 --> 00:16:00,121 IMMUNOLOGY AT THE UNIVERSITY OF 479 00:16:00,121 --> 00:16:00,755 WASHINGTON. 480 00:16:00,755 --> 00:16:05,827 HER FULL BUY Y BIYO IS AVAILABLN 481 00:16:05,827 --> 00:16:07,295 THE PROGRAM BOOKLET LINKED IN 482 00:16:07,295 --> 00:16:08,062 THE CHAT. 483 00:16:08,062 --> 00:16:09,297 DR. BUCKNER IS KNOWN FOR HER 484 00:16:09,297 --> 00:16:10,698 RESEARCH IN TRANSLATIONAL 485 00:16:10,698 --> 00:16:12,867 IMMUNOLOGY, COMBINING GENETICS, 486 00:16:12,867 --> 00:16:13,801 IMMUNOLOGY AND CLINICAL MEDICINE 487 00:16:13,801 --> 00:16:15,803 TO ADVANCE THE UNDERSTANDING OF 488 00:16:15,803 --> 00:16:16,838 THE CAUSES OF AUTOIMMUNE 489 00:16:16,838 --> 00:16:17,939 DISEASES. 490 00:16:17,939 --> 00:16:19,207 SHE HAS BEEN INSTRUMENTAL IN 491 00:16:19,207 --> 00:16:20,542 DEVELOPING THE TRANSLATIONAL 492 00:16:20,542 --> 00:16:22,510 IMMUNOLOGY RESEARCH PROGRAM AND 493 00:16:22,510 --> 00:16:23,511 ESTABLISHING THE BENAROYA 494 00:16:23,511 --> 00:16:25,246 RESEARCH INSTITUTE 495 00:16:25,246 --> 00:16:26,347 BIOREPOSITORY, WHICH CURRENTLY 496 00:16:26,347 --> 00:16:29,083 INCLUDES OVER 350,000 SAMPLES 497 00:16:29,083 --> 00:16:30,952 FROM 14,000 PARTICIPANTS. 498 00:16:30,952 --> 00:16:32,820 DR. BUCKNER HAS MADE SIGNIFICANT 499 00:16:32,820 --> 00:16:33,555 CONTRIBUTIONS TO OUR 500 00:16:33,555 --> 00:16:35,123 UNDERSTANDING OF HOW HUMAN T 501 00:16:35,123 --> 00:16:40,228 CELLS ARE DISREGULATED IN TYPE D 502 00:16:40,228 --> 00:16:41,396 ARTHRITIS AND HAS BEEN A PIONEER 503 00:16:41,396 --> 00:16:43,731 IN THE DEVELOPMENT OF 504 00:16:43,731 --> 00:16:44,199 ANTIGEN-SPECIFIC T REG 505 00:16:44,199 --> 00:16:44,599 THERAPIES. 506 00:16:44,599 --> 00:16:46,134 WE LOOK FORWARD TO LEARNING FROM 507 00:16:46,134 --> 00:16:48,303 HER DURING THIS KEYNOTE ADDRESS. 508 00:16:48,303 --> 00:16:51,973 WELCOME, DR. BUCKNER. 509 00:16:51,973 --> 00:17:02,217 >> THANK YOU. 510 00:17:05,220 --> 00:17:08,656 THANK YOU SO MUCH FOR THAT KIND 511 00:17:08,656 --> 00:17:09,757 INTRODUCTION, AND THIS IS REALLY 512 00:17:09,757 --> 00:17:13,695 AN EXCITING SYMPOSIUM TO BE 513 00:17:13,695 --> 00:17:13,895 PART. 514 00:17:13,895 --> 00:17:15,330 AND TODAY I'M GOING TO TRY TO 515 00:17:15,330 --> 00:17:18,399 GIVE AN OVERVIEW OF HOW WE CAN 516 00:17:18,399 --> 00:17:20,235 LOOK AND UNDERSTAND -- LOOK AT 517 00:17:20,235 --> 00:17:22,770 AUTOIMMUNE DISEASES, UNDERSTAND 518 00:17:22,770 --> 00:17:25,273 THEM, AND ULTIMATELY HOW ARE OUR 519 00:17:25,273 --> 00:17:26,808 STUDIES AND SCIENCE GOING TO 520 00:17:26,808 --> 00:17:35,917 TRANSFORM PATIENTS' LIVES. 521 00:17:35,917 --> 00:17:37,218 ALL RIGHT. 522 00:17:37,218 --> 00:17:39,053 BRIEFLY JUST WANTED TO SHARE MY 523 00:17:39,053 --> 00:17:39,454 DISCLOSURES. 524 00:17:39,454 --> 00:17:41,789 I WILL BE TALKING ABOUT 525 00:17:41,789 --> 00:17:44,525 ENGINEERED REGULATORY T CELLS 526 00:17:44,525 --> 00:17:47,462 DURING THIS TALK. 527 00:17:47,462 --> 00:17:52,200 SO STARTING WITH THE TOP POINT 528 00:17:52,200 --> 00:17:54,068 OF VIEW IS JUST SOME TAKE HOME 529 00:17:54,068 --> 00:17:55,570 MESSAGES TODAY. 530 00:17:55,570 --> 00:17:58,740 IMPORTANTLY, AUTOIMMUNITY 531 00:17:58,740 --> 00:18:03,344 AFFECTS A LARGE MERS TAJ PERCENF 532 00:18:03,344 --> 00:18:05,413 OUR POPULATION. 533 00:18:05,413 --> 00:18:07,248 I PUT TODAY IN PARENTHESES 534 00:18:07,248 --> 00:18:08,716 BECAUSE MY GOAL AND HOPE IS THAT 535 00:18:08,716 --> 00:18:09,817 THIS WILL CHANGE TOMORROW. 536 00:18:09,817 --> 00:18:11,419 THIS HAS ALREADY BEEN MENTIONED, 537 00:18:11,419 --> 00:18:12,854 WOMEN ARE DISPROPORTIONATELY 538 00:18:12,854 --> 00:18:14,622 IMPACTED BY AUTOIMMUNITY, AND 539 00:18:14,622 --> 00:18:15,823 WHEN WE THINK ABOUT AUTOIMMUNE 540 00:18:15,823 --> 00:18:17,759 DISEASES, I'M GOING TO TALK 541 00:18:17,759 --> 00:18:18,793 TODAY ABOUT HOW THE IMMUNE 542 00:18:18,793 --> 00:18:21,162 SYSTEM IS CENTRAL TO AUTOIMMUNE 543 00:18:21,162 --> 00:18:22,697 DISEASES AND THE FACTORS THAT 544 00:18:22,697 --> 00:18:25,333 ARE DRIVING AUTOIMMUNITY 545 00:18:25,333 --> 00:18:26,634 INCLUDING OUR GENETICS AS WELL 546 00:18:26,634 --> 00:18:28,503 AS ENVIRONMENTAL EXPOSURES. 547 00:18:28,503 --> 00:18:30,571 AND WHEN WE THINK OF THOSE 548 00:18:30,571 --> 00:18:31,773 INFLUENCES, THEY'RE BOTH 549 00:18:31,773 --> 00:18:33,741 INFLUENCING THE ULTIMATE 550 00:18:33,741 --> 00:18:35,376 DEVELOPMENT OF AUTOIMMUNITY, BUT 551 00:18:35,376 --> 00:18:38,613 ALSO THE OUTCOMES CLINICALLY FOR 552 00:18:38,613 --> 00:18:39,881 OUR PATIENTS WHO HAVE AUTOIMMUNE 553 00:18:39,881 --> 00:18:41,015 DISEASES. 554 00:18:41,015 --> 00:18:42,617 I'D LIKE TO TALK ON SOME NEW 555 00:18:42,617 --> 00:18:45,119 APPROACHES IN TERMS OF TREATING 556 00:18:45,119 --> 00:18:46,854 AUTOIMMUNITY AND HOW WE CAN 557 00:18:46,854 --> 00:18:50,258 TARGET DISEASE SPECIFICALLY. 558 00:18:50,258 --> 00:18:51,592 AND THEN AT THE END OF THE DAY, 559 00:18:51,592 --> 00:18:53,328 HOW DO WE PREDICT AND PREVENT 560 00:18:53,328 --> 00:18:54,862 THESE DISEASES, BECAUSE THAT'S 561 00:18:54,862 --> 00:19:00,902 THE ULTIMATE FORM OF CURE. 562 00:19:00,902 --> 00:19:02,637 SO I THOUGHT I'D START WITH WHAT 563 00:19:02,637 --> 00:19:05,139 IS AUTOIMMUNITY, AND IT IS -- 564 00:19:05,139 --> 00:19:07,108 THESE ARE DISEASES THAT SHARE IN 565 00:19:07,108 --> 00:19:08,609 COMMON THE FACT THAT THE IMMUNE 566 00:19:08,609 --> 00:19:11,379 SYSTEM IS ATTACKING HEALTHY 567 00:19:11,379 --> 00:19:12,680 TISSUE. 568 00:19:12,680 --> 00:19:14,349 THIS IS A LIST OF SOME 569 00:19:14,349 --> 00:19:15,283 AUTOIMMUNE DISEASE, CERTAINLY 570 00:19:15,283 --> 00:19:16,951 NOT ALL OF THEM. 571 00:19:16,951 --> 00:19:20,121 THEY LOOK DIFFERENT TO THE 572 00:19:20,121 --> 00:19:21,222 PHYSICIANS CARING FOR THESE 573 00:19:21,222 --> 00:19:22,623 PATIENTS AND MANY TIMES WHEN I 574 00:19:22,623 --> 00:19:25,059 TALK TO THE PUBLIC, PEOPLE 575 00:19:25,059 --> 00:19:26,227 AREN'T AWARE THAT SOME OF THESE 576 00:19:26,227 --> 00:19:28,429 DISEASES ARE TRULY AUTOIMMUNE. 577 00:19:28,429 --> 00:19:31,299 THINGS LIKE AUTOIMMUNE THYROID 578 00:19:31,299 --> 00:19:35,870 DISEASE, TYPE 1 DIABETES, 579 00:19:35,870 --> 00:19:36,838 PSORIASIS AND ANY NUMBER OF 580 00:19:36,838 --> 00:19:38,072 DISEASES. 581 00:19:38,072 --> 00:19:39,474 I'M A RHEUMATOLOGIST SO I THINK 582 00:19:39,474 --> 00:19:42,110 A LOT ABOUT JOINT DISEASES AND 583 00:19:42,110 --> 00:19:43,111 RHEUMATOID ARTHRITIS BUT TODAY 584 00:19:43,111 --> 00:19:44,946 YOU'LL HEAR ME TALKING ABOUT 585 00:19:44,946 --> 00:19:46,614 TYPE 1 DIABETES AND HOPEFULLY 586 00:19:46,614 --> 00:19:47,682 YOU'LL UNDERSTAND BY THE END OF 587 00:19:47,682 --> 00:19:50,184 MY TALK WHY A RHEUMATOLOGIST IS 588 00:19:50,184 --> 00:19:52,286 THINKING ABOUT TYPE 1 DIABETES. 589 00:19:52,286 --> 00:19:54,155 SO WHAT I'D LIKE TO EMPHASIZE IS 590 00:19:54,155 --> 00:19:56,858 ALTHOUGH THESE DISEASES LOOK 591 00:19:56,858 --> 00:19:57,992 DIFFERENT, THEY REALLY SHARE 592 00:19:57,992 --> 00:20:00,695 SOME COMMON FEATURES. 593 00:20:00,695 --> 00:20:05,099 BUT BEFORE I GET INTO THE IMMUNE 594 00:20:05,099 --> 00:20:06,501 SYSTEM AND HOW IT'S INVOLVED, 595 00:20:06,501 --> 00:20:08,903 JUST WANT TO AGAIN RE-EMPHASIZE 596 00:20:08,903 --> 00:20:10,271 THAT AUTOIMMUNE DISEASES ARE 597 00:20:10,271 --> 00:20:13,074 CHRONIC, DEBILITATING, COSTLY, 598 00:20:13,074 --> 00:20:15,910 AND CURRENTLY INCURABLE. 599 00:20:15,910 --> 00:20:16,444 THERE'S OVER 110 DIFFERENT 600 00:20:16,444 --> 00:20:18,413 AUTOIMMUNE DISEASES. 601 00:20:18,413 --> 00:20:19,180 THAT NUMBER CHANGES AND KEEPS 602 00:20:19,180 --> 00:20:20,815 GOING UP. 603 00:20:20,815 --> 00:20:21,849 BUT I THINK WHAT'S REALLY 604 00:20:21,849 --> 00:20:23,785 IMPORTANT TO UNDERSTAND IS THAT 605 00:20:23,785 --> 00:20:26,187 MEANS 1 IN 15 AMERICANS HAS AN 606 00:20:26,187 --> 00:20:27,288 AUTOIMMUNE DISEASE AND OF COURSE 607 00:20:27,288 --> 00:20:29,023 THAT MEANS MANY MORE PEOPLE ARE 608 00:20:29,023 --> 00:20:30,992 IMPACTED BY THEM AS THEIR 609 00:20:30,992 --> 00:20:32,293 FAMILIES AND PEOPLE WHO CARE FOR 610 00:20:32,293 --> 00:20:33,961 THEM AND LOVE THEM ARE ALSO 611 00:20:33,961 --> 00:20:35,062 IMPACTED. 612 00:20:35,062 --> 00:20:37,031 THESE ARE COSTLY DISEASES 613 00:20:37,031 --> 00:20:39,300 BECAUSE OF THE CHRONICITY OF THE 614 00:20:39,300 --> 00:20:40,535 DISEASES AND THEY'RE COSTLY BOTH 615 00:20:40,535 --> 00:20:42,170 IN TERMS OF OUR CARE FOR OUR 616 00:20:42,170 --> 00:20:44,806 PATIENTS, BUT CLEARLY THEY'RE 617 00:20:44,806 --> 00:20:45,573 DEBILITATING FOR INDIVIDUALS AS 618 00:20:45,573 --> 00:20:48,042 WELL. 619 00:20:48,042 --> 00:20:49,477 AS WAS ALREADY MENTIONED, WOMEN 620 00:20:49,477 --> 00:20:51,245 ARE MUCH MORE FREQUENTLY 621 00:20:51,245 --> 00:20:53,414 AFFECTED BY AUTOIMMUNITY THAN 622 00:20:53,414 --> 00:20:53,815 MEN. 623 00:20:53,815 --> 00:20:55,249 AND I'D ALSO LIKE TO POINT OUT 624 00:20:55,249 --> 00:20:57,685 THAT THESE DISEASES AFFECT ALL 625 00:20:57,685 --> 00:21:01,522 AGE GROUPS FROM EARLY CHILDHOOD 626 00:21:01,522 --> 00:21:05,226 TO WOMEN WHO MAY BE IN THEIR 627 00:21:05,226 --> 00:21:07,195 20s AND 30s TO THOSE THAT 628 00:21:07,195 --> 00:21:09,397 CAN EVEN BEGIN LATER IN LIFE. 629 00:21:09,397 --> 00:21:12,567 SO REALLY CROSSING THE WHOLE 630 00:21:12,567 --> 00:21:17,138 CONTEXT OF HUMAN HEALTH. 631 00:21:17,138 --> 00:21:19,340 SO WHEN I TALK ABOUT AUTOIMMUNE 632 00:21:19,340 --> 00:21:20,208 DISEASES, WE REALLY HAVE TO 633 00:21:20,208 --> 00:21:22,276 THINK ABOUT HOW IS THE IMMUNE 634 00:21:22,276 --> 00:21:24,278 SYSTEM INVOLVED AND SO FOR 635 00:21:24,278 --> 00:21:25,246 IMMUNOLOGISTS LIKE MYSELF, WE 636 00:21:25,246 --> 00:21:26,347 NEED TO THINK ABOUT THE 637 00:21:26,347 --> 00:21:27,882 STRUCTURES THAT ARE DRIVING 638 00:21:27,882 --> 00:21:29,951 AUTOIMMUNITY. 639 00:21:29,951 --> 00:21:31,819 I'M A T-CELL IMMUNOLOGIST SO I'M 640 00:21:31,819 --> 00:21:33,788 SHOWING YOU A FIGURE THAT 641 00:21:33,788 --> 00:21:35,656 EMPHASIZES T CELLS AND CLEARLY 642 00:21:35,656 --> 00:21:36,958 THAT'S NOT THE ONLY THING 643 00:21:36,958 --> 00:21:37,825 INVOLVED, BUT WHAT WE THINK 644 00:21:37,825 --> 00:21:39,160 ABOUT IS WE KNOW THAT T CELLS 645 00:21:39,160 --> 00:21:41,662 ARE REALLY KIND OF THE GUIDING 646 00:21:41,662 --> 00:21:43,397 FORCE OF THE IMMUNE RESPONSE, 647 00:21:43,397 --> 00:21:45,600 GIVING US A VERY TARGETED 648 00:21:45,600 --> 00:21:47,134 SPECIFIC RESPONSE, HELPING 649 00:21:47,134 --> 00:21:50,404 PROTECT US FROM VIRUSES, 650 00:21:50,404 --> 00:21:53,574 BACTERIA, CANCERS. 651 00:21:53,574 --> 00:21:55,877 AND WHAT HAPPENS IN AUTOIMMUNITY 652 00:21:55,877 --> 00:21:59,146 IS THAT THESE T CELLS THAT ARE 653 00:21:59,146 --> 00:22:03,084 SPECIFIC FOR SELF ANTIGEN BECOME 654 00:22:03,084 --> 00:22:04,619 ACTIVATED AND THEN START DRIVING 655 00:22:04,619 --> 00:22:05,186 THE AUTOIMMUNE RESPONSE. 656 00:22:05,186 --> 00:22:07,455 IT HELPS PROMOTE THE DEVELOPMENT 657 00:22:07,455 --> 00:22:08,890 OF AUTOANTIBODIES, WHICH ARE THE 658 00:22:08,890 --> 00:22:12,727 COMMON MARKER WE USE FOR 659 00:22:12,727 --> 00:22:13,694 AUTOIMMUNITY AND WHICH CAN 660 00:22:13,694 --> 00:22:15,129 DIRECTLY DRIVE DISEASE, BUT ALSO 661 00:22:15,129 --> 00:22:17,765 THESE T CELLS MAY PROMOTE 662 00:22:17,765 --> 00:22:18,733 INFLAMMATION, BRINGING OTHER 663 00:22:18,733 --> 00:22:21,469 CELLS TO A TISSUE AND THEN 664 00:22:21,469 --> 00:22:24,639 CAUSING DAMAGE. 665 00:22:24,639 --> 00:22:25,740 SO TODAY WE'RE GOING TO TALK A 666 00:22:25,740 --> 00:22:27,475 LITTLE BIT ABOUT CERTAIN ASPECTS 667 00:22:27,475 --> 00:22:29,010 OF THIS PATHWAY AND HOW WE CAN 668 00:22:29,010 --> 00:22:31,546 UNDERSTAND IT BETTER. 669 00:22:31,546 --> 00:22:34,715 NOW, WHEN WE THINK ABOUT 670 00:22:34,715 --> 00:22:35,783 AUTOIMMUNITY AS A FAILURE OF 671 00:22:35,783 --> 00:22:37,552 IMMUNE TOLERANCE, ONE OF THE 672 00:22:37,552 --> 00:22:40,755 ISSUES IS THAT THESE ARE 673 00:22:40,755 --> 00:22:43,157 DISEASES THAT OCCUR OVER TIME. 674 00:22:43,157 --> 00:22:45,226 SO THE MAJORITY OF PEOPLE ARE 675 00:22:45,226 --> 00:22:48,195 HEALTHY INITIALLY, BUT THEN AT 676 00:22:48,195 --> 00:22:49,430 SOME POINT, THERE IS A TRIGGER 677 00:22:49,430 --> 00:22:51,365 THAT LEADS TO IMMUNE 678 00:22:51,365 --> 00:22:51,799 DYSREGULATION. 679 00:22:51,799 --> 00:22:54,001 WE TYPICALLY IDENTIFY THOSE 680 00:22:54,001 --> 00:22:56,737 INDIVIDUALS AS HAVING 681 00:22:56,737 --> 00:22:57,505 AUTOANTIBODIES. 682 00:22:57,505 --> 00:22:59,440 THEY DO NOT YET FEEL ILL, THEY 683 00:22:59,440 --> 00:23:00,875 DO NOT YET HAVE INFLAMMATION IN 684 00:23:00,875 --> 00:23:02,310 ANY OF THEIR TISSUES, BUT THEN 685 00:23:02,310 --> 00:23:04,278 THEY WILL GO ON TO START 686 00:23:04,278 --> 00:23:05,479 DEVELOPING DISEASE, DEVELOP 687 00:23:05,479 --> 00:23:07,315 TISSUE INFLAMMATION, AND THEN 688 00:23:07,315 --> 00:23:08,749 OVER TIME, BECAUSE THESE ARE 689 00:23:08,749 --> 00:23:10,484 CHRONIC DISEASES, THERE'S A 690 00:23:10,484 --> 00:23:13,120 PERPETUATION OF THAT 691 00:23:13,120 --> 00:23:14,655 INFLAMMATION, TISSUE 692 00:23:14,655 --> 00:23:15,756 DESTRUCTION, AND EVEN SOMETIMES 693 00:23:15,756 --> 00:23:17,391 MORE SYSTEMIC EFFECTS. 694 00:23:17,391 --> 00:23:19,360 SO THERE'S REALLY A TIMELINE IN 695 00:23:19,360 --> 00:23:20,995 TERMS OF DEVELOPING AUTOIMMUNE 696 00:23:20,995 --> 00:23:24,699 DISEASES. 697 00:23:24,699 --> 00:23:25,700 THEN WHEN WE TRY TO UNDERSTAND 698 00:23:25,700 --> 00:23:26,901 WHAT ARE THE FACTORS THAT ARE 699 00:23:26,901 --> 00:23:27,668 PARTICIPATING IN THE 700 00:23:27,668 --> 00:23:29,003 DEVELOPMENT, WHY DO SOME PEOPLE 701 00:23:29,003 --> 00:23:31,272 GET THESE DISEASES AND OTHERS 702 00:23:31,272 --> 00:23:33,574 NOT, WE KNOW GENETICS IS A 703 00:23:33,574 --> 00:23:34,008 FACTOR. 704 00:23:34,008 --> 00:23:36,110 AUTOIMMUNE DISEASES RUN IN 705 00:23:36,110 --> 00:23:36,877 FAMILIES, SOMETIMES IT'S THE 706 00:23:36,877 --> 00:23:38,512 SAME DISEASE, BUT FREQUENTLY 707 00:23:38,512 --> 00:23:40,514 WE'LL SEE FAMILIES WHERE ONE 708 00:23:40,514 --> 00:23:43,651 INDIVIDUAL MIGHT HAVE RHEUMATOID 709 00:23:43,651 --> 00:23:44,952 ARTHRITIS, A CHILD OF THAT 710 00:23:44,952 --> 00:23:46,387 PARENT MIGHT HAVE TYPE 711 00:23:46,387 --> 00:23:48,356 1 DIABETES AND SOMEONE'S SISTER 712 00:23:48,356 --> 00:23:48,889 HAS THYROID DISEASE. 713 00:23:48,889 --> 00:23:50,524 WHEN I'M IN CLINIC, I HEAR THIS 714 00:23:50,524 --> 00:23:54,362 STORY EVERY WEEK. 715 00:23:54,362 --> 00:23:55,329 SO WE KNOW GENETICS IS 716 00:23:55,329 --> 00:23:56,764 IMPORTANT, IT SETS YOU UP 717 00:23:56,764 --> 00:23:57,999 POTENTIALLY FOR AUTOIMMUNITY. 718 00:23:57,999 --> 00:23:59,467 WE ALSO KNOW IT'S NOT THE ONLY 719 00:23:59,467 --> 00:24:00,835 FACTOR. 720 00:24:00,835 --> 00:24:02,570 IDENTICAL TWINS, ONLY ABOUT 50% 721 00:24:02,570 --> 00:24:04,205 WILL BOTH HAVE AN AUTOIMMUNE 722 00:24:04,205 --> 00:24:04,538 DISEASE. 723 00:24:04,538 --> 00:24:07,274 SO OTHER FACTORS ARE INVOLVED 724 00:24:07,274 --> 00:24:08,576 AND WE KNOW THOSE TEND TO BE 725 00:24:08,576 --> 00:24:11,212 ENVIRONMENTAL FACTORS. 726 00:24:11,212 --> 00:24:14,615 EXPOSURES TO INFECTIONS, 727 00:24:14,615 --> 00:24:18,085 INJURIES, LIFESTYLE STRESS, 728 00:24:18,085 --> 00:24:20,287 CHEMICALS, A CLASSIC EXAMPLE IS 729 00:24:20,287 --> 00:24:21,355 CIGARETTE SMOKING WHERE IF YOU 730 00:24:21,355 --> 00:24:24,325 HAVE THE GENETIC RISK FOR 731 00:24:24,325 --> 00:24:25,760 RHEUMATOID ARTHRITIS, YOU HAVE A 732 00:24:25,760 --> 00:24:27,495 50% GREATER CHANCE OF GETTING 733 00:24:27,495 --> 00:24:28,596 R.A. IF YOU'RE A SMOKER. 734 00:24:28,596 --> 00:24:30,131 SO THE ENVIRONMENT IS REALLY 735 00:24:30,131 --> 00:24:30,464 IMPORTANT. 736 00:24:30,464 --> 00:24:33,234 AND THEN I ALWAYS ADD IN TIME, 737 00:24:33,234 --> 00:24:37,138 BECAUSE AGE, MATURATION, AND 738 00:24:37,138 --> 00:24:39,006 OTHER COMORBIDITIES ALSO 739 00:24:39,006 --> 00:24:42,176 INFLUENCE THE DEVELOPMENT OF 740 00:24:42,176 --> 00:24:43,077 AUTOIMMUNITY AND THEN OF COURSE 741 00:24:43,077 --> 00:24:48,182 THE OUTCOME OF THOSE DISEASES. 742 00:24:48,182 --> 00:24:49,383 SO THE KEY QUESTIONS WE NEED TO 743 00:24:49,383 --> 00:24:51,485 ASK TO UNDERSTAND AUTOIMMUNITY 744 00:24:51,485 --> 00:24:53,421 IS REALLY WHAT FACTORS INITIATE 745 00:24:53,421 --> 00:24:54,755 AND PERPETUATE AUTOIMMUNE 746 00:24:54,755 --> 00:24:55,623 DISEASES. 747 00:24:55,623 --> 00:24:57,324 AND TO DO THAT, WE CAN LOOK AT 748 00:24:57,324 --> 00:25:00,428 THE IMMUNE FEATURES THAT 749 00:25:00,428 --> 00:25:01,295 DIFFERENTIATE INDIVIDUALS WITH 750 00:25:01,295 --> 00:25:04,799 AUTOIMMUNITY FROM THOSE WITHOUT 751 00:25:04,799 --> 00:25:05,466 AUTOIMMUNITY. 752 00:25:05,466 --> 00:25:06,901 THEN ONCE WE IDENTIFY WHAT'S 753 00:25:06,901 --> 00:25:08,202 DIFFERENT, ASK WHAT MECHANISMS 754 00:25:08,202 --> 00:25:09,503 ARE LEADING TO THESE DIFFERENCES 755 00:25:09,503 --> 00:25:12,673 AND THEN ULTIMATELY CAN WE 756 00:25:12,673 --> 00:25:16,277 INTERVENE TO TREAT THESE 757 00:25:16,277 --> 00:25:17,611 MECHANISMS, PREVENT AND CURE 758 00:25:17,611 --> 00:25:20,114 DISEASE. 759 00:25:20,114 --> 00:25:22,316 SO OVER THE LAST 20 YEARS SINCE 760 00:25:22,316 --> 00:25:24,051 I'VE BEEN STUDYING AUTOIMMUNE 761 00:25:24,051 --> 00:25:26,454 DISEASES, I THINK WE'VE 762 00:25:26,454 --> 00:25:27,655 DEVELOPED A PARADIGM FOR 763 00:25:27,655 --> 00:25:29,623 ADVANCING OUR UNDERSTANDING OF 764 00:25:29,623 --> 00:25:31,592 THESE DISEASES AND PARTICULARLY 765 00:25:31,592 --> 00:25:34,328 A PARADIGM THAT ALLOWS US TO 766 00:25:34,328 --> 00:25:35,963 MOVE INTO PATIENTS. 767 00:25:35,963 --> 00:25:38,365 AS A PHYSICIAN, MY GOAL HAS 768 00:25:38,365 --> 00:25:41,235 ALWAYS BEEN TO UNDERSTAND MY 769 00:25:41,235 --> 00:25:42,436 PATIENTS AND WHAT'S DRIVING 770 00:25:42,436 --> 00:25:45,406 THEIR DISEASE. 771 00:25:45,406 --> 00:25:46,474 SO THERE'S CHALLENGES AROUND 772 00:25:46,474 --> 00:25:47,975 THAT BECAUSE STUDYING HUMAN 773 00:25:47,975 --> 00:25:49,777 BEINGS IS COMPLICATED. 774 00:25:49,777 --> 00:25:51,278 SO THIS PARADIGM REALLY STARTS 775 00:25:51,278 --> 00:25:52,713 WITH THE GENERATION OF 776 00:25:52,713 --> 00:25:54,215 HYPOTHESES. 777 00:25:54,215 --> 00:25:56,217 MODEL SYSTEMS CAN BE REALLY 778 00:25:56,217 --> 00:25:59,053 POWERFUL IN HELPING US DEVELOP A 779 00:25:59,053 --> 00:26:00,254 BETTER UNDERSTANDING OF THE 780 00:26:00,254 --> 00:26:01,889 IMMUNE SYSTEM AND THEN 781 00:26:01,889 --> 00:26:03,023 UNDERSTAND HOW CHANGES IN THE 782 00:26:03,023 --> 00:26:05,392 IMMUNE SYSTEM COULD DRIVE 783 00:26:05,392 --> 00:26:06,393 AUTOIMMUNITY. 784 00:26:06,393 --> 00:26:07,695 ADDITIONALLY, WE CAN STUDY 785 00:26:07,695 --> 00:26:08,896 UNIQUE POPULATIONS. 786 00:26:08,896 --> 00:26:10,531 POPULATIONS WHERE THERE MAY BE A 787 00:26:10,531 --> 00:26:14,568 SINGLE GENE MUTATION THAT DRIVES 788 00:26:14,568 --> 00:26:15,269 AUTOIMMUNITY OR GROUPS THAT WE 789 00:26:15,269 --> 00:26:18,839 KNOW HAVE INCREASED RISK FOR 790 00:26:18,839 --> 00:26:20,508 AUTOIMMUNITY. 791 00:26:20,508 --> 00:26:21,642 THEN AS WE LEARN MORE ABOUT 792 00:26:21,642 --> 00:26:23,978 GENES AND THE GENETIC RISK, THAT 793 00:26:23,978 --> 00:26:27,047 HAS BEEN AN AREA THAT HAS REALLY 794 00:26:27,047 --> 00:26:29,884 HELPED US DEVELOP HYPOTHESES 795 00:26:29,884 --> 00:26:31,519 THAT WE CAN THEN GO AND TEST 796 00:26:31,519 --> 00:26:32,086 GROUPS OF PATIENTS. 797 00:26:32,086 --> 00:26:33,420 SO DEVELOPING COHORTS IS REALLY 798 00:26:33,420 --> 00:26:36,390 IMPORTANT. 799 00:26:36,390 --> 00:26:37,124 AND ONE OF THE THINGS THAT IS 800 00:26:37,124 --> 00:26:38,526 VERY IMPORTANT HERE IS NOT JUST 801 00:26:38,526 --> 00:26:40,961 GETTING GROUPS OF PATIENTS WITH 802 00:26:40,961 --> 00:26:42,263 A DISEASE YOU'RE INTERESTED IN, 803 00:26:42,263 --> 00:26:44,999 BUT HAVING A CONTROL POPULATION 804 00:26:44,999 --> 00:26:47,501 TO LOOK AT TO COMPARE THEM TO. 805 00:26:47,501 --> 00:26:49,804 PEOPLE WHO ARE SIMILAR IN AGE, 806 00:26:49,804 --> 00:26:58,679 IN SEX, IN THEIR BACKGROUND AS 807 00:26:58,679 --> 00:27:00,414 WELL,, IS IMPORTANT FOR US SO 808 00:27:00,414 --> 00:27:01,282 DEVELOPING THESE COHORTS HAS 809 00:27:01,282 --> 00:27:02,616 BEEN A PROJECT MANY OF US HAVE 810 00:27:02,616 --> 00:27:03,751 BEEN ENGAGED IN OVER THE LAST 20 811 00:27:03,751 --> 00:27:06,554 YEARS AND I THINK IT BECOME VERY 812 00:27:06,554 --> 00:27:08,622 NOTABLE IN HOW IT HELPS US STUDY 813 00:27:08,622 --> 00:27:08,989 HUMAN DISEASE. 814 00:27:08,989 --> 00:27:11,225 SO WE HAVE A HYPOTHESIS, WE HAVE 815 00:27:11,225 --> 00:27:12,760 A COHORT OF INDIVIDUALS TO STUDY 816 00:27:12,760 --> 00:27:16,497 AND THEN WE CAN ASSESS DIFFERENT 817 00:27:16,497 --> 00:27:19,767 IMMUNOLOGIC PATHWAYS TO 818 00:27:19,767 --> 00:27:21,635 UNDERSTAND IF THESE -- THIS 819 00:27:21,635 --> 00:27:23,504 HYPOTHESIS WE HAVE IS TRUE. 820 00:27:23,504 --> 00:27:25,673 THEN WHAT'S REALLY USEFUL ONCE 821 00:27:25,673 --> 00:27:27,741 WE IDENTIFY PATHWAYS THAT ARE 822 00:27:27,741 --> 00:27:29,844 ALTERED IN INDIVIDUALS WITH AN 823 00:27:29,844 --> 00:27:30,911 AUTOIMMUNE DISEASE IS TO ASK 824 00:27:30,911 --> 00:27:33,547 SOME ADDITIONAL QUESTIONS. 825 00:27:33,547 --> 00:27:34,882 AND ONE OF MY FAVORITE QUESTIONS 826 00:27:34,882 --> 00:27:37,251 IS TO SAY, IS THIS FEATURE 827 00:27:37,251 --> 00:27:38,252 SHARED ACROSS AUTOIMMUNE 828 00:27:38,252 --> 00:27:38,519 DISEASES? 829 00:27:38,519 --> 00:27:41,222 IS THIS SOMETHING THAT WE CAN 830 00:27:41,222 --> 00:27:42,523 EXPAND BEYOND? 831 00:27:42,523 --> 00:27:43,724 SO HAVING OTHER POPULATIONS TO 832 00:27:43,724 --> 00:27:45,025 COMPARE TO, AND THAT HELPS US 833 00:27:45,025 --> 00:27:46,794 THINK DOWN THE ROAD ABOUT WHO TO 834 00:27:46,794 --> 00:27:47,461 TREAT. 835 00:27:47,461 --> 00:27:49,730 WE CAN LOOK AT DISEASE 836 00:27:49,730 --> 00:27:50,397 EVOLUTION. 837 00:27:50,397 --> 00:27:51,832 LOOKING AT INDIVIDUALS WHO ARE 838 00:27:51,832 --> 00:27:54,768 AT RISK, MAYBE FAMILY MEMBERS OF 839 00:27:54,768 --> 00:27:56,303 INDIVIDUALS WITH AUTOIMMUNITY, 840 00:27:56,303 --> 00:27:57,504 AND FOLLOW THEM OVER TIME AS 841 00:27:57,504 --> 00:27:58,906 THEY DEVELOP AN AUTOIMMUNE 842 00:27:58,906 --> 00:27:59,139 DISEASE. 843 00:27:59,139 --> 00:28:00,341 THAT HELPS US KNOW ONCE WE HAVE 844 00:28:00,341 --> 00:28:01,675 A TREATMENT WHEN TO TREAT 845 00:28:01,675 --> 00:28:04,144 PATIENTS. 846 00:28:04,144 --> 00:28:05,379 AND THEN WE ALSO CAN NOW TAKE 847 00:28:05,379 --> 00:28:09,416 ADVANTAGE OF WHAT I CALL IN VIVO 848 00:28:09,416 --> 00:28:09,884 INTERVENTIONS. 849 00:28:09,884 --> 00:28:11,285 THAT MAY BE A CLINICAL TRIAL 850 00:28:11,285 --> 00:28:13,487 WHERE WE DRAW EXTRA SAMPLES AND 851 00:28:13,487 --> 00:28:14,588 TRY TO LOOK AT HOW WE'RE 852 00:28:14,588 --> 00:28:16,123 CHANGING THE IMMUNE SYSTEM. 853 00:28:16,123 --> 00:28:18,926 OR IT MAY BE A STUDY WHERE WE 854 00:28:18,926 --> 00:28:20,461 VERY SPECIFICALLY ASK 855 00:28:20,461 --> 00:28:21,295 INDIVIDUALS TO PARTICIPATE WHERE 856 00:28:21,295 --> 00:28:23,664 WE CAN INTERVENE, GIVE A 857 00:28:23,664 --> 00:28:25,299 VACCINATION, USE A SPECIFIC 858 00:28:25,299 --> 00:28:27,468 DRUG, AND SEE HOW WE'VE CHANGED 859 00:28:27,468 --> 00:28:28,002 THEIR IMMUNE RESPONSE. 860 00:28:28,002 --> 00:28:29,436 AND THAT REALLY HELPS US START 861 00:28:29,436 --> 00:28:31,105 THINKING ABOUT HOW TO TREAT. 862 00:28:31,105 --> 00:28:32,306 I'M GOING TO TRY TO TOUCH ON 863 00:28:32,306 --> 00:28:35,676 EACH OF THESE APPROACHES TODAY. 864 00:28:35,676 --> 00:28:37,778 SO TO START WITH, I THOUGHT I'D 865 00:28:37,778 --> 00:28:39,847 TALK ABOUT REALLY HOW GENETICS 866 00:28:39,847 --> 00:28:44,985 CAN TEACH US ABOUT AUTOIMMUNITY. 867 00:28:44,985 --> 00:28:46,954 AND FOLLOW THIS PATHWAY AND SHOW 868 00:28:46,954 --> 00:28:48,923 YOU HOW UNDERSTANDING ONE SET OF 869 00:28:48,923 --> 00:28:51,225 GENES HAS LED MY GROUP ACTUALLY 870 00:28:51,225 --> 00:28:56,363 TO DEVELOPING A THERAPEUTIC. 871 00:28:56,363 --> 00:28:58,399 SO THE GENOME-WIDE ASSOCIATION 872 00:28:58,399 --> 00:29:00,067 STUDIES WERE PERFORMED IN THE 873 00:29:00,067 --> 00:29:01,502 EARLY 2000s. 874 00:29:01,502 --> 00:29:03,570 AND THOSE STUDIES DEMONSTRATED A 875 00:29:03,570 --> 00:29:06,073 WHOLE SERIES OF GENE OR GENE 876 00:29:06,073 --> 00:29:08,175 REGIONS THAT WERE ASSOCIATED 877 00:29:08,175 --> 00:29:09,043 WITH AUTOIMMUNITY. 878 00:29:09,043 --> 00:29:11,011 SOME PEOPLE WERE DISAPPOINTED 879 00:29:11,011 --> 00:29:12,313 BECAUSE THERE WEREN'T JUST A FEW 880 00:29:12,313 --> 00:29:13,614 GENES, THERE WERE ACTUALLY 881 00:29:13,614 --> 00:29:15,382 HUNDREDS OF GENES. 882 00:29:15,382 --> 00:29:17,584 BUT ONE COULD LOOK AT THE 883 00:29:17,584 --> 00:29:19,119 GENETIC RISK AND HERE'S SHOWING 884 00:29:19,119 --> 00:29:22,156 SOME OF THE GENES THAT WERE 885 00:29:22,156 --> 00:29:23,557 ASSOCIATED WITH TYPE 1 DIABETES. 886 00:29:23,557 --> 00:29:25,092 IN PURPLE, THOSE WERE GENES 887 00:29:25,092 --> 00:29:28,929 INVOLVED THE IN THE IMMUNE SYSM 888 00:29:28,929 --> 00:29:29,596 AND ITS FUNCTION. 889 00:29:29,596 --> 00:29:31,231 SO I WAS PLEASED TO SEE AS AN 890 00:29:31,231 --> 00:29:35,069 EARLY INVESTIGATOR THAT BEING AN 891 00:29:35,069 --> 00:29:36,937 IMMUNOLOGIST AND STUDYING 892 00:29:36,937 --> 00:29:37,471 AUTOIMMUNITY MADE SENSE. 893 00:29:37,471 --> 00:29:41,108 SO THIS IS A STORY ABOUT ONE 894 00:29:41,108 --> 00:29:42,509 GENE CALLED PTPN2. 895 00:29:42,509 --> 00:29:44,044 THEY'RE ALL INVOLVED IN 896 00:29:44,044 --> 00:29:44,378 IL2 SIGNALING. 897 00:29:44,378 --> 00:29:47,548 SO THE GWAS IN TYPE 1 DIABETES 898 00:29:47,548 --> 00:29:49,083 BASICALLY PUT AN ARROW POINTING 899 00:29:49,083 --> 00:29:50,284 AT IL2 AND WE NEEDED TO 900 00:29:50,284 --> 00:29:52,386 UNDERSTAND IT. 901 00:29:52,386 --> 00:29:54,955 SO PTPN2 IS ACTUALLY INVOLVED IN 902 00:29:54,955 --> 00:29:56,757 THE INHIBITION OF THE 903 00:29:56,757 --> 00:29:58,926 IL2 SIGNALING PATHWAY, AND 904 00:29:58,926 --> 00:30:01,228 IL2 IS VITAL TO THE GROWTH AND 905 00:30:01,228 --> 00:30:03,731 SURVIVAL O OF T CELLS BUT 906 00:30:03,731 --> 00:30:04,965 SPECIFICALLY TO REGULATORY T 907 00:30:04,965 --> 00:30:06,800 CELLS. 908 00:30:06,800 --> 00:30:10,971 SO WE CAN STUDY THE ROLE OF 909 00:30:10,971 --> 00:30:12,373 IL2 SIGNALING AND HOW THE 910 00:30:12,373 --> 00:30:14,375 VARIANTS ARE INVOLVED BY LOOKING 911 00:30:14,375 --> 00:30:18,512 AT SIGNALING IN T CELLS. 912 00:30:18,512 --> 00:30:20,047 SO WHAT WE DID EARLY ON WAS WE 913 00:30:20,047 --> 00:30:22,216 HAD A GROUP OF WHAT WE 914 00:30:22,216 --> 00:30:23,751 CONSIDERED HEALTHY CONTROL 915 00:30:23,751 --> 00:30:24,752 INDIVIDUALS. 916 00:30:24,752 --> 00:30:27,054 THESE INDIVIDUALS DID NOT HAVE 917 00:30:27,054 --> 00:30:28,856 ANY CHRONIC CONDITIONS, DID NOT 918 00:30:28,856 --> 00:30:29,990 HAVE ANY AUTOIMMUNE DISEASES, 919 00:30:29,990 --> 00:30:32,393 AND IMPORTANTLY, DIDN'T HAVE ANY 920 00:30:32,393 --> 00:30:33,494 FIRST DEGREE RELATIVES WITH 921 00:30:33,494 --> 00:30:34,228 AUTOIMMUNITY. 922 00:30:34,228 --> 00:30:37,231 SO THEY WERE NOT GENETICALLY 923 00:30:37,231 --> 00:30:38,766 ENRICHED FOR AUTOIMMUNITY. 924 00:30:38,766 --> 00:30:40,634 BUT WE WERE ABLE TO LOOK FOR 925 00:30:40,634 --> 00:30:42,803 THESE GENETIC VARIANTS THAT WERE 926 00:30:42,803 --> 00:30:43,804 ASSOCIATED WITH AUTOIMMUNITY IN 927 00:30:43,804 --> 00:30:45,239 THESE INDIVIDUALS, BECAUSE 928 00:30:45,239 --> 00:30:46,407 THEY'RE COMMON VARIANTS. 929 00:30:46,407 --> 00:30:49,810 SO WHAT I'M SHOWING HERE ON THE 930 00:30:49,810 --> 00:30:53,047 LEFT IS LOOKING AT THE RESPONSE 931 00:30:53,047 --> 00:30:55,182 TO IL2, WE MEASURE THAT AS 932 00:30:55,182 --> 00:30:58,152 PERCENT OF PHOSPHORYLATED STAT5 933 00:30:58,152 --> 00:30:59,787 IN THIS COHORT OF HEALTHY 934 00:30:59,787 --> 00:31:01,055 CONTROLS. 935 00:31:01,055 --> 00:31:04,792 AND WHEN WE LOOK AT THIS, THE 936 00:31:04,792 --> 00:31:06,460 C/C WITH THE STARS ARE 937 00:31:06,460 --> 00:31:07,528 INDIVIDUALS HOMOZYGOUS FOR THE 938 00:31:07,528 --> 00:31:08,328 RISK VARIANT. 939 00:31:08,328 --> 00:31:10,597 AND WE CAN COMPARE THEM TO THE 940 00:31:10,597 --> 00:31:15,936 TT GRO/T GROUP IN BLACK, HOMOZYS 941 00:31:15,936 --> 00:31:16,837 FOR THE NON-RISK. 942 00:31:16,837 --> 00:31:18,472 YOU CAN SEE THERE'S A VERY 943 00:31:18,472 --> 00:31:19,073 SIGNIFICANT DIFFERENCE IN THE 944 00:31:19,073 --> 00:31:20,441 ABILITY TO RESPOND TO 945 00:31:20,441 --> 00:31:22,976 IL2 BETWEEN THE NON-RISK GROUP 946 00:31:22,976 --> 00:31:24,812 AND THE RISK GROUP, AND THEN THE 947 00:31:24,812 --> 00:31:26,146 INDIVIDUALS WHO WERE 948 00:31:26,146 --> 00:31:29,516 HETEROZYGOUS FOR RISK SHOWED AN 949 00:31:29,516 --> 00:31:30,517 INTERMEDIATE PHENOTYPE. 950 00:31:30,517 --> 00:31:32,686 SO SUGGESTING THAT IMPAIRED 951 00:31:32,686 --> 00:31:35,122 RESPONSES TO IL2 IN T CELLS IS 952 00:31:35,122 --> 00:31:37,191 ASSOCIATED WITH THIS GENETIC 953 00:31:37,191 --> 00:31:38,058 RISK VARIANT. 954 00:31:38,058 --> 00:31:39,827 NOW, WHEN WE STUDY 955 00:31:39,827 --> 00:31:41,261 CHARACTERISTICS OF THE IMMUNE 956 00:31:41,261 --> 00:31:42,963 SYSTEM IN INDIVIDUALS, SOME 957 00:31:42,963 --> 00:31:46,033 THINGS VARY WIDELY, DEPENDING ON 958 00:31:46,033 --> 00:31:49,636 THE DAY, THE WEEK AND WHAT 959 00:31:49,636 --> 00:31:51,105 INFECTION YOU HAD RECENTLY. 960 00:31:51,105 --> 00:31:52,706 AND THINGS THAT ARE GENETICALLY 961 00:31:52,706 --> 00:31:54,708 DRIVEN SHOULD ACTUALLY BE VERY 962 00:31:54,708 --> 00:31:55,242 CONSISTENT OVER TIME. 963 00:31:55,242 --> 00:31:57,444 SO WHAT WE'RE ABLE TO DO WITH 964 00:31:57,444 --> 00:31:59,713 OUR COHORTS WHERE WE HAVE 965 00:31:59,713 --> 00:32:01,482 SAMPLES DRAWN AT TWO DIFFERENT 966 00:32:01,482 --> 00:32:03,016 TIME POINTS, IN THIS CASE, 967 00:32:03,016 --> 00:32:05,619 MONTHS TO YEARS APART, WE CAN DO 968 00:32:05,619 --> 00:32:10,324 THE SAME ASSAY WITH THOSE TWO 969 00:32:10,324 --> 00:32:10,991 SAMPLES FROM THE SAME 970 00:32:10,991 --> 00:32:12,626 INDIVIDUALS AND AS YOU CAN SEE 971 00:32:12,626 --> 00:32:14,061 THERE'S A REALLY BEAUTIFUL 972 00:32:14,061 --> 00:32:16,130 LINEAR CORRELATION FOR THE 973 00:32:16,130 --> 00:32:18,866 RESPONSE TO IL2 AND VERY 974 00:32:18,866 --> 00:32:20,667 CONSISTENT IN AN INDIVIDUAL BUT 975 00:32:20,667 --> 00:32:25,205 DIFFERENT BASED ON GENOTYPE. 976 00:32:25,205 --> 00:32:28,509 SO THIS SUGGESTED TO US THAT 977 00:32:28,509 --> 00:32:29,943 IMPAIRED IL2 RESPONSES MAY BE 978 00:32:29,943 --> 00:32:32,880 IMPORTANT IN TYPE 1 DIABETES. 979 00:32:32,880 --> 00:32:35,415 SO TO ASK THAT QUESTION, WE TOOK 980 00:32:35,415 --> 00:32:37,684 OUR CONTROL COHORT WITH A GROUP 981 00:32:37,684 --> 00:32:40,320 OF INDIVIDUALS WITH TYPE 982 00:32:40,320 --> 00:32:41,321 1 DIABETES AND LACKED AT THEIR 983 00:32:41,321 --> 00:32:46,693 LOOKED AT THEIRABILITY TO RESPO. 984 00:32:46,693 --> 00:32:47,828 ON THE LEFT YOU CAN SEE THE SAME 985 00:32:47,828 --> 00:32:50,197 MEASURE, PERCENT OF PHOSPHO 986 00:32:50,197 --> 00:32:51,932 STAT5 IN RESPONSE TO IL2 AND THE 987 00:32:51,932 --> 00:32:53,467 CONTROLS ARE IN BLACK AND THE 988 00:32:53,467 --> 00:32:54,368 TYPE 1 DIABETIC INDIVIDUALS ARE 989 00:32:54,368 --> 00:32:54,768 IN BLUE. 990 00:32:54,768 --> 00:32:55,869 NOW THERE'S A SIGNIFICANTLY 991 00:32:55,869 --> 00:32:58,238 LOWER RESPONSE TO IL2 OVERALL 992 00:32:58,238 --> 00:33:01,875 THAT BUT YOU CAN SEE ACROSS 993 00:33:01,875 --> 00:33:03,210 INDIVIDUALS THERE'S QUITE A 994 00:33:03,210 --> 00:33:03,544 VARIATION. 995 00:33:03,544 --> 00:33:04,578 SO THEN WE WANTED TO SAY HOW 996 00:33:04,578 --> 00:33:09,449 MUCH OF THIS IS DUE TO THE GENE 997 00:33:09,449 --> 00:33:10,417 PTPN2, SO THEN WE'RE ABLE TO 998 00:33:10,417 --> 00:33:12,286 COMPARE THE T/T CONTROLS, THOSE 999 00:33:12,286 --> 00:33:13,387 ARE HEALTHY INDIVIDUALS WHO 1000 00:33:13,387 --> 00:33:17,558 DON'T CARRY THE RISK, SO 1001 00:33:17,558 --> 00:33:19,493 INDIVIDUALS WHO ARE T/T 1002 00:33:19,493 --> 00:33:21,662 DIABETICS, AND YOU CAN SEE THAT 1003 00:33:21,662 --> 00:33:23,530 THEY'RE ALREADY DIFFERENT, EVEN 1004 00:33:23,530 --> 00:33:24,865 THOUGH THAT GENETIC RISK IS NOT 1005 00:33:24,865 --> 00:33:25,499 THERE. 1006 00:33:25,499 --> 00:33:27,034 WHEN WE LOOK WITHIN THE 1007 00:33:27,034 --> 00:33:30,337 DIABETICS, WE CAN TELL THAT 1008 00:33:30,337 --> 00:33:32,973 PTPN2 DOES EVEN FURTHER BLUNT 1009 00:33:32,973 --> 00:33:33,941 IL2 SIGNALING, BUT BY DOING THE 1010 00:33:33,941 --> 00:33:35,609 STUDY IN THIS WAY, WE'RE ABLE TO 1011 00:33:35,609 --> 00:33:37,544 KNOW THAT NOT THIS ONE SINGLE 1012 00:33:37,544 --> 00:33:40,113 GENE ALONE IS CAUSING THE 1013 00:33:40,113 --> 00:33:42,149 BLUNTED IL2 SIGNALING, BUT IT'S 1014 00:33:42,149 --> 00:33:43,750 A MORE COMMON CHARACTERISTIC 1015 00:33:43,750 --> 00:33:45,686 LIKELY DUE TO A COMBINATION OF 1016 00:33:45,686 --> 00:33:47,187 GENETIC RISK VARIANTS, ALL OF 1017 00:33:47,187 --> 00:33:52,459 WHICH AFFECT THE IL2 PATHWAY. 1018 00:33:52,459 --> 00:33:54,328 SO GENETICS IS GREAT, SHOWING 1019 00:33:54,328 --> 00:33:56,396 YOU PHOSPHO STAT5 SIGNALING IS 1020 00:33:56,396 --> 00:33:57,831 NICE, BUT IT REALLY DOESN'T TELL 1021 00:33:57,831 --> 00:34:00,033 US WHAT'S GOING ON IN THE IMMUNE 1022 00:34:00,033 --> 00:34:01,568 SYSTEM, AND SINCE AS I NOTED 1023 00:34:01,568 --> 00:34:04,738 BEFORE THAT IL2 IS REALLY VITAL 1024 00:34:04,738 --> 00:34:07,708 TO THE SURVIVAL AND FUNCTION OF 1025 00:34:07,708 --> 00:34:09,543 REGULATORY T CELLS, WHICH WE 1026 00:34:09,543 --> 00:34:12,613 KNOW ARE VITAL TO CONTROLLING 1027 00:34:12,613 --> 00:34:13,914 AUTOIMMUNITY, WE WANTED TO ASK 1028 00:34:13,914 --> 00:34:15,882 NEXT, WHAT HAPPENS IF YOU'RE AN 1029 00:34:15,882 --> 00:34:19,620 INDIVIDUAL WHO HAS IMPAIRED 1030 00:34:19,620 --> 00:34:19,953 IL2 RESPONSES? 1031 00:34:19,953 --> 00:34:21,588 SO WE LOOKED AT REGULATORY T 1032 00:34:21,588 --> 00:34:22,923 CELLS THAT WE TOOK FROM THE 1033 00:34:22,923 --> 00:34:27,527 BLOOD OF INDIVIDUALS WITH TYPE E 1034 00:34:27,527 --> 00:34:30,030 HERE, OR HEALTHY CONTROLS. 1035 00:34:30,030 --> 00:34:35,769 AND IF YOU LOOK AT THE FIGURE 1036 00:34:35,769 --> 00:34:40,140 AND LOOK AT THE -- WHERE NO 1037 00:34:40,140 --> 00:34:41,541 IL2 IS PRESENT WE CAN SEE A LOSS 1038 00:34:41,541 --> 00:34:43,076 OF REGULATORY T CELLS OVER TIME 1039 00:34:43,076 --> 00:34:44,611 IN BOTH CONTROLS AND TYPE 1040 00:34:44,611 --> 00:34:45,178 1 DIABETICS. 1041 00:34:45,178 --> 00:34:46,480 BUT WHAT'S REALLY THE MOST 1042 00:34:46,480 --> 00:34:50,951 IMPRESSIVE THING IS THAT IF YOU 1043 00:34:50,951 --> 00:34:53,287 INCUBATE WITH IL2, WE LOSE THE 1044 00:34:53,287 --> 00:34:56,123 REGULATORY T CELLS EVEN IN THE 1045 00:34:56,123 --> 00:34:58,659 PRESENCE OF IL2 IF AN INDIVIDUAL 1046 00:34:58,659 --> 00:34:59,760 HAS TYPE 1 DIABETES. 1047 00:34:59,760 --> 00:35:02,929 IT'S SHOWN ON THE LEFT, FOR MANY 1048 00:35:02,929 --> 00:35:04,231 INDIVIDUALS ON THE RIGHT IT 1049 00:35:04,231 --> 00:35:05,299 SHOWED A COMPENDIUM OF 1050 00:35:05,299 --> 00:35:06,233 INDIVIDUALS WITH TYPE 1051 00:35:06,233 --> 00:35:06,800 1 DIABETES. 1052 00:35:06,800 --> 00:35:08,669 SO WHAT THIS SUGGESTS IS THAT IN 1053 00:35:08,669 --> 00:35:12,139 TYPE 1 DIABETES, THERE MAY BE AN 1054 00:35:12,139 --> 00:35:13,573 IMBALANCE WHERE THE EFFECTOR T 1055 00:35:13,573 --> 00:35:15,542 CELLS THAT CAN TARGET THE BETA 1056 00:35:15,542 --> 00:35:17,644 CELL, CAUSE TYPE 1 DIABETES, MAY 1057 00:35:17,644 --> 00:35:19,613 NOT BE REGULATED AND THERE MAY 1058 00:35:19,613 --> 00:35:21,815 BE AN INADEQUATE NUMBER OF 1059 00:35:21,815 --> 00:35:22,783 REGULATORY T CELLS OR THOSE 1060 00:35:22,783 --> 00:35:27,921 CELLS MAY NOT FUNCTION WELL. 1061 00:35:27,921 --> 00:35:29,056 SO BEGINNING WITH A SET OF GENES 1062 00:35:29,056 --> 00:35:30,924 THAT POINTED TO IL2, WE WERE 1063 00:35:30,924 --> 00:35:33,427 THEN ABLE TO FIND 1064 00:35:33,427 --> 00:35:35,262 CHARACTERISTICS THAT CHANGE THE 1065 00:35:35,262 --> 00:35:35,962 IMMUNE SYSTEM AND SUGGEST THAT 1066 00:35:35,962 --> 00:35:38,799 THERE MAY BE FAILED T REG 1067 00:35:38,799 --> 00:35:40,334 FITNESS IN INDIVIDUALS WITH TYPE 1068 00:35:40,334 --> 00:35:43,270 1 DIABETES. 1069 00:35:43,270 --> 00:35:45,005 SO THAT RAISES THE QUESTION, 1070 00:35:45,005 --> 00:35:47,574 COULD WE TREAT TYPE 1 DIABETES 1071 00:35:47,574 --> 00:35:49,009 BY INCREASING REGULATORY T 1072 00:35:49,009 --> 00:35:51,511 CELLS? 1073 00:35:51,511 --> 00:35:53,580 AND THIS IS AN AREA WHERE MANY 1074 00:35:53,580 --> 00:35:55,482 PEOPLE HAVE BEEN INTERESTED IN 1075 00:35:55,482 --> 00:35:56,983 ADDRESSING THE QUESTION AND 1076 00:35:56,983 --> 00:35:58,418 BECAUSE OF THE BRIEF TIME I HAVE 1077 00:35:58,418 --> 00:35:59,553 TODAY, I'M ONLY GOING TO TALK 1078 00:35:59,553 --> 00:36:02,155 ABOUT ONE AREA. 1079 00:36:02,155 --> 00:36:03,490 THERE'S ONE APPROACH PEOPLE HAVE 1080 00:36:03,490 --> 00:36:05,726 TAKEN, IS TO GIVE IL2 TO 1081 00:36:05,726 --> 00:36:07,094 INDIVIDUALS WITH TYPE 1082 00:36:07,094 --> 00:36:08,195 1 DIABETES, THIS HAS ALSO BEEN 1083 00:36:08,195 --> 00:36:09,529 DONE IN OTHER AUTOIMMUNE 1084 00:36:09,529 --> 00:36:10,397 DISEASES. 1085 00:36:10,397 --> 00:36:12,132 AND WHAT WE KNOW FROM THOSE 1086 00:36:12,132 --> 00:36:14,234 STUDIES, IN FACT, ONE STUDY MY 1087 00:36:14,234 --> 00:36:15,969 GROUP WAS INVOLVED IN IS THAT IF 1088 00:36:15,969 --> 00:36:17,504 YOU GIVE INDIVIDUALS IL2 WITH 1089 00:36:17,504 --> 00:36:18,872 DIABETES, YOU CAN INCREASE THE 1090 00:36:18,872 --> 00:36:20,307 NUMBER OF REGULATORY T CELLS 1091 00:36:20,307 --> 00:36:22,042 THAT THEY HAVE, AND IN FACT, YOU 1092 00:36:22,042 --> 00:36:25,112 CAN NORMALIZE THEIR RESPONSE TO 1093 00:36:25,112 --> 00:36:27,314 IL2. 1094 00:36:27,314 --> 00:36:30,951 THE BAD NEWS IS THAT IL2 AFFECTS 1095 00:36:30,951 --> 00:36:32,552 MORE CELL TYPES THAN T-REGS 1096 00:36:32,552 --> 00:36:34,221 ALONE SO WE ACTUALLY WERE NOT 1097 00:36:34,221 --> 00:36:37,491 ABLE TO IMPROVE THE BETA CELL 1098 00:36:37,491 --> 00:36:38,492 FUNCTION IN THE INDIVIDUALS WE 1099 00:36:38,492 --> 00:36:39,893 TESTED AND IN FACT IT 1100 00:36:39,893 --> 00:36:40,694 TRANSIENTLY BECAME WORSE. 1101 00:36:40,694 --> 00:36:41,661 SO THAT CLINICAL STUDY WAS 1102 00:36:41,661 --> 00:36:43,096 REALLY USEFUL, BECAUSE WHAT IT 1103 00:36:43,096 --> 00:36:45,298 TAUGHT US WAS WE HAVE TO BE 1104 00:36:45,298 --> 00:36:47,267 CAREFUL ABOUT HOW WE GIVE IL2 1105 00:36:47,267 --> 00:36:49,236 THERAPY AND JUST INCREASING 1106 00:36:49,236 --> 00:36:51,772 T-REGS ALONE WITH HAVING 1107 00:36:51,772 --> 00:36:52,973 BLINDERS ON EVERYTHING ELSE IS 1108 00:36:52,973 --> 00:36:56,676 NOT REALLY WHERE WE NEED TO GO. 1109 00:36:56,676 --> 00:36:58,245 IT'S LED -- THIS NEGATIVE STUDY 1110 00:36:58,245 --> 00:37:00,647 HAS LED TO MANY NEW DEVELOPMENTS 1111 00:37:00,647 --> 00:37:02,082 IN TRYING TO CREATE A NOVEL, 1112 00:37:02,082 --> 00:37:05,552 BETTER WAY TO ENHANCE T-REGS. 1113 00:37:05,552 --> 00:37:06,920 SO THE OTHER APPROACH WOULD BE 1114 00:37:06,920 --> 00:37:09,256 TO GIVE PEOPLE MORE REGULATORY T 1115 00:37:09,256 --> 00:37:10,724 CELLS. 1116 00:37:10,724 --> 00:37:13,460 AND THAT'S ALSO BEEN DONE WITH 1117 00:37:13,460 --> 00:37:15,862 THE IDEA OF TAKING AN 1118 00:37:15,862 --> 00:37:17,864 INDIVIDUAL'S CELLS, ISOLATING 1119 00:37:17,864 --> 00:37:19,032 REGULATORY T CELLS, EXPANDING 1120 00:37:19,032 --> 00:37:20,600 THEM, AND THEN GIVING THEM BACK 1121 00:37:20,600 --> 00:37:23,336 TO THE PATIENT. 1122 00:37:23,336 --> 00:37:25,872 AND SO THIS IS AN EXAMPLE OF TWO 1123 00:37:25,872 --> 00:37:26,940 DIFFERENT STUDIES. 1124 00:37:26,940 --> 00:37:29,276 ON THE TOP, WHAT WAS DONE IS 1125 00:37:29,276 --> 00:37:31,978 EXACTLY WHAT I'VE DESCRIBED. 1126 00:37:31,978 --> 00:37:33,513 AND WE WERE ABLE TO SHOW THAT 1127 00:37:33,513 --> 00:37:35,382 THOSE REGULATORY T CELLS 1128 00:37:35,382 --> 00:37:36,416 ACTUALLY HAD BETTER FUNCTION 1129 00:37:36,416 --> 00:37:38,919 AFTER THEY WERE EXPANDED IN 1130 00:37:38,919 --> 00:37:41,087 CULTURE AND IN THE PRESENCE OF 1131 00:37:41,087 --> 00:37:43,056 IL2, BEFORE THEY WERE GIVEN BACK 1132 00:37:43,056 --> 00:37:43,723 TO THESE INDIVIDUALS. 1133 00:37:43,723 --> 00:37:48,428 AND ALL OF THESE INDIVIDUALS HAD 1134 00:37:48,428 --> 00:37:50,297 NEW ONSET TYPE 1 DIABETES. 1135 00:37:50,297 --> 00:37:51,331 WHAT'S SHOWN ON THE RIGHT IS 1136 00:37:51,331 --> 00:37:57,304 THAT THERE WAS NO ACTUALLY IMOF 1137 00:37:57,304 --> 00:37:58,839 IMPROVEMENT IN THEIR BETA CELL 1138 00:37:58,839 --> 00:37:59,306 FUNCTION. 1139 00:37:59,306 --> 00:38:00,373 THE GOOD NEWS IS THESE WERE 1140 00:38:00,373 --> 00:38:03,009 SAFE, SO THEN A SECOND TRIAL WAS 1141 00:38:03,009 --> 00:38:05,512 DONE, AND IN THIS TRIAL, AGAIN, 1142 00:38:05,512 --> 00:38:07,080 T-REGS WERE TAKEN FROM PATIENTS, 1143 00:38:07,080 --> 00:38:08,482 EXPANDED AND GIVEN BACK, BUT 1144 00:38:08,482 --> 00:38:11,651 THEY WERE ALSO IL2 AT THE SAME 1145 00:38:11,651 --> 00:38:12,085 TIME. 1146 00:38:12,085 --> 00:38:13,320 WITH THE HOPE THAT THAT WOULD 1147 00:38:13,320 --> 00:38:16,156 KEEP THOSE CELLS GOES IN VIVO. 1148 00:38:16,156 --> 00:38:19,759 BUT THIS ONE AGAIN WAS SAFE, BUT 1149 00:38:19,759 --> 00:38:22,395 DID NOT SHOW EFFICACY. 1150 00:38:22,395 --> 00:38:23,296 SO WHAT'S WRONG HERE? 1151 00:38:23,296 --> 00:38:27,334 WHY ISN'T THIS WORKING? 1152 00:38:27,334 --> 00:38:29,202 WHAT I WOULD SAY IS WE ARE MAYBE 1153 00:38:29,202 --> 00:38:30,537 NOT GIVING THE T-REGS IN THE 1154 00:38:30,537 --> 00:38:33,139 RIGHT WAY. 1155 00:38:33,139 --> 00:38:35,575 OUR CURRENT THERAPIES FOR 1156 00:38:35,575 --> 00:38:37,644 AUTOIMMUNE DISEASES ARE TO 1157 00:38:37,644 --> 00:38:39,412 GENERALLY STUNT THE IMMUNE 1158 00:38:39,412 --> 00:38:39,846 RESPONSE. 1159 00:38:39,846 --> 00:38:43,884 IF WE BLOCK THE IMMUNE RESPONSE, 1160 00:38:43,884 --> 00:38:46,853 WE CAN ACTUALLY TREAT PEOPLE 1161 00:38:46,853 --> 00:38:48,154 WITH AUTOIMMUNITY, BUT WE ALSO 1162 00:38:48,154 --> 00:38:50,357 LEAVE THEM OPEN TO INFECTION, 1163 00:38:50,357 --> 00:38:52,859 COMPLICATIONS DUE TO CANCER, SO 1164 00:38:52,859 --> 00:38:55,428 THERE'S NO SPECIFICITY. 1165 00:38:55,428 --> 00:38:57,631 NOW WHAT REGULATORY T CELLS HAVE 1166 00:38:57,631 --> 00:38:59,032 THAT OTHER APPROACHES DON'T HAVE 1167 00:38:59,032 --> 00:39:03,203 IS THAT THEY ARE ACTUALLY VERY 1168 00:39:03,203 --> 00:39:04,204 SPECIFIC. 1169 00:39:04,204 --> 00:39:05,739 REGULATORY T CELLS ARE DESIGNED 1170 00:39:05,739 --> 00:39:11,111 TO IDENTIFY HEALTHY TISSUE THAT 1171 00:39:11,111 --> 00:39:13,179 IS -- AND TO BLOCK ANY IMPACT OF 1172 00:39:13,179 --> 00:39:14,514 EFFECTOR CELLS TO ATTACK THAT 1173 00:39:14,514 --> 00:39:16,683 HEALTHY TISSUE. 1174 00:39:16,683 --> 00:39:17,651 AND THEY'RE SPECIFIC BY THE FACT 1175 00:39:17,651 --> 00:39:20,854 THAT THEY HAVE A T-CELL RECEPTOR 1176 00:39:20,854 --> 00:39:23,256 THAT RECOGNIZES SELF ANTIGENS 1177 00:39:23,256 --> 00:39:26,760 AND STOPS INFLAMMATION. 1178 00:39:26,760 --> 00:39:28,862 AND I'VE HIGHLIGHTED THAT T-CELL 1179 00:39:28,862 --> 00:39:30,063 RECEPTOR INTERACTION WITH CLASS 1180 00:39:30,063 --> 00:39:32,365 2 AND PEPTIDE HERE IN THE 1181 00:39:32,365 --> 00:39:35,201 FIGURE. 1182 00:39:35,201 --> 00:39:37,203 SO IF WE TOOK ADVANTAGE OF THE 1183 00:39:37,203 --> 00:39:41,007 SPECIFICITY OF T-REGS, COULD WE 1184 00:39:41,007 --> 00:39:42,309 DO BETTER? 1185 00:39:42,309 --> 00:39:44,611 SO OUR GROUP TOOK ON THIS 1186 00:39:44,611 --> 00:39:46,947 QUESTION AFTER TRYING FOR QUITE 1187 00:39:46,947 --> 00:39:49,883 A FEW YEARS WITH SOME SUCCESS. 1188 00:39:49,883 --> 00:39:52,419 SO WHY CONSIDER GIVING THESE -- 1189 00:39:52,419 --> 00:39:54,387 THIS T REG THERAPY? 1190 00:39:54,387 --> 00:39:57,257 WELL, WE KNOW IN MOUSE MODELS 1191 00:39:57,257 --> 00:39:59,960 THAT IF YOU GIVE 1192 00:39:59,960 --> 00:40:00,961 ANTIGEN-SPECIFIC T-REGS, YOU CAN 1193 00:40:00,961 --> 00:40:01,928 ACTUALLY PREVENT OR CURE 1194 00:40:01,928 --> 00:40:02,963 DIABETES. 1195 00:40:02,963 --> 00:40:04,864 AND WE ALSO KNOW THE ANTIGENS 1196 00:40:04,864 --> 00:40:07,334 THAT ARE BEING TARGETED IN 1197 00:40:07,334 --> 00:40:09,769 DIABETES BY T CELLS, SO WE COULD 1198 00:40:09,769 --> 00:40:11,938 ACTUALLY IDENTIFY OR MAKE A 1199 00:40:11,938 --> 00:40:13,473 REGULATORY T-CELL THAT WAS 1200 00:40:13,473 --> 00:40:14,674 SPECIFIC, BUT THERE'S A LOT OF 1201 00:40:14,674 --> 00:40:18,411 CHALLENGES. 1202 00:40:18,411 --> 00:40:19,312 ISLET-SPECIFIC T CELLS ARE 1203 00:40:19,312 --> 00:40:20,280 REALLY RARE IN DIABETES. 1204 00:40:20,280 --> 00:40:22,582 GETTING A PURE POPULATION OF 1205 00:40:22,582 --> 00:40:23,717 ISLET-SPECIFIC REGULATORY T 1206 00:40:23,717 --> 00:40:26,219 CELLS WOULD BE VERY DIFFICULT 1207 00:40:26,219 --> 00:40:28,355 BECAUSE THEY'RE QUITE RARE IN 1208 00:40:28,355 --> 00:40:29,689 THE PERIPHERAL BLOOD. 1209 00:40:29,689 --> 00:40:32,058 THERE'S OTHER PROBLEMS. 1210 00:40:32,058 --> 00:40:33,693 REGULATORY T CELLS CAN CHANGE, 1211 00:40:33,693 --> 00:40:36,630 AND THEY CAN BECOME EFFECTORS. 1212 00:40:36,630 --> 00:40:38,865 AND THAT'S SCARY IF YOU MAKE AN 1213 00:40:38,865 --> 00:40:40,400 ANTIGEN-SPECIFIC CELL AND THEN 1214 00:40:40,400 --> 00:40:42,636 IT DOESN'T REGULATE ANYMORE. 1215 00:40:42,636 --> 00:40:44,504 AND OF COURSE AS I'VE SHOWN YOU, 1216 00:40:44,504 --> 00:40:46,172 THERE'S LESS SENSITIVITY TO IL2 1217 00:40:46,172 --> 00:40:48,375 IN TYPE 1 DIABETES SO THESE 1218 00:40:48,375 --> 00:40:52,412 CELLS MAY NOT BE STABLE. 1219 00:40:52,412 --> 00:40:54,948 SO KNOWING THAT THESE ARE 1220 00:40:54,948 --> 00:40:57,117 PROBLEMS, WE WERE ABLE TO WORK 1221 00:40:57,117 --> 00:40:59,986 WITH A COLLEAGUE TO DEVELOP A 1222 00:40:59,986 --> 00:41:05,692 NEW FORM OF LEG REGULATORY T-CE. 1223 00:41:05,692 --> 00:41:07,560 IN THIS CASE WHAT WE WOULD DO IS 1224 00:41:07,560 --> 00:41:09,663 TAKE CELLS FROM A PATIENT, 1225 00:41:09,663 --> 00:41:10,764 TRANSFORM THOSE CELLS INTO 1226 00:41:10,764 --> 00:41:13,166 REGULATORY CELLS, AND HAVE THEM 1227 00:41:13,166 --> 00:41:14,834 EXPRESS T-CELL RECEPTOR THAT IS 1228 00:41:14,834 --> 00:41:17,437 SPECIFIC FOR THE ISLET, AND THE 1229 00:41:17,437 --> 00:41:18,872 ISLET ANTIGENS THAT WE KNOW ARE 1230 00:41:18,872 --> 00:41:21,041 TARGETED IN TYPE 1 DIABETES. 1231 00:41:21,041 --> 00:41:22,475 WE CAN THEN EXPAND THOSE CELLS 1232 00:41:22,475 --> 00:41:23,677 AND GIVE THEM BACK TO THE 1233 00:41:23,677 --> 00:41:24,244 PATIENT. 1234 00:41:24,244 --> 00:41:25,679 SO THAT'S THE IDEA. 1235 00:41:25,679 --> 00:41:29,315 SO HOW DO WE DO THAT? 1236 00:41:29,315 --> 00:41:31,751 WELL, WE TRIED TO DO THAT FOR 15 1237 00:41:31,751 --> 00:41:33,787 YEARS, AND BECAUSE THE 1238 00:41:33,787 --> 00:41:36,990 REGULATORY T CELLS WERE RARE AND 1239 00:41:36,990 --> 00:41:38,191 UNSTABLE AND SPECIFICITY WAS 1240 00:41:38,191 --> 00:41:40,827 HARD TO GET, WE WERE REALLY 1241 00:41:40,827 --> 00:41:41,327 STYMIED. 1242 00:41:41,327 --> 00:41:43,163 BUT THEN WITH THE DEVELOPMENT OF 1243 00:41:43,163 --> 00:41:45,298 GENE EDITING THROUGH CRISPR/CAS 1244 00:41:45,298 --> 00:41:46,766 9, WE HAD A WAY OUT OF THIS 1245 00:41:46,766 --> 00:41:47,734 PROBLEM. 1246 00:41:47,734 --> 00:41:49,402 AND THE WAY OUT OF THE PROBLEM 1247 00:41:49,402 --> 00:41:53,640 WAS TO TAKE CELLS THAT WERE JUST 1248 00:41:53,640 --> 00:41:55,742 RUN OF THE MILL CONVENTIONAL 1249 00:41:55,742 --> 00:41:58,111 CELLS, EXPRESS A T-CELL RECEPTOR 1250 00:41:58,111 --> 00:41:59,913 DIRECTED TO THE ISLET, WHICH WE 1251 00:41:59,913 --> 00:42:01,881 CAN USE DOING GENE EDITING OR 1252 00:42:01,881 --> 00:42:07,954 USING SOMETHING CALLED -- THEN 1253 00:42:07,954 --> 00:42:12,525 WE WERE ABLE TO USE GENE EDITING 1254 00:42:12,525 --> 00:42:17,163 TO EXPRESS THE GENE FOXP3, AND 1255 00:42:17,163 --> 00:42:20,433 FOXP3 IS CENTRAL TO THE 1256 00:42:20,433 --> 00:42:22,836 STABILITY AND FUNCTION OF 1257 00:42:22,836 --> 00:42:24,170 REGULATORY T CELLS, AND IN DOING 1258 00:42:24,170 --> 00:42:25,371 THAT, WE'VE NOW CREATED A CELL 1259 00:42:25,371 --> 00:42:26,372 THAT IS SUPPRESSIVE AND IS 1260 00:42:26,372 --> 00:42:30,643 SPECIFIC FOR THE ISLET. 1261 00:42:30,643 --> 00:42:32,846 SO WHEN WE DO THESE EXPERIMENTS, 1262 00:42:32,846 --> 00:42:34,180 THESE ARE NOW IN VITRO 1263 00:42:34,180 --> 00:42:35,281 EXPERIMENTS WHERE WE'VE ASKED 1264 00:42:35,281 --> 00:42:36,449 SEVERAL QUESTIONS. 1265 00:42:36,449 --> 00:42:39,219 IF WE TAKE A T-CELL THAT WE KNOW 1266 00:42:39,219 --> 00:42:42,088 TARGETS AN ISLET ANTIGEN, THAT'S 1267 00:42:42,088 --> 00:42:44,257 SHOWN IN BLUE ON THE LEFT -- OR 1268 00:42:44,257 --> 00:42:45,692 IT'S SHOWN IN GREEN ON THE LEFT, 1269 00:42:45,692 --> 00:42:47,460 AND WE USE A REGULATORY T-CELL 1270 00:42:47,460 --> 00:42:49,362 THAT CAN SEE THE SAME ANTIGEN, 1271 00:42:49,362 --> 00:42:51,231 WE CAN ACTUALLY SHOW, AND IT'S 1272 00:42:51,231 --> 00:42:53,399 SHOWN BELOW WITH A RED CIRCLE -- 1273 00:42:53,399 --> 00:42:56,136 RED SQUARE AROUND IT, THAT WE 1274 00:42:56,136 --> 00:42:57,270 CAN SUPPRESS THE PROLIFERATION 1275 00:42:57,270 --> 00:42:59,472 OF THOSE T CELLS. 1276 00:42:59,472 --> 00:43:02,175 AND THE SUPPRESSION ONLY OCCURS 1277 00:43:02,175 --> 00:43:04,077 WHEN THE ENGINEERED REGULATORY 1278 00:43:04,077 --> 00:43:05,278 T-CELL IS THERE IN THE PRESENCE 1279 00:43:05,278 --> 00:43:06,346 OF ITS ANTIGEN. 1280 00:43:06,346 --> 00:43:07,580 THIS IS IMPORTANT. 1281 00:43:07,580 --> 00:43:10,416 WE DON'T WANT THESE CELLS TO GET 1282 00:43:10,416 --> 00:43:11,451 ACTIVATED ANY OLD PLACE. 1283 00:43:11,451 --> 00:43:13,186 WE WANT THEM ACTIVATED WHEN 1284 00:43:13,186 --> 00:43:15,288 THEY'RE IN THE ISLET AND THEY 1285 00:43:15,288 --> 00:43:18,024 HAVE A REASON TO BE ACTIVATED. 1286 00:43:18,024 --> 00:43:19,692 WE'VE ALSO SHOWN THAT THESE 1287 00:43:19,692 --> 00:43:21,528 CELLS CAN SUPPRESS BYSTANDERS. 1288 00:43:21,528 --> 00:43:23,062 THAT MEANS ANOTHER CELL IN THE 1289 00:43:23,062 --> 00:43:26,800 AREA THAT MAY SEE ANOTHER ISLET 1290 00:43:26,800 --> 00:43:27,033 ANTIGEN. 1291 00:43:27,033 --> 00:43:30,003 IN THE MIDDLE, WE HAVE A T-CELL 1292 00:43:30,003 --> 00:43:33,873 THAT CAN SEE TID5-1, THAT'S A 1293 00:43:33,873 --> 00:43:35,775 SPECIFIC PEPTIDE THAT'S SEEN IN 1294 00:43:35,775 --> 00:43:37,877 THE ISLET, AND NOW WE HAVE A 1295 00:43:37,877 --> 00:43:39,479 REGULATORY CELL THAT WE'VE 1296 00:43:39,479 --> 00:43:40,980 ENGINEERED TO SEE A DIFFERENT 1297 00:43:40,980 --> 00:43:42,182 ANTIGEN, AND AGAIN, IT ABLE TO 1298 00:43:42,182 --> 00:43:45,885 SUPPRESS THAT IN A BYSTANDARD 1299 00:43:45,885 --> 00:43:46,286 MANNER. 1300 00:43:46,286 --> 00:43:47,887 SO YOU DON'T HAVE TO KNOW EVERY 1301 00:43:47,887 --> 00:43:49,756 ANTIGEN THAT'S BEING TARGETED IN 1302 00:43:49,756 --> 00:43:50,523 THIS AUTOIMMUNE DISEASE, YOU 1303 00:43:50,523 --> 00:43:51,758 ONLY NEED TO SEE ONE. 1304 00:43:51,758 --> 00:43:54,460 BUT WHEN WE DO THESE EXPERIMENTS 1305 00:43:54,460 --> 00:43:55,695 THE WAY I'VE SHOWN THEM IN THE 1306 00:43:55,695 --> 00:43:58,031 TWO LEFT FIGURES, WE'VE ACTUALLY 1307 00:43:58,031 --> 00:43:59,265 ENGINEERED THE EFFECTOR CELLS AS 1308 00:43:59,265 --> 00:44:02,635 WELL AND THE QUESTION IS, CAN WE 1309 00:44:02,635 --> 00:44:03,803 ACTUALLY SUPPRESS AUTO REACTIVE 1310 00:44:03,803 --> 00:44:05,839 T CELLS FROM PATIENTS WHO HAVE 1311 00:44:05,839 --> 00:44:06,606 DIABETES? 1312 00:44:06,606 --> 00:44:08,474 SO WHAT WE'RE ABLE TO DO IS TAKE 1313 00:44:08,474 --> 00:44:10,977 BLOOD SAMPLES FROM THOSE 1314 00:44:10,977 --> 00:44:14,214 PATIENTS, AND GROW UP THE ONES 1315 00:44:14,214 --> 00:44:15,648 THAT SEE ISLET ANTIGENS AND 1316 00:44:15,648 --> 00:44:17,283 THERE WILL BE MANY DIFFERENT T 1317 00:44:17,283 --> 00:44:23,089 CELLS WITH VERY MANY DIFFERENT 1318 00:44:23,089 --> 00:44:24,190 SPECIFICITIES, THEN WE 1319 00:44:24,190 --> 00:44:25,859 CO-CULTURE THOSE WITH A SINGLE 1320 00:44:25,859 --> 00:44:27,093 ENGINEERED T REG SPECIFICITY AND 1321 00:44:27,093 --> 00:44:29,162 WHAT WE'VE BEEN ABLE TO SHOW IS 1322 00:44:29,162 --> 00:44:29,662 WE CAN SUPPRESS THOSE. 1323 00:44:29,662 --> 00:44:31,130 SO THE BEAUTY OF THIS IS THAT 1324 00:44:31,130 --> 00:44:33,666 WE'RE ABLE TO BE VERY SPECIFIC, 1325 00:44:33,666 --> 00:44:36,269 ONLY SUPPRESS IN THE PRESENCE OF 1326 00:44:36,269 --> 00:44:38,404 AN ISLET ANTIGEN, SO THESE 1327 00:44:38,404 --> 00:44:39,272 REGULATORY T CELLS SHOULDN'T 1328 00:44:39,272 --> 00:44:41,040 SUPPRESS ANY OTHER IMMUNE 1329 00:44:41,040 --> 00:44:41,507 RESPONSES. 1330 00:44:41,507 --> 00:44:43,142 BUT YET WE'RE ABLE TO SUPPRESS 1331 00:44:43,142 --> 00:44:45,645 MORE BROADLY AN IMMUNE RESPONSE 1332 00:44:45,645 --> 00:44:49,782 TARGETING THE ISLET. 1333 00:44:49,782 --> 00:44:51,718 NOW THAT IS ONE APPROACH, AN 1334 00:44:51,718 --> 00:44:54,454 APPROACH WE DEVELOPED FOR TYPE D 1335 00:44:54,454 --> 00:44:56,789 ABOUT, BECAUSE I'M A 1336 00:44:56,789 --> 00:44:57,924 RHEUMATOLOGIST, IS THAT YOU CAN 1337 00:44:57,924 --> 00:45:01,594 DO THIS FOR OTHER ANTIGENS IN 1338 00:45:01,594 --> 00:45:03,229 OTHER TISSUE-SPECIFIC DISEASES. 1339 00:45:03,229 --> 00:45:05,465 SO IN THE LOWER FIGURE, I'VE 1340 00:45:05,465 --> 00:45:07,333 SHOWN AN ENGINEERED T REG THAT 1341 00:45:07,333 --> 00:45:16,209 WE MADE AGAINST AN EPITOPE, ONE 1342 00:45:16,209 --> 00:45:17,410 OF THE ANTIGENS WE THINK DRIVES 1343 00:45:17,410 --> 00:45:19,045 THE T-CELL RESPONSE IN 1344 00:45:19,045 --> 00:45:19,612 RHEUMATOID ARTHRITIS. 1345 00:45:19,612 --> 00:45:22,015 SO THIS IS ONE EXAMPLE. 1346 00:45:22,015 --> 00:45:22,882 OBVIOUSLY YOU COULD THINK OF 1347 00:45:22,882 --> 00:45:25,218 MORE EXAMPLES SO WE'RE EXCITED 1348 00:45:25,218 --> 00:45:25,985 TO THINK ABOUT WHERE YOU COULD 1349 00:45:25,985 --> 00:45:29,389 TAKE THIS MOVING FORWARD. 1350 00:45:29,389 --> 00:45:32,158 SO JUST IN SUMMARY BY 1351 00:45:32,158 --> 00:45:33,293 ENGINEERING A REGULATORY CELL 1352 00:45:33,293 --> 00:45:35,428 AND MAKING IT ANTIGEN-SPECIFIC, 1353 00:45:35,428 --> 00:45:37,764 YOU CAN SPECIFICALLY TARGET A 1354 00:45:37,764 --> 00:45:38,231 TISSUE. 1355 00:45:38,231 --> 00:45:41,467 YOU CAN GET A STABLE REGULATORY 1356 00:45:41,467 --> 00:45:44,804 CELL THAT CONTINUOUSLY EXPRESSES 1357 00:45:44,804 --> 00:45:46,105 FOXP3, AND WE CAN ALSO ENGINEER 1358 00:45:46,105 --> 00:45:49,709 OTHER FEATURES INTO THESE CELLS. 1359 00:45:49,709 --> 00:45:52,211 AND CURRENTLY WE'RE TRYING TO 1360 00:45:52,211 --> 00:45:54,547 ENGINEER ENHANCED RESPONSES TO 1361 00:45:54,547 --> 00:45:56,849 IL2, BUT ALSO ENGINEER THE 1362 00:45:56,849 --> 00:45:58,384 ABILITY TO SECRETE FACTORS THAT 1363 00:45:58,384 --> 00:45:59,752 MAY ENHANCE HEALING IN THE 1364 00:45:59,752 --> 00:46:01,087 TISSUE. 1365 00:46:01,087 --> 00:46:01,955 BUT THERE'S LIMITATIONS WITH 1366 00:46:01,955 --> 00:46:04,891 THIS APPROACH. 1367 00:46:04,891 --> 00:46:06,459 FIRST OF ALL FOR THE ANTIGEN 1368 00:46:06,459 --> 00:46:08,094 SPECIFICITY, WE USE ONLY -- THIS 1369 00:46:08,094 --> 00:46:09,963 IS VERY TARGETED TO HLA, SO IN 1370 00:46:09,963 --> 00:46:12,065 THE CASE OF A TYPE 1 DIABETIC, 1371 00:46:12,065 --> 00:46:16,569 WE MAY BE ABLE TO COVER ALL 40% 1372 00:46:16,569 --> 00:46:18,905 WITH TYPE 1 DIABETES, WE'D HAVE 1373 00:46:18,905 --> 00:46:20,440 TO GENERATE A DIFFERENT 1374 00:46:20,440 --> 00:46:21,541 REGULATORY CELL FOR SOME OF THE 1375 00:46:21,541 --> 00:46:23,743 OTHER INDIVIDUALS. 1376 00:46:23,743 --> 00:46:25,378 CURRENTLY THESE REQUIRE 1377 00:46:25,378 --> 00:46:26,279 AUTOLOGOUS T CELLS SO THAT'S A 1378 00:46:26,279 --> 00:46:28,781 MUCH MORE EXPENSIVE PROCEDURE 1379 00:46:28,781 --> 00:46:29,916 WHERE WE NEED TO GET CELLS FROM 1380 00:46:29,916 --> 00:46:31,684 THE PATIENT TO GIVE THEM BACK. 1381 00:46:31,684 --> 00:46:33,019 AND IT'S EXPENSIVE. 1382 00:46:33,019 --> 00:46:35,621 SO REALLY, THE HOPE IS TO SHOW 1383 00:46:35,621 --> 00:46:37,190 THAT THIS TYPE OF APPROACH 1384 00:46:37,190 --> 00:46:38,624 WORKS, BUT THEN WE NEED TO 1385 00:46:38,624 --> 00:46:40,693 DEVELOP AN OFF THE SHELF 1386 00:46:40,693 --> 00:46:40,927 THERAPY. 1387 00:46:40,927 --> 00:46:42,829 THEN ALSO NOTE I'VE SHOWED YOU 1388 00:46:42,829 --> 00:46:45,131 ONE APPROACH, THE APPROACH WE'VE 1389 00:46:45,131 --> 00:46:45,331 TAKEN. 1390 00:46:45,331 --> 00:46:46,766 OTHERS ARE TAKING OTHER 1391 00:46:46,766 --> 00:46:48,067 APPROACHES INCLUDING PUTTING 1392 00:46:48,067 --> 00:46:50,770 CARS INTO REGULATORY T CELLS, 1393 00:46:50,770 --> 00:46:52,638 AND OTHER APPROACHES TO ENGINEER 1394 00:46:52,638 --> 00:46:53,673 CELLS THAT COULD DO THIS. 1395 00:46:53,673 --> 00:46:55,341 SO I THINK THERE'S A GREAT DEAL 1396 00:46:55,341 --> 00:46:57,010 OF HOPE RIGHT NOW. 1397 00:46:57,010 --> 00:46:57,610 THE FIRST CLINICAL TRIALS ARE 1398 00:46:57,610 --> 00:47:01,280 BEING STARTED WITH 1399 00:47:01,280 --> 00:47:02,582 ANTIGEN-SPECIFIC REGULATORY 1400 00:47:02,582 --> 00:47:02,782 CELLS. 1401 00:47:02,782 --> 00:47:03,850 SO WE'LL LEARN MORE IN THE NEXT 1402 00:47:03,850 --> 00:47:07,687 FEW YEARS. 1403 00:47:07,687 --> 00:47:09,122 SO I'VE TALKED A LITTLE BIT 1404 00:47:09,122 --> 00:47:10,289 ABOUT HOW WE CAN TAKE THIS 1405 00:47:10,289 --> 00:47:11,858 PARADIGM STARTING WITH GENETICS, 1406 00:47:11,858 --> 00:47:13,626 IDENTIFY A PATHWAY THAT'S 1407 00:47:13,626 --> 00:47:15,595 ALTERED IN AN AUTOIMMUNE 1408 00:47:15,595 --> 00:47:16,796 DISEASE, AND THEN THINK ABOUT 1409 00:47:16,796 --> 00:47:18,698 HOW DO WE CREATE THERAPEUTICS, 1410 00:47:18,698 --> 00:47:20,733 BUT I'D LIKE TO SHARE THE OTHER 1411 00:47:20,733 --> 00:47:22,268 TWO PART OF THIS APPROACH, WHICH 1412 00:47:22,268 --> 00:47:25,004 IS LOOKING AT WHO TO TREAT AND 1413 00:47:25,004 --> 00:47:27,140 WHEN TO TREAT. 1414 00:47:27,140 --> 00:47:29,242 AND SO WHAT WE WERE ABLE TO DO 1415 00:47:29,242 --> 00:47:30,777 ONCE WE'D IDENTIFIED THIS 1416 00:47:30,777 --> 00:47:34,747 ALTERATION IN IL2 SIGNALING WAS 1417 00:47:34,747 --> 00:47:37,283 RIGHT OUT TO THE TRIAL NET 1418 00:47:37,283 --> 00:47:38,684 CONSORTIUM, WHICH IS A GROUP 1419 00:47:38,684 --> 00:47:40,920 FUNDED BY THE NIH AND HAS BEEN 1420 00:47:40,920 --> 00:47:42,555 OVER THE YEARS IDENTIFYING 1421 00:47:42,555 --> 00:47:44,090 COHORTS OF FAMILIES WHERE 1422 00:47:44,090 --> 00:47:46,259 INDIVIDUALS HAVE TYPE 1 DIABETES 1423 00:47:46,259 --> 00:47:48,261 AND THEN FOLLOWING SIBLINGS WHO 1424 00:47:48,261 --> 00:47:50,363 ARE AT HIGH RISK OVER TIME. 1425 00:47:50,363 --> 00:47:52,565 SO WE CAN IDENTIFY THOSE 1426 00:47:52,565 --> 00:47:54,300 INDIVIDUALS WHO NEVER GO ON TO 1427 00:47:54,300 --> 00:47:57,403 GET DIABETES, WE'RE CALLING THEM 1428 00:47:57,403 --> 00:47:59,038 FDRs HERE, INDIVIDUALS WHO 1429 00:47:59,038 --> 00:48:00,673 DEVELOP AUTOANTIBODIES, AND THEN 1430 00:48:00,673 --> 00:48:03,876 FOLLOW THEM OVER TIME AS THEY 1431 00:48:03,876 --> 00:48:05,244 MOVE TOWARDS DEVELOPMENT OF 1432 00:48:05,244 --> 00:48:06,312 DIABETES. 1433 00:48:06,312 --> 00:48:07,947 THESE COHORTS HAVE BEEN 1434 00:48:07,947 --> 00:48:09,382 EXCEPTIONALLY USEFUL IN HELPING 1435 00:48:09,382 --> 00:48:12,485 US DEVELOP A PREDICTION PARADIGM 1436 00:48:12,485 --> 00:48:16,556 FOR TYPE 1 DIABETES, BUT FOR ME 1437 00:48:16,556 --> 00:48:18,191 AS AN IMMUNOLOGIST, I WAS ABLE 1438 00:48:18,191 --> 00:48:19,559 TO LOOK AT SAMPLES FROM 1439 00:48:19,559 --> 00:48:21,627 INDIVIDUALS WHO WE FOLLOWED OVER 1440 00:48:21,627 --> 00:48:23,262 TIME AND ASKED, DID THE PEOPLE 1441 00:48:23,262 --> 00:48:27,133 WHO WERE RELATED WHO NEVER GOT 1442 00:48:27,133 --> 00:48:29,569 AN AUTO ANTIBODY, DID THEY HAVE 1443 00:48:29,569 --> 00:48:30,870 ILLINOIS DEFECTS AS COMPARED TO 1444 00:48:30,870 --> 00:48:32,872 THE INDIVIDUAL WHO HAD AUTO 1445 00:48:32,872 --> 00:48:33,406 ANTIBODIES? 1446 00:48:33,406 --> 00:48:35,041 AS YOU CAN SEE ON THE LEFT, 1447 00:48:35,041 --> 00:48:38,478 PEOPLE WHO ARE RELATED TO A TYPE 1448 00:48:38,478 --> 00:48:40,246 1 DIABETIC BUT NEVER GOT 1449 00:48:40,246 --> 00:48:42,415 AUTOANTIBODIES HAVE NORMAL IL2 1450 00:48:42,415 --> 00:48:43,416 RESPONSES. 1451 00:48:43,416 --> 00:48:45,451 WHEREAS THOSE INDIVIDUALS WHO 1452 00:48:45,451 --> 00:48:47,854 HAD AUTOANTIBODIES BUT DID NOT 1453 00:48:47,854 --> 00:48:49,922 YET HAVE TYPE 1 DIABETES HAD 1454 00:48:49,922 --> 00:48:51,157 BLUNTED IL2 RESPONSES. 1455 00:48:51,157 --> 00:48:52,058 SO WHEN DOES THAT HAPPEN? 1456 00:48:52,058 --> 00:48:54,360 AND SO WHAT WE LOOKED AT WAS THE 1457 00:48:54,360 --> 00:48:57,797 NUMBER OF AUTOANTIBODIES AN 1458 00:48:57,797 --> 00:49:00,733 INDIVIDUAL HAD, AND WE KNOW THEY 1459 00:49:00,733 --> 00:49:03,603 ACQUIRE AU AUTOANTIBODIES OVER 1460 00:49:03,603 --> 00:49:03,870 TIME. 1461 00:49:03,870 --> 00:49:05,204 AS YOU CAN SEE ON THE RIGHT, 1462 00:49:05,204 --> 00:49:08,441 INDIVIDUALS WHO HAVE ANY 1463 00:49:08,441 --> 00:49:10,743 AUTOANTIBODIES DIRECTED TO 1464 00:49:10,743 --> 00:49:12,645 THE -- SUGGESTING THAT THIS 1465 00:49:12,645 --> 00:49:17,517 IMPAIRMENT IN IL2 SIGNALING MAY 1466 00:49:17,517 --> 00:49:18,584 BE IMPORTANT EARLY IN THE LOSS 1467 00:49:18,584 --> 00:49:19,919 OF TOLERANCE AND IN THE 1468 00:49:19,919 --> 00:49:21,487 DEVELOPMENT OF AUTOANTIBODIES. 1469 00:49:21,487 --> 00:49:22,755 SO TREATING ILLINOIS 28 AND 1470 00:49:22,755 --> 00:49:30,696 IL2 AND MAYBE EVENT-REGS MAY NEN 1471 00:49:30,696 --> 00:49:31,230 MY MIND. 1472 00:49:31,230 --> 00:49:33,232 THE OTHER THING WE CAN ASK IS, 1473 00:49:33,232 --> 00:49:34,500 IS THIS IL2 STORY IMPORTANT IN 1474 00:49:34,500 --> 00:49:35,434 OTHER DISEASES? 1475 00:49:35,434 --> 00:49:37,003 SO WE CAN LOOK ACROSS COHORTS, 1476 00:49:37,003 --> 00:49:38,638 AND THIS IS WHERE DEVELOPMENT OF 1477 00:49:38,638 --> 00:49:39,739 COHORTS IS VERY IMPORTANT, 1478 00:49:39,739 --> 00:49:42,041 BECAUSE WE WANT TO BE ABLE TO 1479 00:49:42,041 --> 00:49:45,278 COMPARE OUR STUDIES AND OUR 1480 00:49:45,278 --> 00:49:46,145 ASSAYS BETWEEN INDIVIDUALS. 1481 00:49:46,145 --> 00:49:49,515 SO WE HAVE THE GOOD FORTUNE OF 1482 00:49:49,515 --> 00:49:51,984 HAVING OUR BIOREPOSITORY HAVE 1483 00:49:51,984 --> 00:49:52,885 MULTIPLE DIFFERENT AUTOIMMUNE 1484 00:49:52,885 --> 00:49:54,487 DISEASES BUT ALL THE SAMPLES ARE 1485 00:49:54,487 --> 00:49:56,389 HANDLED IN AN IDENTICAL MANNER. 1486 00:49:56,389 --> 00:49:57,623 SO HERE WHAT WE DID IS WE TOOK A 1487 00:49:57,623 --> 00:49:59,525 GROUP OF OUR CONTROLS, 1488 00:49:59,525 --> 00:50:02,195 INDIVIDUALS WITH TYPE 1489 00:50:02,195 --> 00:50:04,564 1 DIABETES, INDIVIDUALS WITH 1490 00:50:04,564 --> 00:50:06,399 RELAPSE -- WITH MULTIPLE 1491 00:50:06,399 --> 00:50:07,500 SCLEROSIS, AND INDIVIDUALS WITH 1492 00:50:07,500 --> 00:50:08,367 LUPUS. 1493 00:50:08,367 --> 00:50:10,636 AND WE ASKED THIS SAME QUESTION 1494 00:50:10,636 --> 00:50:13,472 ABOUT THE RESPONSE TO IL2 AND 1495 00:50:13,472 --> 00:50:15,107 THEIR REGULATORY T-CELLS. 1496 00:50:15,107 --> 00:50:16,409 WHAT YOU CAN SEE FROM THIS GRAPH 1497 00:50:16,409 --> 00:50:17,910 IS THAT INDIVIDUALS WITH 1498 00:50:17,910 --> 00:50:19,745 MULTIPLE SCLEROSIS SIMILAR TO 1499 00:50:19,745 --> 00:50:21,914 DIABETES HAVE IMPAIRED IL2 1500 00:50:21,914 --> 00:50:22,882 SIGNALING, WHEREAS INDIVIDUALS 1501 00:50:22,882 --> 00:50:26,686 WITH LUPUS DO NOT. 1502 00:50:26,686 --> 00:50:27,954 NOW THIS MAKES SENSE BECAUSE WE 1503 00:50:27,954 --> 00:50:31,490 KNOW SOME OF THE SAME GENES 1504 00:50:31,490 --> 00:50:33,793 ASSOCIATED WITH TYPE 1 DIABETES 1505 00:50:33,793 --> 00:50:35,027 ARE ALSO ASSOCIATED WITH M.S. 1506 00:50:35,027 --> 00:50:37,230 AND INVOLVE THE IL2 PATHWAY. 1507 00:50:37,230 --> 00:50:39,298 IT ALSO MAKES SENSE FOR LUPUS 1508 00:50:39,298 --> 00:50:40,766 BECAUSE WE ACTUALLY KNOW IN 1509 00:50:40,766 --> 00:50:43,736 LUPUS THAT THERE'S NOT ENOUGH 1510 00:50:43,736 --> 00:50:45,171 IL2 MADE, BUT THAT THOSE CELLS 1511 00:50:45,171 --> 00:50:46,772 RESPOND TO IL2. 1512 00:50:46,772 --> 00:50:48,941 SO THAT HAS -- IT INFLUENCES THE 1513 00:50:48,941 --> 00:50:50,309 WAY WE WOULD THINK ABOUT 1514 00:50:50,309 --> 00:50:52,345 TARGETING THE IL2 PATHWAY IN 1515 00:50:52,345 --> 00:50:54,513 LUPUS AS COMPARED TO IN TYPE 1516 00:50:54,513 --> 00:50:55,848 1 DIABETES AND M.S. 1517 00:50:55,848 --> 00:50:57,917 BUT IT ALSO MEANS AS WE START 1518 00:50:57,917 --> 00:50:59,552 THINKING ABOUT INTERVENTIONS, IT 1519 00:50:59,552 --> 00:51:05,191 HELPS US NOT LEARN -- LEARN MORE 1520 00:51:05,191 --> 00:51:06,092 FROM ONE DISEASE THAN JUST THAT 1521 00:51:06,092 --> 00:51:06,826 DISEASE ALONE. 1522 00:51:06,826 --> 00:51:08,894 SO I'D LIKE TO END WITH SOME 1523 00:51:08,894 --> 00:51:11,597 COMMENTS ABOUT USING A UNIQUE 1524 00:51:11,597 --> 00:51:14,767 POPULATION TO HELP UNDERSTAND 1525 00:51:14,767 --> 00:51:16,736 AUTOIMMUNITY, AND NOT ONLY 1526 00:51:16,736 --> 00:51:17,837 UNDERSTANDING THEIR DISEASE 1527 00:51:17,837 --> 00:51:20,806 RISK, BUT ALSO OTHER DISEASES. 1528 00:51:20,806 --> 00:51:22,575 AND THE POPULATION THAT WE HAVE 1529 00:51:22,575 --> 00:51:25,845 BECOME VERY INTERESTED IN 1530 00:51:25,845 --> 00:51:28,614 STUDYING IS INDIVIDUALS WHO HAVE 1531 00:51:28,614 --> 00:51:28,981 DOWN SYNDROME. 1532 00:51:28,981 --> 00:51:30,683 THIS WORK HAS BEEN SUPPORTED BY 1533 00:51:30,683 --> 00:51:33,119 THE NIH INCLUDE PROJECT AND HAS 1534 00:51:33,119 --> 00:51:34,920 BEEN REALLY AN EXCITING AREA FOR 1535 00:51:34,920 --> 00:51:38,291 US. 1536 00:51:38,291 --> 00:51:39,959 SO DOWN SYNDROME IS TRISOMY 1537 00:51:39,959 --> 00:51:42,628 21 AND IT OCCURS IN 1 IN 800 1538 00:51:42,628 --> 00:51:44,263 BIRTHS. 1539 00:51:44,263 --> 00:51:45,564 INDIVIDUALS WITH DOWN SYNDROME 1540 00:51:45,564 --> 00:51:46,666 HAVE BEEN KNOWN FOR A LONG TIME 1541 00:51:46,666 --> 00:51:48,334 TO HAVE IMMUNE DYSREGULATION. 1542 00:51:48,334 --> 00:51:50,236 THEY HAVE POOR RESPONSES TO 1543 00:51:50,236 --> 00:51:52,505 VACCINES, THEY HAVE INCREASED 1544 00:51:52,505 --> 00:51:53,806 SUSCEPTIBILITY TO INFECTION. 1545 00:51:53,806 --> 00:51:56,442 BUT AS THE LIFESPAN OF 1546 00:51:56,442 --> 00:51:58,144 INDIVIDUALS WITH DOWN SYNDROME 1547 00:51:58,144 --> 00:51:59,912 HAS EXTENDED BECAUSE OF MUCH 1548 00:51:59,912 --> 00:52:01,647 BETTER ABILITY TO CARE FOR THEIR 1549 00:52:01,647 --> 00:52:04,317 OTHER HEALTH ISSUES, IT'S BECOME 1550 00:52:04,317 --> 00:52:05,084 VERY CLEAR THAT THESE 1551 00:52:05,084 --> 00:52:06,952 INDIVIDUALS ARE AT A MARKED 1552 00:52:06,952 --> 00:52:08,954 INCREASED RISK FOR 1553 00:52:08,954 --> 00:52:09,922 TISSUE-SPECIFIC AUTOIMMUNITY. 1554 00:52:09,922 --> 00:52:13,659 AND I'VE JUST LISTED A FEW HERE. 1555 00:52:13,659 --> 00:52:15,461 TYPE 1 DIABETES ARE 4.5 TIMES 1556 00:52:15,461 --> 00:52:20,166 MORE LIKELY TO HAVE THAT. 1557 00:52:20,166 --> 00:52:23,002 26 FOLD INCREASED RISK OF 1558 00:52:23,002 --> 00:52:31,677 HASHIMOTO'SHASHIMOTO'S THYROIDI6 1559 00:52:31,677 --> 00:52:36,615 TIMES CELIAC DISEASE. 1560 00:52:36,615 --> 00:52:38,217 SO THIS GROUP OF INDIVIDUALS, WE 1561 00:52:38,217 --> 00:52:39,418 THINK IT'S IMPORTANT TO 1562 00:52:39,418 --> 00:52:40,820 UNDERSTAND WHY THEY HAVE 1563 00:52:40,820 --> 00:52:41,921 AUTOIMMUNITY SO WE CAN 1564 00:52:41,921 --> 00:52:43,222 POTENTIALLY TARGET THERAPEUTICS 1565 00:52:43,222 --> 00:52:44,156 THAT COULD PREVENT THIS IN THIS 1566 00:52:44,156 --> 00:52:45,358 GROUP OF INDIVIDUALS, BUT IT 1567 00:52:45,358 --> 00:52:47,660 ALSO MAY BE A WAY FOR US TO 1568 00:52:47,660 --> 00:52:51,364 LEARN MORE ABOUT AUTOIMMUNITY IN 1569 00:52:51,364 --> 00:52:52,098 GENERAL. 1570 00:52:52,098 --> 00:52:54,400 SO WHAT WE HAVE BEEN ABLE TO DO 1571 00:52:54,400 --> 00:52:57,002 IS DEVELOP A COHORT OF 1572 00:52:57,002 --> 00:52:58,771 INDIVIDUALS WITH DOWN SYNDROME, 1573 00:52:58,771 --> 00:53:01,006 RANGING FROM VERY EARLY 1574 00:53:01,006 --> 00:53:04,710 CHILDHOOD INTO THE 50s, AND 1575 00:53:04,710 --> 00:53:05,711 NOW WITH THE HELP OF THE INCLUDE 1576 00:53:05,711 --> 00:53:06,846 PROJECT, HAVE OVER 200 1577 00:53:06,846 --> 00:53:08,581 INDIVIDUALS IN THAT REGISTRY, 1578 00:53:08,581 --> 00:53:11,550 AND WE CAN COMPARE WHAT THEIR 1579 00:53:11,550 --> 00:53:13,753 IMMUNE SYSTEM LOOKS LIKE TO OUR 1580 00:53:13,753 --> 00:53:16,956 TYPICAL CONTROLS, WHO ARE AGE- 1581 00:53:16,956 --> 00:53:19,091 AND SEX-MATCHED AND INDIVIDUALS 1582 00:53:19,091 --> 00:53:21,127 WITH DIABETES WHO ARE ALSO AGE- 1583 00:53:21,127 --> 00:53:22,428 AND SEX-MATCHED. 1584 00:53:22,428 --> 00:53:24,029 AND JUST BRIEFLY, SOME OF OUR 1585 00:53:24,029 --> 00:53:25,664 DATA, THIS HAS BEEN PUBLISHED IN 1586 00:53:25,664 --> 00:53:28,134 SCIENCE TRANSLATIONAL MEDICINE 1587 00:53:28,134 --> 00:53:28,567 IN 2022. 1588 00:53:28,567 --> 00:53:30,736 WHAT WE WERE ABLE TO SHOW SOME 1589 00:53:30,736 --> 00:53:31,971 OF THE T-CELL POPULATIONS THAT 1590 00:53:31,971 --> 00:53:33,839 WE ASSOCIATE WITH AUTOIMMUNITY 1591 00:53:33,839 --> 00:53:37,243 ARE MARKEDLY INCREASED IN 1592 00:53:37,243 --> 00:53:37,943 INDIVIDUALS WITH DOWN SYNDROME. 1593 00:53:37,943 --> 00:53:40,980 THAT INCLUDES GAMMA INTERFERING 1594 00:53:40,980 --> 00:53:44,116 SECRETE TH1 CELLS, GAMMA AND 1595 00:53:44,116 --> 00:53:47,620 TH17 SECRETE TH17.1 CELLS, AND 1596 00:53:47,620 --> 00:53:51,123 THEN STEM CELL MEMORY IN CD4 AND 1597 00:53:51,123 --> 00:53:52,391 CD8, AND THEY'RE THOUGHT TO BE 1598 00:53:52,391 --> 00:53:54,860 THE PRECURSORS OF AUTOIMMUNITY. 1599 00:53:54,860 --> 00:53:58,364 NOW WHEN YOU LOOK AT THE 1600 00:53:58,364 --> 00:54:00,332 DIFFERENCES BETWEEN TYPICAL 1601 00:54:00,332 --> 00:54:01,867 CONTROLS IN DOWN SYNDROME ARE 1602 00:54:01,867 --> 00:54:03,436 VERY OBVIOUS, THESE ARE QUITE 1603 00:54:03,436 --> 00:54:04,103 EXAGGERATED CHANGES. 1604 00:54:04,103 --> 00:54:05,538 AND WHEN WE LOOK IN TYPE 1605 00:54:05,538 --> 00:54:07,273 1 DIABETES, WE SEE MUCH MORE 1606 00:54:07,273 --> 00:54:09,575 MUTED CHANGES BUT THOSE CHANGES 1607 00:54:09,575 --> 00:54:11,510 ARE THERE, AND WE GET 1608 00:54:11,510 --> 00:54:15,448 SIGNIFICANCE WHEN WE LOOK AT THE 1609 00:54:15,448 --> 00:54:16,115 CD8 POPULATION STEM CELLS. 1610 00:54:16,115 --> 00:54:17,917 IF WE LOOK AT ALL OF THE 1611 00:54:17,917 --> 00:54:18,984 DISREGULATED SUBSETS THAT HAVE 1612 00:54:18,984 --> 00:54:20,853 BEEN DESCRIBED IN MULTIPLE 1613 00:54:20,853 --> 00:54:22,488 AUTOIMMUNE DISEASES LIKE 1614 00:54:22,488 --> 00:54:25,591 CROHN'S, M.S., PSORIASIS, R.A. 1615 00:54:25,591 --> 00:54:28,461 AND LUPUS, WE ALSO SEE THOSE 1616 00:54:28,461 --> 00:54:30,396 SAME POPULATIONS ARE, IN FACT, 1617 00:54:30,396 --> 00:54:31,597 DISREGULATED IN DOWN SYNDROME. 1618 00:54:31,597 --> 00:54:33,232 SO THERE ARE SOME COMMON 1619 00:54:33,232 --> 00:54:34,767 PATHWAYS HERE AND IN DOWN 1620 00:54:34,767 --> 00:54:36,802 SYNDROME, THEY APPEAR TO BE MORE 1621 00:54:36,802 --> 00:54:38,437 EXAGGERATED. 1622 00:54:38,437 --> 00:54:43,476 SO MY COLLEAGUE BERNARD KORR WAS 1623 00:54:43,476 --> 00:54:44,977 VERY INTERESTED IN THIS QUESTION 1624 00:54:44,977 --> 00:54:46,812 OF IMMUNE AGING AND SO HE 1625 00:54:46,812 --> 00:54:47,913 DEVELOPED -- HE LOOKED AT THE 1626 00:54:47,913 --> 00:54:49,882 CELL POPULATIONS COMPARING 1627 00:54:49,882 --> 00:54:51,817 TYPICAL CONTROLS TO DOWN 1628 00:54:51,817 --> 00:54:54,987 SYNDROME, AND DEVELOPED AP WAY 1629 00:54:54,987 --> 00:54:56,388 TO LOOK AT IMMUNE AGE. 1630 00:54:56,388 --> 00:54:58,457 AND WHEN WE TAKE TYPICAL 1631 00:54:58,457 --> 00:55:00,759 CONTROLS AND CREATE THAT MODEL, 1632 00:55:00,759 --> 00:55:03,929 WE CAN SEE DOWN SYNDROME HAS A 1633 00:55:03,929 --> 00:55:08,567 MODEST INCREASE IN IMMUNE AGE. 1634 00:55:08,567 --> 00:55:12,304 BUT IN THE ACTUAL THE DS 1635 00:55:12,304 --> 00:55:14,173 FILTERED MODEL, USING HEALTHY 1636 00:55:14,173 --> 00:55:15,875 CONTROLS BUT FOCUSED ON THE 1637 00:55:15,875 --> 00:55:18,077 SUBSETS OR POPULATIONS ALTERED 1638 00:55:18,077 --> 00:55:19,378 IN DOWN SYNDROME, WE ACTUALLY 1639 00:55:19,378 --> 00:55:21,747 HAVE A MODEL OF IMMUNE AGING 1640 00:55:21,747 --> 00:55:23,382 THAT'S QUITE GOOD IN HEALTHY 1641 00:55:23,382 --> 00:55:24,683 INDIVIDUALS BUT IT DEMONSTRATES 1642 00:55:24,683 --> 00:55:26,585 THE EXTREME CHANGE IN IMMUNE AGE 1643 00:55:26,585 --> 00:55:27,052 IN DOWN SYNDROME. 1644 00:55:27,052 --> 00:55:28,787 WHEN WE LOOK THEN AT INDIVIDUALS 1645 00:55:28,787 --> 00:55:30,222 WITH DOWN SYNDROME WHO HAVE 1646 00:55:30,222 --> 00:55:32,591 AUTOIMMUNITY, WE SEE A MUCH MORE 1647 00:55:32,591 --> 00:55:33,359 EXAGGERATED IMMUNE AGE. 1648 00:55:33,359 --> 00:55:36,295 BUT WHAT I FOUND HERE IS THAT 1649 00:55:36,295 --> 00:55:38,297 WHEN WE NOW TAKE THIS MODEL THAT 1650 00:55:38,297 --> 00:55:39,331 WE'VE LEARNED FROM DOWN SYNDROME 1651 00:55:39,331 --> 00:55:42,701 AND APPLY TO TYPE 1 DIABETES, IN 1652 00:55:42,701 --> 00:55:44,236 THE RIGHT LOWER AREA, YOU CAN 1653 00:55:44,236 --> 00:55:46,906 SEE THAT WE NOW SEE THAT 1654 00:55:46,906 --> 00:55:49,975 INDIVIDUAL WITH TYPE 1 DIABETES 1655 00:55:49,975 --> 00:55:51,744 HAVE ENHANCED IMMUNE AGING AS 1656 00:55:51,744 --> 00:55:53,078 WELL, SOMETHING WE WOULDN'T HAVE 1657 00:55:53,078 --> 00:55:56,482 PICKED UP VERY WELL WITH THE 1658 00:55:56,482 --> 00:55:57,049 UNFILTERED MODEL. 1659 00:55:57,049 --> 00:56:01,186 SO SHOWING THAT IMMUNE AGE AND 1660 00:56:01,186 --> 00:56:07,192 INFLA MINFLAMMATION ARE IMPORTAN 1661 00:56:07,192 --> 00:56:08,060 BOTH OF THESE SETTINGS. 1662 00:56:08,060 --> 00:56:12,398 SO THIS PARADIGM CAN HELP US 1663 00:56:12,398 --> 00:56:13,065 UNDERSTAND DOWN SYNDROME AS WELL 1664 00:56:13,065 --> 00:56:13,933 AS MECHANISMS THAT MAY BE 1665 00:56:13,933 --> 00:56:15,668 IMPORTANT IN DIABETES AS WELL AS 1666 00:56:15,668 --> 00:56:18,370 OTHER AUTOIMMUNE DISEASES, AND 1667 00:56:18,370 --> 00:56:20,105 HELP US IDENTIFY THERAPEUTIC 1668 00:56:20,105 --> 00:56:21,006 TREATMENTS. 1669 00:56:21,006 --> 00:56:22,541 SO IN THE LAST FEW MINUTES, I 1670 00:56:22,541 --> 00:56:24,243 JUST THOUGHT I'D WIND UP BY 1671 00:56:24,243 --> 00:56:26,645 BRINGING US BACK TO THIS FIGURE, 1672 00:56:26,645 --> 00:56:28,514 AND IT IS A FIGURE I'VE STARTED 1673 00:56:28,514 --> 00:56:32,418 WITH FOR YEARS, TALKING ABOUT 1674 00:56:32,418 --> 00:56:34,386 HOW PEOPLE MOVE FROM HEALTH TO 1675 00:56:34,386 --> 00:56:35,554 DISEASE PERPETUATION. 1676 00:56:35,554 --> 00:56:37,222 AND OF COURSE I'VE SPENT MURCH 1677 00:56:37,222 --> 00:56:38,891 OF MY CAREER TALKING ABOUT THE 1678 00:56:38,891 --> 00:56:39,892 GENETIC FACTORS THAT DRIVE THIS. 1679 00:56:39,892 --> 00:56:41,193 AND I'VE ALWAYS HAD 1680 00:56:41,193 --> 00:56:44,830 ENVIRONMENTAL FACTORS LISTED, 1681 00:56:44,830 --> 00:56:46,198 AND HAVE VERY RARELY BEEN ABLE 1682 00:56:46,198 --> 00:56:47,299 TO SPEAK TO THEM BECAUSE WE 1683 00:56:47,299 --> 00:56:48,267 THINK OF THE ENVIRONMENTAL 1684 00:56:48,267 --> 00:56:51,537 FACTORS AS BEING VERY -- VERY 1685 00:56:51,537 --> 00:56:53,038 DIFFICULT TO MEASURE AND THERE 1686 00:56:53,038 --> 00:56:54,907 ARE SO MANY OF THEM. 1687 00:56:54,907 --> 00:56:58,844 BUT I THINK THE GREAT NEWS IS 1688 00:56:58,844 --> 00:57:00,479 THAT -- WELL, AND I THOUGHT I'D 1689 00:57:00,479 --> 00:57:02,214 BRING OUT THIS SLIDE BECAUSE 1690 00:57:02,214 --> 00:57:03,482 I'VE BEEN TALKING ABOUT THIS FOR 1691 00:57:03,482 --> 00:57:04,917 YEARS USING THAT FIGURE. 1692 00:57:04,917 --> 00:57:07,086 BUT YOU CAN LOOK AT MULTIPLE 1693 00:57:07,086 --> 00:57:09,788 FIGURES FROM OTHER DISEASES. 1694 00:57:09,788 --> 00:57:10,789 TYPE 1 DIABETES HAS THAT 1695 00:57:10,789 --> 00:57:12,858 ENVIRONMENTAL TRIGGER. 1696 00:57:12,858 --> 00:57:13,759 SYSTEMIC LUPUS HAS AN 1697 00:57:13,759 --> 00:57:14,593 ENVIRONMENTAL TRIGGER. 1698 00:57:14,593 --> 00:57:16,929 AND RHEUMATOID ARTHRITIS HAS AN 1699 00:57:16,929 --> 00:57:19,632 ENVIRONMENTAL TRIGGER. 1700 00:57:19,632 --> 00:57:20,866 AND NOW IT'S REALLY TIME FOR US 1701 00:57:20,866 --> 00:57:22,334 AS WE UNDERSTAND THE IMMUNE 1702 00:57:22,334 --> 00:57:24,403 SYSTEM MUCH BETTER, WE 1703 00:57:24,403 --> 00:57:26,005 UNDERSTAND SOME OF THE DRIVERS 1704 00:57:26,005 --> 00:57:32,645 OF YOU A AUTOIMMUNITY AND THE C 1705 00:57:32,645 --> 00:57:33,746 UNDERPINNINGS TO ACTUALLY TACKLE 1706 00:57:33,746 --> 00:57:34,613 THIS QUESTION OF ENVIRONMENTAL 1707 00:57:34,613 --> 00:57:37,950 RISK FACTORS AND AS WAS DI 1708 00:57:37,950 --> 00:57:40,486 DESCRIBED BEFORE, HOW DO WE ASK 1709 00:57:40,486 --> 00:57:41,687 THIS QUESTION, HOW DO WE USE THE 1710 00:57:41,687 --> 00:57:42,655 TOOLS THAT OTHER PEOPLE IN 1711 00:57:42,655 --> 00:57:43,589 ENVIRONMENTAL HEALTH HAVE 1712 00:57:43,589 --> 00:57:44,356 DEVELOPED, PEOPLE IN OTHER 1713 00:57:44,356 --> 00:57:46,892 FIELDS OF MEDICINE HAVE STARTED 1714 00:57:46,892 --> 00:57:49,962 LOOKING AT AND APPLY TO 1715 00:57:49,962 --> 00:57:51,563 AUTOIMMUNITY, SO I'M REALLY 1716 00:57:51,563 --> 00:57:52,765 EXCITED TO BE PART OF THAT GROUP 1717 00:57:52,765 --> 00:57:53,966 TO START FILLING IN THE BLANK 1718 00:57:53,966 --> 00:57:55,167 THAT I'VE LEFT FOR SO MANY 1719 00:57:55,167 --> 00:57:55,567 YEARS. 1720 00:57:55,567 --> 00:57:58,971 AND THEN FINALLY, AS WE MOVE 1721 00:57:58,971 --> 00:58:01,940 FORWARD, WE THINK ABOUT 1722 00:58:01,940 --> 00:58:03,175 DISEASES, REALLY THE ULTIMATE 1723 00:58:03,175 --> 00:58:04,510 GOAL SHOULD BE TO PREVENT 1724 00:58:04,510 --> 00:58:06,378 DISEASES BECAUSE IT IS THE 1725 00:58:06,378 --> 00:58:06,912 ULTIMATE CURE. 1726 00:58:06,912 --> 00:58:08,747 AND WE ARE GETTING TO THE POINT 1727 00:58:08,747 --> 00:58:10,282 IN AUTOIMMUNITY THAT WE CAN 1728 00:58:10,282 --> 00:58:12,785 START THINKING ABOUT PREDICTING, 1729 00:58:12,785 --> 00:58:14,887 AND IN TYPE 1 DIABETES, WE 1730 00:58:14,887 --> 00:58:16,255 ACTUALLY CAN NOW PREDICT THE 1731 00:58:16,255 --> 00:58:19,992 DEVELOPMENT OF CLINICAL 1732 00:58:19,992 --> 00:58:20,426 DIABETES. 1733 00:58:20,426 --> 00:58:22,361 AS I'VE ALREADY DESCRIBED, 1734 00:58:22,361 --> 00:58:24,263 INDIVIDUALS WHO WERE AT HIGH 1735 00:58:24,263 --> 00:58:26,632 RISK FROM FAMILY MEMBER, WE KNOW 1736 00:58:26,632 --> 00:58:28,801 THEY DEVELOP AUTOANTIBODIES BUT 1737 00:58:28,801 --> 00:58:32,471 WHAT WE ALSO KNOW NOW IS IF YOU 1738 00:58:32,471 --> 00:58:33,906 HAVE TWO AUTOANTIBODIES, YOU 1739 00:58:33,906 --> 00:58:34,540 WILL GET DIABETES. 1740 00:58:34,540 --> 00:58:37,242 IF YOU HAVE TWO AUTOANTIBODIES 1741 00:58:37,242 --> 00:58:38,744 AND IMPAIRED GLUCOSE TOLERANCE, 1742 00:58:38,744 --> 00:58:40,079 YOU WILL GET DIABETES MUCH 1743 00:58:40,079 --> 00:58:41,947 SOONER SO WE CALL THAT STAGE 1744 00:58:41,947 --> 00:58:44,183 TWO, AND STAGE THREE IS WHEN YOU 1745 00:58:44,183 --> 00:58:44,883 REQUIRE INSULIN. 1746 00:58:44,883 --> 00:58:47,052 SO BY HAVING STAGES AND KNOWING 1747 00:58:47,052 --> 00:58:48,687 WE CAN PREDICT IT, WE'VE NOW 1748 00:58:48,687 --> 00:58:50,422 BEEN ABLE TO DO CLINICAL TRIALS 1749 00:58:50,422 --> 00:58:52,257 WHERE WE CAN INTERVENE PRIOR TO 1750 00:58:52,257 --> 00:58:54,326 DEVELOPMENT OF CLINICAL DISEASE. 1751 00:58:54,326 --> 00:58:56,862 AND SO TRIALNET DID ONE SUCH 1752 00:58:56,862 --> 00:59:01,066 TRIAL WITH A DRUG CALLED 1753 00:59:01,066 --> 00:59:02,401 TEPLIZUMAB SEVERAL YEARS AGO, 1754 00:59:02,401 --> 00:59:04,403 IT'S ANTI-CD3 AND IT WAS SHOWN 1755 00:59:04,403 --> 00:59:06,038 FIRST TO BE EFFECTIVE IN STAGE 1756 00:59:06,038 --> 00:59:08,373 III, BUT THEN MOVED TO STAGE II. 1757 00:59:08,373 --> 00:59:11,276 SO INDIVIDUALS WHO DO NOT YET 1758 00:59:11,276 --> 00:59:12,044 REQUIRE INSULIN. 1759 00:59:12,044 --> 00:59:15,214 AND IT WAS SHOWN TO DELAY THE 1760 00:59:15,214 --> 00:59:18,951 TYPE OF TYPE 1 DIABETES BY AT 1761 00:59:18,951 --> 00:59:19,585 LEAST TWO YEARS. 1762 00:59:19,585 --> 00:59:20,886 SOME INDIVIDUALS STILL HAVE NOT 1763 00:59:20,886 --> 00:59:21,854 DEVELOPED DIABETES. 1764 00:59:21,854 --> 00:59:24,389 SO IT'S A DRUG THAT WE'VE NOW 1765 00:59:24,389 --> 00:59:25,791 SHOWN COULD DELAY ONSET OF 1766 00:59:25,791 --> 00:59:26,525 DIABETES. 1767 00:59:26,525 --> 00:59:29,795 AND WHAT'S SO EXCITING IS IT'S 1768 00:59:29,795 --> 00:59:32,097 FDA-APPROVED NOW TO TREAT STAGE 1769 00:59:32,097 --> 00:59:32,297 II. 1770 00:59:32,297 --> 00:59:36,001 SO WE HAVE REASON TO GO TO THE 1771 00:59:36,001 --> 00:59:39,138 CLINIC, PREDICT WHO WILL GET 1772 00:59:39,138 --> 00:59:40,272 DIABETES AND SO THAT WE CAN GET 1773 00:59:40,272 --> 00:59:41,907 THEM THIS THERAPY. 1774 00:59:41,907 --> 00:59:43,408 SOME STUDYS ARE NOW GOING ON IN 1775 00:59:43,408 --> 00:59:45,811 ROOM TIED ARTHRITIS WHERE WE 1776 00:59:45,811 --> 00:59:47,312 HAVE AUTOANTIBODIES THAT CAN 1777 00:59:47,312 --> 00:59:48,080 PREDICT DEVELOPMENT OF DISEASE 1778 00:59:48,080 --> 00:59:49,148 AND TRIALS ARE STARTING TO SHOW 1779 00:59:49,148 --> 00:59:49,915 DELAY OF DISEASE. 1780 00:59:49,915 --> 00:59:51,784 SO WE'VE TALKED ABOUT THIS AND 1781 00:59:51,784 --> 00:59:53,552 DREAMED ABOUT IT FOR YEARS. 1782 00:59:53,552 --> 00:59:54,787 WE'RE NOW AT A PLACE WHERE WE 1783 00:59:54,787 --> 00:59:55,354 CAN MOVE FORWARD. 1784 00:59:55,354 --> 00:59:57,289 AND THEN FINALLY WE'RE AT AN ERA 1785 00:59:57,289 --> 00:59:58,257 WITH GROWING TECHNOLOGIES THAT 1786 00:59:58,257 --> 00:59:59,558 ARE GOING TO CHANGE IN MANY WAYS 1787 00:59:59,558 --> 01:00:01,760 HOW WE THINK AND LEARN ABOUT 1788 01:00:01,760 --> 01:00:03,896 AUTOIMMUNITY, FROM MULTI-OMICS 1789 01:00:03,896 --> 01:00:05,964 WHICH ALLOW US TO LOOK VERY 1790 01:00:05,964 --> 01:00:06,899 DEEPLY INTO THE REGULATION OF 1791 01:00:06,899 --> 01:00:09,535 THE GENOME, AND THE MULTIPLE 1792 01:00:09,535 --> 01:00:12,604 CELL TYPES AND TR TRANSCRIPTIONL 1793 01:00:12,604 --> 01:00:14,306 EXPRESSION, TO LOOKING IN THE 1794 01:00:14,306 --> 01:00:16,408 TISSUES AND LOOKING AT CELL-CELL 1795 01:00:16,408 --> 01:00:16,742 INTERACTIONS. 1796 01:00:16,742 --> 01:00:18,577 AND I THINK THIS IS GOING TO BE 1797 01:00:18,577 --> 01:00:19,878 A GREAT STEP FORWARD. 1798 01:00:19,878 --> 01:00:21,180 WE'VE ALREADY LEARNED SO MUCH 1799 01:00:21,180 --> 01:00:23,682 FROM PROJECTS LIKE AMP AIM. 1800 01:00:23,682 --> 01:00:25,284 BUT I'D ALSO SAY THAT THE RULES 1801 01:00:25,284 --> 01:00:26,418 WON'T CHANGE, AND WE STILL -- 1802 01:00:26,418 --> 01:00:28,821 ONCE WE DEVELOP -- GENERATE 1803 01:00:28,821 --> 01:00:31,990 HYPOTHESES FROM THESE NEW 1804 01:00:31,990 --> 01:00:33,926 TECHNOLOGIES, WE WILL THEN AGAIN 1805 01:00:33,926 --> 01:00:35,894 NEED TO APPLY THEM TO WELL 1806 01:00:35,894 --> 01:00:39,598 CHARACTERIZED COHORTS ANGD BE 1807 01:00:39,598 --> 01:00:42,301 ABLE TO MOVE FORWARD TO 1808 01:00:42,301 --> 01:00:43,302 UNDERSTAND HOW TO INTERVENE, 1809 01:00:43,302 --> 01:00:44,603 WHEN TO INTERVENE AND WHO TO 1810 01:00:44,603 --> 01:00:49,308 INTERVENE WITH. 1811 01:00:49,308 --> 01:00:52,444 SO MY TAKE-HOME MESSAGES, 1812 01:00:52,444 --> 01:00:53,545 AUTOIMMUNE IT AFFECTS A LARGE 1813 01:00:53,545 --> 01:00:54,546 PERCENTAGE OF OUR POPULATION. 1814 01:00:54,546 --> 01:00:56,448 AS OF TODAY, IT'S CHRONIC, 1815 01:00:56,448 --> 01:00:59,218 DEBIDEBILITATING AND INCURABLE T 1816 01:00:59,218 --> 01:01:00,219 TOMORROW, I DON'T THINK IT WILL 1817 01:01:00,219 --> 01:01:00,752 BE. 1818 01:01:00,752 --> 01:01:02,588 IMPORTANTLY FOR WOMEN IS THAT IT 1819 01:01:02,588 --> 01:01:03,555 REALLY DISPROPORTIONATELY 1820 01:01:03,555 --> 01:01:04,656 IMPACTS WOMEN AND I WILL SAY IT 1821 01:01:04,656 --> 01:01:06,058 IMPACTS WOMEN AT RELATIVELY 1822 01:01:06,058 --> 01:01:08,126 YOUNG AGES, SO THEY HAVE A LIFE 1823 01:01:08,126 --> 01:01:11,430 OF LIVING WITH THESE DISEASES. 1824 01:01:11,430 --> 01:01:12,798 SO I THINK IT'S REALLY VITAL AS 1825 01:01:12,798 --> 01:01:15,734 WE THINK ABOUT TREATING WOMEN 1826 01:01:15,734 --> 01:01:18,070 AND GIVING THEM BETTER HEALTH TO 1827 01:01:18,070 --> 01:01:19,771 FOCUS ON AUTOIMMUNITY. 1828 01:01:19,771 --> 01:01:21,974 I'VE TALKED ABOUT HOW THE IMMUNE 1829 01:01:21,974 --> 01:01:23,508 CENTRAL IS CENTRAL AND ITS 1830 01:01:23,508 --> 01:01:24,877 DYSFUNCTION IS DRIVEN BY 1831 01:01:24,877 --> 01:01:25,410 GENETICS AND ENVIRONMENT. 1832 01:01:25,410 --> 01:01:26,645 AND I THINK IF WE COULD 1833 01:01:26,645 --> 01:01:28,046 UNDERSTAND THESE PATHWAYS EVEN 1834 01:01:28,046 --> 01:01:29,882 BETTER THAN WE DO TODAY, WE 1835 01:01:29,882 --> 01:01:32,951 COULD TREAT AUTOIMMUNE DISEASES 1836 01:01:32,951 --> 01:01:35,254 BETTER AND I BELIEVE NEW 1837 01:01:35,254 --> 01:01:36,221 THERAPIES ARE COMING DOWN THE 1838 01:01:36,221 --> 01:01:38,624 PIPE THAT ARE GOING TO LET US 1839 01:01:38,624 --> 01:01:40,158 USE A TARGETED FORM OF THERAPY 1840 01:01:40,158 --> 01:01:43,528 SO WE DON'T GLOBALLY 1841 01:01:43,528 --> 01:01:44,096 IMMUNOSUPPRESS PEOPLE. 1842 01:01:44,096 --> 01:01:46,465 WE ARE REALLY KNOCKING AT THE 1843 01:01:46,465 --> 01:01:47,900 DOOR AT PREDICTION AND 1844 01:01:47,900 --> 01:01:48,200 PREVENTION. 1845 01:01:48,200 --> 01:01:49,201 WE NEED TO INVEST HERE. 1846 01:01:49,201 --> 01:01:50,836 WE NEED TO BRING THIS INTO 1847 01:01:50,836 --> 01:01:51,937 REALITY INTO THE CLINIC SO THAT 1848 01:01:51,937 --> 01:01:53,472 PATIENTS ARE GETTING SCREENED 1849 01:01:53,472 --> 01:01:54,940 JUST LIKE WE SCREEN FOR HIGH 1850 01:01:54,940 --> 01:01:57,576 BLOOD PRESSURE AND HIGH 1851 01:01:57,576 --> 01:01:58,677 CHOLESTEROL, WE COULD SCREEN FOR 1852 01:01:58,677 --> 01:01:59,678 AUTOIMMUNE DISEASES AND PREVENT 1853 01:01:59,678 --> 01:02:01,747 THEM, THAT WOULD BE THE ULTIMATE 1854 01:02:01,747 --> 01:02:02,915 CURE. 1855 01:02:02,915 --> 01:02:05,117 AND JUST FINALLY, MY 1856 01:02:05,117 --> 01:02:05,651 ACKNOWLEDGMENTS. 1857 01:02:05,651 --> 01:02:07,853 INCLUDING THE MEMBERS OF MY LAB 1858 01:02:07,853 --> 01:02:10,789 TEAM, MY INVESTIGATORS BRI, AND 1859 01:02:10,789 --> 01:02:12,424 I HAVE MANY COLLABORATORS. 1860 01:02:12,424 --> 01:02:14,960 I'VE PICTURED SOME OF THE KEY 1861 01:02:14,960 --> 01:02:16,228 PEOPLE HERE WHO HELPED ME WITH 1862 01:02:16,228 --> 01:02:18,997 THIS WORK OVER THE YEARS, AND 1863 01:02:18,997 --> 01:02:24,403 DAVID RAWLINGS IS MY 1864 01:02:24,403 --> 01:02:27,472 LONG-STANDING COLLEAGUE WHO IS 1865 01:02:27,472 --> 01:02:29,541 AN EXPERT IN GENE EDITING AND 1866 01:02:29,541 --> 01:02:32,344 HELPS WITH ENGINEERED REGULATORY 1867 01:02:32,344 --> 01:02:33,445 T CELLS. 1868 01:02:33,445 --> 01:02:35,747 OF COURSE FUNDING IS ALWAYS 1869 01:02:35,747 --> 01:02:37,916 VITAL TO DOING OUR WORK. 1870 01:02:37,916 --> 01:02:41,219 >> THANK YOU, DR. BUCKNER, FOR 1871 01:02:41,219 --> 01:02:43,922 THAT INCREDIBLE WHIRLWIND 1872 01:02:43,922 --> 01:02:45,457 PRESENTATION, REALLY ELEGANT 1873 01:02:45,457 --> 01:02:46,525 EXPLANATION OF HOW YOU THOUGHT 1874 01:02:46,525 --> 01:02:48,961 THROUGH ALL OF THE PATHWAYS AND 1875 01:02:48,961 --> 01:02:50,028 WE'RE CLOSE TO TIME BUT I THINK 1876 01:02:50,028 --> 01:02:55,834 I WANT TO ASK YOU ONE QUESTION. 1877 01:02:55,834 --> 01:02:57,336 CAN YOU TALK A LITTLE BIT ABOUT 1878 01:02:57,336 --> 01:03:03,809 WHERE YOU THINK I NFL AMMAGING 1879 01:03:03,809 --> 01:03:06,578 IS GOING TO LEAD US AND BROADER 1880 01:03:06,578 --> 01:03:07,512 APPLICATIONS OF THAT CONCEPT? 1881 01:03:07,512 --> 01:03:09,314 >> SO I THINK MY COLLEAGUE 1882 01:03:09,314 --> 01:03:10,182 BERNARD ALWAYS TALKS ABOUT 1883 01:03:10,182 --> 01:03:13,485 LOOKING AT OUR PATIENTS AGE, 1884 01:03:13,485 --> 01:03:14,753 THEIR IMMUNE AGE AS OPPOSED TO 1885 01:03:14,753 --> 01:03:16,722 THEIR AGE ON THEIR DRIVER'S 1886 01:03:16,722 --> 01:03:17,155 LICENSE. 1887 01:03:17,155 --> 01:03:19,458 AND SO HOW WE WOULD TREAT PEOPLE 1888 01:03:19,458 --> 01:03:21,760 MAY DEPEND A BIT ON THEIR IMMUNE 1889 01:03:21,760 --> 01:03:23,395 AGE, AND I THINK IT WILL, ONE, 1890 01:03:23,395 --> 01:03:26,865 HELP US THINK ABOUT THEIR RISK 1891 01:03:26,865 --> 01:03:29,634 FOR DISEASE, AND AN IMPORTANT 1892 01:03:29,634 --> 01:03:31,670 EXAMPLE OF THIS IS WE GIVE A 1893 01:03:31,670 --> 01:03:34,940 DIFFERENT VACCINE TO PEOPLE WHO 1894 01:03:34,940 --> 01:03:37,309 ARE OLDER FOR FLU. 1895 01:03:37,309 --> 01:03:38,643 WELL, WE JUST PICK A NUMBER 1896 01:03:38,643 --> 01:03:40,045 TODAY, BUT REALLY SHOULD WE BE 1897 01:03:40,045 --> 01:03:42,848 PICKING THAT NUMBER BASED ON 1898 01:03:42,848 --> 01:03:43,849 YOUR IMMUNE AGE? 1899 01:03:43,849 --> 01:03:45,183 SO ONE OF THE STUDIES BERNARD IS 1900 01:03:45,183 --> 01:03:47,019 DOING RIGHT NOW IN INDIVIDUALS 1901 01:03:47,019 --> 01:03:51,390 WITH DOWN SYNDROME IS TO TEST 1902 01:03:51,390 --> 01:03:52,824 WHETHER WE SHOULD BE GIVING THEM 1903 01:03:52,824 --> 01:03:54,226 A DIFFERENT VACCINE BECAUSE 1904 01:03:54,226 --> 01:03:55,727 THEIR IMMUNE AGE IS REALLY 15 1905 01:03:55,727 --> 01:03:56,028 YEARS OLDER. 1906 01:03:56,028 --> 01:03:57,596 SO THAT'S A SIMPLE EXPLANATION. 1907 01:03:57,596 --> 01:04:00,866 BUT I THINK RISK OF CHRONIC 1908 01:04:00,866 --> 01:04:02,367 ILLNESS AND HOW DO WE DO 1909 01:04:02,367 --> 01:04:04,336 VACCINATIONS WOULD BE ONE EASY 1910 01:04:04,336 --> 01:04:05,137 AND VERY STRAIGHTFORWARD 1911 01:04:05,137 --> 01:04:07,839 APPROACH. 1912 01:04:07,839 --> 01:04:09,908 AND I ALSO -- ONE MORE THING, I 1913 01:04:09,908 --> 01:04:11,109 ACTUALLY THINK THAT BECAUSE WE 1914 01:04:11,109 --> 01:04:14,046 ARE NOT ONLY IDENTIFYING WAYS TO 1915 01:04:14,046 --> 01:04:15,113 IDENTIFY IMMUNE AGE BUT THE 1916 01:04:15,113 --> 01:04:16,748 FACTORS THAT DRIVE IMMUNE AGE, 1917 01:04:16,748 --> 01:04:18,617 WE COULD SLOW IT DOWN WITH 1918 01:04:18,617 --> 01:04:20,252 INTERVENTIONS THAT TARGET THOSE 1919 01:04:20,252 --> 01:04:20,485 DRIVERS. 1920 01:04:20,485 --> 01:04:21,319 >> OKAY. 1921 01:04:21,319 --> 01:04:22,754 WELL, WE ALWAYS WANT TO SLOW 1922 01:04:22,754 --> 01:04:24,089 DOWN AGING OF ALL KINDS, SO 1923 01:04:24,089 --> 01:04:26,558 THANK YOU FOR THAT FASCINATING 1924 01:04:26,558 --> 01:04:28,393 NUGGET THAT YOU LEFT US WITH. 1925 01:04:28,393 --> 01:04:29,828 AGAIN, THANK YOU SO MUCH FOR 1926 01:04:29,828 --> 01:04:32,030 SERVING AS OUR EIGHTH ANNUAL 1927 01:04:32,030 --> 01:04:33,832 VIVIAN PINN SYMPOSIUM KEYNOTE 1928 01:04:33,832 --> 01:04:34,066 SPEAKER. 1929 01:04:34,066 --> 01:04:36,568 YOU'VE GIVEN US SO MUCH TO THINK 1930 01:04:36,568 --> 01:04:38,336 ABOUT, AND WE WILL LOOK FORWARD 1931 01:04:38,336 --> 01:04:40,105 TO ALL THE FOLLOW-UP ON THE 1932 01:04:40,105 --> 01:04:41,907 EXACT PLAN AS WELL, AS YOU'RE 1933 01:04:41,907 --> 01:04:43,442 TAKING A LEADERSHIP ROLE THERE 1934 01:04:43,442 --> 01:04:45,210 TOO, SO THANK YOU SO MUCH, ON 1935 01:04:45,210 --> 01:04:48,246 BEHALF OF OADR AND ORWH, 1936 01:04:48,246 --> 01:04:49,648 DR. BUCKNER, FOR THAT AMAZING 1937 01:04:49,648 --> 01:04:52,050 KEYNOTE SPEECH. 1938 01:04:52,050 --> 01:04:52,451 >> THANK YOU. 1939 01:04:52,451 --> 01:04:54,119 >> AND WITH THAT, WE WILL 1940 01:04:54,119 --> 01:04:58,824 TRANSITION OVER TO DR. VICTORIA 1941 01:04:58,824 --> 01:04:59,191 SHANMUGAM. 1942 01:04:59,191 --> 01:05:03,428 I WANT TO EXHIB INTRODUCE THE FT 1943 01:05:03,428 --> 01:05:06,665 DIRECTOR OF THE OFFICE OF 1944 01:05:06,665 --> 01:05:08,200 AUTOIMMUNE DISEASE RESEARCH IN 1945 01:05:08,200 --> 01:05:09,568 THE OFFICE OF RESEARCH ON 1946 01:05:09,568 --> 01:05:10,235 WOMEN'S HEALTH. 1947 01:05:10,235 --> 01:05:11,503 SHE PREVIOUSLY SERVED AS 1948 01:05:11,503 --> 01:05:13,405 DIRECTOR OF RHEUMATOLOGY AT THE 1949 01:05:13,405 --> 01:05:15,273 GEORGE WASHINGTON UNIVERSITY AND 1950 01:05:15,273 --> 01:05:17,242 NOW SERVES AS OUR FIRST DIRECTOR 1951 01:05:17,242 --> 01:05:18,510 OF THE NIH OFFICE OF AUTOIMMUNE 1952 01:05:18,510 --> 01:05:19,878 DISEASE RESEARCH WITHIN THE 1953 01:05:19,878 --> 01:05:22,547 OFFICE OF RESEARCH ON WOMEN'S 1954 01:05:22,547 --> 01:05:23,615 HEALTH. 1955 01:05:23,615 --> 01:05:24,516 DR. SHANMUGAM TOOK A LEADERSHIP 1956 01:05:24,516 --> 01:05:26,151 ROLE IN DEVELOPING THIS YEAR'S 1957 01:05:26,151 --> 01:05:27,719 VIVIAN PINN SYMPOSIUM PROGRAM, 1958 01:05:27,719 --> 01:05:29,287 SO I WANT TO THANK YOU FOR YOUR 1959 01:05:29,287 --> 01:05:30,489 LEADERSHIP THERE, VICKIE, AND 1960 01:05:30,489 --> 01:05:32,023 I'LL TURN IT OVER TO YOU. 1961 01:05:32,023 --> 01:05:33,658 >> THANK YOU SO MUCH. 1962 01:05:33,658 --> 01:05:36,795 THANK YOU, DR. BUCKNER, FOR THAT 1963 01:05:36,795 --> 01:05:38,997 WONDERFUL TALK AND INTRODUCING 1964 01:05:38,997 --> 01:05:40,132 US AND SETTING THE STAGE AND 1965 01:05:40,132 --> 01:05:41,833 THANK YOU, DR. CLAYTON, FOR THAT 1966 01:05:41,833 --> 01:05:43,235 KIND INTRODUCTION. 1967 01:05:43,235 --> 01:05:45,036 IT'S NOW MY GREAT PLEASURE TO 1968 01:05:45,036 --> 01:05:46,638 KICK OFF OUR INSIDE INNOVATION 1969 01:05:46,638 --> 01:05:48,173 SESSION FOCUSED ON SOME OF THE 1970 01:05:48,173 --> 01:05:50,142 INTRAMURAL PROGRAMS THAT ARE 1971 01:05:50,142 --> 01:05:52,944 HAVING IMPACT AT NIH AND AROUND 1972 01:05:52,944 --> 01:05:53,411 THE WORLD. 1973 01:05:53,411 --> 01:05:54,813 WE HAVE THREE AMAZING SPEAKERS 1974 01:05:54,813 --> 01:05:55,814 FOR YOU TODAY AND WE'RE GOING TO 1975 01:05:55,814 --> 01:05:57,449 SAVE THE PANEL DISCUSSION UNTIL 1976 01:05:57,449 --> 01:05:59,518 THE END SO YOU CAN PUT QUESTIONS 1977 01:05:59,518 --> 01:06:01,386 IN THE Q & A AT ANY POINT DURING 1978 01:06:01,386 --> 01:06:02,454 THESE THREE TALKS, AND I'LL TRY 1979 01:06:02,454 --> 01:06:04,422 TO GET TO AS MANY OF THEM AS WE 1980 01:06:04,422 --> 01:06:08,560 CAN DURING THE DISCUSSION. 1981 01:06:08,560 --> 01:06:09,728 NEXT I'M GOING TO INTRODUCE OUR 1982 01:06:09,728 --> 01:06:11,530 THREE WONDERFUL PANELISTS FOR 1983 01:06:11,530 --> 01:06:15,033 THEIR BIOGRAPHIES, PLEASE REFER 1984 01:06:15,033 --> 01:06:16,668 TO THE PROGRAM BOOKLET WHICH 1985 01:06:16,668 --> 01:06:18,303 WE'RE DROPPING INTO THE CHAT. 1986 01:06:18,303 --> 01:06:19,171 DR. LAURA LEWANDOWSKI IS 1987 01:06:19,171 --> 01:06:19,971 ASSISTANT CLINICAL INVESTIGATOR 1988 01:06:19,971 --> 01:06:21,706 AND HEAD OF THE LUPUS GENOMICS 1989 01:06:21,706 --> 01:06:23,875 AND GLOBAL HEALTH DISPARITIES 1990 01:06:23,875 --> 01:06:25,310 UNIT AT NIAMS. 1991 01:06:25,310 --> 01:06:27,179 HER CURRENT RESEARCH INTERESTS 1992 01:06:27,179 --> 01:06:29,114 INCLUDE CLINICAL AND 1993 01:06:29,114 --> 01:06:30,882 TRANSLATIONAL RESEARCH IN 1994 01:06:30,882 --> 01:06:31,883 PEDIATRIC SYSTEMIC 1995 01:06:31,883 --> 01:06:43,428 LEUKOENCEPHALOPATSYSTEMIC LUPUS. 1996 01:06:43,428 --> 01:06:44,763 DR. STEVEN HOLLAND IS DIRECTOR 1997 01:06:44,763 --> 01:06:47,999 OF THE DIVISION OF INTRAMURAL 1998 01:06:47,999 --> 01:06:49,935 RESEARCH, ALSO SERVES AS CHIEF 1999 01:06:49,935 --> 01:06:52,704 OF THE IMMUNE PATHOGENESIS 2000 01:06:52,704 --> 01:06:54,139 SECTION AND HIS RESEARCH IS 2001 01:06:54,139 --> 01:06:56,074 FOCUSED ON PATHOGENESIS AND 2002 01:06:56,074 --> 01:06:58,810 MANAGEMENT OF CHRONIC 2003 01:06:58,810 --> 01:06:59,578 GRANULOMATOUS DISEASE AS WELL AS 2004 01:06:59,578 --> 01:07:01,413 A LARGE NUMBER OF OTHER IMMUNE 2005 01:07:01,413 --> 01:07:03,181 DEFICIENCIES OF WHICH SOME HE'S 2006 01:07:03,181 --> 01:07:04,916 GOING TO TELL US ABOUT TODAY. 2007 01:07:04,916 --> 01:07:09,187 AND THEN FINALLY, DR. ALISON 2008 01:07:09,187 --> 01:07:10,622 MOTSINGER-REIF IS THE CHIEF AND 2009 01:07:10,622 --> 01:07:11,923 PRINCIPAL INVESTIGATOR IN THE 2010 01:07:11,923 --> 01:07:13,892 BIOSTATISTICS AND COMPUTATIONAL 2011 01:07:13,892 --> 01:07:16,061 BIOLOGY BRANCH AT NIEHS. 2012 01:07:16,061 --> 01:07:18,029 HER WORK FOCUSES ON THE 2013 01:07:18,029 --> 01:07:19,998 DEVELOPMENT AND APPLICATION OF 2014 01:07:19,998 --> 01:07:21,833 MODERN STATISTICAL APPROACHES 2015 01:07:21,833 --> 01:07:23,802 FOR UNDERSTANDING THE ETIOLOGY 2016 01:07:23,802 --> 01:07:27,739 OF COMMON YET COMPLEX DISEASES. 2017 01:07:27,739 --> 01:07:28,907 WE ARE LOOKING FORWARD TO ALL OF 2018 01:07:28,907 --> 01:07:30,475 THE TALKS BUT WITHOUT FURTHER 2019 01:07:30,475 --> 01:07:31,876 ADO, I AM GOING TO PASS THE 2020 01:07:31,876 --> 01:07:33,645 VIRTUAL MICROPHONE OVER TO 2021 01:07:33,645 --> 01:07:34,613 DR. LAURA LEWANDOWSKI TO GET US 2022 01:07:34,613 --> 01:07:36,548 STARTED. 2023 01:07:36,548 --> 01:07:38,583 LAURA. 2024 01:07:38,583 --> 01:07:40,952 >> THANK YOU SO MUCH FOR THAT 2025 01:07:40,952 --> 01:07:41,953 LOVELY INTRODUCTION, AND I'M 2026 01:07:41,953 --> 01:07:43,989 JUST SO EXCITED AND DELIGHTED TO 2027 01:07:43,989 --> 01:07:48,927 BE HERE TODAY AS PART OF THIS 2028 01:07:48,927 --> 01:07:49,394 SYMPOSIUM. 2029 01:07:49,394 --> 01:07:51,863 I AM GOING TO TALK TODAY ABOUT 2030 01:07:51,863 --> 01:07:53,064 UNDERSTANDING GENETIC DRIVERS OF 2031 01:07:53,064 --> 01:07:55,900 EARLY ONSET LUPUS AND GLOBAL 2032 01:07:55,900 --> 01:07:57,002 POPULATIONS, AND I ALWAYS LIKE 2033 01:07:57,002 --> 01:07:58,570 TO PUT MY ACKNOWLEDGMENTS AT THE 2034 01:07:58,570 --> 01:08:01,373 BEGINNING OF MY TALK BECAUSE 2035 01:08:01,373 --> 01:08:03,575 NONE OF THIS WORK WOULD EVER GET 2036 01:08:03,575 --> 01:08:05,310 DONE WITHOUT THESE AMAZING TEAMS 2037 01:08:05,310 --> 01:08:07,178 OF PEOPLE IN MY LAB AND MY 2038 01:08:07,178 --> 01:08:08,480 MENTOR'S LAB AND WITH MY 2039 01:08:08,480 --> 01:08:09,147 COLLABORATORS AROUND THE WORLD, 2040 01:08:09,147 --> 01:08:11,316 SO I JUST WANT TO MAKE SURE TO 2041 01:08:11,316 --> 01:08:12,083 ACKNOWLEDGE THEIR ROLE AND OF 2042 01:08:12,083 --> 01:08:13,852 COURSE THE ROLE OF THE AMAZING 2043 01:08:13,852 --> 01:08:18,089 PATIENTS THAT I WORK WITH. 2044 01:08:18,089 --> 01:08:22,594 SO LUPUS OR SLE IS A CHRONIC 2045 01:08:22,594 --> 01:08:23,995 SYSTEMIC AUTOIMMUNE DISEASE THAT 2046 01:08:23,995 --> 01:08:26,631 CURRENTLY HAS NO CURE. 2047 01:08:26,631 --> 01:08:29,301 BECAUSE IT IS A SYSTEMIC 2048 01:08:29,301 --> 01:08:30,335 AUTOIMMUNE DISEASE, IT CAN 2049 01:08:30,335 --> 01:08:31,336 AFFECT ANY ORGAN SYSTEM. 2050 01:08:31,336 --> 01:08:33,071 YOU CAN SEE SOME OF THE 2051 01:08:33,071 --> 01:08:34,506 MANIFESTATIONS ON THE SLIDE I'VE 2052 01:08:34,506 --> 01:08:36,141 PRESENTED HERE, AND IT IS 2053 01:08:36,141 --> 01:08:37,242 CURRENTLY ONE OF THE LEADING 2054 01:08:37,242 --> 01:08:38,643 CAUSES OF DEATH IN YOUNG WOMEN 2055 01:08:38,643 --> 01:08:40,145 IN THE UNITED STATES FROM 2056 01:08:40,145 --> 01:08:43,014 CHRONIC DISEASE. 2057 01:08:43,014 --> 01:08:45,617 AND MY WORK WITH LUPUS AND 2058 01:08:45,617 --> 01:08:47,786 GLOBAL POPULATIONS REALLY BEGAN 2059 01:08:47,786 --> 01:08:49,154 DURING MY FELLOWSHIP TRAINING, 2060 01:08:49,154 --> 01:08:50,088 WHERE I WORKED AT THE HOSPITAL 2061 01:08:50,088 --> 01:08:52,157 THAT YOU CAN SEE PICTURED ON THE 2062 01:08:52,157 --> 01:08:54,559 LEFT HERE, RED CROSS CHILDREN'S 2063 01:08:54,559 --> 01:08:56,061 HOSPITAL IN CAPETOWN, SOUTH 2064 01:08:56,061 --> 01:09:00,031 AFRICA, AND I WORKED WITH MY 2065 01:09:00,031 --> 01:09:00,699 COLLABORATOR STUDYING LUPUS 2066 01:09:00,699 --> 01:09:02,000 PATIENTS THERE. 2067 01:09:02,000 --> 01:09:03,868 NOW I WAS INTERESTED IN 2068 01:09:03,868 --> 01:09:04,969 CHILDHOOD ONSET LUPUS BECAUSE 2069 01:09:04,969 --> 01:09:06,438 I'M A PEDIATRIC RHEUMATOLOGIST 2070 01:09:06,438 --> 01:09:08,873 AND ACTUALLY ONE OUT OF EVERY 2071 01:09:08,873 --> 01:09:10,408 FIVE LUPUS CASES IS DIAGNOSED 2072 01:09:10,408 --> 01:09:11,276 DURING CHILDHOOD. 2073 01:09:11,276 --> 01:09:13,712 AND CHILDREN HAVE A REALLY 2074 01:09:13,712 --> 01:09:15,980 SEVERE DISEASE MANIFESTATION, SO 2075 01:09:15,980 --> 01:09:16,881 THEY HAVE HIGHER DISEASE 2076 01:09:16,881 --> 01:09:17,949 ACTIVITY, THEY NEED MORE 2077 01:09:17,949 --> 01:09:18,950 THERAPY, THEY'RE MORE LIKELY TO 2078 01:09:18,950 --> 01:09:20,618 HAVE THE SERIOUS MANIFESTATIONS 2079 01:09:20,618 --> 01:09:21,986 OF DISEASE LIKE INFLAMMATION IN 2080 01:09:21,986 --> 01:09:23,321 THEIR BRAINS OR IN THEIR 2081 01:09:23,321 --> 01:09:24,923 KIDNEYS, AND THEY ACTUALLY 2082 01:09:24,923 --> 01:09:26,358 ACCRUE MORE ORGAN DAMAGE THAN 2083 01:09:26,358 --> 01:09:28,193 ADULTS DESPITE HAVING YOUNGER, 2084 01:09:28,193 --> 01:09:28,993 HEALTHIER BODIES. 2085 01:09:28,993 --> 01:09:32,263 WE'VE HEARD A LOT TODAY ABOUT 2086 01:09:32,263 --> 01:09:34,766 THE FEMALE PREDOMINENCE IN 2087 01:09:34,766 --> 01:09:35,533 AUTOIMMUNE DISEASE AND THAT'S 2088 01:09:35,533 --> 01:09:38,136 CERTAINLY TRUE IN LUPUS IN 2089 01:09:38,136 --> 01:09:40,638 ADULTHOOD, BUT INTERESTINGLY IN 2090 01:09:40,638 --> 01:09:42,073 PREPUBERTAL CHILDREN, THE RATIO 2091 01:09:42,073 --> 01:09:43,808 IS ABOUT FOUR FEMALES FOR EVERY 2092 01:09:43,808 --> 01:09:45,343 ONE MALE, AND THEN AS IT GOES 2093 01:09:45,343 --> 01:09:46,644 THROUGH ADOLESCENCE AND 2094 01:09:46,644 --> 01:09:48,079 ADULTHOOD, IT GETS CLOSER TO 2095 01:09:48,079 --> 01:09:49,814 THAT 9 TO 1 RATIO. 2096 01:09:49,814 --> 01:09:51,883 SO STUDYING THIS DISEASE ACROSS 2097 01:09:51,883 --> 01:09:54,185 THE LIFESPAN CAN HELP US KIND OF 2098 01:09:54,185 --> 01:09:55,453 ELUCIDATE THE ROLE OF GENETICS 2099 01:09:55,453 --> 01:09:56,521 AND HORMONES AND SOME OF THE 2100 01:09:56,521 --> 01:10:00,859 OTHER FACTORS IN THE FEMALE 2101 01:10:00,859 --> 01:10:02,394 PREDISPOSITION TO AUTOIMMUNITY. 2102 01:10:02,394 --> 01:10:04,129 AND BECAUSE THEY CAN PRESENT IN 2103 01:10:04,129 --> 01:10:06,531 ANY ORGAN SYSTEM, IT IS VERY 2104 01:10:06,531 --> 01:10:10,235 HETEROGENEOUS AND THAT MAKES 2105 01:10:10,235 --> 01:10:10,802 DEFINING END POINTS FOR 2106 01:10:10,802 --> 01:10:12,437 EVERYBODY AND FINDING EFFECTIVE 2107 01:10:12,437 --> 01:10:13,638 THERAPIES AND CLINICAL TRIALS 2108 01:10:13,638 --> 01:10:14,839 REALLY CHALLENGING BECAUSE 2109 01:10:14,839 --> 01:10:16,474 THERE'S SO MANY WAYS THAT LUPUS 2110 01:10:16,474 --> 01:10:20,078 CAN PRESENT. 2111 01:10:20,078 --> 01:10:21,513 I WAS INTERESTED IN STUDYING 2112 01:10:21,513 --> 01:10:23,248 LUPUS IN CHILDREN IN AFRICA 2113 01:10:23,248 --> 01:10:24,215 BECAUSE WE KNOW THAT LUPUS IS 2114 01:10:24,215 --> 01:10:25,884 MORE SEVERE IN CHILDREN AND MORE 2115 01:10:25,884 --> 01:10:29,587 SEVERE IN PEOPLE WHO ARE AFRICAN 2116 01:10:29,587 --> 01:10:31,556 AMERICAN IN THE U.S., BUT THERE 2117 01:10:31,556 --> 01:10:33,725 WAS VERY LITTLE DATA AT THE TIME 2118 01:10:33,725 --> 01:10:36,694 ON CHILDREN IN AFRICA. 2119 01:10:36,694 --> 01:10:37,996 WHEN I WENT TO SEE IF THEY WERE 2120 01:10:37,996 --> 01:10:39,330 SEVERE AS WELL, THERE WAS JUST 2121 01:10:39,330 --> 01:10:41,065 VERY LITTLE INFORMATION, AND SO 2122 01:10:41,065 --> 01:10:44,235 THERE'S A LACK OF PEDIATRIC 2123 01:10:44,235 --> 01:10:45,537 RHEUMATOLOGY ACCESS IN MANY 2124 01:10:45,537 --> 01:10:46,838 PARTS OF THE WORLD SO FIGURE A 2125 01:10:46,838 --> 01:10:48,807 HERE IS WHERE MOST OF THE 2126 01:10:48,807 --> 01:10:50,875 WORLD'S PEDIATRIC POPULATION IS 2127 01:10:50,875 --> 01:10:51,409 CONCENTRATED. 2128 01:10:51,409 --> 01:10:53,411 THE DARKER THE COLOR, THE MORE 2129 01:10:53,411 --> 01:10:54,245 PEDIATRIC POPULATION. 2130 01:10:54,245 --> 01:10:57,682 AND YOU CAN SEE, IND KOOF OF 2131 01:10:57,682 --> 01:10:58,750 CONCENTRATED IN LESS RESOURCE 2132 01:10:58,750 --> 01:11:01,386 AREAS SO SUB-SAHARAN AFRICA, 2133 01:11:01,386 --> 01:11:02,287 SOUTHEAST ASIA, ASIA. 2134 01:11:02,287 --> 01:11:04,122 IF YOU LOOK AT WHERE MOST OF THE 2135 01:11:04,122 --> 01:11:05,990 WORLD'S PEDIATRIC 2136 01:11:05,990 --> 01:11:06,858 RHEUMATOLOGISTS LIVE IN FIGURE 2137 01:11:06,858 --> 01:11:09,260 B, IT'S KIND OF AN INVERSE MAP. 2138 01:11:09,260 --> 01:11:10,595 SO MOST LIVE IN NORTH AMERICA 2139 01:11:10,595 --> 01:11:10,895 AND EUROPE. 2140 01:11:10,895 --> 01:11:13,097 SO WE ACTUALLY UNDERSTAND VERY 2141 01:11:13,097 --> 01:11:14,732 LITTLE ABOUT THE GLOBAL BURDEN 2142 01:11:14,732 --> 01:11:16,034 OF CHILDHOOD ONSET LUPUS. 2143 01:11:16,034 --> 01:11:19,204 SO I MOVED TO SOUTH AFRICA TO 2144 01:11:19,204 --> 01:11:21,639 STUDY THE LUPUS PATIENTS THERE, 2145 01:11:21,639 --> 01:11:23,475 AND ALONG WITH MY COLLEAGUES, 2146 01:11:23,475 --> 01:11:25,310 DEVELOPED THE LARGEST REGISTRY 2147 01:11:25,310 --> 01:11:27,512 OF CHILDREN WITH LUPUS IN 2148 01:11:27,512 --> 01:11:28,513 SUB-SAHARAN AFER KA. WE FOUND 2149 01:11:28,513 --> 01:11:30,281 THAT THEY DO HAVE MORE SEVERE 2150 01:11:30,281 --> 01:11:31,783 DISEASE THAN THEIR ADULT 2151 01:11:31,783 --> 01:11:32,984 COUNTERPARTS LIKE IN THE U.S., 2152 01:11:32,984 --> 01:11:35,920 BUT EVEN WHEN WE COMPARE THEM TO 2153 01:11:35,920 --> 01:11:37,589 CHILDREN LIVING IN NORTH 2154 01:11:37,589 --> 01:11:46,431 AMERICA, THEY HAVE MORE -- I WAS 2155 01:11:46,431 --> 01:11:48,399 CONVINCED THAT STUDYING LUPUS IN 2156 01:11:48,399 --> 01:11:49,501 MORE DIVERSE POPULATIONS WAS 2157 01:11:49,501 --> 01:11:50,802 CRITICAL TO REALLY UNDERSTANDING 2158 01:11:50,802 --> 01:11:51,703 THE DISEASE. 2159 01:11:51,703 --> 01:11:54,873 BUT IT WASN'T AN EASY TASK TO 2160 01:11:54,873 --> 01:11:56,941 THINK ABOUT BIOLOGIC DRIVERS IN 2161 01:11:56,941 --> 01:11:58,142 DIFFERENT POPULATIONS BECAUSE 2162 01:11:58,142 --> 01:11:59,244 THERE'S UNEQUAL ACCESS TO 2163 01:11:59,244 --> 01:12:00,245 CLINICAL CARE, OF COURSE, BUT 2164 01:12:00,245 --> 01:12:01,980 EVEN MORE UNEQUAL ACCESS TO 2165 01:12:01,980 --> 01:12:04,749 RESEARCH. 2166 01:12:04,749 --> 01:12:08,019 SO UNLIKE SOME TYPES OF 2167 01:12:08,019 --> 01:12:09,020 RESEARCH, TRANSLATIONAL RESEARCH 2168 01:12:09,020 --> 01:12:11,723 NOT ONLY REQUIRES A CLINICAL 2169 01:12:11,723 --> 01:12:12,490 RHEUMATOLOGIST, BUT THERE NEEDS 2170 01:12:12,490 --> 01:12:14,025 TO BE THINGS IN PLACE FOR 2171 01:12:14,025 --> 01:12:16,528 BIOSAMPLE COLLECTION, STORAGE, 2172 01:12:16,528 --> 01:12:18,296 THE ABILITY TO RUN THAT SAMPLE 2173 01:12:18,296 --> 01:12:19,497 AND THEN EXPERIMENT THE ABILITY 2174 01:12:19,497 --> 01:12:20,932 TO ANALYZE THE RESULTS. 2175 01:12:20,932 --> 01:12:24,202 AND THAT REQUIRES SOME REAL 2176 01:12:24,202 --> 01:12:25,069 RESEARCH INFRASTRUCTURE AND 2177 01:12:25,069 --> 01:12:27,372 SUSTAINED FUNDING, WHICH IS NOT 2178 01:12:27,372 --> 01:12:28,506 AVAILABLE IN ALL PLACES IN THE 2179 01:12:28,506 --> 01:12:31,309 WORLD. 2180 01:12:31,309 --> 01:12:34,145 SO THAT HAS REALLY LED TO GLOBAL 2181 01:12:34,145 --> 01:12:35,446 DISPARITIES IN GENETIC RESEARCH. 2182 01:12:35,446 --> 01:12:37,215 THIS IS A FIGURE FROM 2019, AND 2183 01:12:37,215 --> 01:12:40,285 YOU CAN SEE THIS IS ALL 2184 01:12:40,285 --> 01:12:41,686 INDIVIDUALS THAT HAVE BEEN 2185 01:12:41,686 --> 01:12:43,454 SEQUENCED IN THE GENOME-WIDE 2186 01:12:43,454 --> 01:12:47,926 ASSOCIATION CATALOG, AND 80% OF 2187 01:12:47,926 --> 01:12:49,561 THOSE PEOPLE SEQUENCED ARE OF 2188 01:12:49,561 --> 01:12:50,662 EUROPEAN ANCESTRY AND THE REST 2189 01:12:50,662 --> 01:12:52,297 OF THE WORLD'S POPULATION SHARES 2190 01:12:52,297 --> 01:12:55,466 THAT OTHER 20%, SO YOU CAN SEE 2191 01:12:55,466 --> 01:13:00,038 WE HAVE A BIG DISPARITY IN WHAT 2192 01:13:00,038 --> 01:13:01,372 WE KNOW ABOUT THE GENETICS OF 2193 01:13:01,372 --> 01:13:03,007 LUPUS GLOBALLY. 2194 01:13:03,007 --> 01:13:04,108 NOW, THERE'S A LOT OF PEOPLE 2195 01:13:04,108 --> 01:13:05,977 THAT HAVE RECOGNIZED THAT THIS 2196 01:13:05,977 --> 01:13:09,213 IS A HUGE PROBLEM OUTSIDE 2197 01:13:09,213 --> 01:13:09,914 RHEUMATOLOGY AND THE GENETICS 2198 01:13:09,914 --> 01:13:11,215 FIELD IN GENERAL. 2199 01:13:11,215 --> 01:13:12,183 THERE'S MANY EFFORTS SUCH AS 2200 01:13:12,183 --> 01:13:13,618 ALL-OF-US AND OTHERS TRYING TO 2201 01:13:13,618 --> 01:13:16,821 ADDRESS THESE ISSUES, BUT THE 2202 01:13:16,821 --> 01:13:17,889 DISPARITY IS SO BIG, IT'S GOING 2203 01:13:17,889 --> 01:13:19,624 TO TAKE US A WHILE TO KIND OF 2204 01:13:19,624 --> 01:13:21,292 COVER THE GROUND TO TRULY 2205 01:13:21,292 --> 01:13:26,197 ADDRESS THESE DISPARITIES. 2206 01:13:26,197 --> 01:13:29,033 WE KNOW LUPUS IS HERITABLE 2207 01:13:29,033 --> 01:13:30,034 BECAUSE IN IDENTICAL TWINS, 2208 01:13:30,034 --> 01:13:38,343 THERE'S A HIGH CONQU CONCORDANC- 2209 01:13:38,343 --> 01:13:39,210 THERE'S BEEN TWO KIND OF AREAS 2210 01:13:39,210 --> 01:13:39,777 OF STUDY. 2211 01:13:39,777 --> 01:13:42,814 ONE IS COMMON VARIANT STUDIES, 2212 01:13:42,814 --> 01:13:44,682 THESE OCCUR COMMONLY IN A 2213 01:13:44,682 --> 01:13:45,783 POPULATION, THEY'RE NOT TOO 2214 01:13:45,783 --> 01:13:46,651 DAMAGING, THEY'RE KIND OF PASSED 2215 01:13:46,651 --> 01:13:47,752 ALONG THROUGH GENERATIONS AND 2216 01:13:47,752 --> 01:13:50,922 THEY'RE USUALLY NOT IN THE PART 2217 01:13:50,922 --> 01:13:52,223 OF DNA THAT CODES FOR PROTEINS 2218 01:13:52,223 --> 01:13:53,291 AND THEY USUALLY HAVE A SMALL 2219 01:13:53,291 --> 01:13:53,725 EFFECT SIZE. 2220 01:13:53,725 --> 01:13:56,260 SO THEY GIVE YOU 1.2 OR 1.5 THE 2221 01:13:56,260 --> 01:14:01,232 RISK OF LUPUS, AND THEN RARE 2222 01:14:01,232 --> 01:14:05,136 VARIANTS BY DEFINITION OCCUR 2223 01:14:05,136 --> 01:14:06,104 RARELY, THEY'RE USUALLY IN THE 2224 01:14:06,104 --> 01:14:08,172 PART OF THE DNA THAT MAKES A 2225 01:14:08,172 --> 01:14:10,375 PROTEIN AND THEY CHANGE THE 2226 01:14:10,375 --> 01:14:11,676 PROTEINS SO THEY HAVE A BIG 2227 01:14:11,676 --> 01:14:13,111 DAMAGING EFFECT, THEY MAKE THE 2228 01:14:13,111 --> 01:14:13,878 PROTEIN FUNCTION DIFFERENTLY SO 2229 01:14:13,878 --> 01:14:16,381 THEY'RE USUALLY NOT PASSED ON, 2230 01:14:16,381 --> 01:14:17,682 BUT THEY HAVE A REALLY BIG 2231 01:14:17,682 --> 01:14:19,250 EFFECT ON WHAT'S HAPPENING IN 2232 01:14:19,250 --> 01:14:19,684 BIOLOGY. 2233 01:14:19,684 --> 01:14:20,985 AND MOST OF THE STUDIES THAT 2234 01:14:20,985 --> 01:14:24,155 HAVE BEEN DONE IN LUPUS GENETICS 2235 01:14:24,155 --> 01:14:27,291 SO FAR HAS BEEN THESE COMMON 2236 01:14:27,291 --> 01:14:29,093 VARIANT STUDIES IN ADULT 2237 01:14:29,093 --> 01:14:30,194 POPULATIONS WHO ARE KIND OF LESS 2238 01:14:30,194 --> 01:14:33,698 SICK THAN THEIR CHILDHOOD ONSET 2239 01:14:33,698 --> 01:14:34,032 COUNTERPARTS. 2240 01:14:34,032 --> 01:14:35,967 AS TALKED ABOUT EARLIER, THERE'S 2241 01:14:35,967 --> 01:14:37,735 MANY AUTOIMMUNE DISEASES THIS 2242 01:14:37,735 --> 01:14:38,736 GENETIC AND ENVIRONMENTAL 2243 01:14:38,736 --> 01:14:40,471 INTERPLAY, SO THE THOUGHT IS 2244 01:14:40,471 --> 01:14:42,907 THAT THERE'S SOMEBODY WITH A 2245 01:14:42,907 --> 01:14:44,542 GENETIC REDISPOSITION EXPOSED 2246 01:14:44,542 --> 01:14:47,478 THROUGHOUT THEIR LIFETIME TO 2247 01:14:47,478 --> 01:14:50,682 ENVIRONMENTAL EXPOSURES, HAVE 2248 01:14:50,682 --> 01:14:52,083 KIND OF DISREGULATED IMMUNITY 2249 01:14:52,083 --> 01:14:53,951 AND THAT KIND OF TRUCKS ALONG 2250 01:14:53,951 --> 01:14:55,453 UNTIL ALL OF A SUDDEN AN EVENT 2251 01:14:55,453 --> 01:14:57,755 KIND OF TIPS YOU OVER INTO LOSS 2252 01:14:57,755 --> 01:15:01,592 OF TOLERANCE, YOU START MAKING 2253 01:15:01,592 --> 01:15:03,561 AUTOANTIBODIES AGAINST YOUR OWN 2254 01:15:03,561 --> 01:15:06,964 CELLS AN. 2255 01:15:06,964 --> 01:15:08,166 THE THOUGHT IS THAT IN CHILDREN, 2256 01:15:08,166 --> 01:15:10,001 THAT GENETIC PREDISPOSITION IS 2257 01:15:10,001 --> 01:15:11,002 MUCH LARGER AND IT PLAYING A 2258 01:15:11,002 --> 01:15:12,670 MUCH LARGER ROLE SO YOU DO 2259 01:15:12,670 --> 01:15:14,739 HAVE -- YOU HAVE AN 2260 01:15:14,739 --> 01:15:17,008 ENVIRONMENTAL EVENT THAT TIPS 2261 01:15:17,008 --> 01:15:18,443 YOU OVER BUT IT HAPPENS EARLIER 2262 01:15:18,443 --> 01:15:23,047 IN LIFE AND YOUR DISEASE IS MORE 2263 01:15:23,047 --> 01:15:23,381 SEVERE. 2264 01:15:23,381 --> 01:15:24,582 NOW BECAUSE OF THIS HIGHER 2265 01:15:24,582 --> 01:15:26,451 GENETIC LOAD IN PEDIATRICS, 2266 01:15:26,451 --> 01:15:28,186 PROBABLY THE IDEAL POPULATION IN 2267 01:15:28,186 --> 01:15:29,821 WHICH TO STUDY GENETIC 2268 01:15:29,821 --> 01:15:30,588 CONTRIBUTION TO LUPUS AND 2269 01:15:30,588 --> 01:15:33,558 THERE'S A THEER RETHAT OLDER 2270 01:15:33,558 --> 01:15:35,426 PATIENTS, LATER ADOLESCENT, 2271 01:15:35,426 --> 01:15:37,095 PROBABLY HAVE MANY COMMON 2272 01:15:37,095 --> 01:15:38,930 VARIANTS BUT NOT MANY OF THOSE 2273 01:15:38,930 --> 01:15:41,232 BEING DAMAGING VARIANTS. 2274 01:15:41,232 --> 01:15:43,634 EARLY ONSET MIGHT HAVE ONE 2275 01:15:43,634 --> 01:15:46,504 DAMAGING VARIANT BUT THEY DON'T 2276 01:15:46,504 --> 01:15:49,006 REALLY HAVE -- IT'S EITHER BIG 2277 01:15:49,006 --> 01:15:50,875 ADULT COHORTS OR A FEW PATIENTS 2278 01:15:50,875 --> 01:15:54,579 THAT HAVE BEEN SEQUENCED REALLY 2279 01:15:54,579 --> 01:15:56,447 HASN'T BEEN RIGOROUSLY ANALYZED 2280 01:15:56,447 --> 01:15:57,982 IN LARGE COHORTS OF PEDIATRIC 2281 01:15:57,982 --> 01:15:59,617 LUPUS PATIENTS. 2282 01:15:59,617 --> 01:16:01,919 AND SO OUR LAB AS WORKING 2283 01:16:01,919 --> 01:16:03,788 THROUGH COLLABORATION TO REALLY 2284 01:16:03,788 --> 01:16:07,258 ADVANCE THE UNDERSTANDING OF THE 2285 01:16:07,258 --> 01:16:11,295 GENETIC ARCHITECTURE OF CHILD 2286 01:16:11,295 --> 01:16:13,831 ONSET LUPUS. 2287 01:16:13,831 --> 01:16:15,366 WE HAVE SOME OTHER 2288 01:16:15,366 --> 01:16:17,034 COLLABORATIONS IN PAKISTAN, 2289 01:16:17,034 --> 01:16:18,970 MEXICO, CANADA AND THE U.K. 2290 01:16:18,970 --> 01:16:22,707 AND OUR FIRST STUDY USED A 2291 01:16:22,707 --> 01:16:26,177 METHOD CALLED TRANSMISSION 2292 01:16:26,177 --> 01:16:26,677 DISEQUILIBRIUM ANALYSIS. 2293 01:16:26,677 --> 01:16:29,313 WE HAD TRIOS, SO AFFECTED 2294 01:16:29,313 --> 01:16:30,615 PATIENT AND TWO UNAFFECTED 2295 01:16:30,615 --> 01:16:31,949 PARENTS, AND WE HAD THEM FROM 2296 01:16:31,949 --> 01:16:33,017 OUR DIVERSE COHORTS THROUGHOUT 2297 01:16:33,017 --> 01:16:33,584 THE WORLD. 2298 01:16:33,584 --> 01:16:37,855 NOW, WE USED THIS METHOD BECAUSE 2299 01:16:37,855 --> 01:16:39,590 WE HAVE CHILDHOOD ONSET 2300 01:16:39,590 --> 01:16:40,358 POPULATION SO WE OFTEN HAVE 2301 01:16:40,358 --> 01:16:41,993 ACCESS TO PARENT AND WE CAN 2302 01:16:41,993 --> 01:16:43,628 COMPARE HOW OFTEN THE PARENTS 2303 01:16:43,628 --> 01:16:45,963 TRANSMIT EITHER COMMON OR RARE 2304 01:16:45,963 --> 01:16:50,668 VARIANTS TO THEIR OFFSPRING. 2305 01:16:50,668 --> 01:16:52,737 IF SOMETHING IS TRANSMITTED MORE 2306 01:16:52,737 --> 01:16:56,774 FREQUENTLY IN THE LUPUS PATIE 2307 01:16:56,774 --> 01:16:58,342 PATIENTS, THEN TSH AND UNRELATED 2308 01:16:58,342 --> 01:17:00,311 FAMILIES, IT KIND OF RAISES OUR 2309 01:17:00,311 --> 01:17:02,046 AWARENESS THAT THIS MIGHT BE 2310 01:17:02,046 --> 01:17:03,614 INVOLVED IN LUPUS PATHOGENESIS. 2311 01:17:03,614 --> 01:17:05,483 THE OTHER NICE THING ABOUT THIS 2312 01:17:05,483 --> 01:17:06,551 METHODOLOGY IS YOU USE THE 2313 01:17:06,551 --> 01:17:08,419 PARENTS AS THE CONTROL SO 2314 01:17:08,419 --> 01:17:15,827 THEY'RE PERFECTLY -- FROM THE 2315 01:17:15,827 --> 01:17:17,094 COMMON VARIANT SIDE IT WAS A 2316 01:17:17,094 --> 01:17:18,763 SMALL STUDY OF 83 PATIENTS AND 2317 01:17:18,763 --> 01:17:21,899 SO WE DID NOT FIND ANYTHING THAT 2318 01:17:21,899 --> 01:17:22,567 REACHED STATISTICAL 2319 01:17:22,567 --> 01:17:23,601 SIGNIFICANCE, HOWEVER WE DID 2320 01:17:23,601 --> 01:17:26,370 FIND THIS WAS A POPULATION 2321 01:17:26,370 --> 01:17:28,072 REALLY ENRICHED AND NOVEL RARE 2322 01:17:28,072 --> 01:17:30,141 VARIANTS CONTRIBUTING TO LUPUS, 2323 01:17:30,141 --> 01:17:31,008 WE FOUND MANY. 2324 01:17:31,008 --> 01:17:32,643 WITH SOME REALLY EXCITING 2325 01:17:32,643 --> 01:17:40,952 MECHANISMS INCLUDING HNRNPUL2, 1 2326 01:17:40,952 --> 01:17:42,086 OF THE MOST TOXIC THINGS THAT 2327 01:17:42,086 --> 01:17:43,721 THE CELL SENSES, AND YOU COULD 2328 01:17:43,721 --> 01:17:46,691 IMAGINE THAT IT MIGHT TRIGGER 2329 01:17:46,691 --> 01:17:47,892 INFLAMMATION, AND IT IS ALSO 2330 01:17:47,892 --> 01:17:51,629 PART OF THE FAMILY OF PROTEINS 2331 01:17:51,629 --> 01:17:54,465 DESCRIBED IN THE XIST RNP, SO 2332 01:17:54,465 --> 01:17:55,800 THAT HAS BEEN AS WE HEARD 2333 01:17:55,800 --> 01:17:57,768 EARLIER A REALLY EXCITING 2334 01:17:57,768 --> 01:17:59,837 CONTRIBUTOR TO OUR UNDERSTANDING 2335 01:17:59,837 --> 01:18:10,915 OF THE FEMALE PR -- IT MIGHT BE 2336 01:18:14,352 --> 01:18:15,486 ARE TWO UNROW LATED PATIENTS AND 2337 01:18:15,486 --> 01:18:17,255 THEY DON'T HAVE A VARIANT IN THE 2338 01:18:17,255 --> 01:18:18,890 EXACT SAME GENE BUT PATIENT A 2339 01:18:18,890 --> 01:18:21,459 HAS A VARIANT IN PROTEIN A AND 2340 01:18:21,459 --> 01:18:23,728 THIS BIOLOGICAL CASCADE AND 2341 01:18:23,728 --> 01:18:26,364 PATIENT B HAS A PROTEIN IN B AND 2342 01:18:26,364 --> 01:18:28,466 THEY INTERACT WITH EACH OTHER SO 2343 01:18:28,466 --> 01:18:29,667 MOLECULARLY THEY MIGHT LOOK 2344 01:18:29,667 --> 01:18:31,435 REALLY SIMILAR EVEN THOUGH THEY 2345 01:18:31,435 --> 01:18:33,304 DON'T SHARE THE EXACT GENE SO WE 2346 01:18:33,304 --> 01:18:35,373 WANTED TO DEVELOP A METHODOLOGY 2347 01:18:35,373 --> 01:18:36,240 TO UNDERSTAND IMPORTANT 2348 01:18:36,240 --> 01:18:41,245 MECHANISMS IN LUPUS, SO WE DID A 2349 01:18:41,245 --> 01:18:42,747 PATHWAY ANALYSIS TO OUR COHORT. 2350 01:18:42,747 --> 01:18:46,017 WE USED ALL 83 PATIENTS AND 109 2351 01:18:46,017 --> 01:18:46,450 UNAFFECTED PARENTS. 2352 01:18:46,450 --> 01:18:49,253 YOU CAN SEE IN THIS CHART THEY 2353 01:18:49,253 --> 01:18:52,623 WERE VERY DIVERSE GENETIC 2354 01:18:52,623 --> 01:18:54,392 ANCESTRIES AND GEOGRAPHIC 2355 01:18:54,392 --> 01:18:55,826 LOCATIONS, AND SO WE LOOKED FOR 2356 01:18:55,826 --> 01:18:57,261 RARE VARIANTS IN THE PROTEIN 2357 01:18:57,261 --> 01:18:59,563 CODING REGION OF THE GENE. 2358 01:18:59,563 --> 01:19:01,198 WE WERE TRYING TO FIND IMPORTANT 2359 01:19:01,198 --> 01:19:03,701 MECHANISTIC DRIVERS, AND TWO 2360 01:19:03,701 --> 01:19:04,936 UNRELATED LUPUS PATIENTS, AND 2361 01:19:04,936 --> 01:19:07,805 THEN WE ORGANIZED THOSE VARIANTS 2362 01:19:07,805 --> 01:19:12,209 AND GENES INTO BIOLOGICAL 2363 01:19:12,209 --> 01:19:18,115 PATHWAY IN A PROGRAM CA CALLED 2364 01:19:18,115 --> 01:19:18,683 METASCAPE. 2365 01:19:18,683 --> 01:19:20,318 WE CREATED A MAP OF THESE 2366 01:19:20,318 --> 01:19:22,186 BIOLOGICAL PATHWAYS TO TRY TO 2367 01:19:22,186 --> 01:19:23,821 UNDERSTAND WHAT ARE THE 2368 01:19:23,821 --> 01:19:29,293 MECHANISMS DRIVING DISEASE USI 2369 01:19:29,293 --> 01:19:33,431 USING -- SO THIS IS THE RESULT, 2370 01:19:33,431 --> 01:19:35,866 NETWORK OF BIOLOGIC PATHWAYS 2371 01:19:35,866 --> 01:19:38,502 ENRICHED FOR VARIANTS FOUND IN 2372 01:19:38,502 --> 01:19:39,704 CSLE PATIENTS. 2373 01:19:39,704 --> 01:19:40,972 THEY'RE KIND OF CONNECTED BY 2374 01:19:40,972 --> 01:19:42,907 LINES AND YOU CAN SEE THAT WE'RE 2375 01:19:42,907 --> 01:19:45,943 STARTING SPHO UNDERSTAND THE 2376 01:19:45,943 --> 01:19:48,813 MECHANISMS UNDER DRIVING LUPUS 2377 01:19:48,813 --> 01:19:49,814 IN THIS COHORT WE HAVE. 2378 01:19:49,814 --> 01:19:51,015 SOME OF THEM HAVE BEEN REPORTED 2379 01:19:51,015 --> 01:19:53,551 IN OTHER COHORTS THROUGHOUT THE 2380 01:19:53,551 --> 01:19:54,885 WORLD LIKE RNA PRO SESSION OR 2381 01:19:54,885 --> 01:19:56,287 DNA REPAIR AND OTHERS ARE QUITE 2382 01:19:56,287 --> 01:19:56,754 NOVEL. 2383 01:19:56,754 --> 01:19:58,389 SO IN CONCLUSION, I HOPE I'VE 2384 01:19:58,389 --> 01:20:00,691 COCONVINCED YOU THAT WHILE LUPUS 2385 01:20:00,691 --> 01:20:02,460 IS A MIXTURE OF GENETICS AND 2386 01:20:02,460 --> 01:20:03,995 ENVIRONMENT, LUPUS PATIENTS ARE 2387 01:20:03,995 --> 01:20:05,997 THE IDEAL POPULATION TO REALLY 2388 01:20:05,997 --> 01:20:09,333 DEFINE AND WORK OUT GENETIC 2389 01:20:09,333 --> 01:20:12,003 CONTRIBUTORS TO SLE, AND 2390 01:20:12,003 --> 01:20:13,571 STUDYING LARGE COHORTS OF LUPUS 2391 01:20:13,571 --> 01:20:16,874 PATIENTS WILL HELP US TO TAKE US 2392 01:20:16,874 --> 01:20:18,275 FROM THIS BROAD CLINICAL 2393 01:20:18,275 --> 01:20:21,579 PHENOTYPE TO A MORE PRO SEISE 2394 01:20:21,579 --> 01:20:24,115 MOLECULAR PHENOTYPE SO WE CAN 2395 01:20:24,115 --> 01:20:25,016 BETTER TARGET THERAPIES AND 2396 01:20:25,016 --> 01:20:26,083 IMPROVE OUTCOMES FOR THIS 2397 01:20:26,083 --> 01:20:26,617 DEVASTATING DISEASE. 2398 01:20:26,617 --> 01:20:28,953 AND WE NEED STUDIES THAT ARE 2399 01:20:28,953 --> 01:20:30,921 BROADLY INCLUSIVE SO WE CAN 2400 01:20:30,921 --> 01:20:33,791 UNDERSTAND THE BREADTH AND DEPTH 2401 01:20:33,791 --> 01:20:39,130 TO UNDERSTAND ALL LUPUS PATIENTS 2402 01:20:39,130 --> 01:20:39,830 AROUND THE WORLD. 2403 01:20:39,830 --> 01:20:43,000 >> THANK YOU, DR. LEWANDOWSKI. 2404 01:20:43,000 --> 01:20:44,969 DR. HOLLAND, I'M NOW GOING TO 2405 01:20:44,969 --> 01:20:45,836 PASS THE MICROPHONE OVER TO YOU. 2406 01:20:45,836 --> 01:20:49,807 >> ALL RIGHT! 2407 01:20:49,807 --> 01:20:51,876 VERY GOOD. 2408 01:20:51,876 --> 01:20:55,846 MY SLIDES ARE UP? 2409 01:20:55,846 --> 01:20:57,081 >> YOUR SLIDES ARE UP AND YOU 2410 01:20:57,081 --> 01:20:58,482 SHOULD BE ABLE TO TAKE CONTROL. 2411 01:20:58,482 --> 01:20:59,116 >> ALL RIGHT. 2412 01:20:59,116 --> 01:21:00,551 HERE WE GO. 2413 01:21:00,551 --> 01:21:01,519 SO THANK YOU VERY MUCH. 2414 01:21:01,519 --> 01:21:04,688 IT'S A REAL HONOR TO BE HERE 2415 01:21:04,688 --> 01:21:06,891 CELEBRATING THE CAREER OF 2416 01:21:06,891 --> 01:21:09,093 DR. PINN AND TO PARTICIPATE WITH 2417 01:21:09,093 --> 01:21:12,163 SUCH OUTSTANDING SCIENTISTS AND 2418 01:21:12,163 --> 01:21:12,463 PHYSICIANS. 2419 01:21:12,463 --> 01:21:13,798 I'M GOING TO TELL YOU A STORY. 2420 01:21:13,798 --> 01:21:15,766 IT'S A SINGLE STORY BUT I THINK 2421 01:21:15,766 --> 01:21:17,435 YOU'LL SEE WHY IT'S GOT 2422 01:21:17,435 --> 01:21:18,636 COMPONENTS THAT ARE RELEVANT TO 2423 01:21:18,636 --> 01:21:20,037 MANY OF THE TOPICS OF TODAY. 2424 01:21:20,037 --> 01:21:22,373 SO MY STORY STARTS ABOUT A 2425 01:21:22,373 --> 01:21:23,808 HUNDRED 40 YEARS AGO. 2426 01:21:23,808 --> 01:21:25,543 ROBERT KOCH DECIDES THAT HE'S 2427 01:21:25,543 --> 01:21:28,379 GOING TO TELL THE WORLD WHAT 2428 01:21:28,379 --> 01:21:29,747 CAUSES TUBERCULOSIS, SO HE 2429 01:21:29,747 --> 01:21:32,016 INVITES ALL HIS PALS INTO HIS 2430 01:21:32,016 --> 01:21:35,753 HOME TO SHOW THEM M TUBERCULOSIS 2431 01:21:35,753 --> 01:21:36,854 UNDER THE MICROSCOPE. 2432 01:21:36,854 --> 01:21:38,389 BRAND NEW DISCOVERY, AND IT'S 2433 01:21:38,389 --> 01:21:39,824 RIGHT THERE IN HIS KITCHEN, 2434 01:21:39,824 --> 01:21:41,659 WHERE HE DOES HIS SCIENCE. 2435 01:21:41,659 --> 01:21:43,060 HIS FRIENDS ALL LOOK UNDER THE 2436 01:21:43,060 --> 01:21:45,162 MICROSCOPE AND THEY SAY, NO WAY, 2437 01:21:45,162 --> 01:21:47,798 THAT CANNOT BE THE CAUSE OF THAT 2438 01:21:47,798 --> 01:21:49,366 TERRIBLE DISEASE. 2439 01:21:49,366 --> 01:21:51,235 IT'S IT ITTY BITTY AND IT DOESNT 2440 01:21:51,235 --> 01:21:51,969 MAKE ANY SENSE. 2441 01:21:51,969 --> 01:21:52,970 HOW COULD DO THAT? 2442 01:21:52,970 --> 01:21:54,805 THAT'S WHY YOU HAD TO GO ON AND 2443 01:21:54,805 --> 01:21:57,241 DEVELOP THESE THINGS CALLED 2444 01:21:57,241 --> 01:21:58,242 KOCH'S POSTULATES THAT DETERMINE 2445 01:21:58,242 --> 01:21:59,410 HOW WE THINK ABOUT DISEASE. 2446 01:21:59,410 --> 01:22:01,479 THE OTHER BIG OUT COME OF THAT 2447 01:22:01,479 --> 01:22:02,379 EVENING WAS THAT EVERYBODY SAID 2448 01:22:02,379 --> 01:22:04,215 WE ARE NEVER HAVING DINNER AT 2449 01:22:04,215 --> 01:22:05,816 BOB'S HOUSE AGAIN. 2450 01:22:05,816 --> 01:22:07,885 SO THAT WAS 140 YEARS AGO. 2451 01:22:07,885 --> 01:22:10,321 THE DISCOVERY OF M TUBERCULOSIS. 2452 01:22:10,321 --> 01:22:11,889 ON THIS CHART, YOU CAN SEE HERE 2453 01:22:11,889 --> 01:22:14,925 AT THE TOP, PERHAPS, THAT I'VE 2454 01:22:14,925 --> 01:22:19,296 GOT M TUBERCULOSIS AS THE 2455 01:22:19,296 --> 01:22:22,166 VERY -- AS THE APEX PREDATOR OF 2456 01:22:22,166 --> 01:22:23,367 MYCOBACTERIA. 2457 01:22:23,367 --> 01:22:24,335 IT'S VERY VIRULENT. 2458 01:22:24,335 --> 01:22:25,870 PEOPLE GET SICK AND DIE FROM IT. 2459 01:22:25,870 --> 01:22:28,439 BUT THERE ARE ABOUT 150 OTHER 2460 01:22:28,439 --> 01:22:30,474 STRAINS OF MYCOBACTERIA THAT ARE 2461 01:22:30,474 --> 01:22:32,243 NOT M TUBERCULOSIS THAT DON'T 2462 01:22:32,243 --> 01:22:33,811 CAUSE SUCH SEVERE DISEASE. 2463 01:22:33,811 --> 01:22:35,779 AND SO STARTING IN THE 1980s, 2464 01:22:35,779 --> 01:22:40,718 WITH THE ADD VENT ADVENT OF THEV 2465 01:22:40,718 --> 01:22:41,819 EPIDEMIC, PEOPLE REALIZED THAT 2466 01:22:41,819 --> 01:22:44,655 WHEN THE IMMUNE FUNCTION IS 2467 01:22:44,655 --> 01:22:46,190 IMPAIRED, MYCOBACTERIA 2468 01:22:46,190 --> 01:22:47,258 DISSEMINATE WITHIN THE BODY AND 2469 01:22:47,258 --> 01:22:49,593 THAT WAS A MAJOR FEATURE OF 2470 01:22:49,593 --> 01:22:50,261 ADVANCED AIDS. 2471 01:22:50,261 --> 01:22:52,930 SO WHAT MANY OF US DID GOING 2472 01:22:52,930 --> 01:22:54,431 INTO THE 80s AND 90s WAS TO 2473 01:22:54,431 --> 01:22:56,300 SAY, OKAY, WE UNDERSTAND HOW HIV 2474 01:22:56,300 --> 01:22:58,536 DOES THAT, MAKES FOR 2475 01:22:58,536 --> 01:22:59,403 MYCOBACTERIAL DISSEMINATION, BUT 2476 01:22:59,403 --> 01:23:02,139 WHAT ABOUT PEOPLE WHO DEVELOP 2477 01:23:02,139 --> 01:23:03,507 DISSEMINATED MYCOBACTERIAL 2478 01:23:03,507 --> 01:23:05,776 DISEASE WHO DON'T HAVE HIV? 2479 01:23:05,776 --> 01:23:06,377 THERE MUST BE SOMETHING ELSE 2480 01:23:06,377 --> 01:23:07,678 WRONG WITH THEM. 2481 01:23:07,678 --> 01:23:09,647 AND SO OUR LAB AND MANY OTHERS 2482 01:23:09,647 --> 01:23:13,584 STARTED TO LOOK AT THESE 2483 01:23:13,584 --> 01:23:15,219 NON-TUBERCULOUS MYCOBACTERIA 2484 01:23:15,219 --> 01:23:16,353 THAT ARE INVOLVED IN THESE 2485 01:23:16,353 --> 01:23:16,987 DISEASES. 2486 01:23:16,987 --> 01:23:18,856 SO I'LL REFER TO THESE GLOBALLY 2487 01:23:18,856 --> 01:23:21,492 AS NTM OR NON-TUBERCULOUS 2488 01:23:21,492 --> 01:23:21,859 MYCOBACTERIA. 2489 01:23:21,859 --> 01:23:23,060 THEY ARE IN THE ENVIRONMENT, YOU 2490 01:23:23,060 --> 01:23:24,795 ARE EATING THEM, DRINKING THEM, 2491 01:23:24,795 --> 01:23:26,363 INHALING THEM ALL THE TIME, AND 2492 01:23:26,363 --> 01:23:27,898 THE VAST MAJORITY OF US NEVER 2493 01:23:27,898 --> 01:23:30,100 GET SICK FROM THEM. 2494 01:23:30,100 --> 01:23:36,440 NOW, IT TURNS OUT THAT THERE ARE 2495 01:23:36,440 --> 01:23:39,610 A VARIETY OF WAYS THEY CAN 2496 01:23:39,610 --> 01:23:40,411 AFFECT PEOPLE. 2497 01:23:40,411 --> 01:23:45,015 SKIN INFECTION IS COMMON, AND 2498 01:23:45,015 --> 01:23:46,183 HAPPENS TYPICALLY AFTER 2499 01:23:46,183 --> 01:23:46,717 PEDICURES. 2500 01:23:46,717 --> 01:23:47,885 SO IF YOU'RE GOING TO HAVE A 2501 01:23:47,885 --> 01:23:48,953 PEDICURE, DON'T SHAVE BEFORE THE 2502 01:23:48,953 --> 01:23:50,054 PEDICURE, THAT USUALLY WILL GET 2503 01:23:50,054 --> 01:23:51,755 RID OF IT, LUNG DISEASE IS VERY 2504 01:23:51,755 --> 01:23:53,190 COMMON. 2505 01:23:53,190 --> 01:23:55,693 AND IN COUNTRIES THAT HAVE VERY 2506 01:23:55,693 --> 01:23:59,230 LOW RATES OF TUBERCULOSIS, 2507 01:23:59,230 --> 01:24:00,097 NON-TUBERCULOUS LUNG DISEASE IS 2508 01:24:00,097 --> 01:24:01,532 COMMON AND IT'S OVERWHELMINGLY A 2509 01:24:01,532 --> 01:24:02,299 DISEASE OF WOMEN. 2510 01:24:02,299 --> 01:24:03,634 BUT WHAT I'M GOING TO TALK ABOUT 2511 01:24:03,634 --> 01:24:05,502 TODAY IS DISSEMINATED DISEASE. 2512 01:24:05,502 --> 01:24:08,572 AND YOU CAN SEE, AS IT'S TRAW 2513 01:24:08,572 --> 01:24:09,873 FOR MANY THINGS, WE KNOW ABOUT 2514 01:24:09,873 --> 01:24:11,108 THE MOST SEVERE CASES BECAUSE 2515 01:24:11,108 --> 01:24:15,713 THAT'S WHERE THE RATIO OF 2516 01:24:15,713 --> 01:24:18,649 SYMPTOMS TO DISCOVERY IS THE 2517 01:24:18,649 --> 01:24:20,618 BEST. 2518 01:24:20,618 --> 01:24:21,952 SO DISSEMINATED DISEASE, AS YOU 2519 01:24:21,952 --> 01:24:25,055 SEE IN THIS BOY HERE, IS REALLY 2520 01:24:25,055 --> 01:24:26,357 WHAT WE ARE GOING TO TALK ABOUT. 2521 01:24:26,357 --> 01:24:29,727 AND WHAT WE KNOW IS THAT 2522 01:24:29,727 --> 01:24:32,162 MYCOBACTERIA, SHOWN HERE AS 2523 01:24:32,162 --> 01:24:35,499 THESE RED ORGANISMS INSIDE OF 2524 01:24:35,499 --> 01:24:37,635 THE MACROPHAGE, THESE RED 2525 01:24:37,635 --> 01:24:39,503 ORGANISMS, THE MYCOBACTERIA GET 2526 01:24:39,503 --> 01:24:41,071 INGESTED BY MACROPHAGE, AND THAT 2527 01:24:41,071 --> 01:24:43,374 LEADS TO THE PRODUCTION OF IL12 2528 01:24:43,374 --> 01:24:46,677 AND IL23, THAT THEN WORK ON T 2529 01:24:46,677 --> 01:24:49,847 CELLS AND THEN K CELLS TO 2530 01:24:49,847 --> 01:24:51,181 UPREGULATE THE PRODUCTION OF 2531 01:24:51,181 --> 01:24:52,416 INTERFERON GAMMA. 2532 01:24:52,416 --> 01:24:53,917 INTERFERON GAMMA THEN ACTS ON 2533 01:24:53,917 --> 01:24:57,154 ITS RECEPTOR ON MACROPHAGES AND 2534 01:24:57,154 --> 01:24:59,023 ALL OTHER NUCLEATED CELLS TO 2535 01:24:59,023 --> 01:25:02,192 TURN ON A WHOLE SERIES OF 2536 01:25:02,192 --> 01:25:03,127 INTRACELLULAR GENES TO LEAD TO 2537 01:25:03,127 --> 01:25:05,629 THE KILLING OF MYCOBACTERIA 2538 01:25:05,629 --> 01:25:06,163 INSIDE THE CELL. 2539 01:25:06,163 --> 01:25:07,798 IT'S A VERY SIMPLE PATHWAY AND 2540 01:25:07,798 --> 01:25:09,667 YOU MIGHT SAY, STEVE, IT'S SO 2541 01:25:09,667 --> 01:25:10,868 SIMPLE, IT CAN'T POSSIBLY BE 2542 01:25:10,868 --> 01:25:11,201 TRUE. 2543 01:25:11,201 --> 01:25:13,437 THAT MIGHT BE CORRECT, BUT THERE 2544 01:25:13,437 --> 01:25:15,406 ARE REASONS THAT WE THINK IT IS 2545 01:25:15,406 --> 01:25:18,142 THE RIGHT PATHWAY TO FOCUS ON 2546 01:25:18,142 --> 01:25:23,947 AND THOSE REASONS ARE THAT WE'VE 2547 01:25:23,947 --> 01:25:26,050 GOT MENDELIAN MUTATIONS IN ALL 2548 01:25:26,050 --> 01:25:28,652 OF THESE GENES SHOWN HERE IN RED 2549 01:25:28,652 --> 01:25:31,422 THAT LEAD TO DISSEMINATED 2550 01:25:31,422 --> 01:25:31,989 DISEASE. 2551 01:25:31,989 --> 01:25:35,693 AND SO THIS HAS TAKEN ON A NAME 2552 01:25:35,693 --> 01:25:38,429 CALLED MENDELIAN SUSCEPTIBILITY 2553 01:25:38,429 --> 01:25:39,563 TO MYCOB MYCOBACTERIAL DISEASE H 2554 01:25:39,563 --> 01:25:41,398 IS A USEFUL WAY TO THINK ABOUT 2555 01:25:41,398 --> 01:25:42,733 THE SORT OF GLOBAL 2556 01:25:42,733 --> 01:25:44,368 SUSCEPTIBILITY TO DISSEMINATED 2557 01:25:44,368 --> 01:25:44,935 DISEASE. 2558 01:25:44,935 --> 01:25:46,337 IT HAS NOTHING TO DO WITH LUNG 2559 01:25:46,337 --> 01:25:48,339 DISEASE OKAY. 2560 01:25:48,339 --> 01:25:53,177 SO THIS PATHWAY THEN IS REALLY 2561 01:25:53,177 --> 01:25:56,380 CENTRAL TO WHO GET DISSEMINATED 2562 01:25:56,380 --> 01:25:56,914 MYCOBACTERIAL DISEASE. 2563 01:25:56,914 --> 01:25:58,449 BUT HERE'S WHERE IT GETS 2564 01:25:58,449 --> 01:25:59,450 INTERESTING. 2565 01:25:59,450 --> 01:26:01,552 THIS ALMOST ALWAYS OCCURS IN 2566 01:26:01,552 --> 01:26:03,520 CHILDHOOD. 2567 01:26:03,520 --> 01:26:05,723 AND ALMOST ALWAYS AROUND THE 2568 01:26:05,723 --> 01:26:08,792 WORLD OCCURS AFTER PEOPLE ARE 2569 01:26:08,792 --> 01:26:12,730 GIVEN BCG VACCINATION, 2570 01:26:12,730 --> 01:26:15,799 SUBCUTANEOUS OR INTRADERMAL WITH 2571 01:26:15,799 --> 01:26:17,701 LIVE BACTERIA AND THAT LEADS TO 2572 01:26:17,701 --> 01:26:18,335 DISSEMINATED DISEASE IN PEOPLE 2573 01:26:18,335 --> 01:26:19,470 WHO HAVE THE MUTATIONS SHOWN 2574 01:26:19,470 --> 01:26:22,072 HERE. 2575 01:26:22,072 --> 01:26:22,406 OKAY. 2576 01:26:22,406 --> 01:26:26,410 I'M AN INTERNIST, AND MY PATIENT 2577 01:26:26,410 --> 01:26:27,478 IS SHOWN HERE. 2578 01:26:27,478 --> 01:26:30,013 SO THIS IS A 60 YEAR OLD WOMAN 2579 01:26:30,013 --> 01:26:32,683 FROM VIETNAM, WHO HAD SURVIVED 2580 01:26:32,683 --> 01:26:34,551 THE VIETNAM WAR, CAME OUT TO THE 2581 01:26:34,551 --> 01:26:36,620 REFUGEE CAMPS, CAME TO THE 2582 01:26:36,620 --> 01:26:37,654 UNITED STATES AS A YOUNG WOMAN, 2583 01:26:37,654 --> 01:26:39,857 HAD A FAMILY, HAD A JOB, SET UP 2584 01:26:39,857 --> 01:26:43,861 HER OWN BUSINESS, AND AT 59, SHE 2585 01:26:43,861 --> 01:26:46,563 THEN BEGAN TO LOSE WEIGHT AND 2586 01:26:46,563 --> 01:26:48,866 HAVE FEVERS, AND EVENTUALLY WAS 2587 01:26:48,866 --> 01:26:50,334 RECOGNIZED TO HAVE THIS DISEASE, 2588 01:26:50,334 --> 01:26:53,370 AND YOU SEE HERE THESE SPOTS ON 2589 01:26:53,370 --> 01:26:56,140 HER CHEST, AND THEY'RE BECAUSE 2590 01:26:56,140 --> 01:26:57,641 SHE HAD INFECTION IN HER BONES 2591 01:26:57,641 --> 01:26:58,742 THAT WAS RUPTURING OUT THROUGH 2592 01:26:58,742 --> 01:26:59,176 HER SKIN. 2593 01:26:59,176 --> 01:27:02,746 AND THESE INFECTIONS WERE DUE TO 2594 01:27:02,746 --> 01:27:06,116 MYCOBACTEMYCOBACTERIUM AVIUM COE 2595 01:27:06,116 --> 01:27:09,920 OF THE NON-TUBERCULOUS 2596 01:27:09,920 --> 01:27:10,988 MYCOBACTERIA. 2597 01:27:10,988 --> 01:27:13,290 SO WE'RE NO DUMB S, WE LOOKED AT 2598 01:27:13,290 --> 01:27:14,291 THAT AND SAID WAIT A MINUTE, 2599 01:27:14,291 --> 01:27:15,592 THIS LOOKS LIKE THE DISSEMINATED 2600 01:27:15,592 --> 01:27:16,827 DEEDS WE SEE IN CHILDREN, BUT HE 2601 01:27:16,827 --> 01:27:17,594 SH'S NOT A CHILD. 2602 01:27:17,594 --> 01:27:19,463 SO IF IT LOOKS LIKE A GENETIC 2603 01:27:19,463 --> 01:27:21,031 DISEASE AND IT ACTS LIKE A 2604 01:27:21,031 --> 01:27:23,200 GENETIC DISEASE, BUT IT'S COMING 2605 01:27:23,200 --> 01:27:25,736 ON LATE IN LIFE AND IN HER CASE, 2606 01:27:25,736 --> 01:27:28,238 THE IN VITRO CELLULAR BEHAVIOR 2607 01:27:28,238 --> 01:27:29,773 WAS NORMAL, WHAT IN THE WORLD IS 2608 01:27:29,773 --> 01:27:30,707 IT? 2609 01:27:30,707 --> 01:27:33,410 AND SO THE ANSWER HERE IS THAT 2610 01:27:33,410 --> 01:27:36,380 SHE HAS AN AUTO ANTIBODY TO 2611 01:27:36,380 --> 01:27:37,648 INTERFERON GAMMA ITSELF. 2612 01:27:37,648 --> 01:27:39,483 AND THAT AUTO ANTIBODY IS 2613 01:27:39,483 --> 01:27:41,251 COMPLETELY BLOCKING AND GIVES 2614 01:27:41,251 --> 01:27:44,688 HER A PHENOTYPE THAT IS A CARBON 2615 01:27:44,688 --> 01:27:46,323 COPY OF WHAT HAPPENS IF YOU'RE 2616 01:27:46,323 --> 01:27:50,494 MISSING THE RECEPTOR. 2617 01:27:50,494 --> 01:27:53,330 WELL, THAT WAS VERY INTERESTING, 2618 01:27:53,330 --> 01:27:54,898 AND AS WE STARTED TO LOOK AROUND 2619 01:27:54,898 --> 01:27:56,633 A LITTLE BIT AS THIS WAS 2620 01:27:56,633 --> 01:27:59,470 HAPPENING, WE NOTICED HERE ARE 2621 01:27:59,470 --> 01:28:02,673 THE THREE EARLIEST PAPERS IN 2622 01:28:02,673 --> 01:28:03,874 THIS SERIES. 2623 01:28:03,874 --> 01:28:05,943 SO THE VERY FIRST PAPER 2624 01:28:05,943 --> 01:28:07,478 REPORTING A 25-YEAR-OLD THAI 2625 01:28:07,478 --> 01:28:12,916 WOMAN LIVING IN GERMANY WHO HAD 2626 01:28:12,916 --> 01:28:16,787 ONE OF THE NON-TUBERCULOUS 2627 01:28:16,787 --> 01:28:17,654 MYCOBACTERIUM, SHE GOT SICK AND 2628 01:28:17,654 --> 01:28:18,522 DIED. 2629 01:28:18,522 --> 01:28:18,989 25-YEAR-OLD WOMAN. 2630 01:28:18,989 --> 01:28:21,425 THE NEXT PAPER IS A 57-YEAR-OLD 2631 01:28:21,425 --> 01:28:24,161 FILIPINO MAN LIVING IN ENGLAND, 2632 01:28:24,161 --> 01:28:27,097 WHO DEVELOPED -- HAD TB AS A 2633 01:28:27,097 --> 01:28:29,800 YOUNGER MAN AND THEN 2634 01:28:29,800 --> 01:28:31,902 MYCOBACTERIA CHELONAE WITH 2635 01:28:31,902 --> 01:28:33,003 AUTOIMMUNITY AND THEN HE DIED. 2636 01:28:33,003 --> 01:28:34,638 AND WE HAD SEEN SIX WOMEN, ALL 2637 01:28:34,638 --> 01:28:36,306 OF WHOM CAME FROM SOUTHEAST 2638 01:28:36,306 --> 01:28:40,577 ASIA, ALL OF WHOM HAD WIDELY 2639 01:28:40,577 --> 01:28:41,778 DISSEMINATED DISEASE, ALL OF 2640 01:28:41,778 --> 01:28:43,413 WHOM WERE DESPERATELY ILL. 2641 01:28:43,413 --> 01:28:45,048 AND THAT GOT US THINKING, WAIT A 2642 01:28:45,048 --> 01:28:46,750 MINUTE, THIS SEEMS A LITTLE BIT 2643 01:28:46,750 --> 01:28:49,052 TOO MUCH OF A CONNECTION OF 2644 01:28:49,052 --> 01:28:50,787 PEOPLE FROM SOUTHEAST ASIA 2645 01:28:50,787 --> 01:28:56,627 SHOWING UP WITH THESE PROBLEMS. 2646 01:28:56,627 --> 01:28:58,362 SO THE RECURRING STORY, 2647 01:28:58,362 --> 01:29:00,797 SOUTHEAST ASIANS OUTSIDE OF ASIA 2648 01:29:00,797 --> 01:29:04,835 WHO HAVE AUTOANTIBODIES, IGG 2649 01:29:04,835 --> 01:29:06,036 AUTOANTIBODIES TO INTERFERON 2650 01:29:06,036 --> 01:29:09,573 GAMMA THAT LEAD TO DISSEMINATED 2651 01:29:09,573 --> 01:29:10,207 NON-TUBERCULOUS DISEASE AS WELL 2652 01:29:10,207 --> 01:29:11,542 AS SOME OTHER OPPORTUNISTIC 2653 01:29:11,542 --> 01:29:12,309 INFECTIONS I'LL TELL YOU ABOUT 2654 01:29:12,309 --> 01:29:13,710 IN A MINUTE, AND IT'S BAD, THIS 2655 01:29:13,710 --> 01:29:17,080 IS REALLY SEVERE DISEASE. 2656 01:29:17,080 --> 01:29:18,882 SO WE STARTED TO THINK, YOU 2657 01:29:18,882 --> 01:29:21,718 KNOW, IF THIS IS HAPPENING IN 2658 01:29:21,718 --> 01:29:23,587 SOUTHEAST ASIANS OUTSIDE OF 2659 01:29:23,587 --> 01:29:26,857 SOUTHEAST ASIA, WHAT IN THE 2660 01:29:26,857 --> 01:29:28,325 WORLD IS GOING ON IN SOUTHEAST 2661 01:29:28,325 --> 01:29:28,859 ASIA? 2662 01:29:28,859 --> 01:29:31,828 BECAUSE ALL OF THESE PEOPLE WERE 2663 01:29:31,828 --> 01:29:33,697 DIRECT IMMIGRANTS FROM THOSE 2664 01:29:33,697 --> 01:29:34,598 COUNTRY, NOT PEOPLE BORN IN 2665 01:29:34,598 --> 01:29:39,002 EUROPE OR THE UNITED STATES. 2666 01:29:39,002 --> 01:29:42,973 SO THIS PAPER HERE WAS REALLY 2667 01:29:42,973 --> 01:29:45,742 THE SEMINAL PAPER THAT SAID, 2668 01:29:45,742 --> 01:29:48,312 OKAY, LOOK, SHE REPORTED ON 59 2669 01:29:48,312 --> 01:29:51,014 PEOPLE IN THAILAND WHO DID NOT 2670 01:29:51,014 --> 01:29:54,551 HAVE HIV, BUT HAVE WIDESPREAD 2671 01:29:54,551 --> 01:29:56,119 OPPORTUNISTIC INFECTIONS IN 2672 01:29:56,119 --> 01:29:58,422 ADDITION TO NON-TUBERCULOUS 2673 01:29:58,422 --> 01:29:58,755 MYCOBACTERIA. 2674 01:29:58,755 --> 01:30:00,924 SO ALL OF THESE INFECTIONS 2675 01:30:00,924 --> 01:30:02,359 LISTED HERE ON THE RIGHT SIDE 2676 01:30:02,359 --> 01:30:06,530 WERE HAPPENING IN ADDITION TO 2677 01:30:06,530 --> 01:30:07,898 NON-TUBERCULOUS MYCOBACTERIA. 2678 01:30:07,898 --> 01:30:08,899 AND FOR THOSE OF YOU WHO ARE 2679 01:30:08,899 --> 01:30:10,100 REAL NERDS, YOU'LL NOTICE THAT 2680 01:30:10,100 --> 01:30:12,302 MOST OF THESE ARE ORGANISMS THAT 2681 01:30:12,302 --> 01:30:13,837 LIVE INSIDE THE MACRO FRAJ IN 2682 01:30:13,837 --> 01:30:22,012 EMA MACROPHAGE INEXACTLY THE SAE 2683 01:30:22,012 --> 01:30:24,748 NON-TUBERCULOUS MYCOBACTERIA DO. 2684 01:30:24,748 --> 01:30:26,817 AS WELL AS SOME VIRUSES. 2685 01:30:26,817 --> 01:30:30,487 SO WE THEN WORKED WITH PETER 2686 01:30:30,487 --> 01:30:32,122 BURBELO, WHO IS AN INVESTIGATOR 2687 01:30:32,122 --> 01:30:33,857 AT THAT TIME IN THE DENTAL 2688 01:30:33,857 --> 01:30:35,659 INSTITUTE, AND HE DEVELOPED AN 2689 01:30:35,659 --> 01:30:37,527 ASSAY CALLED LIPS, WHICH 2690 01:30:37,527 --> 01:30:41,131 ASSISTANTS FOR LUCIFERASE 2691 01:30:41,131 --> 01:30:41,999 IMMUNOPRECIPITATION SYSTEM. 2692 01:30:41,999 --> 01:30:42,966 YOU'LL NOTICE THAT LIPS ARE THE 2693 01:30:42,966 --> 01:30:44,234 ONE THING HE'S NOT LETTING US 2694 01:30:44,234 --> 01:30:45,435 SEE HERE. 2695 01:30:45,435 --> 01:30:47,170 BUT THIS LIPS ASSAY ALLOWS YOU 2696 01:30:47,170 --> 01:30:50,941 TO READ OUT ANTIBODIES AS 2697 01:30:50,941 --> 01:30:51,742 RELATIVE LIGHT UNITS. 2698 01:30:51,742 --> 01:30:53,143 AND I WON'T GO INTO ALL THE 2699 01:30:53,143 --> 01:30:54,311 DETAILS OF THE STUDY, EXCEPT TO 2700 01:30:54,311 --> 01:30:56,146 SAY THAT WE HAD SEVERAL GROUPS 2701 01:30:56,146 --> 01:30:59,416 OF PATIENTS THAT WE COLLECTED IN 2702 01:30:59,416 --> 01:31:01,284 THAILAND AND TAIWAN AND YOU SEE 2703 01:31:01,284 --> 01:31:06,256 THAT HERE IN THE UPPER PART OF 2704 01:31:06,256 --> 01:31:09,860 THE FIGURE ARE PEOPLE THAT HAVE 2705 01:31:09,860 --> 01:31:10,861 ANTIBODIES AGAINST INTERFERON 2706 01:31:10,861 --> 01:31:11,595 GAMMA. 2707 01:31:11,595 --> 01:31:15,899 YOU'LL SEE PATIENTS WITH 2708 01:31:15,899 --> 01:31:17,868 DISSEMINATED NON-TUBERCULOUS 2709 01:31:17,868 --> 01:31:19,936 MYCOBACTERIAL DISEASE AND THOSE 2710 01:31:19,936 --> 01:31:20,937 WITH OTHER OPPORTUNISTIC 2711 01:31:20,937 --> 01:31:22,939 INFECTIONS WITH OR WITHOUT 2712 01:31:22,939 --> 01:31:23,874 NON-TUBERCULOUS INFECTIONS HAD 2713 01:31:23,874 --> 01:31:26,009 HIGH LEVELS OF THESE 2714 01:31:26,009 --> 01:31:27,511 AUTOANTIBODIES AGAINST 2715 01:31:27,511 --> 01:31:28,245 INTERFATHER ON GAMMA, WHEREAS 2716 01:31:28,245 --> 01:31:31,415 THOSE WITH DISSEMINATED 2717 01:31:31,415 --> 01:31:32,249 TUBERCULOSIS, PULMONARY 2718 01:31:32,249 --> 01:31:33,116 TUBERCULOSIS OR BLOCK BANK 2719 01:31:33,116 --> 01:31:33,817 DONORS DID NOT. 2720 01:31:33,817 --> 01:31:35,318 THIS IS JUST AN EXAMPLE, YOU SAW 2721 01:31:35,318 --> 01:31:36,586 THE WOMAN I MENTIONED AT THE 2722 01:31:36,586 --> 01:31:36,853 BEGINNING. 2723 01:31:36,853 --> 01:31:38,922 HERE IS A MAN ON THE LEFT WHO 2724 01:31:38,922 --> 01:31:45,629 HAS DISSEMINATED TALAROMYCES 2725 01:31:45,629 --> 01:31:48,265 MARNEFFEI, THE WOMAN ON THE 2726 01:31:48,265 --> 01:31:53,236 RIGHT HAS SALMONELLA LIMB FAD 2727 01:31:53,236 --> 01:31:55,205 NIGHTS. 2728 01:31:55,205 --> 01:32:00,544 SALMONELLA LY M.P.H. 2729 01:32:00,544 --> 01:32:03,013 ADENITIS. 2730 01:32:03,013 --> 01:32:03,714 THEY ASKED THIS QUESTION AND 2731 01:32:03,714 --> 01:32:04,948 THEY LOOKED AT THEIR PATIENTS 2732 01:32:04,948 --> 01:32:06,650 AND SAID, OH, YOU KNOW, MAYBE 2733 01:32:06,650 --> 01:32:10,520 THIS IS RELATED TO HLA. 2734 01:32:10,520 --> 01:32:13,356 HLA IS A SET OF PROTEINS THAT 2735 01:32:13,356 --> 01:32:17,561 RESTRICT HOW WE KILOGRAM 2736 01:32:17,561 --> 01:32:19,296 RECOGNIZE ANTIGENS, AND THEY 2737 01:32:19,296 --> 01:32:22,032 REALIZED THAT THERE WERE CERTAIN 2738 01:32:22,032 --> 01:32:23,500 HLA ALLELES THAT YOU SEE HERE 2739 01:32:23,500 --> 01:32:25,268 THAT WERE HIGH LOW 2740 01:32:25,268 --> 01:32:26,470 OVERREPRESENTED IN THESE 2741 01:32:26,470 --> 01:32:29,439 PATIENTS FROM SOUTHEAST ASIA. 2742 01:32:29,439 --> 01:32:30,774 AND HERE DOESN'T MATTER WHAT 2743 01:32:30,774 --> 01:32:33,076 THEY ARE, BUT THEY HAVE 2744 01:32:33,076 --> 01:32:33,744 INCOMPREHENSIBLE NAMES THAT ARE 2745 01:32:33,744 --> 01:32:35,612 HARD TO PRONOUNCE AND REMEMBER, 2746 01:32:35,612 --> 01:32:37,881 BUT THEY'RE VERY HIGHLY 2747 01:32:37,881 --> 01:32:39,082 OVERREPRESENTED IN THIS PATIENT 2748 01:32:39,082 --> 01:32:39,850 GROUP. 2749 01:32:39,850 --> 01:32:41,051 WHY SHOULD THAT BE? 2750 01:32:41,051 --> 01:32:43,253 WHY WOULD THAT BE INTERESTING? 2751 01:32:43,253 --> 01:32:48,525 AND IT TURNS OUT THAT THE 2752 01:32:48,525 --> 01:32:49,960 BINDING GROOVE MADE BY THESE 2753 01:32:49,960 --> 01:32:53,163 ALLELES IS ABLE TO BIND THE LAST 2754 01:32:53,163 --> 01:32:55,265 10 AMINO ACIDS OF THE INTERFERON 2755 01:32:55,265 --> 01:32:56,233 GAMMA MOLECULE. 2756 01:32:56,233 --> 01:32:59,069 AND YOU CAN SEE HERE IN THE 2757 01:32:59,069 --> 01:33:02,739 UNDERLINE IN THE TABLE, THAT IS 2758 01:33:02,739 --> 01:33:05,041 THE SEQUENCE OF THE LAST FEW 2759 01:33:05,041 --> 01:33:07,210 AMINO ACIDS OF INTERFERON GAMMA. 2760 01:33:07,210 --> 01:33:08,779 BUT WE ALL HAVE INTERFERON 2761 01:33:08,779 --> 01:33:09,012 GAMMA. 2762 01:33:09,012 --> 01:33:10,981 LIFE IS INTRINSICALLY BUILT 2763 01:33:10,981 --> 01:33:13,049 AROUND HAVING THAT. 2764 01:33:13,049 --> 01:33:14,050 BUT WHAT THEY NOTICED THAT I 2765 01:33:14,050 --> 01:33:15,418 THINK WAS REALLY INTERESTING IS 2766 01:33:15,418 --> 01:33:18,355 THAT THERE'S AN OVERLAP BETWEEN 2767 01:33:18,355 --> 01:33:20,891 THE SEQUENCE IN INTERFERON GAMMA 2768 01:33:20,891 --> 01:33:31,668 AND A PEPTIDE IN AS P ASPERGILL. 2769 01:33:34,671 --> 01:33:36,339 THEY HAVE AN HLA TYPE THAT 2770 01:33:36,339 --> 01:33:39,075 ALLOWS THEM TO RECOGNIZE EITHER 2771 01:33:39,075 --> 01:33:40,777 INTERFERON OR AN OVERLAPPING 2772 01:33:40,777 --> 01:33:44,614 PEPTIDE IN ASPERGILLUS, SO THE 2773 01:33:44,614 --> 01:33:46,216 HYPOTHESIS IS PEOPLE ARE BEING 2774 01:33:46,216 --> 01:33:53,423 EXPOSED TO ASPERGILLUS, THOSE 2775 01:33:53,423 --> 01:33:57,961 ANTIBODIES NEUTRALIZE AND MAKE 2776 01:33:57,961 --> 01:33:58,528 THEM SICK. 2777 01:33:58,528 --> 01:34:01,131 IT SHOWS IF YOU BRING OUT THE 2778 01:34:01,131 --> 01:34:02,332 RELATIVE EPITOPES, THAT ACTUALLY 2779 01:34:02,332 --> 01:34:04,601 CAN MAKE IT GO AWAY. 2780 01:34:04,601 --> 01:34:06,136 THAT'S A REALLY NIFTY 2781 01:34:06,136 --> 01:34:07,237 RECOGNITION. 2782 01:34:07,237 --> 01:34:09,172 AND THAT WOULD SUGGEST, OKAY, 2783 01:34:09,172 --> 01:34:10,774 NOW WE'VE GOT ANTIBODIES TO 2784 01:34:10,774 --> 01:34:12,209 INTERFERON, WE HAVE AN IDEA WHY 2785 01:34:12,209 --> 01:34:14,945 THEY'RE HAPPENING, AND SO ONCE 2786 01:34:14,945 --> 01:34:16,012 YOU KNOW WHAT THE PROBLEM IS, 2787 01:34:16,012 --> 01:34:18,281 YOU HAVE IDEAS HOW TO TREAT IT. 2788 01:34:18,281 --> 01:34:20,250 AND SO WE WANT TO YOU KNOW THAT 2789 01:34:20,250 --> 01:34:22,485 IT'S ANTIBODY MEDIATED, ONE OF 2790 01:34:22,485 --> 01:34:24,020 THE OBVIOUS THINGS TO DO IS GET 2791 01:34:24,020 --> 01:34:25,989 RID OF THE CELLS, MAKING THOSE 2792 01:34:25,989 --> 01:34:26,489 ANTIBODIES. 2793 01:34:26,489 --> 01:34:30,327 SO THIS IS JUST AN EXAMPLE, 2794 01:34:30,327 --> 01:34:34,064 TREATMENT OF THESE PATIENTS WITH 2795 01:34:34,064 --> 01:34:35,232 RITUXIMAB WHICH KILLS B CELLS. 2796 01:34:35,232 --> 01:34:36,733 YOU CAN SEAT TITERS BEFORE 2797 01:34:36,733 --> 01:34:38,034 TREATMENT WERE HIGH, DURING 2798 01:34:38,034 --> 01:34:39,035 TREATMENT THEY WERE GOING DOWN 2799 01:34:39,035 --> 01:34:40,337 AND AFTER TREATMENT THEY WERE 2800 01:34:40,337 --> 01:34:41,238 EVEN LOWER. 2801 01:34:41,238 --> 01:34:42,906 IN THE ONE PATIENT HERE WHOSE 2802 01:34:42,906 --> 01:34:44,641 PICTURE I SHOWED YOU AT THE 2803 01:34:44,641 --> 01:34:46,409 BEGINNING, WHEN WE STOPPED 2804 01:34:46,409 --> 01:34:47,711 THERAPY ALONG THE WAY, HER B 2805 01:34:47,711 --> 01:34:50,347 CELLS CAME BACK, HER TITERS WENT 2806 01:34:50,347 --> 01:34:51,648 UP, VERY SELLED DISEASE AGAIN, 2807 01:34:51,648 --> 01:34:54,317 WE TREATED HER AND IT WENT AWAY. 2808 01:34:54,317 --> 01:34:55,752 NOW WHY AM I TELLING YOU THIS 2809 01:34:55,752 --> 01:34:56,953 STORY HERE? 2810 01:34:56,953 --> 01:34:59,289 BECAUSE WHAT'S FASCINATING ABOUT 2811 01:34:59,289 --> 01:35:03,660 THIS IS THAT THE DISEASE OCCURS 2812 01:35:03,660 --> 01:35:04,861 IN SOUTHEAST ASIA, SOUTHERN 2813 01:35:04,861 --> 01:35:06,296 CHINA AND SOUTHEAST ASIA. 2814 01:35:06,296 --> 01:35:08,031 IT ALSO OCCURS IN EUROPE, THE 2815 01:35:08,031 --> 01:35:09,733 UNITED STATES AND AUSTRALIA. 2816 01:35:09,733 --> 01:35:14,271 BUT ALMOST EXCLUSIVELY IN PEOPLE 2817 01:35:14,271 --> 01:35:16,139 WHO WERE BORN IN SOUTHEAST ASIA 2818 01:35:16,139 --> 01:35:17,007 AND EMIGRATED. 2819 01:35:17,007 --> 01:35:19,209 IT IS NOT OCCURRING IN PEOPLE OF 2820 01:35:19,209 --> 01:35:20,810 EXACTLY THE SAME ETHNIC AND 2821 01:35:20,810 --> 01:35:21,878 GENETIC BACKGROUND WHO WERE BORN 2822 01:35:21,878 --> 01:35:24,414 IN THIS COUNTRY. 2823 01:35:24,414 --> 01:35:26,549 THE OTHER THING THAT'S REALLY 2824 01:35:26,549 --> 01:35:27,751 STAGGERING, LOOK AT THE NUMBERS 2825 01:35:27,751 --> 01:35:28,952 HERE, LOOK AT THE RATIO OF MALE 2826 01:35:28,952 --> 01:35:33,323 TO FEMALE IN THAILAND ON THE 2827 01:35:33,323 --> 01:35:33,957 LEFT. 2828 01:35:33,957 --> 01:35:35,458 IT'S ABOUT 6 TO 4. 2829 01:35:35,458 --> 01:35:38,428 BUT ONCE YOU GET OUT OF 2830 01:35:38,428 --> 01:35:40,730 THAILAND, OR SOUTHEAST ASIA, 2831 01:35:40,730 --> 01:35:43,300 IT'S LIKE, YOU KNOW, 9 TO 1. 2832 01:35:43,300 --> 01:35:46,036 SO WHAT IS GOING ON THAT ARE 2833 01:35:46,036 --> 01:35:47,437 CHANGES, WHY IS IT THAT IT'S 2834 01:35:47,437 --> 01:35:49,472 ONLY IN PEOPLE BORN IN SOUTHEAST 2835 01:35:49,472 --> 01:35:51,141 ASIA, THAT SUGGESTS THAT THERE'S 2836 01:35:51,141 --> 01:35:52,542 A GEOGRAPHIC COMPONENT, BUT 2837 01:35:52,542 --> 01:35:55,178 THERE'S ALSO CLEARLY A GENDER 2838 01:35:55,178 --> 01:35:56,746 COMPONENT, AND THERE'S A GENETIC 2839 01:35:56,746 --> 01:36:00,050 COMPONENT. 2840 01:36:00,050 --> 01:36:01,117 SO I'M TELLING YOU THIS STORY 2841 01:36:01,117 --> 01:36:02,485 BECAUSE I THINK IT'S A PARADIGM 2842 01:36:02,485 --> 01:36:04,554 FOR MANY OF THE THINGS WE'VE 2843 01:36:04,554 --> 01:36:06,556 HEARD ABOUT TODAY. 2844 01:36:06,556 --> 01:36:07,657 THERE'S GENETICS, THERE'S 2845 01:36:07,657 --> 01:36:09,592 CLEARLY AN EXPOSOME COMPONENT, 2846 01:36:09,592 --> 01:36:12,028 AS WELL AS A CRITICAL GENDER 2847 01:36:12,028 --> 01:36:12,295 COMPONENT. 2848 01:36:12,295 --> 01:36:14,297 ALL OF THOSE ARE CONSPIRING TO 2849 01:36:14,297 --> 01:36:16,366 GIVE THESE WOMEN PARTICULARLY 2850 01:36:16,366 --> 01:36:18,535 BAD DISEASE. 2851 01:36:18,535 --> 01:36:20,236 SO I'VE TRIED TO TELL YOU ABOUT 2852 01:36:20,236 --> 01:36:22,639 A SYNDROME THAT IS REALLY QUITE 2853 01:36:22,639 --> 01:36:25,408 INTERESTING IN TERMS OF 2854 01:36:25,408 --> 01:36:27,310 DEVELOPMENT OF AUTOIMMUNITY. 2855 01:36:27,310 --> 01:36:28,845 IT'S ASSOCIATED WITH MULTIPLE 2856 01:36:28,845 --> 01:36:29,579 OPPORTUNISTIC INFECTIONS. 2857 01:36:29,579 --> 01:36:32,549 IT'S GOT AN HLA ASSOCIATION. 2858 01:36:32,549 --> 01:36:33,717 IT'S PREDOMINANTLY WOMEN, AND WE 2859 01:36:33,717 --> 01:36:35,352 KNOW HOW TO TREAT IT. 2860 01:36:35,352 --> 01:36:37,854 AS LONG AS WE CATCH IT IN TIME. 2861 01:36:37,854 --> 01:36:39,089 I'LL STOP THERE AND I LOOK 2862 01:36:39,089 --> 01:36:40,590 FORWARD TO TAKE ANY QUESTIONS IN 2863 01:36:40,590 --> 01:36:41,024 THE QUESTION PERIOD. 2864 01:36:41,024 --> 01:36:45,061 THANK YOU. 2865 01:36:45,061 --> 01:36:46,463 >> THANK YOU SO MUCH, 2866 01:36:46,463 --> 01:36:46,763 DR. HOLLAND. 2867 01:36:46,763 --> 01:36:49,466 WE'RE GOING TO MOVE SWIFTLY ON 2868 01:36:49,466 --> 01:36:50,233 TO DR. MOTSINGER-REIF AND 2869 01:36:50,233 --> 01:36:50,767 QUESTIONS AT THE END. 2870 01:36:50,767 --> 01:36:51,735 >> THANK YOU SO MUCH. 2871 01:36:51,735 --> 01:36:53,069 I REALLY APPRECIATE THE 2872 01:36:53,069 --> 01:36:54,137 OPPORTUNITY TO SPEAK AND THE 2873 01:36:54,137 --> 01:36:58,942 SUPPORT FROM YOUR OFFICE. 2874 01:36:58,942 --> 01:37:00,143 SO OUR PREVIOUS SPEAKERS HAVE 2875 01:37:00,143 --> 01:37:01,678 DISCUSSED THE IMPORTANT ROLE OF 2876 01:37:01,678 --> 01:37:05,248 THE ENVIRONMENT AND RISK OF 2877 01:37:05,248 --> 01:37:06,116 DISEASES AND THAT'S WHAT I'M 2878 01:37:06,116 --> 01:37:08,385 GOING TO FOCUS ON HERE. 2879 01:37:08,385 --> 01:37:09,652 I'M TALKING ABOUT SOME WORK A 2880 01:37:09,652 --> 01:37:10,520 LITTLE BIT IN THE PRELIMINARY 2881 01:37:10,520 --> 01:37:11,821 STAGE BUT REALLY GETTING 2882 01:37:11,821 --> 01:37:13,156 ROLLING. 2883 01:37:13,156 --> 01:37:14,858 SOME WORK IN THIS SPACE IN A 2884 01:37:14,858 --> 01:37:16,493 NORTH CAROLINA BASED COHORT THAT 2885 01:37:16,493 --> 01:37:19,763 I'M CO-PI ON CALLED PEGS, THE 2886 01:37:19,763 --> 01:37:20,397 PERSONALIZED ENVIRONMENT AND 2887 01:37:20,397 --> 01:37:20,797 GENES STUDY. 2888 01:37:20,797 --> 01:37:22,332 I SPENT THE LAST ABOUT FIVE 2889 01:37:22,332 --> 01:37:23,533 YEARS ASSEMBLING A LARGE AMOUNT 2890 01:37:23,533 --> 01:37:26,369 OF DATA AROUND THESE 2891 01:37:26,369 --> 01:37:27,404 PARTICIPANTS AND WOULD LIKE TO 2892 01:37:27,404 --> 01:37:28,705 SHARE SOME OF THE OUTCOMES OF 2893 01:37:28,705 --> 01:37:29,472 OUR ASSOCIATIONS WITH 2894 01:37:29,472 --> 01:37:34,210 ENVIRONMENTAL FACTORS. 2895 01:37:34,210 --> 01:37:35,678 SO JUST SOME QUICK SNAPSHOTS OF 2896 01:37:35,678 --> 01:37:36,012 PEGS. 2897 01:37:36,012 --> 01:37:38,281 SO IT'S A NORTH CAROLINA-BASED 2898 01:37:38,281 --> 01:37:38,848 COHORT. 2899 01:37:38,848 --> 01:37:40,984 IN TOTAL WE HAVE ABOUT -- ALMOST 2900 01:37:40,984 --> 01:37:42,285 20,000 PEOPLE ENROLLED, AND WE 2901 01:37:42,285 --> 01:37:43,720 HAVE EXTENSIVE HEALTH AND 2902 01:37:43,720 --> 01:37:45,855 EXPOSURE DATA ON ALMOST 10,000 2903 01:37:45,855 --> 01:37:47,190 OF THOSE 20,000. 2904 01:37:47,190 --> 01:37:49,259 HERE'S JUST A SNAPSHOT OF SOME 2905 01:37:49,259 --> 01:37:51,661 OF THE DEMOGRAPHICS, OUR AVERAGE 2906 01:37:51,661 --> 01:37:55,065 AGE IS JUST UNDER 50, WE'RE A 2907 01:37:55,065 --> 01:37:56,766 RELATIVELY DIVERSE COHORT IN 2908 01:37:56,766 --> 01:37:58,268 TERMS OF EDUCATION, 2909 01:37:58,268 --> 01:37:59,969 SOCIOECONOMIC STATUS, GENDER, 2910 01:37:59,969 --> 01:38:01,704 AND RACE/ETHNICITY. 2911 01:38:01,704 --> 01:38:05,442 WHICH IS REALLY A WONDERFUL SORT 2912 01:38:05,442 --> 01:38:08,244 OF A ASPECT AND POWERFUL ASPECTF 2913 01:38:08,244 --> 01:38:12,415 THIS STUDY. 2914 01:38:12,415 --> 01:38:16,519 I MIPTIO MENTIONED WE HAVE EXTEE 2915 01:38:16,519 --> 01:38:17,487 HEALTH AND EXPOSURE DATA FROM 2916 01:38:17,487 --> 01:38:18,054 OUR PARTICIPANTS. 2917 01:38:18,054 --> 01:38:21,391 SO WE HAVE EXTENSIVE SURVEY DATA 2918 01:38:21,391 --> 01:38:22,358 ON THREE DIFFERENT SURVEYS. 2919 01:38:22,358 --> 01:38:23,660 THE FIRST ONE IS WHAT WE CALL 2920 01:38:23,660 --> 01:38:25,028 HEALTH AND EXPOSURE, AND I'VE 2921 01:38:25,028 --> 01:38:25,929 GOT SOME SNAPSHOTS HERE. 2922 01:38:25,929 --> 01:38:28,565 SO HERE WE ASK, HAS A DOCTOR 2923 01:38:28,565 --> 01:38:30,366 EVER DIAGNOSED YOU WITH A, B OR 2924 01:38:30,366 --> 01:38:31,668 C, AND HAVE YOU EVER BEEN 2925 01:38:31,668 --> 01:38:34,070 EXPOSED TO X, Y AND Z IN YOUR 2926 01:38:34,070 --> 01:38:35,705 HOME, AT YOUR WORK, ET CETERA? 2927 01:38:35,705 --> 01:38:37,140 WHEN I SAY EXTENSIVE 2928 01:38:37,140 --> 01:38:38,007 QUESTIONNAIRES, I'M REQUESTING 2929 01:38:38,007 --> 01:38:40,376 TO GIVE YOU THE NUMBER OF 2930 01:38:40,376 --> 01:38:41,344 QUESTIONS SO IT'S GOING TO TIE 2931 01:38:41,344 --> 01:38:43,646 INTO SORT OF THE ANALYSIS 2932 01:38:43,646 --> 01:38:44,514 STRATEGY USED DOWNSTREAM. 2933 01:38:44,514 --> 01:38:45,882 SO HEALTH AND EXPOSURE SURVEY, 2934 01:38:45,882 --> 01:38:48,485 WE HAVE ALMOST 500 QUESTIONS ON, 2935 01:38:48,485 --> 01:38:50,253 AGAIN, SELF-REPORTED DISEASES OR 2936 01:38:50,253 --> 01:38:52,055 CONDITIONS, LIFESTYLE FACTORS 2937 01:38:52,055 --> 01:38:54,357 AND EXPOSURES. 2938 01:38:54,357 --> 01:38:56,426 WE HAVE TWO ADDITIONAL SURVEYS 2939 01:38:56,426 --> 01:39:01,764 WE CALL OUR EXPOSOME -- HERE 2940 01:39:01,764 --> 01:39:03,833 WE'VE GOT OVER 600 QUESTIONS 2941 01:39:03,833 --> 01:39:06,369 RELATED TO YOUR EXTERNAL 2942 01:39:06,369 --> 01:39:07,170 EXPOSOME. 2943 01:39:07,170 --> 01:39:11,341 SO WHAT YOU ARE EXPOSED TO -- 2944 01:39:11,341 --> 01:39:12,242 OCCUPATIONALLY, WHAT IN YOUR 2945 01:39:12,242 --> 01:39:13,877 HOMES, WHAT ARE SOME OF YOUR 2946 01:39:13,877 --> 01:39:16,779 HOBBY BASED EXPOSURES, DETAILS 2947 01:39:16,779 --> 01:39:19,048 ON YOUR HOUSING AND DISTANCE TO 2948 01:39:19,048 --> 01:39:19,716 ENVIRONMENTAL BADS. 2949 01:39:19,716 --> 01:39:21,484 AND AGAIN, JUST SOME SNAPSHOTS 2950 01:39:21,484 --> 01:39:23,019 HERE, BUT REMEMBER, ALMOST 600 2951 01:39:23,019 --> 01:39:25,455 QUESTIONS. 2952 01:39:25,455 --> 01:39:27,724 WE ALSO HAVE OUR INTERNAL 2953 01:39:27,724 --> 01:39:29,025 EXPOSOME SURVEY WHICH IS OVER 2954 01:39:29,025 --> 01:39:34,597 700 QUESTION QES ON S ON THE INL 2955 01:39:34,597 --> 01:39:38,201 EXPOSOME. 2956 01:39:38,201 --> 01:39:39,736 LIFESTYLE, DIET, PHYSICAL 2957 01:39:39,736 --> 01:39:40,703 ACTIVITIES, SLEEP, MEDICATIONS 2958 01:39:40,703 --> 01:39:42,005 THAT YOU'RE TAKING, INFECTIOUS 2959 01:39:42,005 --> 01:39:43,373 DISEASES YOU'VE BEEN EXPOSED TO 2960 01:39:43,373 --> 01:39:43,673 AND CAUGHT. 2961 01:39:43,673 --> 01:39:45,475 SO AGAIN, A PRETTY EXTENSIVE 2962 01:39:45,475 --> 01:39:48,745 AMOUNT OF EXPOSURE DATA. 2963 01:39:48,745 --> 01:39:50,613 AND THIS IS JUST ONE OF THE DATA 2964 01:39:50,613 --> 01:39:52,515 DMEENTS WE HAVE IN THIS STUDY. 2965 01:39:52,515 --> 01:39:53,850 AND I'M MENTIONING THIS BECAUSE 2966 01:39:53,850 --> 01:39:55,151 WHILE WE SPENT A LOT OF TIME 2967 01:39:55,151 --> 01:39:57,020 GATHERING THE DATA, AND BECAUSE 2968 01:39:57,020 --> 01:39:58,721 WE LOVE TO HAND IT OUT TO PEOPLE 2969 01:39:58,721 --> 01:40:00,924 THAT WANT TO ASK AND ANSWER 2970 01:40:00,924 --> 01:40:01,891 INTERESTING QUESTIONS. 2971 01:40:01,891 --> 01:40:04,027 SO ALREADY MENTIONED WE'VE GOT 2972 01:40:04,027 --> 01:40:05,361 EXTENSIVE HEALTH AND EXPOSURE 2973 01:40:05,361 --> 01:40:06,229 DATA FROM QUESTIONNAIRES. 2974 01:40:06,229 --> 01:40:08,731 WE ALSO HAVE A GROWING NUMBER OF 2975 01:40:08,731 --> 01:40:09,999 GEOSPATIAL ESTIMATES OF 2976 01:40:09,999 --> 01:40:10,567 EXPOSURE. 2977 01:40:10,567 --> 01:40:12,869 WE HAVE ADDRESSES AND ADVERSE 2978 01:40:12,869 --> 01:40:13,937 HISTORY FOR ALL OF OUR 2979 01:40:13,937 --> 01:40:14,871 PARTICIPANTS, SO WE'VE LINKED 2980 01:40:14,871 --> 01:40:16,206 SORT OF OUR PARTICIPANTS TO 2981 01:40:16,206 --> 01:40:18,508 ESTIMATES OF AIR POLLUTION, OF 2982 01:40:18,508 --> 01:40:21,010 WATER SOURCE CONTAMINATION, OF 2983 01:40:21,010 --> 01:40:22,478 SOCIAL DETERMINANTS AND 2984 01:40:22,478 --> 01:40:24,013 PLACE-BASED DISPARITIES, GREEN 2985 01:40:24,013 --> 01:40:24,847 SPACE, HEALTHCARE ACCESS, ET 2986 01:40:24,847 --> 01:40:26,549 CETERA. 2987 01:40:26,549 --> 01:40:28,351 AGAIN WE'VE GOT PHENOTYPE DATA 2988 01:40:28,351 --> 01:40:32,388 FROM OUR SELF-REPORTED SURVEY 2989 01:40:32,388 --> 01:40:32,755 QUESTIONS. 2990 01:40:32,755 --> 01:40:34,490 WE'RE IN THE PROCESS NOW OF 2991 01:40:34,490 --> 01:40:35,758 LINKING OUR PARTICIPANTS TO 2992 01:40:35,758 --> 01:40:37,660 HEALTH RECORDS FROM BOTH UNC AND 2993 01:40:37,660 --> 01:40:39,262 CHAPEL HILL, AND THEN WE HAVE A 2994 01:40:39,262 --> 01:40:40,863 GROWING NUMBER OF GENOMIC 2995 01:40:40,863 --> 01:40:41,931 COMPONENTS THAT WE'RE 2996 01:40:41,931 --> 01:40:42,265 COLLECTING. 2997 01:40:42,265 --> 01:40:43,766 WE HAVE WHOLE GENOME SEQUENCING 2998 01:40:43,766 --> 01:40:45,235 ON A SUBSET OF OUR PARTICIPANTS, 2999 01:40:45,235 --> 01:40:47,904 WHICH MEANS YOU CAN GET SINGLE 3000 01:40:47,904 --> 01:40:49,339 NUCLEOTIDE VARIANTS, RARE 3001 01:40:49,339 --> 01:40:51,374 VARIANTS, STRUCTURAL VARIANTS, 3002 01:40:51,374 --> 01:40:55,078 HLA THAT GOT SPOKEN OF EARLIER, 3003 01:40:55,078 --> 01:40:57,480 WE'VE ALSO JUST RECENTLY GOTTEN 3004 01:40:57,480 --> 01:40:58,982 EPIGENETIC DATA WE'RE WORKING 3005 01:40:58,982 --> 01:41:00,316 OUR WAY AND PROCESSING NOW. 3006 01:41:00,316 --> 01:41:02,485 SO REALLY MULTI-DIMENSIONAL DATA 3007 01:41:02,485 --> 01:41:06,923 SET AND AS A BIOSTATISTICIAN, 3008 01:41:06,923 --> 01:41:08,224 STATISTICAL GENETICIST, BIG DATA 3009 01:41:08,224 --> 01:41:09,325 PERSON, THIS IS REALLY EXCITING 3010 01:41:09,325 --> 01:41:11,594 TO HAVE ALL THESE COMPONENTS. 3011 01:41:11,594 --> 01:41:14,030 SO USING THIS RESOURCE, WE'VE 3012 01:41:14,030 --> 01:41:16,099 DONE EXPOSOME-WIDE ASSOCIATION 3013 01:41:16,099 --> 01:41:17,967 STUDIES OF AUTOIMMUNE DISEASES 3014 01:41:17,967 --> 01:41:19,335 IN THE PEGS COHORT. 3015 01:41:19,335 --> 01:41:21,070 SO WE TAKE THE SURVEY DATA THAT 3016 01:41:21,070 --> 01:41:24,073 I MENTIONED BEFORE SO WE'VE GOT 3017 01:41:24,073 --> 01:41:26,376 EXTENSIVE -- ALMOST 1700 3018 01:41:26,376 --> 01:41:29,245 QUESTIONS ON EXPOSURES ACROSS 3019 01:41:29,245 --> 01:41:30,446 THESE INDIVIDUALS FOR THE 3020 01:41:30,446 --> 01:41:33,683 AUTOIMMUNE DISEASES -- FOR 3021 01:41:33,683 --> 01:41:35,652 PARTICIPANTS WITH AUTOIMMUNE 3022 01:41:35,652 --> 01:41:36,953 DISEASES AND THE DISEASES WE'RE 3023 01:41:36,953 --> 01:41:38,921 ABLE TO INCLUDE BECAUSE OF A 3024 01:41:38,921 --> 01:41:40,957 REASONABLY HIGH PREVALENCE IS 3025 01:41:40,957 --> 01:41:46,195 ALLERGIC RHINITIS, ALLERGIC 3026 01:41:46,195 --> 01:41:49,766 RHINITIS, HYPOTHYROIDISM, 3027 01:41:49,766 --> 01:41:50,800 HYPERTHYROIDISM AND PSORIASIS. 3028 01:41:50,800 --> 01:41:54,170 SO FOR EACH ONE, WSH YOU LOOK 3029 01:41:54,170 --> 01:41:55,271 ACROSS THE GENOME, WE'RE GOING 3030 01:41:55,271 --> 01:41:57,440 TO LOOK AT THOSE THOUSANDS OF 3031 01:41:57,440 --> 01:41:58,741 EXPOSURES IN A SERIES OF 3032 01:41:58,741 --> 01:42:00,276 REGRESSION MODELS. 3033 01:42:00,276 --> 01:42:01,878 SO VERY SIMPLE STARTING OFF VERY 3034 01:42:01,878 --> 01:42:04,180 SIMPLY ASKING EXPOSURE BY 3035 01:42:04,180 --> 01:42:06,015 EXPOSURE, WHAT IS ASSOCIATED 3036 01:42:06,015 --> 01:42:07,383 WITH THESE DISEASES. 3037 01:42:07,383 --> 01:42:10,453 WE DO MULTIPLE -- FALSE POSITIVE 3038 01:42:10,453 --> 01:42:11,888 CONTROL, AND THEN CAN LOOK AT 3039 01:42:11,888 --> 01:42:14,891 WHAT IS UNIQUE AND SHARED IN 3040 01:42:14,891 --> 01:42:16,659 SORT OF ASSOCIATIONS WITH THESE 3041 01:42:16,659 --> 01:42:17,527 DISEASE. 3042 01:42:17,527 --> 01:42:19,295 WE ALSO ARE INTERESTED IN HOW 3043 01:42:19,295 --> 01:42:21,364 THESE EXPOSURES CORRELATE AND WE 3044 01:42:21,364 --> 01:42:23,966 DO MULTIVARIABLE MODELING WHERE 3045 01:42:23,966 --> 01:42:27,036 WE JOINT LOW LOOK AT THESE 3046 01:42:27,036 --> 01:42:28,771 EXPOSURES AND DO SELECTION TO 3047 01:42:28,771 --> 01:42:31,040 FIND THE MOST IMPORTANT 3048 01:42:31,040 --> 01:42:35,311 EXPOSURES TO FIT WITHIN -- WE 3049 01:42:35,311 --> 01:42:39,015 FOLLOW WORKFLOW FOR ALL THESE 3050 01:42:39,015 --> 01:42:39,782 AUTOIMMUNE DISEASES. 3051 01:42:39,782 --> 01:42:41,617 SO HERE ARE OUR STUDY GOALS TO 3052 01:42:41,617 --> 01:42:43,353 INVESTIGATE THE RELATIONSHIP 3053 01:42:43,353 --> 01:42:45,188 BETWEEN EXPOSURES AND THESE 3054 01:42:45,188 --> 01:42:49,058 COMMON AUTOIMMUNE DISEASES. 3055 01:42:49,058 --> 01:42:52,862 SENATE SHOTS, NUMBERS, SAMPLE 3056 01:42:52,862 --> 01:42:53,730 SIZES. 3057 01:42:53,730 --> 01:42:56,199 SO HERE I'M SHOWING YOU SOME OF 3058 01:42:56,199 --> 01:42:56,833 THOSE RESULTS. 3059 01:42:56,833 --> 01:42:58,534 I KNOW THIS IS SMALL AND NOT 3060 01:42:58,534 --> 01:43:00,603 EASY TO WALK THROUGH. 3061 01:43:00,603 --> 01:43:02,372 AND I'M SHOWING THE RESULTS OF 3062 01:43:02,372 --> 01:43:04,307 SORT OF THE SIGNIFICANT 3063 01:43:04,307 --> 01:43:07,343 ASSOCIATIONS AT AN FDR LEVEL OF 3064 01:43:07,343 --> 01:43:11,080 .001, WHICH IS -- VERY, VERY 3065 01:43:11,080 --> 01:43:11,848 TIGHT CONTROL. 3066 01:43:11,848 --> 01:43:15,251 THE WAY YOU SPHN -- EVERYTHING 3067 01:43:15,251 --> 01:43:18,354 I'M CALLING SIGNIFICANT, I ONLY 3068 01:43:18,354 --> 01:43:25,528 EXPECT .1% OF THOSE TO . 3069 01:43:25,528 --> 01:43:27,597 SO REALLY STRINGENT CONTROL. 3070 01:43:27,597 --> 01:43:28,698 WE'RE FINDING THINGS IN 3071 01:43:28,698 --> 01:43:29,565 RHEUMATOID ARTHRITIS WITH THE 3072 01:43:29,565 --> 01:43:32,268 SMOKING INDOORS TO -- EXPOSED TO 3073 01:43:32,268 --> 01:43:34,570 DAILY CONDITIONS, PESTICIDES IN 3074 01:43:34,570 --> 01:43:36,072 YOUR WORK, ET CETERA. 3075 01:43:36,072 --> 01:43:38,040 WE'RE SHOWING THE TABLES AND 3076 01:43:38,040 --> 01:43:39,542 THESE FOREST PLOTS THAT SHOW 3077 01:43:39,542 --> 01:43:39,909 EXPOSURES. 3078 01:43:39,909 --> 01:43:42,445 WE ALSO FOUND A NUMBER OF 3079 01:43:42,445 --> 01:43:45,314 RESULTS FOR VIE CYST. 3080 01:43:45,314 --> 01:43:46,416 I KNOW I'M GOING THROUGH THEM 3081 01:43:46,416 --> 01:43:47,717 VERY QUICK LE AND YOU CAN'T SEE 3082 01:43:47,717 --> 01:43:49,419 THEM BUT I'LL SHOW YOU THE 3083 01:43:49,419 --> 01:43:50,486 SUMMARIES. 3084 01:43:50,486 --> 01:43:58,394 HYPERTHYROIDISM AND HIGH -- 3085 01:43:58,394 --> 01:44:00,129 THERE ARE SO MANY SIGNIFICANT 3086 01:44:00,129 --> 01:44:01,631 ASSOCIATIONS IT'S ALMOST 3087 01:44:01,631 --> 01:44:02,064 UNINTERPRETABLE. 3088 01:44:02,064 --> 01:44:03,166 SO I'M GOING TO NARROW IT DOWN 3089 01:44:03,166 --> 01:44:05,034 BUT JUST KNOW WE HAVE AN 3090 01:44:05,034 --> 01:44:06,302 INCREDIBLE NUMBER OF 3091 01:44:06,302 --> 01:44:07,403 ASSOCIATIONS WITH ALLERGIC 3092 01:44:07,403 --> 01:44:11,441 RHINITIS. 3093 01:44:11,441 --> 01:44:12,742 SO I'M SHOWING YOU A BUNCH OF 3094 01:44:12,742 --> 01:44:14,143 RESULTS YOU CAN'T VISUALIZE OR 3095 01:44:14,143 --> 01:44:14,510 SUMMARIZE HERE. 3096 01:44:14,510 --> 01:44:16,879 SO WHAT I'M SHOWING HERE IS A 3097 01:44:16,879 --> 01:44:18,314 MIAMI PLOT SUMMARIZING THE 3098 01:44:18,314 --> 01:44:19,816 EXPOSURES THAT WERE SIGNIFICANT 3099 01:44:19,816 --> 01:44:22,652 BY GROUPS, LIKE I SAID, WE ASKED 3100 01:44:22,652 --> 01:44:25,288 THOUSANDS OF QUESTIONS, SO SHOWN 3101 01:44:25,288 --> 01:44:26,989 HERE WHAT CAME UP AS SIGNIFICANT 3102 01:44:26,989 --> 01:44:28,291 FOR R.A. 3103 01:44:28,291 --> 01:44:30,059 SO SEVERAL QUESTIONS ABOUT YOUR 3104 01:44:30,059 --> 01:44:31,260 GENERAL HEALTH, THERE WERE A LOT 3105 01:44:31,260 --> 01:44:34,931 OF ASSOCIATIONS WITH 3106 01:44:34,931 --> 01:44:35,598 QUESTIONNAIRES RELATED TO YOUR 3107 01:44:35,598 --> 01:44:36,933 HOME LIFE AND EXPOSURES THERE. 3108 01:44:36,933 --> 01:44:38,634 A NUMBER OF ASSOCIATIONS WITH 3109 01:44:38,634 --> 01:44:41,471 MOOD-BASED QUESTIONS. 3110 01:44:41,471 --> 01:44:44,540 WHICH ALSO IS RIGHT FOR REVERSE 3111 01:44:44,540 --> 01:44:46,075 CAUSALITY, BUT A LOT OF 3112 01:44:46,075 --> 01:44:47,510 PSYCHOLOGICAL QUESTIONNAIRES 3113 01:44:47,510 --> 01:44:50,313 COMING UP. 3114 01:44:50,313 --> 01:44:51,948 EXPOSURES HERE, SORT OF YOUR 3115 01:44:51,948 --> 01:44:55,518 CLASSICAL BIG E KINDS OF 3116 01:44:55,518 --> 01:44:57,920 EXPOSURES, OCCUPATIONAL 3117 01:44:57,920 --> 01:44:58,354 EXPOSURES. 3118 01:44:58,354 --> 01:45:00,089 SO A LOT OF ASSOCIATION WITH 3119 01:45:00,089 --> 01:45:02,158 FATIGUE AND RELATED VARIABLES, 3120 01:45:02,158 --> 01:45:06,863 ANOTHER ASSOCIATION WITH -- 3121 01:45:06,863 --> 01:45:07,830 STRONG ASSOCIATIONS WITH 3122 01:45:07,830 --> 01:45:08,764 OCCUPATION QUESTIONNAIRES AS 3123 01:45:08,764 --> 01:45:12,201 WELL. 3124 01:45:12,201 --> 01:45:14,704 SIMILAR THINGS WERE FOUND FOR 3125 01:45:14,704 --> 01:45:16,539 HYPERTHYROIDISM, SO WE CAN SEE 3126 01:45:16,539 --> 01:45:19,909 HERE, SORT OF A LARGE NUMBER OF 3127 01:45:19,909 --> 01:45:21,244 ASSOCIATIONS ACROSS THESE 3128 01:45:21,244 --> 01:45:28,017 DIFFERENT BROAD CATEGORIES. 3129 01:45:28,017 --> 01:45:29,986 HYPOTHYROIDISM LOOKS VERY 3130 01:45:29,986 --> 01:45:31,053 SIMILAR, STRONGER ASSOCIATIONS 3131 01:45:31,053 --> 01:45:32,021 WITH FATIGUE, AND ACTUALLY SOME 3132 01:45:32,021 --> 01:45:33,456 OF THE STRONGEST MAGNITUDE 3133 01:45:33,456 --> 01:45:36,826 ASSOCIATIONS WERE SEEN IN 3134 01:45:36,826 --> 01:45:37,460 HYPOTHYROIDISM. 3135 01:45:37,460 --> 01:45:40,296 QUESTIONS ABOUT GENERAL HEALTH, 3136 01:45:40,296 --> 01:45:42,498 MOOD, FATIGUE, AND OCCUPATIONAL 3137 01:45:42,498 --> 01:45:44,667 EXPOSURES REALLY HAVING LARGE 3138 01:45:44,667 --> 01:45:48,170 EFFECT SIZES. 3139 01:45:48,170 --> 01:45:49,739 SIMILAR RESULTS HERE FOR 3140 01:45:49,739 --> 01:45:50,339 PSORIASIS. 3141 01:45:50,339 --> 01:45:51,440 PSORIASIS HAD STRONGER 3142 01:45:51,440 --> 01:45:53,042 ASSOCIATIONS WITH 3143 01:45:53,042 --> 01:45:53,843 LIFESTYLE-BASED QUESTIONNAIRES 3144 01:45:53,843 --> 01:45:56,312 THAN SOME OF THE OTHERS. 3145 01:45:56,312 --> 01:45:58,714 REALLY STRONG ASSOCIATIONS WITH 3146 01:45:58,714 --> 01:45:59,682 FATIGUE AND VERY STRONG 3147 01:45:59,682 --> 01:46:00,683 ASSOCIATIONS WITH PSYCHOLOGICAL 3148 01:46:00,683 --> 01:46:05,821 AND MOOD SORT OF QUESTIONNAIRES. 3149 01:46:05,821 --> 01:46:07,456 SO OUR NEXT STEPS ARE TO 3150 01:46:07,456 --> 01:46:09,191 CONTINUE DIGESTING THESE 3151 01:46:09,191 --> 01:46:09,525 RESULTS. 3152 01:46:09,525 --> 01:46:12,562 WE'VE ALSO CONDUCTED STRATIFIED 3153 01:46:12,562 --> 01:46:14,096 ANALYSES. 3154 01:46:14,096 --> 01:46:15,431 ONE OF THE GOALS OF THIS 3155 01:46:15,431 --> 01:46:17,233 WORKSHOP IS FOCUSED OND WOMEN'S 3156 01:46:17,233 --> 01:46:18,067 HEALTH, WE FIND DIFFERENT 3157 01:46:18,067 --> 01:46:19,635 RESULTS WHEN WE STRATIFY BY MEN 3158 01:46:19,635 --> 01:46:21,070 AND WOMEN IN OUR COHORT AND 3159 01:46:21,070 --> 01:46:22,805 WE'RE TRYING TO DIGEST THOSE. 3160 01:46:22,805 --> 01:46:25,541 WE'RE WORKING ON TRYING TO 3161 01:46:25,541 --> 01:46:27,310 INTERPRET AND SYNERGIZE SORT OF 3162 01:46:27,310 --> 01:46:29,979 THE RESULTS ACROSS DISEASES AND 3163 01:46:29,979 --> 01:46:31,480 ACROSS STRATA, WHICH EXPOSURES 3164 01:46:31,480 --> 01:46:34,584 ARE SHARED AMONGST THESE 3165 01:46:34,584 --> 01:46:36,886 DISEASES, WHICH ONES ARE UNIQUE 3166 01:46:36,886 --> 01:46:38,287 AND THE SAME THING ACROSS 3167 01:46:38,287 --> 01:46:39,689 STRATA, WHAT IS SHARED, WHAT IS 3168 01:46:39,689 --> 01:46:40,356 UNIQUE. 3169 01:46:40,356 --> 01:46:41,958 WHAT ARE OVERALL PATTERNS OF 3170 01:46:41,958 --> 01:46:44,360 EXPOSURE AND MORE COMPLEX 3171 01:46:44,360 --> 01:46:46,128 MULTIVARIATE MODELING. 3172 01:46:46,128 --> 01:46:48,831 WE'VE ALSO -- I MENTIONED WE 3173 01:46:48,831 --> 01:46:51,133 HAVE GIS-BASED ESTIMATES OF 3174 01:46:51,133 --> 01:46:53,536 EXPOSURE, IN THE MIDDLE OF 3175 01:46:53,536 --> 01:46:57,773 CONDUCTING EX-WAS WITH GIS-BASED 3176 01:46:57,773 --> 01:46:58,641 ESTIMATES OF EXPOSURE. 3177 01:46:58,641 --> 01:47:01,243 WE'RE ALSO WORKING TO LEVERAGE 3178 01:47:01,243 --> 01:47:02,778 THE MULTIPLE OMICS THAT WE HAVE 3179 01:47:02,778 --> 01:47:03,546 COLLECTED IN PEGS. 3180 01:47:03,546 --> 01:47:07,650 SO I'M HIGHLIGHTING OUR EX-WAS 3181 01:47:07,650 --> 01:47:07,984 STRATEGY HERE. 3182 01:47:07,984 --> 01:47:10,319 WE'RE ALSO RUNNING GWAS TO LOOK 3183 01:47:10,319 --> 01:47:11,320 AT GENETIC ASSOCIATIONS THAT WE 3184 01:47:11,320 --> 01:47:12,622 SEE IN OUR COHORT. 3185 01:47:12,622 --> 01:47:14,590 YOU CAN IMAGINE THE OPPORTUNITY 3186 01:47:14,590 --> 01:47:15,658 FOR GENE ENVIRONMENT 3187 01:47:15,658 --> 01:47:17,226 INTERACTIONS AS SOMETHING WE ARE 3188 01:47:17,226 --> 01:47:18,494 REALLY INTERESTED IN. 3189 01:47:18,494 --> 01:47:21,364 FOLKS BROUGHT UP PTPN AS ONE OF 3190 01:47:21,364 --> 01:47:22,765 THE CANDIDATE GENES THAT'S 3191 01:47:22,765 --> 01:47:24,634 EMERGED IN THIS SPACE. 3192 01:47:24,634 --> 01:47:26,469 WE'RE ACTUALLY SEEING VERY 3193 01:47:26,469 --> 01:47:27,770 STRONG GENE-ENVIRONMENT 3194 01:47:27,770 --> 01:47:29,939 INTERACTIONS WITH PTPN AND THE 3195 01:47:29,939 --> 01:47:32,541 DISTANCE TO CAGED ANIMAL FEEDING 3196 01:47:32,541 --> 01:47:34,276 OPERATIONS WHERE PARTICIPANTS 3197 01:47:34,276 --> 01:47:34,477 LIVE. 3198 01:47:34,477 --> 01:47:36,712 SO WE'RE LOOKING AT BOTH 3199 01:47:36,712 --> 01:47:40,750 CANDIDATE GENE AND SORT OF BRO 3200 01:47:40,750 --> 01:47:42,284 BROADER -- IN THIS DATA AND AS 3201 01:47:42,284 --> 01:47:43,019 WE INTEGRATE IT. 3202 01:47:43,019 --> 01:47:45,321 THEN WE'RE COMMITTED TO VERY 3203 01:47:45,321 --> 01:47:47,523 TRANSPARENT DATA SHARING. 3204 01:47:47,523 --> 01:47:49,225 SO IF YOU'RE INTERESTED IN 3205 01:47:49,225 --> 01:47:52,061 LOOKING AT BROADLY OUR RESULTS, 3206 01:47:52,061 --> 01:47:55,464 WE'VE DONE EX-WAS FOR NOT 3207 01:47:55,464 --> 01:47:57,633 AUTOIMMUNE TRAITS BUT A LOT OF 3208 01:47:57,633 --> 01:47:59,602 OUR COMMON COMPLEX DISEASES AND 3209 01:47:59,602 --> 01:48:06,609 WE'VE DISSEMINATED THOSE ON -- 3210 01:48:06,609 --> 01:48:09,979 WE SHOW THEM ALL THE RESULTS. 3211 01:48:09,979 --> 01:48:11,847 I AM NOT AN EXPERT IN EVERY 3212 01:48:11,847 --> 01:48:14,250 DISEASE, NOT AN EXPERT IN EVERY 3213 01:48:14,250 --> 01:48:15,985 EXPOSURE BUT WE PUT THE DATA OUT 3214 01:48:15,985 --> 01:48:17,086 THERE, MAKE IT SEARCHABLE SO IF 3215 01:48:17,086 --> 01:48:18,487 YOU HAVE HYPOTHESES THAT YOU'RE 3216 01:48:18,487 --> 01:48:20,856 INTERESTED IN, YOU CAN FIND SORT 3217 01:48:20,856 --> 01:48:26,162 OF THE RESULTS FROM PEGS TO HELP 3218 01:48:26,162 --> 01:48:26,562 INTERPRET. 3219 01:48:26,562 --> 01:48:28,330 SO WE PUT THOSE RESULTS OUT 3220 01:48:28,330 --> 01:48:30,833 THERE, BOTH FOR THE COHORT AS A 3221 01:48:30,833 --> 01:48:31,934 WHOLE, WITH DIFFERENT STRATA, 3222 01:48:31,934 --> 01:48:33,769 YOU CAN CHOOSE DIFFERENT 3223 01:48:33,769 --> 01:48:35,538 COVARIATES FOR SENSITIVITY SORT 3224 01:48:35,538 --> 01:48:37,373 OF ANALYSIS, AND THEN WE ALSO 3225 01:48:37,373 --> 01:48:39,675 SHARE EXPOSOME GLOBES. 3226 01:48:39,675 --> 01:48:42,311 WE KNOW EXPOSURES NEVER COME 3227 01:48:42,311 --> 01:48:43,212 UNIQUELY. 3228 01:48:43,212 --> 01:48:45,114 WE'RE CONSTANTLY EXPOSED TO 3229 01:48:45,114 --> 01:48:47,950 MIXTURES IN OUR LIFE AND IN OUR 3230 01:48:47,950 --> 01:48:50,352 WORK, SO LET YOU INTERACT WITH 3231 01:48:50,352 --> 01:48:53,656 WHAT EXPOSURES HAPPEN TOGETHER. 3232 01:48:53,656 --> 01:48:55,391 WHAT IS FURTHER CORRELATION 3233 01:48:55,391 --> 01:48:59,228 STRUCTURE ACROSS THE EXPOSOME. 3234 01:48:59,228 --> 01:49:00,429 SO I'LL TRY TO GET US BACK ON 3235 01:49:00,429 --> 01:49:03,566 TRACK A LITTLE BIT ON TIMING 3236 01:49:03,566 --> 01:49:04,033 HERE. 3237 01:49:04,033 --> 01:49:05,201 THERE'S SO MANY PEOPLE TO THANK 3238 01:49:05,201 --> 01:49:05,801 AND ACKNOWLEDGE. 3239 01:49:05,801 --> 01:49:07,303 WHEN I SAY WE, I'M NEVER DOING 3240 01:49:07,303 --> 01:49:09,171 ANY OF THAT WORK MYSELF. 3241 01:49:09,171 --> 01:49:14,310 SO I HAVE TO THANK MYCOPIJAN 3242 01:49:14,310 --> 01:49:16,512 HALL AND LEADERSHIP IN PEGS, A 3243 01:49:16,512 --> 01:49:18,247 TEAM THAT WORKS ON THE GIS 3244 01:49:18,247 --> 01:49:20,750 MODELING, PARTICULARLY I HAVE TO 3245 01:49:20,750 --> 01:49:21,751 HIGHLIGHT GRADUATE STUDENT 3246 01:49:21,751 --> 01:49:22,952 DILLON LLOYD THAT'S REALLY BEEN 3247 01:49:22,952 --> 01:49:25,121 LEADING THE WORK IN THE EXWAS 3248 01:49:25,121 --> 01:49:29,191 WORK WE'RE DOING, HE'S ON THE OE 3249 01:49:29,191 --> 01:49:30,326 JOB MARKET. 3250 01:49:30,326 --> 01:49:32,294 LOTS OF SUPPORT FOR 3251 01:49:32,294 --> 01:49:33,295 BIOINFORMATICS AND DATA 3252 01:49:33,295 --> 01:49:34,163 INTEGRATION AND THEN WE PARTNER 3253 01:49:34,163 --> 01:49:35,931 WITH A NUMBER OF COLLABORATORS 3254 01:49:35,931 --> 01:49:39,568 FOR DOMAIN EXPERTISE INCLUDING 3255 01:49:39,568 --> 01:49:42,171 FOLKS THAT HAVE HELPED DEFINE 3256 01:49:42,171 --> 01:49:44,006 AND REFINE OUR AUTOIMMUNE 3257 01:49:44,006 --> 01:49:45,407 PHENOTYPING AND WILL HELP US 3258 01:49:45,407 --> 01:49:47,476 INTERPRET, AND THEN OF COURSE 3259 01:49:47,476 --> 01:49:48,811 FIRST AND FOREMOST I HAVE TO 3260 01:49:48,811 --> 01:49:50,479 THANK THE PEGS PARTICIPANTS THAT 3261 01:49:50,479 --> 01:49:51,514 SHARE THIS EXTENSIVE DATA WITH 3262 01:49:51,514 --> 01:49:54,583 US. 3263 01:49:54,583 --> 01:49:55,251 THANKS SO MUCH. 3264 01:49:55,251 --> 01:49:56,986 I'LL STOP THERE. 3265 01:49:56,986 --> 01:49:57,520 >> GREAT. 3266 01:49:57,520 --> 01:50:00,189 THANK YOU SO MUCH, 3267 01:50:00,189 --> 01:50:00,623 DR. MOTSINGER-REIF. 3268 01:50:00,623 --> 01:50:03,025 I'M GOING TO HAVE OUR OTHER 3269 01:50:03,025 --> 01:50:07,463 PANELISTS, DR. HOLLAND AND 3270 01:50:07,463 --> 01:50:08,030 DR. LEWANDOWSKI JOIN US. 3271 01:50:08,030 --> 01:50:08,998 I'M GOING TO ASK THE SAME 3272 01:50:08,998 --> 01:50:11,400 QUESTION FROM ALL OF YOU BUT A 3273 01:50:11,400 --> 01:50:12,601 VERY QUICK ANSWER FROM EACH OF 3274 01:50:12,601 --> 01:50:13,202 YOU. 3275 01:50:13,202 --> 01:50:15,638 AND THAT IS WE'VE HEARD A LOT 3276 01:50:15,638 --> 01:50:17,173 TODAY ABOUT THE FACT THAT THE 3277 01:50:17,173 --> 01:50:18,474 GENETICS DOESN'T EXPLAIN 3278 01:50:18,474 --> 01:50:20,109 EVERYTHING, AND WE'VE GOT OTHER 3279 01:50:20,109 --> 01:50:21,744 TRIGGERS THAT ARE TRIGGERING THE 3280 01:50:21,744 --> 01:50:22,711 IMMUNE SYSTEM. 3281 01:50:22,711 --> 01:50:25,347 SO MY QUESTION IS, WHAT NEEDS TO 3282 01:50:25,347 --> 01:50:27,583 HAPPEN TO ADVANCE THIS SCIENCE? 3283 01:50:27,583 --> 01:50:28,918 CLEARLY WHEN YOU'RE LOOKING AT 3284 01:50:28,918 --> 01:50:30,986 THE GENETICS ALONE, YOU NEED 3285 01:50:30,986 --> 01:50:33,022 PRETTY LARGE SAMPLE SIZES OF 3286 01:50:33,022 --> 01:50:34,423 POPULATIONS IN ORDER TO STUDY, 3287 01:50:34,423 --> 01:50:38,260 BUT IF WE'RE THEN LAYERING ON 3288 01:50:38,260 --> 01:50:40,830 EXPOSURES, WHAT'S THE ANSWER, 3289 01:50:40,830 --> 01:50:42,598 AND HOW CAN WE ADVANCE THAT 3290 01:50:42,598 --> 01:50:42,832 SCIENCE? 3291 01:50:42,832 --> 01:50:47,636 AND I WILL ASK -- LET'S DO IT 3292 01:50:47,636 --> 01:50:49,505 BACKWARDS, DR. MOTSINGER-REIF 3293 01:50:49,505 --> 01:50:49,705 FIRST. 3294 01:50:49,705 --> 01:50:50,906 >> SO I'LL TRY TO BE BRIEF. 3295 01:50:50,906 --> 01:50:52,241 I THINK ONE REALLY EXCITING 3296 01:50:52,241 --> 01:50:53,609 EFFORT WHEN WE THINK ABOUT 3297 01:50:53,609 --> 01:50:54,610 ADDING ENVIRONMENTAL DATA TO 3298 01:50:54,610 --> 01:50:57,313 SOME OF THESE BIG COHORTS IS I 3299 01:50:57,313 --> 01:50:58,848 KNOW AND I'VE WORKED WITH 3300 01:50:58,848 --> 01:50:59,915 LEADERSHIP AT ALL-OF-US, FOR 3301 01:50:59,915 --> 01:51:01,016 EXAMPLE, ON INCORPORATING 3302 01:51:01,016 --> 01:51:03,419 ENVIRONMENTAL EXPOSURES INTO 3303 01:51:03,419 --> 01:51:05,054 THEIR MEGA BIOBANK, I THINK 3304 01:51:05,054 --> 01:51:08,190 WE'RE GOING TO NEED TO ADD 3305 01:51:08,190 --> 01:51:09,291 ENVIRONMENTAL DATA TO THESE 3306 01:51:09,291 --> 01:51:10,726 ALREADY WELL ESTABLISHED AND 3307 01:51:10,726 --> 01:51:12,361 VERY WELL POWERED GENETICS 3308 01:51:12,361 --> 01:51:15,331 COHORT. 3309 01:51:15,331 --> 01:51:15,931 S. 3310 01:51:15,931 --> 01:51:16,298 >> DR. HOLLAND. 3311 01:51:16,298 --> 01:51:17,166 >> I THINK YOU'RE SEEING IT 3312 01:51:17,166 --> 01:51:17,600 RIGHT HERE. 3313 01:51:17,600 --> 01:51:19,335 IT'S EXACTLY THIS KIND OF 3314 01:51:19,335 --> 01:51:20,636 INTERACTION WHERE YOU'VE GOT 3315 01:51:20,636 --> 01:51:21,837 TERRIFIC INVESTIGATORS PUTTING 3316 01:51:21,837 --> 01:51:23,606 ALL OF THE DATA TOGETHER AND 3317 01:51:23,606 --> 01:51:25,007 TRYING TO COORDINATE IT. 3318 01:51:25,007 --> 01:51:26,742 I DON'T THINK IT'S GOING TO BE 3319 01:51:26,742 --> 01:51:27,710 THAT DIFFICULT TO DO. 3320 01:51:27,710 --> 01:51:28,944 IT'S LIKE MOST THINGS IN 3321 01:51:28,944 --> 01:51:30,246 MEDICINE, YOU HAVE TO ASK THE 3322 01:51:30,246 --> 01:51:31,747 QUESTION TO FIND THE ANSWER. 3323 01:51:31,747 --> 01:51:32,815 YOU'VE GOT PEOPLE ASKING THE 3324 01:51:32,815 --> 01:51:33,716 RIGHT QUESTION, THEY'RE GOING TO 3325 01:51:33,716 --> 01:51:35,417 GET THE ANSWERS. 3326 01:51:35,417 --> 01:51:37,653 I'M EXCITED. 3327 01:51:37,653 --> 01:51:40,022 >> DR. LEWANDOWSKI, YOU'RE GOING 3328 01:51:40,022 --> 01:51:41,290 TO TELL ME THE KIDS HAVE THE 3329 01:51:41,290 --> 01:51:41,523 ANSWER. 3330 01:51:41,523 --> 01:51:43,392 >> OF COURSE, OF COURSE. 3331 01:51:43,392 --> 01:51:45,027 CHILDREN ARE OUR FUTURE. 3332 01:51:45,027 --> 01:51:48,430 NO, I THINK THAT I'LL JUST ECHO 3333 01:51:48,430 --> 01:51:49,531 WHAT EVERYBODY ELSE SAID, I 3334 01:51:49,531 --> 01:51:52,434 THINK IT'S GOING TO TAKE A LOT 3335 01:51:52,434 --> 01:51:53,235 OF TEAM WORK. 3336 01:51:53,235 --> 01:51:54,570 IT'S GOING TO TAKE A LOT OF 3337 01:51:54,570 --> 01:51:56,939 SMART PEOPLE GETTING IN THE ROOM 3338 01:51:56,939 --> 01:51:58,240 AND COMBINING DIFFERENT 3339 01:51:58,240 --> 01:51:59,008 TECHNIQUES AND DIFFERENT 3340 01:51:59,008 --> 01:52:00,743 APPROACHES TO THIS QUESTION, AND 3341 01:52:00,743 --> 01:52:02,611 THEN IT'S GOING TO TAKE SOME 3342 01:52:02,611 --> 01:52:04,013 TIME TO KIND OF PUT THE PIECES 3343 01:52:04,013 --> 01:52:05,114 OF THE PUZZLE TOGETHER. 3344 01:52:05,114 --> 01:52:06,615 WE'LL WORK OUT THE GENETICS 3345 01:52:06,615 --> 01:52:07,816 PIECE, WE'LL LAYER ON THESE 3346 01:52:07,816 --> 01:52:09,518 OTHER OMICS AND TOGETHER WE'LL 3347 01:52:09,518 --> 01:52:12,087 WORK TO ADVANCE THE FIELD. 3348 01:52:12,087 --> 01:52:13,589 >> THAT WAS A WONDERFUL SESSION. 3349 01:52:13,589 --> 01:52:16,792 I WANT TO THANK YOU ALL FOR 3350 01:52:16,792 --> 01:52:19,128 GIVING US THAT WONDERFUL TOUR OF 3351 01:52:19,128 --> 01:52:19,695 YOUR SCIENCE. 3352 01:52:19,695 --> 01:52:22,731 I'M GOING TO GIVE OUR AUDIENCE A 3353 01:52:22,731 --> 01:52:23,132 VERY BRIEF BREAK. 3354 01:52:23,132 --> 01:52:25,234 WE ARE GOING TO BREAK FROM NOW 3355 01:52:25,234 --> 01:52:26,669 UNTIL 3:00 P.M. 3356 01:52:26,669 --> 01:52:29,605 BUT THEN JOIN US BACK DIRECTLY 3357 01:52:29,605 --> 01:52:31,040 AT 3:00 P.M., WE HAVE EXCELLENT 3358 01:52:31,040 --> 01:52:33,208 CHAT WITH DR. DAVID FAJGENBAUM, 3359 01:52:33,208 --> 01:52:34,310 YOU WON'T WANT TO MISS IT, SO 3360 01:52:34,310 --> 01:52:36,783 WE'LL SEE YOU BACK SHORTLY. 3361 01:52:38,588 --> 01:52:40,924 >> WELCOME BACK, EVERYONE, AND I 3362 01:52:40,924 --> 01:52:42,759 AM NOW REALLY HONORED TO 3363 01:52:42,759 --> 01:52:46,363 INTRODUCE OUR NEXT SPEAKER, 3364 01:52:46,363 --> 01:52:46,830 DR. DAVID FAJGENBAUM. 3365 01:52:46,830 --> 01:52:47,998 MANY OF YOU MAY HAVE HEARD HIS 3366 01:52:47,998 --> 01:52:48,999 NAME BEFORE BECAUSE HE'S 3367 01:52:48,999 --> 01:52:51,935 SOMEWHAT OF A LEGEND IN THE RARE 3368 01:52:51,935 --> 01:52:52,769 DISEASE COMMUNITY. 3369 01:52:52,769 --> 01:52:58,141 HE WAS DIAGNOSED WITH CASSELMAN 3370 01:52:58,141 --> 01:53:00,677 DISEASE AS A STUDENT AND WENT ON 3371 01:53:00,677 --> 01:53:02,846 TO FOUND THE NETWORK AND HAS 3372 01:53:02,846 --> 01:53:04,147 DEDICATED HIS LIFE TO 3373 01:53:04,147 --> 01:53:05,582 DISCOVERING NEW TREATMENTS AND 3374 01:53:05,582 --> 01:53:07,217 POTENTIAL CURES FOR PREVIOUSLY 3375 01:53:07,217 --> 01:53:11,254 DEADLY DISORDERS INCLUDING 3376 01:53:11,254 --> 01:53:13,857 CASSELMAN'S DISEASE. 3377 01:53:13,857 --> 01:53:15,191 IT IS A CONDITION THAT SITS 3378 01:53:15,191 --> 01:53:16,893 RIGHT AT THE INTERSECTION OF 3379 01:53:16,893 --> 01:53:18,094 AUTOIMMUNITY AND CANCER, AND 3380 01:53:18,094 --> 01:53:21,264 IT'S IN THE LIST OF DISEASES 3381 01:53:21,264 --> 01:53:24,434 THAT THE OFFICE OF AUTOIMMUNE 3382 01:53:24,434 --> 01:53:27,938 DISEASE RESEARCH IS ASKED TO 3383 01:53:27,938 --> 01:53:30,106 CONSIDER. 3384 01:53:30,106 --> 01:53:31,074 THERE'S ALSO A NOVEL CONNECTION 3385 01:53:31,074 --> 01:53:32,609 I WANT TO HIGHLIGHT WITH OUR 3386 01:53:32,609 --> 01:53:33,710 AUDIENCE BECAUSE THIS SYMPOSIUM 3387 01:53:33,710 --> 01:53:35,478 AS WE'VE SAID, THE EIGHTH ANNUAL 3388 01:53:35,478 --> 01:53:38,415 VIVIAN PINN SYMPOSIUM, HONORS 3389 01:53:38,415 --> 01:53:40,116 THE FIRST TIME -- DIRECTOR OF 3390 01:53:40,116 --> 01:53:40,951 THE OFFICE OF RESEARCH ON 3391 01:53:40,951 --> 01:53:43,887 WOMEN'S HELD, DR. VIVIAN PINN. 3392 01:53:43,887 --> 01:53:45,088 DR. PINN IS AN ACCOMPLISHED 3393 01:53:45,088 --> 01:53:46,656 PATHOLOGIST, SHE WAS THE FIRST 3394 01:53:46,656 --> 01:53:49,693 AFRICAN AMERICAN WOMAN TO CHAIR 3395 01:53:49,693 --> 01:53:50,760 A PATHOLOGY DEPARTMENT IN THE 3396 01:53:50,760 --> 01:53:51,628 UNITED STATES BUT THERE IS A 3397 01:53:51,628 --> 01:53:53,096 PIECE OF DR. PINN'S HISTORY THAT 3398 01:53:53,096 --> 01:53:54,965 I ONLY FOUND OUT ABOUT QUITE 3399 01:53:54,965 --> 01:53:57,767 RECENTLY AFTER WE'D SELECTED THE 3400 01:53:57,767 --> 01:54:02,672 SPEAKERS, AND THAT IS THAT 3401 01:54:02,672 --> 01:54:04,240 DR. PINN WAS RECRUITED TO 3402 01:54:04,240 --> 01:54:10,814 RESIDENCY AND MENTORED BY 3403 01:54:10,814 --> 01:54:14,951 DR. CASTLEMAN. 3404 01:54:14,951 --> 01:54:16,386 YOU ARE AN ACCOMPLISHED 3405 01:54:16,386 --> 01:54:17,687 PHYSICIAN SCIENTIST, YOU'RE A 3406 01:54:17,687 --> 01:54:18,688 RECOGNIZED LEADER IN THE FIELD 3407 01:54:18,688 --> 01:54:20,123 OF HEALTHCARE, YOU'VE RECEIVED A 3408 01:54:20,123 --> 01:54:22,425 NUMBER OF AWARDS AND BEEN 3409 01:54:22,425 --> 01:54:25,795 PROFILED IN MANY, MANY 3410 01:54:25,795 --> 01:54:26,863 NEWSPAPERS, "THE NEW YORK 3411 01:54:26,863 --> 01:54:27,364 TIMES," "THE WALL STREET 3412 01:54:27,364 --> 01:54:28,298 JOURNAL," SCIENCE, AND YOU'VE 3413 01:54:28,298 --> 01:54:30,266 BEEN ON THE TODAY SHOW IT'S 3414 01:54:30,266 --> 01:54:31,735 REALLY A DELIGHT TO HAVE YOU 3415 01:54:31,735 --> 01:54:33,269 JOIN US TODAY AND TELL US THE 3416 01:54:33,269 --> 01:54:35,438 STORY OF HOW YOU WENT FROM A 3417 01:54:35,438 --> 01:54:38,008 COLLEGE FOOTBALL PLAYER TO NIH 3418 01:54:38,008 --> 01:54:40,176 FUNDED PHYSICIAN SCIENTIST 3419 01:54:40,176 --> 01:54:42,479 SEARCHING FOR CURES FOR RARE 3420 01:54:42,479 --> 01:54:43,780 DISEASES. 3421 01:54:43,780 --> 01:54:46,082 WELCOME TO THE VIVIAN PINN 3422 01:54:46,082 --> 01:54:46,349 SYMPOSIUM. 3423 01:54:46,349 --> 01:54:47,951 >> VICKI, THANK YOU SO MUCH FOR 3424 01:54:47,951 --> 01:54:48,818 THAT KIND INTRODUCTION. 3425 01:54:48,818 --> 01:54:50,220 IT'S REALLY SUCH AN HONOR TO BE 3426 01:54:50,220 --> 01:54:53,723 WITH ALL OF YOU AND TO HEAR 3427 01:54:53,723 --> 01:54:56,092 ABOUT THE CONNECTION TO 3428 01:54:56,092 --> 01:54:57,894 CASTLEMAN DISEASE WITH DR. PINN 3429 01:54:57,894 --> 01:55:01,664 IS JUST SO, SO INCREDIBLE. 3430 01:55:01,664 --> 01:55:03,033 I APPRECIATE BEING WITH YOU ALL. 3431 01:55:03,033 --> 01:55:05,368 >> I WANTED TO START NOT AT THE 3432 01:55:05,368 --> 01:55:06,569 BEGINNING OF YOUR STORY BUT 3433 01:55:06,569 --> 01:55:07,237 SOMEWHERE IN THE MIDDLE, WHICH 3434 01:55:07,237 --> 01:55:08,438 IS THE POINT OF YOUR DIAGNOSIS. 3435 01:55:08,438 --> 01:55:10,306 AT THAT POINT I THINK THERE'S A 3436 01:55:10,306 --> 01:55:11,207 PICTURE SHOWING ON THE SCREEN, 3437 01:55:11,207 --> 01:55:13,276 YOU'D BEEN VERY UNWELL FOR QUITE 3438 01:55:13,276 --> 01:55:16,146 SOME TIME, YOU'D HAD MANY 3439 01:55:16,146 --> 01:55:17,781 HOSPITALIZATIONS, I THINK AT 3440 01:55:17,781 --> 01:55:19,616 THIS POINT IN TIME YOU WERE IN 3441 01:55:19,616 --> 01:55:20,850 THE INTENSIVE CARE UNIT AND 3442 01:55:20,850 --> 01:55:22,318 ULTIMATELY YOU AS THE KIND OF 3443 01:55:22,318 --> 01:55:23,520 ADVOCATE FOR YOUR OWN ILLNESS 3444 01:55:23,520 --> 01:55:25,155 SAID YOU NEEDED A LYMPH NODE 3445 01:55:25,155 --> 01:55:26,623 BIOPSY BECAUSE TISSUE WAS THE 3446 01:55:26,623 --> 01:55:27,424 ISSUE. 3447 01:55:27,424 --> 01:55:28,058 DR. PINN WOULD BE VERY PROUD OF 3448 01:55:28,058 --> 01:55:30,627 YOU. 3449 01:55:30,627 --> 01:55:31,728 I WONDERED IF YOU COULD SHARE 3450 01:55:31,728 --> 01:55:32,762 WITH OUR AUDIENCE WHAT HAPPENED 3451 01:55:32,762 --> 01:55:35,598 WHEN YOU WERE HANDED THAT 3452 01:55:35,598 --> 01:55:36,699 PATHOLOGY REPORT THAT ULTIMATELY 3453 01:55:36,699 --> 01:55:37,467 DELIVERED YOUR DIAGNOSIS. 3454 01:55:37,467 --> 01:55:42,672 >> WELL, IT WAS SOMETHING WE'D 3455 01:55:42,672 --> 01:55:45,108 BEEN SEARCHING FOR FOR 11 WEEKS, 3456 01:55:45,108 --> 01:55:46,076 A DIAGNOSIS, WHAT WAS IT THAT 3457 01:55:46,076 --> 01:55:47,510 HAD PUT ME IN THE INTENSIVE 3458 01:55:47,510 --> 01:55:48,945 CARE, WHAT WAS IT THAT CAUSED 3459 01:55:48,945 --> 01:55:52,082 ALL MY ORGANS TO SHUT DOWN, WHAT 3460 01:55:52,082 --> 01:55:53,550 WAYS LITERALLY DYING FROM. 3461 01:55:53,550 --> 01:55:54,717 FINALLY WE GOT THIS PATHOLOGY 3462 01:55:54,717 --> 01:55:59,322 REPORT AND ON IT SAID CONSISTENT 3463 01:55:59,322 --> 01:56:04,427 WITH IDIOPATHIC MULTICENTRIC 3464 01:56:04,427 --> 01:56:04,994 CASTLEMAN'S DISEASE. 3465 01:56:04,994 --> 01:56:06,763 I WAS A THIRD YEAR MED STUDENT 3466 01:56:06,763 --> 01:56:08,498 AT THE TIME, I HAVE TO ADMIT I 3467 01:56:08,498 --> 01:56:09,933 DIDN'T REMEMBER LEARNING ABOUT 3468 01:56:09,933 --> 01:56:10,967 IT, I CERTAINLY DIDN'T KNOW WHAT 3469 01:56:10,967 --> 01:56:11,468 IT WAS. 3470 01:56:11,468 --> 01:56:13,937 FOR SO MANY PEOPLE WITH 3471 01:56:13,937 --> 01:56:15,038 AUTOIMMUNE DISEASES AND THESE 3472 01:56:15,038 --> 01:56:16,906 SORT OF EXCEPTIONAL AUTOIMMUNE 3473 01:56:16,906 --> 01:56:18,308 SYNDROMES THAT MAYBE AREN'T EVEN 3474 01:56:18,308 --> 01:56:23,947 ABLE TO BE CLASSIFIED, WE FIGHT 3475 01:56:23,947 --> 01:56:25,715 SO HARD TO GET A DIAGNOSIS BUT 3476 01:56:25,715 --> 01:56:26,883 SOMETIMES IT DOESN'T GIVE ALL 3477 01:56:26,883 --> 01:56:27,584 THAT MANY ANSWERS. 3478 01:56:27,584 --> 01:56:33,690 WE HAD A LOT MORE ANS MORE QUESN 3479 01:56:33,690 --> 01:56:33,923 ANSWERS. 3480 01:56:33,923 --> 01:56:35,325 >> TELL US KIND OF WHAT HAPPENED 3481 01:56:35,325 --> 01:56:36,559 NEXT IN THE STORY. 3482 01:56:36,559 --> 01:56:37,994 >> SURE. 3483 01:56:37,994 --> 01:56:41,164 SO I WAS A FORMER HEALTHY 3484 01:56:41,164 --> 01:56:42,699 COLLEGE QUARTERBACK AND I WAS A 3485 01:56:42,699 --> 01:56:43,266 MEDICAL STUDENT. 3486 01:56:43,266 --> 01:56:46,336 I WANTED TO BE AN ONCOLOGIST, I 3487 01:56:46,336 --> 01:56:47,403 WANTED TO TREAT PATIENTS IN 3488 01:56:47,403 --> 01:56:50,006 MEMORY OF MY MOM WHEN OUT OF 3489 01:56:50,006 --> 01:56:51,007 NOWHERE I'D GOTTEN SO SICK. 3490 01:56:51,007 --> 01:56:54,077 SO WITH THIS DIAGNOSIS OF 3491 01:56:54,077 --> 01:56:55,245 CASTLEMAN DISEASE, FORTUNATELY 3492 01:56:55,245 --> 01:56:57,580 CAME A LOT OF TREATMENT. 3493 01:56:57,580 --> 01:57:00,617 THANKFULLY, I WAS GIVEN FIRST 3494 01:57:00,617 --> 01:57:06,756 RITUXIMAB AND THEN IL-6 BLOCK 3495 01:57:06,756 --> 01:57:09,659 BLOCKADE, TOCILIZUMAB, 3496 01:57:09,659 --> 01:57:10,460 UNFORTUNATELY IL-6 BLOCKADE DID 3497 01:57:10,460 --> 01:57:11,761 NOT WORK FOR CASTLEMAN DISEASE 3498 01:57:11,761 --> 01:57:14,097 SO I ENDED UP RECEIVING A 3499 01:57:14,097 --> 01:57:15,999 COMBINATION OF 17 3500 01:57:15,999 --> 01:57:17,400 CHEMOTHERAPIES. 3501 01:57:17,400 --> 01:57:20,036 IT WAS THAT COMBINATION OF 3502 01:57:20,036 --> 01:57:21,137 CHEMOTHERAPIES THAT JUST 3503 01:57:21,137 --> 01:57:26,609 COMPLETELY OWE B OBLITERATED MYE 3504 01:57:26,609 --> 01:57:27,377 SYSTEM. 3505 01:57:27,377 --> 01:57:31,881 THTHE PA -- CASTLEMAN'S AS YOU 3506 01:57:31,881 --> 01:57:33,283 MENTIONED REALLY SITS AT THE 3507 01:57:33,283 --> 01:57:34,584 INTERSECTION -- THERE'S CLEARLY 3508 01:57:34,584 --> 01:57:36,786 AUTOIMMUNE FEATURES BUT THERE'S 3509 01:57:36,786 --> 01:57:39,022 ALSO THIS LYMPHOPROLIFERATIVE 3510 01:57:39,022 --> 01:57:41,191 FEATURE TO THE DISEASE AS WELL, 3511 01:57:41,191 --> 01:57:43,393 AND THANKFULLY THE CHEMOTHERAPY 3512 01:57:43,393 --> 01:57:43,927 SAVED MY LIFE. 3513 01:57:43,927 --> 01:57:45,461 YOU CAN SEE SOME PICTURES ON THE 3514 01:57:45,461 --> 01:57:48,398 SCREEN OF ME WITH MY DAD. 3515 01:57:48,398 --> 01:57:49,732 MY MOM HAD PASSED AWAY FROM 3516 01:57:49,732 --> 01:57:52,835 CANCER A FEW YEARS BEFORE, BUT 3517 01:57:52,835 --> 01:57:54,470 MY DAD NEVER LEFT MY SIDE. 3518 01:57:54,470 --> 01:57:55,905 HE WAS SPENDING THE NIGHT IN THE 3519 01:57:55,905 --> 01:57:57,307 HOSPITAL ROOM WITH ME FOR SIX 3520 01:57:57,307 --> 01:57:58,575 MONTHS THAT I WAS HOSPITALIZED. 3521 01:57:58,575 --> 01:58:00,743 >> AND SO TELL US A BIT MORE 3522 01:58:00,743 --> 01:58:03,846 ABOUT KIND OF YOUR JOURNEY 3523 01:58:03,846 --> 01:58:07,217 THROUGH THIS PERIOD OF GETTING 3524 01:58:07,217 --> 01:58:08,251 TO YOUR DIAGNOSIS AND STARTING 3525 01:58:08,251 --> 01:58:09,953 ON TREATMENT. 3526 01:58:09,953 --> 01:58:12,055 YOU TALK A LITTLE BIT IN SOME OF 3527 01:58:12,055 --> 01:58:14,357 THE STORIES THAT YOU TOLD 3528 01:58:14,357 --> 01:58:16,092 ELSEWHERE ABOUT HOPE AND THE 3529 01:58:16,092 --> 01:58:19,062 DIFFERENCES BETWEEN HOPE AND 3530 01:58:19,062 --> 01:58:20,263 OPTIMISM, AND AT SOME POINT IN 3531 01:58:20,263 --> 01:58:21,464 THIS JOURNEY, YOU HAD THIS KIND 3532 01:58:21,464 --> 01:58:22,999 OF INFLECTION POINT WHERE YOU 3533 01:58:22,999 --> 01:58:24,767 REALIZED THAT HOPE WASN'T THE 3534 01:58:24,767 --> 01:58:25,602 WHOLE ANSWER AND THAT YOU NEEDED 3535 01:58:25,602 --> 01:58:26,102 SOMETHING ELSE. 3536 01:58:26,102 --> 01:58:28,738 CAN YOU TELL US MORE ABOUT THAT 3537 01:58:28,738 --> 01:58:29,639 PIECE OF THE STORY? 3538 01:58:29,639 --> 01:58:31,908 >> SURE. 3539 01:58:31,908 --> 01:58:34,010 YOU KNOW, YOU VICKI, WHEN I WAS 3540 01:58:34,010 --> 01:58:37,046 A MEDICAL STUDENT AT PENN, I WAS 3541 01:58:37,046 --> 01:58:37,880 HEARING ABOUT ALL THESE BREAK 3542 01:58:37,880 --> 01:58:39,148 THROUGHS HAPPENING, FOLLOWING 3543 01:58:39,148 --> 01:58:40,617 SCIENCE AND MEDICINE AND SO 3544 01:58:40,617 --> 01:58:42,852 HOPEFUL AND OPTIMISTIC THAT, OH, 3545 01:58:42,852 --> 01:58:44,254 MY GOSH, THERE ARE EITHER CURES 3546 01:58:44,254 --> 01:58:45,888 FOR EVERY DISEASE OUT THERE OR 3547 01:58:45,888 --> 01:58:47,257 THERE'S CURES THAT ARE ON THEIR 3548 01:58:47,257 --> 01:58:47,890 WAY. 3549 01:58:47,890 --> 01:58:51,928 IN HINDSIGHT, IT WAS MAYBE A BIT 3550 01:58:51,928 --> 01:58:53,896 NAIVE BUT CERTAINLY I WAS A 3551 01:58:53,896 --> 01:58:55,565 REALLY, REALLY HOPEFUL MEDICAL 3552 01:58:55,565 --> 01:58:55,798 STUDENT. 3553 01:58:55,798 --> 01:58:57,734 ALL OF A SUDDEN WITH A DIAGNOSIS 3554 01:58:57,734 --> 01:58:58,968 OF CASTLEMAN DISEASE, I LEARNED 3555 01:58:58,968 --> 01:59:01,604 THAT THERE WERE DISEASES LIKE 3556 01:59:01,604 --> 01:59:02,372 CASTLEMANs WHERE WE HAVE A 3557 01:59:02,372 --> 01:59:05,642 NAME FOR IT. 3558 01:59:05,642 --> 01:59:06,542 THANKFULLY BENJAMIN CASTLEMAN 3559 01:59:06,542 --> 01:59:07,543 DID IMPORTANT WORK SO WE'VE GOT 3560 01:59:07,543 --> 01:59:11,681 A NAME FOR IT BUT WE REALLY KNOW 3561 01:59:11,681 --> 01:59:12,815 SO LITTLE ABOUT HOW THE DISEASE 3562 01:59:12,815 --> 01:59:13,983 WORKS AND SO LITTLE ABOUT HOW TO 3563 01:59:13,983 --> 01:59:14,250 TREAT IT. 3564 01:59:14,250 --> 01:59:15,785 SO I REALLY HAD A MAJOR CHANGE 3565 01:59:15,785 --> 01:59:17,754 RIGHT AROUND THE TIME THAT I 3566 01:59:17,754 --> 01:59:19,055 RELAPSED ON IL-6 BLOCKADE. 3567 01:59:19,055 --> 01:59:20,957 SO I MENTIONED IL-6 BLOCKADE 3568 01:59:20,957 --> 01:59:23,092 DIDN'T WORK FOR ME IN MY ACUTE 3569 01:59:23,092 --> 01:59:23,559 PHASE OF THE DISEASE. 3570 01:59:23,559 --> 01:59:26,095 WE THOUGHT THAT MAYBE IL-6 3571 01:59:26,095 --> 01:59:27,730 BLOCKADE WITH A DRUG SUL TUCKS 3572 01:59:27,730 --> 01:59:30,300 MAN TO KEEP MY DISEASE IN REMIX, 3573 01:59:30,300 --> 01:59:31,301 INTERLEUKIN 6, EVERY1 ON THIS 3574 01:59:31,301 --> 01:59:34,337 CALL WILL BE VERY FAMILIAR WITH 3575 01:59:34,337 --> 01:59:36,539 IL-6, PLAYS AN IMPORTANT ROLE IN 3576 01:59:36,539 --> 01:59:40,009 A NUMBER OF AUTOIMMUNE 3577 01:59:40,009 --> 01:59:42,979 CONDITIONS. 3578 01:59:42,979 --> 01:59:47,317 TOCILUZUMAB WAS FIRST DEVELOPED 3579 01:59:47,317 --> 01:59:48,818 FOR CASTLEMAN DISEASE. 3580 01:59:48,818 --> 01:59:50,453 THEY DEVELOPED IT FOR 3581 01:59:50,453 --> 01:59:51,421 CASTLEMAN'S. 3582 01:59:51,421 --> 01:59:52,422 IT'S ACTUALLY A PRETTY 3583 01:59:52,422 --> 01:59:55,191 INCREDIBLE STORY. 3584 01:59:55,191 --> 01:59:56,426 THEY DISCOVERED I. 3585 01:59:56,426 --> 01:59:57,727 WILL 6 WAS IMPORTANT, THEY 3586 01:59:57,727 --> 02:00:01,431 DEVELOPED THIS IL-6 RECEPTOR 3587 02:00:01,431 --> 02:00:01,698 ANTIBODY. 3588 02:00:01,698 --> 02:00:02,999 BEFORE HE GAVE TO THE VERY FIRST 3589 02:00:02,999 --> 02:00:05,501 PATIENT WITH CASTLEMAN EA HE 3590 02:00:05,501 --> 02:00:07,804 ACTUALLY DECIDED TO TRY IT ON 3591 02:00:07,804 --> 02:00:09,439 HIMSELF TO PROVE IT WAS SAFE. 3592 02:00:09,439 --> 02:00:10,873 I'M NOT RECOMMENDING THIS FOR 3593 02:00:10,873 --> 02:00:12,642 ANYONE THAT YOU SHOULD BE 3594 02:00:12,642 --> 02:00:14,210 TESTING NOVEL COMPOUNDS ON 3595 02:00:14,210 --> 02:00:15,244 HIMSELF, BUT WHEN HE DIDN'T HAVE 3596 02:00:15,244 --> 02:00:16,779 ANY HORRIBLE REACTION TO IT, HE 3597 02:00:16,779 --> 02:00:18,614 WENT ON TO STUDY IT IN A PHASE 3598 02:00:18,614 --> 02:00:20,817 ONE CLINICAL TRIAL IN JAPAN FOR 3599 02:00:20,817 --> 02:00:22,118 CASTLEMAN'S PATIENTS. 3600 02:00:22,118 --> 02:00:23,886 IT GOT FIRST APPROVED FOR 3601 02:00:23,886 --> 02:00:25,188 CASTLEMAN'S IN JAPAN AND THEN 3602 02:00:25,188 --> 02:00:26,322 EVERYONE ON THIS CALL WILL KNOW 3603 02:00:26,322 --> 02:00:27,590 THAT IT THEN CAME TO THE UNITED 3604 02:00:27,590 --> 02:00:29,492 STATES WHERE WE GOT APPROVAL FOR 3605 02:00:29,492 --> 02:00:35,398 ROOM TIERHEUMATOID ARTHRITIS, ME 3606 02:00:35,398 --> 02:00:37,100 RECENTLY IN COVID, BUT THIS WAS 3607 02:00:37,100 --> 02:00:38,134 A CASTLEMAN'S DRUG THAT WAS 3608 02:00:38,134 --> 02:00:40,136 DEVELOPED BECAUSE INTERLEUKIN 3609 02:00:40,136 --> 02:00:40,670 6 WAS SO IMPORTANT. 3610 02:00:40,670 --> 02:00:42,305 SO IL-6 HAS BEEN SORT OF THE ONE 3611 02:00:42,305 --> 02:00:45,174 THING WE'VE KNOWN ABOUT 3612 02:00:45,174 --> 02:00:46,509 IDIOPATHIC MULTICENTRIC 3613 02:00:46,509 --> 02:00:49,779 CASTLEMAN'S DISEASE ALL THESE -- 3614 02:00:49,779 --> 02:00:51,814 BUT IT TURNS OUT IT ONLY WORKS 3615 02:00:51,814 --> 02:00:53,015 IN ABOUT ONE HALF OF PATIENTS. 3616 02:00:53,015 --> 02:00:56,185 SO I LEARNED THAT I FALL INTO 3617 02:00:56,185 --> 02:00:57,453 THAT CATEGORY OF PATIENTS, THE 3618 02:00:57,453 --> 02:00:58,821 TWO THIRDS OR SO OF PATIENTS 3619 02:00:58,821 --> 02:01:01,090 THAT DON'T BENEFIT FROM IL-6 3620 02:01:01,090 --> 02:01:04,494 BLOCKADE, AND SO FOR ME, 3621 02:01:04,494 --> 02:01:06,062 EMOTIONALLY, THAT WAS SUCH A LOW 3622 02:01:06,062 --> 02:01:08,131 POINT, BECAUSE HERE I WAS WITH 3623 02:01:08,131 --> 02:01:09,665 THIS DISEASE THAT'S DEADLY BUT, 3624 02:01:09,665 --> 02:01:11,334 HEY, AT LEAST WE CAN BLOCK IL-6 3625 02:01:11,334 --> 02:01:12,668 AND MAYBE THIS WON'T COME BACK 3626 02:01:12,668 --> 02:01:13,836 AGAIN, BUT THEN WE BLOCK THE 3627 02:01:13,836 --> 02:01:16,072 HECK OUT OF IL-6, AND IT STILL 3628 02:01:16,072 --> 02:01:16,939 CAME BACK AND SO THE PICTURE ON 3629 02:01:16,939 --> 02:01:18,374 THE LEFT IS FROM MY FOURTH 3630 02:01:18,374 --> 02:01:20,009 RELAPSE OF THE DISEASE, AND 3631 02:01:20,009 --> 02:01:22,011 THAT'S WHILE I WAS ON THIS DRUG 3632 02:01:22,011 --> 02:01:23,413 SUL TUCKS MAN, AND THAT'S REALLY 3633 02:01:23,413 --> 02:01:25,081 SORT OF TO ANSWER YOUR QUESTION, 3634 02:01:25,081 --> 02:01:27,383 WHEN MY LIFE CHANGED, WHEN I 3635 02:01:27,383 --> 02:01:28,151 WENT FROM SAYING I'M GOING TO 3636 02:01:28,151 --> 02:01:29,452 HOPE THAT SOME RESEARCHERS 3637 02:01:29,452 --> 02:01:30,453 SOMEWHERE COULD FIGURE OUT 3638 02:01:30,453 --> 02:01:32,188 SOMETHING FOR CASTLEMAN'S TO 3639 02:01:32,188 --> 02:01:33,256 SAYING IF I'M GOING TO HOPE 3640 02:01:33,256 --> 02:01:35,758 THERE COULD BE A TREATMENT FOR 3641 02:01:35,758 --> 02:01:37,660 CASTLEMAN EA I NEED TO TURN MY 3642 02:01:37,660 --> 02:01:38,194 HOPE INTO ACTION. 3643 02:01:38,194 --> 02:01:39,762 AND I WASN'T NAIVE INTO THINKING 3644 02:01:39,762 --> 02:01:40,930 I COULD DEVELOP SOME NEW DRUG 3645 02:01:40,930 --> 02:01:41,597 FROM SCRATCH. 3646 02:01:41,597 --> 02:01:42,965 FRANKLY THERE WEREN'T ANY NOVEL 3647 02:01:42,965 --> 02:01:44,867 TARGETS TO GO AFTER ANYWAY BUT I 3648 02:01:44,867 --> 02:01:45,768 CERTAINLY DIDN'T HAVE A BILLION 3649 02:01:45,768 --> 02:01:46,836 DOLLARS AND 10 YEARS TO CREATE 3650 02:01:46,836 --> 02:01:51,174 SOMETHING NEW, SO FROM MAY OF 20 3651 02:01:51,174 --> 02:01:52,842 2012, WHEN I HAD THAT FOURTH 3652 02:01:52,842 --> 02:01:53,943 DEADLY FLARE OF MY DISEASE, FROM 3653 02:01:53,943 --> 02:01:56,546 THAT MOMENT, EXACTLY 12 YEARS 3654 02:01:56,546 --> 02:01:58,314 AGO, I MADE THE DECISION THAT I 3655 02:01:58,314 --> 02:01:59,849 WOULD DO DEEP IMMUNE PROFILING 3656 02:01:59,849 --> 02:02:03,286 OF MY OWN IMMUNE SYSTEM AND 3657 02:02:03,286 --> 02:02:06,022 OTHER CASTLEMAN'S PATIENTS' 3658 02:02:06,022 --> 02:02:07,290 IMMUNE SYSTEMS AND SEE IF THERE 3659 02:02:07,290 --> 02:02:08,324 WERE EXISTING DRUGS THAT COULD 3660 02:02:08,324 --> 02:02:08,791 BE REPURPOSE DOLLARS. 3661 02:02:08,791 --> 02:02:11,360 ALL OF US IN AUTOIMMUNITY KNOW 3662 02:02:11,360 --> 02:02:12,895 DRUGS GET REPURPOSED ALL THE 3663 02:02:12,895 --> 02:02:14,997 TIME, THERE WERE NO DRUGS IN 3664 02:02:14,997 --> 02:02:15,765 DEVELOPMENT FOR CASTLEMAN'S SO 3665 02:02:15,765 --> 02:02:18,367 THE QUESTION WAS COULD I UNCOVER 3666 02:02:18,367 --> 02:02:20,570 A MECHANISM, REALLY TO YOUR 3667 02:02:20,570 --> 02:02:22,438 QUESTION, IT WAS REALLY BECAUSE 3668 02:02:22,438 --> 02:02:24,040 I REALIZED I COULDN'T JUST HOPE 3669 02:02:24,040 --> 02:02:25,241 AND WAIT, I WOULD NEED TO TURN 3670 02:02:25,241 --> 02:02:26,042 MY HOPE INTO ACTION. 3671 02:02:26,042 --> 02:02:28,010 >> I'M GOING TO TAKE IT BACK A 3672 02:02:28,010 --> 02:02:29,645 LITTLE BIT AND WE'RE GOING TO 3673 02:02:29,645 --> 02:02:30,713 COME BACK TO HOW YOU KIND OF 3674 02:02:30,713 --> 02:02:31,280 MOVE THIS FORWARD. 3675 02:02:31,280 --> 02:02:33,683 WHEN YOU GOT TREATMENT WITH SELL 3676 02:02:33,683 --> 02:02:36,519 TUCKS MAN, IT WAS STILL A DRUG 3677 02:02:36,519 --> 02:02:37,753 IN CLINICAL TRIAL FOR 3678 02:02:37,753 --> 02:02:38,788 CASTLEMAN'S. 3679 02:02:38,788 --> 02:02:41,424 SO YOU WERE TRYING TO ACTUALLY 3680 02:02:41,424 --> 02:02:42,558 ENROLL IN A CLINICAL TRIAL AND 3681 02:02:42,558 --> 02:02:45,294 THEN YOU HAD A RELAPSE THAT 3682 02:02:45,294 --> 02:02:47,029 MEANT YOU WERE SUDDENLY TOO SICK 3683 02:02:47,029 --> 02:02:48,698 TO ENROLL IN THE CLINICAL TRIAL. 3684 02:02:48,698 --> 02:02:49,966 YOUR DOCTORS HAD TO APPEAL TO 3685 02:02:49,966 --> 02:02:53,703 THE FDA TO GET IT APPROVED AS 3686 02:02:53,703 --> 02:02:55,338 EXPERIMENTAL THERAPY OUTSIDE OF 3687 02:02:55,338 --> 02:02:59,909 A CLINICAL TRIAL CAN YOU TELL US 3688 02:02:59,909 --> 02:03:01,010 A LITTLE ABOUT HOW THAT FELT, 3689 02:03:01,010 --> 02:03:04,947 WHAT THAT EXPERIENCE WAS LIKE, 3690 02:03:04,947 --> 02:03:05,848 AND JUST SHARE WITH US WHAT THAT 3691 02:03:05,848 --> 02:03:08,084 FELT LIKE? 3692 02:03:08,084 --> 02:03:08,684 >> SURE. 3693 02:03:08,684 --> 02:03:10,720 I WAS SO HOPEFUL THIS DRUG WAS 3694 02:03:10,720 --> 02:03:12,588 GOING TO KEEP ME IN REMISSION 3695 02:03:12,588 --> 02:03:13,956 LONG TERM AND THAT BLOCKING IL-6 3696 02:03:13,956 --> 02:03:15,925 WAS GOING TO BE THE SOLUTION. 3697 02:03:15,925 --> 02:03:17,560 MAYBE IT COULD HELP TO KEEP ME 3698 02:03:17,560 --> 02:03:19,862 IN REMISSION. 3699 02:03:19,862 --> 02:03:21,063 WHEN ALL OF A SUDDEN I STARTED 3700 02:03:21,063 --> 02:03:22,265 TO RELAPSE JUST BEFORE I COULD 3701 02:03:22,265 --> 02:03:24,267 GET STARTED ON THIS -- JOIN THE 3702 02:03:24,267 --> 02:03:27,870 TROIL, IT WAS HEARTBREAKING. 3703 02:03:27,870 --> 02:03:30,039 SO MANY OF US ON THE CALL THAT 3704 02:03:30,039 --> 02:03:31,040 ENROLL PATIENTS IN CLINICAL 3705 02:03:31,040 --> 02:03:32,775 TRIALS, YOU ALL KNOW SOMETIMES 3706 02:03:32,775 --> 02:03:33,676 CLINICAL TRIALS ARE OUR ONLY 3707 02:03:33,676 --> 02:03:34,076 HOPE. 3708 02:03:34,076 --> 02:03:35,945 SO IT GO FROM BEING SO EXCITED, 3709 02:03:35,945 --> 02:03:37,079 SEEING MY DOCTOR SAYING YOU'RE 3710 02:03:37,079 --> 02:03:39,248 GOING TO GET ON THIS DRUG AND IT 3711 02:03:39,248 --> 02:03:40,449 WILL HOPEFULLY KEEP YOU IN 3712 02:03:40,449 --> 02:03:42,184 REMISSION TO THEN NOT BEING 3713 02:03:42,184 --> 02:03:45,788 ELIGIBLE, THAT WAS HEARTBREA 3714 02:03:45,788 --> 02:03:46,122 HEARTBREAKING. 3715 02:03:46,122 --> 02:03:48,424 THE FLIP SIDE OF IT WAS IT WAS 3716 02:03:48,424 --> 02:03:49,859 SO EXCITING FOR MY FAMILY AND I 3717 02:03:49,859 --> 02:03:55,331 WHEN WE FOUND OUT THAT THE FDA 3718 02:03:55,331 --> 02:03:57,066 HAD GRANTED ME EMERGENCY 3719 02:03:57,066 --> 02:03:58,701 COMPASSIONATE USE. 3720 02:03:58,701 --> 02:03:59,902 AMAZINGLY WITHIN ABOUT 48 HOURS 3721 02:03:59,902 --> 02:04:01,637 OF THE REQUEST GOING IN, WE HAD 3722 02:04:01,637 --> 02:04:03,506 AMAZING, AMAZING OFFICIALS 3723 02:04:03,506 --> 02:04:04,507 WITHIN THE FDA THAT DEAL WITH 3724 02:04:04,507 --> 02:04:06,142 THESE ON SHORT NOTICE, NIGHTS, 3725 02:04:06,142 --> 02:04:08,311 WEEKENDS, THEY GRANTED ME 3726 02:04:08,311 --> 02:04:10,079 EMERGENCY BE COMPASSIONATE USE, 3727 02:04:10,079 --> 02:04:11,714 THE DRUG COMPANY GRANTED -- 3728 02:04:11,714 --> 02:04:12,715 AGREED TO THE EMERGENCY 3729 02:04:12,715 --> 02:04:13,616 COMPASSIONATE USE SO I WAS ABLE 3730 02:04:13,616 --> 02:04:14,584 TO GET THAT DRUG. 3731 02:04:14,584 --> 02:04:16,652 SO SORT OF FROM THE LOWEST OF -- 3732 02:04:16,652 --> 02:04:20,756 OR HIGHEST OF HIGH, LOWEST OF 3733 02:04:20,756 --> 02:04:22,391 LOWS, BACK TO HIGHEST OF HIGH, 3734 02:04:22,391 --> 02:04:23,693 AND AS YOU KNOW, VICKI, THAT 3735 02:04:23,693 --> 02:04:25,161 DRUG ENDED UP NOT WORKING, SO 3736 02:04:25,161 --> 02:04:26,495 BACK TO THE LOWEST OF LOWS. 3737 02:04:26,495 --> 02:04:32,535 >> AND THEN, YOU KNOW, YOU 3738 02:04:32,535 --> 02:04:34,837 RECOVERED FROM THAT FLARE WITH 3739 02:04:34,837 --> 02:04:36,038 KIND OF FAIRLY BROAD 3740 02:04:36,038 --> 02:04:36,372 CHEMOTHERAPY. 3741 02:04:36,372 --> 02:04:38,908 I MEAN, THEY TREATED YOU 3742 02:04:38,908 --> 02:04:40,776 EXTREMELY AGGRESSIVELY, AND 3743 02:04:40,776 --> 02:04:41,844 YOU'D HAD THIS KIND OF SHIFT IN 3744 02:04:41,844 --> 02:04:44,146 KIND OF, OH, WE NEED TO LOOK 3745 02:04:44,146 --> 02:04:45,348 FURTHER AT RARE DISEASES, WHAT 3746 02:04:45,348 --> 02:04:46,349 OTHER DRUGS ARE OUT THERE AND 3747 02:04:46,349 --> 02:04:48,951 HOW CAN WE REPURPOSE THEM. 3748 02:04:48,951 --> 02:04:50,720 TELL US A LITTLE BIT ABOUT WHAT 3749 02:04:50,720 --> 02:04:53,155 YOU DID WITH THE CASTLEMAN 3750 02:04:53,155 --> 02:04:54,657 DISEASE COMMUNITY, BECAUSE YOU 3751 02:04:54,657 --> 02:04:56,392 WERE STILL A MEDICAL STUDENT. 3752 02:04:56,392 --> 02:04:58,194 YOU HAD NOT PUBLISHED PAPERS. 3753 02:04:58,194 --> 02:05:01,697 YOU HAD NOT GOT CREDIBILITY IN 3754 02:05:01,697 --> 02:05:02,798 THE SCIENTIFIC FIELD, BUT YET 3755 02:05:02,798 --> 02:05:04,467 YOU WERE ABLE TO REALLY 3756 02:05:04,467 --> 02:05:06,736 GALVANIZE THIS COMMUNITY AND 3757 02:05:06,736 --> 02:05:08,738 SORT OF COME OUT WITH A STRATEGY 3758 02:05:08,738 --> 02:05:09,839 TO ADVANCE THE SCIENCE. 3759 02:05:09,839 --> 02:05:10,973 CAN YOU SHARE WITH US A LITTLE 3760 02:05:10,973 --> 02:05:12,408 BIT ABOUT WHAT YOU DID? 3761 02:05:12,408 --> 02:05:13,476 >> SURE. 3762 02:05:13,476 --> 02:05:14,677 I THINK A COUPLE THINGS 3763 02:05:14,677 --> 02:05:16,379 IMMEDIATELY COME TO MIND. 3764 02:05:16,379 --> 02:05:19,281 SO FIRST OFF, I WAS A THIRD YEAR 3765 02:05:19,281 --> 02:05:20,549 MEDICAL STUDENT, SO I DIDN'T 3766 02:05:20,549 --> 02:05:21,517 KNOW ANYTHING ABOUT ANYTHING. 3767 02:05:21,517 --> 02:05:23,252 I DIDN'T KNOW ANYTHING ABOUT HOW 3768 02:05:23,252 --> 02:05:24,420 DISEASES WORKED, I DIDN'T KNOW 3769 02:05:24,420 --> 02:05:25,755 HOW MEDICAL RESEARCH HAPPENED, I 3770 02:05:25,755 --> 02:05:28,958 HAD SOME IDEAS, BUT THAT SORT OF 3771 02:05:28,958 --> 02:05:30,559 LIKE NOT KNOWING HOW THE SYSTEM 3772 02:05:30,559 --> 02:05:33,529 WORKED, I THINK HELPED IN MANY 3773 02:05:33,529 --> 02:05:36,832 WAYS BECAUSE I GOT INVOLVED WITH 3774 02:05:36,832 --> 02:05:37,833 PENN'S ORPHAN DISEASE CENTER 3775 02:05:37,833 --> 02:05:39,335 RIGHT AROUND THAT TIME AND I 3776 02:05:39,335 --> 02:05:40,636 STARTED DIGGING DEEPLY INTO HOW 3777 02:05:40,636 --> 02:05:41,570 RARE DISEASE RESEARCH WAS 3778 02:05:41,570 --> 02:05:43,005 HAPPENING, AND I WAS SO CONFUSED 3779 02:05:43,005 --> 02:05:44,540 BECAUSE WHAT I LEARNED WAS THAT 3780 02:05:44,540 --> 02:05:45,641 GROUPS WOULD RAISE MONEY AND 3781 02:05:45,641 --> 02:05:46,909 THEN THEY WOULD INVITE 3782 02:05:46,909 --> 02:05:48,110 RESEARCHERS TO APPLY FOR THE 3783 02:05:48,110 --> 02:05:49,979 FUNDS AND THEN YOU SORT OF HOPE 3784 02:05:49,979 --> 02:05:50,680 THAT THE RIGHT RESEARCHER 3785 02:05:50,680 --> 02:05:51,681 APPLIES FOR THE RIGHT PROJECT AT 3786 02:05:51,681 --> 02:05:52,214 THE RIGHT TIME. 3787 02:05:52,214 --> 02:05:53,516 AND THAT WORKS REALLY WELL IF 3788 02:05:53,516 --> 02:05:54,684 YOU'RE THE NIH AND YOU'RE 3789 02:05:54,684 --> 02:05:56,185 GETTING THOUSANDS OF APPLICANTS. 3790 02:05:56,185 --> 02:05:57,720 BUT IT WORKS REALLY POORLY IF 3791 02:05:57,720 --> 02:05:59,422 YOU'RE A RARE DISEASE WITH TWO 3792 02:05:59,422 --> 02:06:00,089 OR THREE APPLICANTS. 3793 02:06:00,089 --> 02:06:02,258 WHAT'S THE CHANCE THAT YOUR TWO 3794 02:06:02,258 --> 02:06:04,226 OR THREE APPLICANTS ARE GOING TO 3795 02:06:04,226 --> 02:06:05,828 HAVE THE RIGHT IDEA FOR WHAT 3796 02:06:05,828 --> 02:06:07,263 RESEARCH SHOULD BE DONE AND THE 3797 02:06:07,263 --> 02:06:08,264 CAPABILITIES TO PERFORM THAT 3798 02:06:08,264 --> 02:06:08,564 RESEARCH. 3799 02:06:08,564 --> 02:06:11,367 SO WE JUST ASKED A SIMPLE 3800 02:06:11,367 --> 02:06:14,003 QUESTION, WHAT IF INSTEAD OF 3801 02:06:14,003 --> 02:06:14,770 RAISING MONEY AND HOPING THE 3802 02:06:14,770 --> 02:06:16,338 RIGHT RESEARCHER APPLIES, WHAT 3803 02:06:16,338 --> 02:06:18,307 IF WE ACTUALLY ASK PHYSICIANS, 3804 02:06:18,307 --> 02:06:19,108 RESEARCHERS AND PATIENT, WHAT 3805 02:06:19,108 --> 02:06:20,042 ARE THE IMPORTANT QUESTIONS THAT 3806 02:06:20,042 --> 02:06:21,343 SHOULD BE ASKED ABOUT CASTLEMAN 3807 02:06:21,343 --> 02:06:22,545 DISEASE IN THE LABORATORY, 3808 02:06:22,545 --> 02:06:24,280 CLINICALLY, WHAT ARE THOSE 3809 02:06:24,280 --> 02:06:25,314 QUESTIONS, AND THEN ONCE WE 3810 02:06:25,314 --> 02:06:26,215 PRIORITIZE WHAT THEY ARE, LET'S 3811 02:06:26,215 --> 02:06:27,717 GO FIND THE BEST PERSON IN THE 3812 02:06:27,717 --> 02:06:28,918 WORLD TO COME STUDY THOSE 3813 02:06:28,918 --> 02:06:29,785 QUESTIONS. 3814 02:06:29,785 --> 02:06:31,854 SO WE RECRUIT AMAZING 3815 02:06:31,854 --> 02:06:35,124 RESEARCHERS LIKE PJ ETZ TO STUDY 3816 02:06:35,124 --> 02:06:36,058 CASTLEMAN DISEASE. 3817 02:06:36,058 --> 02:06:37,727 WE RECRUIT THE BEST PROTEOMICS 3818 02:06:37,727 --> 02:06:38,694 RESEARCHERS TO STUDY CASTLEMAN 3819 02:06:38,694 --> 02:06:38,928 DISEASE. 3820 02:06:38,928 --> 02:06:42,198 SO IT'S ABOUT WHAT SHOULD BE 3821 02:06:42,198 --> 02:06:43,365 DONE AND BRINGING IN THE RIGHT 3822 02:06:43,365 --> 02:06:44,633 PEOPLE TO DO IT, AND IT WAS SUCH 3823 02:06:44,633 --> 02:06:46,168 A SIMPLE CONCEPT THAT REQUIRED 3824 02:06:46,168 --> 02:06:48,204 NO BRILLIANCE WHATSOEVER, BUT 3825 02:06:48,204 --> 02:06:49,505 THAT WAS REALLY TRANS FOIRMTIVE. 3826 02:06:49,505 --> 02:06:50,973 SO NOW WE KNEW WHAT WE NEEDED TO 3827 02:06:50,973 --> 02:06:51,540 GO AFTER. 3828 02:06:51,540 --> 02:06:53,075 WE HAD A PLAN. 3829 02:06:53,075 --> 02:06:54,643 AND THE SECOND PIECE WAS THAT 3830 02:06:54,643 --> 02:06:56,345 NOW THAT WE HAD PLAN, WE REALLY 3831 02:06:56,345 --> 02:06:57,847 NEED TO BUILD A TEAM AROUND US. 3832 02:06:57,847 --> 02:06:59,048 THE FIRST WAS REACHING OUT TO 3833 02:06:59,048 --> 02:07:00,049 PATIENTS, PHYSICIANS, 3834 02:07:00,049 --> 02:07:01,450 RESEARCHERS, REALLY BUILDING 3835 02:07:01,450 --> 02:07:02,752 THIS COMMUNITY FIRST VIRTUALLY 3836 02:07:02,752 --> 02:07:03,686 CONNECTING AND THEN ALSO 3837 02:07:03,686 --> 02:07:04,787 CONNECTING IN PERSON AND THEN 3838 02:07:04,787 --> 02:07:06,122 YOU CAN SEE FROM THESE PICTURES, 3839 02:07:06,122 --> 02:07:07,523 I WAS A MEDICAL STUDENT AND THEN 3840 02:07:07,523 --> 02:07:09,024 I DID BUSINESS SCHOOL HERE AT 3841 02:07:09,024 --> 02:07:10,226 PENN RIGHT AFTERWARDS, SO I 3842 02:07:10,226 --> 02:07:11,627 REACHED OUT TO ALL MY CLASSMATES 3843 02:07:11,627 --> 02:07:12,595 IN MED SCHOOL AND BUSINESS 3844 02:07:12,595 --> 02:07:13,896 SCHOOL AND ASKED THEM TO BE A 3845 02:07:13,896 --> 02:07:16,665 PART OF OUR TEAM, AND YOU CAN 3846 02:07:16,665 --> 02:07:19,068 SEE LITERALLY DOZENS, EVEN 3847 02:07:19,068 --> 02:07:20,469 HUNDREDS OF MEDICAL SCHOOL AND 3848 02:07:20,469 --> 02:07:21,937 BUSINESS SCHOOL CLASSMATES OF 3849 02:07:21,937 --> 02:07:24,607 MINE FROM PENN GOT INVOLVED IN 3850 02:07:24,607 --> 02:07:27,443 HELPING TO ORGANIZE CASTLEMAN'S 3851 02:07:27,443 --> 02:07:29,178 MEETINGS, ONLINE DISCUSSION 3852 02:07:29,178 --> 02:07:30,346 BOARDS, SUPPLEMENTS, RAISING 3853 02:07:30,346 --> 02:07:31,680 FUNDS FOR RESEARCH THAT REALLY 3854 02:07:31,680 --> 02:07:32,548 WAS SUCH A TEAM EFFORT. 3855 02:07:32,548 --> 02:07:34,450 >> IT'S AMAZING TO ME, WHAT YOU 3856 02:07:34,450 --> 02:07:38,354 WERE ABLE TO DO, BUT THAT YOU 3857 02:07:38,354 --> 02:07:41,857 DID THIS AT FIRST BY NOT TELLING 3858 02:07:41,857 --> 02:07:45,127 ANYONE THAT YOU HAD CASTLEMAN'S 3859 02:07:45,127 --> 02:07:46,595 DISEASE, YOU JUST TRIED TO SORT 3860 02:07:46,595 --> 02:07:47,897 OF GALVANIZE THE FIELD WITHOUT 3861 02:07:47,897 --> 02:07:50,766 EXPLAINING THAT YOU ALSO HAD THE 3862 02:07:50,766 --> 02:07:52,001 DISEASE. 3863 02:07:52,001 --> 02:07:53,469 BUT YOU KIND OF CROWDSOURCED THE 3864 02:07:53,469 --> 02:07:53,836 PROBLEM. 3865 02:07:53,836 --> 02:07:54,937 YOU BASICALLY WENT TO THE 3866 02:07:54,937 --> 02:07:56,005 SCIENTISTS AND THE OTHER 3867 02:07:56,005 --> 02:07:57,039 PATIENTS AROUND THE WORLD AND 3868 02:07:57,039 --> 02:08:00,209 REALLY BROUGHT THIS COMMUNITY 3869 02:08:00,209 --> 02:08:01,644 TOGETHER, MADE YOUR KIND OF LIST 3870 02:08:01,644 --> 02:08:03,913 OF LIKE WHAT STEPS NEED TO 3871 02:08:03,913 --> 02:08:05,915 HAPPEN IN ORDER TO ADVANCE THIS 3872 02:08:05,915 --> 02:08:08,984 FIELD, AND THEN SORT OF ALMOST 3873 02:08:08,984 --> 02:08:10,619 UPVOTED THEM TO, LIKE, WHAT 3874 02:08:10,619 --> 02:08:12,288 NEEDS TO HAPPEN RIGHT NOW, 3875 02:08:12,288 --> 02:08:13,155 WHAT'S THE FIRST NEXT STEP, AND 3876 02:08:13,155 --> 02:08:15,991 HOW WOULD WE MAKE THAT HAPPEN. 3877 02:08:15,991 --> 02:08:21,497 AND THEN YOU TELL A STORY ALSO 3878 02:08:21,497 --> 02:08:26,302 IN SOME OF YOUR BOOKS, YOU TALK 3879 02:08:26,302 --> 02:08:27,636 ABOUT THIS SEARCH WHERE YOU 3880 02:08:27,636 --> 02:08:29,505 REALIZE THE FIRST NEXT STEP 3881 02:08:29,505 --> 02:08:31,941 NEEDED A CERTAIN NUMBER OF LYMPH 3882 02:08:31,941 --> 02:08:35,110 NODE BIOPSIES AND THAT PEOPLE -- 3883 02:08:35,110 --> 02:08:36,278 NO ONE SINGLE CASTLEMAN DISEASE 3884 02:08:36,278 --> 02:08:37,279 RESEARCHER WOULD HAVE THAT MANY 3885 02:08:37,279 --> 02:08:37,546 SAMPLES. 3886 02:08:37,546 --> 02:08:40,816 CAN YOU SHARE THAT STORY WITH 3887 02:08:40,816 --> 02:08:40,983 US? 3888 02:08:40,983 --> 02:08:42,251 >> SURE, THIS IS AN IMPORTANT 3889 02:08:42,251 --> 02:08:43,452 LESSON FOR ALL OF US TO DO RARE 3890 02:08:43,452 --> 02:08:44,453 DISEASE RESEARCH, AND THAT'S 3891 02:08:44,453 --> 02:08:47,957 THAT NONE OF US AT ANY ONE OF 3892 02:08:47,957 --> 02:08:49,258 OUR CENTERS WILL EVER HAVE 3893 02:08:49,258 --> 02:08:50,359 ENOUGH SAMPLES OR PATIENTS TO 3894 02:08:50,359 --> 02:08:51,460 LEARN ENOUGH ABOUT OUR RARE 3895 02:08:51,460 --> 02:08:53,329 DISEASES. 3896 02:08:53,329 --> 02:08:55,898 IT REQUIRES COLLABORATION AND SO 3897 02:08:55,898 --> 02:08:57,266 YOU'RE EXACTLY RIGHT, SO WE 3898 02:08:57,266 --> 02:08:58,033 REALIZED NO INDIVIDUAL CENTER 3899 02:08:58,033 --> 02:08:59,235 WOULD HAVE ENOUGH SAMPLES AND 3900 02:08:59,235 --> 02:09:00,402 GOSH, WE ALL KNOW HOW DIFFICULT 3901 02:09:00,402 --> 02:09:03,539 IT IS TO PUT IT TOGETHER, 3902 02:09:03,539 --> 02:09:04,406 MATERIAL TRANSFER AGREEMENTS AND 3903 02:09:04,406 --> 02:09:06,275 GET SAMPLES SHARED BETWEEN 3904 02:09:06,275 --> 02:09:10,746 PLACES LIKE THE NIH P AND PENN 3905 02:09:10,746 --> 02:09:13,048 FOR EXAMPLE. 3906 02:09:13,048 --> 02:09:14,884 WHAT IF WE CAN START ENROLLING 3907 02:09:14,884 --> 02:09:15,718 PATIENTS DIRECTLY INTO OUR 3908 02:09:15,718 --> 02:09:16,385 STUDIES. 3909 02:09:16,385 --> 02:09:18,187 SO CREATING ONE CENTRAL IRB 3910 02:09:18,187 --> 02:09:19,121 WHERE PATIENTS CAN CONSENT FROM 3911 02:09:19,121 --> 02:09:20,222 ANYWHERE IN THE WORLD TO GIVE 3912 02:09:20,222 --> 02:09:23,392 BLOOD SAMPLES, TO HAVE EXCESS 3913 02:09:23,392 --> 02:09:24,760 TISSUE AT THEIR SITE BUT THEN 3914 02:09:24,760 --> 02:09:25,928 SENT TO US BY THE PATIENT 3915 02:09:25,928 --> 02:09:27,363 DIRECTLY TO OUR BIOBANK SO WE 3916 02:09:27,363 --> 02:09:28,631 CAN PROCESS AND THEN MAKE IT 3917 02:09:28,631 --> 02:09:31,500 AVAILABLE TO THE WORLD. 3918 02:09:31,500 --> 02:09:32,601 THAT WAS SO IMPORTANT FOR US 3919 02:09:32,601 --> 02:09:33,802 BECAUSE WE CAN'T LIVE IN A WORLD 3920 02:09:33,802 --> 02:09:35,404 WHERE EVERY ONE OF THE FIVE OR 3921 02:09:35,404 --> 02:09:38,207 SIX CENTERS THAT'S INTERESTED IN 3922 02:09:38,207 --> 02:09:40,476 CASTLEMAN'S WERE ALL STUDYING A 3923 02:09:40,476 --> 02:09:41,877 HANDFUL OF SAMPLES EACH AND 3924 02:09:41,877 --> 02:09:43,479 WE'RE PUBLISHING PAPERS ON A 3925 02:09:43,479 --> 02:09:44,146 HANDFUL OF PATIENTS. 3926 02:09:44,146 --> 02:09:45,648 WE'VE GOT TO PULL SAMPLES 3927 02:09:45,648 --> 02:09:46,448 TOGETHER. 3928 02:09:46,448 --> 02:09:47,883 BECAUSE IMPORTANTLY THERE'S ALSO 3929 02:09:47,883 --> 02:09:48,751 ACTUALLY A LOT OF PATIENTS WITH 3930 02:09:48,751 --> 02:09:49,818 THESE RARE DISEASES THAT DON'T 3931 02:09:49,818 --> 02:09:51,487 GO TO THOSE HANDFUL OF CENTERS 3932 02:09:51,487 --> 02:09:52,688 THAT ARE REALLY THE LEADING 3933 02:09:52,688 --> 02:09:54,023 CENTERS, SO NEED TO FIGURE OUT 3934 02:09:54,023 --> 02:09:55,557 WAYS TO REACH OUT TO THEM AND 3935 02:09:55,557 --> 02:09:56,225 CONNECT WITH THOSE PATIENTS TOO. 3936 02:09:56,225 --> 02:10:00,162 >> AND I WANTED TO PULL YOU BACK 3937 02:10:00,162 --> 02:10:00,930 TO SORT OF SOME OF THE 3938 02:10:00,930 --> 02:10:02,798 EXPERIENCES YOU'VE HAD IN YOUR 3939 02:10:02,798 --> 02:10:05,434 LIFE THAT PREPARED YOU FOR 3940 02:10:05,434 --> 02:10:08,170 BRINGING THIS COMMUNITY 3941 02:10:08,170 --> 02:10:09,471 TOGETHER, AND I GUESS I MISSED A 3942 02:10:09,471 --> 02:10:13,309 FEW PARTS OF YOUR STORY BY 3943 02:10:13,309 --> 02:10:14,076 STARTING IN THE MIDDLE. 3944 02:10:14,076 --> 02:10:15,611 YOU HAD FACED A FEW CHALLENGES 3945 02:10:15,611 --> 02:10:19,181 BEFORE YOU FACED THIS CHALLENGE 3946 02:10:19,181 --> 02:10:20,449 WITH CASTLEMAN'S DISEASE. 3947 02:10:20,449 --> 02:10:22,518 YOU'D OBVIOUSLY BEEN A VERY 3948 02:10:22,518 --> 02:10:23,285 COMPETITIVE COLLEGE ATHLETE. 3949 02:10:23,285 --> 02:10:25,287 YOU KNEW ABOUT SUCCESS AND 3950 02:10:25,287 --> 02:10:26,055 FAILURE. 3951 02:10:26,055 --> 02:10:26,956 YOU KNEW ABOUT WHAT WAS NEEDED 3952 02:10:26,956 --> 02:10:29,692 TO TRAIN TO A HIGH LEVEL. 3953 02:10:29,692 --> 02:10:31,760 BUT YOU ALSO KNEW ABOUT GRIEF, 3954 02:10:31,760 --> 02:10:32,661 BECAUSE YOUR MOTHER HAD DIED 3955 02:10:32,661 --> 02:10:35,698 WHEN YOU WERE AN UNDERGRADUATE 3956 02:10:35,698 --> 02:10:37,366 STUDENT, AND YOU KNEW ABOUT 3957 02:10:37,366 --> 02:10:39,601 BRINGING COMMUNITIES TOGETHER 3958 02:10:39,601 --> 02:10:40,769 BECAUSE IN HER MEMORY, YOU WOULD 3959 02:10:40,769 --> 02:10:43,272 SET UP A FOUNDATION TO HELP 3960 02:10:43,272 --> 02:10:45,341 OTHER COLLEGE STUDENTS WORKING 3961 02:10:45,341 --> 02:10:45,674 THROUGH GRIEF. 3962 02:10:45,674 --> 02:10:47,009 CAN YOU TELL US A LITTLE BIT 3963 02:10:47,009 --> 02:10:48,544 ABOUT HOW THOSE PREVIOUS 3964 02:10:48,544 --> 02:10:50,546 EXPERIENCES REALLY HELPED YOU? 3965 02:10:50,546 --> 02:10:52,848 >> THEY HELPED IN SO MANY WAYS. 3966 02:10:52,848 --> 02:10:54,717 SO FIRST OFF MY MOM WAS THE MOST 3967 02:10:54,717 --> 02:10:57,219 INCREDIBLE PERSON IN THE WORLD. 3968 02:10:57,219 --> 02:11:00,522 SHE WAS JUST -- WAS ALWAYS THE 3969 02:11:00,522 --> 02:11:01,523 SUPPORTER FOR EVERYONE ELSE AND 3970 02:11:01,523 --> 02:11:04,126 SHE LIVED THIS JUST -- SUCH A 3971 02:11:04,126 --> 02:11:05,160 PURPOSE-DRIVEN, MISSION-DRIVEN 3972 02:11:05,160 --> 02:11:05,361 LIFE. 3973 02:11:05,361 --> 02:11:09,598 SO WITH HER PASSING, THAT WAS SO 3974 02:11:09,598 --> 02:11:10,933 DIFFICULT FOR ME, I WAS 19 YEARS 3975 02:11:10,933 --> 02:11:12,634 OLD, AND FOR ME IT WAS OKAY, I'M 3976 02:11:12,634 --> 02:11:14,169 GOING TO DEDICATE MY LIFE TO 3977 02:11:14,169 --> 02:11:15,437 GOING INTO A CAREER IN MEDICINE 3978 02:11:15,437 --> 02:11:16,638 AND MEDICAL RESEARCH TO TRY TO 3979 02:11:16,638 --> 02:11:17,906 FIND TREATMENTS FOR PATIENTS 3980 02:11:17,906 --> 02:11:20,376 LIKE HER. 3981 02:11:20,376 --> 02:11:21,677 THAT EXPERIENCE ALSO LED ME AS 3982 02:11:21,677 --> 02:11:22,978 YOU MENTIONED TO START THAT 3983 02:11:22,978 --> 02:11:25,748 ORGANIZATION CALLED AMF, AMF 3984 02:11:25,748 --> 02:11:26,949 STOOD FOR ACTIVELY MOVING 3985 02:11:26,949 --> 02:11:28,250 FORWARD, IT STILL STANDS FOR 3986 02:11:28,250 --> 02:11:30,019 ACTIVELY MOVE FORWARD BUT ALSO 3987 02:11:30,019 --> 02:11:33,956 MY MOM'S INITIAL, ANNE MARIE 3988 02:11:33,956 --> 02:11:34,957 FAJGENBAUM, SO AS A WAY TO KEEP 3989 02:11:34,957 --> 02:11:36,258 THE LEGACY GOING OF THIS PERSON 3990 02:11:36,258 --> 02:11:37,292 WHO WAS ALWAYS THERE FOR 3991 02:11:37,292 --> 02:11:39,161 EVERYONE ELSE. 3992 02:11:39,161 --> 02:11:44,333 AND SO THROUGH AMF, GEORGETOWN'S 3993 02:11:44,333 --> 02:11:45,034 CAMPUS, JUST DOWN THE ROAD FOR A 3994 02:11:45,034 --> 02:11:46,535 FEW OF YOU, WHEREAS YOU 3995 02:11:46,535 --> 02:11:47,736 MENTIONED I ALSO PLAYED ON THE 3996 02:11:47,736 --> 02:11:48,871 FOOTBALL TEAM. 3997 02:11:48,871 --> 02:11:49,972 WE LOST MOST OF OUR GAMES AT 3998 02:11:49,972 --> 02:11:50,873 GEORGETOWN, THE FOOTBALL TEAM, 3999 02:11:50,873 --> 02:11:52,041 SO YOU PROBABLY WEREN'T AWARE 4000 02:11:52,041 --> 02:11:53,208 THAT WE HAVE A FOOTBALL TEAM BUT 4001 02:11:53,208 --> 02:11:56,145 WE DO HAVE ONE, BUT DURING MY 4002 02:11:56,145 --> 02:11:57,813 TIME AT GEORGETOWN, WE GREW A 4003 02:11:57,813 --> 02:11:59,081 MANAGEMENT F FROM A GROUP AT 4004 02:11:59,081 --> 02:12:00,783 YORNLG TOWN TO A NON-PROFIT THAT 4005 02:12:00,783 --> 02:12:01,617 SUPPORTED COLLEGE STUDENTS ALL 4006 02:12:01,617 --> 02:12:04,186 OVER THE UNITED STATES. 4007 02:12:04,186 --> 02:12:06,355 AT OUR PEAK WE HAD OVER 200 4008 02:12:06,355 --> 02:12:07,556 COLLEGE CAMPUSES WITH PEER-LED 4009 02:12:07,556 --> 02:12:08,323 SUPPORT GROUPS WHERE STUDENTS 4010 02:12:08,323 --> 02:12:09,825 WERE SUPPORTING ONE ANOTHER AND 4011 02:12:09,825 --> 02:12:10,726 ALSO GETTING INVOLVED IN 4012 02:12:10,726 --> 02:12:11,960 COMMUNITY SERVICE IN MEMORY OF 4013 02:12:11,960 --> 02:12:13,362 THEIR LOVED ONES WHO HAD PASSED 4014 02:12:13,362 --> 02:12:14,363 AWAY. 4015 02:12:14,363 --> 02:12:17,766 AMF STILL CONTINUES, IT DIDN'T 4016 02:12:17,766 --> 02:12:19,168 HAVE AS MANY CHAPTERS BUT IT 4017 02:12:19,168 --> 02:12:21,503 STILL SUPPORTS STUDENTS AT 4018 02:12:21,503 --> 02:12:22,504 CAMPUSES ALL OVER THE COUNTRY. 4019 02:12:22,504 --> 02:12:24,373 I HAVEN'T BEEN INVOLVED WITH 4020 02:12:24,373 --> 02:12:26,008 MAMF FOR ALMOST 10 YEARS NOW BUT 4021 02:12:26,008 --> 02:12:27,643 I STILL LOVE TO HEAR ABOUT THE 4022 02:12:27,643 --> 02:12:29,645 GREAT JOB IT'S DOING SUPPORTING 4023 02:12:29,645 --> 02:12:30,546 PEOPLE EVEN JUST DOWN THE STREET 4024 02:12:30,546 --> 02:12:31,747 AT PENN. 4025 02:12:31,747 --> 02:12:32,915 SO THAT EXPERIENCE OF BUILDING 4026 02:12:32,915 --> 02:12:34,149 THIS NON-PROFIT AND TAKING ON 4027 02:12:34,149 --> 02:12:37,886 WHAT REALLY WAS A SYSTEMIC 4028 02:12:37,886 --> 02:12:39,521 CHALLENGE OR ISSUE ON CAMPUSES 4029 02:12:39,521 --> 02:12:41,023 AND THAT'S THAT THERE WERE A LOT 4030 02:12:41,023 --> 02:12:43,459 OF STUDENTS DEALING WITH GRIEF, 4031 02:12:43,459 --> 02:12:44,893 BUT NO ONE WAS TALKING ABOUT IT 4032 02:12:44,893 --> 02:12:46,795 SO EVERYONE FELT ALONE AND IT'S 4033 02:12:46,795 --> 02:12:48,097 BECAUSE THERE WASN'T A PLACE FOR 4034 02:12:48,097 --> 02:12:48,764 GRIEVING COLLEGE STUDENTS TO 4035 02:12:48,764 --> 02:12:49,198 COME TOGETHER. 4036 02:12:49,198 --> 02:12:50,632 THE EXPERIENCE OF BUILDING THAT 4037 02:12:50,632 --> 02:12:51,533 NON-PROFIT, GETTING PEOPLE 4038 02:12:51,533 --> 02:12:53,836 TOGETHER TO SOLVE THAT PROBLEM 4039 02:12:53,836 --> 02:12:55,571 MEANT THAT WHEN I WAS CONFRONTED 4040 02:12:55,571 --> 02:12:57,005 WITH CASTLEMAN'S AND I DECIDED I 4041 02:12:57,005 --> 02:12:59,641 WAS GOING TO TAKE IT ON ALONG 4042 02:12:59,641 --> 02:13:01,743 WITH MY COLLEAGUE FRITZ VAN RIE, 4043 02:13:01,743 --> 02:13:03,045 THAT I COLLEEN ON THAT 4044 02:13:03,045 --> 02:13:06,982 EXPCOULD LEAN ON THATEXPERIENCED 4045 02:13:06,982 --> 02:13:08,317 CERTAINLY IT HELPED 4046 02:13:08,317 --> 02:13:08,650 TREMENDOUSLY. 4047 02:13:08,650 --> 02:13:10,619 >> AND I THINK SOMETIMES WE 4048 02:13:10,619 --> 02:13:13,589 DON'T ALWAYS REALIZE THAT 4049 02:13:13,589 --> 02:13:14,690 HISTORY IS PREPARING US FOR 4050 02:13:14,690 --> 02:13:15,657 SOMETHING THAT WE'RE GOING TO 4051 02:13:15,657 --> 02:13:19,761 FACE IN THE FUTURE AND IT JUST 4052 02:13:19,761 --> 02:13:20,963 REALLY STRUCK ME AS I WAS 4053 02:13:20,963 --> 02:13:22,064 READING YOUR STORY THAT THAT WAS 4054 02:13:22,064 --> 02:13:23,432 THE CASE IN YOUR CASE. 4055 02:13:23,432 --> 02:13:28,337 YOU ALSO HAD GOOD BACKGROUND IN 4056 02:13:28,337 --> 02:13:30,739 ACADEMICS AND RESEARCH. 4057 02:13:30,739 --> 02:13:32,875 YOU HAD OBVIOUSLY COMPLETED YOUR 4058 02:13:32,875 --> 02:13:35,144 UNDERGRAD AT GEORGETOWN, BUT 4059 02:13:35,144 --> 02:13:36,912 THEN ALSO HAD A MASTER'S THAT 4060 02:13:36,912 --> 02:13:40,849 YOU COMPLETED AT OXFORD 4061 02:13:40,849 --> 02:13:41,950 UNIVERSITY, GIVEN YOU SET UP THE 4062 02:13:41,950 --> 02:13:43,385 FRAMEWORK FOR ANALYZING AND 4063 02:13:43,385 --> 02:13:44,119 ANSWERING THESE COMPLEX 4064 02:13:44,119 --> 02:13:44,386 PROBLEMS. 4065 02:13:44,386 --> 02:13:46,455 TELL US A LITTLE BIT ABOUT HOW 4066 02:13:46,455 --> 02:13:48,991 YOU USED THOSE SKILLS. 4067 02:13:48,991 --> 02:13:50,159 DURING THAT TIME WHEN YOU WERE 4068 02:13:50,159 --> 02:13:51,160 STILL A MEDICAL STUDENT WHEN YOU 4069 02:13:51,160 --> 02:13:54,630 WERE TRYING TO GET THE CASTLEMAN 4070 02:13:54,630 --> 02:13:55,297 DISEASE COLLABORATIVE NETWORK TO 4071 02:13:55,297 --> 02:13:56,999 KIND OF MOVE THE SCIENCE 4072 02:13:56,999 --> 02:13:58,734 FORWARD, HOW DID YOU TAKE THOSE 4073 02:13:58,734 --> 02:14:00,502 SKILLS AND DO THAT STILL AS A 4074 02:14:00,502 --> 02:14:02,504 MEDICAL STUDENT? 4075 02:14:02,504 --> 02:14:04,039 >> YOU KNOW, I THINK ALL OF 4076 02:14:04,039 --> 02:14:05,407 THOSE EXPERIENCES HELPED ME SO 4077 02:14:05,407 --> 02:14:05,674 MUCH. 4078 02:14:05,674 --> 02:14:07,342 I THINK I ALSO -- IT'S VERY 4079 02:14:07,342 --> 02:14:08,977 IMPORTANT TO EMPHASIZE THIS 4080 02:14:08,977 --> 02:14:12,281 AMAZING TEAM OF PEOPLE. 4081 02:14:12,281 --> 02:14:14,116 SO YES I RECEIVED THE TRAINING 4082 02:14:14,116 --> 02:14:15,284 AT OXFORD THAT CERTAINLY HELPED 4083 02:14:15,284 --> 02:14:16,285 WITH SOME OF THE METHODOLOGIES 4084 02:14:16,285 --> 02:14:17,853 THAT I WAS USING, BUT I ALSO HAD 4085 02:14:17,853 --> 02:14:19,188 THESE AMAZING CLASSMATES THAT I 4086 02:14:19,188 --> 02:14:21,790 TURNED TO, THAT WERE DOING 4087 02:14:21,790 --> 02:14:23,525 PH.D.s IN VARIOUS DISCIPLINES 4088 02:14:23,525 --> 02:14:25,494 THAT WERE DOING MBAs AND WHO 4089 02:14:25,494 --> 02:14:27,696 WOULD HAVE NECESSARILY THOUGHT 4090 02:14:27,696 --> 02:14:30,365 THAT AN MBA STUDENT ISNESS 4091 02:14:30,365 --> 02:14:32,201 SAIRLY GOING TO BE HELP YOU BE 4092 02:14:32,201 --> 02:14:33,535 ABLE TO ADVANCE RESEARCH FOR A 4093 02:14:33,535 --> 02:14:34,036 DISEASE? 4094 02:14:34,036 --> 02:14:35,370 THE TRUTH IS A LOT OF MEDICAL 4095 02:14:35,370 --> 02:14:37,673 RESEARCH IS ABOUT ORGANIZING AND 4096 02:14:37,673 --> 02:14:39,374 UTILIZING FINITE RESOURCES AND 4097 02:14:39,374 --> 02:14:41,243 BEING EFFICIENT AND BUILDING 4098 02:14:41,243 --> 02:14:42,444 STRATEGIES, AND SO IT TURNED OUT 4099 02:14:42,444 --> 02:14:44,479 THAT, YES, I WAS CERTAINLY 4100 02:14:44,479 --> 02:14:45,547 PREPARED FOR MY TRAINING, BUT 4101 02:14:45,547 --> 02:14:46,949 MAYBE THE MOST IMPORTANT THING 4102 02:14:46,949 --> 02:14:48,517 WAS THAT I WAS ABLE TO JUST 4103 02:14:48,517 --> 02:14:50,219 BUILD AN AMAZING TEAM AND TO QO 4104 02:14:50,219 --> 02:14:54,156 NECONNECT WITH PEOPLE SO WE COUD 4105 02:14:54,156 --> 02:14:56,491 CREATE REALLY A UNIFIED STRATEGY 4106 02:14:56,491 --> 02:14:58,660 THAT THE WORLD OF CASTLEMAN'S 4107 02:14:58,660 --> 02:15:00,295 RESEARCHERS AND PHYSICIANS COULD 4108 02:15:00,295 --> 02:15:01,430 REALLY GET BEHIND, AND ONCE WE 4109 02:15:01,430 --> 02:15:02,864 BUILT THAT CONSENSUS AND WE HAD 4110 02:15:02,864 --> 02:15:05,701 A CLEAR PLAN, IT WAS JUST 4111 02:15:05,701 --> 02:15:06,068 EXECUTION. 4112 02:15:06,068 --> 02:15:08,670 >> YEAH, AND YOU YOURSELF, I 4113 02:15:08,670 --> 02:15:11,540 THINK, REALIZED PRETTY EARLY ON 4114 02:15:11,540 --> 02:15:13,709 THAT YOU NEEDED TO HAVE THE 4115 02:15:13,709 --> 02:15:15,244 SCIENCE BACKGROUND BUT THAT YOU 4116 02:15:15,244 --> 02:15:17,446 ALSO NEEDED THE BUSINESS 4117 02:15:17,446 --> 02:15:18,680 BACKGROUND, SO AFTER YOU FIN 4118 02:15:18,680 --> 02:15:21,717 ESFINISHED MEDICAL SCHOOL, YOU 4119 02:15:21,717 --> 02:15:22,985 WENT TO BUSINESS SCHOOL, YOU 4120 02:15:22,985 --> 02:15:24,152 WERE PRETTY ACTIVE AT THAT POINT 4121 02:15:24,152 --> 02:15:26,188 IN THE RARE DISEASES CENTER AT 4122 02:15:26,188 --> 02:15:26,388 PENN. 4123 02:15:26,388 --> 02:15:27,623 CAN YOU TELL US ABOUT THAT 4124 02:15:27,623 --> 02:15:28,423 DECISION? 4125 02:15:28,423 --> 02:15:30,592 WHY DID THE BUSINESS SCHOOL 4126 02:15:30,592 --> 02:15:31,260 TRAINING MAKE SENSE AND HOW HAVE 4127 02:15:31,260 --> 02:15:33,161 YOU USED TO MOVE THINGS FORWARD? 4128 02:15:33,161 --> 02:15:34,930 >> SO THERE WERE A FEW THINGS 4129 02:15:34,930 --> 02:15:35,597 THAT SORT OF CAME TOGETHER ALL 4130 02:15:35,597 --> 02:15:37,132 AT ONCE THAT LED ME TO DO THAT. 4131 02:15:37,132 --> 02:15:38,100 THE FIRST IS THAT AS YOU KNOW, I 4132 02:15:38,100 --> 02:15:39,468 WAS CONTINUING TO RELAPSE FROM 4133 02:15:39,468 --> 02:15:40,769 MY CASTLEMAN DISEASE, SO EVERY 4134 02:15:40,769 --> 02:15:42,170 EIGHT TO 12 MONTHS, I WAS BACK 4135 02:15:42,170 --> 02:15:44,206 IN THE ICU FOR A MONTH AT A 4136 02:15:44,206 --> 02:15:45,741 TIME, WITH ALL OF MY ORGANS 4137 02:15:45,741 --> 02:15:51,179 FAILING, ON DIALYSIS, VERY, VERY 4138 02:15:51,179 --> 02:15:53,415 ILL, MULTI-AGENT CHEMOTHERAPY 4139 02:15:53,415 --> 02:15:55,284 WOULD SORT OF BRING ME FROM THE 4140 02:15:55,284 --> 02:15:57,552 BRINK OF DEATH BUT I'D BE SORT 4141 02:15:57,552 --> 02:16:00,255 OF BACK THERE NOT TOO LONG 4142 02:16:00,255 --> 02:16:00,689 AFTER. 4143 02:16:00,689 --> 02:16:03,859 SO I KIND OF LIMPED THROUGH THE 4144 02:16:03,859 --> 02:16:05,060 FINISH LINE OF GRADUATING FROM 4145 02:16:05,060 --> 02:16:05,994 MEDICAL SCHOOL. 4146 02:16:05,994 --> 02:16:07,429 THE QUESTION IS, YOU KNOW, 4147 02:16:07,429 --> 02:16:09,031 DAVID, DO YOU GO DO A RESIDENCY, 4148 02:16:09,031 --> 02:16:11,433 DO YOU DO A POSTDOC, AN MBA, 4149 02:16:11,433 --> 02:16:12,734 WHAT DO YOU DO HERE? 4150 02:16:12,734 --> 02:16:14,703 AND I DECIDED TO DO AN MBA FOR A 4151 02:16:14,703 --> 02:16:15,404 FEW REASONS. 4152 02:16:15,404 --> 02:16:17,839 ONE IS THAT I KNEW I WOULD HAVE 4153 02:16:17,839 --> 02:16:20,676 BANDWIDTH TO BE ABLE TO ACTUALLY 4154 02:16:20,676 --> 02:16:23,011 WORK IN THE LAB, SO JUST DOWN 4155 02:16:23,011 --> 02:16:24,413 THE STREET, A TRANSLATIONAL 4156 02:16:24,413 --> 02:16:25,514 RESEARCH LABORATORY, I HAD SOME 4157 02:16:25,514 --> 02:16:26,181 LAB SPACE. 4158 02:16:26,181 --> 02:16:29,117 SO I KNEW I HAD SOME BANDWIDTH 4159 02:16:29,117 --> 02:16:30,585 TO ACTUALLY WORK IN THE LAB AND 4160 02:16:30,585 --> 02:16:32,220 SPECIFICALLY WHY THE MBA IS THAT 4161 02:16:32,220 --> 02:16:33,622 AS I WAS DOING MORE AND MORE 4162 02:16:33,622 --> 02:16:35,123 WORK IN TRYING TO BRING TOGETHER 4163 02:16:35,123 --> 02:16:36,491 PEOPLE, I REALIZED THAT THE 4164 02:16:36,491 --> 02:16:37,759 SCIENCE AND THE TECHNOLOGY 4165 02:16:37,759 --> 02:16:39,294 ACTUALLY WAS ALREADY THERE. 4166 02:16:39,294 --> 02:16:42,497 THE ISSUE WAS JUST GETTING THE 4167 02:16:42,497 --> 02:16:44,132 RIGHT RESOURCES AND SORT OF 4168 02:16:44,132 --> 02:16:45,467 LEVERAGING THE TOOLS THAT 4169 02:16:45,467 --> 02:16:46,134 ALREADY EXISTED. 4170 02:16:46,134 --> 02:16:49,004 SO SINGLE CELL RNA SEQUENCING 4171 02:16:49,004 --> 02:16:50,839 WAS COMING ON THE XENO. 4172 02:16:50,839 --> 02:16:56,978 ON THE SCENE, THETECHNIQUES WER. 4173 02:16:56,978 --> 02:16:58,146 IT WASN'T WE HAVE TO CREATE SOME 4174 02:16:58,146 --> 02:16:58,480 NEW TECHNIQUE. 4175 02:16:58,480 --> 02:16:59,815 IT WAS LIKE HOW DO WE LEVERAGE 4176 02:16:59,815 --> 02:17:01,483 THEM, HOW DO WE UTILIZE THEM IN 4177 02:17:01,483 --> 02:17:02,351 THE RIGHT WAY WITH THE RIGHT 4178 02:17:02,351 --> 02:17:03,251 SAMPLES WITH THE RIGHT FUNDING 4179 02:17:03,251 --> 02:17:03,552 AMOUNTS. 4180 02:17:03,552 --> 02:17:05,887 SO I THOUGHT THAT AN MBA WOULD 4181 02:17:05,887 --> 02:17:08,056 HELP TO BUILD THE SKILLS TO BE 4182 02:17:08,056 --> 02:17:10,058 ABLE TO DO THOSE THINGS, AND I'M 4183 02:17:10,058 --> 02:17:11,693 SO GLAD THAT I DID, BECAUSE 4184 02:17:11,693 --> 02:17:13,795 EVERYONE ON THIS CALL WILL 4185 02:17:13,795 --> 02:17:14,896 CERTAINLY APPRECIATE, WHETHER 4186 02:17:14,896 --> 02:17:16,965 YOU RUN A LAB, YOU'RE PART OF A 4187 02:17:16,965 --> 02:17:18,433 TEAM, YOU'RE PART OF A CENTER, 4188 02:17:18,433 --> 02:17:20,502 IT'S ALL ABOUT THE TEAM AND HOW 4189 02:17:20,502 --> 02:17:22,037 YOU WORK TOGETHER WITHIN AN 4190 02:17:22,037 --> 02:17:23,038 ORGANIZATION, AND I WAS REALLY 4191 02:17:23,038 --> 02:17:24,373 HAPPY I DID THE PROGRAM. 4192 02:17:24,373 --> 02:17:27,743 >> YEAH, AND IT HAS ALLOWED YOU 4193 02:17:27,743 --> 02:17:31,713 TO REALLY TRANSFORM SOME OF HOW 4194 02:17:31,713 --> 02:17:33,115 WE DO RESEARCH, WHICH IS 4195 02:17:33,115 --> 02:17:33,415 INCREDIBLE. 4196 02:17:33,415 --> 02:17:35,584 TELL US A LITTLE BIT ABOUT WHAT 4197 02:17:35,584 --> 02:17:40,989 YOU ARE DOING NOW IN TERMS OF 4198 02:17:40,989 --> 02:17:42,724 HARNESSING SOME OF THESE LARGE 4199 02:17:42,724 --> 02:17:45,994 LANGUAGE MODELS, A.I., TO KIND 4200 02:17:45,994 --> 02:17:51,400 OF MINE BIG DATASETS FOR DRUG 4201 02:17:51,400 --> 02:17:51,700 REPURPOSING. 4202 02:17:51,700 --> 02:17:55,771 >> SURE. 4203 02:17:55,771 --> 02:17:57,539 WE WERE FOCUSED ON REPURPOSING 4204 02:17:57,539 --> 02:18:00,409 TO TRY TO TAKE ON CASTLEMAN'S, 4205 02:18:00,409 --> 02:18:03,578 WE KNEW WE COULDN'T COME UP WITH 4206 02:18:03,578 --> 02:18:06,648 A NEW DRUG FROM SCRATCH, 4207 02:18:06,648 --> 02:18:08,049 DISCOVERED THERE WAS INCREASED 4208 02:18:08,049 --> 02:18:11,753 MTOR ACTIVATION IN MY OWN 4209 02:18:11,753 --> 02:18:13,622 LYMPHOTISSUE, MY IMMUNE SYSTEM 4210 02:18:13,622 --> 02:18:15,724 HAD HYPERACTIVATION OF THE MTOR 4211 02:18:15,724 --> 02:18:16,925 SIGNALING PATHWAY WHICH LED ME 4212 02:18:16,925 --> 02:18:23,999 TO TRY TO REPURPOSE CERILIMUS, 4213 02:18:23,999 --> 02:18:26,034 I'LL QUICKLY WALK YOU THROUGH 4214 02:18:26,034 --> 02:18:28,303 IT, SO THE TOP OF THE SCREEN IS 4215 02:18:28,303 --> 02:18:31,406 A REACTIVE LYMPH NODE, JUST ONE 4216 02:18:31,406 --> 02:18:35,811 IMAGE OF MTOR ACTIVATION OR 4217 02:18:35,811 --> 02:18:36,812 PHOSPHO -- 6 EXPRESSION IN A 4218 02:18:36,812 --> 02:18:37,579 TYPICAL LYMPH NODE. 4219 02:18:37,579 --> 02:18:39,147 WHAT YOU'LL NOTICE IS THE VAST 4220 02:18:39,147 --> 02:18:40,482 MAJORITY OF CELLS ARE BLUE, 4221 02:18:40,482 --> 02:18:41,249 THEY'RE COUNTER STAINED SO 4222 02:18:41,249 --> 02:18:43,452 THEY'RE NOT EXPRESSING 4223 02:18:43,452 --> 02:18:44,953 PHOSPHO -- 6, MTOR IS NOT TURNED 4224 02:18:44,953 --> 02:18:46,721 ON IN THE VAST MAJORITY OF 4225 02:18:46,721 --> 02:18:48,123 IMMUNE CELLS IN THE LYMPH NODE. 4226 02:18:48,123 --> 02:18:49,724 I REPEATED THE SAME EXPERIMENT 4227 02:18:49,724 --> 02:18:51,092 ON MY OWN LYMPH NODE TISSUE AND 4228 02:18:51,092 --> 02:18:52,194 WAS REALLY -- WHICH IS THE 4229 02:18:52,194 --> 02:18:54,229 BOTTOM OF THE SCREEN, AND I WAS 4230 02:18:54,229 --> 02:18:55,230 JUST BLOWN AWAY BY THE 4231 02:18:55,230 --> 02:18:56,431 TREMENDOUS AMOUNT OF MTOR 4232 02:18:56,431 --> 02:18:57,632 ACTIVATION, AND I WAS LED TO 4233 02:18:57,632 --> 02:18:59,935 MTOR BASED ON A LARGE SERUM 4234 02:18:59,935 --> 02:19:02,003 PROTEOMICS ANALYSIS I DID WITH 4235 02:19:02,003 --> 02:19:04,406 SIM LO JIX WHICH GAVE ME A 4236 02:19:04,406 --> 02:19:07,442 MINUTE THAT THERE WAS AN MTOR 4237 02:19:07,442 --> 02:19:08,410 SIGNATURE WHICH LED US TO 4238 02:19:08,410 --> 02:19:09,277 CONFIRM IT IN THE LABORATORY 4239 02:19:09,277 --> 02:19:09,678 HERE. 4240 02:19:09,678 --> 02:19:11,680 SO THAT LED ME TO THEN ACTUALLY 4241 02:19:11,680 --> 02:19:15,851 START TREATING THIS DISEASE WITH 4242 02:19:15,851 --> 02:19:17,152 CIRALIMUS, ACTUALLY IT WAS A 4243 02:19:17,152 --> 02:19:18,620 COLLEAGUE AT THE NIH, I WALKED 4244 02:19:18,620 --> 02:19:19,621 INTO THE NIH CLINICAL CENTER 4245 02:19:19,621 --> 02:19:21,323 WITH THESE IMAGES AND I DROPPED 4246 02:19:21,323 --> 02:19:22,824 THEM ON THE TABLE IN FRONT OF 4247 02:19:22,824 --> 02:19:24,593 THE ABP, WHICH I'M SURE YOU ALL 4248 02:19:24,593 --> 02:19:26,361 HAVE SPENT A LOT OF TIME AT AT 4249 02:19:26,361 --> 02:19:28,096 THE NIH CLINICAL CENTER, SHOWED 4250 02:19:28,096 --> 02:19:30,265 TO MY COLLEAGUE AND WE DISCUSS 4251 02:19:30,265 --> 02:19:31,366 WHRAD TO DO AND HE SAID I THINK 4252 02:19:31,366 --> 02:19:33,902 WE SHOULD TRY AN MTOR INHIBITOR, 4253 02:19:33,902 --> 02:19:37,372 LET'S GO WITH CIROLIMUS SO THAT 4254 02:19:37,372 --> 02:19:38,974 WAS THE IMPETUS FOR TRYING THE 4255 02:19:38,974 --> 02:19:39,808 DRUG. 4256 02:19:39,808 --> 02:19:41,376 THIS PAST JANUARY MARKS 10 YEARS 4257 02:19:41,376 --> 02:19:43,311 I'VE BEEN IN REMISSION, SO AFTER 4258 02:19:43,311 --> 02:19:45,413 RELAPSING AND NEARLY DYING FIVE 4259 02:19:45,413 --> 02:19:49,284 TIMES IN ABOUT FIVE YEARS BEFORE 4260 02:19:49,284 --> 02:19:50,585 SERALIMUS, NOW IT'S BEEN OVER 10 4261 02:19:50,585 --> 02:19:52,187 YEARS IN REMISSION ON IT. 4262 02:19:52,187 --> 02:19:53,388 SO THIS IS A PICTURE OF MY WIFE 4263 02:19:53,388 --> 02:19:55,590 AND MY TWO KIDS, BY OF COURSE IT 4264 02:19:55,590 --> 02:19:57,125 JUST FEELS LIKE A DREAM THAT I'M 4265 02:19:57,125 --> 02:20:00,095 HERE WITH YOU TODAY, TALKING 4266 02:20:00,095 --> 02:20:02,063 ABOUT OUR WORK, AND I HAVE THESE 4267 02:20:02,063 --> 02:20:03,832 AMAZING KIDS AND SUCH A SPECIAL 4268 02:20:03,832 --> 02:20:04,266 FAMILY. 4269 02:20:04,266 --> 02:20:06,234 BUT FOR ME, THIS DIDN'T JUST 4270 02:20:06,234 --> 02:20:06,868 SAVE MY LIFE. 4271 02:20:06,868 --> 02:20:08,837 IT JUST OPENED MY EYES UP TO 4272 02:20:08,837 --> 02:20:09,971 SOMETHING THAT EVERYONE ON THIS 4273 02:20:09,971 --> 02:20:11,740 CALL ALREADY KNOWS, AND THAT'S 4274 02:20:11,740 --> 02:20:13,875 THAT THE DRUGS THAT WE HAVE THAT 4275 02:20:13,875 --> 02:20:15,277 ARE FDA-APPROVED HAVE ADDITIONAL 4276 02:20:15,277 --> 02:20:16,912 POTENTIAL TO HELP MORE PATIENTS 4277 02:20:16,912 --> 02:20:17,512 AND MORE DISEASES THAN THEY 4278 02:20:17,512 --> 02:20:19,681 CURRECURRENTLY DO. 4279 02:20:19,681 --> 02:20:20,949 AND THE MORE AND MORE I DUG INTO 4280 02:20:20,949 --> 02:20:22,250 THIS, THE MORE AND MORE I 4281 02:20:22,250 --> 02:20:24,719 LEARNED THAT THERE IS -- THERE 4282 02:20:24,719 --> 02:20:25,854 ARE TREMENDOUS AMOUNTS OF DATA 4283 02:20:25,854 --> 02:20:27,789 THAT CAN LINK EXISTING DRUGS TO 4284 02:20:27,789 --> 02:20:29,424 DISEASES THAT DON'T HAVE ANY 4285 02:20:29,424 --> 02:20:30,659 TREATMENTS, BUT THE PROBLEM IS 4286 02:20:30,659 --> 02:20:33,194 THAT THERE ARE SYSTEMIC BARRIERS 4287 02:20:33,194 --> 02:20:34,829 THAT PREVENT US FROM FULLY 4288 02:20:34,829 --> 02:20:36,631 UTILIZING EXISTING MEDICINE. 4289 02:20:36,631 --> 02:20:38,533 SO PROBABLY THE MOST IMPORTANT 4290 02:20:38,533 --> 02:20:40,902 ONE ARE FINANCIAL BARRIERS, SO 4291 02:20:40,902 --> 02:20:42,804 OVER 80% OF FDA-APPROVED DRUGS 4292 02:20:42,804 --> 02:20:43,705 ARE ALREADY GENERIC, WHICH MEANS 4293 02:20:43,705 --> 02:20:45,006 THAT THERE'S NO INCENTIVE FOR 4294 02:20:45,006 --> 02:20:47,208 DRUG COMPANIES TO DO FURTHER R & 4295 02:20:47,208 --> 02:20:49,010 D ON 80% OF THE DRUGS THAT ARE 4296 02:20:49,010 --> 02:20:51,646 IN OUR CVS, THAT COULD HELP 4297 02:20:51,646 --> 02:20:52,781 PEOPLE TOMORROW, WE'RE NOT DOING 4298 02:20:52,781 --> 02:20:53,214 R & D ON. 4299 02:20:53,214 --> 02:20:54,983 IN ADDITION TO THAT, THERE'S 4300 02:20:54,983 --> 02:20:56,484 NEVER BEEN A CENTRALIZED PLACE 4301 02:20:56,484 --> 02:20:57,986 FOR DATA SHARING AROUND NEW USES 4302 02:20:57,986 --> 02:20:59,054 FOR EXISTING MEDICINES. 4303 02:20:59,054 --> 02:21:00,388 WE SORT OF ALL WORK IN OUR 4304 02:21:00,388 --> 02:21:01,957 SILOS, YOU KNOW, I REPURPOSE 4305 02:21:01,957 --> 02:21:03,692 DRUGS FOR CASTLEMAN'S HERE, WE 4306 02:21:03,692 --> 02:21:04,459 COME ACROSS DRUGS THAT MAYBE 4307 02:21:04,459 --> 02:21:07,596 THEY COULD BE USED FOR 4308 02:21:07,596 --> 02:21:08,697 IDG4 RELATED DISEASE BUT THAT'S 4309 02:21:08,697 --> 02:21:11,533 NOT WHAT YOU STUDY SO I SORT OF 4310 02:21:11,533 --> 02:21:13,201 KEEP DOWN MY CASTLEMAN'S TRACK. 4311 02:21:13,201 --> 02:21:14,269 THEN IMPORTANTLY THERE ACTUALLY 4312 02:21:14,269 --> 02:21:16,504 ISN'T A PLAYER IN OUR MEDICAL 4313 02:21:16,504 --> 02:21:18,540 SYSTEM THAT IS RESPONSIBLE FOR 4314 02:21:18,540 --> 02:21:19,641 MAKING SURE THAT FDA-APPROVED 4315 02:21:19,641 --> 02:21:20,842 DRUGS ARE USED FOR ALL THE 4316 02:21:20,842 --> 02:21:21,576 DISEASES POSSIBLE. 4317 02:21:21,576 --> 02:21:23,078 THAT'S NOT THE FDA'S JOB. 4318 02:21:23,078 --> 02:21:25,246 THE FDA'S JOB IS TO SAY, BASED 4319 02:21:25,246 --> 02:21:26,815 ON THE INDICATION THAT'S BEEN 4320 02:21:26,815 --> 02:21:28,383 SUBMITTED, IS THIS DRUG SAFE AND 4321 02:21:28,383 --> 02:21:29,684 EFFECTIVE FOR THAT INDICATION. 4322 02:21:29,684 --> 02:21:31,419 IT'S NOT WHAT ARE THE OTHER 4323 02:21:31,419 --> 02:21:32,621 INDICATIONS THAT THIS DRUG COULD 4324 02:21:32,621 --> 02:21:33,555 BE USEFUL FOR. 4325 02:21:33,555 --> 02:21:34,889 NIH DOESN'T HAVE THAT REMIT, 4326 02:21:34,889 --> 02:21:36,091 PHARMA DOESN'T HAVE THAT REMIT, 4327 02:21:36,091 --> 02:21:37,859 REALLY KNOW ONE HAS A REMIT 4328 02:21:37,859 --> 02:21:38,960 SAYING IF IT'S ON THE PHARMACY 4329 02:21:38,960 --> 02:21:42,897 SHELF FOR ONE THING, WHAT ARE 4330 02:21:42,897 --> 02:21:45,667 THE OTHER THINGS, BUT WES ARE 4331 02:21:45,667 --> 02:21:48,770 SORT OF DO IT FOR OUR OWN 4332 02:21:48,770 --> 02:21:49,738 FAVORITE DISEASE AT A TIME. 4333 02:21:49,738 --> 02:21:50,939 SO IT BECAME VERY CLEAR, THE 4334 02:21:50,939 --> 02:21:52,273 MORE DAYS AND MONTHS THAT WENT 4335 02:21:52,273 --> 02:21:53,441 BY THAT I WAS IN REMISSION AND 4336 02:21:53,441 --> 02:21:54,409 THE MORE PATIENTS WE TREATED 4337 02:21:54,409 --> 02:21:55,944 WITH MTOR INHIBITION FOR 4338 02:21:55,944 --> 02:21:58,179 CASTLEMAN DISEASE, THE CLEARER 4339 02:21:58,179 --> 02:21:59,481 IT WAS THAT THIS WASN'T JUST 4340 02:21:59,481 --> 02:22:00,815 SORT OF A ONE-OFF THING. 4341 02:22:00,815 --> 02:22:03,885 WE'RE LIKE, OH, CERILIMUS 4342 02:22:03,885 --> 02:22:04,919 HAPPENED TO BE WAITING THERE. 4343 02:22:04,919 --> 02:22:06,554 THERE'S ACTUALLY A LOT OF OTHER 4344 02:22:06,554 --> 02:22:08,056 DRUGS WAITING TO BE USED IN NEW 4345 02:22:08,056 --> 02:22:08,356 WAYS. 4346 02:22:08,356 --> 02:22:10,358 SO ABOUT TWO YEARS AGO, WE 4347 02:22:10,358 --> 02:22:11,426 LAUNCHED A NON-PROFIT 4348 02:22:11,426 --> 02:22:12,894 ORGANIZATION CALLED EVERY YEAR, 4349 02:22:12,894 --> 02:22:18,933 AND E --CALLED EVERY CURE. 4350 02:22:18,933 --> 02:22:20,402 WE BELIEVE NO ONE SHOULD SUFFER 4351 02:22:20,402 --> 02:22:21,469 LIKE I DID FOR THREE YEARS WHILE 4352 02:22:21,469 --> 02:22:23,438 THERE'S A TREATMENT SITTING ON 4353 02:22:23,438 --> 02:22:25,473 THE PHARMACY SHELF WAITING TO BE 4354 02:22:25,473 --> 02:22:25,740 UNLOCKED. 4355 02:22:25,740 --> 02:22:27,909 THE REASON WE DECIDED TO START A 4356 02:22:27,909 --> 02:22:29,310 COUPLE YEARS AGO IS THAT WE 4357 02:22:29,310 --> 02:22:30,578 UTILIZED ARTIFICIAL INTELLIGENCE 4358 02:22:30,578 --> 02:22:32,647 IN A NUMBER OF MACHINE LEARNING 4359 02:22:32,647 --> 02:22:33,548 ALGORITHMS, ACTUALLY SEVERAL OF 4360 02:22:33,548 --> 02:22:35,216 WHICH WERE DEVELOPED THANKS TO 4361 02:22:35,216 --> 02:22:38,153 FUNDING FROM NCATS, ON DATASETS 4362 02:22:38,153 --> 02:22:39,888 AGAIN THAT WERE CONSTRUCTED WITH 4363 02:22:39,888 --> 02:22:42,057 FUNDING FROM NCATS. 4364 02:22:42,057 --> 02:22:42,924 THIS INCREDIBLE PROGRAM CALLED 4365 02:22:42,924 --> 02:22:43,892 THE TRANSLATOR PROGRAM. 4366 02:22:43,892 --> 02:22:45,760 SO COME UP WITH PREDICTIVE 4367 02:22:45,760 --> 02:22:47,262 SCORES FOR THE LIKELIHOOD OF 4368 02:22:47,262 --> 02:22:48,363 EVERY SINGLE DRUG TO TREAT EVERY 4369 02:22:48,363 --> 02:22:48,697 DISEASE. 4370 02:22:48,697 --> 02:22:50,632 SO IT WAS ABOUT 3,000 4371 02:22:50,632 --> 02:22:52,667 FDA-APPROVED DRUGS AND ABOUT 4372 02:22:52,667 --> 02:22:53,768 22,000 HUMAN DISEASES, SO 4373 02:22:53,768 --> 02:22:55,837 UTILIZING THIS REALLY ROBUST 4374 02:22:55,837 --> 02:22:57,238 DATA INFRASTRUCTURE AND A 4375 02:22:57,238 --> 02:22:59,441 HANDFUL OF MACHINE LEARNING 4376 02:22:59,441 --> 02:23:00,742 ALGORITHMS, WE CAN QUANTIFY THE 4377 02:23:00,742 --> 02:23:01,943 STRENGTH OF EVIDENCE FOR EVERY 4378 02:23:01,943 --> 02:23:03,411 MATCH AND THEN THAT CAN SERVE AS 4379 02:23:03,411 --> 02:23:05,246 A STARTING PLACE FOR THEN US TO 4380 02:23:05,246 --> 02:23:07,115 SAY WHAT'S THE TOP HIT OR WHAT'S 4381 02:23:07,115 --> 02:23:08,550 THE TOP -- WHAT ARE THE TOP 4382 02:23:08,550 --> 02:23:10,251 1,000 HITS FOR DRUGS VERSUS 4383 02:23:10,251 --> 02:23:11,553 DISEASES THAT MAYBE DESERVE 4384 02:23:11,553 --> 02:23:13,321 FURTHER RESEARCH, WHETHER OR NOT 4385 02:23:13,321 --> 02:23:15,690 THEY COULD EVER BE PROFITABLE 4386 02:23:15,690 --> 02:23:16,858 FOR A PHARMACEUTICAL COMPANY. 4387 02:23:16,858 --> 02:23:18,093 >> MAYBE YOU ALSO NEED TO 4388 02:23:18,093 --> 02:23:21,596 PROGRAM IN THE NEED FROM THE 4389 02:23:21,596 --> 02:23:21,996 PATIENT END. 4390 02:23:21,996 --> 02:23:23,131 >> ABSOLUTELY. 4391 02:23:23,131 --> 02:23:24,499 >> SOME OF THESE DISEASES REALLY 4392 02:23:24,499 --> 02:23:26,000 HAVE NOTHING AND MAYBE THOSE ARE 4393 02:23:26,000 --> 02:23:28,970 THE ONES THAT SHOULD KIND OF 4394 02:23:28,970 --> 02:23:31,005 FALL TO THE TOP OF THE LIST. 4395 02:23:31,005 --> 02:23:33,641 YOU RECENTLY, OR YOUR 4396 02:23:33,641 --> 02:23:34,609 NON-PROFIT, I BELIEVE, RECENTLY 4397 02:23:34,609 --> 02:23:37,612 ALSO RECEIVED A HUGE GRANT FROM 4398 02:23:37,612 --> 02:23:39,047 ARPA-H FOR PART OF THIS WORK. 4399 02:23:39,047 --> 02:23:40,482 CAN YOU TELL US ANY MORE ABOUT 4400 02:23:40,482 --> 02:23:41,349 THAT? 4401 02:23:41,349 --> 02:23:42,617 >> SURE. 4402 02:23:42,617 --> 02:23:44,686 YEAH, SO WE'RE SO THRILLED. 4403 02:23:44,686 --> 02:23:47,088 ARPA-H, BRAND NEW FEDERAL AGENCY 4404 02:23:47,088 --> 02:23:49,190 MODELED AFTER DARPA, BUT FOCUSED 4405 02:23:49,190 --> 02:23:49,858 ON HEALTH. 4406 02:23:49,858 --> 02:23:52,160 THEY ARE DOING SOME REALLY 4407 02:23:52,160 --> 02:23:53,895 AMAZING THINGS IN THE BIOMEDICAL 4408 02:23:53,895 --> 02:23:55,897 RESEARCH SPACE, AND THEY MADE AN 4409 02:23:55,897 --> 02:23:58,500 EARLY INVESTMENT INTO THIS 4410 02:23:58,500 --> 02:24:00,034 NON-PROFIT, EVERY CURE, 4411 02:24:00,034 --> 02:24:01,536 SPECIFICALLY TO BUILD OUT OUR 4412 02:24:01,536 --> 02:24:02,103 A.I. PLATFORM. 4413 02:24:02,103 --> 02:24:03,605 SO TO TAKE IT FROM WHERE WE ARE 4414 02:24:03,605 --> 02:24:05,740 NOW, WE ACTUALLY RAN IT FOR THE 4415 02:24:05,740 --> 02:24:07,509 FIRST TIME EVER LAST MARCH, SO 4416 02:24:07,509 --> 02:24:09,010 CLOSING IN AROUND 15 MONTHS, 4417 02:24:09,010 --> 02:24:10,211 WE'VE CONTINUED TO REFINE IT, 4418 02:24:10,211 --> 02:24:12,680 BUT TO GO FROM THIS SORT OF BETA 4419 02:24:12,680 --> 02:24:14,749 VERSION OF THE ALGORITHM AND OUR 4420 02:24:14,749 --> 02:24:17,085 PLATFORM TO A FULLY BUILT OUT 4421 02:24:17,085 --> 02:24:19,220 PLATFORM WHERE THE WORLD'S 4422 02:24:19,220 --> 02:24:20,088 BIOMEDICAL KNOWLEDGE IS 4423 02:24:20,088 --> 02:24:21,189 HARNESSED TO COME UP WITH A 4424 02:24:21,189 --> 02:24:22,824 SCORE FOR EVERY DRUG VERSUS 4425 02:24:22,824 --> 02:24:24,826 EVERY DISEASE, AND THE 4426 02:24:24,826 --> 02:24:26,027 ALGORITHMS WE USE ARE OPTIMIZED, 4427 02:24:26,027 --> 02:24:27,695 RIGHT NOW WE USE FIVE DIFFERENT 4428 02:24:27,695 --> 02:24:28,563 A.I. ALGORITHMS. 4429 02:24:28,563 --> 02:24:31,099 WE WANT TO WORK TOWARDS ONE THAT 4430 02:24:31,099 --> 02:24:32,033 COMBINES THE BEST OF EACH, AND 4431 02:24:32,033 --> 02:24:33,668 THEN WE'RE GOING TO SHARE THOSE 4432 02:24:33,668 --> 02:24:35,603 RESULTS WITH THE WORLD, ACTUALLY 4433 02:24:35,603 --> 02:24:37,205 WITHIN 18 TO 24 MONTHS, THERE 4434 02:24:37,205 --> 02:24:39,307 WILL BE A SCORE FOR EVERY DRUG 4435 02:24:39,307 --> 02:24:40,608 VERSUS EVERY DISEASE, WHICH FOR 4436 02:24:40,608 --> 02:24:41,810 EVERYONE ON THE CALL THAT'S A 4437 02:24:41,810 --> 02:24:43,444 CLINICIAN, THAT MIGHT SEEM MAYBE 4438 02:24:43,444 --> 02:24:45,380 KIND OF, I DON'T KNOW, SCARY BUT 4439 02:24:45,380 --> 02:24:46,815 SORT OF POTENTIALLY CHALLENGING 4440 02:24:46,815 --> 02:24:48,650 IN SOME WAYS, BECAUSE YOU CAN 4441 02:24:48,650 --> 02:24:51,853 IMAGINE YOUR PATIENT CAN GO 4442 02:24:51,853 --> 02:24:55,156 ONLINE AND RHEUMATOID ARTHRITIS, 4443 02:24:55,156 --> 02:24:55,957 3,000 DRU AND THERE WILL BE A 4444 02:24:55,957 --> 02:24:57,258 SCORE NEXT TO EVERY DRUG FOR 4445 02:24:57,258 --> 02:24:57,759 R.A. 4446 02:24:57,759 --> 02:24:59,961 SO JUST TO SORT OF -- FOR ANYONE 4447 02:24:59,961 --> 02:25:01,262 WHO IS ANXIOUS WHEN THEY HEAR 4448 02:25:01,262 --> 02:25:02,363 THAT, WE'RE GOING TO START OUT 4449 02:25:02,363 --> 02:25:03,665 WITH WHAT WE PROVIDE BEING FIRST 4450 02:25:03,665 --> 02:25:07,235 WHAT ARE THE DRUGS THAT ARE 4451 02:25:07,235 --> 02:25:08,870 FDA-APPROVED FOR THAT KRNTION 4452 02:25:08,870 --> 02:25:10,738 SECONDLY WHAT ARE THE DRUGS THAT 4453 02:25:10,738 --> 02:25:12,540 ARE ALREADY INCLUDED IN THE WELL 4454 02:25:12,540 --> 02:25:13,441 ESTABLISHED GUIDELINES. 4455 02:25:13,441 --> 02:25:15,944 AND BY THE TIME YOU CLICK THE 4456 02:25:15,944 --> 02:25:17,111 THIRD, YOU'RE GOING TO GET THIS 4457 02:25:17,111 --> 02:25:19,414 VERY MUCH RESEARCH SCORE GREAT 4458 02:25:19,414 --> 02:25:21,382 FROM ZERO TO 1 FOR EVERY OTHER 4459 02:25:21,382 --> 02:25:22,383 DRUG AGAINST THAT DISEASE OF 4460 02:25:22,383 --> 02:25:23,785 INTEREST, SO WE'LL BE MAKING IT 4461 02:25:23,785 --> 02:25:24,619 AVAILABLE TO THE WORLD, SO IT'S 4462 02:25:24,619 --> 02:25:27,589 JUST AN INCREDIBLE INVESTMENT TO 4463 02:25:27,589 --> 02:25:29,324 BUILD THE TEAM NECESSARY, AND 4464 02:25:29,324 --> 02:25:30,258 THEN AT THE SAME TIME, WE'RE 4465 02:25:30,258 --> 02:25:31,359 ALSO BUILDING A MEDICAL TEAM SO 4466 02:25:31,359 --> 02:25:35,096 THAT WE CAN PICK OUT AMONG THOSE 4467 02:25:35,096 --> 02:25:36,664 66 MILLION POSSIBILITIES WHICH 4468 02:25:36,664 --> 02:25:37,565 DRUGS FOR WHAT DISEASES LOOK 4469 02:25:37,565 --> 02:25:39,734 MOST PROMISING THAT WE WANT TO 4470 02:25:39,734 --> 02:25:40,401 DO CLINICAL TRIALS. 4471 02:25:40,401 --> 02:25:42,237 SO EVEN IF THERE IS AN INCENTIVE 4472 02:25:42,237 --> 02:25:43,771 FOR DRUG COMPANIES TO DO T WE 4473 02:25:43,771 --> 02:25:45,173 CAN DO THE TRIAL SO THAT 4474 02:25:45,173 --> 02:25:46,507 HOPEFULLY RESULT IN THAT DRUG 4475 02:25:46,507 --> 02:25:47,775 BEING UTILIZED IN A DISEASE 4476 02:25:47,775 --> 02:25:47,976 AREA. 4477 02:25:47,976 --> 02:25:49,611 >> SO I HAVE TO ASK BECAUSE I'LL 4478 02:25:49,611 --> 02:25:50,945 GET IN TROUBLE WITH DR. CLAYTON 4479 02:25:50,945 --> 02:25:52,647 IF I DON'T ASK THIS. 4480 02:25:52,647 --> 02:25:54,616 SO IN YOUR LARGE DATASET, I 4481 02:25:54,616 --> 02:25:57,051 ASSUME YOU'RE LOOKING AT MEN AND 4482 02:25:57,051 --> 02:25:58,086 WOMEN IN THE DATASET? 4483 02:25:58,086 --> 02:26:01,689 GLA?>> ABSOLUTELY. 4484 02:26:01,689 --> 02:26:02,390 THANK YOU FOR ASKING. 4485 02:26:02,390 --> 02:26:04,392 >> BECAUSE WE DO KNOW THAT 4486 02:26:04,392 --> 02:26:05,693 SOMETIMES WOMEN RESPOND TO DRUGS 4487 02:26:05,693 --> 02:26:05,994 DIFFERENTLY. 4488 02:26:05,994 --> 02:26:06,661 >> ABSOLUTELY. 4489 02:26:06,661 --> 02:26:08,263 AND I THINK IT'S AN IMPORTANT 4490 02:26:08,263 --> 02:26:09,664 QUESTION YOU BRING UP. 4491 02:26:09,664 --> 02:26:11,666 A, BECAUSE IT'S ESSENTIAL BUT B, 4492 02:26:11,666 --> 02:26:12,934 BALLS HISTORICALLY, THAT'S NOT 4493 02:26:12,934 --> 02:26:14,402 THE WAY THAT RESEARCH HAS BEEN 4494 02:26:14,402 --> 02:26:17,739 DONE, AND SO WE ARE ALREADY A 4495 02:26:17,739 --> 02:26:19,841 BIT BEHIND THE 8 BALL IN THE 4496 02:26:19,841 --> 02:26:21,776 SENSE THAT THERE HAS NOT 4497 02:26:21,776 --> 02:26:23,177 HISTORICALLY BEEN ENOUGH 4498 02:26:23,177 --> 02:26:25,013 RESEARCH IN WOMEN TO DATE AND 4499 02:26:25,013 --> 02:26:27,515 ALSO A NUMBER OF OTHER IMPORTANT 4500 02:26:27,515 --> 02:26:28,850 POPULATIONS, WHICH MEANS THAT 4501 02:26:28,850 --> 02:26:32,520 THE DATASETS, THE WORLD'S WORLDS 4502 02:26:32,520 --> 02:26:33,288 BIOMEDICAL KNOWLEDGE IS MISSING 4503 02:26:33,288 --> 02:26:35,223 A LOT OF BIOMEDICAL KNOWLEDGE. 4504 02:26:35,223 --> 02:26:38,826 SO WE START BY RELYING ON 4505 02:26:38,826 --> 02:26:40,261 PUBLICLY AVAILABLE BIOMEDICAL 4506 02:26:40,261 --> 02:26:41,362 KNOWLEDGE, BUT ONE THING WE'RE 4507 02:26:41,362 --> 02:26:42,330 DOING THAT'S DIFFERENT FROM 4508 02:26:42,330 --> 02:26:43,398 OTHER GROUPS IS WE'RE WORKING 4509 02:26:43,398 --> 02:26:45,934 REALLY HARD TO FILL IN THE GAPS, 4510 02:26:45,934 --> 02:26:48,937 WE CALL IT THE IGNOROME, ALL THE 4511 02:26:48,937 --> 02:26:52,640 SPOTS OF THE KNOWLEDGE IMRAF KNH 4512 02:26:52,640 --> 02:26:54,242 THAT DON'T INCLUDE PEOPLE OF 4513 02:26:54,242 --> 02:26:55,810 CERTAIN RACE, CERTAIN GENDERS. 4514 02:26:55,810 --> 02:26:57,946 THAT'S THE IGNOROME. 4515 02:26:57,946 --> 02:26:59,247 SO WE WANT TO USE OUR GAPS TO 4516 02:26:59,247 --> 02:27:01,582 FIGURE OUT WHAT IS THE IGNOROME, 4517 02:27:01,582 --> 02:27:02,483 THE GAPS IN THE MEDICAL 4518 02:27:02,483 --> 02:27:04,352 KNOWLEDGE SO WE CAN PROPERLY 4519 02:27:04,352 --> 02:27:04,686 FILL IT. 4520 02:27:04,686 --> 02:27:05,820 >> WONDERFUL TO HEAR. 4521 02:27:05,820 --> 02:27:07,689 I'M GOING TO TAKE YOU BACK NOW 4522 02:27:07,689 --> 02:27:09,824 FULL CIRCLE TO SOME OF THE 4523 02:27:09,824 --> 02:27:10,825 THINGS THAT YOU KIND OF BROUGHT 4524 02:27:10,825 --> 02:27:13,995 UP EARLIER. 4525 02:27:13,995 --> 02:27:16,297 WHAT YOU'RE DOING NOW IS SORT OF 4526 02:27:16,297 --> 02:27:18,433 FILLING ME WITH OPTIMISM. 4527 02:27:18,433 --> 02:27:19,968 IS IT FILLING YOU WITH OPTIMISM 4528 02:27:19,968 --> 02:27:22,370 TOO, AND IS THERE AN OUNCE OF 4529 02:27:22,370 --> 02:27:23,171 HOPE STILL? 4530 02:27:23,171 --> 02:27:24,872 >> YES, THERE IS. 4531 02:27:24,872 --> 02:27:30,645 I AM SO EXCITED. 4532 02:27:30,645 --> 02:27:33,047 OBVIOUSLY I SHARED MY OWN 4533 02:27:33,047 --> 02:27:33,915 PERSONAL EXPERIENCE BUT MAYBE 4534 02:27:33,915 --> 02:27:35,850 I'LL SHARE ANOTHER COUPLE 4535 02:27:35,850 --> 02:27:37,385 ANECDOTES, REASONS WHY I'M SUPER 4536 02:27:37,385 --> 02:27:38,386 EXCITED. 4537 02:27:38,386 --> 02:27:41,055 SO AN EXAMPLE OF A DISEASE THAT 4538 02:27:41,055 --> 02:27:42,590 WOULD FALL INTO AS MAYBE YOU 4539 02:27:42,590 --> 02:27:44,225 DESCRIBE IT AS LOW HANGING FRUIT 4540 02:27:44,225 --> 02:27:45,159 OR SORT OF TOP OF THE LIST IS 4541 02:27:45,159 --> 02:27:46,427 ONE THAT MANY ON THIS CALL WILL 4542 02:27:46,427 --> 02:27:48,129 BE FAMILIAR WITH, AND THAT'S 4543 02:27:48,129 --> 02:27:50,331 DATA 2, DEFICIENCY OF ADA2, 4544 02:27:50,331 --> 02:27:52,266 WHICH YOU MAY BE FAMILIAR WITH 4545 02:27:52,266 --> 02:27:53,368 THE WONDERFUL WORK THAT'S BEEN 4546 02:27:53,368 --> 02:27:56,337 DONE AT NIH AND ELSEWHERE TO 4547 02:27:56,337 --> 02:27:57,905 IDENTIFY TNF INHIBITION. 4548 02:27:57,905 --> 02:27:59,807 >> YEAH, AND I ACTUALLY HAD A 4549 02:27:59,807 --> 02:28:01,542 PATIENT WITH DATA 2 ONCE. 4550 02:28:01,542 --> 02:28:02,910 VERY RARE DISEASE. 4551 02:28:02,910 --> 02:28:03,945 >> WOW. 4552 02:28:03,945 --> 02:28:06,314 DID YOU HAVE THE PATIENT ON A 4553 02:28:06,314 --> 02:28:07,315 TNF INHIBITOR AND THE PATIENT 4554 02:28:07,315 --> 02:28:07,615 DID WELL? 4555 02:28:07,615 --> 02:28:08,149 >> HE DID. 4556 02:28:08,149 --> 02:28:09,384 >> AMAZING! 4557 02:28:09,384 --> 02:28:11,886 SO FOR THOSE THAT HAVEN'T MAYBE 4558 02:28:11,886 --> 02:28:13,187 SEEN THE DATA 2 PATIENT OR ARE 4559 02:28:13,187 --> 02:28:14,822 NOT AWARE OF THIS AMAZING STORY, 4560 02:28:14,822 --> 02:28:16,090 BUT ABOUT 15 YEARS AGO, 4561 02:28:16,090 --> 02:28:17,392 RESEARCHERS BOTH AT THE NIH BUT 4562 02:28:17,392 --> 02:28:19,160 ALSO IN A FEW OTHER PARTS OF THE 4563 02:28:19,160 --> 02:28:20,862 WORLD WERE REALLY HONING IN ON 4564 02:28:20,862 --> 02:28:22,530 WHAT IS THIS SYNDROME, 4565 02:28:22,530 --> 02:28:24,165 DEFICIENCY OF ADA2? 4566 02:28:24,165 --> 02:28:28,302 CHISH WCHILDREN WERE EXPERIENCIG 4567 02:28:28,302 --> 02:28:30,138 DOZENS AND DOZENS OF STROKES, 4568 02:28:30,138 --> 02:28:31,439 REALLY DEBILITATING STROKES, 4569 02:28:31,439 --> 02:28:31,839 WASN'T CLEAR WHY. 4570 02:28:31,839 --> 02:28:34,809 A RESEARCHER DECIDED TO TRY A 4571 02:28:34,809 --> 02:28:42,650 TNF I INHIBITOR OFF LABEL, NO 4572 02:28:42,650 --> 02:28:44,819 STROKE, ZERO STROKES AFTER THE 4573 02:28:44,819 --> 02:28:45,486 FIRST DOSE. 4574 02:28:45,486 --> 02:28:48,956 IT TOOK ABOUT 10 YEARS BETWEEN 4575 02:28:48,956 --> 02:28:51,259 THAT FIRST PATIENT GETTING -- WE 4576 02:28:51,259 --> 02:28:53,661 PARTNER WITH A GROUP CALLED THE 4577 02:28:53,661 --> 02:28:56,397 DATA 2 FOUNDATION. 4578 02:28:56,397 --> 02:28:57,432 THE FIRST EVER TREATMENT 4579 02:28:57,432 --> 02:28:58,332 GUIDELINES PUBLISHED ABOUT A 4580 02:28:58,332 --> 02:28:58,766 YEAR AGO. 4581 02:28:58,766 --> 02:29:00,168 OVER THE COARSE OF THOSE 10 4582 02:29:00,168 --> 02:29:03,104 YEARS, SOME PATIENTS GOT IT, 4583 02:29:03,104 --> 02:29:04,405 SOME PATIENTS DIDN'T, I'M SO 4584 02:29:04,405 --> 02:29:06,808 GLAD TO HEAR THAT, BUT BECAUSE 4585 02:29:06,808 --> 02:29:07,809 GUIDELINES HASN'T BEEN 4586 02:29:07,809 --> 02:29:09,110 DEVELOPED, THE WORLD HASN'T COME 4587 02:29:09,110 --> 02:29:10,845 TOGETHER TO SAY THIS IS HOW YOU 4588 02:29:10,845 --> 02:29:12,713 TREAT DATA TWO, PATIENTS 4589 02:29:12,713 --> 02:29:13,915 SUFFERED WHEN THERE WAS 4590 02:29:13,915 --> 02:29:15,583 LITERALLY SOMETHING THAT COULD 4591 02:29:15,583 --> 02:29:17,051 HAVE BEEN LIFE SAVING FOR THEM. 4592 02:29:17,051 --> 02:29:18,119 NOW THERE ARE GUIDELINES AND 4593 02:29:18,119 --> 02:29:19,554 WHAT I HEAR FROM CHIP IS THAT 4594 02:29:19,554 --> 02:29:22,256 EVERYONE WHO HAS DATA 2 IS 4595 02:29:22,256 --> 02:29:25,426 ACCESSING A TNF INHIBITOR 4596 02:29:25,426 --> 02:29:28,362 DESPITE THE FACT IT'S NOT -- A 4597 02:29:28,362 --> 02:29:29,897 CLINICAL TRIAL HASN'T BEEN DONE 4598 02:29:29,897 --> 02:29:32,500 BUT THE NATURAL HISTORY IS SO -- 4599 02:29:32,500 --> 02:29:35,570 IF YOU DON'T GIVE THESE KIDS TNF 4600 02:29:35,570 --> 02:29:37,271 INHIBITION, THEY ARE DEBILITATED 4601 02:29:37,271 --> 02:29:39,373 WITH STROKES, IF YOU DO, THEY 4602 02:29:39,373 --> 02:29:40,675 LIVE FULL LIVES. 4603 02:29:40,675 --> 02:29:43,811 SO THAT, FOR ME, PART OF THE 4604 02:29:43,811 --> 02:29:45,446 PROBLEM IS SOMETIMES WE DO 4605 02:29:45,446 --> 02:29:47,215 THINGS SOMEWHERE CLINICALLY AND 4606 02:29:47,215 --> 02:29:48,282 IT DOESN'T EVER SORT OF RISE TO 4607 02:29:48,282 --> 02:29:48,950 THE TOP. 4608 02:29:48,950 --> 02:29:50,118 WE WANT TO FIND THOSE 4609 02:29:50,118 --> 02:29:50,918 OPPORTUNITIES BUT IT ALSO 4610 02:29:50,918 --> 02:29:53,087 PROVIDES ME A LOT OF HOPE AND 4611 02:29:53,087 --> 02:29:53,621 EXCITEMENT. 4612 02:29:53,621 --> 02:29:54,922 MAYBE I'LL SHARE ONE MORE 4613 02:29:54,922 --> 02:29:55,890 EXAMPLE. 4614 02:29:55,890 --> 02:29:58,459 AND THAT'S THAT WE RAN ALGORITHM 4615 02:29:58,459 --> 02:30:01,596 FOR THE FIRST TIME LAST MARCH 4616 02:30:01,596 --> 02:30:04,765 AND YOU END UP GETTING ALL 4617 02:30:04,765 --> 02:30:05,833 66 MILLION SCORES, YOU CAN 4618 02:30:05,833 --> 02:30:10,471 IMAGINE I'M BIASED SO I LOOKED 4619 02:30:10,471 --> 02:30:11,439 AT CASTLEMAN'S. 4620 02:30:11,439 --> 02:30:12,473 NORMALIZED ACROSS DISEASES 4621 02:30:12,473 --> 02:30:15,309 MEANING A .89 FOR A DRUG FOR 4622 02:30:15,309 --> 02:30:17,712 LUPUS IS BETTER THAN A .75 FOR A 4623 02:30:17,712 --> 02:30:19,013 DRUG FOR CASTLEMAN'S. 4624 02:30:19,013 --> 02:30:20,748 THE SCORE IS NORMALIZED SO THAT 4625 02:30:20,748 --> 02:30:22,450 THE TOP HITS FOR ONE TEASE COULD 4626 02:30:22,450 --> 02:30:24,185 BE COMPARABLE TO THE TOP HITS 4627 02:30:24,185 --> 02:30:24,986 FOR ANOTHER DISEASE. 4628 02:30:24,986 --> 02:30:28,589 BUT I ZOOMED IN ON CASTLEMAN'S 4629 02:30:28,589 --> 02:30:30,858 OBVIOUSLY, AND WAS REALLY, 4630 02:30:30,858 --> 02:30:32,260 REALLY INTERESTED TO SEE THE TOP 4631 02:30:32,260 --> 02:30:34,562 HIT BECAUSE JUST A COUPLE WEEKS 4632 02:30:34,562 --> 02:30:37,064 BEFORE, WE HAD COMPLETED A LARGE 4633 02:30:37,064 --> 02:30:39,033 PROTEOMICS STUDY WHICH LED US TO 4634 02:30:39,033 --> 02:30:43,271 ACTUALLY USE A TNF INHIBITOR IN 4635 02:30:43,271 --> 02:30:45,039 A CASTLEMAN'S PATIENT, GETTING 4636 02:30:45,039 --> 02:30:46,674 READY TO GO INTO HOSPICE CARE. 4637 02:30:46,674 --> 02:30:49,810 WE USED THIS TNF INHIBITOR FOR 4638 02:30:49,810 --> 02:30:52,680 THE FIRST TIME WE'RE AWARE -- 4639 02:30:52,680 --> 02:30:55,283 BUT IT ACTUALLY WORKED REALLY 4640 02:30:55,283 --> 02:30:58,853 WELL FOR THE PATIENT, IT'S WELL 4641 02:30:58,853 --> 02:31:02,623 OVER A YEAR, HE'S IN REMISSION, 4642 02:31:02,623 --> 02:31:04,158 WHAT WAS SO COOL TO SEE WAS THE 4643 02:31:04,158 --> 02:31:05,359 NUMBER ONE DRUG PREDICTED FOR 4644 02:31:05,359 --> 02:31:06,460 CASTLEMAN'S DISEASE AND THE 4645 02:31:06,460 --> 02:31:08,996 NUMBER THREE DRUG FOR CASTLEMAN 4646 02:31:08,996 --> 02:31:12,567 EAZ WERE BOTH TNF INHIBITORS. 4647 02:31:12,567 --> 02:31:13,968 THERE'S A LOT OF REASON TO 4648 02:31:13,968 --> 02:31:14,869 BELIEVE FROM THE INTERSECTION 4649 02:31:14,869 --> 02:31:18,339 AND SIMILARITIES BETWEEN CASS 4650 02:31:18,339 --> 02:31:19,941 MAN AND OTHER AUTOIMMUNE 4651 02:31:19,941 --> 02:31:20,908 DISEASES, THAT MAYBE ONE WOULD 4652 02:31:20,908 --> 02:31:22,510 PREDICT THAT, BUT IT STILL WAS 4653 02:31:22,510 --> 02:31:23,978 REALLY EXCITING FOR US TO SEE. 4654 02:31:23,978 --> 02:31:25,346 >> AND I DO THINK THAT'S 4655 02:31:25,346 --> 02:31:30,785 EXCITING TO SEE AND HEAR AND THE 4656 02:31:30,785 --> 02:31:32,553 REALITY IS WE DO AS 4657 02:31:32,553 --> 02:31:33,754 RHEUMATOLOGISTS END UP USING OFF 4658 02:31:33,754 --> 02:31:34,789 LABEL TREATMENTS. 4659 02:31:34,789 --> 02:31:35,056 >> YES. 4660 02:31:35,056 --> 02:31:36,457 >> AND IT WOULD BE GREAT TO HAVE 4661 02:31:36,457 --> 02:31:37,892 BETTER EVIDENCE TO GUIDE SOME OF 4662 02:31:37,892 --> 02:31:40,161 THAT AND TO DRIVE LIKE DECISIONS 4663 02:31:40,161 --> 02:31:41,462 ABOUT WHICH CLINICAL TRIALS 4664 02:31:41,462 --> 02:31:43,130 SHOULD BE RUN BECAUSE THAT'S 4665 02:31:43,130 --> 02:31:46,367 ANOTHER PROBLEM WE HAVE, AND WE 4666 02:31:46,367 --> 02:31:48,002 WOULD DEARLY LIKE YOU TO LET US 4667 02:31:48,002 --> 02:31:50,738 KNOW WHAT WE SHOULD BE LOOKING 4668 02:31:50,738 --> 02:31:51,806 AT IN LUPUS. 4669 02:31:51,806 --> 02:31:53,174 >> YES, LUPUS IS A GREAT 4670 02:31:53,174 --> 02:31:54,375 EXAMPLE, RIGHT, AND I THINK 4671 02:31:54,375 --> 02:31:56,277 THAT, YOU KNOW, WHAT I WOULD 4672 02:31:56,277 --> 02:31:59,380 LOVE IS FOR THIS TO BE REALLY A 4673 02:31:59,380 --> 02:32:00,348 TWO-WAY DIALOGUE BETWEEN THE 4674 02:32:00,348 --> 02:32:02,083 SYSTEM AND BETWEEN OUR MEDICAL 4675 02:32:02,083 --> 02:32:04,485 COMMUNITY, WHERE OBVIOUSLY WE 4676 02:32:04,485 --> 02:32:06,854 UTILIZE THESE BIOMEDICAL 4677 02:32:06,854 --> 02:32:08,322 KNOWLEDGE GAPS, WE GIVE SCORES 4678 02:32:08,322 --> 02:32:11,692 TO THE COMMUNITY SO THE NUMBER 4679 02:32:11,692 --> 02:32:14,595 THREE PREDICTED -- BUT WE ALSO 4680 02:32:14,595 --> 02:32:16,030 WANT THE MEDICAL COMMUNITY TO 4681 02:32:16,030 --> 02:32:17,531 SHARE YOUR FEEDBACK AND YOUR 4682 02:32:17,531 --> 02:32:19,066 INSIGHTS WITH US SO THAT WAY WE 4683 02:32:19,066 --> 02:32:21,369 CAN REFINE OUR SCORES AND MAYBE 4684 02:32:21,369 --> 02:32:23,104 SOMETHING THAT GOT A REALLY 4685 02:32:23,104 --> 02:32:25,239 GREAT SCORE, IT'S NONSENSICAL OR 4686 02:32:25,239 --> 02:32:27,174 VICE VERSA, YOU KNOW, WE WANT TO 4687 02:32:27,174 --> 02:32:28,709 ENGAGE AND WE WANT TO HEAR ABOUT 4688 02:32:28,709 --> 02:32:30,211 PATIENTS WHERE YOU'VE TREATED -- 4689 02:32:30,211 --> 02:32:32,813 USED A DRUG, IT'S WORKED, CAN WE 4690 02:32:32,813 --> 02:32:34,048 UTILIZE THAT AS WE THINK ABOUT 4691 02:32:34,048 --> 02:32:35,149 WHAT TRIALS TO MOVE FORWARD. 4692 02:32:35,149 --> 02:32:36,317 >> AND I THINK THAT'S SOMETHING 4693 02:32:36,317 --> 02:32:39,720 THAT YOU'VE DONE SO WELL AND 4694 02:32:39,720 --> 02:32:42,657 THESE OTHER DISEASES, KIND OF 4695 02:32:42,657 --> 02:32:43,624 BRINGING COMMUNITY OF SCIENTISTS 4696 02:32:43,624 --> 02:32:44,292 AND PATIENTS TOGETHER AND BEING 4697 02:32:44,292 --> 02:32:45,593 ABLE TO KIND OF SCALE THAT TO 4698 02:32:45,593 --> 02:32:47,461 OTHER DISEASES WOULD BE REALLY 4699 02:32:47,461 --> 02:32:47,895 WONDERFUL. 4700 02:32:47,895 --> 02:32:49,196 WE'VE ONLY GOT A FEW MINUTES 4701 02:32:49,196 --> 02:32:50,965 LEFT, SO I WANTED TO GIVE YOU A 4702 02:32:50,965 --> 02:32:53,367 CHANCE TO TELL PEOPLE, HOW CAN 4703 02:32:53,367 --> 02:32:54,769 THEY LEARN MORE ABOUT YOUR STORY 4704 02:32:54,769 --> 02:32:57,305 AND HOW CAN THEY LEARN MORE 4705 02:32:57,305 --> 02:33:00,274 ABOUT WHAT YOUR FOUNDATION IS 4706 02:33:00,274 --> 02:33:00,474 DOING? 4707 02:33:00,474 --> 02:33:00,808 >> SURE. 4708 02:33:00,808 --> 02:33:03,010 SO YOU CAN GO TO EVERYCURE.ORG 4709 02:33:03,010 --> 02:33:04,312 TO LEARN MORE ABOUT WHAT WE'RE 4710 02:33:04,312 --> 02:33:05,746 DOING WITH THIS NON-PROFIT 4711 02:33:05,746 --> 02:33:07,148 THAT'S LOOKING -- I WAS GOING TO 4712 02:33:07,148 --> 02:33:09,016 SAY FOCUS ON ALL DRUGS AND ALL 4713 02:33:09,016 --> 02:33:10,117 DISEASES BUT I DON'T THINK FOCUS 4714 02:33:10,117 --> 02:33:12,620 IS THE RIGHT TERM WHEN LITERALLY 4715 02:33:12,620 --> 02:33:14,155 EVERY DRUG AND EVERY DISEASE IS 4716 02:33:14,155 --> 02:33:15,389 IN SCOPE FOR US. 4717 02:33:15,389 --> 02:33:16,824 SO CHECK OUT EVERYCURE.ORG. 4718 02:33:16,824 --> 02:33:18,125 I SEE ON THE SCREEN THERE'S A 4719 02:33:18,125 --> 02:33:19,860 PHOTO OF THE BOOK THAT I WROTE 4720 02:33:19,860 --> 02:33:21,529 ABOUT MY JOURNEY CALLED CHASING 4721 02:33:21,529 --> 02:33:23,698 MY CURE, WHICH FOR ME WAS SO 4722 02:33:23,698 --> 02:33:25,032 SPECIAL TO BE ABLE TO SHARE THIS 4723 02:33:25,032 --> 02:33:26,701 EXPERIENCE, WHAT MY FAMILY, WHAT 4724 02:33:26,701 --> 02:33:28,336 I WENT THROUGH GOING FROM BEING 4725 02:33:28,336 --> 02:33:30,171 A HEALTHY MEDICAL STUDENT TO A 4726 02:33:30,171 --> 02:33:31,272 SICK MEDICAL STUDENT TO A 4727 02:33:31,272 --> 02:33:34,642 MEDICAL RESEARCHER AND AN 4728 02:33:34,642 --> 02:33:35,976 ADVOCATE, SO A REAL HONOR FOR ME 4729 02:33:35,976 --> 02:33:37,978 TO WRITE, BUT I DO THINK THE 4730 02:33:37,978 --> 02:33:38,846 TITLE SHOULD ACTUALLY BE 4731 02:33:38,846 --> 02:33:39,180 DIFFERENT. 4732 02:33:39,180 --> 02:33:40,915 IT SHOULDN'T BE CHASTING MY 4733 02:33:40,915 --> 02:33:43,384 CURE, IT SHOULD BE CHASING OUR 4734 02:33:43,384 --> 02:33:44,118 CURE BECAUSE I THINK BHA YOU 4735 02:33:44,118 --> 02:33:45,519 HEARD ME SAY EARLIER IS IT 4736 02:33:45,519 --> 02:33:46,821 CERTAINLY WASN'T ME ON MY OWN 4737 02:33:46,821 --> 02:33:48,055 BECAUSE IF IT WAS ME ON MY OWN, 4738 02:33:48,055 --> 02:33:50,024 I WOULD NOT BE ALIVE RIGHT NOW. 4739 02:33:50,024 --> 02:33:51,225 IT WAS BECAUSE I HAD THIS 4740 02:33:51,225 --> 02:33:53,794 AMAZING TEAM, MEDICAL STUDENTS, 4741 02:33:53,794 --> 02:33:55,196 COLLEAGUES AT NIH AND BEYOND 4742 02:33:55,196 --> 02:33:56,430 THAT WERE PART OF THIS EFFORT. 4743 02:33:56,430 --> 02:34:01,168 SO IT SHOULD HAVE BEEN CHAIT CHG 4744 02:34:01,168 --> 02:34:02,403 OUR CURES, SO OBVIOUSLY YOU CAN 4745 02:34:02,403 --> 02:34:03,738 CHECK OUT THE STORY THERE. 4746 02:34:03,738 --> 02:34:08,075 BUT MOST IMPORTANTLY, FEEL FREE 4747 02:34:08,075 --> 02:34:09,276 TO -- IF YOU -- THERE ACTUALLY 4748 02:34:09,276 --> 02:34:10,845 IS A LOT OF OVERLAP. 4749 02:34:10,845 --> 02:34:12,213 IF YOU EVER SEE A CASTLEMAN'S 4750 02:34:12,213 --> 02:34:14,615 PATIENT, PLEASE DO EMAIL ME. 4751 02:34:14,615 --> 02:34:18,219 VERY EASY TO FIND, PLEASE REACH 4752 02:34:18,219 --> 02:34:20,187 OUT TO ME, WE'D LOVE TO GET THAT 4753 02:34:20,187 --> 02:34:22,022 PATIENT INTO ONE OF OUR STUDY, 4754 02:34:22,022 --> 02:34:23,891 GET SAMPLES, GET THEM INTO OUR 4755 02:34:23,891 --> 02:34:25,292 REGISTRY AND ALSO JUST EAGER TO 4756 02:34:25,292 --> 02:34:26,927 SHARE WITH OTHERS ABOUT OUR 4757 02:34:26,927 --> 02:34:28,462 APPROACH, AND JUST THANKFUL FOR 4758 02:34:28,462 --> 02:34:32,733 ALL OF YOU, REALLY SUCH AN HONOR 4759 02:34:32,733 --> 02:34:35,069 TO BE A PART OF THIS, AND OF 4760 02:34:35,069 --> 02:34:37,738 COURSE AN EVENT NAMED AFTER 4761 02:34:37,738 --> 02:34:38,005 DR. PINN. 4762 02:34:38,005 --> 02:34:40,141 >> I REALLY WANT TO THANK YOU, 4763 02:34:40,141 --> 02:34:42,009 DAVID, FOR JOINING US TODAY, FOR 4764 02:34:42,009 --> 02:34:43,177 SHARING YOUR STORY WITH OUR 4765 02:34:43,177 --> 02:34:43,744 COMMUNITY. 4766 02:34:43,744 --> 02:34:46,580 YOUR BOOK RESONATED WITH ME, THE 4767 02:34:46,580 --> 02:34:47,681 THING THAT PROMPTED ME TO INVITE 4768 02:34:47,681 --> 02:34:50,384 YOU TODAY, AND THIS WAS JUST 4769 02:34:50,384 --> 02:34:52,787 SUCH AN ENJOYABLE EVENT AND I 4770 02:34:52,787 --> 02:34:53,888 REALLY THANK YOU AGAIN FOR 4771 02:34:53,888 --> 02:34:59,894 TAKING THE TIME TO JOIN US. 4772 02:34:59,894 --> 02:35:01,662 I'LL PASS THINGS BACK OVER TO 4773 02:35:01,662 --> 02:35:03,597 DR. CLAYTON TO INTRODUCE 4774 02:35:03,597 --> 02:35:03,864 DR. KARR. 4775 02:35:03,864 --> 02:35:13,274 >> THANK YOU SO MUCH, DR 4776 02:35:13,274 --> 02:35:16,644 DR. FAJGENBAUM. 4777 02:35:16,644 --> 02:35:18,312 DR. KARR'S CAREER HAS HAD SO 4778 02:35:18,312 --> 02:35:19,713 MANY HIGHLIGHTS SO FAR. 4779 02:35:19,713 --> 02:35:22,249 CAN YOU READ THE FULL BIO IN THE 4780 02:35:22,249 --> 02:35:24,218 PROGRAM BOOKLET THAT'S ONLINE 4781 02:35:24,218 --> 02:35:28,355 BUT I WOULD LIKE TO MEX MENTIONA 4782 02:35:28,355 --> 02:35:28,522 FEW. 4783 02:35:28,522 --> 02:35:32,092 SHE RECEIVED A SPECIAL 4784 02:35:32,092 --> 02:35:32,560 RECOGNITION AWARD FOR 4785 02:35:32,560 --> 02:35:34,061 CONTRIBUTIONS TO THE STUDIES ON 4786 02:35:34,061 --> 02:35:36,564 THE TREATMENT AND PATHOGENESIS 4787 02:35:36,564 --> 02:35:44,638 OF SYSTEMIC VASCULITIS. 4788 02:35:44,638 --> 02:35:46,474 IN THE D.C. ACADEMIC COMMUNITY. 4789 02:35:46,474 --> 02:35:48,542 AND THESE ARE JUST A FEW OF HER 4790 02:35:48,542 --> 02:35:49,009 ACCOMPLISHMENTS. 4791 02:35:49,009 --> 02:35:55,216 AND IN 2019, DR. KARR KERR WASE 4792 02:35:55,216 --> 02:35:59,620 FIRST TO USE THE FIRST 4793 02:35:59,620 --> 02:36:00,488 RHEUMATOLOGIST TO RECEIVE THE 4794 02:36:00,488 --> 02:36:01,989 JOHNS HAPPEN KINS UNIVERSITY 4795 02:36:01,989 --> 02:36:05,659 16TH MYRON BISFELT DISTINGUISHED 4796 02:36:05,659 --> 02:36:07,394 VISITING PROFESSORSHIP IN 4797 02:36:07,394 --> 02:36:09,463 DIVERSITY. 4798 02:36:09,463 --> 02:36:12,766 DR. KERR'S CLINICAL RESEARCH 4799 02:36:12,766 --> 02:36:15,703 ACTIVITIES HAVE BEEN BASED ON 4800 02:36:15,703 --> 02:36:19,940 CLINICAL AND OBSERVATIONAL -- OF 4801 02:36:19,940 --> 02:36:22,142 CHRONIC DISEASE, ALL REFLECTING 4802 02:36:22,142 --> 02:36:24,478 REAL WORLD CARE. 4803 02:36:24,478 --> 02:36:25,779 AND I'M GOING TO END BY SAYING 4804 02:36:25,779 --> 02:36:28,549 SHE IS ALSO THE 2023 RECIPIENT 4805 02:36:28,549 --> 02:36:30,751 OF THE AMERICAN COLLEGE OF 4806 02:36:30,751 --> 02:36:33,854 PHYSICIANS D.C. CHAPTER 4807 02:36:33,854 --> 02:36:35,189 EXCELLENCE IN TEACHING AWARD, 4808 02:36:35,189 --> 02:36:37,024 AND NOT MANY PEOPLE ARE 4809 02:36:37,024 --> 02:36:39,226 RECEIVING EXCELLENCE IN TEACHING 4810 02:36:39,226 --> 02:36:40,327 AND CLINICAL CARE AND IN 4811 02:36:40,327 --> 02:36:41,228 RESEARCH. 4812 02:36:41,228 --> 02:36:44,064 AND IN 2023, DR. GAIL KERR WAS 4813 02:36:44,064 --> 02:36:47,568 ALSO DESIGNATED AS A MASTER OF 4814 02:36:47,568 --> 02:36:48,869 THE AMERICAN COLLEGE OF 4815 02:36:48,869 --> 02:36:50,004 RHEUMATOLOGY, THE FIRST BLACK 4816 02:36:50,004 --> 02:36:52,373 WOMAN TO RECEIVE ITS HIGHEST 4817 02:36:52,373 --> 02:36:53,007 HONOR. 4818 02:36:53,007 --> 02:36:54,675 AS A FRIEND AND COLLEAGUE, 4819 02:36:54,675 --> 02:36:57,411 PLEASE JOIN ME IN WELCOMING 4820 02:36:57,411 --> 02:36:59,580 DR. GAIL KERR FOR OUR CAPSTONE 4821 02:36:59,580 --> 02:37:02,049 ADDRESS, WHICH SHE HAS ENTITLED 4822 02:37:02,049 --> 02:37:03,751 "MAKING A DIFFERENCE." 4823 02:37:03,751 --> 02:37:03,984 GAIL? 4824 02:37:03,984 --> 02:37:06,287 >> THANK YOU VERY MUCH, 4825 02:37:06,287 --> 02:37:07,821 DR. CLAYTON, AND THANKS, 4826 02:37:07,821 --> 02:37:08,822 EVERYONE, WHO CONSIDERED ME TO 4827 02:37:08,822 --> 02:37:10,224 TAKE PART IN THIS. 4828 02:37:10,224 --> 02:37:13,294 IT IS INDEED A PRIVILEGE. 4829 02:37:13,294 --> 02:37:18,198 A DISTINCT ONE, BECAUSE DR. PINN 4830 02:37:18,198 --> 02:37:19,466 IS ON THE LINE SO THANK YOU VERY 4831 02:37:19,466 --> 02:37:20,834 MUCH. 4832 02:37:20,834 --> 02:37:26,407 IT'S AN OPPORTUNITY FOR ME FOR 4833 02:37:26,407 --> 02:37:27,975 SHARING SOME THOUGHTS, REGARDING 4834 02:37:27,975 --> 02:37:28,542 PROVIDING BETTER CARE FOR 4835 02:37:28,542 --> 02:37:34,882 PATIENTS. 4836 02:37:34,882 --> 02:37:35,649 THANK YOU VERY MUCH FOR BEING 4837 02:37:35,649 --> 02:37:36,183 HERE. 4838 02:37:36,183 --> 02:37:38,619 IT'S A PRIVILEGE TO PARTICIPATE, 4839 02:37:38,619 --> 02:37:42,222 PARTICULARLY WITH DR. PINN ON 4840 02:37:42,222 --> 02:37:44,725 THE LINE, TOWARDS TAKING CARE 4841 02:37:44,725 --> 02:37:45,960 AND BETTER CARE OF PATIENTS WITH 4842 02:37:45,960 --> 02:37:46,627 RHEUMATIC DISEASES. 4843 02:37:46,627 --> 02:37:55,169 THESE ARE MY DISCLOSURES. 4844 02:37:55,169 --> 02:37:58,238 MY MOTIVATION REALLY TO BECOME A 4845 02:37:58,238 --> 02:37:59,440 RHEUMATOLOGIST STARTED MANY 4846 02:37:59,440 --> 02:38:01,475 YEARS AGO, WHEN I WAS ASKED TO 4847 02:38:01,475 --> 02:38:07,014 SEE A PATIENT, A KAU S CAUCASIAN 4848 02:38:07,014 --> 02:38:15,889 WITH MALAISE, ARTHRALGIA, AND 4849 02:38:15,889 --> 02:38:16,857 WHAT BROUGHT HER IN WAS THIS 4850 02:38:16,857 --> 02:38:17,825 RASH INITIALLY IN THE FEET BUT 4851 02:38:17,825 --> 02:38:20,361 THEN LATER WENT ON TO DEVELOP -- 4852 02:38:20,361 --> 02:38:21,462 TO INVOLVE HER HANDS AND 4853 02:38:21,462 --> 02:38:27,067 FINGERS. 4854 02:38:27,067 --> 02:38:28,802 AM I BEING ALLOWED TO ADVANCE MY 4855 02:38:28,802 --> 02:38:31,872 SLIDES? 4856 02:38:31,872 --> 02:38:33,674 SO THIS IS THE RASH SHE HAD ON 4857 02:38:33,674 --> 02:38:35,376 HER PALMS AND HANDS AND MOST 4858 02:38:35,376 --> 02:38:36,610 SIGNIFICANT WAS ONE ON THE 4859 02:38:36,610 --> 02:38:39,146 FINGER, A PAINLESS NODULAR 4860 02:38:39,146 --> 02:38:40,114 HEMORRHAGIC LESION. 4861 02:38:40,114 --> 02:38:45,052 THAT ALONG WITH MID SYSTOLIC 4862 02:38:45,052 --> 02:38:47,354 MURMUR IN THE MITRAL AREA AND 4863 02:38:47,354 --> 02:38:49,223 ELEVATED SED RATE LED ME TO MAKE 4864 02:38:49,223 --> 02:38:53,027 THE DIAGNOSIS OF EN ENDOCARDITI. 4865 02:38:53,027 --> 02:38:55,929 I ORDERED BLOOD CULTURES, ECHO 4866 02:38:55,929 --> 02:38:57,031 AND STARTED APPROPRIATE 4867 02:38:57,031 --> 02:38:57,331 ANTIBIOTICS. 4868 02:38:57,331 --> 02:39:00,868 THIS OCCURRED MANY YEARS AGO, 4869 02:39:00,868 --> 02:39:03,270 WHEN I WAS A RESIDENT WHERE I 4870 02:39:03,270 --> 02:39:04,505 TRAINED, AT THE UNIVERSITY OF 4871 02:39:04,505 --> 02:39:06,473 WEST INDIES IN JAMAICA. 4872 02:39:06,473 --> 02:39:08,909 THE NEXT MORNING, MY ATTENDING 4873 02:39:08,909 --> 02:39:13,280 ASKED IF I HAD CONSIDERED 4874 02:39:13,280 --> 02:39:19,520 HYPERSENSITIVITY VASCULITIS. 4875 02:39:19,520 --> 02:39:21,188 THAT INDEED IT WAS, BECAUSE IN 4876 02:39:21,188 --> 02:39:22,956 HER MEDICAL HISTORY, SHE IN FACT 4877 02:39:22,956 --> 02:39:33,300 HAD TAKEN TRIMETH 4878 02:39:36,704 --> 02:39:37,237 TRIMETHOPRIM-SULFAMETHOXAZOLE 4879 02:39:37,237 --> 02:39:38,372 THE WEEK BEFORE. 4880 02:39:38,372 --> 02:39:39,640 EVERY PAPER I PULLED WAS 4881 02:39:39,640 --> 02:39:43,610 ACTUALLY BY THE SAME GENTLEMAN. 4882 02:39:43,610 --> 02:39:45,045 ALL THE PAPERS. 4883 02:39:45,045 --> 02:39:46,847 IT OCCURRED IN A PLACE I HAD 4884 02:39:46,847 --> 02:39:49,550 NEVER HEARD. 4885 02:39:49,550 --> 02:39:50,384 THE NATIONAL INSTITUTES OF 4886 02:39:50,384 --> 02:39:53,253 HEALTH IN A PLACE OF BETHESDA, 4887 02:39:53,253 --> 02:39:53,520 MARYLAND. 4888 02:39:53,520 --> 02:39:54,688 AND WHO WOULD HAVE THOUGHT THAT 4889 02:39:54,688 --> 02:39:56,757 SOME YEARS LATER, I WOULD 4890 02:39:56,757 --> 02:39:59,626 ACTUALLY BE PART OF THAT GROUP 4891 02:39:59,626 --> 02:40:03,363 AND WRITING PAPERS ON SYSTEMIC 4892 02:40:03,363 --> 02:40:05,666 VASCULITIS IN ITS EARLY DAYS OF 4893 02:40:05,666 --> 02:40:10,471 THE VASCULITIS NETWORK. 4894 02:40:10,471 --> 02:40:12,473 IT IS THAT EXPOSURE AND 4895 02:40:12,473 --> 02:40:14,675 OPPORTUNITY THAT LED TO THE 4896 02:40:14,675 --> 02:40:15,776 TRANSITION AND THE ASSOCIATIONS 4897 02:40:15,776 --> 02:40:18,078 WITH THE THREE INSTITUTIONS THAT 4898 02:40:18,078 --> 02:40:20,581 I NOW REPRESENT, AND THAT HAS 4899 02:40:20,581 --> 02:40:22,382 MERGED INTO UNION OF SUPPORT, 4900 02:40:22,382 --> 02:40:25,085 AND FOR THE PAST THAT I'VE 4901 02:40:25,085 --> 02:40:25,853 SUBSEQUENTLY TAKEN. 4902 02:40:25,853 --> 02:40:27,821 SO IF I'M TO TAKE YOU DOWN THOSE 4903 02:40:27,821 --> 02:40:29,189 PATH AND SUMMARIZE THEM AS 4904 02:40:29,189 --> 02:40:31,592 OBJECTIVES TO MEET MY ASSIGNED 4905 02:40:31,592 --> 02:40:33,660 TOPIC THAT IS MAKING A 4906 02:40:33,660 --> 02:40:35,696 DIFFERENCE, IT WOULD INVOLVE 4907 02:40:35,696 --> 02:40:37,598 THESE THREE THINGS AND NOT 4908 02:40:37,598 --> 02:40:38,332 NECESSARILY IN SEQUENTIAL ORDER 4909 02:40:38,332 --> 02:40:40,300 AND THEY'RE NOT MUTUALLY 4910 02:40:40,300 --> 02:40:40,567 EXCLUSIVE. 4911 02:40:40,567 --> 02:40:42,936 AND THAT IS CREATING 4912 02:40:42,936 --> 02:40:44,571 COLLABORATIONS, 4913 02:40:44,571 --> 02:40:45,172 RECOGNIZING/IDENTIFYING GAPS, 4914 02:40:45,172 --> 02:40:48,342 AND SEEING THE BIG PICTURE. 4915 02:40:48,342 --> 02:40:50,410 AFTER LEAVING THE NIH, I HAVE 4916 02:40:50,410 --> 02:40:52,913 BEEN A MEMBER OF THE VETERANS 4917 02:40:52,913 --> 02:40:57,084 HEALTH AFFAIRS AT THE 4918 02:40:57,084 --> 02:40:58,852 WASHINGTON, D.C. V.A. MEDICAL 4919 02:40:58,852 --> 02:40:59,953 CENTER FOR THE PAST 28 YEARS, 4920 02:40:59,953 --> 02:41:01,722 AND NOT UNLIKE THE NIH, IT IS A 4921 02:41:01,722 --> 02:41:03,791 VERY LARGE INSTITUTION AND WE 4922 02:41:03,791 --> 02:41:06,293 SERVE ABOUT 5 MILLION VETERANS. 4923 02:41:06,293 --> 02:41:09,730 IN FACT, A RECENT CDC COHORT 4924 02:41:09,730 --> 02:41:11,732 ANALYSIS OF THE BEHAVIORAL RISK 4925 02:41:11,732 --> 02:41:13,467 FACTOR SURVEILLANCE SYSTEM DATA 4926 02:41:13,467 --> 02:41:15,803 SHOWED THAT A THIRD OF VETERANS 4927 02:41:15,803 --> 02:41:18,071 ARE DIAGNOSED WITH ARTHRITIS. 4928 02:41:18,071 --> 02:41:21,008 AND THIS OCCURS IN THEIR 4929 02:41:21,008 --> 02:41:22,876 PRODUCTIVE YEARS, BETWEEN THE 4930 02:41:22,876 --> 02:41:25,412 AGES OF 18 TO 44, THERE ARE 4931 02:41:25,412 --> 02:41:27,915 TWICE AS MANY VETERANS WHO HAVE 4932 02:41:27,915 --> 02:41:28,916 ARTHRITIS COMPARED TO 4933 02:41:28,916 --> 02:41:31,185 NON-VETERANS AND 60% MORE 4934 02:41:31,185 --> 02:41:32,553 PREVALENCE IN FEMALES. 4935 02:41:32,553 --> 02:41:34,388 SO WE HAVE A LOT OF PATIENT WITH 4936 02:41:34,388 --> 02:41:37,925 RHEUMATIC DISEASES TO CARE FOR. 4937 02:41:37,925 --> 02:41:39,860 ON MY EYE RIFLE, I WAS 4938 02:41:39,860 --> 02:41:41,628 DESIGNATED AS THE CHAIR OF THE 4939 02:41:41,628 --> 02:41:43,030 RHEUMATOLOGY FIELD ADVISORY 4940 02:41:43,030 --> 02:41:46,200 COMMITTEE, AND I TOOK THAT ROLE 4941 02:41:46,200 --> 02:41:48,101 AND TYPE LITERALLY AND MY JOB, 4942 02:41:48,101 --> 02:41:49,870 THEREFORE, WAS TO BRING 4943 02:41:49,870 --> 02:41:51,371 INFORMATION FROM THE FIELD TO 4944 02:41:51,371 --> 02:41:53,941 CENTRAL OFFICE TO INITIATE 4945 02:41:53,941 --> 02:41:55,676 DISCOURSE AND THEN GO BACK TO 4946 02:41:55,676 --> 02:41:57,010 THE CLINIC TO GIVE BEST CARE TO 4947 02:41:57,010 --> 02:41:58,846 THE PATIENTS. 4948 02:41:58,846 --> 02:42:01,081 I ALONG WITH MY PROGRAM 4949 02:42:01,081 --> 02:42:02,382 ASSISTANT AT THE TIME CALLED ALL 4950 02:42:02,382 --> 02:42:03,584 VAs IN THE COUNTRY AND GOT A 4951 02:42:03,584 --> 02:42:05,953 FULL LIST OF THE RHEUMATOLOGISTS 4952 02:42:05,953 --> 02:42:06,954 THERE, SOME OF WHICH WERE 4953 02:42:06,954 --> 02:42:09,022 ACTUALLY UNDER THEIR UNIVERSITY 4954 02:42:09,022 --> 02:42:09,890 DESIGNATION EVEN THOUGH THEY'RE 4955 02:42:09,890 --> 02:42:13,527 BEING PAID BY THE V.A. 4956 02:42:13,527 --> 02:42:14,528 ABOUT THE SAME TIME, THERE WAS A 4957 02:42:14,528 --> 02:42:15,596 KNOCK ON MY DOOR, AND THIS WAS 4958 02:42:15,596 --> 02:42:17,130 FROM THE HENRY JACKSON 4959 02:42:17,130 --> 02:42:19,132 FOUNDATION WHO CAME TO LET ME 4960 02:42:19,132 --> 02:42:21,034 KNOW THAT THEY HAD AN 4961 02:42:21,034 --> 02:42:23,570 EDUCATIONAL GRANT SPECIFIC FOR 4962 02:42:23,570 --> 02:42:23,971 RHEUMATOLOGY. 4963 02:42:23,971 --> 02:42:25,472 SO THE STARS WERE ALIGNED. 4964 02:42:25,472 --> 02:42:28,408 AND SO I GOT TOGETHER A GROUP OF 4965 02:42:28,408 --> 02:42:29,543 RHEUMATOLOGISTS IN 2001 AND WE 4966 02:42:29,543 --> 02:42:32,913 FIRST MET IN SANTA MONICA FOR 4967 02:42:32,913 --> 02:42:34,448 OUR FIRST MEETING, ABOUT 30 OF 4968 02:42:34,448 --> 02:42:36,083 US, AND IT WAS AROUND THE TIME 4969 02:42:36,083 --> 02:42:38,518 OF THE TNF INHIBITORS, WHICH 4970 02:42:38,518 --> 02:42:41,054 WERE ON THE MARKET SO WE HAD VA 4971 02:42:41,054 --> 02:42:42,289 PHARMACY, A ROBUST DISCUSSION. 4972 02:42:42,289 --> 02:42:45,525 BUT THAT GATHERING AND THE 4973 02:42:45,525 --> 02:42:46,526 COLLEGIALITY HATCHED WHAT WAS 4974 02:42:46,526 --> 02:42:49,129 DESIGNATED THEREAFTER AS THE VA 4975 02:42:49,129 --> 02:42:50,998 RHEUMATOLOGY CONSORTIUM, VARC. 4976 02:42:50,998 --> 02:42:52,399 AND I PULLED THIS SLIDE FROM ONE 4977 02:42:52,399 --> 02:42:56,336 OF MY OLD STATE OF THE 4978 02:42:56,336 --> 02:42:57,638 CONSORTIUM ADDRESS AT ONE OF OUR 4979 02:42:57,638 --> 02:42:59,473 ANNUAL MEETINGS. 4980 02:42:59,473 --> 02:43:02,109 AND I CHANGED THE ORDER A BIT. 4981 02:43:02,109 --> 02:43:04,077 I'M SORRY, THERE'S A BIG LAG 4982 02:43:04,077 --> 02:43:04,478 HERE. 4983 02:43:04,478 --> 02:43:07,180 I CHANGED THE ORDER A BIT, AND 4984 02:43:07,180 --> 02:43:09,149 REALLY TO EMPHASIZE THAT 4985 02:43:09,149 --> 02:43:11,218 WHATEVER WE DO, WHATEVER 4986 02:43:11,218 --> 02:43:13,086 INITIATIVE WE HAVE, THAT WHAT 4987 02:43:13,086 --> 02:43:14,955 MAKES IT ENDURING, AND YOU'VE 4988 02:43:14,955 --> 02:43:16,723 HEARD THIS THEME ACROSS ALL THE 4989 02:43:16,723 --> 02:43:19,126 PRESENTERS, THAT COLLABORATION. 4990 02:43:19,126 --> 02:43:24,298 THE CAMARADERIE, THE BONHOMIE IN 4991 02:43:24,298 --> 02:43:25,165 SOME INSTANCES. 4992 02:43:25,165 --> 02:43:26,333 THAT VALIDATED WHAT WAS REQUIRED 4993 02:43:26,333 --> 02:43:28,568 OF THE FIELD ADVISORY COMMITTEE. 4994 02:43:28,568 --> 02:43:29,770 WE NOT ONLY BROUGHT 4995 02:43:29,770 --> 02:43:30,671 RHEUMATOLOGISTS OUT OF THE 4996 02:43:30,671 --> 02:43:32,940 SHADOWS, BUT WE'RE NOW ABLE AND 4997 02:43:32,940 --> 02:43:34,741 FAMILIAR WITH EVERYBODY BY NAME 4998 02:43:34,741 --> 02:43:35,609 AND THEIR LOCATION. 4999 02:43:35,609 --> 02:43:37,277 AND THAT TURNED OUT TO BE MUSIC 5000 02:43:37,277 --> 02:43:38,912 TO THE EARS OF THE VETERANS WHEN 5001 02:43:38,912 --> 02:43:40,681 THEY WERE RELOCATING AND WE 5002 02:43:40,681 --> 02:43:42,115 COULD ACTUALLY TELL THEM THE 5003 02:43:42,115 --> 02:43:43,283 NAME OF THE PHYSICIAN THEY WERE 5004 02:43:43,283 --> 02:43:44,618 GOING TO SEE. 5005 02:43:44,618 --> 02:43:46,320 AND THEY WERE COMFORTED AND 5006 02:43:46,320 --> 02:43:47,587 REASSURED BY THE FACT THAT THEY 5007 02:43:47,587 --> 02:43:50,891 WOULD REMAIN IN THE V.A. ROOM 5008 02:43:50,891 --> 02:43:51,892 GROUP PRACTICE. 5009 02:43:51,892 --> 02:43:53,327 THE COLLEGIALITY LED TO A NUMBER 5010 02:43:53,327 --> 02:43:54,461 OF OTHER ACHIEVEMENTS. 5011 02:43:54,461 --> 02:43:59,132 WE WERE ABLE TO PROVIDE 5012 02:43:59,132 --> 02:44:00,934 RECOMMENDATIONS ON WORKLOAD AND 5013 02:44:00,934 --> 02:44:04,104 PERFORMANCE ISSUES, HAD A 5014 02:44:04,104 --> 02:44:05,973 UNIFIED SYSTEM WITHOUT LOSING 5015 02:44:05,973 --> 02:44:08,575 OUR INDIVIDUALITY, AND WE WERE 5016 02:44:08,575 --> 02:44:10,277 ABLE TO DEVELOP SPECIFIC DISEASE 5017 02:44:10,277 --> 02:44:11,445 TEMPLATES FOR OUR ELECTRONIC 5018 02:44:11,445 --> 02:44:12,245 HEALTH RECORDS. 5019 02:44:12,245 --> 02:44:17,050 BUT WHAT IS MOST NOTABLE WAS THE 5020 02:44:17,050 --> 02:44:18,085 COLLABORATION THAT LED TO THE 5021 02:44:18,085 --> 02:44:20,587 DEVELOPMENT OF OUR CHRONIC 5022 02:44:20,587 --> 02:44:22,789 DISEASE REGISTRIES. 5023 02:44:22,789 --> 02:44:24,624 AND THERE ARE THREE OF THEM. 5024 02:44:24,624 --> 02:44:27,160 THE FIRST WAS THE VA RHEUMATOID 5025 02:44:27,160 --> 02:44:29,997 ARTHRITIS LED BY TED MICHAELS IN 5026 02:44:29,997 --> 02:44:31,098 OMAHA, NEBRASKA, AND THEN A 5027 02:44:31,098 --> 02:44:32,566 PROGRAM TO UNDERSTAND THE LONG 5028 02:44:32,566 --> 02:44:37,671 TERM OUTCOMES OF THE AXSPA 5029 02:44:37,671 --> 02:44:40,107 PULSAR, CO-LED IN TEXAS. 5030 02:44:40,107 --> 02:44:43,543 AND CRYSTAL, RELOCATED BACK TO 5031 02:44:43,543 --> 02:44:47,047 L.A. WHERE IT WAS FIRST STARTED, 5032 02:44:47,047 --> 02:44:49,750 NOW IN MICHIGAN, AND NOW ALSO 5033 02:44:49,750 --> 02:44:51,551 ALONG WITH JOHN FITZGERALD. 5034 02:44:51,551 --> 02:44:53,787 BUT IT'S THE VARA REGISTRY 5035 02:44:53,787 --> 02:44:56,723 THAT'S BEEN THE LONGEST TENURE, 5036 02:44:56,723 --> 02:44:58,592 AND REALLY HAS SET THE BAR FOR 5037 02:44:58,592 --> 02:45:00,994 REGISTRIES NOT ONLY IN THE V.A., 5038 02:45:00,994 --> 02:45:03,897 BUT ALL ACROSS ALL REGISTRIES. 5039 02:45:03,897 --> 02:45:08,068 IT'S REALLY MASTERED THE SOURCES 5040 02:45:08,068 --> 02:45:11,004 THAT WE HAVE, BECAUSE ALONG WITH 5041 02:45:11,004 --> 02:45:13,206 LONGITUDAL OBSERVATIONAL DATA WE 5042 02:45:13,206 --> 02:45:14,875 COLLECT IN CLINIC THAT'S 5043 02:45:14,875 --> 02:45:18,278 EXTRACTED ON THE BACK END INTO 5044 02:45:18,278 --> 02:45:21,548 FIELDS, AND INTEGRATION WITH 5045 02:45:21,548 --> 02:45:23,283 LINKAGE TO V.A. CLAIMS DATA AND 5046 02:45:23,283 --> 02:45:26,620 NATIONAL V.A. DATA, WE'RE ABLE 5047 02:45:26,620 --> 02:45:29,423 TO POSE VARIOUS HYPOTHESES 5048 02:45:29,423 --> 02:45:30,757 DRIVEN QUERIES. 5049 02:45:30,757 --> 02:45:35,629 WE CAN ALSO LOOK AT ADHERENCE OF 5050 02:45:35,629 --> 02:45:37,497 MEDICATION AND DEVELOP 5051 02:45:37,497 --> 02:45:40,567 ALGORITHMS TO ASSESS TREATMENT 5052 02:45:40,567 --> 02:45:42,002 EFFICACY THAT'S USED IN 5053 02:45:42,002 --> 02:45:47,040 REGISTRIES AS WELL. 5054 02:45:47,040 --> 02:45:48,875 WITH RHEUMATOID ARTHRITIS, 5055 02:45:48,875 --> 02:45:49,543 INTERSTITIAL LUNG DISEASE. 5056 02:45:49,543 --> 02:45:52,446 THE GROUP HAS HAD MULTIPLE 5057 02:45:52,446 --> 02:45:53,780 FUNDING WITHIN AND OUTSIDE THE 5058 02:45:53,780 --> 02:45:57,384 V.A., AND IT ALSO HAS TAKEN ON 5059 02:45:57,384 --> 02:46:01,555 MENTORING, AND TO NAME A FEW -- 5060 02:46:01,555 --> 02:46:02,989 ENGLAND AND JOSH BAKER AND THOSE 5061 02:46:02,989 --> 02:46:03,523 THAT FOLLOW. 5062 02:46:03,523 --> 02:46:06,293 AND IT'S BEEN VERY PRODUCTIVE IN 5063 02:46:06,293 --> 02:46:07,394 PUBLICATIONS, OVER 120 AT LAST 5064 02:46:07,394 --> 02:46:10,530 YEAR'S ACR MEETING, WE HAD OVER 5065 02:46:10,530 --> 02:46:12,365 23 ABSTRACTS, MANY WERE PLENARY. 5066 02:46:12,365 --> 02:46:14,234 AND IT'S A LESSON IN TEAM 5067 02:46:14,234 --> 02:46:16,303 SCIENCE AS TED MICHAELS HAS 5068 02:46:16,303 --> 02:46:19,473 INDICATED. 5069 02:46:19,473 --> 02:46:20,740 AND IT ALLOWS THE GROUP THAT 5070 02:46:20,740 --> 02:46:22,476 WHEN WE HAVE QUERIES THAT 5071 02:46:22,476 --> 02:46:25,645 REQUIRE SURVEYS, THEY'RE VERY 5072 02:46:25,645 --> 02:46:26,480 RESPONSIVE. 5073 02:46:26,480 --> 02:46:27,380 TO GIVE YOU AN IDEA, THE 5074 02:46:27,380 --> 02:46:29,649 RESPONSE RATE WE GET IS CLOSE TO 5075 02:46:29,649 --> 02:46:30,217 7%. 5076 02:46:30,217 --> 02:46:33,186 MOST SURVEYS ONLY EXPECT ABOUT 5077 02:46:33,186 --> 02:46:35,622 30%. 5078 02:46:35,622 --> 02:46:37,157 BUT WHAT WE'RE PROUD OF OTHER 5079 02:46:37,157 --> 02:46:38,358 THAN THE SMILES YOU SEE ON 5080 02:46:38,358 --> 02:46:39,459 EVERYONE'S FACES HERE WHEN WE 5081 02:46:39,459 --> 02:46:41,761 GATHER IS THE DIVERSITY OF THE 5082 02:46:41,761 --> 02:46:42,529 GROUP. 5083 02:46:42,529 --> 02:46:45,465 THAT IS NOT SOMETHING THAT CAN 5084 02:46:45,465 --> 02:46:47,400 BE REPLICATED VERY EASILY IN OUR 5085 02:46:47,400 --> 02:46:48,401 FIELD OF MEDICINE. 5086 02:46:48,401 --> 02:46:50,704 AND MANY OF YOU ARE ALREADY 5087 02:46:50,704 --> 02:46:57,144 FAMILIAR WITH THIS DATA. 5088 02:46:57,144 --> 02:46:59,246 THERE IS LACK OF DIVERSITY IN 5089 02:46:59,246 --> 02:47:00,247 THE WORKFORCE AND ALSO IN 5090 02:47:00,247 --> 02:47:01,348 RHEUMATOLOGY AND THAT'S 5091 02:47:01,348 --> 02:47:04,518 NATIONWIDE, AND MANY OF THAT HAS 5092 02:47:04,518 --> 02:47:06,419 NOT CHANGED OVER THE PAST 5093 02:47:06,419 --> 02:47:06,987 CENTURY. 5094 02:47:06,987 --> 02:47:09,156 THIS HAS BEEN DOCUMENTED WITH 5095 02:47:09,156 --> 02:47:13,326 BLACK PHYSICIANS IN PARTICULAR, 5096 02:47:13,326 --> 02:47:15,562 EITHER AS A GROUP OR CATEGORIZED 5097 02:47:15,562 --> 02:47:16,530 BY GENDER AND THERE HAS BEEN AN 5098 02:47:16,530 --> 02:47:17,964 OVERALL DECLINE IN MALE 5099 02:47:17,964 --> 02:47:18,265 PHYSICIANS. 5100 02:47:18,265 --> 02:47:20,367 AND THE PROJECTIONS APPEAR THAT 5101 02:47:20,367 --> 02:47:21,935 IT REMAINS STATIC AT LEAST FOR A 5102 02:47:21,935 --> 02:47:23,904 NUMBER OF YEARS, AND ANY 5103 02:47:23,904 --> 02:47:26,840 INCREASE IN PHYSICIANS AND IN 5104 02:47:26,840 --> 02:47:28,275 ETHNIC MINORITY PHYSICIANS, AT 5105 02:47:28,275 --> 02:47:30,810 LEAST BY THE YEAR 2060, IS 5106 02:47:30,810 --> 02:47:32,345 PRIMARY GOING DOING FILLED BY 5107 02:47:32,345 --> 02:47:36,316 HISPANICS AND ASIANS. 5108 02:47:36,316 --> 02:47:37,617 AND THE REASON IT'S DUPLICATED 5109 02:47:37,617 --> 02:47:39,286 AT THE SOURCE IN MEDICAL 5110 02:47:39,286 --> 02:47:40,954 SCHOOLS, MEDICAL DEGREES GRANTED 5111 02:47:40,954 --> 02:47:42,455 FROM U.S. SCHOOLS OVER THE PAST 5112 02:47:42,455 --> 02:47:44,124 30 YEARS WHEREAS THERE'S BEEN 5113 02:47:44,124 --> 02:47:47,727 INCREASE IN FEMALES MAINLY DUE 5114 02:47:47,727 --> 02:47:49,229 TO INCREASE IN ASIANS, OVERALL 5115 02:47:49,229 --> 02:47:51,398 MEN ARE DECREASED IN MEDICAL 5116 02:47:51,398 --> 02:47:53,733 SCHOOLS AND THEY'RE STILL ON THE 5117 02:47:53,733 --> 02:47:55,702 REPRESENTATION IN THE ETHNIC 5118 02:47:55,702 --> 02:47:56,870 MINORITIES, BLACKS, HISPANICS, 5119 02:47:56,870 --> 02:47:59,372 NATIVE AMERICANS, AND FAR BELOW 5120 02:47:59,372 --> 02:48:01,775 THEIR RESPECTIVE PERCENTAGES IN 5121 02:48:01,775 --> 02:48:04,945 THE U.S. CENSUS. 5122 02:48:04,945 --> 02:48:07,514 THIS OCCURS FOR TWO REASONS, TWO 5123 02:48:07,514 --> 02:48:08,782 HISTORICAL ACTS. 5124 02:48:08,782 --> 02:48:09,583 ONE IS SEGREGATION. 5125 02:48:09,583 --> 02:48:11,751 AS EXPECTED, YOU KNOW THAT 5126 02:48:11,751 --> 02:48:13,954 BLACKS WERE BANNED IN THE SOUTH 5127 02:48:13,954 --> 02:48:15,288 AND DISCOURAGED IN THE NORTH 5128 02:48:15,288 --> 02:48:17,791 FROM SEEKING HIGHER EDUCATION, 5129 02:48:17,791 --> 02:48:18,992 AND THEREFORE HAD TO DEVELOP 5130 02:48:18,992 --> 02:48:21,194 THEIR OWN INSTITUTES OF 5131 02:48:21,194 --> 02:48:22,662 LEARNING, HISTORICALLY BLACK 5132 02:48:22,662 --> 02:48:23,330 COLLEGES PRIMARILY. 5133 02:48:23,330 --> 02:48:27,234 AND THE SECOND ACT, THE SECOND 5134 02:48:27,234 --> 02:48:29,202 ACT WAS THE FLEXNER REPORT, AND 5135 02:48:29,202 --> 02:48:31,238 IN THAT ONE, IN AN ATTEMPT TO 5136 02:48:31,238 --> 02:48:32,872 VALIDATE ALL MEDICAL SCHOOLS OF 5137 02:48:32,872 --> 02:48:37,244 WHICH THERE WERE 155, THE BLACK 5138 02:48:37,244 --> 02:48:38,211 SCHOOLS WITHOUT THE FUNDING 5139 02:48:38,211 --> 02:48:39,279 COULD NOT MAKE THOSE 5140 02:48:39,279 --> 02:48:39,913 ADJUSTMENTS, AND THEREFORE MANY 5141 02:48:39,913 --> 02:48:41,581 OF THEM WERE CLOSED, AND THIS 5142 02:48:41,581 --> 02:48:44,784 WAS SIGNIFICANT NOT FOR TEACHING 5143 02:48:44,784 --> 02:48:47,721 STUDENTS, BUT ALSO FOR PATIENT 5144 02:48:47,721 --> 02:48:48,922 CARE, BECAUSE IT NOT ONLY 5145 02:48:48,922 --> 02:48:50,657 PROVIDED CARE TO BLACK PATIENTS 5146 02:48:50,657 --> 02:48:52,459 BUT ALSO POOR RURAL WHITES. 5147 02:48:52,459 --> 02:48:57,931 AND THIS IS A SLIDE THAT SHOWS A 5148 02:48:57,931 --> 02:49:00,333 HYPOTHETICAL MODEL EXAMINED THE 5149 02:49:00,333 --> 02:49:01,167 WHAT IF. 5150 02:49:01,167 --> 02:49:04,437 AND THEY PRESUME THAT IF FIVE OF 5151 02:49:04,437 --> 02:49:05,405 THOSE 13 BLACK SCHOOLS HAD 5152 02:49:05,405 --> 02:49:07,307 REMAINED OPEN AND MET THOSE 5153 02:49:07,307 --> 02:49:08,975 CRITERIA OF VALIDATION, WE WOULD 5154 02:49:08,975 --> 02:49:11,811 HAVE ABOUT 35,000 MORE GRADUATES 5155 02:49:11,811 --> 02:49:12,212 IN 2019. 5156 02:49:12,212 --> 02:49:15,448 THAT'S ABOUT A 30% INCREASE IN 5157 02:49:15,448 --> 02:49:16,549 AFRICAN AMERICANS. 5158 02:49:16,549 --> 02:49:18,752 AND THE NEXT SLIDE WILL TELL US 5159 02:49:18,752 --> 02:49:20,587 WHAT HAS HAPPENED AS A RESULT OF 5160 02:49:20,587 --> 02:49:21,655 THAT, BECAUSE THAT IS HISTORY 5161 02:49:21,655 --> 02:49:25,458 AND THIS IS THE HERE AND NOW. 5162 02:49:25,458 --> 02:49:27,661 FROM THAT, WE HAVE TWO THAT WERE 5163 02:49:27,661 --> 02:49:33,333 LEFT, HOWARD UNIVERSITY AND M 5164 02:49:33,333 --> 02:49:37,170 MEHARY, AND SINCE THEN TWO MORE, 5165 02:49:37,170 --> 02:49:39,306 CHARLES R. DREW AND MOREHOUSE 5166 02:49:39,306 --> 02:49:43,643 SCHOOL OF MEDICINE IN ATLANTA. 5167 02:49:43,643 --> 02:49:45,078 THE NEXT SLIDE TELLS YOU WHAT WE 5168 02:49:45,078 --> 02:49:47,914 DID AT HOWARD UNIVERSITY. 5169 02:49:47,914 --> 02:49:50,917 AND AROUND 2009, WE WENT IN AND 5170 02:49:50,917 --> 02:49:52,552 SAID WE WANT EVERY RESIDENT TO 5171 02:49:52,552 --> 02:49:53,853 ROTATE IN OUR SPECIALTY. 5172 02:49:53,853 --> 02:49:55,822 WE REQUESTED TWO RESIDENTS AS 5173 02:49:55,822 --> 02:49:58,291 THEY DO FOR CARDIOLOGY. 5174 02:49:58,291 --> 02:49:59,726 FOR ADDED VALUE. 5175 02:49:59,726 --> 02:50:02,996 AND THEY HAD A STRUCTURED 5176 02:50:02,996 --> 02:50:04,998 ROTATION WITH FOUR OUTPATIENT 5177 02:50:04,998 --> 02:50:06,700 CLINICS, WEEKLY LECTURES AND 5178 02:50:06,700 --> 02:50:08,501 CONFERENCES, AND LIKE FIRST YEAR 5179 02:50:08,501 --> 02:50:10,470 FELLOW, THEY WERE ON THE CALL 5180 02:50:10,470 --> 02:50:11,671 SCHEDULE FOR INPATIENTS AND 5181 02:50:11,671 --> 02:50:11,971 OUTPATIENTS. 5182 02:50:11,971 --> 02:50:13,139 THESE RESIDENTS WOULD THEN 5183 02:50:13,139 --> 02:50:16,543 COMPETE TO PRESENT EF AT OUR 5184 02:50:16,543 --> 02:50:18,144 ANNUAL KENNETH AUSTIN 5185 02:50:18,144 --> 02:50:19,112 RHEUMATOLOGY SYMPOSIUM FOR THE 5186 02:50:19,112 --> 02:50:20,213 BEST PRESENTATION OF A CLINICAL 5187 02:50:20,213 --> 02:50:21,514 CASE FROM THE CLINIC. 5188 02:50:21,514 --> 02:50:23,516 AND OUR PRESENTER AT OUR 5189 02:50:23,516 --> 02:50:25,485 SYMPOSIUM THIS APRIL WAS A 5190 02:50:25,485 --> 02:50:29,322 ROTATING DERMATOLOGY RESIDENT. 5191 02:50:29,322 --> 02:50:31,191 THE NECTS SLADE SHOWS WHAT 5192 02:50:31,191 --> 02:50:31,791 HAPPENS -- WHAT HAPPENED FROM 5193 02:50:31,791 --> 02:50:33,393 THAT EFFORT. 5194 02:50:33,393 --> 02:50:34,728 AND OVER THE PAST FEW YEARS, WE 5195 02:50:34,728 --> 02:50:38,832 HAVE PRODUCED 15 ETHNIC MINORITY 5196 02:50:38,832 --> 02:50:40,133 RHEUMATOLOGIES TO THE WORKFORCE, 5197 02:50:40,133 --> 02:50:41,534 TAKING INTO MIND OUR 5198 02:50:41,534 --> 02:50:43,370 DENOMINATOR, IT'S THE MOST FROM 5199 02:50:43,370 --> 02:50:46,005 ANY SINGLE INSTITUTION. 5200 02:50:46,005 --> 02:50:47,540 AND THEY HAVE PERFORMED NO LESS 5201 02:50:47,540 --> 02:50:51,044 THAN EXPECTED, NOR THAN ANY 5202 02:50:51,044 --> 02:50:52,912 OTHER ETHNIC MINORITY CANDIDATE 5203 02:50:52,912 --> 02:50:55,582 OVER THE YEARS, AND A THIRD OF 5204 02:50:55,582 --> 02:50:57,250 THEM HAVE ENTERED THE ACADEMICS 5205 02:50:57,250 --> 02:50:57,650 FAIR. 5206 02:50:57,650 --> 02:51:02,722 SO THE QUESTION WAS WHETHER THIS 5207 02:51:02,722 --> 02:51:03,857 MODEL OF THIS ONE INSTITUTION 5208 02:51:03,857 --> 02:51:05,125 COULD BE TAKEN ELSEWHERE AND 5209 02:51:05,125 --> 02:51:06,659 LEAD TO SIMILAR EFFECTS, 5210 02:51:06,659 --> 02:51:08,895 INCREASING THE WORKFORCE AND 5211 02:51:08,895 --> 02:51:10,330 SPECIFICALLY IN ETHNIC 5212 02:51:10,330 --> 02:51:10,730 MINORITIES. 5213 02:51:10,730 --> 02:51:11,965 AND THE NEXT SLIDE SHOWS YOU 5214 02:51:11,965 --> 02:51:14,167 SUCH AN ENDEAVOR. 5215 02:51:14,167 --> 02:51:15,702 I'M PRIVILEGED TO BE INCLUDED AS 5216 02:51:15,702 --> 02:51:19,873 A COLLABORATOR ON THIS ARTHRITIS 5217 02:51:19,873 --> 02:51:20,774 FOUNDATION SPONSORED GRANT. 5218 02:51:20,774 --> 02:51:23,209 IT'S LED IN STELLAR FASHION BY 5219 02:51:23,209 --> 02:51:24,544 CANDACE FELDMAN AT THE BRIGHAM, 5220 02:51:24,544 --> 02:51:26,513 ALONG WITH A STAR CAST OF 5221 02:51:26,513 --> 02:51:28,148 EDUCATORS AND LEADERS, WHO AIM 5222 02:51:28,148 --> 02:51:30,784 TO BUILD A WEB-BASED PROGRAM TO 5223 02:51:30,784 --> 02:51:32,919 SUPPORT WORKFORCE EXPANSION 5224 02:51:32,919 --> 02:51:34,654 AIMED PRIMARILY AT INCREASING 5225 02:51:34,654 --> 02:51:37,290 ETHNIC MINORITY RECRUITMENT. 5226 02:51:37,290 --> 02:51:39,626 CALLED THE AWARD PROGRAM. 5227 02:51:39,626 --> 02:51:42,495 THE GROUP HAS -- THE GOALS ARE 5228 02:51:42,495 --> 02:51:44,431 AS LISTED HERE, TO FOSTER 5229 02:51:44,431 --> 02:51:46,433 COMMUNITY, TO COORDINATE 5230 02:51:46,433 --> 02:51:51,704 NATIONAL EFFORTS, AND CREATE A 5231 02:51:51,704 --> 02:51:57,510 DIVERSE RHEUM WORKFORCE, AND 5232 02:51:57,510 --> 02:51:58,878 QUANTIFIABLE METRICS OF 5233 02:51:58,878 --> 02:51:59,846 ACCOUNTABILITY. 5234 02:51:59,846 --> 02:52:02,148 I HAVE BEEN CHARGED WITH 5235 02:52:02,148 --> 02:52:03,550 DEVELOPING PILLAR 2, AND THE 5236 02:52:03,550 --> 02:52:05,552 GROUP CONSISTS OF A MEDICAL 5237 02:52:05,552 --> 02:52:06,586 STUDENT, RESIDENT AND ALLIED 5238 02:52:06,586 --> 02:52:07,687 HEALTH PROVIDER AS WELL. 5239 02:52:07,687 --> 02:52:10,423 IN MY CHARGE AS A PILLAR 5240 02:52:10,423 --> 02:52:12,225 2 LEADER, I HAVE TO DEVELOP 5241 02:52:12,225 --> 02:52:13,293 INFORMATIONAL TOOL KITS AND 5242 02:52:13,293 --> 02:52:15,929 PIPELINE OF OPPORTUNITIES, WHILE 5243 02:52:15,929 --> 02:52:24,070 PILLAR 1 IS LED BY -- AND WITH 5244 02:52:24,070 --> 02:52:25,605 WORK TO PILOT ADAPTATIONS IN THE 5245 02:52:25,605 --> 02:52:26,806 CURRICULUM TO INCREASE AWARENESS 5246 02:52:26,806 --> 02:52:29,609 OF SOCIAL AND RACIAL BARRIERS IN 5247 02:52:29,609 --> 02:52:31,478 ACHIEVES EQUITY AND MAKE THEM 5248 02:52:31,478 --> 02:52:33,446 DISEASE-SPECIFIC. 5249 02:52:33,446 --> 02:52:35,048 AND TO SENSITIZE ALL CANDIDATES 5250 02:52:35,048 --> 02:52:37,550 TO AREAS OF LEADERSHIP SO THAT 5251 02:52:37,550 --> 02:52:39,853 WHEN THEY ARE IN A POSITION SO 5252 02:52:39,853 --> 02:52:41,488 CHOSEN, THEY HAVE THE SKILLS TO 5253 02:52:41,488 --> 02:52:43,723 SEEK AND PERFORM THESE ROLES, 5254 02:52:43,723 --> 02:52:46,259 AND THIS PILLAR IS LED BY 5255 02:52:46,259 --> 02:52:47,660 VALERIE STONE, SO WE'RE VERY 5256 02:52:47,660 --> 02:52:48,428 EXCITED ABOUT THIS. 5257 02:52:48,428 --> 02:52:49,496 WE MEET WEEKLY. 5258 02:52:49,496 --> 02:52:51,130 WE'RE NOW IN THE PHASE ONE 5259 02:52:51,130 --> 02:52:51,898 INFRASTRUCTURE DEVELOPMENT AND 5260 02:52:51,898 --> 02:52:53,766 LOOK FORWARD TO ITS 5261 02:52:53,766 --> 02:52:55,368 DISSEMINATION AND EXPANSION IN 5262 02:52:55,368 --> 02:52:56,102 PHASE TWO. 5263 02:52:56,102 --> 02:52:57,437 BUT THE NEXT SLIDE SHOWS 5264 02:52:57,437 --> 02:52:59,405 SOMETHING ELSE THAT WAS OBVIOUS 5265 02:52:59,405 --> 02:53:01,374 FROM THAT GROUP OF RESIDENTS, 5266 02:53:01,374 --> 02:53:04,310 AND THAT IS THE NEXT INDICATOR 5267 02:53:04,310 --> 02:53:07,113 WAS THAT 50% OF THEM WERE WOMEN. 5268 02:53:07,113 --> 02:53:09,315 AND WE ARE EXPERIENCING AS THE 5269 02:53:09,315 --> 02:53:11,651 NEXT SLIDE SHOWS A SHIFT IN THE 5270 02:53:11,651 --> 02:53:12,519 GENDER DISTRIBUTION IN THE 5271 02:53:12,519 --> 02:53:15,154 WORKFORCE IN MEDICINE. 5272 02:53:15,154 --> 02:53:17,257 THE SPECIALTIES WITH THE HIGHEST 5273 02:53:17,257 --> 02:53:19,259 PERCENTAGE ARE PRIMARILY FOCUSED 5274 02:53:19,259 --> 02:53:20,560 ON CHILDREN AND WOMEN. 5275 02:53:20,560 --> 02:53:26,599 PEDIATRICS IS UP TO 64%, OB-GYN 5276 02:53:26,599 --> 02:53:28,134 59, ENDOCRINE NOLG 52, 5277 02:53:28,134 --> 02:53:29,702 DERMATOLOGY AT 50 AS IS FOR 5278 02:53:29,702 --> 02:53:33,640 RHEUMATOLOGY AND WAS THE CASE IN 5279 02:53:33,640 --> 02:53:37,710 MY RESIDENTS. 5280 02:53:37,710 --> 02:53:43,182 AS DR. CLAYTON SHOWED, OF THE 5281 02:53:43,182 --> 02:53:44,150 FEMALENESS OF THE DISEASE, SHE 5282 02:53:44,150 --> 02:53:46,152 WENT THROUGH THIS QUITE 5283 02:53:46,152 --> 02:53:46,753 ELOQUENTLY, THE TRANSITION OF 5284 02:53:46,753 --> 02:53:48,021 THE MALE MICE TO WOMEN AS IT 5285 02:53:48,021 --> 02:53:48,354 WERE. 5286 02:53:48,354 --> 02:53:52,258 AND I'D JUST LIKE TO ADD TO 5287 02:53:52,258 --> 02:53:55,194 FURTHER SUPPORT, IS THAT 5288 02:53:55,194 --> 02:53:56,729 ANTIBODIES TO THIS COMPLEX WHO 5289 02:53:56,729 --> 02:53:59,132 HAVE BEEN FOUND IN PATIENTS WITH 5290 02:53:59,132 --> 02:54:00,800 AUTOIMMUNE DISEASE, IT'S ABSENT 5291 02:54:00,800 --> 02:54:01,701 IN THOSE WITHOUT. 5292 02:54:01,701 --> 02:54:04,771 AND LIKE ALL DISCOVERIES AS 5293 02:54:04,771 --> 02:54:07,674 DR. BUCKNER SHOWED, IT SEEMS TO 5294 02:54:07,674 --> 02:54:09,309 BE A MULTI-POLICE ILTITY IS 5295 02:54:09,309 --> 02:54:14,147 MULTIPLICITY IS GOING TOGIVE USS 5296 02:54:14,147 --> 02:54:16,015 CERTAINLY EXPANDS THE POBLGHTS. 5297 02:54:16,015 --> 02:54:17,450 BECAUSE IT MAY PROVIDE 5298 02:54:17,450 --> 02:54:19,385 BIOMARKERS OR PROVIDE SOME AREAS 5299 02:54:19,385 --> 02:54:19,919 OR TARGETS FOR PREVENTION. 5300 02:54:19,919 --> 02:54:20,920 BUT WHERE WE HAVE MADE PROGRESS 5301 02:54:20,920 --> 02:54:22,255 IS IN FERTILITY AND PREGNANCY ON 5302 02:54:22,255 --> 02:54:26,960 THE NEXT SLIDE. 5303 02:54:26,960 --> 02:54:27,827 AND WE'VE DONE THIS BECAUSE WE 5304 02:54:27,827 --> 02:54:28,828 CAN DIAGNOSE DISEASES EARLIER 5305 02:54:28,828 --> 02:54:30,263 AND WE HAVE BETTER THERAPIES IF 5306 02:54:30,263 --> 02:54:33,299 WE CAN GET THEM TO THE PATIENT 5307 02:54:33,299 --> 02:54:34,867 AND THESE AUTHORS HAVE WORKED TO 5308 02:54:34,867 --> 02:54:36,836 PROVIDE THESE DATA. 5309 02:54:36,836 --> 02:54:37,937 BUT FIRST WE HAVE TO APPRECIATE 5310 02:54:37,937 --> 02:54:41,240 THAT WE PROBABLY ARE NOT DOING A 5311 02:54:41,240 --> 02:54:46,512 VERY GOOD JOB AT INCLUDING 5312 02:54:46,512 --> 02:54:47,080 DISCUSSIONS IN EDUCATION AND 5313 02:54:47,080 --> 02:54:49,949 CHILD BEARING, AND WE WERE USING 5314 02:54:49,949 --> 02:54:52,151 A CONTRACEPTIVE HISTORY AS A 5315 02:54:52,151 --> 02:54:53,686 SURROGATE OF THAT EFFORT. 5316 02:54:53,686 --> 02:55:02,562 I THINK WE'VE FAILED BECAUSE I - 5317 02:55:02,562 --> 02:55:04,530 THE TOPIC WE USE TO GET THAT 5318 02:55:04,530 --> 02:55:06,299 HISTORY WHEN WE'RE CONCERNED 5319 02:55:06,299 --> 02:55:09,636 ABOUT A TERATOGENIC MEDICATION, 5320 02:55:09,636 --> 02:55:11,070 AND IT'S EVEN WORSE COLLECTION 5321 02:55:11,070 --> 02:55:15,008 OF THIS DATA IN ETHNIC 5322 02:55:15,008 --> 02:55:15,441 MINORITIES. 5323 02:55:15,441 --> 02:55:18,344 A CREEKY JOINT SURVEY SHOWED 65% 5324 02:55:18,344 --> 02:55:24,584 OF WOMEN DID USE SOME FORMT OF 5325 02:55:24,584 --> 02:55:26,019 EFFECTIVE CONTRACEPTION BUT WHEN 5326 02:55:26,019 --> 02:55:27,920 THERE WAS NO CONTRACEPTION THIS 5327 02:55:27,920 --> 02:55:29,555 WAS MOSTLY THE PSORIATIC 5328 02:55:29,555 --> 02:55:30,223 ARTHRITIS PATIENTS. 5329 02:55:30,223 --> 02:55:31,591 THEREFORE IMPLYING THE 5330 02:55:31,591 --> 02:55:32,792 DISCUSSION IS NOT BEING HAD. 5331 02:55:32,792 --> 02:55:35,228 BUT WHEN THERE IS PREGNANCY AS 5332 02:55:35,228 --> 02:55:36,663 OCCURS IN LUPUS, THERE IS A 5333 02:55:36,663 --> 02:55:39,432 DOCUMENTED WORSE OUT COME AND 5334 02:55:39,432 --> 02:55:42,035 PARTICULARLY IN ETHNIC 5335 02:55:42,035 --> 02:55:42,669 MINORITIES. 5336 02:55:42,669 --> 02:55:45,705 PATIENT SAMPLE DATA OVER A 5337 02:55:45,705 --> 02:55:46,706 TWO-YEAR PERIOD AND 13,000 5338 02:55:46,706 --> 02:55:49,308 DELIVERIES SHOWED THAT THERE WAS 5339 02:55:49,308 --> 02:55:53,046 40% MORE CESAREAN SECTIONS 5340 02:55:53,046 --> 02:55:54,447 COMPARED TO THE 12 MILLION 5341 02:55:54,447 --> 02:55:56,482 WITHOUT LUPUS, AND IN ETHNIC 5342 02:55:56,482 --> 02:55:58,351 MINORITY PATIENTS, THE BLACKS 5343 02:55:58,351 --> 02:56:01,354 AND HISPANICS HAD TWICE AS MUCH 5344 02:56:01,354 --> 02:56:03,990 PRETERM LABOR AND 20% INCREASE 5345 02:56:03,990 --> 02:56:05,291 IN PREECLAMPSIA AND GESTATIONAL 5346 02:56:05,291 --> 02:56:08,261 HYPERTENSION. 5347 02:56:08,261 --> 02:56:09,662 SO IT IS CLEAR WE HAVE TO 5348 02:56:09,662 --> 02:56:10,630 EDUCATE PATIENTS ON THE BEST 5349 02:56:10,630 --> 02:56:11,731 OUTCOMES AND WE DO IN CLINIC AND 5350 02:56:11,731 --> 02:56:13,499 TRY TO TELL THAT THE BEST OUT 5351 02:56:13,499 --> 02:56:15,802 COME IS WHEN DISEASE IS 5352 02:56:15,802 --> 02:56:16,636 INACTIVE. 5353 02:56:16,636 --> 02:56:18,538 BUT WE KNOW THAT DOES NOT WORK 5354 02:56:18,538 --> 02:56:20,173 ALL THE TIME. 5355 02:56:20,173 --> 02:56:24,944 AND THE WORK OF CLOWSE IN 5356 02:56:24,944 --> 02:56:25,945 DEVELOPING THESE HEALTHY 5357 02:56:25,945 --> 02:56:28,114 OUTCOMES IN PREGNANCY WITH SLE 5358 02:56:28,114 --> 02:56:29,649 THROUGH EDUCATION, AND I'LL SAY 5359 02:56:29,649 --> 02:56:32,785 HERE WITH AND OF PROVIDERS, IS 5360 02:56:32,785 --> 02:56:34,854 VERY, VERY HELPFUL, AND SHE 5361 02:56:34,854 --> 02:56:39,625 DEVELOPED THIS AND PILOTED IT AT 5362 02:56:39,625 --> 02:56:41,928 ONE OF THE WOMEN IN RHEUMATOLOGY 5363 02:56:41,928 --> 02:56:42,462 MEETINGS. 5364 02:56:42,462 --> 02:56:43,930 AND IT HAS PROMOTED THE 5365 02:56:43,930 --> 02:56:45,331 EDUCATION OF RHEUMATOLOGISTS TO 5366 02:56:45,331 --> 02:56:47,033 UNDERSTAND AND EMBRACE THE 5367 02:56:47,033 --> 02:56:48,334 OVERWHELMING REPRODUCTIVE DESIRE 5368 02:56:48,334 --> 02:56:50,737 OF MOST OF OUR PATIENTS. 5369 02:56:50,737 --> 02:56:54,407 AND IF WE REPLACE DISEASE 5370 02:56:54,407 --> 02:56:56,309 REMISSION WITH GOOD PREGNANCY 5371 02:56:56,309 --> 02:56:58,111 OUT COME MOTHER AND CHILD AND 5372 02:56:58,111 --> 02:56:59,879 SERVE THAT AS A SURROGATE AND 5373 02:56:59,879 --> 02:57:01,714 HAVE THOSE DISCUSSIONS 5374 02:57:01,714 --> 02:57:04,417 REPEATEDLY AND PLAN ACCORDINGLY, 5375 02:57:04,417 --> 02:57:07,286 WE WILL GET BETTER DISEASE 5376 02:57:07,286 --> 02:57:09,088 ACTIVITY CONTROL AND BETTER 5377 02:57:09,088 --> 02:57:09,822 ADHERENCE OF MEDICATIONS. 5378 02:57:09,822 --> 02:57:12,859 WE CAN EDUCATE THEM ON ALL THESE 5379 02:57:12,859 --> 02:57:16,829 ASPECTS, AND THE NEXT LINK SHOWS 5380 02:57:16,829 --> 02:57:19,999 ACTUALLY HER WEBPAGE THAT'S VERY 5381 02:57:19,999 --> 02:57:21,768 USEFUL THAT I KEEP WITH ME IN 5382 02:57:21,768 --> 02:57:24,704 THE CLINIC TO FACILITATE THOSE 5383 02:57:24,704 --> 02:57:26,005 DISCUSSIONS AND TO TALK ABOUT 5384 02:57:26,005 --> 02:57:27,073 THE MEDICATIONS THAT ARE 5385 02:57:27,073 --> 02:57:32,211 APPROPRIATE. 5386 02:57:32,211 --> 02:57:33,880 BUT THE WORKFORCE IS OF WORRY TO 5387 02:57:33,880 --> 02:57:35,047 EVERYONE AND RHEUMATOLOGY IS NO 5388 02:57:35,047 --> 02:57:36,115 DIFFERENT AND THE DANGER ON THE 5389 02:57:36,115 --> 02:57:37,116 NEXT SLIDE SHOWS THIS. 5390 02:57:37,116 --> 02:57:39,385 AN ASSESSMENT OVER A 10-YEAR 5391 02:57:39,385 --> 02:57:40,586 PERIOD SHOWS THAT THERE MAY BE 5392 02:57:40,586 --> 02:57:44,290 GOOD NEWS, 23% EXPANSION IN 5393 02:57:44,290 --> 02:57:45,291 RHEUMATOLOGISTS, AND AN 5394 02:57:45,291 --> 02:57:46,659 EXPLOSION ACTUALLY OF THE 5395 02:57:46,659 --> 02:57:50,029 ADVANCED PRACTICE PROVIDERS. 5396 02:57:50,029 --> 02:57:51,798 BUT THE DEVIL IS IN THE DETAILS 5397 02:57:51,798 --> 02:57:54,033 IN THAT THERE IS ONLY ONE 5398 02:57:54,033 --> 02:57:56,869 RHEUMATOLOGIST FOR 30,000 5399 02:57:56,869 --> 02:57:59,772 PATIENTS, AND IN RURAL COUNTIES, 5400 02:57:59,772 --> 02:58:01,374 90% OF THEM HAVE NO 5401 02:58:01,374 --> 02:58:01,974 RHEUMATOLOGISTS AND IT'S NOT 5402 02:58:01,974 --> 02:58:03,409 THAT MUCH BETTER WITH URBAN 5403 02:58:03,409 --> 02:58:03,843 COUNTIES. 5404 02:58:03,843 --> 02:58:05,678 HALF OF THEM DON'T HAVE A 5405 02:58:05,678 --> 02:58:07,513 RHEUMATOLOGIST. 5406 02:58:07,513 --> 02:58:10,149 FURTHER, IT SEEMS THAT PEOPLE 5407 02:58:10,149 --> 02:58:11,784 LEAVE AND WHEN YOU LOOK AT THE 5408 02:58:11,784 --> 02:58:13,686 ABSOLUTE INCREASE IN NUMBERS 5409 02:58:13,686 --> 02:58:15,121 OVER THAT TIME PERIOD STATED, 5410 02:58:15,121 --> 02:58:17,190 IT'S ONLY A THOUSAND 5411 02:58:17,190 --> 02:58:17,957 RHEUMATOLOGISTS. 5412 02:58:17,957 --> 02:58:20,626 THE POPULATION HAS EXPANDED, AND 5413 02:58:20,626 --> 02:58:23,062 THAT NUMBER 5600 IF MY MEMORY 5414 02:58:23,062 --> 02:58:24,697 SERVES ME RIGHT WAS ABOUT THE 5415 02:58:24,697 --> 02:58:27,834 SAME NUMBER IN 2015 WHEN WE WERE 5416 02:58:27,834 --> 02:58:28,568 FOREWARNED THAT THERE WAS GOING 5417 02:58:28,568 --> 02:58:32,605 TO BE A WORKFORCE SHORTAGE. 5418 02:58:32,605 --> 02:58:34,540 SO IT SEEMS AS IF THERE'S AN 5419 02:58:34,540 --> 02:58:36,709 ATTRITION IN THE RANKS AND 43% 5420 02:58:36,709 --> 02:58:39,879 OF THEM ARE, IN FACT, FEMALES. 5421 02:58:39,879 --> 02:58:42,114 THEY LEAVE AT ABOUT AGE 62 YEARS 5422 02:58:42,114 --> 02:58:42,682 OF AGE. 5423 02:58:42,682 --> 02:58:45,651 AND MOST OF THEM WILL LEAVE IF 5424 02:58:45,651 --> 02:58:47,186 THEY'RE IN A BIG HEALTHCARE 5425 02:58:47,186 --> 02:58:47,620 SYSTEM. 5426 02:58:47,620 --> 02:58:48,955 SOMEHOW THAT DOESN'T WORK WELL. 5427 02:58:48,955 --> 02:58:51,257 AND MORE LIKELY TO STAY IN A 5428 02:58:51,257 --> 02:58:53,059 SMALLER PRACTICE, ONE TO TWO 5429 02:58:53,059 --> 02:58:55,027 INDIVIDUALS, AND IF THEY'RE 5430 02:58:55,027 --> 02:58:58,231 LOCATED IN THE SOUTH. 5431 02:58:58,231 --> 02:59:00,633 SO MEASURES HAVE TO BE HAD AND 5432 02:59:00,633 --> 02:59:03,135 INTERVENTIONS MADE, AND THE NEXT 5433 02:59:03,135 --> 02:59:04,937 SLIDE GIVES US A FEW POINTERS. 5434 02:59:04,937 --> 02:59:11,677 AND THAT WE HAVE TO LOOK OUT FOR 5435 02:59:11,677 --> 02:59:13,880 WORK-LIFE BALANCE, ROSETTA 5436 02:59:13,880 --> 02:59:14,547 STONE, THESE ARE SOME OF THE 5437 02:59:14,547 --> 02:59:15,214 STRATEGIES LISTED HERE. 5438 02:59:15,214 --> 02:59:16,282 THEY HAVE TO BE REAL AND THEY 5439 02:59:16,282 --> 02:59:17,516 HAVE TO BE ACTIVE. 5440 02:59:17,516 --> 02:59:21,287 AND THE SAME ATTRACTIVENESS OF 5441 02:59:21,287 --> 02:59:23,389 RHEUMATOLOGY TO WOMEN IS ALSO 5442 02:59:23,389 --> 02:59:25,791 SOME OF THE ATTRITION THAT TAKES 5443 02:59:25,791 --> 02:59:30,396 PLACE BECAUSE THEY ARE THE 5444 02:59:30,396 --> 02:59:31,564 DECISIONS TO HAVE FAMILY BUT 5445 02:59:31,564 --> 02:59:32,565 THEY SHOULDN'T BE PENALIZED FOR 5446 02:59:32,565 --> 02:59:33,099 THAT. 5447 02:59:33,099 --> 02:59:34,767 WE SHOULD HAVE WAYS OF HAVING 5448 02:59:34,767 --> 02:59:36,502 FLEXIBLE WORK OPTIONS, MAKING 5449 02:59:36,502 --> 02:59:41,007 ADAP TAI DAITIONS FOR CHILD CAR, 5450 02:59:41,007 --> 02:59:43,743 ESPECIALLY FOR SIX CHILDREN SICN 5451 02:59:43,743 --> 02:59:45,745 BECAUSE THAT'S WHO ACHES THEM TO 5452 02:59:45,745 --> 02:59:47,647 THE PHYSICIAN, AND WE ARE 5453 02:59:47,647 --> 02:59:48,614 REQUIRED TO HAVE LACTATION 5454 02:59:48,614 --> 02:59:49,582 FACILITIES, BUT WE HAVE TO HAVE 5455 02:59:49,582 --> 02:59:52,351 THEM FUNDED TO BE FUNCTIONAL 5456 02:59:52,351 --> 02:59:53,452 WITH REFRIGERATORS AND HYGIENE 5457 02:59:53,452 --> 02:59:55,288 AS WELL. 5458 02:59:55,288 --> 02:59:58,257 SO IT REQUIRES A LOT OF 5459 02:59:58,257 --> 03:00:00,226 ADAPTATIONS TO MAKE THIS WORK. 5460 03:00:00,226 --> 03:00:02,128 AND THE OTHER FACTOR THAT MIGHT 5461 03:00:02,128 --> 03:00:04,196 EFFECT SOME OF THE ATTRITION IS 5462 03:00:04,196 --> 03:00:06,165 THEY'RE WORKING HARD AS ANYONE 5463 03:00:06,165 --> 03:00:10,903 ELSE, AND THE NEXT SLIDE SHOWS A 5464 03:00:10,903 --> 03:00:12,004 RECALCITRANT PROBLEM WE'VE HAD, 5465 03:00:12,004 --> 03:00:14,307 AND THAT'S A DIFFERENCE IN 5466 03:00:14,307 --> 03:00:15,775 COMPENSATION BY GENDER. 5467 03:00:15,775 --> 03:00:17,710 AND THIS APPLIES TO RHEUMATOLOGY 5468 03:00:17,710 --> 03:00:20,913 BUT ALSO OTHER SPECIALTIES. 5469 03:00:20,913 --> 03:00:24,917 A SURVEY OF 29 -- 13,000 5470 03:00:24,917 --> 03:00:26,786 PHYSICIANS OVER A FOUR-YEAR 5471 03:00:26,786 --> 03:00:29,055 PERIOD EXCEPT FOR 2019 SHOWS 5472 03:00:29,055 --> 03:00:30,823 THERE WAS A PERSISTENT 17% 5473 03:00:30,823 --> 03:00:33,192 DIFFERENCE IN PAY, AND THAT'S 5474 03:00:33,192 --> 03:00:35,594 BEEN UNCHANGED SINCE THEN, AND 5475 03:00:35,594 --> 03:00:37,663 WE WONDER WHETHER THESE ARE EVEN 5476 03:00:37,663 --> 03:00:41,600 WORSE FOLLOWING THE COVID ERA. 5477 03:00:41,600 --> 03:00:42,668 WHAT HAPPENS OVER THE LIFETIME 5478 03:00:42,668 --> 03:00:44,003 OF A PHYSICIAN? 5479 03:00:44,003 --> 03:00:45,604 A FEMALE PHYSICIAN? 5480 03:00:45,604 --> 03:00:47,807 AND THE NEXT SLIDE SHOWS THAT 5481 03:00:47,807 --> 03:00:48,908 WITH WHITE MALES AS A REFERENCE. 5482 03:00:48,908 --> 03:00:50,309 AND MANY OF YOU ARE FAMILIAR 5483 03:00:50,309 --> 03:00:52,611 WITH THESE DATA, THE EQUAL 5484 03:00:52,611 --> 03:00:55,848 PAYDAY. 5485 03:00:55,848 --> 03:00:57,917 AND HERE IT SHOWS IF A WHITE 5486 03:00:57,917 --> 03:01:00,119 MALE FINISHES OR GETS INCOME AT 5487 03:01:00,119 --> 03:01:02,188 THAT TIME, THE AMOUNT OF 5488 03:01:02,188 --> 03:01:04,690 ADDITIONAL TIME, VARIOUS ETHNIC 5489 03:01:04,690 --> 03:01:06,892 SUBSETS OF FEMALES HAVE TO WORK 5490 03:01:06,892 --> 03:01:09,462 TO MEET AND MATCH HIS INCOME, 5491 03:01:09,462 --> 03:01:10,997 AND IF THEY'RE MOTHERS AS WELL, 5492 03:01:10,997 --> 03:01:12,732 THEY ALSO HAVE AN EXTENDED 5493 03:01:12,732 --> 03:01:13,733 PERIOD. 5494 03:01:13,733 --> 03:01:15,534 TRANSLATING THIS TO A LIFE OR A 5495 03:01:15,534 --> 03:01:18,337 CAREER IN PRACTICE, 40 YEARS, IT 5496 03:01:18,337 --> 03:01:20,639 MEANS THAT THEY'RE BEHIND 5497 03:01:20,639 --> 03:01:22,575 1.8 MILLION IN THEIR RETIREMENT 5498 03:01:22,575 --> 03:01:22,775 FUNDS. 5499 03:01:22,775 --> 03:01:25,644 OR THEY'LL HAVE TO WORK AN 5500 03:01:25,644 --> 03:01:26,412 ADDITIONAL 8.2 YEARS TO MATCH 5501 03:01:26,412 --> 03:01:29,148 THEIR INCOME. 5502 03:01:29,148 --> 03:01:31,917 AND IT TRICKLES OVER INTO 5503 03:01:31,917 --> 03:01:32,184 ACADEMIA. 5504 03:01:32,184 --> 03:01:33,052 AND THE NEXT SLIDE WILL SHOW 5505 03:01:33,052 --> 03:01:36,088 SOME OF THESE DATA, WHERE THERE 5506 03:01:36,088 --> 03:01:38,057 IS ALSO A DIFFERENCE EVEN AS WE 5507 03:01:38,057 --> 03:01:39,592 APPROACH 50/50 IN THE WORKFORCE 5508 03:01:39,592 --> 03:01:43,429 IN RHEUMATOLOGY. 5509 03:01:43,429 --> 03:01:45,331 AND AT THE HIGHER RANKS, THERE'S 5510 03:01:45,331 --> 03:01:46,999 DEFINITELY FEWER WOMEN IN THOSE 5511 03:01:46,999 --> 03:01:48,200 POSITIONS, THEY'RE ALSO IN FEWER 5512 03:01:48,200 --> 03:01:53,105 ROLES OF LEADERSHIP, SUCH AS -- 5513 03:01:53,105 --> 03:01:54,407 SIMILARLY WHEN WE DID TO 5514 03:01:54,407 --> 03:01:56,042 RESEARCH WHEN WE WANT TO GET 5515 03:01:56,042 --> 03:01:58,577 MORE WOMEN IN TO SEEK ANSWERS, 5516 03:01:58,577 --> 03:02:00,713 50% OF THEM HAVE LESS 5517 03:02:00,713 --> 03:02:01,781 AUTHORSHIP, EITHER SENIOR OR 5518 03:02:01,781 --> 03:02:04,016 FIRST AUTHOR, AND ALSO IN 5519 03:02:04,016 --> 03:02:05,885 ACHIEVING ANY GRANTS INCLUDING 5520 03:02:05,885 --> 03:02:06,952 NIH FUNDING. 5521 03:02:06,952 --> 03:02:08,687 SO THE THING IS, JUST LIKE OUR 5522 03:02:08,687 --> 03:02:10,656 DISEASES WHERE WE SEEK VARIABLES 5523 03:02:10,656 --> 03:02:12,391 TO MAKE DIAGNOSIS AND MEASURE 5524 03:02:12,391 --> 03:02:14,060 EFFICACY, WE HAVE TO DO THE SAME 5525 03:02:14,060 --> 03:02:16,328 WITH ANY DISPARITY AND GENDER 5526 03:02:16,328 --> 03:02:16,529 BIAS. 5527 03:02:16,529 --> 03:02:19,065 WE HAVE TO ACKNOWLEDGE IT 5528 03:02:19,065 --> 03:02:21,700 EXISTS, SEEK MEASURES -- SEEK 5529 03:02:21,700 --> 03:02:24,270 VARIABLES OF MEASUREMENT, AND 5530 03:02:24,270 --> 03:02:26,038 ALSO ANALYZE OUR ORGANIZATIONAL 5531 03:02:26,038 --> 03:02:26,972 STRUCTURE. 5532 03:02:26,972 --> 03:02:28,541 TO IDENTIFY POINTS OF INEQUITY 5533 03:02:28,541 --> 03:02:32,344 AND SEE WHERE ANY EVALUATION 5534 03:02:32,344 --> 03:02:33,145 PROCESS CAN BE INSTITUTED AND 5535 03:02:33,145 --> 03:02:34,346 REVIEW ANY POLICIES THAT NEED TO 5536 03:02:34,346 --> 03:02:38,517 BE CHANGED. 5537 03:02:38,517 --> 03:02:40,052 BUT WHILE AT HOWARD I DISCOVERED 5538 03:02:40,052 --> 03:02:42,421 SOMETHING ELSE AS WELL. 5539 03:02:42,421 --> 03:02:45,257 THE NEXT SLIDE TELLS YOU AS I 5540 03:02:45,257 --> 03:02:46,659 PONDERED WHAT COULD BE DONE TO 5541 03:02:46,659 --> 03:02:53,099 INCLUDE ON THE NEXT SLIDE, THESE 5542 03:02:53,099 --> 03:02:54,500 ARE THE ONES EXISTING AT THAT 5543 03:02:54,500 --> 03:02:56,135 TIME. 5544 03:02:56,135 --> 03:03:05,511 OVERALL, FEW OF THEM -- 5545 03:03:05,511 --> 03:03:08,447 COREVITAS, PREVIOUSLY 5546 03:03:08,447 --> 03:03:11,517 CORONAVIRUS, HAD VERY FEW. 5547 03:03:11,517 --> 03:03:17,623 THE CLEAR DATABASE PRIMARILY 5548 03:03:17,623 --> 03:03:19,358 DEALT WITH EARLY RA AND WAS 5549 03:03:19,358 --> 03:03:20,426 FOCUSED OND GENETICS AND WAS 5550 03:03:20,426 --> 03:03:21,260 REGIONAL. 5551 03:03:21,260 --> 03:03:22,761 AND THE NATIONAL DATABASE HAD NO 5552 03:03:22,761 --> 03:03:25,231 OTHER DATA EXCEPT THOSE ENTERED 5553 03:03:25,231 --> 03:03:27,733 BY THE PATIENTS. 5554 03:03:27,733 --> 03:03:29,068 SO UNDER THE UMBRELLA OF HOWARD 5555 03:03:29,068 --> 03:03:32,771 AND THE NEXT SLIDE IT DEVELOPED 5556 03:03:32,771 --> 03:03:34,573 ANOTHER REGISTRY CALLED THE 5557 03:03:34,573 --> 03:03:35,908 ETHNIC MINORITY RHEUMATOID 5558 03:03:35,908 --> 03:03:37,443 ARTHRITIS CORE SORE SHUM. 5559 03:03:37,443 --> 03:03:40,012 THERE WERE EIGHT MEMBERS WHO 5560 03:03:40,012 --> 03:03:42,548 STEPPED UP AND THEY SAW 5561 03:03:42,548 --> 03:03:44,550 PRIMARILY ETHNIC MINORITY 5562 03:03:44,550 --> 03:03:44,817 PATIENTS. 5563 03:03:44,817 --> 03:03:47,086 FOUR OF THOSE CENTERS WERE 5564 03:03:47,086 --> 03:03:49,054 ACADEMIC, FOUR WERE IN PRIVATE 5565 03:03:49,054 --> 03:03:49,488 PRACTICE. 5566 03:03:49,488 --> 03:03:51,257 AND WE COLLECTED ONLY CLINICAL 5567 03:03:51,257 --> 03:03:53,726 DATA, NO SEROUS SAMPLES, AND WE 5568 03:03:53,726 --> 03:03:55,561 AIMED TO HAVE A MINIMUM OF TWO 5569 03:03:55,561 --> 03:03:57,897 OUTPATIENT VISITS A YEAR BUT AS 5570 03:03:57,897 --> 03:03:59,765 MANY AS POSSIBLE. 5571 03:03:59,765 --> 03:04:04,003 AT THE END OF THE DAY, WE HAD 5572 03:04:04,003 --> 03:04:06,172 ABOUT -- WITH ALMOST COMPLETE 5573 03:04:06,172 --> 03:04:07,373 DATASET, 1500 PATIENTS AND ENDED 5574 03:04:07,373 --> 03:04:11,610 UP WITH ABOUT 40% WHITES, 30% 5575 03:04:11,610 --> 03:04:13,812 BLACKS, 13% HISPANICS AND 10% 5576 03:04:13,812 --> 03:04:15,548 ASIANS, AND THIS IS ONE OF THE 5577 03:04:15,548 --> 03:04:18,384 FEW CORE HORTS ACTUALLY FOR 5578 03:04:18,384 --> 03:04:19,919 RHEUMATOID ARTHRITIS THAT HAS 5579 03:04:19,919 --> 03:04:23,389 SUCH A DIVERSE CLIENTELE. 5580 03:04:23,389 --> 03:04:24,790 THE NEXT SLIDE SHOWS SOME OF OUR 5581 03:04:24,790 --> 03:04:28,527 FINDINGS OVER THE YEAR, YEAR, E 5582 03:04:28,527 --> 03:04:30,029 WERE ABLE TO VALIDATE WHAT WAS 5583 03:04:30,029 --> 03:04:32,331 REPORTED BY MANY OTHERS, SUCH AS 5584 03:04:32,331 --> 03:04:35,134 THAT BLACKS AND HISPANICS HAVE 5585 03:04:35,134 --> 03:04:36,202 ESTABLISHED DISEASE, LESS 5586 03:04:36,202 --> 03:04:37,603 EDUCATION, BUT ALSO ENDORSE THE 5587 03:04:37,603 --> 03:04:42,007 FACT THAT ACROSS VARIOUS -- THAT 5588 03:04:42,007 --> 03:04:47,279 ALL PATIENTS WE SAW IN THE REAL 5589 03:04:47,279 --> 03:04:50,749 WORLD RARELY MET A RANDOMIZED 5590 03:04:50,749 --> 03:04:52,952 CONTROL TRIAL ENTRY CRITERIA, 5591 03:04:52,952 --> 03:04:55,221 LESS THAN 5%. 5592 03:04:55,221 --> 03:05:00,226 BUT WE WERE ALSO ABLE TO AT -- 5593 03:05:00,226 --> 03:05:02,428 BUT LED TO MORE PROGRESSION OF 5594 03:05:02,428 --> 03:05:05,064 THAT DISEASE. 5595 03:05:05,064 --> 03:05:07,533 AND VULNERABILITY NOT ONLY 5596 03:05:07,533 --> 03:05:08,467 DELAYED DIAGNOSIS AND TREATMENT 5597 03:05:08,467 --> 03:05:18,978 BUT IT WAS ALSO ARE -- RODOLFO 5598 03:05:24,817 --> 03:05:26,051 PEREZ-ALAMINO WAS ABLE TO 5599 03:05:26,051 --> 03:05:29,555 DEMONSTRATE THERE WAS SOME -- 5600 03:05:29,555 --> 03:05:31,757 BETWEEN TOBACCO ABUSE AND ETHNIC 5601 03:05:31,757 --> 03:05:34,260 MINORITY STATUS. 5602 03:05:34,260 --> 03:05:36,128 ALL WHAT WE CONTINUALLY DESCRIBE 5603 03:05:36,128 --> 03:05:37,396 ABOUT DISPARITY, WE USE THIS 5604 03:05:37,396 --> 03:05:39,465 INFORMATION TO ACT. 5605 03:05:39,465 --> 03:05:41,900 AND WE DID DO THINGS, AND THAT 5606 03:05:41,900 --> 03:05:45,337 WAS A WEB-BASED PROGRAM TO ALLOW 5607 03:05:45,337 --> 03:05:49,708 EARLIER REFERRAL, FILL IN THE 5608 03:05:49,708 --> 03:05:56,849 CRITERIA FOR RHEUMATOID 5609 03:05:56,849 --> 03:05:57,816 ARTHRITIS, THE RESULT, WE SAW 5610 03:05:57,816 --> 03:05:59,451 THEM WITHIN TWO WEEKS COMPARED 5611 03:05:59,451 --> 03:05:59,985 TO FOUR MONTHS. 5612 03:05:59,985 --> 03:06:02,621 THAT WAS ROUTINE. 5613 03:06:02,621 --> 03:06:05,591 75% OF THE PATIENTS WE SAW GOT 5614 03:06:05,591 --> 03:06:10,162 THEIR DMARD AT THE FIRST VISIT, 5615 03:06:10,162 --> 03:06:11,830 100% IN THE YEAR, AND BY 12 5616 03:06:11,830 --> 03:06:14,133 MONTHS, ONLY 20% OF THEM WERE ON 5617 03:06:14,133 --> 03:06:14,767 PREDNISONE. 5618 03:06:14,767 --> 03:06:15,734 SOMETHING WE'RE ALL TRYING TO 5619 03:06:15,734 --> 03:06:18,203 REDUCE IN OUR PRACTICE. 5620 03:06:18,203 --> 03:06:20,139 THE NEXT THING WE DID ON THE 5621 03:06:20,139 --> 03:06:22,875 NEXT CLICK WAS TO FOCUS ON 5622 03:06:22,875 --> 03:06:25,411 EDUCATING PATIENTS AND THE 5623 03:06:25,411 --> 03:06:28,447 IMPORTANCE OF TREE TO TARGET AS 5624 03:06:28,447 --> 03:06:30,416 YOU DO FOR DIABETES OR 5625 03:06:30,416 --> 03:06:31,150 HYPERTENSION. 5626 03:06:31,150 --> 03:06:33,352 BY USING A PATIENT NAVIGATOR, WE 5627 03:06:33,352 --> 03:06:34,887 EDUCATED THEM SO THEY COULD 5628 03:06:34,887 --> 03:06:35,487 UNDERSTAND THE NEED TO CHANGE 5629 03:06:35,487 --> 03:06:36,722 MEDICINE IF THIS WAS NOT 5630 03:06:36,722 --> 03:06:37,856 ACHIEVED. 5631 03:06:37,856 --> 03:06:38,691 THE RESULT? 5632 03:06:38,691 --> 03:06:40,359 WE HAD SIGNIFICANT IMPROVEMENT 5633 03:06:40,359 --> 03:06:42,161 IN DISEASE ACTIVITY. 5634 03:06:42,161 --> 03:06:44,463 50% CHANGED THEIR MEDICATION TO 5635 03:06:44,463 --> 03:06:45,030 ACHIEVE THIS. 5636 03:06:45,030 --> 03:06:47,166 BUT WE REALIZED ANOTHER THING, 5637 03:06:47,166 --> 03:06:50,903 THAT THIS PATIENT EDUCATION 5638 03:06:50,903 --> 03:06:51,870 INTERACTION UNDERSCORED THE 5639 03:06:51,870 --> 03:06:53,405 IMPORTANCE OF TRUST BETWEEN 5640 03:06:53,405 --> 03:06:55,474 PHYSICIAN AND PATIENT IN 5641 03:06:55,474 --> 03:07:00,279 ACHIEVING A GOOD OUTCOME. 5642 03:07:00,279 --> 03:07:03,148 THE NEXT SLIDE SHOWS OUR FINAL 5643 03:07:03,148 --> 03:07:05,317 MANUSCRIPT ON ALL DATA, AND WE 5644 03:07:05,317 --> 03:07:07,252 WANTED TO LOOK AT SOMETHING 5645 03:07:07,252 --> 03:07:08,887 DIFFERENT AND USING THE FOUR 5646 03:07:08,887 --> 03:07:10,122 ETHNIC SUBSETS. 5647 03:07:10,122 --> 03:07:11,557 THIS IS A MANUSCRIPT CURRENTLY 5648 03:07:11,557 --> 03:07:12,825 UNDER REVIEW AND WE SPOKE TO HOW 5649 03:07:12,825 --> 03:07:15,260 WE MAKE DECISIONS TO TREAT 5650 03:07:15,260 --> 03:07:17,629 PATIENTS UNDER DISEASE MEASURES. 5651 03:07:17,629 --> 03:07:20,566 AND WE FOUND THAT WHEN WE BUNDLE 5652 03:07:20,566 --> 03:07:22,868 DISEASE ACTIVITY MEASURES AND 5653 03:07:22,868 --> 03:07:24,937 INCLUDED A LAB VALUE, THAT MORE 5654 03:07:24,937 --> 03:07:26,505 PEOPLE WERE IN REMISSION. 5655 03:07:26,505 --> 03:07:29,341 IN CONTRAST TO WHAT IS USUALLY 5656 03:07:29,341 --> 03:07:31,610 USED IN THE OFFICE, THE 5657 03:07:31,610 --> 03:07:32,177 CONVENIENT PATIENT-REPORTED 5658 03:07:32,177 --> 03:07:34,580 MEASURE ALONE, AND MAYBE WE NEED 5659 03:07:34,580 --> 03:07:36,448 TO REVIEW THAT. 5660 03:07:36,448 --> 03:07:38,617 AND ALSO NO MATTER WHAT WE USED, 5661 03:07:38,617 --> 03:07:41,220 THE BLACK PARTICIPANTS WERE LESS 5662 03:07:41,220 --> 03:07:43,188 FREQUENTLY IN REMISSION ACROSS 5663 03:07:43,188 --> 03:07:45,791 ALL STATES, ALL MEASURES, AND 5664 03:07:45,791 --> 03:07:47,426 THEY ARE THE ONES ACTUALLY THAT 5665 03:07:47,426 --> 03:07:49,661 MET THE RANDOMIZED CONTROL TRIAL 5666 03:07:49,661 --> 03:07:52,131 INCLUSIONS. 5667 03:07:52,131 --> 03:07:53,832 SO WE SUGGESTED THAT THERE 5668 03:07:53,832 --> 03:07:55,300 SHOULD BE SOME STANDARDIZATION 5669 03:07:55,300 --> 03:07:57,669 OF R.A. MEASURES IN ETHNIC 5670 03:07:57,669 --> 03:08:00,406 MINORITIES BECAUSE IT'S SO 5671 03:08:00,406 --> 03:08:01,940 IMPORTANT TO DETERMINE THERAPY 5672 03:08:01,940 --> 03:08:04,143 AND ALSO TELLS US THAT THEY CAN 5673 03:08:04,143 --> 03:08:06,311 ACTUALLY QUALIFY FOR TRIALS. 5674 03:08:06,311 --> 03:08:08,280 ONE OF THE CHALLENGES IN TRYING 5675 03:08:08,280 --> 03:08:10,182 TO MAKE INTERVENTIONS IS TO 5676 03:08:10,182 --> 03:08:10,916 RECOGNIZE WHAT YOU CAN CHANGE 5677 03:08:10,916 --> 03:08:15,154 AND WHAT YOU CAN'T CHANGE, AND 5678 03:08:15,154 --> 03:08:15,921 SOME OF THESE DISPARITIES, 5679 03:08:15,921 --> 03:08:18,457 HOWEVER, ARE OF OUR OWN 5680 03:08:18,457 --> 03:08:18,757 CREATION. 5681 03:08:18,757 --> 03:08:21,260 AND THE NEXT SLIDE SHOWS THAT 5682 03:08:21,260 --> 03:08:22,828 SOMETIMES IT'S THE SYSTEM AND 5683 03:08:22,828 --> 03:08:25,631 THE HEALTH SYSTEM, AND HERE I 5684 03:08:25,631 --> 03:08:27,399 WANTED TO SEE WHETHER RACE ALONE 5685 03:08:27,399 --> 03:08:29,668 WAS A DETERMINANT OR ASSOCIATED 5686 03:08:29,668 --> 03:08:30,702 WITH UTILIZATION OF BIOLOGIC 5687 03:08:30,702 --> 03:08:32,938 THERAPY. 5688 03:08:32,938 --> 03:08:34,907 AND I CHOSE THE RELATIVELY PRY 5689 03:08:34,907 --> 03:08:43,749 VAT SEPRIVATE SECTOR AND VA SYS, 5690 03:08:43,749 --> 03:08:45,617 RELATIVELY UNGETTERS CARE 5691 03:08:45,617 --> 03:08:47,986 TREATMENTS, ACCESS TO CARE AT 5692 03:08:47,986 --> 03:08:49,421 THE TIME, WE DIDN'T HAVE A 5693 03:08:49,421 --> 03:08:51,290 PREFERRED BIOLOGIC FORMULARY 5694 03:08:51,290 --> 03:08:53,225 THEN AND WE FOLLOWED DISEASE 5695 03:08:53,225 --> 03:08:53,659 TREATMENT GUIDELINE. 5696 03:08:53,659 --> 03:08:56,728 I WAS SURPRISED TO FIND OUT WE 5697 03:08:56,728 --> 03:08:57,930 PARSED INDIVIDUALS ONLY BY THEIR 5698 03:08:57,930 --> 03:08:59,865 RACE, THERE WAS ACTUALLY NO 5699 03:08:59,865 --> 03:09:02,734 DIFFERENCE. 5700 03:09:02,734 --> 03:09:06,772 EQUAL, EITHER PREDNISONE, A 5701 03:09:06,772 --> 03:09:08,106 DMARD OR BIOLOGIC THERAPY. 5702 03:09:08,106 --> 03:09:10,909 WHEN I PUT THEM BACK INTO THEIR 5703 03:09:10,909 --> 03:09:11,777 SYSTEM, HOWEVER, THAT'S WHERE 5704 03:09:11,777 --> 03:09:13,545 THE DISPARITIES OCCURRED. 5705 03:09:13,545 --> 03:09:15,347 THE NEXT SLIDE SHOWS THAT THERE 5706 03:09:15,347 --> 03:09:18,350 WAS DIFFERENCES BETWEEN THEM, 5707 03:09:18,350 --> 03:09:20,853 WITHIN THEIR SYSTEMS, BUT 5708 03:09:20,853 --> 03:09:22,154 THROUGH THE QUESTION BEING ASKED 5709 03:09:22,154 --> 03:09:24,122 ABOUT UTILIZATION OF BIOLOGICS, 5710 03:09:24,122 --> 03:09:26,959 IT APPEARED THAT IN THE PRIVATE 5711 03:09:26,959 --> 03:09:29,027 SECTOR, THERE'S TWICE AS MUCH 5712 03:09:29,027 --> 03:09:32,064 USE IN CAUCASIANS COMPARED TO 5713 03:09:32,064 --> 03:09:33,732 CAUCASIANS IN THE V.A., AND 5714 03:09:33,732 --> 03:09:35,100 SIMILAR USE, MORE INCREASED USE 5715 03:09:35,100 --> 03:09:38,770 IN THE NON-CAUCASIANS BUT WAS 5716 03:09:38,770 --> 03:09:43,642 NOT STA T STATISTICALLY SIGNIFI. 5717 03:09:43,642 --> 03:09:44,276 THE CLEAR LIMITATION HERE IS 5718 03:09:44,276 --> 03:09:46,144 THAT WE DID NOT HAVE 5719 03:09:46,144 --> 03:09:47,913 SOCIOECONOMIC STATUS, 5720 03:09:47,913 --> 03:09:49,882 COMORBIDITIES AND THIS WAS NOT 5721 03:09:49,882 --> 03:09:51,383 ALGORITHMIC TREATMENT IN EITHER 5722 03:09:51,383 --> 03:09:51,950 GROUP. 5723 03:09:51,950 --> 03:09:55,320 AND WE DIDN'T CALL OUT -- BUT 5724 03:09:55,320 --> 03:09:57,289 WHAT IT DID SHOW HOWEVER IN A 5725 03:09:57,289 --> 03:09:58,357 SYSTEM THAT DIDN'T HAVE TO GO 5726 03:09:58,357 --> 03:10:05,998 THROUGH THE RIGORS OR BA BA BARS 5727 03:10:05,998 --> 03:10:07,799 OF ACCESS TO PIE LO JIX THAT 5728 03:10:07,799 --> 03:10:09,701 THERE WAS NOT OVER UTILIZATION 5729 03:10:09,701 --> 03:10:10,769 OF BIOLOGIC THERAPY. 5730 03:10:10,769 --> 03:10:12,538 WHICH BY THE WAY THERE WAS 5731 03:10:12,538 --> 03:10:14,072 EQUIVALENT DISEASE ACTIVITY 5732 03:10:14,072 --> 03:10:14,606 BETWEEN THESE TWO GROUPS. 5733 03:10:14,606 --> 03:10:16,275 SO AT THE END OF DAY I MUST SAY 5734 03:10:16,275 --> 03:10:18,343 I WAS SCRATCHING MY HEAD MOST OF 5735 03:10:18,343 --> 03:10:19,444 THE TIME TO SEE WHAT I COULD DO 5736 03:10:19,444 --> 03:10:20,946 TO MAKE THINGS BETTER, AND THE 5737 03:10:20,946 --> 03:10:22,814 NEXT SLIDE SHOWS MY CONCLUSION, 5738 03:10:22,814 --> 03:10:30,722 THAT IT'S REALLY COMPLICATED. 5739 03:10:30,722 --> 03:10:35,460 ALL OF THESE VARIOUS VARIAB 5740 03:10:35,460 --> 03:10:36,828 VARIABLES -- SO I WONDERED IF 5741 03:10:36,828 --> 03:10:38,030 THERE WERE OTHERS WHO HAD THE 5742 03:10:38,030 --> 03:10:41,099 SAME EXPERIENCES I WAS HAVING, 5743 03:10:41,099 --> 03:10:42,200 AND IN DIFFERENT AREAS OF THE 5744 03:10:42,200 --> 03:10:44,903 COUNTRY. 5745 03:10:44,903 --> 03:10:48,373 SO I SORT OF PULLED OUT, ZOOMED 5746 03:10:48,373 --> 03:10:49,808 OUT AND TOOK A DRONE VIEW OF 5747 03:10:49,808 --> 03:10:52,844 THINGS, AND THE NEXT SLIDE SHOWS 5748 03:10:52,844 --> 03:10:56,181 THAT -- I PULLED ON THE 5749 03:10:56,181 --> 03:10:57,783 ASSOCIATION OF WOMEN IN 5750 03:10:57,783 --> 03:10:59,318 RHEUMATOLOGY TO SEE THEIR 5751 03:10:59,318 --> 03:11:00,285 INTEREST, AND THE ISSUE HERE WAS 5752 03:11:00,285 --> 03:11:02,487 TO SEE WHETHER THE PATIENTS I 5753 03:11:02,487 --> 03:11:07,726 WAS SEEING, WHETHER THEY WERE 5754 03:11:07,726 --> 03:11:09,461 SEEING A SIMILAR PROFILE IN 5755 03:11:09,461 --> 03:11:15,133 MEETING THAT TASK WERE ASSIGNED 5756 03:11:15,133 --> 03:11:16,702 BY OUR COLLEGE AND THAT WAS 5757 03:11:16,702 --> 03:11:20,505 DISEASE REMISSION IN RHEUMATOID 5758 03:11:20,505 --> 03:11:21,440 ARTHRITIS, WHERE WE'RE ALL AT 5759 03:11:21,440 --> 03:11:26,979 THE SAME STARTING POINT. 5760 03:11:26,979 --> 03:11:28,814 HUGE REGISTRY OF 190 SITE ACROSS 5761 03:11:28,814 --> 03:11:31,583 THE COUNTRY, ABOUT 180,000 5762 03:11:31,583 --> 03:11:38,090 ENTRIES, AND WE DID THE SO 5763 03:11:38,090 --> 03:11:40,525 CONCENTRATION OF HIGH DISEASE 5764 03:11:40,525 --> 03:11:42,361 ACTIVITY, CRITICAL MORBIDITY AND 5765 03:11:42,361 --> 03:11:43,962 VULNERABLE PATIENTS IN THE SOUTH 5766 03:11:43,962 --> 03:11:45,864 PRACTICES AND MOST OF THEM ARE 5767 03:11:45,864 --> 03:11:47,733 COVERED ACTUALLY BY MEDICARE AND 5768 03:11:47,733 --> 03:11:53,105 MEDICAID, AND THEN WE UN -- ON 5769 03:11:53,105 --> 03:11:53,872 THE NEXT SLADE, WE FOUND THAT 5770 03:11:53,872 --> 03:11:57,609 VERY FEW PRACTICES TO BEGIN WITH 5771 03:11:57,609 --> 03:11:58,577 SAW MEDICAID PATIENTS AND THOSE 5772 03:11:58,577 --> 03:12:02,914 THAT DID ONLY ABOUT 20 -- TALLLY 5773 03:12:02,914 --> 03:12:05,217 10% OF THOSE PRACTICING SITES 5774 03:12:05,217 --> 03:12:07,853 CARE FOR MORE THAN 50% OF THOSE 5775 03:12:07,853 --> 03:12:08,854 PATIENTS. 5776 03:12:08,854 --> 03:12:10,656 SO IN THE NEXT SLIDE, WE CALL 5777 03:12:10,656 --> 03:12:13,625 THIS A MISMATCH IN CARE IN RAM 5778 03:12:13,625 --> 03:12:16,828 TOYED ARTHRITIS. 5779 03:12:16,828 --> 03:12:17,729 RHEUMATOID ARTHRITIS IN THAT 5780 03:12:17,729 --> 03:12:19,765 MUCH WAS BEING ASKED OF THE VERY 5781 03:12:19,765 --> 03:12:22,367 FEW WHO SAW THESE VULNERABLE, 5782 03:12:22,367 --> 03:12:23,001 COMPLICATED CO-MORBID PATIENTS. 5783 03:12:23,001 --> 03:12:24,936 AND IT CLEARLY NEEDS AN 5784 03:12:24,936 --> 03:12:26,838 EXPANSION OF MEDICAID 5785 03:12:26,838 --> 03:12:29,074 REIMBURSEMENT OF MEDICAID, AND 5786 03:12:29,074 --> 03:12:31,076 SOME BILLING MODIFICATIONS FOR 5787 03:12:31,076 --> 03:12:33,345 THAT INDIVIDUAL PRACTICE, THAT 5788 03:12:33,345 --> 03:12:35,113 PRACTITIONER, WHO SEES THOSE 5789 03:12:35,113 --> 03:12:39,985 COMPLICATED PATIENTS. 5790 03:12:39,985 --> 03:12:40,919 DOES COST SHARING HAVE ANYTHING 5791 03:12:40,919 --> 03:12:42,287 TO SOLVE THE PROBLEM? 5792 03:12:42,287 --> 03:12:43,955 AND THE NEXT SLIDE WE LOOKED AT 5793 03:12:43,955 --> 03:12:46,224 THE RELATIONSHIP OF THIS DISEASE 5794 03:12:46,224 --> 03:12:48,527 BURDEN WITH HOW MUCH THEY HAD TO 5795 03:12:48,527 --> 03:12:50,062 PAY EITHER AT AN OFFICE VISIT OR 5796 03:12:50,062 --> 03:12:52,564 TO GET THE MEDICATIONS THAT WE 5797 03:12:52,564 --> 03:12:54,733 PRESCRIBED. 5798 03:12:54,733 --> 03:12:56,501 AND ALTHOUGH ACROSS THE BOARD A 5799 03:12:56,501 --> 03:12:58,370 SIMPLE CO-PAY OF $10 WAS THE 5800 03:12:58,370 --> 03:13:03,809 ORDER OF THE DAY, IN THE SOUTH 5801 03:13:03,809 --> 03:13:05,911 AGAIN, WHICH HAD MORE CO-MORBID 5802 03:13:05,911 --> 03:13:08,080 DISEASE ON THE Y AXIS, THAT 5803 03:13:08,080 --> 03:13:09,748 HIGHER CATEGORIES OF CO-PAY WAS 5804 03:13:09,748 --> 03:13:10,382 MORE PREVALENT. 5805 03:13:10,382 --> 03:13:11,683 AND THEREFORE, IT IS CLEAR THAT 5806 03:13:11,683 --> 03:13:12,551 CHANGES HAVE TO BE MADE. 5807 03:13:12,551 --> 03:13:14,186 ON THE NEXT SLIDE, WE SUGGESTED 5808 03:13:14,186 --> 03:13:16,621 A MODIFICATION OF COST SHARING, 5809 03:13:16,621 --> 03:13:19,491 EVEN AT THE BARGAIN PRICE OF 5810 03:13:19,491 --> 03:13:21,426 $10, IN THOSE PATIENTS WHO HAVE 5811 03:13:21,426 --> 03:13:22,294 MULTIPLE COMORBIDITIES. 5812 03:13:22,294 --> 03:13:25,997 A PATIENT WHO HAS HYPERTENSION, 5813 03:13:25,997 --> 03:13:28,734 DIABETES, HYPERLIPIDEMIA, NOT 5814 03:13:28,734 --> 03:13:30,736 ONLY HAS TO SEE RHEUMATOLOGY, 5815 03:13:30,736 --> 03:13:33,238 HAS TO SEE EITHER A SPECIALIST 5816 03:13:33,238 --> 03:13:35,674 FOR THOSE DISEASES OR MULTIPLE 5817 03:13:35,674 --> 03:13:37,209 VISIT FOR THEIR PRIMARY CARE AND 5818 03:13:37,209 --> 03:13:38,410 THAT $10 BECOMES CUMULATIVE SO 5819 03:13:38,410 --> 03:13:39,611 WE HAVE TO THINK OF OTHER WAYS 5820 03:13:39,611 --> 03:13:41,446 TO KEEP ADHERENCE TO MEDICATION 5821 03:13:41,446 --> 03:13:42,547 AND VISITS FOR THIS VULNERABLE 5822 03:13:42,547 --> 03:13:43,749 POPULATION. 5823 03:13:43,749 --> 03:13:45,417 SO WHAT DOES THAT MEAN? 5824 03:13:45,417 --> 03:13:47,152 I THINK IF WE TRANSLATE THIS TO 5825 03:13:47,152 --> 03:13:48,587 WHAT WE'RE BEING ASKED TO DO ON 5826 03:13:48,587 --> 03:13:52,958 THE NEXT SLIDE, AS FOR ALL OUR 5827 03:13:52,958 --> 03:13:53,859 DISEASES, IS THAT IF WE HAVE 5828 03:13:53,859 --> 03:13:55,494 THIS TARGET WE WANT TO ACHIEVE, 5829 03:13:55,494 --> 03:13:57,496 IN ANYTHING, THAT THE STARTING 5830 03:13:57,496 --> 03:13:59,030 POINT FOR THE PEOPLE WHO WALK 5831 03:13:59,030 --> 03:14:01,633 INTO OUR OFFICE ARE NOT ALL THE 5832 03:14:01,633 --> 03:14:02,834 SAME. 5833 03:14:02,834 --> 03:14:05,137 SOME HAVE UNFETTERED AK SE SOME 5834 03:14:05,137 --> 03:14:06,872 HAVE ADMINISTRATIVE HURDLES TO 5835 03:14:06,872 --> 03:14:08,640 GO OVER, SOME HAVE A LOT OF 5836 03:14:08,640 --> 03:14:10,041 BAGGAGE TO GO AT THE START. 5837 03:14:10,041 --> 03:14:11,743 , AND SIMPLY SAYING ON THE NEXT 5838 03:14:11,743 --> 03:14:15,013 CLICK THAT THEY HAVE EQUAL 5839 03:14:15,013 --> 03:14:18,183 INSURANCE OR THEY HAVE LOW 5840 03:14:18,183 --> 03:14:19,651 CO-PAY, IT DOESN'T QUITE GET 5841 03:14:19,651 --> 03:14:19,951 THEM THERE. 5842 03:14:19,951 --> 03:14:21,453 AND WHAT WE HAVE TO SEEK IS THAT 5843 03:14:21,453 --> 03:14:22,888 OF EQUITY ON THE NEXT CLICK. 5844 03:14:22,888 --> 03:14:25,524 AND THE CMS DEFINITION OF THIS 5845 03:14:25,524 --> 03:14:28,493 IS THE ATTAINMENT OF THE HIGHEST 5846 03:14:28,493 --> 03:14:31,563 LEVEL OF HEALTH BY A FAIR AND 5847 03:14:31,563 --> 03:14:32,864 JUST OPPORTUNITIES REGARDLESS OF 5848 03:14:32,864 --> 03:14:34,065 RACE, SOCIOECONOMIC STATUS, AND 5849 03:14:34,065 --> 03:14:38,036 ALL THE OTHER CONFOUNDERS AND 5850 03:14:38,036 --> 03:14:39,304 BARRIERS THAT POPULATES OUR 5851 03:14:39,304 --> 03:14:41,173 LITERATURE. 5852 03:14:41,173 --> 03:14:44,342 BUT I MUST SAY THE THAT ON THE 5853 03:14:44,342 --> 03:14:47,245 NEXT SLIDE, I AM ONE VOICE, AND 5854 03:14:47,245 --> 03:14:51,349 AS ONE OF MY COLLEAGUES HAS 5855 03:14:51,349 --> 03:14:54,319 SAID, A ROOM TOLL JILS FROM A 5856 03:14:54,319 --> 03:14:56,054 JOURNAL, SO MANY OF OUR ISSUES 5857 03:14:56,054 --> 03:14:57,355 CAN ONLY BE EFFECTIVELY MANAGED, 5858 03:14:57,355 --> 03:15:00,125 TREATED OR CURED AT A SOCIETAL 5859 03:15:00,125 --> 03:15:00,625 LEVEL. 5860 03:15:00,625 --> 03:15:02,961 AND MY VOICE AND MY ASSOCIATIONS 5861 03:15:02,961 --> 03:15:05,597 AND BODIES ARE JUST A FINITE 5862 03:15:05,597 --> 03:15:08,200 NUMBER, AND WE HAVE TO ADVOCATE 5863 03:15:08,200 --> 03:15:08,400 MORE. 5864 03:15:08,400 --> 03:15:10,101 BUT THIS IS NOT PART OF OUR 5865 03:15:10,101 --> 03:15:11,636 TRAINING CURRICULUM, NONE OF THE 5866 03:15:11,636 --> 03:15:13,371 PROGRAMS IN RHEUMATOLOGY AT 5867 03:15:13,371 --> 03:15:16,107 LEAST HAVE ADVOCACY AS A PART OF 5868 03:15:16,107 --> 03:15:16,775 THIS. 5869 03:15:16,775 --> 03:15:19,644 SO I ALONG WITH THREE OF MY 5870 03:15:19,644 --> 03:15:25,083 FELLOWS, THE ECR GOVERNMENT 5871 03:15:25,083 --> 03:15:28,553 REPRESENTATIVE AT THE TIME, WE 5872 03:15:28,553 --> 03:15:34,593 DEVELOPED A TOOL TO SENSITIZE 5873 03:15:34,593 --> 03:15:36,728 FELLOWS AT THE EARLY STAGE TO 5874 03:15:36,728 --> 03:15:37,529 EMPHASIZE THE IMPORTANCE OF 5875 03:15:37,529 --> 03:15:37,729 THIS. 5876 03:15:37,729 --> 03:15:38,864 IT'S ABOUT EIGHT CASES, TAKES 5877 03:15:38,864 --> 03:15:40,599 ABOUT AN HOUR TO DO. 5878 03:15:40,599 --> 03:15:42,133 I INVITE ANYONE TO VISIT THIS ON 5879 03:15:42,133 --> 03:15:44,336 THAT WEBSITE UNDER ADVOCACY, AND 5880 03:15:44,336 --> 03:15:47,072 WE'VE SENT IT OUT AND HAD A GOOD 5881 03:15:47,072 --> 03:15:48,139 RESPONSE FROM OTHER 5882 03:15:48,139 --> 03:15:48,607 INSTITUTIONS. 5883 03:15:48,607 --> 03:15:50,342 AND WE MAKE CHANGES ACCORDING TO 5884 03:15:50,342 --> 03:15:52,310 THE CURRENCY OF LEGISLATION 5885 03:15:52,310 --> 03:15:54,713 THAT'S REQUIRES. 5886 03:15:54,713 --> 03:15:57,115 WE ALSO TAKE -- GEOGRAPHIC 5887 03:15:57,115 --> 03:15:59,317 LOCATION AND WE GO ON THE HILL 5888 03:15:59,317 --> 03:16:01,086 EACH SEPTEMBER AND THAT IS A 5889 03:16:01,086 --> 03:16:03,755 CALENDAR ITEM ON OUR TREANING 5890 03:16:03,755 --> 03:16:03,989 PROGRAM. 5891 03:16:03,989 --> 03:16:04,890 SO IT SOMETHING WE HAVE TO 5892 03:16:04,890 --> 03:16:08,493 EXPAND AND EMPHASIZE. 5893 03:16:08,493 --> 03:16:12,464 SO FINALLY, I THINK OUR TIME OR 5894 03:16:12,464 --> 03:16:15,100 MY TIME, THE NEXT SLIDE, IS 5895 03:16:15,100 --> 03:16:18,703 FINITE, AND WE'RE CHALLENGED TO 5896 03:16:18,703 --> 03:16:20,205 MAKE OUR ACTIONS AND 5897 03:16:20,205 --> 03:16:23,742 CONTRIBUTIONS ENDURING, SO WE 5898 03:16:23,742 --> 03:16:25,577 SO THE WORLD AROUND US I THINK 5899 03:16:25,577 --> 03:16:28,213 IS BECOMING MORE AND MORE CLEAR 5900 03:16:28,213 --> 03:16:30,582 THAT WE WHAT WE EAT, DRINK AND 5901 03:16:30,582 --> 03:16:32,217 BREATHE IS BECOMING MORE 5902 03:16:32,217 --> 03:16:35,186 IMPORTANT, AND WE NEED DATA TO 5903 03:16:35,186 --> 03:16:37,122 VALIDATE OUR INTUITIONS BEFORE 5904 03:16:37,122 --> 03:16:38,123 WE CAN ACT. 5905 03:16:38,123 --> 03:16:40,191 AND NEXT WE HAVE TO ADVANCE AS 5906 03:16:40,191 --> 03:16:43,862 WE ADVANCE, WE MUST ALWAYS AND 5907 03:16:43,862 --> 03:16:45,563 IN TANDEM SEEK AND REA INSPECT 5908 03:16:45,563 --> 03:16:48,500 THE PATIENT'S VIEW BECAUSE WE 5909 03:16:48,500 --> 03:16:51,036 MAY KNOW WHAT'S BEST FOR THEM 5910 03:16:51,036 --> 03:16:53,338 BUT THEY MAY KNOW BETTER, AND IF 5911 03:16:53,338 --> 03:16:54,973 WE WORK WITH THEM, WE CAN 5912 03:16:54,973 --> 03:16:56,942 DEVELOP EVEN BETTER BEST 5913 03:16:56,942 --> 03:17:03,281 PRACTICES, SO WE HAVE TO -- BOTH 5914 03:17:03,281 --> 03:17:04,282 STRUCTURAL AND ADMINISTRATIVE. 5915 03:17:04,282 --> 03:17:06,017 AND WE NEED MORE OF US ACROSS 5916 03:17:06,017 --> 03:17:07,118 THE BOARD. 5917 03:17:07,118 --> 03:17:08,853 MORE SLOTS FOR TRAINING. 5918 03:17:08,853 --> 03:17:10,288 MORE SENSITIZATION TO OUR 5919 03:17:10,288 --> 03:17:11,256 SPECIALTY AND OTHERS. 5920 03:17:11,256 --> 03:17:13,792 SO WE CAN MANAGE AND INVESTIGATE 5921 03:17:13,792 --> 03:17:19,064 ALL THAT WE WANT TO. 5922 03:17:19,064 --> 03:17:20,365 EVEN THOUGH MY REMARKS ARE 5923 03:17:20,365 --> 03:17:21,700 MOSTLY ABOUT RHEUMATOLOGY, WE 5924 03:17:21,700 --> 03:17:23,768 TEND TO SPEND SO MUCH TIME IN 5925 03:17:23,768 --> 03:17:24,402 SILOS MEAND OF THE PREVIOUS 5926 03:17:24,402 --> 03:17:31,142 AND MANY OF THE SPEAKERSHAVE EMO 5927 03:17:31,142 --> 03:17:34,546 COLLABORATE, AND WE HAVE TO JOIN 5928 03:17:34,546 --> 03:17:37,048 TO DO THIS AND I LOOK FORWARD TO 5929 03:17:37,048 --> 03:17:38,817 WHAT THE INSTITUTE HAS TO OFFER 5930 03:17:38,817 --> 03:17:40,118 FOR US TO DO JUST THAT. 5931 03:17:40,118 --> 03:17:42,320 AND MY LAST SLIDE, THANKS TO ALL 5932 03:17:42,320 --> 03:17:44,556 OF THOSE I'VE WORKED WITH WHO 5933 03:17:44,556 --> 03:17:45,557 HAVE CONTRIBUTED TREMENDOUSLY TO 5934 03:17:45,557 --> 03:17:46,224 ALL THIS WORK. 5935 03:17:46,224 --> 03:17:46,958 THANK YOU VERY MUCH. 5936 03:17:46,958 --> 03:17:49,527 >> THANK YOU SO MUCH, DR. KERR, 5937 03:17:49,527 --> 03:17:53,665 FOR THAT INCREDIBLE PRESENTA 5938 03:17:53,665 --> 03:17:57,268 PRESENTATION. 5939 03:17:57,268 --> 03:18:00,138 WHAT A WONDERFUL SUMMARY OF SO 5940 03:18:00,138 --> 03:18:01,439 MUCH WORK THAT'S BEEN DONE BY SO 5941 03:18:01,439 --> 03:18:02,374 MANY INDIVIDUALS. 5942 03:18:02,374 --> 03:18:03,174 AND I JUST WANT TO COMMEND YOU 5943 03:18:03,174 --> 03:18:05,010 FOR YOUR LEADERSHIP IN THIS 5944 03:18:05,010 --> 03:18:09,614 SPACE AND THE VERY THOUGHTFUL, 5945 03:18:09,614 --> 03:18:10,682 METHODICAL AND RIGOROUS APPROACH 5946 03:18:10,682 --> 03:18:11,916 YOU'VE TAKEN TO THIS WORK THAT'S 5947 03:18:11,916 --> 03:18:12,650 SO IMPORTANT. 5948 03:18:12,650 --> 03:18:14,285 YOU BROUGHT US BACK TO SOME OF 5949 03:18:14,285 --> 03:18:16,221 THE ISSUES THAT ARE STILL FACING 5950 03:18:16,221 --> 03:18:20,291 US IN MEDICINE, AND HEALTH 5951 03:18:20,291 --> 03:18:21,526 DISPARITIES, HEALTH EQUITY AND 5952 03:18:21,526 --> 03:18:23,194 THEN DIVERSITY IN OUR WORKFORCE, 5953 03:18:23,194 --> 03:18:24,396 DIVERSITY IN OUR RESEARCH 5954 03:18:24,396 --> 03:18:25,797 WORKFORCE, ALL OF THOSE ARE 5955 03:18:25,797 --> 03:18:26,564 CRITICAL. 5956 03:18:26,564 --> 03:18:30,068 I AM GOING TO ASK YOU ONE 5957 03:18:30,068 --> 03:18:31,669 QUESTION, AND DR. SHANMUGAM IS 5958 03:18:31,669 --> 03:18:34,139 ON THE SCREEN AS WELL. 5959 03:18:34,139 --> 03:18:36,474 I SEE DR. PINN IS THERE. 5960 03:18:36,474 --> 03:18:40,979 WE ARE GOOD WITH TIME, RIGHT, I 5961 03:18:40,979 --> 03:18:41,179 VICKI? 5962 03:18:41,179 --> 03:18:42,247 >> YOU'RE GOOD. 5963 03:18:42,247 --> 03:18:43,581 >> SO GAIL, IF YOU KNEW 5964 03:18:43,581 --> 03:18:46,651 EVERYTHING YOU KNOW NOW, AND YOU 5965 03:18:46,651 --> 03:18:48,720 WERE TALKING TO YOUR YOUNGER 5966 03:18:48,720 --> 03:18:51,089 SELF -- I KNOW THIS IS KIND OF A 5967 03:18:51,089 --> 03:18:52,424 HOKEY QUESTION, BUT IT REALLY 5968 03:18:52,424 --> 03:18:53,625 MAKES YOU THINK ABOUT WHAT 5969 03:18:53,625 --> 03:18:55,760 ADVICE WOULD YOU GIVE SOMEONE 5970 03:18:55,760 --> 03:18:57,295 ENTERING THE SPACE WHERE THE 5971 03:18:57,295 --> 03:19:00,031 CHALLENGES WE HAVE FOR MEDICINE 5972 03:19:00,031 --> 03:19:01,766 AND DELIVERING HIGH QUALITY CARE 5973 03:19:01,766 --> 03:19:03,935 TO EVERYONE ARE VAST, BUT THE 5974 03:19:03,935 --> 03:19:05,136 KNOWLEDGE WE HAVE TO GAIN 5975 03:19:05,136 --> 03:19:10,608 THROUGH RESEARCH IS STILL THE 5976 03:19:10,608 --> 03:19:12,377 PROMISE FOR DELIVERING THE BEST 5977 03:19:12,377 --> 03:19:13,711 CARE TO EVERYONE, WHAT WOULD YOU 5978 03:19:13,711 --> 03:19:15,313 SAY TO YOUR YOUNGER SELF 5979 03:19:15,313 --> 03:19:16,948 ENTERING, YOU KNOW, RHEUMATOLOGY 5980 03:19:16,948 --> 03:19:18,049 FELLOWSHIP, YES, YOU'RE OVER 5981 03:19:18,049 --> 03:19:19,751 HERE IN BUILDING 10, YOU'RE 5982 03:19:19,751 --> 03:19:23,354 ROUNDING WITH TONY FAUCI, AND SO 5983 03:19:23,354 --> 03:19:25,390 THAT'S WHERE YOU ARE, WHAT WOULD 5984 03:19:25,390 --> 03:19:26,858 YOU SAY TO YOUR YOUNGER SELF? 5985 03:19:26,858 --> 03:19:31,563 >> SO I THINK IT TAKES TIME TO 5986 03:19:31,563 --> 03:19:34,966 REALIZE WHAT YOU CAN DO AND 5987 03:19:34,966 --> 03:19:35,366 WHAT'S NEEDED. 5988 03:19:35,366 --> 03:19:37,435 YOU DON'T WAKE UP AND DECIDE I'M 5989 03:19:37,435 --> 03:19:39,304 GOING TO DO RESEARCH OR ASK A 5990 03:19:39,304 --> 03:19:42,640 SPECIFIC QUESTION. 5991 03:19:42,640 --> 03:19:43,875 AND IF ANYBODY TOLD ME THAT I 5992 03:19:43,875 --> 03:19:47,145 WOULD BE DOING RESEARCH AT ANY 5993 03:19:47,145 --> 03:19:52,283 KIND OF LEVEL, I WOULD NOT THINK 5994 03:19:52,283 --> 03:19:53,785 THEY WERE IN THEIR RIGHT MIND. 5995 03:19:53,785 --> 03:19:58,156 AND IT CAME FROM SEEING PATIENTS 5996 03:19:58,156 --> 03:19:59,791 PRIMARILY, SEEING THAT I KNEW 5997 03:19:59,791 --> 03:20:01,860 WHAT I HAD TO DO AND WHAT NEEDED 5998 03:20:01,860 --> 03:20:03,528 TO BE DONE BUT I COULDN'T GET IT 5999 03:20:03,528 --> 03:20:05,063 DONE. 6000 03:20:05,063 --> 03:20:07,198 AND YOU HAVE TWO CHOICES AT THAT 6001 03:20:07,198 --> 03:20:07,832 POINT. 6002 03:20:07,832 --> 03:20:09,567 YOU CAN TURN AND WALK AWAY OR 6003 03:20:09,567 --> 03:20:16,241 YOU CAN DO SOMETHING. 6004 03:20:16,241 --> 03:20:18,176 AND THAT SAYING, THAT FORK IN 6005 03:20:18,176 --> 03:20:18,943 THE ROAD THAT YOU AS AN 6006 03:20:18,943 --> 03:20:21,146 INDIVIDUAL BECAUSE OF WHO YOU 6007 03:20:21,146 --> 03:20:22,147 ARE WILL HAVE TO ANSWER. 6008 03:20:22,147 --> 03:20:23,148 I DON'T THINK THAT'S SOMETHING 6009 03:20:23,148 --> 03:20:24,949 THAT CAN BE NECESSARILY TAUGHT. 6010 03:20:24,949 --> 03:20:27,252 THEY CAN SEE YOU DO IT AND MAYBE 6011 03:20:27,252 --> 03:20:29,654 TAKE THAT ADVICE. 6012 03:20:29,654 --> 03:20:34,626 HAVING SAID THAT, TRY AND 6013 03:20:34,626 --> 03:20:36,728 NURTURE SOME CURIOSITY IN YOUR 6014 03:20:36,728 --> 03:20:37,061 TRAINEES. 6015 03:20:37,061 --> 03:20:40,632 YOU ASK QUESTIONS AND MOST OF 6016 03:20:40,632 --> 03:20:41,399 THE TIMES I DON'T KNOW THE 6017 03:20:41,399 --> 03:20:43,468 ANSWER BUT I'M ASKING THE 6018 03:20:43,468 --> 03:20:43,735 QUESTIONS. 6019 03:20:43,735 --> 03:20:47,472 SO WE ALL LOOK IT UP. 6020 03:20:47,472 --> 03:20:48,473 YOU INTERACT WITH THE PATIENT TO 6021 03:20:48,473 --> 03:20:50,108 LET THEM KNOW IT'S NOT JUST A 6022 03:20:50,108 --> 03:20:53,111 MATTER OF TAKING THOSE ITEMS IN 6023 03:20:53,111 --> 03:20:57,849 THE HISTORY, BUT I ALSO ASK THEM 6024 03:20:57,849 --> 03:21:01,452 QUESTIONS ABOUT THEIR LIFE AND 6025 03:21:01,452 --> 03:21:02,754 YOU GET INTO THE LIFE AND SEE 6026 03:21:02,754 --> 03:21:04,155 WHAT'S IMPORTANT TO THEM. 6027 03:21:04,155 --> 03:21:04,822 AND THEN AT SOME POINT, MAYBE 6028 03:21:04,822 --> 03:21:07,125 THAT WILL COME TOGETHER, AND 6029 03:21:07,125 --> 03:21:08,693 SOMETIMES THE MOST UNLIKELY 6030 03:21:08,693 --> 03:21:10,361 PEOPLE ARE THE ONES WHO DECIDE 6031 03:21:10,361 --> 03:21:12,664 TO STEP INTO THAT RESEARCH 6032 03:21:12,664 --> 03:21:15,400 ARENA. 6033 03:21:15,400 --> 03:21:16,501 AND MAYBE NOT CALLING IT 6034 03:21:16,501 --> 03:21:18,136 RESEARCH IN THE INITIAL STAGES 6035 03:21:18,136 --> 03:21:19,971 MIGHT BE MORE ATTRACTIVE. 6036 03:21:19,971 --> 03:21:21,272 JUST SAYING, I WONDER WHAT THE 6037 03:21:21,272 --> 03:21:23,007 ANSWER IS TO THIS. 6038 03:21:23,007 --> 03:21:24,442 START WITH THAT. 6039 03:21:24,442 --> 03:21:25,843 AND MAYBE THAT'S A WAY TO GET 6040 03:21:25,843 --> 03:21:27,612 THESE PEOPLE IN. 6041 03:21:27,612 --> 03:21:30,315 I THINK A KEY THING, THOUGH, FOR 6042 03:21:30,315 --> 03:21:34,352 EVERYTHING I HAVE DONE OR 6043 03:21:34,352 --> 03:21:36,888 ACHIEVED, IT SAYS IT HAS NOT 6044 03:21:36,888 --> 03:21:40,658 BEEN A SOLO EFFORT, A CRAZY 6045 03:21:40,658 --> 03:21:42,093 PERSON TRYING TO DO THINGS, BUT 6046 03:21:42,093 --> 03:21:43,394 THE INDULGENCE, THE KINDNESS OF 6047 03:21:43,394 --> 03:21:44,729 OTHERS AND THE COLLABORATION IS 6048 03:21:44,729 --> 03:21:46,130 SO IMPORTANT, OF LIKE-MINDED 6049 03:21:46,130 --> 03:21:49,067 PEOPLE BUT ALSO PEOPLE YOU MAY 6050 03:21:49,067 --> 03:21:50,401 DISA GREE WITH, BUT YOU COME 6051 03:21:50,401 --> 03:21:51,402 TOGETHER AND THAT'S PART OF THE 6052 03:21:51,402 --> 03:21:54,105 TRAINING OF LEADERSHIP, SEEING 6053 03:21:54,105 --> 03:21:54,872 THINGS DIFFERENTLY. 6054 03:21:54,872 --> 03:21:56,407 CREATING THE THE SAME STORY TO 6055 03:21:56,407 --> 03:21:58,176 GET THE SAME ANSWER. 6056 03:21:58,176 --> 03:22:00,979 SO THAT'S ALSO IMPORTANT. 6057 03:22:00,979 --> 03:22:05,350 SO I LIKE OTHERS ON THIS CALL 6058 03:22:05,350 --> 03:22:06,351 ARE LOOKING FORWARD TO WORKING 6059 03:22:06,351 --> 03:22:07,952 WITH THE INSTITUTE, BECAUSE I 6060 03:22:07,952 --> 03:22:12,857 THINK THIS IS THE FIRST OUTREACH 6061 03:22:12,857 --> 03:22:14,792 TO OUR COMMUNITY TO HAVE THIS AT 6062 03:22:14,792 --> 03:22:17,662 SUCH A HIGH LEVEL, AND I'M 6063 03:22:17,662 --> 03:22:19,530 HOPING -- BECAUSE NOT ALL OF US 6064 03:22:19,530 --> 03:22:22,800 ARE BASIC SCIENTISTS, BUT WE 6065 03:22:22,800 --> 03:22:25,169 WANT THE SAME THING, AND I'M 6066 03:22:25,169 --> 03:22:27,038 HOPING THAT WE CAN BE INCLUDED 6067 03:22:27,038 --> 03:22:29,974 AT SOME LEVEL, EVERYBODY'S 6068 03:22:29,974 --> 03:22:31,709 INTEREST, TO ACHIEVE WHAT'S BEEN 6069 03:22:31,709 --> 03:22:35,446 ASSIGNED TO US. 6070 03:22:35,446 --> 03:22:36,848 >> THANKS SO MUCH FOR THOSE 6071 03:22:36,848 --> 03:22:37,782 COMMENTS. 6072 03:22:37,782 --> 03:22:41,019 THE WAY THIS SYMPOSIUM HAS BEEN 6073 03:22:41,019 --> 03:22:42,220 ORGANIZED, I WANT TO GIVE 6074 03:22:42,220 --> 03:22:43,388 DR. SHANMUGAM A SHOUT OUT ON 6075 03:22:43,388 --> 03:22:44,622 THIS, IS REALLY THE WAY WE THINK 6076 03:22:44,622 --> 03:22:46,224 ABOUT THESE ISSUES, THAT WE NEED 6077 03:22:46,224 --> 03:22:48,293 TO ATTACK THEM AND ADDRESS THEM 6078 03:22:48,293 --> 03:22:49,494 FROM MULTIPLE ADVANTAGE TAJ 6079 03:22:49,494 --> 03:22:54,799 VANTAGE POINT ANDOUR POWER IS T, 6080 03:22:54,799 --> 03:22:56,067 COLLECTIVELY. 6081 03:22:56,067 --> 03:22:58,002 WE FEEL VERY PRIVILEGED TO HAVE 6082 03:22:58,002 --> 03:22:58,936 BEEN IDENTIFIED TO HAVE THE 6083 03:22:58,936 --> 03:23:01,172 OFFICE OF AUTOIMMUNE DISEASE 6084 03:23:01,172 --> 03:23:05,209 RESEARCH WITHIN ORWH, AND FEEL 6085 03:23:05,209 --> 03:23:07,011 FREE TO COMMENT HERE, THE 6086 03:23:07,011 --> 03:23:08,313 CHALLENGE IS VERY CLEAR FOR US 6087 03:23:08,313 --> 03:23:10,982 TO DO THINGS IN A COORDINATED, 6088 03:23:10,982 --> 03:23:12,717 CONCERTED, INTERDISCIPLINARY WAY 6089 03:23:12,717 --> 03:23:14,152 AT NIH. 6090 03:23:14,152 --> 03:23:16,854 AND ORWH HAS ALWAYS WORKED IN 6091 03:23:16,854 --> 03:23:18,923 PARTNERSHIP, EVERYTHING WE DO IS 6092 03:23:18,923 --> 03:23:20,224 IN COLLABORATION AND 6093 03:23:20,224 --> 03:23:22,093 PARTNERSHIP, AND SO I THINK THIS 6094 03:23:22,093 --> 03:23:23,928 IS A LITTLE BIT OF AN EXPERIMENT 6095 03:23:23,928 --> 03:23:26,364 IF YOU THINK ABOUT HOW NIH IS 6096 03:23:26,364 --> 03:23:32,370 SET UP, EACH TIME SOMETHING GETS 6097 03:23:32,370 --> 03:23:34,772 FORMED, THERE'S A NEW OFFICE, A 6098 03:23:34,772 --> 03:23:35,907 NEW INSTITUTE OR NEW 6099 03:23:35,907 --> 03:23:36,941 ORGANIZATIONAL UNIT, SO VICKI 6100 03:23:36,941 --> 03:23:38,910 MAYBE YOU WANT TO COMMENT ON 6101 03:23:38,910 --> 03:23:42,313 YOUR THOUGHTS ON -- ESPECIALLY 6102 03:23:42,313 --> 03:23:43,981 IN LIGHT OF GAIL'S COMMENTS 6103 03:23:43,981 --> 03:23:46,351 ABOUT HOW WE NEED TO BRANCH THE 6104 03:23:46,351 --> 03:23:48,519 LAB AND THE CLINIC AND REAL 6105 03:23:48,519 --> 03:23:49,954 WORLD SETTINGS, BECAUSE ALL OF 6106 03:23:49,954 --> 03:23:52,790 THAT NEEDS TO COME TOGETHER TO 6107 03:23:52,790 --> 03:23:53,758 ADDRESS THE NEEDS THAT OUR 6108 03:23:53,758 --> 03:23:55,660 PATIENTS HAVE. 6109 03:23:55,660 --> 03:24:00,098 >> I APPRECIATE THAT, BRINGING 6110 03:24:00,098 --> 03:24:01,399 OUT THAT POINT AND THANK YOU SO 6111 03:24:01,399 --> 03:24:03,034 MUCH, GAIL, FOR THAT WONDERFUL, 6112 03:24:03,034 --> 03:24:03,501 WONDERFUL TALK. 6113 03:24:03,501 --> 03:24:06,070 IT'S JUST WITH BEEN A PLEASURE O 6114 03:24:06,070 --> 03:24:06,537 WATCH. 6115 03:24:06,537 --> 03:24:08,773 AS ONE OF YOUR FORMER TRAINEES, 6116 03:24:08,773 --> 03:24:10,341 I AM JUST AMAZED BY EVERYTHING 6117 03:24:10,341 --> 03:24:11,142 YOU DO. 6118 03:24:11,142 --> 03:24:12,443 SO FROM THE POINT OF VIEW OF THE 6119 03:24:12,443 --> 03:24:14,078 OFFICE, YES, ABSOLUTELY. 6120 03:24:14,078 --> 03:24:17,915 EVERYTHING WE DO, WE DO IN 6121 03:24:17,915 --> 03:24:19,117 COLLABORATION WITH BOTH THE 6122 03:24:19,117 --> 03:24:20,184 INSTITUTES AND CENTERS IN NIH 6123 03:24:20,184 --> 03:24:22,387 AND THEN ACROSS THE COMMUNITIES 6124 03:24:22,387 --> 03:24:24,989 THAT WE SERVE, AND I THINK THE 6125 03:24:24,989 --> 03:24:25,857 BREADTH AND SCOPE OF WHAT WE'VE 6126 03:24:25,857 --> 03:24:27,325 BEEN ASKED TO DO COULD NOT BE 6127 03:24:27,325 --> 03:24:30,361 DONE ALONE AND I THINK IT'S ONE 6128 03:24:30,361 --> 03:24:31,729 OF THOSE UNIQUE OPPORTUNITIES TO 6129 03:24:31,729 --> 03:24:35,600 GO SOMEWHAT UPSTREAM OF ANY ONE 6130 03:24:35,600 --> 03:24:36,434 INDIVIDUAL DISEASE TO THINK 6131 03:24:36,434 --> 03:24:37,869 ABOUT COMMONALITIES AND 6132 03:24:37,869 --> 03:24:40,271 DIFFERENCES, TO THINK ABOUT WHY 6133 03:24:40,271 --> 03:24:42,774 DO WOMEN GET MORE AUTOIMMUNE 6134 03:24:42,774 --> 03:24:44,642 DISEASE BUT MEN OFTEN GET MORE 6135 03:24:44,642 --> 03:24:45,410 SEVERE AUTOIMMUNE DISEASE AND 6136 03:24:45,410 --> 03:24:49,447 TRYING TO UNDERSTAND THOSE 6137 03:24:49,447 --> 03:24:52,049 DISCORDANT FINDINGS, AND BEING 6138 03:24:52,049 --> 03:24:55,453 GIVEN AN OPPORTUNITY TO 6139 03:24:55,453 --> 03:24:56,654 RECOGNIZE THE BIOLOGY IS TELLING 6140 03:24:56,654 --> 03:24:57,722 US SOMETHING AND WE NEED TO 6141 03:24:57,722 --> 03:24:59,157 FIGURE OUT HOW TO HELP THE 6142 03:24:59,157 --> 03:25:00,124 SCIENCE TO GO IN THE RIGHT 6143 03:25:00,124 --> 03:25:02,026 DIRECTION, AND I THINK THAT'S 6144 03:25:02,026 --> 03:25:03,628 ONE OF THE GOALS OF OUR OFFICE 6145 03:25:03,628 --> 03:25:05,062 AND THE WORK THAT WE'RE TRYING 6146 03:25:05,062 --> 03:25:08,266 TO DO TOGETHER. 6147 03:25:08,266 --> 03:25:10,401 >> THANKS SO MUCH, VICKI. 6148 03:25:10,401 --> 03:25:10,968 GAIL, I WANT TO GIVE YOU THE 6149 03:25:10,968 --> 03:25:12,170 CHANCE TO HAVE THE LAST WORD, 6150 03:25:12,170 --> 03:25:15,673 AND I WILL SHARE THAT I REALLY 6151 03:25:15,673 --> 03:25:17,074 LIKE WHAT YOU SAID ABOUT NOT 6152 03:25:17,074 --> 03:25:19,477 NECESSARILY CALLING IT RESEARCH, 6153 03:25:19,477 --> 03:25:21,546 BECAUSE IT IS AS YOU SAID A VERY 6154 03:25:21,546 --> 03:25:25,049 INDIVIDUAL DECISION, AND SOME 6155 03:25:25,049 --> 03:25:26,417 PEOPLE ARE JUST REALLY INNATELY 6156 03:25:26,417 --> 03:25:26,884 CURIOUS. 6157 03:25:26,884 --> 03:25:28,453 THEY JUST WANT TO KNOW WHY. 6158 03:25:28,453 --> 03:25:29,754 AND THAT'S THE WAY THEIR BRAIN 6159 03:25:29,754 --> 03:25:32,590 WORKS. 6160 03:25:32,590 --> 03:25:34,025 BUT WE ALSO CAN ASK LOTS OF 6161 03:25:34,025 --> 03:25:35,226 DIFFERENT QUESTIONS THAT GET US 6162 03:25:35,226 --> 03:25:36,294 LOTS OF DIFFERENT -- THAT WILL 6163 03:25:36,294 --> 03:25:38,429 HELP US TO FORM A COMPLETE 6164 03:25:38,429 --> 03:25:39,330 PICTURE, AND WE NEED ALL OF 6165 03:25:39,330 --> 03:25:41,098 THOSE VOICES AND WE NEED ALL OF 6166 03:25:41,098 --> 03:25:42,400 THOSE QUESTIONS. 6167 03:25:42,400 --> 03:25:45,136 WOULD YOU LEAVE US WITH A 6168 03:25:45,136 --> 03:25:46,671 CHALLENGE, YOU KNOW, A CALL TO 6169 03:25:46,671 --> 03:25:47,638 ACTION FOR US? 6170 03:25:47,638 --> 03:25:51,042 I'M GIVING YOU A CHANCE, I DON'T 6171 03:25:51,042 --> 03:25:56,814 USUALLY DO THAT. 6172 03:25:56,814 --> 03:25:58,015 I'LL GIVE YOU THE CHANCE TO GIVE 6173 03:25:58,015 --> 03:25:58,883 US A CHALLENGE THIS TIME. 6174 03:25:58,883 --> 03:26:00,952 >> I THINK EVERYBODY ON THE CALL 6175 03:26:00,952 --> 03:26:02,587 TODAY AND THOSE THAT SIGNED IN, 6176 03:26:02,587 --> 03:26:04,222 YOU HAD A VERY GOOD TURNOUT, 6177 03:26:04,222 --> 03:26:05,957 THEY HAVE THROWN DOWN THE 6178 03:26:05,957 --> 03:26:06,858 GAUNTLET FOR THIS AND THERE'S 6179 03:26:06,858 --> 03:26:11,329 HIGH EXPECTATIONS HERE. 6180 03:26:11,329 --> 03:26:14,499 AND THE CHALLENGE TO USE IS TO 6181 03:26:14,499 --> 03:26:16,234 PICK THE IMPORTANT ONES AND PUT 6182 03:26:16,234 --> 03:26:17,568 THEM TOGETHER TO GIVE AN OUTCOME 6183 03:26:17,568 --> 03:26:18,970 AND BE REALISTIC ABOUT THE 6184 03:26:18,970 --> 03:26:21,606 TIMELINES AND TO GET PEOPLE, IF 6185 03:26:21,606 --> 03:26:25,376 THEY COMMIT TO KEEP THAT 6186 03:26:25,376 --> 03:26:25,710 COMMITMENT -- 6187 03:26:25,710 --> 03:26:27,044 >> I THINK THAT'S GOING TO BE 6188 03:26:27,044 --> 03:26:27,478 HOW IT WORKS. 6189 03:26:27,478 --> 03:26:30,248 >> THANK YOU SO MUCH, DR. KERR, 6190 03:26:30,248 --> 03:26:31,949 FOR AN INCREDIBLE PRESENTATION, 6191 03:26:31,949 --> 03:26:33,718 A LOVELY DISCUSSION, AND I'M 6192 03:26:33,718 --> 03:26:35,987 GOING TO TURN IT BACK OVER TO 6193 03:26:35,987 --> 03:26:37,355 YOU, DR. SHANMUGAM. 6194 03:26:37,355 --> 03:26:38,055 >> THANK YOU. 6195 03:26:38,055 --> 03:26:39,757 SO IT'S MY VERY GREAT PLEASURE 6196 03:26:39,757 --> 03:26:41,893 NOW TO INTRODUCE DR. VIVIAN 6197 03:26:41,893 --> 03:26:43,294 PINN. 6198 03:26:43,294 --> 03:26:44,962 DR. PINN WAS THE INAUGURAL 6199 03:26:44,962 --> 03:26:45,730 FULL-TIME DIRECTOR OF THE OFFICE 6200 03:26:45,730 --> 03:26:48,332 OF RESEARCH ON WOMEN'S HEALTH 6201 03:26:48,332 --> 03:26:51,502 FROM 1991 UNTIL HER RETIREMENT 6202 03:26:51,502 --> 03:26:52,270 IN 2011. 6203 03:26:52,270 --> 03:26:54,672 DR. PINN WAS ALSO THE NIH'S 6204 03:26:54,672 --> 03:26:56,340 ASSOCIATE DIRECTOR FOR RESEARCH 6205 03:26:56,340 --> 03:26:59,710 ON WOMEN'S HEALTH, AND UNDER DRE 6206 03:26:59,710 --> 03:27:01,712 OFFICE LED THE IMPLEMENTATION OF 6207 03:27:01,712 --> 03:27:05,650 NIH INCLUSION POLICIES FOR WOMEN 6208 03:27:05,650 --> 03:27:08,052 AND GROUPS IN RESEARCH, 6209 03:27:08,052 --> 03:27:09,820 DEVELOPED THE FIRST IN SEVERAL 6210 03:27:09,820 --> 03:27:12,323 SUBSEQUENT NATIONAL STRATEGIC 6211 03:27:12,323 --> 03:27:12,857 PLANS FOR WOMEN'S HEALTH 6212 03:27:12,857 --> 03:27:13,891 RESEARCH AND ESTABLISHED MANY 6213 03:27:13,891 --> 03:27:15,526 NEW RESEARCH FUNDING INITIATIVES 6214 03:27:15,526 --> 03:27:18,095 AND CAREER DEVELOPMENT PROGRAMS. 6215 03:27:18,095 --> 03:27:20,831 DR. PINN AS WE MENTIONED IS AN 6216 03:27:20,831 --> 03:27:21,599 ACCOMPLISHED PATHOLOGIST. 6217 03:27:21,599 --> 03:27:23,501 SHE'S RECEIVED MORE THAN 300 6218 03:27:23,501 --> 03:27:24,035 AWARDS AND HONORS. 6219 03:27:24,035 --> 03:27:25,469 WE CAN'T INCLUDE THEM ALL BUT WE 6220 03:27:25,469 --> 03:27:26,971 DID INCLUDE HER BIOGRAPHY IF 6221 03:27:26,971 --> 03:27:28,673 YOU'D LIKE TO READ MORE ABOUT 6222 03:27:28,673 --> 03:27:35,246 DR. PIRN IN PINN IN THE PROGRAM 6223 03:27:35,246 --> 03:27:36,247 BOOKLEATHER ONLINE. 6224 03:27:36,247 --> 03:27:40,418 IT'S REALLY A DELIGHT, DR. PINN, 6225 03:27:40,418 --> 03:27:41,085 THE MICROPHONE IS YOURS. 6226 03:27:41,085 --> 03:27:42,486 >> THANK YOU, AND WHAT A 6227 03:27:42,486 --> 03:27:43,087 WONDERFUL CONFERENCE THIS HAS 6228 03:27:43,087 --> 03:27:44,455 BEEN TODAY. 6229 03:27:44,455 --> 03:27:46,324 I WAS THINKING BACK WHEN THE 6230 03:27:46,324 --> 03:27:48,626 OFFICE FIRST STARTED, AUTOIMMUNE 6231 03:27:48,626 --> 03:27:49,594 DISEASES WERE ALWAYS AT THE TOP 6232 03:27:49,594 --> 03:27:52,897 OF OUR LIST OF WHAT SHOULD BE 6233 03:27:52,897 --> 03:27:54,732 PRIORITIES FOR OUR OFFICE TO 6234 03:27:54,732 --> 03:28:00,204 LOOK INTO, CONSIDERING WHAT'S 6235 03:28:00,204 --> 03:28:01,205 IMPORTANT TOPICS FOR WOMEN'S 6236 03:28:01,205 --> 03:28:02,006 HEALTH RESEARCH. 6237 03:28:02,006 --> 03:28:05,009 SO I WAS ALWAYS THERE AND I WAS 6238 03:28:05,009 --> 03:28:05,810 THINKING HOW DIFFERENT IT WAS 6239 03:28:05,810 --> 03:28:07,111 BECAUSE I REMEMBER I WOULD START 6240 03:28:07,111 --> 03:28:08,279 THOSE CONFERENCES WITH, IT'S 6241 03:28:08,279 --> 03:28:09,046 IMPORTANT TO FUND RESEARCH TO 6242 03:28:09,046 --> 03:28:11,248 HELP US LEARN WHY MORE WOMEN 6243 03:28:11,248 --> 03:28:13,417 THAN MEN ARE AFFECTED BY 6244 03:28:13,417 --> 03:28:15,920 AUTOIMMUNE DISEASES. 6245 03:28:15,920 --> 03:28:17,254 AND TODAY WE STARTED OFF WITH A 6246 03:28:17,254 --> 03:28:18,456 PRESENTATION, IN FACT, 6247 03:28:18,456 --> 03:28:21,058 DR. CLAYTON INCLUDED IN HER 6248 03:28:21,058 --> 03:28:23,361 PRESENTATION SOME OF THE 6249 03:28:23,361 --> 03:28:25,863 RESEARCH TODAY SHOWING THE 6250 03:28:25,863 --> 03:28:27,064 GENETIC BASIS OF THAT DISEASE 6251 03:28:27,064 --> 03:28:28,265 AND WHAT ARE PROBABLY SOME OF 6252 03:28:28,265 --> 03:28:31,435 THE MAJOR CONTRIBUTORS TO THAT 6253 03:28:31,435 --> 03:28:33,638 DIFFERENCE, SEX DIFFERENCE IN 6254 03:28:33,638 --> 03:28:34,505 THE OCCURRENCE OF THE DISEASES. 6255 03:28:34,505 --> 03:28:36,907 SO WE'VE COME A LONG WAY, I 6256 03:28:36,907 --> 03:28:38,342 REALLY ENJOYED EVERY 6257 03:28:38,342 --> 03:28:39,510 PRESENTATION AND HEARING WHAT 6258 03:28:39,510 --> 03:28:43,047 WAS PRESENTED WITH DR. BUCKNER 6259 03:28:43,047 --> 03:28:44,448 REALLY GIVING A WONDERFUL 6260 03:28:44,448 --> 03:28:45,983 OVERVIEW AND REALLY SETTING US 6261 03:28:45,983 --> 03:28:48,386 UP WITH A BASIC UNDERSTANDING OF 6262 03:28:48,386 --> 03:28:50,154 THE GENETIC IMPLICATIONS OF 6263 03:28:50,154 --> 03:28:51,889 AUTOIMMUNE DISEASES. 6264 03:28:51,889 --> 03:28:52,890 AS WE KNOW THEM TODAY. 6265 03:28:52,890 --> 03:28:54,959 AND BELIEVE ME, WE'VE COME A 6266 03:28:54,959 --> 03:28:58,029 LONG WAY SINCE WE FIRST STARTED. 6267 03:28:58,029 --> 03:28:58,729 OBVIOUSLY THIS HAS BEEN 6268 03:28:58,729 --> 03:29:00,231 IMPORTANT TO ME PERSONALLY, AND 6269 03:29:00,231 --> 03:29:01,599 I RECALL WHEN THE OFFICE WAS 6270 03:29:01,599 --> 03:29:03,634 FIRST SET UP THERE WAS A CALL 6271 03:29:03,634 --> 03:29:06,604 FOR SETTING UP A SEPARATE OFFICE 6272 03:29:06,604 --> 03:29:09,206 OF AUTOIMMUNE DISEASES BY THE 6273 03:29:09,206 --> 03:29:12,043 ADVOCACY COMMUNITY. 6274 03:29:12,043 --> 03:29:13,444 ACD WE PROTESTED SAYING REALLY 6275 03:29:13,444 --> 03:29:15,079 WE WERE FOCUSING ON AUTOIMMUNE 6276 03:29:15,079 --> 03:29:16,180 DISEASES WITHIN OUR OFFICE 6277 03:29:16,180 --> 03:29:19,483 BECAUSE IT'S PRIMARILY A DISEASE 6278 03:29:19,483 --> 03:29:21,318 OF WOMEN AND IN THE FEW 6279 03:29:21,318 --> 03:29:22,520 INSTANCES WHEN IT AFFECTED MEN 6280 03:29:22,520 --> 03:29:24,822 MORE AS WE LOOKED AT SEX AGENDA 6281 03:29:24,822 --> 03:29:27,224 DIFFERENCES, THAT REALLY FELL, 6282 03:29:27,224 --> 03:29:29,860 WE THOUGHT, WITHIN OUR SCOPE, 6283 03:29:29,860 --> 03:29:31,595 OUR MISSION, SO ACTUALLY I WAS 6284 03:29:31,595 --> 03:29:33,130 DELIGHTED WHEN THIS NEW OFFICE 6285 03:29:33,130 --> 03:29:36,434 WAS ACTUALLY ESTABLISHED 6286 03:29:36,434 --> 03:29:37,735 WITHIN THE OFFICE OF RESEARCH ON 6287 03:29:37,735 --> 03:29:38,169 WOMEN'S HEALTH. 6288 03:29:38,169 --> 03:29:39,937 I THINK THAT'S A WONDERFUL WAY 6289 03:29:39,937 --> 03:29:42,640 TO WORK TOGETHER TO SHOW THE 6290 03:29:42,640 --> 03:29:44,341 TEAM WORK AND THE COLLABORATION, 6291 03:29:44,341 --> 03:29:48,045 AND VICKI, I'M SURE YOU WILL GET 6292 03:29:48,045 --> 03:29:50,414 THE SUPPORT OR ARE GETTING THE 6293 03:29:50,414 --> 03:29:51,215 SUPPORT THAT YOU NEED TO TAKE 6294 03:29:51,215 --> 03:29:54,819 FORWARD THE AUTOIMMUNE STRATEGIC 6295 03:29:54,819 --> 03:29:56,120 IDEAS FOR RESEARCH. 6296 03:29:56,120 --> 03:30:00,825 I HEARD SO MUCH WITH THE 6297 03:30:00,825 --> 03:30:02,460 INTRAMURAL RESEARCH AND EXAMPLES 6298 03:30:02,460 --> 03:30:05,296 OF MAJOR STUDIES WHICH ARE 6299 03:30:05,296 --> 03:30:06,397 SHEDDING INFORMATION WE NEED 6300 03:30:06,397 --> 03:30:09,366 JUST TO BETTER UNDERSTAND 6301 03:30:09,366 --> 03:30:10,468 AUTOIMMUNE DISEASES AND OF 6302 03:30:10,468 --> 03:30:12,970 COURSE I LOVE THE CONCEPT OF 6303 03:30:12,970 --> 03:30:16,807 TISSUE IS THE ISSUE, HOW WHEN 6304 03:30:16,807 --> 03:30:18,275 DR. -- AND THEN I'M GOING TO 6305 03:30:18,275 --> 03:30:21,278 BLANK ON HIS NAME -- GAVE SUCH A 6306 03:30:21,278 --> 03:30:24,348 WONDERFUL, WONDERFUL FIRESIDE 6307 03:30:24,348 --> 03:30:26,250 CHAT, AND OF COURSE I REALLY 6308 03:30:26,250 --> 03:30:30,921 RELATED TO THAT BECAUSE I DID 6309 03:30:30,921 --> 03:30:36,994 TRAIN UNDER CASTLEMAN, DR. CAST, 6310 03:30:36,994 --> 03:30:38,329 DR. CASTLEMAN DID SELECT ME FOR 6311 03:30:38,329 --> 03:30:39,930 AN NIH FELLOWSHIP IN -- NOW I'M 6312 03:30:39,930 --> 03:30:42,366 BLANKING ON THE WORD -- 6313 03:30:42,366 --> 03:30:44,668 FELLOWSHIP IN AUTOIMMUNE, THAT'S 6314 03:30:44,668 --> 03:30:46,637 NOT THE WORD I WANT ANYWAY, TO 6315 03:30:46,637 --> 03:30:48,405 WORK IN AUTOIMMUNE DISEASE IS 6316 03:30:48,405 --> 03:30:51,976 WHAT I DID AS AN NIH FELLOW AT 6317 03:30:51,976 --> 03:30:53,577 MGH. 6318 03:30:53,577 --> 03:30:54,578 AND OF COURSE THAT TIME WE 6319 03:30:54,578 --> 03:30:56,113 DIDN'T HAVE ALL THE GENETIC WORK 6320 03:30:56,113 --> 03:30:59,583 THAT YOU HAVE NOW PROTESTING, SO 6321 03:30:59,583 --> 03:31:03,220 MOST OF THE WORK ON THE BASIS OF 6322 03:31:03,220 --> 03:31:05,923 BIOPSIES AND SERUM STUDIES AND 6323 03:31:05,923 --> 03:31:08,125 BIOPSIES, AND I MADE SO MANY 6324 03:31:08,125 --> 03:31:10,127 PRIMARY DIAGNOSES OF AUTOIMMUNE 6325 03:31:10,127 --> 03:31:12,062 DISEASES ON THE BASIS OF A 6326 03:31:12,062 --> 03:31:13,831 KIDNEY BIOPSY OR SKIN BIOPSY, 6327 03:31:13,831 --> 03:31:16,901 BUT MOST OFTEN THE KIDNEY BIOPSY 6328 03:31:16,901 --> 03:31:18,869 TO EITHER FIRST PROPOSE A 6329 03:31:18,869 --> 03:31:20,504 DISEASE OF AUTOIMMUNE ORIGIN OR 6330 03:31:20,504 --> 03:31:23,240 TO MAKE THE DIAGNOSIS BECAUSE OF 6331 03:31:23,240 --> 03:31:26,143 SOME OF THE SPECIFIC TRAITS WE 6332 03:31:26,143 --> 03:31:27,211 SEE IN THE KIDNEY. 6333 03:31:27,211 --> 03:31:29,313 SO I REALLY WAS ALWAYS ONE WHO 6334 03:31:29,313 --> 03:31:31,615 REALLY AGREED WITH GIVE ME A 6335 03:31:31,615 --> 03:31:32,817 PIECE OF TISSUE AND I'LL GIVE 6336 03:31:32,817 --> 03:31:35,753 YOU A DIAGNOSIS. 6337 03:31:35,753 --> 03:31:38,289 BUT I LOVED THE PRESENTATION OF 6338 03:31:38,289 --> 03:31:39,590 DR. FAJGENBAUM, PROBABLY 6339 03:31:39,590 --> 03:31:40,591 MISPRONOUNCED HIS NAME, AND THE 6340 03:31:40,591 --> 03:31:42,626 FACT THAT ALL THE WORK HE HAS 6341 03:31:42,626 --> 03:31:45,362 DONE AS A PATIENT WHO WAS 6342 03:31:45,362 --> 03:31:46,831 SUBJECTED TO OR WHO HAS BEEN 6343 03:31:46,831 --> 03:31:48,132 SUBJECTED TO AND SUFFERING FROM 6344 03:31:48,132 --> 03:31:49,767 ASPECTS OF CASTLEMAN DISEASE, 6345 03:31:49,767 --> 03:31:52,636 HOW HE WENT AHEAD ON HIS OWN AND 6346 03:31:52,636 --> 03:31:54,705 COMPLETED MULTIPLE DEGREES, 6347 03:31:54,705 --> 03:31:57,107 BECOMING A PHYSICIAN, AND 6348 03:31:57,107 --> 03:31:58,676 LEADING RESEARCH IN THIS AREA. 6349 03:31:58,676 --> 03:32:00,611 I KNOW DR. CASTLEMAN WOULD JUST 6350 03:32:00,611 --> 03:32:02,479 BE SO DELIGHTED, HE WOULD BE 6351 03:32:02,479 --> 03:32:04,048 SMILING AND HE WAS ONE THAT 6352 03:32:04,048 --> 03:32:05,749 COULD REALLY -- IF HE WAS 6353 03:32:05,749 --> 03:32:07,084 PLEASED, GIVE YOU A WONDERFUL 6354 03:32:07,084 --> 03:32:07,284 SMILE. 6355 03:32:07,284 --> 03:32:09,386 AND I CAN JUST SEE HIM SMILING 6356 03:32:09,386 --> 03:32:12,790 AT THE WORK YOU'RE DOING TO 6357 03:32:12,790 --> 03:32:13,724 LEARN MORE ABOUT THIS DISEASE 6358 03:32:13,724 --> 03:32:15,092 THAT WAS NAMED FOR HIM, BECAUSE 6359 03:32:15,092 --> 03:32:17,494 VERY LITTLE WAS KNOWN OTHER THAN 6360 03:32:17,494 --> 03:32:19,230 THE DIAGNOSIS WHEN IT FIRST WAS 6361 03:32:19,230 --> 03:32:24,168 YOU BE GIVEGIVEN HIS NAME. 6362 03:32:24,168 --> 03:32:25,936 I LOVE THE CONCEPT OF SYNERGY IN 6363 03:32:25,936 --> 03:32:26,904 SCIENCE, THAT'S SOMETHING THE 6364 03:32:26,904 --> 03:32:28,305 OFFICE HAS REALLY BROUGHT 6365 03:32:28,305 --> 03:32:29,406 FORWARD OVER THE YEARS AND THAT 6366 03:32:29,406 --> 03:32:30,674 WAS REALLY THE INTENT WE TALKED 6367 03:32:30,674 --> 03:32:31,742 ABOUT, TEAM WORK, THAT WAS 6368 03:32:31,742 --> 03:32:35,112 REALLY THE INTENT OF THE 6369 03:32:35,112 --> 03:32:38,082 INTERDISCIPLINARY PROGRAMS, THE 6370 03:32:38,082 --> 03:32:39,083 BIRCH PROGRAM AND THE SCORE 6371 03:32:39,083 --> 03:32:42,353 PROGRAM AND THE OTHERS, TO SHOW 6372 03:32:42,353 --> 03:32:43,554 THE SYNERGY OF GETTING RESULTS 6373 03:32:43,554 --> 03:32:45,189 WHEN YOU BRING THE WISDOM FROM 6374 03:32:45,189 --> 03:32:46,423 DIFFERENT AREAS WORKING 6375 03:32:46,423 --> 03:32:48,826 TOGETHER, AND I WAS DELIGHTED TO 6376 03:32:48,826 --> 03:32:50,227 HEAR OVER AND OVER TODAY THE 6377 03:32:50,227 --> 03:32:52,429 CONCEPT OF THE NEED FOR 6378 03:32:52,429 --> 03:32:53,864 COLLABORATION AND WORKING 6379 03:32:53,864 --> 03:32:54,965 TOGETHER. 6380 03:32:54,965 --> 03:32:57,268 AND OF COURSE DR. KERR, YOUR 6381 03:32:57,268 --> 03:32:58,602 COMMENTS, ALL THAT YOU DID, IT 6382 03:32:58,602 --> 03:33:01,138 WOULD TAKE AN HOUR TO SORT OF 6383 03:33:01,138 --> 03:33:01,906 SUMMARIZE, THERE'S SO MANY 6384 03:33:01,906 --> 03:33:03,173 THINGS THAT YOU HAVE DONE AND 6385 03:33:03,173 --> 03:33:04,808 HAVE ACCOMPLISHED, BUT I LOVE 6386 03:33:04,808 --> 03:33:08,979 THE FACT THAT YOU'VE WORKED ON 6387 03:33:08,979 --> 03:33:11,715 NOT ONLY THE DISEASE AND 6388 03:33:11,715 --> 03:33:12,483 CLINICAL APPLICATION OF WHAT WE 6389 03:33:12,483 --> 03:33:14,018 KNOW TO AUTOIMMUNE DISEASES, BUT 6390 03:33:14,018 --> 03:33:16,453 ALSO LOOKING AT HOW TO GENERATE 6391 03:33:16,453 --> 03:33:17,988 AND VALIDATE COLLABORATIVE 6392 03:33:17,988 --> 03:33:19,957 RESEARCH AND THEN DEALING ALSO, 6393 03:33:19,957 --> 03:33:22,393 SO YOU DEALT WITH THE CLINICAL 6394 03:33:22,393 --> 03:33:27,064 ASPECT, THE RESEARCH -- AND MORE 6395 03:33:27,064 --> 03:33:28,832 WITH THE IDEA OF DIVERSITY IN 6396 03:33:28,832 --> 03:33:30,034 THE WORKFORCE AND YOU HAVE PUT 6397 03:33:30,034 --> 03:33:32,136 FORTH SOME WONDERFUL IDEAS THAT 6398 03:33:32,136 --> 03:33:35,005 YOU'VE HELPED TO DEVELOP OR ARE 6399 03:33:35,005 --> 03:33:38,075 WORKING WITH, THE DIVERSITY THAT 6400 03:33:38,075 --> 03:33:38,876 WE SO NEED. 6401 03:33:38,876 --> 03:33:39,843 I HAVE TO ADD ONE MORE THING. 6402 03:33:39,843 --> 03:33:42,913 YOU MENTIONED THE KENNETH AUSTIN 6403 03:33:42,913 --> 03:33:44,481 SYMPOSIUM, AND I'M NOT SURE 6404 03:33:44,481 --> 03:33:45,816 EVERYONE KNOWS, BUT WHEN I WAS 6405 03:33:45,816 --> 03:33:47,318 AT HOWARD, THE RHEUMATOLOGIST 6406 03:33:47,318 --> 03:33:50,154 THAT I WORKED WITH WAS 6407 03:33:50,154 --> 03:33:52,222 DR. KENNETH AUSTIN, WHO WAS A 6408 03:33:52,222 --> 03:33:53,324 FABULOUS IMMUNOLOGIST, AND OF 6409 03:33:53,324 --> 03:33:56,627 COURSE AGAIN AS YOU POINTED OUT, 6410 03:33:56,627 --> 03:33:57,962 DR. KER, HE WAS THE ONLY 6411 03:33:57,962 --> 03:33:58,829 RHEUMATOLOGIST THERE, BUT HE 6412 03:33:58,829 --> 03:34:03,667 HAPPENS TO BE DR. JANINE AUSTIN 6413 03:34:03,667 --> 03:34:04,535 CLAYTON'S FATHER, SO SHE 6414 03:34:04,535 --> 03:34:05,536 CERTAINLY HAS BEEN BROUGHT UP IN 6415 03:34:05,536 --> 03:34:08,138 A WORLD THAT ACKNOWLEDGES AND 6416 03:34:08,138 --> 03:34:12,276 THAT VALUES THE AREA OF 6417 03:34:12,276 --> 03:34:13,210 RHEUMATOLOGY BECAUSE SHE WAS 6418 03:34:13,210 --> 03:34:14,945 BROUGHT UP THAT WAY. 6419 03:34:14,945 --> 03:34:17,381 NOW OTHER THAN MY OLD AGE SAYING 6420 03:34:17,381 --> 03:34:21,785 I'VE FORGOTTEN WHAT IT WAS I 6421 03:34:21,785 --> 03:34:23,187 TRAINED AS IN PATHOLOGY, LET ME 6422 03:34:23,187 --> 03:34:25,656 JUST SAY THAT THIS WAS A 6423 03:34:25,656 --> 03:34:26,090 WONDERFUL OCCASION. 6424 03:34:26,090 --> 03:34:29,793 I HAVE TO THANK BOTH OF YOU, 6425 03:34:29,793 --> 03:34:31,195 VICKI AND JANINE, FOR CARRYING 6426 03:34:31,195 --> 03:34:31,962 MY NAME FORWARD. 6427 03:34:31,962 --> 03:34:33,664 I SO APPRECIATE THAT. 6428 03:34:33,664 --> 03:34:36,000 I ENJOYED MY YEARS IN ORWH, AND 6429 03:34:36,000 --> 03:34:37,801 I'M DELIGHTED WITH HOW YOU'RE 6430 03:34:37,801 --> 03:34:39,203 TAKING FORWARD AND IMPROVING ON 6431 03:34:39,203 --> 03:34:41,505 WHAT WE DID DURING THE TIME I 6432 03:34:41,505 --> 03:34:43,007 WAS THERE, AND SEEING SO MANY 6433 03:34:43,007 --> 03:34:45,342 NEW PROGRAMS, SO MANY NEW IDEAS, 6434 03:34:45,342 --> 03:34:47,411 AND SO MANY NEW RESEARCH 6435 03:34:47,411 --> 03:34:48,078 PROJECTS COMING OUT. 6436 03:34:48,078 --> 03:34:50,047 SO WITH THAT, I THINK I'VE 6437 03:34:50,047 --> 03:34:50,581 TALKED A LOT. 6438 03:34:50,581 --> 03:34:52,016 I WANT TO THANK YOU FOR 6439 03:34:52,016 --> 03:34:53,650 INCLUDING ME FOR HONORING ME, 6440 03:34:53,650 --> 03:34:56,020 AND I WANT TO CONGRATULATE ALL 6441 03:34:56,020 --> 03:34:58,822 OF YOU WHO SPOKE TODAY. 6442 03:34:58,822 --> 03:35:00,024 WHAT SUPERB PRESENTATIONS. 6443 03:35:00,024 --> 03:35:03,594 JANINE, YOU REALLY PICKED A GOOD 6444 03:35:03,594 --> 03:35:04,661 CREW AND A GOOD PROGRAM, AND I'M 6445 03:35:04,661 --> 03:35:05,596 GOING TO SAY THANK YOU, AND 6446 03:35:05,596 --> 03:35:06,630 THANK YOU FOR INCLUDING ME IN 6447 03:35:06,630 --> 03:35:07,664 ALL OF THIS. 6448 03:35:07,664 --> 03:35:08,699 AND I LEARNED A LOT. 6449 03:35:08,699 --> 03:35:10,667 I TOOK NOTES, AND I'M RETIRED 6450 03:35:10,667 --> 03:35:13,103 BUT I'M TAKING NOTES FROM WHAT I 6451 03:35:13,103 --> 03:35:13,404 HEARD TODAY. 6452 03:35:13,404 --> 03:35:14,138 IT WAS JUST WONDERFUL. 6453 03:35:14,138 --> 03:35:17,274 THANK YOU. 6454 03:35:17,274 --> 03:35:19,543 >> THANK YOU SO MUCH, DR. PINN. 6455 03:35:19,543 --> 03:35:21,111 I'M GOING TO TURN TO YOU IN ONE 6456 03:35:21,111 --> 03:35:23,280 SECOND, VICKI. 6457 03:35:23,280 --> 03:35:24,181 IMMUNOPATHOLOGY, I MEAN, AND 6458 03:35:24,181 --> 03:35:26,183 YOUR WORK IN THE RENAL PATHOLOGY 6459 03:35:26,183 --> 03:35:27,051 SPACE, IMMUNOLOGY WAS SOMETHING 6460 03:35:27,051 --> 03:35:29,119 THAT YOU WORKED ON FROM THE 6461 03:35:29,119 --> 03:35:30,320 BEGINNING, AND IN FACT, IT WAS 6462 03:35:30,320 --> 03:35:32,990 ACTUALLY THE FIRST COLLEGE 6463 03:35:32,990 --> 03:35:34,525 COURSE THAT I TOOK, BECAUSE IT'S 6464 03:35:34,525 --> 03:35:36,593 JUST MY FIRST LOVE, FROM A 6465 03:35:36,593 --> 03:35:37,161 SCIENCE PERSPECTIVE. 6466 03:35:37,161 --> 03:35:38,629 SO JUST WANTED TO PERSONALLY SAY 6467 03:35:38,629 --> 03:35:41,632 THANK YOU FOR TAKING YOUR TIME. 6468 03:35:41,632 --> 03:35:43,767 YOU DID AN INCREDIBLE WRAP-UP, 6469 03:35:43,767 --> 03:35:45,269 AND OVER TO YOU, VICKI, TO CLOSE 6470 03:35:45,269 --> 03:35:47,905 US OUT. 6471 03:35:47,905 --> 03:35:48,906 >> WONDERFUL. 6472 03:35:48,906 --> 03:35:50,441 SO THANK YOU BOTH, AND ON BEHALF 6473 03:35:50,441 --> 03:35:52,309 OF THE OFFICE OF RESEARCH ON 6474 03:35:52,309 --> 03:35:53,944 WOMEN'S HEALTH AND THE OFFICE OF 6475 03:35:53,944 --> 03:35:54,978 AUTOIMMUNE DISEASE RESEARCH, 6476 03:35:54,978 --> 03:35:56,346 THANK YOU TO ALL OF OUR 6477 03:35:56,346 --> 03:35:58,449 EXCELLENT PRESENTERS TODAY. 6478 03:35:58,449 --> 03:35:59,983 WE DEEPLY APPRECIATE YOUR TIME, 6479 03:35:59,983 --> 03:36:02,086 YOUR COMMITMENT, YOUR EXPERTISE, 6480 03:36:02,086 --> 03:36:05,456 AND YOUR ENERGY ON THE IMPORTANT 6481 03:36:05,456 --> 03:36:06,824 TOPIC OF AUTOIMMUNE DISEASE 6482 03:36:06,824 --> 03:36:07,091 RESEARCH. 6483 03:36:07,091 --> 03:36:08,559 I WANT TO ALSO TAKE A MOMENT TO 6484 03:36:08,559 --> 03:36:10,260 SAY A SPECIAL THANK YOU TO ALL 6485 03:36:10,260 --> 03:36:13,530 OF THE ORWH AND NIH STAFF WHO 6486 03:36:13,530 --> 03:36:15,165 SUPPORTED THIS EVENT. 6487 03:36:15,165 --> 03:36:18,001 MANY OF WHOM PROVIDED TECHNICAL 6488 03:36:18,001 --> 03:36:19,970 ASSISTANCE AND ALL OF THE 6489 03:36:19,970 --> 03:36:21,572 ASSISTANCE GETTING THE 6490 03:36:21,572 --> 03:36:23,273 ORGANIZATION OF THIS EVENT 6491 03:36:23,273 --> 03:36:23,674 TOGETHER. 6492 03:36:23,674 --> 03:36:25,342 THERE WILL BE SOME POST EVENT 6493 03:36:25,342 --> 03:36:26,643 MATERIALS INCLUDING THE 6494 03:36:26,643 --> 03:36:28,645 RECORDING AND A SUMMARY UP ON 6495 03:36:28,645 --> 03:36:30,514 OUR WEBSITE SOON. 6496 03:36:30,514 --> 03:36:33,917 AND AGAIN, THANK YOU ALL FOR 6497 03:36:33,917 --> 03:36:37,554 ATTENDING, WITH THESE CLOSING 6498 03:36:37,554 --> 03:36:42,025 REMARKS, THIS YEAR'S -- IS NOW 6499 03:36:42,025 --> 03:36:42,793 ADJOURNED, THANK YOU AGAIN FOR 6500 03:36:42,793 --> 03:36:50,434 JOINING US.