1 00:00:04,685 --> 00:00:06,220 SO GOOD MORNING 2 00:00:06,220 --> 00:00:07,655 EVERYONE. 3 00:00:07,655 --> 00:00:09,857 WELCOME TO THE 2024 SYMPOSIUM OF 4 00:00:09,857 --> 00:00:13,527 THE NIH DISTINGUISHED SCHOLARS 5 00:00:13,527 --> 00:00:13,761 PROGRAM. 6 00:00:13,761 --> 00:00:20,034 I'M THE DIRECTOR FROM THE OFFICE 7 00:00:20,034 --> 00:00:26,173 OF INTRAMURAL RESEARCH AND IT'S 8 00:00:26,173 --> 00:00:28,743 MY PLEASURE TO INTRODUCE 9 00:00:28,743 --> 00:00:36,684 DR. SHORE. 10 00:00:36,684 --> 00:00:42,690 >> THANK YOU, DR. HASHIMOTO FOR 11 00:00:42,690 --> 00:00:46,060 COMING AND LISTENING ONLINE. 12 00:00:46,060 --> 00:00:52,333 I'M THE NIH DEPUTY DIRECTOR FOR 13 00:00:52,333 --> 00:00:53,601 INTRAMURAL RESEARCH AND HAVE THE 14 00:00:53,601 --> 00:00:56,137 HONOR AND PLEASURE EVERY SINGLE 15 00:00:56,137 --> 00:00:59,507 YEAR OF OPENING THE NIH RESEARCH 16 00:00:59,507 --> 00:01:00,641 FESTIVAL. 17 00:01:00,641 --> 00:01:03,911 I WELCOME ALL OF YOU BOTH ONLINE 18 00:01:03,911 --> 00:01:08,082 AND IN PERSON TO WHAT I TRULY 19 00:01:08,082 --> 00:01:11,218 KNOW WILL BE THREE FANTASTIC 20 00:01:11,218 --> 00:01:13,921 DAYS OF NIH SCIENCE. 21 00:01:13,921 --> 00:01:18,993 THE NIH RED SOX BEGAN IN 1986 AS 22 00:01:18,993 --> 00:01:21,996 NIH RESEARCH DAY. 23 00:01:21,996 --> 00:01:26,867 AND THE FESTIVAL HAS BEEN HELD 24 00:01:26,867 --> 00:01:27,635 ANNUALLY SINCE THEN WITH THE 25 00:01:27,635 --> 00:01:31,639 EXCEPTION OF 1987 WHEN THEY 26 00:01:31,639 --> 00:01:33,341 DECIDED TO CELEBRATE THE 27 00:01:33,341 --> 00:01:35,376 CENTENNIAL OF NIH INSTEAD. 28 00:01:35,376 --> 00:01:39,013 IN 2000 AS YOU LIKELY KNOW, THE 29 00:01:39,013 --> 00:01:41,282 FESTIVAL WENT VIRTUAL AND 30 00:01:41,282 --> 00:01:42,950 PRESENTED THE SAME CUTTING EDGE 31 00:01:42,950 --> 00:01:46,354 SCIENCE BUT IN A DIGITAL ONLY 32 00:01:46,354 --> 00:01:46,754 FORMAT. 33 00:01:46,754 --> 00:01:49,857 LAST YEAR IT CAME BACK IN PERSON 34 00:01:49,857 --> 00:01:52,059 WITH A VIRTUAL OPTION FOR MANY 35 00:01:52,059 --> 00:01:54,395 OF ITS OFFERINGS AND WAS SO 36 00:01:54,395 --> 00:01:56,731 SUCCESSFUL THAT WE DECIDED TO DO 37 00:01:56,731 --> 00:01:58,866 MUCH OF SAME THING THIS YEAR BUT 38 00:01:58,866 --> 00:02:01,302 WITH THE HOPE MORE AND MORE OF 39 00:02:01,302 --> 00:02:04,572 OUR AUDIENCES WILL BE RIGHT 40 00:02:04,572 --> 00:02:05,206 THERE IN THE SAME ROOM WITH THE 41 00:02:05,206 --> 00:02:10,344 SPEAKERS. 42 00:02:10,344 --> 00:02:18,052 IN ADDITION TO OUR SYMPOSIA AND 43 00:02:18,052 --> 00:02:19,987 LECTURES THERE'S RESOURCE TABLES 44 00:02:19,987 --> 00:02:21,322 I HOPE YOU'LL FREQUENT. 45 00:02:21,322 --> 00:02:24,692 NEW THIS YEAR ARE THE INCLUSION 46 00:02:24,692 --> 00:02:25,960 IN THE FESTIVAL ON WEDNESDAY OF 47 00:02:25,960 --> 00:02:30,698 THE DR. PHILLIP CHEN JR. LECTURE 48 00:02:30,698 --> 00:02:32,033 ON INNOVATION AND TECHNOLOGY 49 00:02:32,033 --> 00:02:37,538 TRANSFER. 50 00:02:37,538 --> 00:02:41,075 THE LECTURE ON NIH HISTORY AND 51 00:02:41,075 --> 00:02:42,443 THIS WEEK'S WALS LECTURE. 52 00:02:42,443 --> 00:02:45,913 WHAT A LINEUP WE HAVE. 53 00:02:45,913 --> 00:02:48,749 WELL, THE FESTIVAL SHOWCASES THE 54 00:02:48,749 --> 00:02:52,453 BREADTH AND DEPTH OF NIH 55 00:02:52,453 --> 00:02:53,954 INTRAMURAL SCIENCE, THE 56 00:02:53,954 --> 00:02:56,757 DIVERSITY OF VIEW POINTS, 57 00:02:56,757 --> 00:02:59,693 APPROACHES AND SCIENTIFIC 58 00:02:59,693 --> 00:03:01,562 BACKGROUND OF THE NIH INTRAMURAL 59 00:03:01,562 --> 00:03:03,464 SCIENTIST AND THE JOY AND 60 00:03:03,464 --> 00:03:06,167 CHALLENGE OF FINDING ANSWERS TO 61 00:03:06,167 --> 00:03:08,135 QUESTIONS THAT NO ONE ELSE EVEN 62 00:03:08,135 --> 00:03:10,638 THOUGHT TO ASK. 63 00:03:10,638 --> 00:03:15,176 I HOPE OVER THE NEXT THREE DAYS 64 00:03:15,176 --> 00:03:16,510 EVERY NIH INTRAMURAL SCIENTIST 65 00:03:16,510 --> 00:03:21,982 WILL GET TO TAKE PART IN SOME 66 00:03:21,982 --> 00:03:23,984 WAY IN THE PRESENTATIONS, 67 00:03:23,984 --> 00:03:25,486 FESTIVITIES AND THE 68 00:03:25,486 --> 00:03:26,153 COLLABORATIVE SPIRIT OF THE NIH 69 00:03:26,153 --> 00:03:33,928 RESEARCH FESTIVAL. 70 00:03:33,928 --> 00:03:36,764 IT'S NO ACCIDENT THE 71 00:03:36,764 --> 00:03:38,499 DISTINGUISHED SCHOLARS SYMPOSIUM 72 00:03:38,499 --> 00:03:42,069 IS THE OPENING EVENT OF THE 2024 73 00:03:42,069 --> 00:03:44,038 RESEARCH FESTIVAL. 74 00:03:44,038 --> 00:03:48,275 INDEED, DEDICATION OF THE DSP TO 75 00:03:48,275 --> 00:03:50,845 WELCOMING, NURTURING AND 76 00:03:50,845 --> 00:03:51,712 SUPPORTING A SCIENTIFIC 77 00:03:51,712 --> 00:03:53,514 WORKFORCE THAT REPRESENTS THE 78 00:03:53,514 --> 00:03:57,751 FULL BREADTH BOTH OF HUMAN KIND 79 00:03:57,751 --> 00:04:00,754 AND OF INTELLECTUAL PURSUIT 80 00:04:00,754 --> 00:04:03,157 MIRRORS PRECISELY WHAT NIH SEES 81 00:04:03,157 --> 00:04:04,892 AS THE BEST FUTURE FOR SCIENCE 82 00:04:04,892 --> 00:04:07,394 AND MEDICINE. 83 00:04:07,394 --> 00:04:10,131 THE SYMPOSIUM WILL SHOWCASE THE 84 00:04:10,131 --> 00:04:12,766 WORK OF INTRAMURAL INVESTIGATORS 85 00:04:12,766 --> 00:04:14,034 AT DIFFERENT STAGES OF THEIR 86 00:04:14,034 --> 00:04:18,205 CAREERS ENGAGED IN STUDIES OF 87 00:04:18,205 --> 00:04:20,074 DIFFERENT KINDS OF BIOMEDICAL 88 00:04:20,074 --> 00:04:30,484 AND BEHAVIORAL SCIENCE. 89 00:04:31,252 --> 00:04:34,588 TOGETHER MAKING IT MORE 90 00:04:34,588 --> 00:04:36,123 QUESTIONING OF THE SCIENTIFIC 91 00:04:36,123 --> 00:04:36,757 STATUS QUO. 92 00:04:36,757 --> 00:04:39,593 IT'S A PLEASURE TO OPEN THE 93 00:04:39,593 --> 00:04:40,227 DISTINGUISHED SCHOLARS PROGRAM 94 00:04:40,227 --> 00:04:44,498 SYMPOSIUM AND TO APPROACH THE 95 00:04:44,498 --> 00:04:46,467 DAY WHEN ANYONE WHO ASPIRES TO 96 00:04:46,467 --> 00:04:49,270 AND WORK TOWARDS A CAREER IN 97 00:04:49,270 --> 00:04:53,174 SCIENCE OR MEDICINE CAN HONESTLY 98 00:04:53,174 --> 00:04:54,275 SAY I BELONG. 99 00:04:54,275 --> 00:04:58,979 NOW I'M GOING TO TURN THE PODIUM 100 00:04:58,979 --> 00:05:01,115 OVER TO OUR DISTINGUISHED 101 00:05:01,115 --> 00:05:10,891 SCHOLAR MASTER OF CEREMONIES. 102 00:05:10,891 --> 00:05:12,927 >> THANK YOU VERY MUCH, 103 00:05:12,927 --> 00:05:17,798 DR. SHORE AND DR. HASHIMOTO AND 104 00:05:17,798 --> 00:05:19,266 THE DSP. 105 00:05:19,266 --> 00:05:20,434 WE HAD A CONVERSATION THAT 106 00:05:20,434 --> 00:05:23,137 MEETING IN PERSON IS SO MUCH 107 00:05:23,137 --> 00:05:24,138 MORE CONDUCIVE TO INNOVATION AND 108 00:05:24,138 --> 00:05:26,006 NICE TO SEE YOU IN THE AUDIENCE 109 00:05:26,006 --> 00:05:27,508 AND THOSE ONLINE AS WELL. 110 00:05:27,508 --> 00:05:30,844 FOR THE FIRST SPEAKER IS 111 00:05:30,844 --> 00:05:38,586 DR. ANGELA BALLESTEROS ON 112 00:05:38,586 --> 00:05:40,754 INSIGHTS IN THE TRANSDUCTION 113 00:05:40,754 --> 00:05:48,729 CHANNEL ESSENTIAL FOR HEARING. 114 00:05:48,729 --> 00:05:59,273 >> HI, EVERYBODY THANK YOU FOR 115 00:06:02,109 --> 00:06:04,211 JOINING US. 116 00:06:04,211 --> 00:06:07,114 ALLOW ME TO START THE AMAZING 117 00:06:07,114 --> 00:06:11,986 SYMPOSIUM BY GIVING FUNCTIONAL 118 00:06:11,986 --> 00:06:12,753 INSIGHTS INTO THE TRANSDUCTION 119 00:06:12,753 --> 00:06:15,322 CHANNEL FOR HEARING. 120 00:06:15,322 --> 00:06:16,991 WHEN I STARTED MY POSTDOC I 121 00:06:16,991 --> 00:06:20,027 WANTED TO CONTRIBUTE TO ANSWER 122 00:06:20,027 --> 00:06:24,131 THE QUESTION SHOWN IN PINK. 123 00:06:24,131 --> 00:06:25,232 WE KNOW THE MOLECULES FOR 124 00:06:25,232 --> 00:06:27,268 SENSING THE OTHER SENSES WE THEN 125 00:06:27,268 --> 00:06:31,238 KNOW THE MOLECULAR IDENTITY OF 126 00:06:31,238 --> 00:06:33,674 THE TRANSDUCTION CHANNEL 127 00:06:33,674 --> 00:06:35,342 RESPONSIBLE FOR HEARING AND 128 00:06:35,342 --> 00:06:35,809 BALANCE. 129 00:06:35,809 --> 00:06:37,611 I WAS STRUCK BY THIS BECAUSE 130 00:06:37,611 --> 00:06:40,914 HEARING LOSS IS THE MOST COMMON 131 00:06:40,914 --> 00:06:44,752 SENSORY DISORDER AND AFFECTS 132 00:06:44,752 --> 00:06:48,722 PEOPLE DRAMATICALLY INCREASING 133 00:06:48,722 --> 00:06:56,730 LONGER AND MOVING TO 134 00:06:56,730 --> 00:06:58,232 INDUSTRIALIZED CITIES. 135 00:06:58,232 --> 00:07:04,405 WE CAN NOW SAY THE MC1 AND MC2 136 00:07:04,405 --> 00:07:08,309 ARE RESPONSIBLE FOR HEARING AND 137 00:07:08,309 --> 00:07:08,742 BALANCE. 138 00:07:08,742 --> 00:07:11,445 LET ME TELL YOU ABOUT THE SYSTEM 139 00:07:11,445 --> 00:07:12,980 WE WORK WITH. 140 00:07:12,980 --> 00:07:15,783 THE SOUND WAVES TRAVEL FROM THE 141 00:07:15,783 --> 00:07:20,054 OUTER EAR TO THE MIDDLE EAR TO 142 00:07:20,054 --> 00:07:22,856 THE INNER EAR TO THE COCHLEA. 143 00:07:22,856 --> 00:07:27,561 THAT'S WHERE WE HAVE THE 144 00:07:27,561 --> 00:07:28,729 AUDITORY SENSOR AND IT'S A 145 00:07:28,729 --> 00:07:32,066 SPECIFIC REGION IS WHERE WE HAVE 146 00:07:32,066 --> 00:07:33,901 THE AUDITORY SENSORY CELLS WE 147 00:07:33,901 --> 00:07:35,869 CALL THE HAIR CELLS. 148 00:07:35,869 --> 00:07:36,737 AND THEY'RE CALLED THE HAIR 149 00:07:36,737 --> 00:07:43,010 CELLS OF THE INNER EAR BECAUSE 150 00:07:43,010 --> 00:07:49,249 THEY HAVE HAIR-LIKE BUNDLES. 151 00:07:49,249 --> 00:07:51,285 SO EVERY HAIR CELL HAS ONE 152 00:07:51,285 --> 00:07:54,288 BUNDLE THAT IS LOCATED AT THE 153 00:07:54,288 --> 00:07:59,760 REGION OF THE SENSORY HAIR CELLS 154 00:07:59,760 --> 00:08:09,703 AND THIS IS THE MECHANO SENSORY 155 00:08:09,703 --> 00:08:14,074 OF SOUND AND THUS TRANSFORMING 156 00:08:14,074 --> 00:08:15,642 THE STIMULI INTO ELECTRICAL 157 00:08:15,642 --> 00:08:17,077 SIGNALS TO BE TRANSFERRED TO THE 158 00:08:17,077 --> 00:08:18,312 BRAIN. 159 00:08:18,312 --> 00:08:19,880 SO LET ME TELL YOU A LITTLE BIT 160 00:08:19,880 --> 00:08:24,752 HOW THE MECHANO SENSORY 161 00:08:24,752 --> 00:08:28,021 ORGANELLE DOES THIS. 162 00:08:28,021 --> 00:08:34,695 WE HAVE A PROTEIN FILAMENT THAT 163 00:08:34,695 --> 00:08:37,264 CONNECTS THE CILIA AND WHEN THE 164 00:08:37,264 --> 00:08:40,801 SOUND WAVES GO INTO OUR INNER 165 00:08:40,801 --> 00:08:47,574 EAR AND BEND THE BUNDLE IT WILL 166 00:08:47,574 --> 00:08:51,044 PULL FROM THE MEMBRANE OF THE 167 00:08:51,044 --> 00:08:52,112 CILIA LEADING TO THE OPENING OF 168 00:08:52,112 --> 00:08:54,415 THE MECHANO SENSITIVE CHANNEL 169 00:08:54,415 --> 00:08:57,751 THAT IS GOING TO ALLOW FOR THE 170 00:08:57,751 --> 00:09:00,754 PERMEATION OF THE IONS IN THE 171 00:09:00,754 --> 00:09:10,964 HAIR CELLS. 172 00:09:12,399 --> 00:09:15,002 WE KNOW IT MAKES THE MECHANO 173 00:09:15,002 --> 00:09:16,737 COMPLEX AND ONE OF THE BIG 174 00:09:16,737 --> 00:09:17,604 QUESTIONS THAT REMAIN IN THE 175 00:09:17,604 --> 00:09:20,741 FIELD IS WHICH ONE OF THESE 176 00:09:20,741 --> 00:09:25,946 TRANS MEMBRANE PROTEINS WERE THE 177 00:09:25,946 --> 00:09:32,686 ION CHANNEL AND HAVE THE MECHANO 178 00:09:32,686 --> 00:09:33,720 ELECTRICAL TRANSACTION COMPLEX. 179 00:09:33,720 --> 00:09:37,424 ING THE THE IDENTITY OF THESE 180 00:09:37,424 --> 00:09:40,727 PROTEINS WAS NOT ONLY IMPORTANT 181 00:09:40,727 --> 00:09:44,064 TO IDENTIFY THE MOLECULE 182 00:09:44,064 --> 00:09:48,202 RESPONSIBLE FOR HEARING AND 183 00:09:48,202 --> 00:09:52,339 DRUGS BUT WITH HAVE DRUGS USED 184 00:09:52,339 --> 00:09:56,009 IN CLINIC LIKE ANTIBIOTICS THAT 185 00:09:56,009 --> 00:09:57,911 CAN ALSO PERMEATE THROUGH THIS 186 00:09:57,911 --> 00:10:02,082 CHANNEL AND ACCUMULATE INTO HAIR 187 00:10:02,082 --> 00:10:05,652 CELLS AND KILL THE HAIR CELLS 188 00:10:05,652 --> 00:10:08,055 LEADING TO PERMANENT HEARING 189 00:10:08,055 --> 00:10:12,526 LOSS AND BY GETTING FUNCTIONAL 190 00:10:12,526 --> 00:10:14,962 INFORMATION WE CAN MOTIVATE THE 191 00:10:14,962 --> 00:10:18,232 DESIGN OF STUDIES TO REDUCE 192 00:10:18,232 --> 00:10:24,037 TOXICITY OF THESE MOLECULES. 193 00:10:24,037 --> 00:10:25,772 WE HAVE A LOT OF EXPERIMENTAL 194 00:10:25,772 --> 00:10:27,274 EVIDENCE POINTING TO THE 195 00:10:27,274 --> 00:10:28,775 PROTEINS SHOWN IN GRAY AS BEING 196 00:10:28,775 --> 00:10:39,019 THIS IONIC CHANNEL. 197 00:10:39,019 --> 00:10:41,188 WE TRIED TO GENERATE STRUCTURAL 198 00:10:41,188 --> 00:10:42,222 MODELS FOR THE PROTEINS TO SEE 199 00:10:42,222 --> 00:10:44,725 WHAT THEY ARE LOOK LIKE. 200 00:10:44,725 --> 00:10:47,094 WE LOOKED FOR A DISTANT RELATED 201 00:10:47,094 --> 00:10:48,595 PROTEIN THAT WE ALREADY HAVE 202 00:10:48,595 --> 00:10:50,063 STRUCTURE WE CAN USE AS A 203 00:10:50,063 --> 00:10:53,800 TEMPLATE TO MODEL THE STRUCTURE 204 00:10:53,800 --> 00:10:56,069 AND WE FOUND OUT THERE ARE TWO 205 00:10:56,069 --> 00:11:04,645 OTHER FAMILY OF PROTEINS AND THE 206 00:11:04,645 --> 00:11:06,413 TMEM 16 PROGRAMS HAVE CONSERVED 207 00:11:06,413 --> 00:11:07,981 PROTEINS WITH THE TMC PROTEINS. 208 00:11:07,981 --> 00:11:10,517 AND THE OTHER FAMILY OF PROTEINS 209 00:11:10,517 --> 00:11:13,253 ARE ACTUALLY PART OF THE TMCs OF 210 00:11:13,253 --> 00:11:17,558 THE SAME SUPER FAMILY OF 211 00:11:17,558 --> 00:11:19,393 PROTEINS AND IT WAS SO IN THE 212 00:11:19,393 --> 00:11:20,060 EVOLUTIONARY STUDY. 213 00:11:20,060 --> 00:11:21,962 SO WE HAVE MORE INFORMATION 214 00:11:21,962 --> 00:11:23,830 ABOUT THESE TWO OTHER PROTEINS. 215 00:11:23,830 --> 00:11:25,432 WE HAVE A STRUCTURAL INFORMATION 216 00:11:25,432 --> 00:11:27,968 AND KNOW HOW THE PROTEINS LOOK 217 00:11:27,968 --> 00:11:33,173 LIKE AND ALSO KNOW WHAT IS THEIR 218 00:11:33,173 --> 00:11:33,840 FUNCTION. 219 00:11:33,840 --> 00:11:35,709 THE PROTEINS ARE BOTH FAMILIES 220 00:11:35,709 --> 00:11:38,011 THAT CAN FUNCTION AS IONIC 221 00:11:38,011 --> 00:11:39,980 CHANNELS AND SUGGEST THE TMCs 222 00:11:39,980 --> 00:11:42,115 MAY ALSO FUNCTION AS A CHANNEL 223 00:11:42,115 --> 00:11:45,452 BUT INTERESTINGLY THE TMC 224 00:11:45,452 --> 00:11:51,625 PROTEINS CAN HAVE MEMBRANE 225 00:11:51,625 --> 00:11:54,795 REGULATORY FUNCTION IN A COUPLE 226 00:11:54,795 --> 00:11:55,395 SLIDES. 227 00:11:55,395 --> 00:11:56,730 THIS IS HOW THE STRUCTURAL MODEL 228 00:11:56,730 --> 00:11:58,932 OF THE TMC LOOKS LIKE. 229 00:11:58,932 --> 00:12:00,601 THIS IS THE FIRST STRUCTURAL 230 00:12:00,601 --> 00:12:04,037 INFORMATION WE GOT ON THE TMC 231 00:12:04,037 --> 00:12:04,738 PROTEINS. 232 00:12:04,738 --> 00:12:07,474 THEY HAVE 10,000 MEMBRANE 233 00:12:07,474 --> 00:12:07,975 DOMAINS. 234 00:12:07,975 --> 00:12:10,043 MORE IMPORTANTLY THE GENERATION 235 00:12:10,043 --> 00:12:13,914 WILL ALLOW US TO LOCATE 22 236 00:12:13,914 --> 00:12:14,181 MUTATIONS. 237 00:12:14,181 --> 00:12:16,483 THIS IS GOING TO HELP US 238 00:12:16,483 --> 00:12:18,986 UNDERSTAND HOW THE POINT 239 00:12:18,986 --> 00:12:19,886 MUTATIONS ALTER THE FUNCTION OF 240 00:12:19,886 --> 00:12:22,522 THESE PROTEINS AND LEAD TO 241 00:12:22,522 --> 00:12:23,423 HEARING LOSS. 242 00:12:23,423 --> 00:12:26,593 WHEN WE LOOK FROM THE SIDE, WE 243 00:12:26,593 --> 00:12:29,363 CAN SEE THE PRESENT OF A CAVITY 244 00:12:29,363 --> 00:12:31,131 AT THE PROTEIN MEMBRANE 245 00:12:31,131 --> 00:12:35,302 INTERFACE AND IT FUNCTIONS AS 246 00:12:35,302 --> 00:12:38,038 THE ION PERMEATION PATHWAY OR 247 00:12:38,038 --> 00:12:41,908 PORE RELATED TO THE PROTEINS AND 248 00:12:41,908 --> 00:12:43,010 WE THOUGHT IT COULD ALSO 249 00:12:43,010 --> 00:12:46,480 FUNCTION AS A PORT IN THE TMC 250 00:12:46,480 --> 00:12:48,982 PROTEINS THE PORT OF THE 251 00:12:48,982 --> 00:12:51,284 ELECTRICAL TRANSACTION CHANNEL. 252 00:12:51,284 --> 00:12:53,754 WE LOOK AT THESE MORE IN DETAIL. 253 00:12:53,754 --> 00:12:58,325 I'LL SHOW YOU A PICTURE LOOKING 254 00:12:58,325 --> 00:13:00,727 FROM THE SIDES AND SEE THE 255 00:13:00,727 --> 00:13:02,963 CAVITY AND THESE ARE ALL 256 00:13:02,963 --> 00:13:08,435 HIGHLIGHTS THE IONS OR THE DRUGS 257 00:13:08,435 --> 00:13:12,072 WILL HAVE TO FOLLOW TO ENTER THE 258 00:13:12,072 --> 00:13:12,572 HAIR CELLS. 259 00:13:12,572 --> 00:13:16,677 THIS MODEL NOT ONLY SUPPORT 260 00:13:16,677 --> 00:13:23,617 FUNCTIONAL DATA FROM AN 261 00:13:23,617 --> 00:13:24,751 ELECTRICO PHYSIOLOGY MODEL BUT 262 00:13:24,751 --> 00:13:28,722 SUPPORTS THE PROTEINS AND THE 263 00:13:28,722 --> 00:13:30,290 CHANNELS FOR HEARING AND 264 00:13:30,290 --> 00:13:31,258 BALANCE. 265 00:13:31,258 --> 00:13:34,294 ONE OF THE COOL THINGS I KEPT 266 00:13:34,294 --> 00:13:36,730 WONDERING WHEN I LOOK AT THESE 267 00:13:36,730 --> 00:13:39,433 STRUCTURAL MODELS WAS THESE 268 00:13:39,433 --> 00:13:40,734 PARTIALLY OPEN TO THE PLASMA 269 00:13:40,734 --> 00:13:44,004 MEMBRANE AND KEPT LOOKING AT HOW 270 00:13:44,004 --> 00:13:45,839 THE IONS GO TO THE PLASMA 271 00:13:45,839 --> 00:13:50,644 MEMBRANE AND LOOK AT HOW THE TMC 272 00:13:50,644 --> 00:13:52,245 PROTEINS FUNCTION NOT ONLY AS 273 00:13:52,245 --> 00:13:55,182 THE CHANNEL BUT THEY WORK. 274 00:13:55,182 --> 00:14:01,121 SO IN THE TMC PROTEIN HAVE DUAL 275 00:14:01,121 --> 00:14:07,561 FUNCTION AND IT ALLOWS FOR THE 276 00:14:07,561 --> 00:14:11,665 PERMUTATION OF THE PHOSPHO LIPID 277 00:14:11,665 --> 00:14:15,335 GROUP IS THOUGHT TO PARTICIPATE 278 00:14:15,335 --> 00:14:18,472 IN THE SEALING OF THOSE IONS 279 00:14:18,472 --> 00:14:21,041 FROM THE PLASMA MEMBRANE. 280 00:14:21,041 --> 00:14:22,976 SO I HYPOTHESIZE MAYBE THE 281 00:14:22,976 --> 00:14:26,079 PROTEINS CANNOT ONLY FUNCTION AS 282 00:14:26,079 --> 00:14:30,350 IONIC CHANNELS BUT CAN ALSO HAVE 283 00:14:30,350 --> 00:14:31,518 A LIPID FUNCTION AND REGULATE 284 00:14:31,518 --> 00:14:35,922 THE HAIR CELL MEMBRANE. 285 00:14:35,922 --> 00:14:37,457 BEFORE I SHOW YOU A BIT OF DATA 286 00:14:37,457 --> 00:14:41,094 I NEED TO TELL YOU HOW THE 287 00:14:41,094 --> 00:14:41,895 LIPIDS WORK. 288 00:14:41,895 --> 00:14:46,900 SO THE PLASMA MEMBRANE THE CELL 289 00:14:46,900 --> 00:14:52,739 MEMBRANE IS ASYMMETRIC AND 290 00:14:52,739 --> 00:14:54,274 THEY'RE ALWAYS LOCATED IN THE 291 00:14:54,274 --> 00:14:55,475 INSIDE OF THE CELLS. 292 00:14:55,475 --> 00:15:02,015 AND WHEN WE HAVE AN ACTIVATED 293 00:15:02,015 --> 00:15:12,559 LIPID SCRAMBLASE TO WHAT IS NOT 294 00:15:15,529 --> 00:15:17,898 ACCESSIBLE AND LOST INTERACTIONS 295 00:15:17,898 --> 00:15:20,667 BETWEEN THE PLASMA MEMBRANE AND 296 00:15:20,667 --> 00:15:25,739 CANNOT SHOW WHAT IS BEING 297 00:15:25,739 --> 00:15:26,006 GENERATED. 298 00:15:26,006 --> 00:15:27,641 WE CAN USE PROOF TRADITIONALLY 299 00:15:27,641 --> 00:15:30,977 LABELLED TO TO DETECT THE 300 00:15:30,977 --> 00:15:32,212 PHOSPHO LIPIDS BY DOING THESE 301 00:15:32,212 --> 00:15:37,584 KINDS OF ASSAYS WE CANNOT ONLY 302 00:15:37,584 --> 00:15:39,753 TEST THE HAIR CELL BUNDLE BUT TO 303 00:15:39,753 --> 00:15:44,057 TEST THE HYPOTHESIS OF THE TMCs 304 00:15:44,057 --> 00:15:47,494 PLAYING A ROLE IN THESE NEW 305 00:15:47,494 --> 00:15:47,761 FUNCTION. 306 00:15:47,761 --> 00:15:49,529 I DON'T HAVE TIME TO SHOW YOU 307 00:15:49,529 --> 00:15:51,665 HERE ALL THE DIFFERENT 308 00:15:51,665 --> 00:15:52,632 EXPERIMENTS WE PERFORM USING 309 00:15:52,632 --> 00:15:54,935 KNOCKOUT MODELS FOR THE TMC 310 00:15:54,935 --> 00:15:58,405 PROTEINS AND DIFFERENT 311 00:15:58,405 --> 00:16:00,106 MANIPULATIONS AND EVEN THE PLANS 312 00:16:00,106 --> 00:16:03,043 FOR A MOUSE MODEL HAVING POINT 313 00:16:03,043 --> 00:16:03,677 MUTATIONS. 314 00:16:03,677 --> 00:16:10,650 BUT WHAT WE SAW IS THERE IS THIS 315 00:16:10,650 --> 00:16:15,889 TMC1 DEPENDENT EXTERNALIZATION 316 00:16:15,889 --> 00:16:21,962 AT THE BUNDLE DEMONSTRATING THEY 317 00:16:21,962 --> 00:16:22,696 CANNOT FUNCTION WITH 318 00:16:22,696 --> 00:16:24,130 DYSREGULATED MEMBRANE. 319 00:16:24,130 --> 00:16:26,533 WE THINK WHEN THE ION CHANNEL OF 320 00:16:26,533 --> 00:16:30,804 THE TMC PROTEINS IS WORKING THE 321 00:16:30,804 --> 00:16:33,940 MEMBRANE IS PRESERVED BUT WHEN 322 00:16:33,940 --> 00:16:38,078 WE HAVE MUTATIONS AT TMC1 THIS 323 00:16:38,078 --> 00:16:44,050 FUNCTION GETS ACTIVATED AND IT 324 00:16:44,050 --> 00:16:46,519 GETS EXTERNALIZED AND OBSERVE 325 00:16:46,519 --> 00:16:48,388 THESE THAT ARE NOT ONLY ALTERING 326 00:16:48,388 --> 00:16:56,062 THE PROTEINS BUT AFFECT 327 00:16:56,062 --> 00:16:56,396 TRANSDUCTION. 328 00:16:56,396 --> 00:16:58,565 WE THINK WHEN THIS IS HAPPENING 329 00:16:58,565 --> 00:17:00,634 IN AN UNREGULATED WAY IT MAY BE 330 00:17:00,634 --> 00:17:02,135 A MECHANISM THE HAIR CELLS ARE 331 00:17:02,135 --> 00:17:10,243 USING TO RECYCLE NOT FUNCTIONAL 332 00:17:10,243 --> 00:17:11,945 COMPLICE BUT WHEN IN AN 333 00:17:11,945 --> 00:17:13,914 UNREGULATED WAY MAY BE TO HAIR 334 00:17:13,914 --> 00:17:15,148 CELL DEATH AND HEARING LOSS. 335 00:17:15,148 --> 00:17:18,818 OUR LAB IS NOT ONLY INTERESTED 336 00:17:18,818 --> 00:17:22,589 IN THE CATHETERIZATION OF THE 337 00:17:22,589 --> 00:17:24,457 TMC PROTEINS BUT ALSO IN 338 00:17:24,457 --> 00:17:28,395 UNDERSTANDING HOW THE MEMBRANE 339 00:17:28,395 --> 00:17:29,863 REGULATORY FUNCTIONALITIERS HAIR 340 00:17:29,863 --> 00:17:30,697 CELL PHYSIOLOGY. 341 00:17:30,697 --> 00:17:33,033 SO WITH THAT I WOULD LIKE TO 342 00:17:33,033 --> 00:17:35,869 THANK MY FORMER LAB AND MENTORS 343 00:17:35,869 --> 00:17:37,570 AND COLLABORATORS FOR ALL THEIR 344 00:17:37,570 --> 00:17:43,376 SUPPORT, THE DSP PROGRAM FOR 345 00:17:43,376 --> 00:17:53,186 THIS AMAZING OPPORTUNITY AND 346 00:17:53,186 --> 00:17:54,321 WITH THAT I'LL BE HAPPY TO TAKE 347 00:17:54,321 --> 00:18:03,430 ANY QUESTIONS IF I HAVE TIME. 348 00:18:03,430 --> 00:18:04,764 >> THANK YOU, DR. BALLESTEROS. 349 00:18:04,764 --> 00:18:06,566 IF YOU HAVE QUESTIONS COME UP TO 350 00:18:06,566 --> 00:18:08,101 THE MIKE AND INTRODUCE YOURSELF 351 00:18:08,101 --> 00:18:10,804 AND POSE ANY QUESTIONS. 352 00:18:10,804 --> 00:18:12,305 DO WE HAVE SOMEONE MONITORING 353 00:18:12,305 --> 00:18:12,739 QUESTIONS ONLINE? 354 00:18:12,739 --> 00:18:13,840 THIS IS GREAT. 355 00:18:13,840 --> 00:18:15,642 I HAVE A LOT OF QUESTIONS. 356 00:18:15,642 --> 00:18:15,909 FANTASTIC. 357 00:18:15,909 --> 00:18:18,745 BY BACKGROUND I'M A VASCULAR 358 00:18:18,745 --> 00:18:20,747 CARDIOLOGIST SO THIS IS VERY 359 00:18:20,747 --> 00:18:22,882 INTERESTING WE THINK OF THESE 360 00:18:22,882 --> 00:18:24,617 SCRAMBLASES PROTEINS AS BEING 361 00:18:24,617 --> 00:18:28,722 IMPORTANT IN REGULATING 362 00:18:28,722 --> 00:18:31,958 ENDOTHELIAL HEALTH BECAUSE THE 363 00:18:31,958 --> 00:18:33,793 PHOSPHO LIPIDS GET EXPOSED AND 364 00:18:33,793 --> 00:18:35,962 GET CLOTS AND YOU NOTICE THE 365 00:18:35,962 --> 00:18:37,931 FLIP BASES HAVE A SIMILAR 366 00:18:37,931 --> 00:18:40,734 PHENOTYPE MODULATED BY TMC1 OR 367 00:18:40,734 --> 00:18:42,969 THIS RESTRICTED TO THE 368 00:18:42,969 --> 00:18:43,870 SCRAMBLASE FAMILY? 369 00:18:43,870 --> 00:18:48,475 >> GOOD QUESTION. 370 00:18:48,475 --> 00:18:49,209 WE KNOW MUTATIONS ALSO CAUSE 371 00:18:49,209 --> 00:18:54,647 HEARING LOSS AND DEAFNESS SO 372 00:18:54,647 --> 00:18:55,982 MEMBRANE RESOLUTION IS IMPORTANT 373 00:18:55,982 --> 00:18:57,784 FOR PROPER HEARING AND BALANCE. 374 00:18:57,784 --> 00:19:00,720 FOR NOW WE THINK -- AND THIS IS 375 00:19:00,720 --> 00:19:03,356 NEW AND WE NEED TO DO MORE WORK, 376 00:19:03,356 --> 00:19:07,227 WE THINK THE TMC FUNCTIONS 377 00:19:07,227 --> 00:19:08,728 BECAUSE OF THE DATA GENERATED IN 378 00:19:08,728 --> 00:19:14,100 OUR LAB WE KNOW THEY'RE NOT 379 00:19:14,100 --> 00:19:16,102 LIPID SPECIFIC LIKE OTHER 380 00:19:16,102 --> 00:19:17,737 SCRAMBLASES SUGGESTING THEY 381 00:19:17,737 --> 00:19:18,938 DON'T NEED ENERGY LIKE OTHERS 382 00:19:18,938 --> 00:19:20,073 AND SO THEY'RE A LITTLE BIT 383 00:19:20,073 --> 00:19:20,340 DIFFERENT. 384 00:19:20,340 --> 00:19:23,109 THEY'RE ALSO NOT REGULATED AS 385 00:19:23,109 --> 00:19:26,513 THE TME16 SO THEY HAVE THINGS IN 386 00:19:26,513 --> 00:19:28,748 COMMON WITH OTHER LIPIDS BUT 387 00:19:28,748 --> 00:19:32,719 DIFFERENT IN SOME WAYS. 388 00:19:32,719 --> 00:19:34,254 >> THAT'S WONDERFUL, THANK YOU. 389 00:19:34,254 --> 00:19:35,789 DO THE HAIR CELLS REGENERATE? 390 00:19:35,789 --> 00:19:36,489 >> THEY DO NOT. 391 00:19:36,489 --> 00:19:38,091 I FORGOT TO MENTION THAT, THANK 392 00:19:38,091 --> 00:19:38,425 YOU. 393 00:19:38,425 --> 00:19:40,994 >> SO IF THEY DON'T REGENERATE I 394 00:19:40,994 --> 00:19:43,463 THINK THERE'S IMPORTANCE IN 395 00:19:43,463 --> 00:19:44,097 PRESERVING THEM. 396 00:19:44,097 --> 00:19:44,731 >> YES. 397 00:19:44,731 --> 00:19:45,298 THANK YOU SO MUCH. 398 00:19:45,298 --> 00:19:48,735 >> ARE THERE OTHER QUESTIONS 399 00:19:48,735 --> 00:19:52,405 FROM THE AUDIENCE? 400 00:19:52,405 --> 00:19:53,339 OKAY, WONDERFUL. 401 00:19:53,339 --> 00:19:57,277 THANK YOU VERY MUCH, DR 402 00:19:57,277 --> 00:19:58,278 DR. BALLESTEROS. 403 00:19:58,278 --> 00:20:02,082 I TRIED TO TAKE EVERY SEMINAR 404 00:20:02,082 --> 00:20:02,916 FLA CARDIOVASCULAR. 405 00:20:02,916 --> 00:20:04,217 THE NEXT SPEAKER IS 406 00:20:04,217 --> 00:20:06,052 DR. JACQUELINE HAVE TO TALKING 407 00:20:06,052 --> 00:20:08,088 ABOUT TREATMENT RELATED 408 00:20:08,088 --> 00:20:09,456 CARDIOVASCULAR DISEASE AND 409 00:20:09,456 --> 00:20:12,759 HEALTH INEQUITIES AMONG BREAST 410 00:20:12,759 --> 00:20:15,228 CANCER SURVIVORS AND WILL BE 411 00:20:15,228 --> 00:20:19,199 PRESENTING VIRTUALLY. 412 00:20:19,199 --> 00:20:23,770 WELCOME, DR. HAVE TO. 413 00:20:23,770 --> 00:20:34,080 -- WELCOME DR. VO. 414 00:20:43,123 --> 00:20:45,692 >> THANK YOU FOR THE 415 00:20:45,692 --> 00:20:47,026 INTRODUCTION AND GOOD MORNING 416 00:20:47,026 --> 00:20:52,499 FROM LOS ANGELES, CALIFORNIA. 417 00:20:52,499 --> 00:20:56,102 THANK YOU FOR THE ORGANIZATION. 418 00:20:56,102 --> 00:21:02,075 I'M AT A CONFERENCE THIS WEEK A 419 00:21:02,075 --> 00:21:04,244 JUNIOR INVESTIGATOR AND 420 00:21:04,244 --> 00:21:05,745 DELIGHTED TO SHARE A BRIEF 421 00:21:05,745 --> 00:21:06,312 DESCRIPTION OF ANY RESEARCH 422 00:21:06,312 --> 00:21:13,753 PORTFOLIO. 423 00:21:13,753 --> 00:21:16,756 THERE ARE OVER 4 MILLION BREAST 424 00:21:16,756 --> 00:21:18,258 CANCER SURVIVORS IN THE UNITED 425 00:21:18,258 --> 00:21:18,658 STATES. 426 00:21:18,658 --> 00:21:24,497 THEY'RE LIVING LONGER DUE TO 427 00:21:24,497 --> 00:21:25,064 ADVANCES IN SCREENING AND 428 00:21:25,064 --> 00:21:27,200 TREATMENT AND SURVIVAL. 429 00:21:27,200 --> 00:21:29,335 BECAUSE THEY'RE LIVING LONGER 430 00:21:29,335 --> 00:21:30,036 DOESN'T NECESSARILY MEAN THEY'RE 431 00:21:30,036 --> 00:21:31,571 LIVING BETTER. 432 00:21:31,571 --> 00:21:35,742 MANY CANCER TREATMENTS CAN 433 00:21:35,742 --> 00:21:37,810 UNFORTUNATELY CAUSE ADVERSE 434 00:21:37,810 --> 00:21:39,412 HEALTH EFFECTS. 435 00:21:39,412 --> 00:21:42,315 BREAST CANCER SURVIVORS FACE 436 00:21:42,315 --> 00:21:45,952 RISK OF CARDIOVASCULAR COMPARED 437 00:21:45,952 --> 00:21:48,288 TO WOMEN WITHOUT BREAST CANCER 438 00:21:48,288 --> 00:21:58,631 DUE TO CHEMOTHERAPY. 439 00:21:59,165 --> 00:22:02,101 WE REPORTED AN INTERESTING TREND 440 00:22:02,101 --> 00:22:05,738 IN HEART DISEASE MORTALITY AMONG 441 00:22:05,738 --> 00:22:08,107 WOMEN TREATED WITH CHEMOTHERAPY 442 00:22:08,107 --> 00:22:11,244 FROM 1975 TO 2016 THE RISK WAS 443 00:22:11,244 --> 00:22:20,086 DRIVEN BY CHEMOTHERAPY BUT IT 444 00:22:20,086 --> 00:22:28,728 DOES NOT HAVE CHEMOTHERAPY 445 00:22:28,728 --> 00:22:28,962 TYPES. 446 00:22:28,962 --> 00:22:37,503 AND THERE'S A LACK OF DATA 447 00:22:37,503 --> 00:22:40,506 DRIVEN STUDIES AND DON'T HAVE 448 00:22:40,506 --> 00:22:41,841 AGE SPECIFIC RECOMMENDATIONS. 449 00:22:41,841 --> 00:22:44,077 THE FINDINGS OF ONE OF MY 450 00:22:44,077 --> 00:22:45,945 STUDIES AND THE AIM WAS TO 451 00:22:45,945 --> 00:22:48,748 EVALUATE THE LONG-TERM RISK OF 452 00:22:48,748 --> 00:22:51,251 INCIDENT OF CARDIOVASCULAR 453 00:22:51,251 --> 00:22:53,219 DISEASE AFTER TREATMENT AMONG 454 00:22:53,219 --> 00:22:56,522 APPROXIMATELY 10,000, ONE-YEAR 455 00:22:56,522 --> 00:23:06,032 BREAST CANCER SURVIVORS. 456 00:23:06,032 --> 00:23:06,766 WE HAVE A BREAST CANCER 457 00:23:06,766 --> 00:23:08,735 SURVIVORS COHORT WITH 458 00:23:08,735 --> 00:23:10,803 PROSPECTIVE FOLLOW-UP USING DATA 459 00:23:10,803 --> 00:23:13,840 FROM CANCER REGISTRIES AND 460 00:23:13,840 --> 00:23:14,641 ELECTRONIC HEALTH RECORDS AND 461 00:23:14,641 --> 00:23:16,709 DEATH DATA. 462 00:23:16,709 --> 00:23:19,879 THE CO-P.I. ALONGSIDE HERE AND 463 00:23:19,879 --> 00:23:22,215 THE TEAM IS HIGHLIGHTED TO THE 464 00:23:22,215 --> 00:23:24,817 RIGHT AND OUR COLLABORATORS 465 00:23:24,817 --> 00:23:25,251 BELOW. 466 00:23:25,251 --> 00:23:32,091 THE PRESENT STUDY LEVERAGED DATA 467 00:23:32,091 --> 00:23:36,429 FROM KAISER PERMANENTEs. 468 00:23:36,429 --> 00:23:40,733 THE PRIMARY EXPOSURE IS REGIMENT 469 00:23:40,733 --> 00:23:45,438 TYPE BASED ON TOXICITY AND 470 00:23:45,438 --> 00:23:46,439 OTHERS IN THE REFERENCE GROUP. 471 00:23:46,439 --> 00:23:49,709 FOR OUTCOME OF INTEREST WE 472 00:23:49,709 --> 00:23:51,244 INCLUDED CAUSE SPECIFIC 473 00:23:51,244 --> 00:23:52,712 CARDIOVASCULAR DISEASE AND HEART 474 00:23:52,712 --> 00:23:56,082 FAILURE AND ISCHEMIC HEART 475 00:23:56,082 --> 00:23:58,318 DISEASE AND STROKE. 476 00:23:58,318 --> 00:24:03,890 I'LL ONLY PRESENT THE CAR 477 00:24:03,890 --> 00:24:05,291 CARDIOPATHY RESULTS. 478 00:24:05,291 --> 00:24:09,595 WE HAD INCIDENTS ACCOUNTING FOR 479 00:24:09,595 --> 00:24:12,732 COMPETING EVENT AND USED A 480 00:24:12,732 --> 00:24:16,569 REGRESSION MODEL TO ACCOUNT OR 481 00:24:16,569 --> 00:24:17,370 THE CARDIOVASCULAR RISK WITH AGE 482 00:24:17,370 --> 00:24:23,276 AND CHARACTERISTICS AND OTHER 483 00:24:23,276 --> 00:24:24,744 BREAST CANCER TREATMENTS AND 484 00:24:24,744 --> 00:24:27,180 OTHER RISKS. 485 00:24:27,180 --> 00:24:28,848 THESE ARE THE PATIENT AND BREAST 486 00:24:28,848 --> 00:24:39,258 CANCER CHARACTERISTICS. 487 00:24:40,793 --> 00:24:42,528 AND DIAGNOSED AT YOUNGER AGES 488 00:24:42,528 --> 00:24:47,934 AND MORE ADVANCED STAGE AND MORE 489 00:24:47,934 --> 00:24:51,371 AGGRESSIVE TYPES COMPARED TO 490 00:24:51,371 --> 00:24:56,008 WOMEN WHO RECEIVE OTHER 491 00:24:56,008 --> 00:24:59,445 CHEMOTHERAPIES OR NO 492 00:24:59,445 --> 00:24:59,779 CHEMOTHERAPY. 493 00:24:59,779 --> 00:25:04,317 THIS IS TYPE STRATIFIED BY AGE 494 00:25:04,317 --> 00:25:09,922 AND THESE ARE WOMEN LESS THAN' 495 00:25:09,922 --> 00:25:12,191 55 YEARS OF AGE AND THE RIGHT IS 496 00:25:12,191 --> 00:25:14,026 WOMEN 65 YEARS AND OLDER. 497 00:25:14,026 --> 00:25:17,230 ON THE X AXIS IS YEARS SINCE 498 00:25:17,230 --> 00:25:20,333 BREAST CANCER DIAGNOSIS. 499 00:25:20,333 --> 00:25:25,204 AT 10 YEARS AFTER BREAST CANCER 500 00:25:25,204 --> 00:25:31,878 DIAGNOSIS THE RISK DIFFERENCES 501 00:25:31,878 --> 00:25:39,685 FOR CARDIO MIOPANELY. 502 00:25:39,685 --> 00:25:42,989 YOU CAN SEE THE WOMEN TREATED 503 00:25:42,989 --> 00:25:46,325 WITH THESE SPECIFICALLY THE 10 504 00:25:46,325 --> 00:25:49,195 YEAR INCIDENT WAS 1 IN 29 FOR 505 00:25:49,195 --> 00:25:51,264 WOMEN LESS THAN 55 YEARS AND 506 00:25:51,264 --> 00:25:54,600 LESS THAN 1 IN 10 FOR WOMEN 55 507 00:25:54,600 --> 00:25:59,705 TO 64 YEARS. 508 00:25:59,705 --> 00:26:02,074 NO DIFFERENCES FOR WOMEN TREATED 509 00:26:02,074 --> 00:26:08,080 OLDER THAN 65. 510 00:26:08,080 --> 00:26:12,752 WE LOOKED AT WOMEN WHO DID NOT 511 00:26:12,752 --> 00:26:20,092 RECEIVE CHEMOTHERAPY AND A 512 00:26:20,092 --> 00:26:30,503 BREAST CANCER DIAGNOSIS. 513 00:26:33,906 --> 00:26:39,178 WOMEN TREATED THIS HAD HIRE 514 00:26:39,178 --> 00:26:40,713 INSTANCES. 515 00:26:40,713 --> 00:26:43,950 THESE RISKS PERSIST LONG TERM 516 00:26:43,950 --> 00:26:46,919 FROM FIVE TO NINE YEARS AFTER 517 00:26:46,919 --> 00:26:48,721 DIAGNOSIS AND 10 PLUS YEARS 518 00:26:48,721 --> 00:26:50,957 AFTER AND WE FOUND RESULTS FOR 519 00:26:50,957 --> 00:26:52,425 BREAST CANCER SURVIVORS LESS 520 00:26:52,425 --> 00:26:54,126 THAN 65 YEARS. 521 00:26:54,126 --> 00:26:56,729 THE HIGHEST RISKS WERE OBSERVED 522 00:26:56,729 --> 00:27:00,733 AMONG THE YOUNGEST GROUP AGE 20 523 00:27:00,733 --> 00:27:04,737 TO 64 YEARS RECEIVING THIS HAD A 524 00:27:04,737 --> 00:27:08,074 THREE TIMES HIGHER RISK OF 525 00:27:08,074 --> 00:27:09,742 DEVELOPING CARDIOMYOPATHY 526 00:27:09,742 --> 00:27:12,778 COMPARED TO THOSE WHO DID NOT 527 00:27:12,778 --> 00:27:14,080 RECEIVE ANY THERAPY. 528 00:27:14,080 --> 00:27:16,115 ACROSS 24 YEARS OF FOLLOW-UP 529 00:27:16,115 --> 00:27:19,218 BREAST CANCER SURVIVORS TREATED 530 00:27:19,218 --> 00:27:20,720 WITH THESE WERE AT INCREASED 531 00:27:20,720 --> 00:27:22,922 RISK OF HEART FAILURE AND THE 532 00:27:22,922 --> 00:27:27,093 RISKS PERSISTED EVEN AFTER 10 533 00:27:27,093 --> 00:27:28,261 YEARS AFTER BREAST CANCER 534 00:27:28,261 --> 00:27:30,129 TREATMENT AND AMONG WOMEN 535 00:27:30,129 --> 00:27:32,231 DIAGNOSED WITH BREAST CANCER 536 00:27:32,231 --> 00:27:36,636 BEFORE AGE 65. 537 00:27:36,636 --> 00:27:37,904 NOT EVERY PATIENT WHO RECEIVED 538 00:27:37,904 --> 00:27:40,740 THESE WILL GO ON TO DEVELOP A 539 00:27:40,740 --> 00:27:41,440 CARDIOVASCULAR DISEASE. 540 00:27:41,440 --> 00:27:44,076 WHO ARE THE PATIENTS AT HIGHEST 541 00:27:44,076 --> 00:27:50,082 RISK FOR DEVELOPING A TREATMENT 542 00:27:50,082 --> 00:27:52,618 IMPLICATED DISEASE AND WANT TO 543 00:27:52,618 --> 00:27:55,588 HIGHLIGHT THE NEED TO LOOK AT 544 00:27:55,588 --> 00:27:58,491 HIGH RISK PATIENTS ESPECIALLY 545 00:27:58,491 --> 00:28:02,094 YOUNGER WOMEN SURVIVING MANY 546 00:28:02,094 --> 00:28:12,505 DECADES AFTER TREATMENT. 547 00:28:21,180 --> 00:28:24,216 AND I LOOKED AT DIFFERENT 548 00:28:24,216 --> 00:28:26,118 POPULATIONS AND THOSE IN THE 549 00:28:26,118 --> 00:28:30,189 LOWEST ECONOMIC STRATS. 550 00:28:30,189 --> 00:28:30,523 STATUS. 551 00:28:30,523 --> 00:28:32,325 ONE AREA OF HEALTH DISPARITY 552 00:28:32,325 --> 00:28:33,759 RESEARCH I'M PARTICULARLY 553 00:28:33,759 --> 00:28:38,898 INTERESTED IN IS ASIAN AMERICANS 554 00:28:38,898 --> 00:28:42,335 WHO COMPRISE DIFFERENT AND 555 00:28:42,335 --> 00:28:47,473 DISTINCT RACIAL GROUPS AND IN 556 00:28:47,473 --> 00:28:50,409 THE STUDY WE LOOKED AT ASIAN 557 00:28:50,409 --> 00:28:52,211 AMERICAN AND PACIFIC ISLANDER 558 00:28:52,211 --> 00:28:53,179 POPULATION. 559 00:28:53,179 --> 00:28:53,779 AND I'VE HIGHLIGHT THE FEMALE 560 00:28:53,779 --> 00:29:03,990 POPULATION. 561 00:29:04,790 --> 00:29:12,732 CANCER MORTALITY WAS TWO TIMES 562 00:29:12,732 --> 00:29:14,400 HIGHER FOR SOME GROUPS AND 563 00:29:14,400 --> 00:29:16,736 LOOKED AT DISPARITIES WHO 564 00:29:16,736 --> 00:29:22,141 RESPONSE A SMALL PERCENT OF THE 565 00:29:22,141 --> 00:29:22,742 GROUP. 566 00:29:22,742 --> 00:29:24,377 TO ACCOMPLISH ANY GOAL I 567 00:29:24,377 --> 00:29:28,848 INCREASED THE RACIAL DIVERSITY 568 00:29:28,848 --> 00:29:32,118 WITHIN THE COHORT WITH THE THE 569 00:29:32,118 --> 00:29:42,662 SUPPORT OF THE NIH DISTINGUISHED 570 00:29:43,496 --> 00:29:48,067 SCHOLAR PROGRAM AND I LOOKED IF 571 00:29:48,067 --> 00:29:51,103 AND HOW IT IMPACTED MINORITIZED 572 00:29:51,103 --> 00:29:53,506 CANCER SURVIVORS AND LOOKED AT 573 00:29:53,506 --> 00:29:56,776 CARDIOVASCULAR DISEASE AND 574 00:29:56,776 --> 00:29:58,778 MORTALITY AND RACE AND ETHNICITY 575 00:29:58,778 --> 00:30:00,413 AND ACCOUNTING FOR SOCIO 576 00:30:00,413 --> 00:30:01,147 ECONOMIC STATUS. 577 00:30:01,147 --> 00:30:03,082 WITH THAT I'D LIKE TO 578 00:30:03,082 --> 00:30:04,717 ACKNOWLEDGE AND THANK MY MENTORS 579 00:30:04,717 --> 00:30:07,119 AND COLLEAGUES AND COLLABORATORS 580 00:30:07,119 --> 00:30:09,855 AND MY MENTEE IN THE NIH 581 00:30:09,855 --> 00:30:12,024 DISTINGUISHED SCHOLARS PROGRAM 582 00:30:12,024 --> 00:30:15,861 AND IT'S BEEN A WONDERFUL YEAR 583 00:30:15,861 --> 00:30:17,296 IN THE DSP AND I LOOK FORWARD TO 584 00:30:17,296 --> 00:30:21,000 THE YEARS TO COME. 585 00:30:21,000 --> 00:30:27,173 THANK YOU. 586 00:30:27,173 --> 00:30:27,840 >> THANK YOU. 587 00:30:27,840 --> 00:30:30,309 LEAVE IT TO THE DSP SCHOLARS TO 588 00:30:30,309 --> 00:30:30,810 STAY ON TIME. 589 00:30:30,810 --> 00:30:35,448 IT'S INTERESTING WORK AND 590 00:30:35,448 --> 00:30:36,248 CONGRATULATIONS ON SEEING DIRECT 591 00:30:36,248 --> 00:30:37,850 AND IMMEDIATE OUTCOMES OF YOUR 592 00:30:37,850 --> 00:30:39,652 WORK CHANGING THE WAY DATA IS 593 00:30:39,652 --> 00:30:40,686 COLLECTED TO THEN THINK ABOUT 594 00:30:40,686 --> 00:30:41,620 WHAT COMES AFTER THAT. 595 00:30:41,620 --> 00:30:45,157 THERE'S QUESTIONS IN THE 596 00:30:45,157 --> 00:30:46,726 AUDIENCE, DR. PLATT. 597 00:30:46,726 --> 00:30:48,160 >> THIS IS NICE. 598 00:30:48,160 --> 00:30:49,962 I'M CURIOUS ABOUT DIABETES. 599 00:30:49,962 --> 00:30:52,531 IT KEPT SHOWING UP AND KNOW IT'S 600 00:30:52,531 --> 00:30:54,133 INCREASED IN CERTAIN 601 00:30:54,133 --> 00:30:54,867 MINORITIZED. 602 00:30:54,867 --> 00:30:58,003 WHAT'S THE SUGGESTION FOR BREAST 603 00:30:58,003 --> 00:31:00,673 CANCER DOCTORS IN DEALING WITH 604 00:31:00,673 --> 00:31:02,108 PATIENTS WITH DIABETES AND WHERE 605 00:31:02,108 --> 00:31:05,077 IT MAY BE A COMPLICATION OF 606 00:31:05,077 --> 00:31:05,911 BREAST CANCER. 607 00:31:05,911 --> 00:31:08,414 I'M CURIOUS FOR ANY ADVICE ON 608 00:31:08,414 --> 00:31:08,714 THAT. 609 00:31:08,714 --> 00:31:14,286 >> THAT'S A GOOD QUESTION AND 610 00:31:14,286 --> 00:31:17,556 CONSIDERING WE HAVE 611 00:31:17,556 --> 00:31:19,725 COMORBIDITIES SO COMMON AND 612 00:31:19,725 --> 00:31:20,059 CO-OCCURRING. 613 00:31:20,059 --> 00:31:24,730 I DON'T HAVE PARTICULAR ADVICE 614 00:31:24,730 --> 00:31:28,234 FOR CLINICIANS AT THE MOMENT FOR 615 00:31:28,234 --> 00:31:29,702 DIABETES BUT IT NEEDS TO BE 616 00:31:29,702 --> 00:31:32,004 RESEARCHED FURTHER AND LOOKING 617 00:31:32,004 --> 00:31:34,540 AT CARDIOVASCULAR IN OUR STUDY 618 00:31:34,540 --> 00:31:36,709 WE DIDN'T ACCOUNT FOR DIABETES 619 00:31:36,709 --> 00:31:39,712 BUT IT'S SOMETHING WE'RE 620 00:31:39,712 --> 00:31:41,514 CONSIDERING IN THE FUTURE FOR 621 00:31:41,514 --> 00:31:44,116 PATIENT WHO'S PRESENT WITH 622 00:31:44,116 --> 00:31:47,553 CO-MORBIDITIES HOW THEIR RISK OF 623 00:31:47,553 --> 00:31:50,122 CARDIOVASCULAR DISEASE MAY CARE 624 00:31:50,122 --> 00:31:52,725 IN PARTICULAR TO THEIR CANCER 625 00:31:52,725 --> 00:31:55,427 TREATMENT. 626 00:31:55,427 --> 00:31:55,694 THANK YOU. 627 00:31:55,694 --> 00:31:59,165 >> I WAS INTRIGUED BY THE FACT 628 00:31:59,165 --> 00:32:00,733 THAT WOMEN OLDER THAN 65 WERE 629 00:32:00,733 --> 00:32:02,902 KIND OF PROTECTED. 630 00:32:02,902 --> 00:32:06,872 I WAS WONDERING IF YOU HAVE ANY 631 00:32:06,872 --> 00:32:08,107 HYPOTHESES IN TERMS OF MECHANISM 632 00:32:08,107 --> 00:32:09,975 WHETHER THAT WAS MAYBE IN 633 00:32:09,975 --> 00:32:13,546 THEY'RE IN SENESCENCE TO SOME 634 00:32:13,546 --> 00:32:16,715 DEGREE AND THEY'RE HEART CELLS 635 00:32:16,715 --> 00:32:24,723 ARE NOT AS VULNERABLE TO THE 636 00:32:24,723 --> 00:32:26,425 ANTHRACYCLINE TREATMENT AND 637 00:32:26,425 --> 00:32:27,827 WHETHER YOU'RE PLANNING STUDIES 638 00:32:27,827 --> 00:32:30,563 IN THE FUTURE TO ELUCIDATE THAT. 639 00:32:30,563 --> 00:32:35,434 >> THAT'S A GREAT QUESTION. 640 00:32:35,434 --> 00:32:38,804 AMONG OLDER WOMEN THEIR HEART 641 00:32:38,804 --> 00:32:40,706 WOULDN'T NECESSARILY BE 642 00:32:40,706 --> 00:32:41,907 PROTECTED FROM THE CARDIO 643 00:32:41,907 --> 00:32:44,109 TOXICITY I THINK WE'RE 644 00:32:44,109 --> 00:32:47,012 HIGHLIGHTING A POTENTIAL 645 00:32:47,012 --> 00:32:48,948 DIFFERENCE IN MAYBE HEALTH CARE 646 00:32:48,948 --> 00:32:52,551 AND TREATMENT ACCESS FOR OLDER 647 00:32:52,551 --> 00:32:52,785 PATIENT. 648 00:32:52,785 --> 00:32:56,055 AS YOU GET OLDER THE RISK OF 649 00:32:56,055 --> 00:32:57,523 CARDIOVASCULAR DISEASE INCREASES 650 00:32:57,523 --> 00:33:00,626 SO CLINICIANS MAY BE MORE 651 00:33:00,626 --> 00:33:02,795 CAUTIOUS WHETHER TO GIVE THEM A 652 00:33:02,795 --> 00:33:05,564 CARDIO TOXIC DRUG WHEN THEY KNOW 653 00:33:05,564 --> 00:33:08,100 THEIR RISK IS HIGHER THAN FOR A 654 00:33:08,100 --> 00:33:11,570 YOUNGER WOMEN WHO ARE MUCH 655 00:33:11,570 --> 00:33:13,305 HEALTHIER AND HAVE LESS 656 00:33:13,305 --> 00:33:13,606 COMORBIDITY. 657 00:33:13,606 --> 00:33:19,345 I DON'T KNOW IF THAT'S PER SE 658 00:33:19,345 --> 00:33:21,046 THE CONSIDERATION AND BIOMARKERS 659 00:33:21,046 --> 00:33:22,147 ARE AN IMPORTANT CONTEXT. 660 00:33:22,147 --> 00:33:26,986 WE COLLECTED SOME INFORMATION 661 00:33:26,986 --> 00:33:30,256 BUT IT'S ON BASED ON THE 662 00:33:30,256 --> 00:33:30,956 ELECTRONIC HEALTH RECORDS BUT 663 00:33:30,956 --> 00:33:32,725 SOMETHING WE'RE TRYING TO 664 00:33:32,725 --> 00:33:33,158 ELUCIDATE FURTHER. 665 00:33:33,158 --> 00:33:33,893 >> THANK YOU VERY MUCH. 666 00:33:33,893 --> 00:33:35,861 THAT WAS INTERESTING WORK. 667 00:33:35,861 --> 00:33:40,733 YOU SHOWED YOUR DATA IN 668 00:33:40,733 --> 00:33:44,103 LONG-TERM CARDIOVASCULAR DISEASE 669 00:33:44,103 --> 00:33:50,542 AFTER SOME INHIBITOR? 670 00:33:50,542 --> 00:33:51,176 >> GREAT QUESTION. 671 00:33:51,176 --> 00:33:54,647 THE STUDY WE HAVE IS ONGOING AND 672 00:33:54,647 --> 00:33:55,247 HOPEFULLY WE CAN PRESENT THAT 673 00:33:55,247 --> 00:34:05,524 MAYBE NEXT YEAR. 674 00:34:07,660 --> 00:34:10,095 >> THE TREATMENT WITH 675 00:34:10,095 --> 00:34:13,232 NON-CHEMOTHERAPY MAKES WE WONDER 676 00:34:13,232 --> 00:34:14,633 WHETHER THERE'S AN INCREASE IN 677 00:34:14,633 --> 00:34:15,868 CARDIOVASCULAR DISEASE COMPARED 678 00:34:15,868 --> 00:34:20,306 WITH THE NORMAL OR NON-CANCER 679 00:34:20,306 --> 00:34:21,206 POPULATION. 680 00:34:21,206 --> 00:34:23,142 >> GOOD POINT. 681 00:34:23,142 --> 00:34:26,812 I THINK ONE OF THE MAIN ASPECTS 682 00:34:26,812 --> 00:34:28,948 HERE IS THAT CARDIOVASCULAR 683 00:34:28,948 --> 00:34:32,117 DISEASE AND BREAST CANCER ARE 684 00:34:32,117 --> 00:34:38,123 DISEASES THAT HAVE SOME RARE 685 00:34:38,123 --> 00:34:39,491 RISK FACTORS AND SOMETIMES 686 00:34:39,491 --> 00:34:40,859 BREAST CANCER SURVIVORS ARE AT 687 00:34:40,859 --> 00:34:49,234 AN INCREASED RISK COMPARED TO 688 00:34:49,234 --> 00:34:51,770 WOMEN NAON-CANCER AND LIKELY TO 689 00:34:51,770 --> 00:34:52,705 DIE OF CARDIOVASCULAR DISEASE 690 00:34:52,705 --> 00:35:00,446 AND WE TOOK THAT INTO PLAY. 691 00:35:00,446 --> 00:35:02,481 >> THE DATA YOU SHOWED THAT LAGS 692 00:35:02,481 --> 00:35:04,750 OF TENDS TO LAG A COUPLE YEARS 693 00:35:04,750 --> 00:35:07,386 BEHIND WITH THE INCREASED USE OF 694 00:35:07,386 --> 00:35:08,754 IMMUNOTHERAPY DO YOU KNOW IF 695 00:35:08,754 --> 00:35:10,356 THERE'S A SIGNAL THERE THAT 696 00:35:10,356 --> 00:35:12,324 MIGHT POINT IN THE SAME 697 00:35:12,324 --> 00:35:14,159 DIRECTION OR NO COMPARISON WITH 698 00:35:14,159 --> 00:35:16,729 CHEMOTHERAPY? 699 00:35:16,729 --> 00:35:20,766 >> I THINK WITH AMONG THE BREAST 700 00:35:20,766 --> 00:35:23,435 CANCER POPULATION IMMUNOTHERAPY 701 00:35:23,435 --> 00:35:28,307 IS MORE RECENT AND TO ELUCIDATE 702 00:35:28,307 --> 00:35:32,945 LONG-TERM RISK WILL TAKE MORE 703 00:35:32,945 --> 00:35:34,413 TIME AND HOPE THAT'S SOMETHING 704 00:35:34,413 --> 00:35:38,250 WE CAN CAPTURE IN THE FOLLOW-UP. 705 00:35:38,250 --> 00:35:44,123 WE'RE EXCITED TO BE ABLE TO 706 00:35:44,123 --> 00:35:45,991 ELUCIDATE THESE QUESTIONS IN THE 707 00:35:45,991 --> 00:35:51,597 FUT 708 00:35:51,597 --> 00:35:51,830 FUTURE. 709 00:35:51,830 --> 00:35:54,533 >> IT MAY APPLY TO OTHER DISEASE 710 00:35:54,533 --> 00:35:57,102 STATES LIKE CARDIOVASCULAR 711 00:35:57,102 --> 00:35:59,304 DISEASE AND ATHEROSCLEROSIS AND 712 00:35:59,304 --> 00:35:59,838 OTHERS AS WELL. 713 00:35:59,838 --> 00:36:02,141 THIS IS AN INTERESTING AREA AND 714 00:36:02,141 --> 00:36:06,311 WE'LL STAY TUNED FOR WHAT YOU 715 00:36:06,311 --> 00:36:08,113 PRESENT. 716 00:36:08,113 --> 00:36:12,618 THANK YOU, DR. VO. 717 00:36:12,618 --> 00:36:15,687 WE'LL STAY ON THE FEMALE 718 00:36:15,687 --> 00:36:19,491 IMMUNOTHERAPY, DR. ROSEA NYUYEN 719 00:36:19,491 --> 00:36:26,165 FROM THE 2023 COHORT ON 720 00:36:26,165 --> 00:36:29,201 IMMUNOTHERAPIES FOR PEDIATRIC 721 00:36:29,201 --> 00:36:29,868 NEUROBLASTOMA FROM BENCH TO THE 722 00:36:29,868 --> 00:36:40,045 BED SIDE. 723 00:36:46,018 --> 00:36:47,686 >> I'M EXCITED TO BE HERE AND 724 00:36:47,686 --> 00:36:50,923 WANT TO USE MY 10 MINUTES TO 725 00:36:50,923 --> 00:36:54,793 TALK WITH YOU ABOUT 726 00:36:54,793 --> 00:36:56,128 IMMUNOTHERAPIES FOR PEDIATRIC 727 00:36:56,128 --> 00:36:59,398 NEUROBLASTOMA AND START WITH A 728 00:36:59,398 --> 00:37:00,466 PICTURE OF MY LAB. 729 00:37:00,466 --> 00:37:03,335 THE SOLID TUMOR AND IMMUNOLOGY 730 00:37:03,335 --> 00:37:04,103 SECTION. 731 00:37:04,103 --> 00:37:06,839 A DIVERSE GROUP OF PEOPLE FROM 732 00:37:06,839 --> 00:37:08,140 SEVEN DIFFERENT NATIONS AND FUN 733 00:37:08,140 --> 00:37:09,875 BUT DEDICATED COME TO THE LAB 734 00:37:09,875 --> 00:37:15,447 EVERY DAY TO WORK ON DEVELOPING 735 00:37:15,447 --> 00:37:16,982 NEW IMMUNOTHERAPIES WITH FOR 736 00:37:16,982 --> 00:37:19,651 CHILDREN WITH SOLID TUMORS WITH 737 00:37:19,651 --> 00:37:21,320 THE FOCUS ON NEUROBLASTOMA. 738 00:37:21,320 --> 00:37:26,125 ONE OF THE APPROACHES I'LL SHARE 739 00:37:26,125 --> 00:37:31,096 IS INTEGRATING THE GAMMA C 740 00:37:31,096 --> 00:37:32,698 CYTOKINES AND AMONG THE GROUP 741 00:37:32,698 --> 00:37:34,700 WE'RE PARTICULARLY INTERESTED IN 742 00:37:34,700 --> 00:37:39,671 INTERLEUKIN 15 AND 21 TO IMPROVE 743 00:37:39,671 --> 00:37:42,474 ANTIBODY THERAPY AND CAR T CELL 744 00:37:42,474 --> 00:37:42,708 THERAPY. 745 00:37:42,708 --> 00:37:45,711 NEURO BLASTOMA IS A SOLID TUMOR 746 00:37:45,711 --> 00:37:47,779 THAT ORIGINATES FROM THE NEURAL 747 00:37:47,779 --> 00:37:49,781 CREST AND YOUNG CHILDREN AND 748 00:37:49,781 --> 00:37:52,484 TODDLERS ARE PREDOMINANTLY 749 00:37:52,484 --> 00:37:52,751 AFFECTED. 750 00:37:52,751 --> 00:37:55,587 PEDIATRIC ONCOLOGY AND CANCERS 751 00:37:55,587 --> 00:37:56,922 IN GENERAL ARE VERY RARE AND 752 00:37:56,922 --> 00:38:00,959 AMONG THIS GROUP OF PATIENTS WE 753 00:38:00,959 --> 00:38:08,133 ONLY HAVE 650 NEW CASES A YEAR 754 00:38:08,133 --> 00:38:12,004 BUT PUTS US AT THIS PART IN 755 00:38:12,004 --> 00:38:13,772 CHILDREN AND THEY'RE AT HIGH 756 00:38:13,772 --> 00:38:16,141 RISK FOR RELAPSE OR REFRACTORY 757 00:38:16,141 --> 00:38:16,708 DISEASE OR DEATH. 758 00:38:16,708 --> 00:38:18,710 IT'S NOT SURPRISING WHEN I TELL 759 00:38:18,710 --> 00:38:22,548 YOU 15% OF ALL CANCER RELATED 760 00:38:22,548 --> 00:38:24,082 DEATHS IN CHILDREN ARE CAUSED BY 761 00:38:24,082 --> 00:38:28,720 NEURO BLASTOMA. 762 00:38:28,720 --> 00:38:30,556 NOT BECAUSE WE DON'T TREAT THEM 763 00:38:30,556 --> 00:38:32,658 THEY GET THE KITCHEN SINK AND 764 00:38:32,658 --> 00:38:34,826 30% WITHIN THE POPULATION OF 765 00:38:34,826 --> 00:38:36,728 HIGH-RISK PATIENTS CAN ACHIEVE 766 00:38:36,728 --> 00:38:37,996 LONG-TERM REMISSIONS. 767 00:38:37,996 --> 00:38:41,633 A BIG BREAKTHROUGH IN THE FIELD 768 00:38:41,633 --> 00:38:44,703 WAS ACTUALLY THE FDA APPROVAL OF 769 00:38:44,703 --> 00:38:50,809 THE ANTI-GD2 ANTIBODY THE FIRST 770 00:38:50,809 --> 00:38:53,946 IMMUNOTHERAPY IN SOLID TUMOR AND 771 00:38:53,946 --> 00:38:57,249 THE PHASE 3 TRIAL, CHILDREN WITH 772 00:38:57,249 --> 00:38:59,885 NEURO BLASTOMA THAT ATTAINED A 773 00:38:59,885 --> 00:39:02,087 STATE OF MINIMUM RESIDUAL 774 00:39:02,087 --> 00:39:04,089 DISEASE WERE RANDOMIZED TO 775 00:39:04,089 --> 00:39:07,960 RECEIVE STANDARD OF CARE OR THE 776 00:39:07,960 --> 00:39:13,098 ANTIBODY WITH CYTOKINES AND A 777 00:39:13,098 --> 00:39:15,400 TRIAL BENEFIT AND THIS BECAME 778 00:39:15,400 --> 00:39:19,471 THE STANDARD OF CARE. 779 00:39:19,471 --> 00:39:20,639 THE ANTIBODY WORKS -- IT'S QUITE 780 00:39:20,639 --> 00:39:24,409 FASCINATING THERAPY IN MY MIND. 781 00:39:24,409 --> 00:39:26,378 IT BRINGS TOGETHER EFFECTER 782 00:39:26,378 --> 00:39:28,547 CELLS OF THE IMMUNE SYSTEM AND 783 00:39:28,547 --> 00:39:30,315 TUMOR CELLS BY RECOGNIZING HIGH 784 00:39:30,315 --> 00:39:33,018 LEVELS OF AN ANTIGEN IN THIS 785 00:39:33,018 --> 00:39:36,054 CASE GD2 AND LEADS TO THE 786 00:39:36,054 --> 00:39:39,024 KILLING OF THE TUMOR CELLS BY 787 00:39:39,024 --> 00:39:41,627 THESE EFFECTER CELLS AND YOU CAN 788 00:39:41,627 --> 00:39:43,629 MODULATE THE REACTION FOR 789 00:39:43,629 --> 00:39:49,034 EXAMPLE BY ADDING CYTOKINES THAT 790 00:39:49,034 --> 00:39:50,636 EITHER ENHANCE OR SUPPRESS THE 791 00:39:50,636 --> 00:39:52,704 TUMOR CELLS AND CAN TAKE THE 792 00:39:52,704 --> 00:39:55,173 CYTOKINES AND TETHER THEM TO THE 793 00:39:55,173 --> 00:39:57,643 ANTIBODY SO YOU ONLY HAVE LOCAL 794 00:39:57,643 --> 00:40:00,712 EXPOSURE OF THESE VERY POTENT 795 00:40:00,712 --> 00:40:02,114 YET TOXIC MOLECULES. 796 00:40:02,114 --> 00:40:04,716 AND THAT'S WHAT WE DID. 797 00:40:04,716 --> 00:40:08,553 WE CREATED THESE IMMUNOCYTOKINES 798 00:40:08,553 --> 00:40:10,489 BY USING THE ANTIBODY AND 799 00:40:10,489 --> 00:40:13,492 TETHERING IL15 OR 21 TO THEM AND 800 00:40:13,492 --> 00:40:19,364 COMPARED THEM TO AN EXISTING 801 00:40:19,364 --> 00:40:21,767 IMMUNOCYTOKINE FROM THE GAMMA C 802 00:40:21,767 --> 00:40:22,200 FAMILY. 803 00:40:22,200 --> 00:40:24,002 AND WE TESTED THIS IN VITRO AND 804 00:40:24,002 --> 00:40:24,703 IN VIVO. 805 00:40:24,703 --> 00:40:27,239 I'M SHOWING DATA FROM AN IN VIVO 806 00:40:27,239 --> 00:40:28,707 EXPERIMENT FROM ANIMALS. 807 00:40:28,707 --> 00:40:36,648 THESE WERE IMMUNOCOMPETENT MICE 808 00:40:36,648 --> 00:40:38,116 ENGRAFTED AND RANDOMIZED TO 809 00:40:38,116 --> 00:40:40,719 RECEIVE ONE OF THE FOUR 810 00:40:40,719 --> 00:40:41,420 TREATMENTS. 811 00:40:41,420 --> 00:40:48,760 WE THEN PERFORMED BIO ILLUME 812 00:40:48,760 --> 00:40:49,127 NE 813 00:40:49,127 --> 00:40:52,731 ESSENCE AND BY DAY 30 THE ONES 814 00:40:52,731 --> 00:40:55,667 THAT RECEIVED NO TREATMENT OR 815 00:40:55,667 --> 00:40:59,304 THE CYTOKINE WITH IL2 HAD 816 00:40:59,304 --> 00:41:03,241 SUBSTANTIALLY HIGHER TUMOR 817 00:41:03,241 --> 00:41:05,711 BURDEN AND IN A SEPARATE COHORT 818 00:41:05,711 --> 00:41:08,213 WE LET THE ANIMALS AGE OUT UNTIL 819 00:41:08,213 --> 00:41:10,949 DAY 100 AND THERE WAS A CLEAR 820 00:41:10,949 --> 00:41:12,284 WINNER. 821 00:41:12,284 --> 00:41:20,726 THE ONES THAT RECEIVE HE HAD -- 822 00:41:20,726 --> 00:41:24,730 RECEIVED THE IL15 RECEIVED THE 823 00:41:24,730 --> 00:41:28,700 GOOD MACROPHAGES AND A LOWER 824 00:41:28,700 --> 00:41:33,105 LEVEL OF IMMUNE EXPRESSIVE T 825 00:41:33,105 --> 00:41:35,340 REGULATORY IN THE ANIMALS THAT 826 00:41:35,340 --> 00:41:37,576 RECEIVE THE TWO NEW CYTOKINES 827 00:41:37,576 --> 00:41:39,144 COMPARED TO THOSE WITH 2. 828 00:41:39,144 --> 00:41:41,046 THIS IS THE PRECLINICAL 829 00:41:41,046 --> 00:41:44,116 RATIONALE TO GO IN THE CLINIC. 830 00:41:44,116 --> 00:41:46,985 NOW WE'RE TRANSLATING THIS TO A 831 00:41:46,985 --> 00:41:48,754 CLINICAL STUDY USING THE 832 00:41:48,754 --> 00:41:51,723 ANTIBODY AND IL15 FIRST 833 00:41:51,723 --> 00:41:52,290 SEPARATELY. 834 00:41:52,290 --> 00:41:56,695 AND LOOKING FOR TOLERABILITY AND 835 00:41:56,695 --> 00:41:57,996 BIOLOGIC SIGNAL AND HOPEFULLY 836 00:41:57,996 --> 00:41:59,664 THIS WILL BE THE FOUND TO PAVE 837 00:41:59,664 --> 00:42:02,134 THE WAY FOR THE CLINICAL 838 00:42:02,134 --> 00:42:04,636 TRANSLATION OF THE 839 00:42:04,636 --> 00:42:06,805 IMMUNOCYTOKINE WITH IL15. 840 00:42:06,805 --> 00:42:09,708 I'LL USE THE SECOND HALF OF THE 841 00:42:09,708 --> 00:42:14,112 TALK TO TALK ABOUT CAR T CELLS. 842 00:42:14,112 --> 00:42:16,381 I'M SURE YOU KNOW THEY HAVE 843 00:42:16,381 --> 00:42:19,217 TRANSFORMED THE TREATMENT OF 844 00:42:19,217 --> 00:42:21,453 PATIENTS WITH LEUKEMIA AND 845 00:42:21,453 --> 00:42:23,955 LYMPHOMA BUT IN SOLID TUMORS OUR 846 00:42:23,955 --> 00:42:24,956 RESPONSES WERE NOT THAT GREAT AS 847 00:42:24,956 --> 00:42:28,326 YOU CAN SEE HERE IN THE TABLE 848 00:42:28,326 --> 00:42:31,129 THAT SUMMARIZES ALL THE 849 00:42:31,129 --> 00:42:33,298 PEDIATRIC SOLID TUMOR CAR T CELL 850 00:42:33,298 --> 00:42:35,534 TRIALS DONE THUS FAR. 851 00:42:35,534 --> 00:42:37,102 FOCUSSING ON THE BLUE COLUMN YOU 852 00:42:37,102 --> 00:42:39,571 CAN SEE WE ACHIEVED COMPLETE 853 00:42:39,571 --> 00:42:43,275 REMISSION IN ONLY A FEW PATIENTS 854 00:42:43,275 --> 00:42:50,048 AND LOOKING CLOSER THEY HAD 855 00:42:50,048 --> 00:42:53,685 LIMITED DISEASE BURDEN. 856 00:42:53,685 --> 00:42:55,887 THERE'S A LOT OF DIFFERENCES 857 00:42:55,887 --> 00:42:57,489 BETWEEN LEUKEMIA AND SOLID 858 00:42:57,489 --> 00:42:57,722 TUMORS. 859 00:42:57,722 --> 00:43:04,696 CELLS HAVE I -- A HARDER TIME 860 00:43:04,696 --> 00:43:07,899 GETTING IN THE TUMOR AND HAVE 861 00:43:07,899 --> 00:43:09,768 LESS REPERTOIRE TO TARGET AND 862 00:43:09,768 --> 00:43:12,204 THE T CELLS WHEN THEY GET IN THE 863 00:43:12,204 --> 00:43:17,075 TME THEY ENCOUNTER A HOSTILE 864 00:43:17,075 --> 00:43:19,077 ENVIRONMENT THAT PROHIBITS THEIR 865 00:43:19,077 --> 00:43:20,679 FUNCTION AND HOW CAN WE OVERCOME 866 00:43:20,679 --> 00:43:22,781 THE CHALLENGES? 867 00:43:22,781 --> 00:43:24,616 WE TURN TO THE IL15 AND 21. 868 00:43:24,616 --> 00:43:28,720 THIS IS WORK DONE BY ONE OF THE 869 00:43:28,720 --> 00:43:31,356 POSTDOCS IN THE LAB. 870 00:43:31,356 --> 00:43:36,294 WE USED GPC2 CAR T CELLS IN THE 871 00:43:36,294 --> 00:43:38,530 TARGET AND THE TARGET WAS 872 00:43:38,530 --> 00:43:40,031 DISCOVERED HERE AT THE NCI. 873 00:43:40,031 --> 00:43:41,933 HE MADE A CAR AND GAVE IT TO US 874 00:43:41,933 --> 00:43:45,904 AND WE OPTIMIZE IT FOR CLINICAL 875 00:43:45,904 --> 00:43:46,938 TRANSLATION BUT ALREADY THINKING 876 00:43:46,938 --> 00:43:49,140 ABOUT THE NEXT GENERATION TO 877 00:43:49,140 --> 00:43:51,243 MAKE IT MORE POTENT PARTICULARLY 878 00:43:51,243 --> 00:43:52,344 FOR PATIENTS FOR EXAMPLE WITH 879 00:43:52,344 --> 00:43:57,749 LARGE TUMOR BURDEN. 880 00:43:57,749 --> 00:44:04,789 AND USED THIS AND ENGINEERED A 881 00:44:04,789 --> 00:44:08,126 VECTOR TO TETHER THEM TO THE 882 00:44:08,126 --> 00:44:11,263 CELL MEMBRANE. 883 00:44:11,263 --> 00:44:15,400 HE USED TWO NEUROBLASTOMA CELL 884 00:44:15,400 --> 00:44:17,769 LINES AND IT'S AN IN VITRO CELL 885 00:44:17,769 --> 00:44:19,170 CULTURE ASSAY WHERE YOU ADD 886 00:44:19,170 --> 00:44:22,474 EVERY TWO TO THREE DAYS TUMOR 887 00:44:22,474 --> 00:44:26,378 CELLS TO CAR T CELLS AND SEE HOW 888 00:44:26,378 --> 00:44:28,713 WELL THEY ARE PERFORM WITH THE 889 00:44:28,713 --> 00:44:31,116 CONSECUTIVE TUMOR RE-CHALLENGE. 890 00:44:31,116 --> 00:44:34,286 AS THE GRAPH INCREASES HERE IT 891 00:44:34,286 --> 00:44:35,687 MEANS THE TUMORS GROW THROUGH 892 00:44:35,687 --> 00:44:38,123 AND POPULATE THE WELL. 893 00:44:38,123 --> 00:44:42,360 YOU SEE VERY NICELY OVER TIME 894 00:44:42,360 --> 00:44:45,697 INITIALLY THE BLUE AND RED LINE 895 00:44:45,697 --> 00:44:46,965 REALLY RUN TOGETHER. 896 00:44:46,965 --> 00:44:50,602 THE BLUE REPRESENTING THE CARS 897 00:44:50,602 --> 00:44:54,472 ALONE AS THE RED IL15 AND 21. 898 00:44:54,472 --> 00:45:00,712 AFTER TWO TO THREE RECHALLENGES 899 00:45:00,712 --> 00:45:03,582 THE GRADUALLY DEMONSTRATE THE 900 00:45:03,582 --> 00:45:04,716 CAR T CELLS PERFORM BETTER IN 901 00:45:04,716 --> 00:45:05,250 CULTURE. 902 00:45:05,250 --> 00:45:08,353 HE WAS ALSO ABLE TO SHOW THIS IN 903 00:45:08,353 --> 00:45:14,125 VIVO IN AN ORTHOTOPIC XENO GRAPH 904 00:45:14,125 --> 00:45:17,395 MODEL TO INJECT THE ML5 CELLS IN 905 00:45:17,395 --> 00:45:23,735 THE PERIDROMAL FAT PAD AND THEN 906 00:45:23,735 --> 00:45:25,670 TREAT THEM AND IT'S NOT 907 00:45:25,670 --> 00:45:31,042 SURPRISING WITH A LARGE TUMOR 908 00:45:31,042 --> 00:45:34,946 THE CARS ALONE DO NOT DO DAMAGE 909 00:45:34,946 --> 00:45:40,318 BECAUSE THE TUMOR LINES JUST 910 00:45:40,318 --> 00:45:47,425 PERSIST UP HERE AND YOU CAN SEE 911 00:45:47,425 --> 00:45:49,928 WHEN THE TUMOR BURDEN DECREASES 912 00:45:49,928 --> 00:45:51,396 BY WEEK THREE AND FOUR. 913 00:45:51,396 --> 00:45:52,931 WITH THIS EFFORT WE'RE LOOKING 914 00:45:52,931 --> 00:45:56,134 TO UNDERSTAND THE MECHANISMS 915 00:45:56,134 --> 00:45:57,636 BETTER IN THE TUMOR ENVIRONMENT 916 00:45:57,636 --> 00:46:04,709 AND WHAT IL15 AND 21 DOES OR DO 917 00:46:04,709 --> 00:46:12,050 TO THE IMMUNE CELLS AND WE 918 00:46:12,050 --> 00:46:22,594 LIMITED THE CONSITUTIVE PORTION 919 00:46:25,997 --> 00:46:28,700 AND THIS IS THE END OF THE TALK. 920 00:46:28,700 --> 00:46:31,870 I'D LIKE AGAIN TO THANK MY LAB 921 00:46:31,870 --> 00:46:36,908 AS WELL AS ALL THE COLLABORATE 922 00:46:36,908 --> 00:46:40,712 ERS AND INDUSTRY PARTNERS AND 923 00:46:40,712 --> 00:46:44,549 OUR FUNDING SOURCES AND THE NIH 924 00:46:44,549 --> 00:46:46,785 DSP PROGRAM AND PATIENTS AND 925 00:46:46,785 --> 00:46:48,653 FAMILIES AND THIS TALK CAME AT 926 00:46:48,653 --> 00:46:51,523 AN OPPORTUNITY TIME BECAUSE THIS 927 00:46:51,523 --> 00:46:52,957 MONTH IS CHILDHOOD CANCER 928 00:46:52,957 --> 00:46:56,127 AWARENESS MONTH AND I'M HAPPY TO 929 00:46:56,127 --> 00:46:56,561 TAKE ANY QUESTIONS. 930 00:46:56,561 --> 00:47:04,669 THANK YOU. 931 00:47:04,669 --> 00:47:05,336 >> THANK YOU. 932 00:47:05,336 --> 00:47:05,737 FASCINATING WORK. 933 00:47:05,737 --> 00:47:07,839 WE HAVE A QUESTION ON THE LEFT 934 00:47:07,839 --> 00:47:14,112 SIDE OF THE AUDITORIUM. 935 00:47:14,112 --> 00:47:17,816 >> BEAUTIFUL WORK. 936 00:47:17,816 --> 00:47:20,719 I'M LUIS FRANCO SCHOLAR FROM 937 00:47:20,719 --> 00:47:24,155 2020 I THINK. 938 00:47:24,155 --> 00:47:24,723 SAME CLASS. 939 00:47:24,723 --> 00:47:29,928 SO TWO QUESTIONS ON THE ADCC 940 00:47:29,928 --> 00:47:33,398 APPROACH WITH THE IL15 941 00:47:33,398 --> 00:47:36,634 CONJUGATES IS IT THE MACROPHAGES 942 00:47:36,634 --> 00:47:38,403 MATTER COMPARED TO ACTIVATION OF 943 00:47:38,403 --> 00:47:39,971 THE NK CELLS? 944 00:47:39,971 --> 00:47:43,742 >> WE DID THAT AND LOOKED AT IT 945 00:47:43,742 --> 00:47:45,910 AND THE NK CELL MODELS WERE NOT 946 00:47:45,910 --> 00:47:46,177 EXPANDED. 947 00:47:46,177 --> 00:47:47,746 AND AT LEAST AT THE TIME POINT 948 00:47:47,746 --> 00:47:54,085 WHEN WE DID OUR SINGLE CELL RNA 949 00:47:54,085 --> 00:47:59,023 SEQ AND FLOW CYTOMETRY BUT IL15 950 00:47:59,023 --> 00:48:02,694 IS THE JUICE FOR NK CELLS AND T 951 00:48:02,694 --> 00:48:04,696 CELLS AND THERE'S CLINICAL 952 00:48:04,696 --> 00:48:08,133 STUDIES WHEN YOU INFUSE IT AS A 953 00:48:08,133 --> 00:48:13,772 FREE FLOATING AGENT YOU GET 954 00:48:13,772 --> 00:48:16,708 MASSIVE EXPANSION OF NK CELLS OR 955 00:48:16,708 --> 00:48:17,809 T CELLS AND I SUSPECT HAD IT 956 00:48:17,809 --> 00:48:19,377 GONE LONGER WE WOULD HAVE SEEN 957 00:48:19,377 --> 00:48:22,413 THAT PLUS THIS IS ONE OF THE 958 00:48:22,413 --> 00:48:26,117 STUDIES IN THE CLINICAL TRIAL. 959 00:48:26,117 --> 00:48:27,118 >> THE OTHER QUESTION WHAT'S THE 960 00:48:27,118 --> 00:48:30,655 RELATIONSHIP BETWEEN THESE 961 00:48:30,655 --> 00:48:31,356 TUMORS AND THE BLOOD BRAIN 962 00:48:31,356 --> 00:48:32,123 BARRIER? 963 00:48:32,123 --> 00:48:37,195 DO THEY NEED TO CROSS THE BLOOD 964 00:48:37,195 --> 00:48:39,164 BRAIN BARRIER OR NOT? 965 00:48:39,164 --> 00:48:42,167 >> IT'S A NON-CNS SO MOST THE 966 00:48:42,167 --> 00:48:43,968 TUMOR BURDEN IS PERIPHERAL BUT 967 00:48:43,968 --> 00:48:45,103 THE MOLECULAR OF THE MOLECULES 968 00:48:45,103 --> 00:48:47,839 IS TOO BIG TO CROSS SO YOU WOULD 969 00:48:47,839 --> 00:48:50,708 PROBABLY HAVE TO RE-ENGINEER IT 970 00:48:50,708 --> 00:48:52,710 INTO A DYE BODY OR SOMETHING 971 00:48:52,710 --> 00:48:54,579 SMALLER TO MAKE IT GO THROUGH. 972 00:48:54,579 --> 00:48:56,614 >> I WAS WONDERING ABOUT NANO 973 00:48:56,614 --> 00:49:01,186 BODIES AND SINGLE DOMAIN 974 00:49:01,186 --> 00:49:03,254 ANTIBODIES WHICH SUPPOSEDLY HAVE 975 00:49:03,254 --> 00:49:04,489 BETTER PENETRATION OF TISSUES. 976 00:49:04,489 --> 00:49:07,659 >> I THINK IT'S A GREAT THOUGHT. 977 00:49:07,659 --> 00:49:09,427 WE'RE PLAYING AROUND WITH THIS A 978 00:49:09,427 --> 00:49:13,398 LITTLE BIT NOT WITH THE GD2 979 00:49:13,398 --> 00:49:15,166 ANTIBODY BECAUSE THAT'S HIGHLY 980 00:49:15,166 --> 00:49:20,138 EXPRESSED ON NERVES IN THE CNS. 981 00:49:20,138 --> 00:49:25,343 WE HAVE TO BE A LITTLE CAREFUL 982 00:49:25,343 --> 00:49:27,645 WITH TEXOXICITIES BUT IT'S A GRT 983 00:49:27,645 --> 00:49:27,879 THOUGHT. 984 00:49:27,879 --> 00:49:29,414 >> TO BUILD ON THAT I WAS ALSO 985 00:49:29,414 --> 00:49:32,650 THINKING OF THIS FROM THE 986 00:49:32,650 --> 00:49:33,218 STANDPOINT OF BLOOD BRAIN 987 00:49:33,218 --> 00:49:36,254 BARRIER TRANSMISSION AND 988 00:49:36,254 --> 00:49:37,722 WONDERING WHAT CYTOTOXICITY 989 00:49:37,722 --> 00:49:41,593 WOULD YOU EXPECT TO SEE AND WHAT 990 00:49:41,593 --> 00:49:44,128 SYSTEMIC TOXICITIES MIGHT YOU 991 00:49:44,128 --> 00:49:51,936 EXPECT FROM THE UNRESTRAINED 992 00:49:51,936 --> 00:49:52,704 SIGNALLING? 993 00:49:52,704 --> 00:49:56,174 >> IT CAN CAUSE SERIOUS 994 00:49:56,174 --> 00:50:02,146 NEUROTOXICITY IN TERMS OF PAIN 995 00:50:02,146 --> 00:50:11,890 AND WE GIVE MORPHINE AND TRY TO 996 00:50:11,890 --> 00:50:15,827 TITRATE IT UP AND THERE'S FORMS 997 00:50:15,827 --> 00:50:20,565 OF ANTIBODIES WITH MUTATIONS 998 00:50:20,565 --> 00:50:21,900 THAT DON'T ENGAGE THE COMPLEMENT 999 00:50:21,900 --> 00:50:24,135 SYSTEM THAT MADE IT BETTER. 1000 00:50:24,135 --> 00:50:25,270 FOR THIS COMBINATION I THINK 1001 00:50:25,270 --> 00:50:30,575 THERE WILL STILL BE PAIN. 1002 00:50:30,575 --> 00:50:37,982 WE'RE GIVING THE TITRATION 1003 00:50:37,982 --> 00:50:41,753 SLOWLY BECAUSE THE OVERLAPPING 1004 00:50:41,753 --> 00:50:43,922 TOXICITY WOULD BE YOUR 1005 00:50:43,922 --> 00:50:44,389 INFLAMMATORY RESPONSE. 1006 00:50:44,389 --> 00:50:47,292 YOU HAVE TO BE CAREFUL. 1007 00:50:47,292 --> 00:50:52,363 IT CAN CAUSE BASICALLY 1008 00:50:52,363 --> 00:50:52,931 HYPERTENSION, RESPIRATORY 1009 00:50:52,931 --> 00:50:55,867 PROBLEMS DUE TO PULMONARY EDEMA 1010 00:50:55,867 --> 00:50:59,504 AND SLOW TRITATION OVER TIME IS 1011 00:50:59,504 --> 00:51:01,539 IMPORTANT AND PLUS THE WAY I 1012 00:51:01,539 --> 00:51:11,416 DESIGN THE TRIAL WAS NOT AS A 1013 00:51:11,416 --> 00:51:12,717 BOLUS BUT LONG-TERM INFUSION AND 1014 00:51:12,717 --> 00:51:14,786 THEY'RE TRULY WARRIORS AND I 1015 00:51:14,786 --> 00:51:17,221 DON'T THINK NONE OF US IN THE 1016 00:51:17,221 --> 00:51:19,190 ROOM WOULD BE ABLE TO TOLERATE A 1017 00:51:19,190 --> 00:51:24,128 TENTH OF THIS TREATMENT. 1018 00:51:24,128 --> 00:51:25,163 >> THANK YOU. 1019 00:51:25,163 --> 00:51:27,999 TRULY INSPIRING WORK. 1020 00:51:27,999 --> 00:51:34,439 THANK YOU, DR. NGUYEN. 1021 00:51:34,439 --> 00:51:40,712 OUR NEXT SPEAKER IS DR. DIANA 1022 00:51:40,712 --> 00:51:44,716 MONTEIRO TALKING ABOUT PROTEIN 1023 00:51:44,716 --> 00:51:46,718 CRYSTALLOGRAPHY AS A GATEWAY FOR 1024 00:51:46,718 --> 00:51:48,353 DRUG DISCOVERY. 1025 00:51:48,353 --> 00:51:49,387 THE TOPICS TRANSITION 1026 00:51:49,387 --> 00:51:49,687 BEAUTIFULLY. 1027 00:51:49,687 --> 00:51:52,056 >> THIS IS THE POINT WHERE I 1028 00:51:52,056 --> 00:51:54,859 SHOULD HAVE TURNED MY COMPUTER 1029 00:51:54,859 --> 00:52:02,133 ON WHEN I WAS STILL SITTING 1030 00:52:02,133 --> 00:52:11,175 THERE. 1031 00:52:11,175 --> 00:52:11,576 MIN 1032 00:52:11,576 --> 00:52:11,976 MIN 1033 00:52:11,976 --> 00:52:14,145 I THINK THIS IS GOING TO BE 1034 00:52:14,145 --> 00:52:15,079 DIFFERENT FROM EVERYTHING WE 1035 00:52:15,079 --> 00:52:19,217 HEARD SO FAR AND I'M A PROTEIN 1036 00:52:19,217 --> 00:52:21,486 CRYSTALLOGRAPHY AND STARTED AS A 1037 00:52:21,486 --> 00:52:24,722 CHEMIST AND I TOOK A BIG DETOUR 1038 00:52:24,722 --> 00:52:27,125 TO PROTEIN CRYSTALLOGRAPHY AND 1039 00:52:27,125 --> 00:52:30,061 COMING TO NCI MEANS I GET TO GO 1040 00:52:30,061 --> 00:52:32,430 BACK TO MY ROOTS IN DRUG 1041 00:52:32,430 --> 00:52:34,332 DISCOVERY WHICH IS WONDERFUL AND 1042 00:52:34,332 --> 00:52:36,501 INTERACT WITH BIOLOGISTS BECAUSE 1043 00:52:36,501 --> 00:52:38,503 I'M NOT A BIOLOGIST. 1044 00:52:38,503 --> 00:52:40,204 MY GROUP IS TECHNOLOGY AND 1045 00:52:40,204 --> 00:52:41,305 TECHNIQUE DRIVEN AND BRINGING 1046 00:52:41,305 --> 00:52:44,342 THIS AND I THINK IF YOU ALL JUST 1047 00:52:44,342 --> 00:52:46,377 TUNE OUT OF MY TALK JUST LOOK AT 1048 00:52:46,377 --> 00:52:48,579 THE LAST SLIDE MOSTLY AND THINK 1049 00:52:48,579 --> 00:52:49,914 ABOUT THE TECHNOLOGY THAT WE'RE 1050 00:52:49,914 --> 00:52:52,116 BRINGING IN BECAUSE I WOULD LOVE 1051 00:52:52,116 --> 00:52:55,253 TO HEAR ABOUT TARGETS AND THINGS 1052 00:52:55,253 --> 00:52:58,656 OF IMPORTANCE FROM THE PEOPLE 1053 00:52:58,656 --> 00:53:06,831 WHO UNDERSTAND CANCER FROM THIS 1054 00:53:06,831 --> 00:53:10,601 POINT OF VIEW OF ORGANS AND 1055 00:53:10,601 --> 00:53:15,773 SCALES WHICH IS DIFFERENT FROM I 1056 00:53:15,773 --> 00:53:16,140 WORK. 1057 00:53:16,140 --> 00:53:18,810 AND AND HAVING SPENT TIME IN 1058 00:53:18,810 --> 00:53:24,715 DYNAMIC CRYSTALLOGRAPHY I'M OF 1059 00:53:24,715 --> 00:53:26,717 THE OPINION THAT THEY'RE 1060 00:53:26,717 --> 00:53:28,753 MOLECULAR MEASURES AND FOR ME 1061 00:53:28,753 --> 00:53:30,721 AND MY GROUP WE DETERMINE HIGH 1062 00:53:30,721 --> 00:53:31,422 RESOLUTION STRUCTURES IN THIS 1063 00:53:31,422 --> 00:53:33,157 CASE NOW ONCOPROTEINS. 1064 00:53:33,157 --> 00:53:36,194 IT'S MY FIRST RODEO IN THE REALM 1065 00:53:36,194 --> 00:53:39,564 OF CANCER BUT ALL THE 1066 00:53:39,564 --> 00:53:40,631 TECHNOLOGY'S TRANSLATABLE. 1067 00:53:40,631 --> 00:53:45,470 WE ALSO LOOK AT PROTEIN LIGAND 1068 00:53:45,470 --> 00:53:46,037 COMPLEXES. 1069 00:53:46,037 --> 00:53:48,172 THIS MEANS WE DETERMINE 1070 00:53:48,172 --> 00:53:48,873 MECHANISMS. 1071 00:53:48,873 --> 00:53:50,475 AT THE POINT OF VIEW OF AU 1072 00:53:50,475 --> 00:53:55,213 TOMMIC MECHANISMS WE DEFINE THE 1073 00:53:55,213 --> 00:53:56,147 PROTEIN-PROTEIN INTERACTIONS 1074 00:53:56,147 --> 00:53:58,983 IMPORTANT FOR DEVELOPING OF 1075 00:53:58,983 --> 00:54:00,651 DRUGS AND GET STRUCTURED 1076 00:54:00,651 --> 00:54:02,587 ACTIVITY RELATIONSHIPS AND ALL 1077 00:54:02,587 --> 00:54:05,056 THIS IN AS HIGH THROUGHPUT TO 1078 00:54:05,056 --> 00:54:06,791 ACCELERATE EVERYTHING AND 1079 00:54:06,791 --> 00:54:07,892 MINIMIZE SAMPLE CONSUMPTION 1080 00:54:07,892 --> 00:54:10,928 BECAUSE AS IT TURNS OUT THE MORE 1081 00:54:10,928 --> 00:54:12,697 COMPLEX PROTEINS THE HARDER THEY 1082 00:54:12,697 --> 00:54:14,332 ARE TO MAKE AND MORE 1083 00:54:14,332 --> 00:54:15,299 APPRECIATION THEY BECOME AND 1084 00:54:15,299 --> 00:54:17,568 NEED TO TAKE THAT INTO ACCOUNT. 1085 00:54:17,568 --> 00:54:19,904 I HAVE A SOFT SPOT FOR THE 1086 00:54:19,904 --> 00:54:20,138 DYNAMIC. 1087 00:54:20,138 --> 00:54:23,341 AND THE DYNAMICS ARE OVERLOOKED. 1088 00:54:23,341 --> 00:54:24,809 I'LL SHOW A QUICK EXAMPLE OF A 1089 00:54:24,809 --> 00:54:29,080 PROJECT WE STARTED BACK IN MARCH 1090 00:54:29,080 --> 00:54:32,150 WHERE DYNAMICS WERE CLEARLY 1091 00:54:32,150 --> 00:54:34,185 HAVING AN INFLUENCE ON HOW THE 1092 00:54:34,185 --> 00:54:37,121 SMALL MOLECULES THAT WERE BEING 1093 00:54:37,121 --> 00:54:38,156 DESIGN WERE EFFECTIVELY 1094 00:54:38,156 --> 00:54:40,391 CORRECTED AT THE BEGINNING. 1095 00:54:40,391 --> 00:54:44,162 SMALL MOLECULES WE JUST LEARNED 1096 00:54:44,162 --> 00:54:45,363 ABOUT IMMUNOTHERAPIES. 1097 00:54:45,363 --> 00:54:48,266 AND THIS IS STILL THE HIGHEST 1098 00:54:48,266 --> 00:54:51,736 PERCENTAGE OF FDA APPROVED 1099 00:54:51,736 --> 00:54:51,936 DRUGS. 1100 00:54:51,936 --> 00:54:54,672 THERE'S SO MUCH HAPPENING IN 1101 00:54:54,672 --> 00:54:57,909 PROTEIN IMMUNOTHERAPY AND SMALL 1102 00:54:57,909 --> 00:54:59,377 MOLECULES STILL REPRESENTS A BIG 1103 00:54:59,377 --> 00:55:01,179 PART AND FROM ONE OF THE 1104 00:55:01,179 --> 00:55:03,748 PROJECTS I'LL TOUCH ON THE LAST 1105 00:55:03,748 --> 00:55:05,750 SLIDE IS LIKE COTHERAPIES TO 1106 00:55:05,750 --> 00:55:08,386 IMPROVE THE ABILITY OF DRUGS TO 1107 00:55:08,386 --> 00:55:09,587 WORK. 1108 00:55:09,587 --> 00:55:13,958 SO FOR US MAKING SMARTER DRUGS 1109 00:55:13,958 --> 00:55:14,792 AND SMARTER DESIGN WE'RE TRYING 1110 00:55:14,792 --> 00:55:17,428 TO TARGET THE RELEVANT BIOLOGY 1111 00:55:17,428 --> 00:55:20,164 AND HAVE TARGETED THERAPIES AND 1112 00:55:20,164 --> 00:55:22,233 LOWER OFF TARGET EFFECTS. 1113 00:55:22,233 --> 00:55:24,368 THESE ARE THINGS WE CAN TRY TO 1114 00:55:24,368 --> 00:55:25,369 MODULATE LOOKING AT SMALL 1115 00:55:25,369 --> 00:55:27,605 MOLECULES AND LOOK AT THE 1116 00:55:27,605 --> 00:55:28,639 STRUCTURES AND DYNAMICS. 1117 00:55:28,639 --> 00:55:31,876 SO BASICALLY HERE'S WHERE WE 1118 00:55:31,876 --> 00:55:32,143 ARE. 1119 00:55:32,143 --> 00:55:36,414 I DISCOVERED THE ONCOGENIC 1120 00:55:36,414 --> 00:55:39,684 PROTEIN AND WANT TO UNDERSTAND 1121 00:55:39,684 --> 00:55:41,285 THE MECHANISM AND CREATE A DRUG 1122 00:55:41,285 --> 00:55:44,155 TO TARGET OR I HAVE A DRUG FOR 1123 00:55:44,155 --> 00:55:45,256 THE PROTEINS BUT IT DOESN'T WORK 1124 00:55:45,256 --> 00:55:47,425 VERY WELL SO WHAT CAN I DO? 1125 00:55:47,425 --> 00:55:50,628 THIS IS REALLY WHERE THE 1126 00:55:50,628 --> 00:55:52,063 STRUCTURE ACTIVITY RELATIONSHIPS 1127 00:55:52,063 --> 00:55:57,535 COME IN FOR DRUG DESIGN. 1128 00:55:57,535 --> 00:56:01,339 I MOVED TO NCI LAST YEAR AND MY 1129 00:56:01,339 --> 00:56:02,673 LAB BECAME OPERATIONAL IN 1130 00:56:02,673 --> 00:56:04,842 FEBRUARY AND THIS IS THE FIRST 1131 00:56:04,842 --> 00:56:09,013 PROJECT WE TOOK ON. 1132 00:56:09,013 --> 00:56:14,151 OUR LITTLE PAC-MAN IS A PROTEASE 1133 00:56:14,151 --> 00:56:17,188 AND I WAS APPROACHED ABOUT THIS 1134 00:56:17,188 --> 00:56:17,722 PRE TEEN. 1135 00:56:17,722 --> 00:56:24,362 AND OUR COLLABORATOR WAS MAKING 1136 00:56:24,362 --> 00:56:27,465 INHIBITORS IT'S A SERINE 1137 00:56:27,465 --> 00:56:30,101 PROTEASE AND IT CLEAVES 1138 00:56:30,101 --> 00:56:30,368 PEPTIDES. 1139 00:56:30,368 --> 00:56:33,771 IT'S INVOLVED IN THE MATURATION 1140 00:56:33,771 --> 00:56:35,840 AND DEGRADATION OF NEUROPEPTIDES 1141 00:56:35,840 --> 00:56:38,142 AND INVOLVED IN DISEASES OF THE 1142 00:56:38,142 --> 00:56:41,279 BRAIN EFFECTIVELY AND PEPTIDE 1143 00:56:41,279 --> 00:56:43,614 HORMONES AND IT'S EFFECTIVELY 1144 00:56:43,614 --> 00:56:45,750 SOMEHOW -- NO ONE FULLY 1145 00:56:45,750 --> 00:56:48,419 UNDERSTANDS THIS COMPLETELY BUT 1146 00:56:48,419 --> 00:56:50,154 IT'S CONNECTED TO 1147 00:56:50,154 --> 00:56:51,122 NEURODEGENERATIVE DISEASES. 1148 00:56:51,122 --> 00:56:53,958 THEY FIRST STARTED BY TAKING 1149 00:56:53,958 --> 00:57:02,099 WHAT IS A PREVIOUS STRUCTURE OF 1150 00:57:02,099 --> 00:57:03,301 PREP AND DOTTING MOLECULES. 1151 00:57:03,301 --> 00:57:05,603 THIS IS THE MOLECULE THEY WERE 1152 00:57:05,603 --> 00:57:06,037 LOOKING AT. 1153 00:57:06,037 --> 00:57:08,139 YOU CAN'T REALLY SEE IT HERE 1154 00:57:08,139 --> 00:57:10,374 VERY WELL BUT I'LL SHOW A 1155 00:57:10,374 --> 00:57:12,710 DIFFERENT VIEW IN A SECOND. 1156 00:57:12,710 --> 00:57:14,412 IT'S LINKED. 1157 00:57:14,412 --> 00:57:17,648 SO THEY BUILT NEW MOLECULES THEY 1158 00:57:17,648 --> 00:57:20,117 THOUGHT WOULD MIMIC THIS WELL 1159 00:57:20,117 --> 00:57:28,492 AND DIDN'T WORK AS WELL AS 1160 00:57:28,492 --> 00:57:28,759 EXPECTED. 1161 00:57:28,759 --> 00:57:31,762 THE STRUCTURES POSED SOME ISSUES 1162 00:57:31,762 --> 00:57:34,598 TO GET GOOD STRUCTURES OUT AND 1163 00:57:34,598 --> 00:57:36,567 TOOK THE COMPOUND AND SOLVED THE 1164 00:57:36,567 --> 00:57:37,735 STRUCTURE AND IT LOOKS VERY 1165 00:57:37,735 --> 00:57:38,002 DIFFERENT. 1166 00:57:38,002 --> 00:57:39,837 I CAN SHOW THE OVERLAY. 1167 00:57:39,837 --> 00:57:42,506 IT'S NOT THE SAME MOLECULE BUT 1168 00:57:42,506 --> 00:57:44,141 THE ORANGE MOLECULE BASED ON THE 1169 00:57:44,141 --> 00:57:47,678 GREEN AND YOU CAN SEE IT SITS IN 1170 00:57:47,678 --> 00:57:50,081 A DIFFERENT POSITION AND IF THAT 1171 00:57:50,081 --> 00:57:52,717 WASN'T ENOUGH I'LL GIVE YOU THE 1172 00:57:52,717 --> 00:57:53,818 90 DEGREE VIEW. 1173 00:57:53,818 --> 00:57:59,023 IT'S A COMPLETELY DIFFERENT 1174 00:57:59,023 --> 00:58:00,191 POSITION. 1175 00:58:00,191 --> 00:58:02,159 TO SAY THE DOCKING IS VERY 1176 00:58:02,159 --> 00:58:04,095 USEFUL BUT IF YOU HAVE A SITE 1177 00:58:04,095 --> 00:58:06,797 THAT IS HUGE AND DYNAMIC AND 1178 00:58:06,797 --> 00:58:09,900 START WITH A STATIC CRYSTAL 1179 00:58:09,900 --> 00:58:11,669 STRUCTURE AND DESIGN FROM THAT 1180 00:58:11,669 --> 00:58:13,137 YOU RUN INTO PROBLEMS. 1181 00:58:13,137 --> 00:58:17,074 SO NOW THEY'RE STARTING TO 1182 00:58:17,074 --> 00:58:19,043 REDESIGN TO MAKE MORE POTENT 1183 00:58:19,043 --> 00:58:19,443 INHIBITORS. 1184 00:58:19,443 --> 00:58:22,780 WARE ALSO LOOKING INTO GETTING 1185 00:58:22,780 --> 00:58:25,383 THE STRUCTURES AT ROOM 1186 00:58:25,383 --> 00:58:25,983 TEMPERATURE. 1187 00:58:25,983 --> 00:58:28,386 THIS DID DONE AT CRYO 1188 00:58:28,386 --> 00:58:29,320 TEMPERATURES AND THAT'S ALSO 1189 00:58:29,320 --> 00:58:30,488 GOING TO CHANGE. 1190 00:58:30,488 --> 00:58:33,357 HOW WILL WE EXPAND ON THIS? 1191 00:58:33,357 --> 00:58:35,593 IT'S A HUGE SITE AND THE IN 1192 00:58:35,593 --> 00:58:37,361 SILICO IS A PROBLEM. 1193 00:58:37,361 --> 00:58:38,696 THOUGH THEY STARTED BECAUSE WE 1194 00:58:38,696 --> 00:58:40,631 FOND SOME INTERACTIONS THAT WERE 1195 00:58:40,631 --> 00:58:42,967 SUITABLE TO GUIDE THE STRUCTURAL 1196 00:58:42,967 --> 00:58:44,535 DESIGN AND MAKING NEW COMPOUNDS 1197 00:58:44,535 --> 00:58:50,141 WE'RE COMING IN WITH WHAT WE 1198 00:58:50,141 --> 00:58:54,712 CALL FRAGMENT BASED DISCOVERY. 1199 00:58:54,712 --> 00:58:56,680 FOR THOSE WHO KNOW WHAT THIS IS, 1200 00:58:56,680 --> 00:58:58,315 YOU CAN TUNE OUT BUT FOR THOSE 1201 00:58:58,315 --> 00:59:01,619 THAT DON'T IT'S COOL. 1202 00:59:01,619 --> 00:59:04,388 IT'S THE BACKBONE OF THE 1203 00:59:04,388 --> 00:59:06,190 MOLECULES AND THE INDUSTRY HAS 1204 00:59:06,190 --> 00:59:08,359 TAKEN HOLD OF THIS FROM MANY 1205 00:59:08,359 --> 00:59:11,829 YEARS. 1206 00:59:11,829 --> 00:59:12,863 FROM THE TECHNOLOGY PERSPECTIVE 1207 00:59:12,863 --> 00:59:14,698 ONE OF THE FIRST JOBS I HAD 1208 00:59:14,698 --> 00:59:16,700 COMING HERE WAS TO ESTABLISH THE 1209 00:59:16,700 --> 00:59:17,902 PIPELINE. 1210 00:59:17,902 --> 00:59:22,740 SO THE WAY IT WORKS IS THAT THIS 1211 00:59:22,740 --> 00:59:24,542 IS WHAT WE USED TO CRYSTALIZE 1212 00:59:24,542 --> 00:59:27,878 OUR PROTEINS AND EFFECTIVELY PUT 1213 00:59:27,878 --> 00:59:31,549 THESE LITTLE 200 DROPS OF 1214 00:59:31,549 --> 00:59:35,686 PROTEINS AND THERE'S REAL 1215 00:59:35,686 --> 00:59:36,687 CRYSTAL FROM PREP AND WE COLLECT 1216 00:59:36,687 --> 00:59:39,223 DATA AND TAKE A FRAGMENT 1217 00:59:39,223 --> 00:59:39,457 LIBRARY. 1218 00:59:39,457 --> 00:59:41,625 THESE ARE TINY MOLECULES AND 1219 00:59:41,625 --> 00:59:43,360 SOAK THEM IN AND HAVE 1220 00:59:43,360 --> 00:59:45,629 EFFECTIVELY NOT JUST 96 BUT 1221 00:59:45,629 --> 00:59:49,266 ABOUT 1,000 OF THEM AND THEN 1222 00:59:49,266 --> 00:59:51,202 THIS IS THE HARD PART. 1223 00:59:51,202 --> 00:59:53,604 WE MANUALLY MOUNT THEM AND SO MY 1224 00:59:53,604 --> 00:59:55,105 GROUP WITHIN THE FIVE PEOPLE 1225 00:59:55,105 --> 00:59:56,707 HAVE BEEN TOLD EVEN IF IT'S NOT 1226 00:59:56,707 --> 00:59:59,410 YOUR PROJECT WHEN WE HAVE THIS 1227 00:59:59,410 --> 01:00:00,478 YOU'LL SIT DOWN WITH THE 1228 01:00:00,478 --> 01:00:02,680 MICROSCOPE AND HELP WITH THE 1229 01:00:02,680 --> 01:00:04,682 CRYSTALS. 1230 01:00:04,682 --> 01:00:08,819 AND THEY'RE OKAY WITH THAT. 1231 01:00:08,819 --> 01:00:09,954 I HOPE. 1232 01:00:09,954 --> 01:00:10,254 LEAD 1233 01:00:10,254 --> 01:00:11,388 I EXAMPLE EVERY TIME. 1234 01:00:11,388 --> 01:00:13,891 SO WHEN WE HAVE THIS THE OTHER 1235 01:00:13,891 --> 01:00:15,326 IMPORTANT PART IS WE DO THE 1236 01:00:15,326 --> 01:00:16,594 INITIAL DATA COLLECTION IS JUST 1237 01:00:16,594 --> 01:00:17,928 A FEW CRYSTALS AND WE'RE TRYING 1238 01:00:17,928 --> 01:00:21,232 TO SOLVE A STRUCTURE WE DO IT 1239 01:00:21,232 --> 01:00:24,702 MANUALLY AND EVENTUALLY WE 1240 01:00:24,702 --> 01:00:26,737 AUTOMATE THIS AND HAVE CLOSE 1241 01:00:26,737 --> 01:00:29,306 RELATIONSHIPS WHERE WE RUN THIS 1242 01:00:29,306 --> 01:00:32,176 AND GET THE AUTOMATION TO WORK 1243 01:00:32,176 --> 01:00:32,510 WELL. 1244 01:00:32,510 --> 01:00:34,311 THERE'S A ROBOT IF ANYONE WANTS 1245 01:00:34,311 --> 01:00:35,045 TO COME AND WATCH DATA 1246 01:00:35,045 --> 01:00:36,647 COLLECTION IT'S PRETTY FUN. 1247 01:00:36,647 --> 01:00:38,949 COME AND LET ME KNOW. 1248 01:00:38,949 --> 01:00:40,684 THEY SHOOT X-RAYS AND COLLECT 1249 01:00:40,684 --> 01:00:43,687 THE DATA AND DO THE PROCESSING 1250 01:00:43,687 --> 01:00:48,826 AND GET THOUSANDS OF STRUCTURES 1251 01:00:48,826 --> 01:00:52,429 OUT AND THERE'S OTHER SOFTWARE 1252 01:00:52,429 --> 01:00:54,965 THAT WAS DEVELOPED BY A FRIEND 1253 01:00:54,965 --> 01:00:57,635 OF MINE IN SWEDEN THAT IS 1254 01:00:57,635 --> 01:01:01,272 FILTERING AND WE GET ABOUT 10% 1255 01:01:01,272 --> 01:01:02,973 OF HITS AND HAVE SOMEBODY BOUND 1256 01:01:02,973 --> 01:01:05,910 AND NEW AND NOVEL AND NEW 1257 01:01:05,910 --> 01:01:07,044 CHEMISTRY AND SOMETHING WE 1258 01:01:07,044 --> 01:01:11,315 HAVEN'T SEEN BEFORE AND THEN DO 1259 01:01:11,315 --> 01:01:13,517 THE MANUAL INSPECTION AND 1260 01:01:13,517 --> 01:01:15,252 CORRELATE IT TO THE LIBRARY. 1261 01:01:15,252 --> 01:01:17,888 OF COURSE WHAT I'M ABOUT TO SHOW 1262 01:01:17,888 --> 01:01:19,123 YOU IS THEORETICAL BECAUSE WE 1263 01:01:19,123 --> 01:01:20,024 STARTED IN FEBRUARY. 1264 01:01:20,024 --> 01:01:22,059 THIS IS OUR FIRST CAMPAIGN. 1265 01:01:22,059 --> 01:01:23,527 WE DON'T YET HAVE DATA TO SHOW 1266 01:01:23,527 --> 01:01:25,062 YOU BUT THE WAY IT WORKS IN THE 1267 01:01:25,062 --> 01:01:27,798 CASE OF PREP WE HAVE A HUGE 1268 01:01:27,798 --> 01:01:28,699 ACTIVE SITE. 1269 01:01:28,699 --> 01:01:31,268 WE'LL LOAD THE PROTEIN WITH A 1270 01:01:31,268 --> 01:01:32,703 SHORTER VERSION OF THE WAR HEADS 1271 01:01:32,703 --> 01:01:35,472 WE KNOW WORKS AND WE WANT TO 1272 01:01:35,472 --> 01:01:36,907 KNOW HOW WE EXPAND IT AND LOAD 1273 01:01:36,907 --> 01:01:43,881 IT WITH FRAGMENTS AND YOU 1274 01:01:43,881 --> 01:01:47,017 BASICALLY GET OTHER FRAGMENTS IN 1275 01:01:47,017 --> 01:01:48,185 YOUR ACTIVE SITES AND TRY TO 1276 01:01:48,185 --> 01:01:54,925 LINK THEM TO MAKE A MOLECULE 1277 01:01:54,925 --> 01:01:57,294 THAT IS TITER BINDING. 1278 01:01:57,294 --> 01:02:00,698 THIS IS OUR PIPELINE. 1279 01:02:00,698 --> 01:02:03,901 WE TYPICALLY START WITH PROTEIN 1280 01:02:03,901 --> 01:02:04,702 EXPRESSION PURIFICATION THAT'S 1281 01:02:04,702 --> 01:02:06,770 THE BIGGEST TIME WE SPEND TRYING 1282 01:02:06,770 --> 01:02:08,172 TO MAKE THE PROTEINS. 1283 01:02:08,172 --> 01:02:10,407 WE HAVE A LOT OF INFRASTRUCTURE. 1284 01:02:10,407 --> 01:02:12,276 THINGS THAT HELP ONE IN HIGH 1285 01:02:12,276 --> 01:02:14,011 THROUGHPUT AND ROBOTS AND DO 1286 01:02:14,011 --> 01:02:19,483 THIS WITH HIGH ACCURACY AND 1287 01:02:19,483 --> 01:02:20,184 REPRODUCIBILITY AND WE COLLECT 1288 01:02:20,184 --> 01:02:21,685 THE DATA. 1289 01:02:21,685 --> 01:02:24,388 THIS IS A MASSIVE ACCELERATOR 1290 01:02:24,388 --> 01:02:26,557 THAT PRODUCES VERY BRIGHT 1291 01:02:26,557 --> 01:02:27,691 X-RAYS. 1292 01:02:27,691 --> 01:02:31,428 MOST IS REMOTE NOW BUT I TRY TO 1293 01:02:31,428 --> 01:02:33,263 GO A COUPLE TIMES A YEAR THERE. 1294 01:02:33,263 --> 01:02:35,299 ONCE WE HAVE INITIAL STRUCTURES 1295 01:02:35,299 --> 01:02:38,002 AND READY TO GO HIGH THROUGHPUT 1296 01:02:38,002 --> 01:02:41,472 WE HAVE AN ACOUSTIC DROPLET 1297 01:02:41,472 --> 01:02:44,174 GENERATOR AND THE CRYSTALS ARE 1298 01:02:44,174 --> 01:02:46,777 SENSITIVE AND WE DO EVERYTHING 1299 01:02:46,777 --> 01:02:49,813 ACOUSTICALLY AND HAVE A SET THAT 1300 01:02:49,813 --> 01:02:51,281 HELPS MOUNT THE CRYSTALS. 1301 01:02:51,281 --> 01:02:53,517 AND WHAT WE'RE DOING IS BRINGING 1302 01:02:53,517 --> 01:02:56,153 THIS INFRASTRUCTURE IN. 1303 01:02:56,153 --> 01:02:58,856 RIGHT NOW WE ARE FINALIZING THE 1304 01:02:58,856 --> 01:03:00,691 INSTRUMENTATION IN THE LAB AND 1305 01:03:00,691 --> 01:03:02,159 THE PIPELINES AND IT IS UNIQUE 1306 01:03:02,159 --> 01:03:05,162 AND SIMILAR TO ONE OTHER 1307 01:03:05,162 --> 01:03:07,064 INSTITUTE THAT HAS IT BACK IN 1308 01:03:07,064 --> 01:03:10,100 CAMBRIDGE THE FIRST THAT BROUGHT 1309 01:03:10,100 --> 01:03:12,102 THIS TO ACADEMIC SCIENCE. 1310 01:03:12,102 --> 01:03:13,370 WE HAVE OTHER PROJECTS. 1311 01:03:13,370 --> 01:03:15,339 I WON'T HAVE TIME TO TALK ABOUT 1312 01:03:15,339 --> 01:03:20,177 THIS BUT HAVE PROJECTS REGULATED 1313 01:03:20,177 --> 01:03:23,714 TO THIS QUANTITATIVE CARBOXYLASE 1314 01:03:23,714 --> 01:03:25,983 INVOLVED IN METABOLISM AND SHOWN 1315 01:03:25,983 --> 01:03:28,052 TO BE HIGHLY EXPRESSED IN TUMORS 1316 01:03:28,052 --> 01:03:31,588 WHEN PEOPLE HAVE BAD OUTCOMES 1317 01:03:31,588 --> 01:03:32,623 WITH THEIR THERAPY. 1318 01:03:32,623 --> 01:03:36,326 WE'RE LOOKING INTO POTENTIALLY 1319 01:03:36,326 --> 01:03:38,562 MAKING DRUGS TOWARDS THIS. 1320 01:03:38,562 --> 01:03:41,932 THIS WAS THE ONE PROJECT FROM MY 1321 01:03:41,932 --> 01:03:45,069 PREVIOUS LIFE ANTIMICROBIALS 1322 01:03:45,069 --> 01:03:47,404 AGAINST PATHOGENS AND 60% 1323 01:03:47,404 --> 01:03:48,505 MORTALITY IF PEOPLE ARE IN 1324 01:03:48,505 --> 01:03:51,175 LONG-TERM CARE. 1325 01:03:51,175 --> 01:03:53,711 WE HAVE SOMETHING CALLED PROTAX 1326 01:03:53,711 --> 01:03:54,611 MOLECULES THAT NOT JUST 1327 01:03:54,611 --> 01:03:59,049 BYPRODUCT TO THE PROTEIN BUT 1328 01:03:59,049 --> 01:04:00,384 TRIGGER THE DEGRADATION AND 1329 01:04:00,384 --> 01:04:02,152 EFFECTIVELY TAKE THE PROTEIN OUT 1330 01:04:02,152 --> 01:04:05,389 OF THE EQUATION AND THIS IS THE 1331 01:04:05,389 --> 01:04:06,790 HOLY GRAIL DEALING WITH 1332 01:04:06,790 --> 01:04:09,660 ONCOGENIC FUSION PROTEINS. 1333 01:04:09,660 --> 01:04:10,627 THESE ARE DIFFICULT. 1334 01:04:10,627 --> 01:04:12,229 THEY'RE VERY SPAGHETTI LIKE. 1335 01:04:12,229 --> 01:04:17,301 THE FIRST POINT IS TO TRY TO DO 1336 01:04:17,301 --> 01:04:19,103 COMPUTATION TO FIND BINDING PARD 1337 01:04:19,103 --> 01:04:22,639 OF PARTNERS OR REGIONS TO LOOK 1338 01:04:22,639 --> 01:04:23,440 AT AND DISRUPT. 1339 01:04:23,440 --> 01:04:25,342 WITH THAT I WANT TO SAY THANK 1340 01:04:25,342 --> 01:04:27,611 YOU TO MY GROUP AS. 1341 01:04:27,611 --> 01:04:30,914 MOST THE PEOPLE WORKING HAVE 1342 01:04:30,914 --> 01:04:33,784 STARTED IN APRIL, MAY. 1343 01:04:33,784 --> 01:04:36,120 ALL THE WORK HAS BEEN DONE AND 1344 01:04:36,120 --> 01:04:39,189 THEY'VE BEEN PUSHING IT. 1345 01:04:39,189 --> 01:04:40,991 I HOPE YOU KEEP THIS IN MIND. 1346 01:04:40,991 --> 01:04:43,460 IF YOU HAVE A TARGET PROTEIN 1347 01:04:43,460 --> 01:04:44,762 YOU'RE INTERESTED IN AND MAKING 1348 01:04:44,762 --> 01:04:46,730 NEW DRUGS, COME AND TALK TO US 1349 01:04:46,730 --> 01:04:48,465 AND MAKE USE OF THIS TECHNOLOGY 1350 01:04:48,465 --> 01:04:48,899 WE HAVE AVAILABLE. 1351 01:04:48,899 --> 01:04:56,073 AND THANK YOU. 1352 01:04:56,073 --> 01:04:57,474 >> THANK YOU. 1353 01:04:57,474 --> 01:04:59,076 THAT WAS FANTASTIC. 1354 01:04:59,076 --> 01:05:01,378 I WANT TO COME MAKE A FIELD TRIP 1355 01:05:01,378 --> 01:05:02,379 TO SEE THIS IN ACTION. 1356 01:05:02,379 --> 01:05:04,715 DO WE HAVE QUESTIONS FROM THE 1357 01:05:04,715 --> 01:05:09,953 AUDIENCE AT ALL? 1358 01:05:09,953 --> 01:05:10,788 >> GREAT TALK. 1359 01:05:10,788 --> 01:05:13,123 I HAVE A PUBLIC HEALTH I'D LIKE 1360 01:05:13,123 --> 01:05:14,358 TO COLLABORATE WITH YOU. 1361 01:05:14,358 --> 01:05:16,727 MAYBE WE CAN CONNECT LATER. 1362 01:05:16,727 --> 01:05:19,363 >> SOUNDS GREAT. 1363 01:05:19,363 --> 01:05:22,566 >> THAT'S ALL I WANT TO SAY. 1364 01:05:22,566 --> 01:05:23,500 >> FANTASTIC. 1365 01:05:23,500 --> 01:05:25,936 THAT'S WHAT WE'RE HERE FOR. 1366 01:05:25,936 --> 01:05:29,306 >> YOU STARTED WITH CARBOXYLASE 1367 01:05:29,306 --> 01:05:31,975 AND WONDER ON ONE OF YOUR FINAL 1368 01:05:31,975 --> 01:05:35,913 SLIDES YOU MENTIONED AN 1369 01:05:35,913 --> 01:05:37,080 ONCOTARGET PROTEINS AND WHAT'S 1370 01:05:37,080 --> 01:05:39,316 THE DIFFERENCE BETWEEN TRYING TO 1371 01:05:39,316 --> 01:05:41,919 DESIGN MOLECULES THAT WILL BIND 1372 01:05:41,919 --> 01:05:47,691 TO AND ACTIVE ENZYMES VERSUS 1373 01:05:47,691 --> 01:05:48,125 NON-ENZYMATIC. 1374 01:05:48,125 --> 01:05:50,661 >> THEY'RE THE TYPICAL TARGETS. 1375 01:05:50,661 --> 01:05:52,262 THEY'RE PRETTY CONSTRAINED. 1376 01:05:52,262 --> 01:05:54,698 YOU HAVE VERY CLEAR INTERACTIONS 1377 01:05:54,698 --> 01:05:56,700 THAT HAPPEN BETWEEN YOUR PROTEIN 1378 01:05:56,700 --> 01:05:58,235 AND SUBSTRATE SO THIS IS 1379 01:05:58,235 --> 01:05:59,369 TYPICALLY WHAT YOU TARGET. 1380 01:05:59,369 --> 01:06:01,505 YOU HAVE THE PROBLEM IF YOU'RE 1381 01:06:01,505 --> 01:06:03,307 TARGETING SOMETHING THAT HAS A 1382 01:06:03,307 --> 01:06:05,409 SUBSTRATE THAT IS SIMILAR TO 1383 01:06:05,409 --> 01:06:07,444 WHAT HAPPENS IN THE CELL YOU MAY 1384 01:06:07,444 --> 01:06:09,446 HAVE OFF TARGET EFFECTS. 1385 01:06:09,446 --> 01:06:11,481 THE OTHER PROBLEM IS TYPICALLY 1386 01:06:11,481 --> 01:06:13,417 YOU START GAINING RESISTANCE. 1387 01:06:13,417 --> 01:06:16,920 SINGLE POINT MUTATIONS IN YOUR 1388 01:06:16,920 --> 01:06:18,155 SITE AND MOLECULE. 1389 01:06:18,155 --> 01:06:20,157 IN TERMS OF OTHER THINGS THAT 1390 01:06:20,157 --> 01:06:23,961 ARE NOT ENZYMES, TYPICALLY THEY 1391 01:06:23,961 --> 01:06:26,496 WORK BY THE MAJORITY OF CASES I 1392 01:06:26,496 --> 01:06:28,098 KNOW THEY WORK BY CONTACTING 1393 01:06:28,098 --> 01:06:30,434 WITH OTHER PROTEINS OR OTHER 1394 01:06:30,434 --> 01:06:32,169 LARGER ENTITIES IN THE CELLS. 1395 01:06:32,169 --> 01:06:34,905 SO NOW WE'RE LOOKING AT 1396 01:06:34,905 --> 01:06:36,106 PROTEIN-PROTEIN INTERACTIONS. 1397 01:06:36,106 --> 01:06:41,345 IF WE LOOK HERE AT THE 1398 01:06:41,345 --> 01:06:51,889 SIMULATION THERE'S LARGER AREAS 1399 01:06:57,094 --> 01:06:59,863 THAT BINDS AND FOR LESS 1400 01:06:59,863 --> 01:07:01,164 MUTATIONAL BURDEN IT KILLS 1401 01:07:01,164 --> 01:07:04,701 THERAPIES AND IT DISRUPTS 1402 01:07:04,701 --> 01:07:08,171 SPECIFIC INTERACTIONS. 1403 01:07:08,171 --> 01:07:18,582 FOR US WE'LL LIKELY TRY 1404 01:07:19,283 --> 01:07:24,221 DIFFERENT COMPOUNDS. 1405 01:07:24,221 --> 01:07:28,659 SO THAT'S FROM THIS WON'T WE CAN 1406 01:07:28,659 --> 01:07:31,128 CO BY CRYSTALLOGRAPHY BUT IT 1407 01:07:31,128 --> 01:07:32,162 WORKS IN THE SAME WAY. 1408 01:07:32,162 --> 01:07:38,168 >> QUICK QUESTION. 1409 01:07:38,168 --> 01:07:44,174 I'M FROM THE 2023 COHORT AND THE 1410 01:07:44,174 --> 01:07:47,277 LATEST ALLITERATIONS ARE 1411 01:07:47,277 --> 01:07:48,679 PROMISING. 1412 01:07:48,679 --> 01:07:54,351 >> THAT IS ALPHA FOLD. 1413 01:07:54,351 --> 01:07:58,288 IT HELPS BUT I DON'T KNOW IF 1414 01:07:58,288 --> 01:08:00,090 ANYONE HAS ALPHA FOLD. 1415 01:08:00,090 --> 01:08:02,426 IT HAS A TENDENCY TO PICK THINGS 1416 01:08:02,426 --> 01:08:03,727 THAT MAY NOT BE REAL. 1417 01:08:03,727 --> 01:08:06,964 WE USE IT ESPECIALLY FOR THINGS 1418 01:08:06,964 --> 01:08:09,399 LIKE THE ONCOGENIC FUSION 1419 01:08:09,399 --> 01:08:10,467 PROTEINS WHERE WE ARE TRYING TO 1420 01:08:10,467 --> 01:08:12,002 SEE -- BY QUICK BACKGROUND, THE 1421 01:08:12,002 --> 01:08:15,038 THING YOU SEE HERE STARTED WITH 1422 01:08:15,038 --> 01:08:19,810 A LIST OF HITS FROM BIO-I.D. 1423 01:08:19,810 --> 01:08:20,110 ASSAYS. 1424 01:08:20,110 --> 01:08:21,712 THINGS CLOSE TOGETHER IN THE 1425 01:08:21,712 --> 01:08:23,146 CELLS AND NOW EFFECTIVELY GOING 1426 01:08:23,146 --> 01:08:26,149 THROUGH 400 PAIRS AND SEEING IF 1427 01:08:26,149 --> 01:08:36,693 WE CAN SEE INDCATIONS ARE REAL 1428 01:08:40,430 --> 01:08:41,698 AND WE'LL HAVE TO SEE IF THEY 1429 01:08:41,698 --> 01:08:43,467 FIND AND IF THEY DO WE FOLLOW 1430 01:08:43,467 --> 01:08:44,368 THROUGH WITH A DRUG DISCOVERY 1431 01:08:44,368 --> 01:08:48,705 ASSAY. 1432 01:08:48,705 --> 01:08:58,115 IT'S COMPLETELY A HYPOTHESIS. 1433 01:08:58,115 --> 01:09:00,684 YOU CAN'T TAKE IT AT POINT VALUE 1434 01:09:00,684 --> 01:09:02,185 AND WE'VE SEEP THAT. 1435 01:09:02,185 --> 01:09:03,820 -- SEEN THAT. 1436 01:09:03,820 --> 01:09:08,191 >> WONDERFUL, THANK YOU VERY 1437 01:09:08,191 --> 01:09:08,692 MUCH. 1438 01:09:08,692 --> 01:09:12,596 THIS IS WONDERFUL. 1439 01:09:12,596 --> 01:09:13,697 WE'LL TAKE A SIX MINUTE BREAK 1440 01:09:13,697 --> 01:09:14,197 AND RESUME AT 11:15. 1441 01:09:14,197 --> 01:09:14,264 1442 01:09:16,767 --> 01:09:22,773 THANK YOU. 1443 01:09:22,773 --> 01:09:26,176 THE STRUCTURE SYMPOSIUM IS THREE 1444 01:09:26,176 --> 01:09:28,145 GROUPS OF DSP SCHOLARS 1445 01:09:28,145 --> 01:09:29,212 PRESENTING WORK AND THE SECOND 1446 01:09:29,212 --> 01:09:32,182 HALF OF THE FIRST COHORT IS WHAT 1447 01:09:32,182 --> 01:09:33,236 WE'LL NEED TO HEAR FROM IN FIVE 1448 01:09:33,236 --> 01:09:35,701 MINUTES. 1449 01:09:35,701 --> 01:09:39,305 GOOD MORNING. 1450 01:09:39,305 --> 01:09:39,805 WELCOME BACK. 1451 01:09:39,805 --> 01:09:43,609 FLEX YOUR ANKLES AND GET SOME 1452 01:09:43,609 --> 01:09:44,610 BLOOD CIRCULATION. 1453 01:09:44,610 --> 01:09:47,380 EXCITED ABOUT OUR NEXT SPEAKER. 1454 01:09:47,380 --> 01:09:55,054 THIS IS DR. MINKYO SONG ABOUT 1455 01:09:55,054 --> 01:10:03,963 THE IMMUNOEPIDEMIOLOGY OF AUTO 1456 01:10:03,963 --> 01:10:07,033 IMMUNITY AND AGING. 1457 01:10:07,033 --> 01:10:10,603 >> I LEAD THE LABORATORY OF 1458 01:10:10,603 --> 01:10:14,907 EPIDEMIOLOGY AND POPULATION 1459 01:10:14,907 --> 01:10:15,174 SCIENCES. 1460 01:10:15,174 --> 01:10:17,677 I'D LIKE TO THANK THE DSP FOR 1461 01:10:17,677 --> 01:10:24,150 SUPPORTING MY RESEARCH AND WOULD 1462 01:10:24,150 --> 01:10:26,485 LIKE TO TALK ABOUT 1463 01:10:26,485 --> 01:10:27,053 IMMUNOEPIDEMIOLOGY. 1464 01:10:27,053 --> 01:10:28,621 IT'S A TWO DISCIPLINES AND IT 1465 01:10:28,621 --> 01:10:30,790 CAN BE DEFINED AS A FIELD OF 1466 01:10:30,790 --> 01:10:35,995 STUDY THAT ADDRESSES HOW 1467 01:10:35,995 --> 01:10:36,762 DIFFERENCES AFFECT THE 1468 01:10:36,762 --> 01:10:40,333 EPIDEMIOLOGY OF INFECTIOUS 1469 01:10:40,333 --> 01:10:44,237 DISEASES, CANCER AND AUTO 1470 01:10:44,237 --> 01:10:46,606 IMMUNITY. 1471 01:10:46,606 --> 01:10:48,274 IT AFFECTS LIFE IN VARIOUS WAYS 1472 01:10:48,274 --> 01:10:49,942 IN AGING. 1473 01:10:49,942 --> 01:10:52,211 WHEN A PERSON GETS BORN THE 1474 01:10:52,211 --> 01:10:57,049 IMMUNE MATURES WITH THE AGING 1475 01:10:57,049 --> 01:11:00,486 PROCESS AND EVENTUALLY IMMUNITY 1476 01:11:00,486 --> 01:11:04,523 GET OLD IN IMMUNOSENESCENCE AND 1477 01:11:04,523 --> 01:11:05,992 T CELLS GO DOWN AND RESPONSES 1478 01:11:05,992 --> 01:11:07,627 ARE REDUCED AND THE INFECTION 1479 01:11:07,627 --> 01:11:10,730 RATE AND CANCER AND AUTO IMMUNE 1480 01:11:10,730 --> 01:11:13,599 DISEASES GO UP. 1481 01:11:13,599 --> 01:11:20,273 IN ORDER TO ANSWER THIS OVER 1482 01:11:20,273 --> 01:11:24,010 ARCHING RESEARCH QUESTION AND WE 1483 01:11:24,010 --> 01:11:26,245 FACE ALTERED IMMUNITY AND I'M 1484 01:11:26,245 --> 01:11:28,614 LOOKING AT AUTO IMMUNITY. 1485 01:11:28,614 --> 01:11:30,950 YOU CAN SEE ON THE SCIENCE COVER 1486 01:11:30,950 --> 01:11:34,787 IN 2022 -- I DON'T NO FEZ TOO 1487 01:11:34,787 --> 01:11:36,489 SMALL BUT AUTO IMMUNITY SAYS IS 1488 01:11:36,489 --> 01:11:40,593 THE DARK SIDE OF THE HOST 1489 01:11:40,593 --> 01:11:41,460 DEFENSE MEANING IMMUNITY THAT'S 1490 01:11:41,460 --> 01:11:43,696 SUPPOSED TO PROTECT THE HOST 1491 01:11:43,696 --> 01:11:46,499 GOES WRONG AND IS ATTACKING 1492 01:11:46,499 --> 01:11:46,732 ITSELF. 1493 01:11:46,732 --> 01:11:47,900 THAT'S THE DEFINITION IN SHORT. 1494 01:11:47,900 --> 01:11:50,436 I'D LIKE TO SAY THIS IS AN 1495 01:11:50,436 --> 01:11:52,605 EXCITING AND TIMELY OPPORTUNITY 1496 01:11:52,605 --> 01:11:54,707 TO CONDUCT RESEARCH IN AUTO 1497 01:11:54,707 --> 01:11:56,842 IMMUNITY AND AGING. 1498 01:11:56,842 --> 01:12:00,146 NUMBER ONE IT'S IN INCREASED 1499 01:12:00,146 --> 01:12:01,414 BURDEN OF DISEASES. 1500 01:12:01,414 --> 01:12:05,151 IT'S ESTIMATED AROUND 10% OF THE 1501 01:12:05,151 --> 01:12:10,623 WORLD'S POPULATION IS AFFECTED 1502 01:12:10,623 --> 01:12:16,262 BY AUTO IMMUNE DISEASE. 1503 01:12:16,262 --> 01:12:17,563 AUTO IMMUNE PATIENTS ARE LIVING 1504 01:12:17,563 --> 01:12:20,166 LONGER THANKS TO TREATMENT BUT 1505 01:12:20,166 --> 01:12:21,867 ANOTHER THING IS WOMEN ARE MORE 1506 01:12:21,867 --> 01:12:23,102 AFFECTED BY THE DISEASE MEANING 1507 01:12:23,102 --> 01:12:24,503 THESE ARE THE MAIN CARE TAKERS 1508 01:12:24,503 --> 01:12:28,341 OF THE FAMILY AND WILL AFFECT 1509 01:12:28,341 --> 01:12:28,908 THE HOUSEHOLD AND COMMUNITY 1510 01:12:28,908 --> 01:12:32,011 MORE. 1511 01:12:32,011 --> 01:12:34,847 THERE'S STILL LIMITED 1512 01:12:34,847 --> 01:12:37,883 UNDERSTANDING OF AUTO IMMUNE 1513 01:12:37,883 --> 01:12:40,619 DISEASE EPIDEMIOLOGY. 1514 01:12:40,619 --> 01:12:47,993 WE DON'T KNOW THE GEOGRAPHICAL 1515 01:12:47,993 --> 01:12:48,894 DIFFERENCES AND LACK SPECIFIC 1516 01:12:48,894 --> 01:12:51,497 DESIGNS AND NOT OF THE STUDIES 1517 01:12:51,497 --> 01:12:53,032 TAKE INTO CONSIDERING THE 1518 01:12:53,032 --> 01:12:55,034 EMERGING RISK FACTORS SUCH AS 1519 01:12:55,034 --> 01:12:58,304 NEW DRUGS AND INFECTIONS OR 1520 01:12:58,304 --> 01:12:58,671 CLIMATE CHANGE. 1521 01:12:58,671 --> 01:13:01,741 BUT WE ARE IN GOOD HANDS. 1522 01:13:01,741 --> 01:13:04,443 THERE'S IMMUNOLOGY AND THERE'S 1523 01:13:04,443 --> 01:13:06,946 MORE DATA VALUABLE NOW AND NOT 1524 01:13:06,946 --> 01:13:08,781 JUST THE CLASSIC DESIGN STUDIES 1525 01:13:08,781 --> 01:13:15,054 BUT SECONDARY STUDIES WE CAN 1526 01:13:15,054 --> 01:13:15,888 UTILIZE. 1527 01:13:15,888 --> 01:13:18,324 AND THE NATIONAL ACADEMIES OF 1528 01:13:18,324 --> 01:13:20,659 SCIENCE AND ENGINEERING THOUGHT 1529 01:13:20,659 --> 01:13:23,929 THIS WAS ALSO A GREAT NEED. 1530 01:13:23,929 --> 01:13:25,364 THEY PRODUCED THIS STUDY REPORT 1531 01:13:25,364 --> 01:13:28,300 IN 2022 FOR ENHANCING NIH 1532 01:13:28,300 --> 01:13:30,403 RESEARCH ON AUTO IMMUNE 1533 01:13:30,403 --> 01:13:31,036 DISEASES. 1534 01:13:31,036 --> 01:13:36,375 IN RESPONSE TO CONGRESS THE 1535 01:13:36,375 --> 01:13:38,444 OFFICE OF AUTOIMMUNE RESEARCH 1536 01:13:38,444 --> 01:13:39,812 WAS CREATED IN THE OFFICE ON 1537 01:13:39,812 --> 01:13:40,613 WOMEN'S HEALTH AND THE 1538 01:13:40,613 --> 01:13:44,049 INITIATIVE ON WOMEN'S HEALTH 1539 01:13:44,049 --> 01:13:45,351 RESEARCH ALSO EMPHASIZED AUTO 1540 01:13:45,351 --> 01:13:50,823 IMMUNE DISEASE IS ONE OF THEIR 1541 01:13:50,823 --> 01:13:52,591 PRIORITY AREAS AND LOOKING AT 1542 01:13:52,591 --> 01:13:55,060 AGE-ED DISEASES ONE OF THE 1543 01:13:55,060 --> 01:13:57,930 BIGGEST CHALLENGE IS TO 1544 01:13:57,930 --> 01:13:59,031 DISENTANGLE THE DIRECTIONALITY 1545 01:13:59,031 --> 01:14:00,166 OF AGING. 1546 01:14:00,166 --> 01:14:03,068 AS I SAID, WITH AGING AUTO 1547 01:14:03,068 --> 01:14:05,471 IMMUNE DISEASES INCREASE BUT 1548 01:14:05,471 --> 01:14:08,174 IT'S ALSO TRUE WITH AUTO IMMUNE 1549 01:14:08,174 --> 01:14:11,043 DISEASES AGE-RELATED DISEASE 1550 01:14:11,043 --> 01:14:15,047 SUCH AS CARDIOVASCULAR DISEASE 1551 01:14:15,047 --> 01:14:16,348 AND CANCER CELLS ALSO INCREASE. 1552 01:14:16,348 --> 01:14:20,319 AND WE'RE NOT SO SURE ABOUT THE 1553 01:14:20,319 --> 01:14:21,821 ASSOCIATIONS IN DIFFERENT RISK 1554 01:14:21,821 --> 01:14:22,054 GROUPS. 1555 01:14:22,054 --> 01:14:25,691 THERE'S TWO AIMS OF MY RESEARCH. 1556 01:14:25,691 --> 01:14:27,793 ONE IS TO UNRAVEL THE 1557 01:14:27,793 --> 01:14:28,594 ASSOCIATION BETWEEN AUTO IMMUNE 1558 01:14:28,594 --> 01:14:29,462 AND AIMING. 1559 01:14:29,462 --> 01:14:31,030 I'M LOOKING AT THE EFFECT OF 1560 01:14:31,030 --> 01:14:33,132 AGING ON THE RISK OF AUTO IMMUNE 1561 01:14:33,132 --> 01:14:35,034 DISEASES AND THE EFFECT OF AUTO 1562 01:14:35,034 --> 01:14:38,804 IMMUNE DISEASES ON THE AGING 1563 01:14:38,804 --> 01:14:39,038 PROCESS. 1564 01:14:39,038 --> 01:14:43,309 I'M INCORPORATING LONGITUDINAL 1565 01:14:43,309 --> 01:14:44,510 STUDY DESIGNS AND LIFE TIME 1566 01:14:44,510 --> 01:14:48,314 COURSE AND RISK FACTORS SUCH AS 1567 01:14:48,314 --> 01:14:49,248 INFECTION, MEDICATIONS OR 1568 01:14:49,248 --> 01:14:50,149 CLIMATE CHANGE. 1569 01:14:50,149 --> 01:14:52,618 A SECOND AREA IS TO DEVELOP 1570 01:14:52,618 --> 01:14:55,654 METHODS TO BETTER ASCERTAIN AUTO 1571 01:14:55,654 --> 01:14:56,322 IMMUNE DISEASE. 1572 01:14:56,322 --> 01:15:00,159 THEY'RE OFTEN UNDER DIAGNOSED 1573 01:15:00,159 --> 01:15:01,927 AND A LOT OF AUTO IMMUNE 1574 01:15:01,927 --> 01:15:04,063 PATIENTS ARE ASYMPTOMATIC. 1575 01:15:04,063 --> 01:15:06,332 YOU'LL SEE THE TIP OF THE 1576 01:15:06,332 --> 01:15:09,602 ICEBERG IN THIS FIELD. 1577 01:15:09,602 --> 01:15:12,872 TO BETTER QUANTIFY AUTO IMMUNE 1578 01:15:12,872 --> 01:15:14,306 DISEASE AND IMMUNITY I'M 1579 01:15:14,306 --> 01:15:15,474 UTILIZING THE CLINICAL 1580 01:15:15,474 --> 01:15:16,609 BIOMARKERS AND DEVELOPING NEW 1581 01:15:16,609 --> 01:15:19,812 BIOMARKERS FOR DETECTING THESE 1582 01:15:19,812 --> 01:15:22,381 AUTO IMMUNE DISEASES. 1583 01:15:22,381 --> 01:15:24,717 TODAY I WOULD LIKE TO INTRODUCE 1584 01:15:24,717 --> 01:15:27,686 YOU TO MY THREE EXCITING 1585 01:15:27,686 --> 01:15:29,622 PROJECTS I'VE LAUNCHED SINCE 1586 01:15:29,622 --> 01:15:33,259 ONBOARDING LAST YEAR INVOLVING 1587 01:15:33,259 --> 01:15:35,728 THE LONGITUDINAL AND LIFE COURSE 1588 01:15:35,728 --> 01:15:37,196 DESIGNS AND QUANTIFICATION OF 1589 01:15:37,196 --> 01:15:40,599 AUTO IMMUNE DISEASES AND ALSO 1590 01:15:40,599 --> 01:15:44,637 INCORPORATION OF CLIMATE CHANGE. 1591 01:15:44,637 --> 01:15:47,006 SO I DID TELL YOU AUTO IMMUNITY 1592 01:15:47,006 --> 01:15:48,707 INCREASES WITH AGE BUT THERE'S 1593 01:15:48,707 --> 01:15:54,380 NOT SO MANY DATA OUT THERE THAT 1594 01:15:54,380 --> 01:15:57,182 HAS DOCUMENTED THE AUTO ANTIBODY 1595 01:15:57,182 --> 01:15:58,617 CHANGE WITHIN AN INDIVIDUAL OR 1596 01:15:58,617 --> 01:16:01,387 WHETHER THE TRAJECTORIES DIFFER 1597 01:16:01,387 --> 01:16:04,657 BY SEX. 1598 01:16:04,657 --> 01:16:12,998 SO I AM UTILIZING THIS BALTIMORE 1599 01:16:12,998 --> 01:16:15,668 LONGITUDINAL STUDY OF AGING 1600 01:16:15,668 --> 01:16:18,504 SINCE 1958 WITH MORE THAN 3,000 1601 01:16:18,504 --> 01:16:19,805 VOLUNTEERS WITH LONGITUDINAL 1602 01:16:19,805 --> 01:16:24,043 DATA AND THERE'S CLINICAL AND 1603 01:16:24,043 --> 01:16:25,911 BIOMEDICAL AND FUNCTIONAL 1604 01:16:25,911 --> 01:16:27,079 MEASUREMENTS AND BIO SPECIMEN. 1605 01:16:27,079 --> 01:16:31,050 AND I AM INCORPORATING THE CASE 1606 01:16:31,050 --> 01:16:34,420 COHORT STUDY SELECTING 250 1607 01:16:34,420 --> 01:16:35,054 AUTOIMMUNE DISEASE AND COMPARING 1608 01:16:35,054 --> 01:16:37,923 THAT TO THE COHORT OF RANDOMLY 1609 01:16:37,923 --> 01:16:38,791 SELECTED INDIVIDUALS. 1610 01:16:38,791 --> 01:16:42,461 AND THEN I'M MEASURING THE 1611 01:16:42,461 --> 01:16:46,599 ANTI-NUCLEAR ANTIBODIES WHICH IS 1612 01:16:46,599 --> 01:16:49,401 ONE OF THE MOST COMMON 1613 01:16:49,401 --> 01:16:50,202 ANTIBODIES FOUND IN THE AUTO 1614 01:16:50,202 --> 01:16:53,939 IMMUNE DISEASE AND INCORPORATE 1615 01:16:53,939 --> 01:16:57,676 THE NOVEL TECHNOLOGY THE PROTEIN 1616 01:16:57,676 --> 01:17:02,748 ARRAY AND I'LL BE SELECTING 300 1617 01:17:02,748 --> 01:17:06,251 AUTOANTIBODY TO SEE IF THERE'S 1618 01:17:06,251 --> 01:17:07,820 ANY ANTIBODIES DOCUMENTABLE 1619 01:17:07,820 --> 01:17:08,621 WITHIN THE POMP. 1620 01:17:08,621 --> 01:17:12,891 SO WE'LL LOOK AT AGE-RELATED 1621 01:17:12,891 --> 01:17:14,960 CHANGINGS OF THE ANTIBODIES AND 1622 01:17:14,960 --> 01:17:18,864 THE RELATIONSHIP TO THE AUTO 1623 01:17:18,864 --> 01:17:19,765 IMMUNE DISEASES AND OTHER TYPES 1624 01:17:19,765 --> 01:17:22,901 OF AGE-RELATED DISEASE OTHER 1625 01:17:22,901 --> 01:17:24,837 THAN AUTOIMMUNE DISEASE. 1626 01:17:24,837 --> 01:17:26,839 I HAVE A LOT OF COLLABORATORS 1627 01:17:26,839 --> 01:17:28,607 THERE AND THIS HAS BEEN 1628 01:17:28,607 --> 01:17:30,409 CO-FUNDED BY THE OFFICE OF AUTO 1629 01:17:30,409 --> 01:17:34,613 IMMUNE DISEASE RESEARCH I 1630 01:17:34,613 --> 01:17:36,715 MENTIONED EARLIER IN THE 1631 01:17:36,715 --> 01:17:37,883 PRESENTATION. 1632 01:17:37,883 --> 01:17:43,489 THOUGH BLSA IS A UNIQUE DATA SET 1633 01:17:43,489 --> 01:17:46,458 IT'S VERY SMALL AND I NEEDED A 1634 01:17:46,458 --> 01:17:49,995 BIG DATA SET. 1635 01:17:49,995 --> 01:17:53,332 SO I WENT TO THIS HISPANIC 1636 01:17:53,332 --> 01:17:57,202 COMMUNITY HEALTH STUDIES THAT IS 1637 01:17:57,202 --> 01:18:01,373 AN NIH FUNDED COHORT WITH 16,000 1638 01:18:01,373 --> 01:18:03,809 HISPANICS WITH A WIDE AGE RANGE 1639 01:18:03,809 --> 01:18:04,877 THAT COVERS THE YOUNGER YEARS 1640 01:18:04,877 --> 01:18:10,616 MORE PRONE TO AGE-RELATED 1641 01:18:10,616 --> 01:18:12,084 AUTOIMMUNE DISEASES. 1642 01:18:12,084 --> 01:18:14,720 THERE'S A RICH COLLECT OF 1643 01:18:14,720 --> 01:18:15,654 LIFESTYLE FACTORS AND SOCIAL 1644 01:18:15,654 --> 01:18:16,622 DETERMINATES AND NEIGHBORHOOD 1645 01:18:16,622 --> 01:18:19,692 AND ENVIRONMENTAL FACTORS AND 1646 01:18:19,692 --> 01:18:21,627 YOU CAN SEE ON THE FIGURE ON THE 1647 01:18:21,627 --> 01:18:26,699 RIGHT THERE'S JUST SO MANY 1648 01:18:26,699 --> 01:18:29,501 THINGS WE CAN UTILIZE HERE. 1649 01:18:29,501 --> 01:18:34,640 HERE I'M ALSO DEFINING AUTO 1650 01:18:34,640 --> 01:18:37,109 IMMUNITY USING ANTIBODIES AND 1651 01:18:37,109 --> 01:18:41,647 USING ANTIGENS FROM THE AG ATLAS 1652 01:18:41,647 --> 01:18:43,048 THE LITERATURE-BASED 1653 01:18:43,048 --> 01:18:44,917 ACCUMULATION OF DIFFERENT 1654 01:18:44,917 --> 01:18:46,819 ANTIBODIES AND THEN TESTING 1655 01:18:46,819 --> 01:18:47,986 AROUND 1700 ANTIBODIES WITHIN 1656 01:18:47,986 --> 01:18:53,292 THE 10% OF THE POPULATION TO 1657 01:18:53,292 --> 01:18:56,328 SELECT THE MOST IMPORTANT WHICH 1658 01:18:56,328 --> 01:18:58,097 WILL BE AROUND 300 1659 01:18:58,097 --> 01:19:00,466 AUTO-ANTIBODIES WITHIN THE 1660 01:19:00,466 --> 01:19:02,134 16,000 POPULATION. 1661 01:19:02,134 --> 01:19:03,235 AND COMPARING THOSE ANTIBODY 1662 01:19:03,235 --> 01:19:04,970 LEVELS WITH RISK FACTORS 1663 01:19:04,970 --> 01:19:10,642 SURVEYED OR MEASURED WITHIN THE 1664 01:19:10,642 --> 01:19:13,479 COHORT AND LOOKING AT THE 1665 01:19:13,479 --> 01:19:14,913 ASSOCIATION WITH INFECTION AGENT 1666 01:19:14,913 --> 01:19:20,018 BECAUSE IT'S SUPPOSED TO BE A 1667 01:19:20,018 --> 01:19:22,888 TRIGGER FOR AUTOIMMUNE DISEASE 1668 01:19:22,888 --> 01:19:25,290 AND LOOK AT LATER RISK OF 1669 01:19:25,290 --> 01:19:27,860 DIFFERENT PHENOTYPES. 1670 01:19:27,860 --> 01:19:30,896 AND THEN ONE IMPORTANT THING IS 1671 01:19:30,896 --> 01:19:33,065 THAT SINCE THE COHORT IS 1672 01:19:33,065 --> 01:19:33,899 DISTRIBUTED ACROSS DIFFERENT 1673 01:19:33,899 --> 01:19:36,568 AREAS OF THE U.S., THEY HAVE 1674 01:19:36,568 --> 01:19:38,871 MEASUREMENTS AND THERE'S A 1675 01:19:38,871 --> 01:19:41,039 WORKING GROUP FOR CLIMATE CHANGE 1676 01:19:41,039 --> 01:19:42,474 AND I PLAN TO COLLABORATE WITH 1677 01:19:42,474 --> 01:19:49,148 THIS GROUP TO LOOK AT THE 1678 01:19:49,148 --> 01:19:51,016 CLIMATE CHANGE I'M INTERESTED UP 1679 01:19:51,016 --> 01:19:54,419 AND THE LAST PROJECT IS THE 1680 01:19:54,419 --> 01:19:55,354 CLIMATE CHANGE CONSEQUENCES AND 1681 01:19:55,354 --> 01:19:56,889 BIOMARKERS IN THAT SENSE. 1682 01:19:56,889 --> 01:19:59,758 AMONGST MANY CLIMATE CHANGES I 1683 01:19:59,758 --> 01:20:01,794 LOOKED AT HURRICANES AND IT'S 1684 01:20:01,794 --> 01:20:04,096 SUPPOSED TO HAVE INTERDIRECT OR 1685 01:20:04,096 --> 01:20:09,434 DIRECT EFFECT ON HUMAN HEALTH 1686 01:20:09,434 --> 01:20:11,270 THROUGH SOCIO AND PSYCHO 1687 01:20:11,270 --> 01:20:12,771 ENVIRONMENTAL STRESS AND FINALLY 1688 01:20:12,771 --> 01:20:16,642 TO THE CHRONIC OR STRUCTURAL 1689 01:20:16,642 --> 01:20:17,242 EFFECTS. 1690 01:20:17,242 --> 01:20:20,579 I'M UTILIZING THE ACTION TO 1691 01:20:20,579 --> 01:20:21,613 CONTROL CARDIOVASCULAR RISK IN 1692 01:20:21,613 --> 01:20:24,116 DIABETES WHICH IS AN 1693 01:20:24,116 --> 01:20:27,519 INTERVENTION TRIAL OF CONTROL 1694 01:20:27,519 --> 01:20:29,955 10,000 PEOPLE WITH LONGITUDINAL 1695 01:20:29,955 --> 01:20:30,222 SPECIMENS. 1696 01:20:30,222 --> 01:20:34,092 THIS IS UNIQUE BECAUSE IT'S BEEN 1697 01:20:34,092 --> 01:20:37,329 AFFECTED BY HURRICANE KATRINA IN 1698 01:20:37,329 --> 01:20:38,630 THE SOUTHEAST NETWORK AS YOU CAN 1699 01:20:38,630 --> 01:20:40,632 SEE ON THE MAP. 1700 01:20:40,632 --> 01:20:45,404 I'M COMPARING THE TULANE CITY 1701 01:20:45,404 --> 01:20:48,073 WITHIN THE LOUISIANA CLINICS AND 1702 01:20:48,073 --> 01:20:50,576 COMPARED TO OTHERS IN YELLOW 1703 01:20:50,576 --> 01:20:52,644 USING THE DIFFERENCE METHODS 1704 01:20:52,644 --> 01:20:55,047 TRYING TO FIGURE OUT THE 1705 01:20:55,047 --> 01:20:56,215 ADDITIONAL EFFECT OF HURRICANE 1706 01:20:56,215 --> 01:20:59,785 ON THE BIOMARKERS. 1707 01:20:59,785 --> 01:21:01,887 AND I'M USING OLINK UP WITH OF 1708 01:21:01,887 --> 01:21:03,322 THE MOST FAMOUS PROTEOMIC 1709 01:21:03,322 --> 01:21:05,524 PLATFORM AND WE'RE LOOKING AT 1710 01:21:05,524 --> 01:21:08,961 THE CHANGES OF SIGNATURES PRE 1711 01:21:08,961 --> 01:21:10,896 AND POST HURRICANE KATRINA AND 1712 01:21:10,896 --> 01:21:12,231 TO FIND OUT WHICH PROTEIN 1713 01:21:12,231 --> 01:21:15,033 MARKERS ARE PREDICTIVE OF THE 1714 01:21:15,033 --> 01:21:17,603 DIFFERENCES AND THOSE OF 1715 01:21:17,603 --> 01:21:19,037 COGNITIVE FUNCTION INCLUDED IN 1716 01:21:19,037 --> 01:21:20,639 OUR STUDY. 1717 01:21:20,639 --> 01:21:24,176 THIS WAS AWARD BY THE INTRAMURAL 1718 01:21:24,176 --> 01:21:26,511 CLIMATE CHANGE AND HEALTH 1719 01:21:26,511 --> 01:21:29,948 PROGRAM 2023. 1720 01:21:29,948 --> 01:21:39,024 THE TAKE HOME MESSAGE IS AUTO 1721 01:21:39,024 --> 01:21:40,626 IMMUNITY IS AN APPROACH TO THE 1722 01:21:40,626 --> 01:21:42,361 ROLE IN AGING. 1723 01:21:42,361 --> 01:21:44,463 THERE'S PROSPECTS IN CONDUCTING 1724 01:21:44,463 --> 01:21:45,864 RESEARCH IN THE AUTO IMMUNITY 1725 01:21:45,864 --> 01:21:50,402 AND IN ACCORD ANGST WITH THE 1726 01:21:50,402 --> 01:21:52,037 PHYSIOLOGICAL CHANGE IMMUNITY IS 1727 01:21:52,037 --> 01:21:56,141 CRITICAL AND DEVELOPING NEW 1728 01:21:56,141 --> 01:21:57,809 BIOMARKERS MAY HELP UNDERSTAND 1729 01:21:57,809 --> 01:22:01,780 THE AGING PROCESS AND HOPEFULLY 1730 01:22:01,780 --> 01:22:03,048 THE IDENTIFICATION OF HIGH RISK 1731 01:22:03,048 --> 01:22:04,182 INDIVIDUALS MAY LOOK AT 1732 01:22:04,182 --> 01:22:06,752 INTERVENTION AT EARLY STAGE. 1733 01:22:06,752 --> 01:22:11,189 I CAN'T DO THIS BY MYSELF AND 1734 01:22:11,189 --> 01:22:12,991 HERE'S MY SEAM THAT'S SUPPORTING 1735 01:22:12,991 --> 01:22:13,225 ME. 1736 01:22:13,225 --> 01:22:15,294 -- TEAM THAT IS SUPPORTING ME. 1737 01:22:15,294 --> 01:22:16,929 THANK YOU. 1738 01:22:16,929 --> 01:22:17,996 >> THANK YOU, DR. SONG. 1739 01:22:17,996 --> 01:22:19,031 IT SOUNDS LIKE INTERESTING AND 1740 01:22:19,031 --> 01:22:22,634 IMPORTANT WORK. 1741 01:22:22,634 --> 01:22:24,770 WE HAVE TIME FOR ONE QUESTION. 1742 01:22:24,770 --> 01:22:25,470 I LOVE IT. 1743 01:22:25,470 --> 01:22:27,039 I'LL ASK A QUESTION. 1744 01:22:27,039 --> 01:22:28,407 IT'S GOOD TO MODERATE BECAUSE I 1745 01:22:28,407 --> 01:22:29,875 CAN USE THE TIME HOW I WANT. 1746 01:22:29,875 --> 01:22:32,911 I KEEP LOOKING AT THE DATA OF 1747 01:22:32,911 --> 01:22:36,448 THE INCREASED INCIDENTS OF 1748 01:22:36,448 --> 01:22:39,618 CARDIOVASCULAR DISEASE, CANCER, 1749 01:22:39,618 --> 01:22:40,419 NEURODEGENERATIVE DISEASE AND 1750 01:22:40,419 --> 01:22:43,055 AUTO IMMUNITY WITH AGING AND 1751 01:22:43,055 --> 01:22:45,257 KEEP ASKING MYSELF IS THERE 1752 01:22:45,257 --> 01:22:46,625 ANYTHING GOOD ABOUT GETTING OLD? 1753 01:22:46,625 --> 01:22:49,728 >> I HAVEN'T GIVEN THAT THOUGHT 1754 01:22:49,728 --> 01:22:50,295 PHYSIOLOGICALLY. 1755 01:22:50,295 --> 01:22:56,068 ONE PART IS YOU'RE GETTING 1756 01:22:56,068 --> 01:22:56,768 WISER. 1757 01:22:56,768 --> 01:22:58,603 MORE TOLERABLE AND DON'T GET SO 1758 01:22:58,603 --> 01:23:00,205 MUCH STRESS IN SESSIONS LIKE 1759 01:23:00,205 --> 01:23:00,605 THESE. 1760 01:23:00,605 --> 01:23:01,306 >> WONDERFUL. 1761 01:23:01,306 --> 01:23:03,041 WE'LL LEAVE IT AT THAT THEN. 1762 01:23:03,041 --> 01:23:05,243 THANK YOU VERY MUCH, DR. SONG. 1763 01:23:05,243 --> 01:23:07,612 >> THANK YOU. 1764 01:23:07,612 --> 01:23:15,020 OUR NEXT SPEAKER IS DR. MANNU 1765 01:23:15,020 --> 01:23:20,292 PLATT FROM NIBIB TALKING ABOUT 1766 01:23:20,292 --> 01:23:24,329 DYNAMIC INTERPLAY BETWEENIO 1767 01:23:24,329 --> 01:23:26,665 MECHANICS AND BIOCHEMISTRY IN 1768 01:23:26,665 --> 01:23:27,666 SICKLE CELL DISEASE DISEASE 1769 01:23:27,666 --> 01:23:28,400 LARGE ARTERY DAMAGE. 1770 01:23:28,400 --> 01:23:29,368 >> LET'S DO IT. 1771 01:23:29,368 --> 01:23:39,811 IS THERE A LASER POINTER? 1772 01:23:41,213 --> 01:23:41,380 OKAY. 1773 01:23:41,380 --> 01:23:41,713 ALL RIGHT. 1774 01:23:41,713 --> 01:23:43,615 GREAT, THANK YOU ALL FOR HAVING 1775 01:23:43,615 --> 01:23:43,782 ME. 1776 01:23:43,782 --> 01:23:46,118 IT'S GREAT TO HEAR FROM MY OTHER 1777 01:23:46,118 --> 01:23:48,020 DISTINGUISHED SCHOLARS AND THOSE 1778 01:23:48,020 --> 01:23:51,957 IN MY SMALL MENTOR GROUP. 1779 01:23:51,957 --> 01:23:55,027 I FOUND OUT I'M A SENIOR 1780 01:23:55,027 --> 01:23:58,630 DISTINGUISHED SCHOLAR WHICH GOOD 1781 01:23:58,630 --> 01:24:00,665 THINGS ABOUT AGING. 1782 01:24:00,665 --> 01:24:03,035 I'M AT THE NATIONAL INSTITUTE OF 1783 01:24:03,035 --> 01:24:07,039 BIO MEDICAL ENGINEERING AND TALK 1784 01:24:07,039 --> 01:24:07,339 ABOUT 1785 01:24:07,339 --> 01:24:09,341 I WORK IN SICKLE CELL DISEASE 1786 01:24:09,341 --> 01:24:10,409 AND I'M AN INTRAMURAL 1787 01:24:10,409 --> 01:24:11,543 INVESTIGATOR AND THE DIRECTOR 1788 01:24:11,543 --> 01:24:15,814 NEWLY FORMED DATA CENTER FOR THE 1789 01:24:15,814 --> 01:24:19,017 CENTER FOR BIOMEDICAL ENGIN 1790 01:24:19,017 --> 01:24:20,786 ENGINEERING ACCELERATION. 1791 01:24:20,786 --> 01:24:24,856 OUR GOAL IS TO HELP BRING 1792 01:24:24,856 --> 01:24:26,925 PRINCIPLE TO THE NIH IRP AND 1793 01:24:26,925 --> 01:24:28,627 HELP ACCESS THE TECHNOLOGIES AND 1794 01:24:28,627 --> 01:24:32,330 BUILD COMMUNITY ON CAMPUS AROUND 1795 01:24:32,330 --> 01:24:34,099 BIOMEDICAL ENGINEERING AND USING 1796 01:24:34,099 --> 01:24:34,733 DIVERSITY, EQUITY AND INCLUSION 1797 01:24:34,733 --> 01:24:35,634 AS DRIVING PRINCIPLES FOR WHAT 1798 01:24:35,634 --> 01:24:36,234 WE DO. 1799 01:24:36,234 --> 01:24:42,240 WITH THAT WE WANT TO OFFER OUR 1800 01:24:42,240 --> 01:24:42,974 SCIENCE CONCIERGE SERVICE TO YOU 1801 01:24:42,974 --> 01:24:45,544 ALL AND HAVE BEEN PARTNERING 1802 01:24:45,544 --> 01:24:47,979 WITH THE RESOURCES AT NIBIB AND 1803 01:24:47,979 --> 01:24:51,016 BRINGING ONLINE NEW CAPABILITIES 1804 01:24:51,016 --> 01:24:53,452 SUCH AS SYSTEMS IN COMPUTATIONAL 1805 01:24:53,452 --> 01:24:55,020 BIOLOGY AND SOFT BIO MATERIALS 1806 01:24:55,020 --> 01:24:56,888 AND BUILDING NIH'S FIRST MAKER 1807 01:24:56,888 --> 01:24:58,924 SPACE TO COME IN AND MODIFY AND 1808 01:24:58,924 --> 01:25:00,992 MAKE YOUR OWN TOOLS AND RESEARCH 1809 01:25:00,992 --> 01:25:04,029 FOR YOUR ACTIVITIES COMING 1810 01:25:04,029 --> 01:25:04,629 ONLINE SOON. 1811 01:25:04,629 --> 01:25:07,499 WE BUILT OUR STAFF AND OUR 1812 01:25:07,499 --> 01:25:09,468 MANAGER AND TWO OF OUR STAFF 1813 01:25:09,468 --> 01:25:10,635 RESEARCHERS THAT WILL HELP GET 1814 01:25:10,635 --> 01:25:11,870 YOUR WORK DONE. 1815 01:25:11,870 --> 01:25:14,473 SO THERE'S OUR E-MAIL ADDRESS. 1816 01:25:14,473 --> 01:25:17,309 IF YOU'RE NOT ON OUR LIST SERVE 1817 01:25:17,309 --> 01:25:19,144 AND WANT ACCESS SEND US AN 1818 01:25:19,144 --> 01:25:23,048 E-MAIL WE'RE HAPPY TO HAVE YOU 1819 01:25:23,048 --> 01:25:25,117 AND MEET AND GREETS TO GET TO 1820 01:25:25,117 --> 01:25:28,086 KNOW YOU AND WE RUN TRAINING 1821 01:25:28,086 --> 01:25:29,488 PROGRAMS TO RECRUIT NEW BIO 1822 01:25:29,488 --> 01:25:32,190 ENGINEERS AND HELP SHOW THEM 1823 01:25:32,190 --> 01:25:36,094 WHAT THE NIH IRB CAN DO AND MANY 1824 01:25:36,094 --> 01:25:37,596 DON'T REALIZE THE EXCITING THING 1825 01:25:37,596 --> 01:25:41,333 HAPPENING HERE AND WE HAVE THE 1826 01:25:41,333 --> 01:25:44,870 LONG RUNNING PROGRAM AND 1827 01:25:44,870 --> 01:25:46,638 INTERNSHIP PROGRAM AND NIBIB 1828 01:25:46,638 --> 01:25:49,474 FUNDS THE STUDENTS BUT 1829 01:25:49,474 --> 01:25:52,644 DISTRIBUTE THEM TO INVESTIGATORS 1830 01:25:52,644 --> 01:25:55,046 AND WOULD LOVE TO SEE NEW 1831 01:25:55,046 --> 01:25:57,282 SCHOLARS AND YOU CAN MENTOR ONE 1832 01:25:57,282 --> 01:25:59,017 OF THESE STUDENTS AT NIBIB'S 1833 01:25:59,017 --> 01:26:01,119 COST AND IF OTHERS WOULD LIKE TO 1834 01:26:01,119 --> 01:26:02,754 CONTRIBUTE FUNDS WE'RE EXCITED 1835 01:26:02,754 --> 01:26:05,590 TO HAVE YOU JOIN US. 1836 01:26:05,590 --> 01:26:10,128 AND WE'VE OPENED IT UP TO NOT 1837 01:26:10,128 --> 01:26:15,033 JUST BIOMEDICAL BUT S.T.E.M. 1838 01:26:15,033 --> 01:26:16,501 MAJORS. 1839 01:26:16,501 --> 01:26:17,702 ALSO, ANOTHER OPPORTUNITY 1840 01:26:17,702 --> 01:26:20,138 OCTOBER 22 WE'RE HOSTING A BIG 1841 01:26:20,138 --> 01:26:21,740 BIO ENGINEERING DAY ON THE NIH 1842 01:26:21,740 --> 01:26:21,973 CAMPUS. 1843 01:26:21,973 --> 01:26:22,641 IF YOU HAVEN'T HEARD I'M 1844 01:26:22,641 --> 01:26:24,609 PITCHING IT. 1845 01:26:24,609 --> 01:26:25,710 YOU CAN STILL APPLY. 1846 01:26:25,710 --> 01:26:31,049 FREE REGISTRATION AND WE'RE 1847 01:26:31,049 --> 01:26:37,022 TRYING TO BRIDGE EXTRAMURAL AND 1848 01:26:37,022 --> 01:26:39,024 INTRAMURAL AND WE'RE HAVING 1849 01:26:39,024 --> 01:26:40,625 EVERYONE IN BETHESDA MEET US AND 1850 01:26:40,625 --> 01:26:42,861 BLEND OF POSTERS AND PITCHING 1851 01:26:42,861 --> 01:26:44,262 OUR WARES HOME TO AND GETTING 1852 01:26:44,262 --> 01:26:46,631 THEM TO WANT TO WORK WITH US. 1853 01:26:46,631 --> 01:26:53,872 TWO KEY NOTES FROM A COLLISION 1854 01:26:53,872 --> 01:26:55,073 GROUNDBREAKING ON SECOND HALF 1855 01:26:55,073 --> 01:26:57,742 AND ANOTHER ON DIAGNOSTICS. 1856 01:26:57,742 --> 01:26:57,943 OKAY. 1857 01:26:57,943 --> 01:27:01,580 NOW I GET TO TALK ABOUT ME. 1858 01:27:01,580 --> 01:27:04,049 I HAVE TO PLUG MY DATA CENTER 1859 01:27:04,049 --> 01:27:06,384 WORK SO IT CUTS MY TIME SHORT. 1860 01:27:06,384 --> 01:27:09,454 I RUN THE MATRICES LAB AND 1861 01:27:09,454 --> 01:27:12,057 MECHANICS AND TISSUE REMODELLING 1862 01:27:12,057 --> 01:27:13,191 AND COMPUTATIONAL EXPERIMENTAL 1863 01:27:13,191 --> 01:27:13,792 SYSTEMS. 1864 01:27:13,792 --> 01:27:15,026 I HOPE TO SHOW YOU A LITTLE BIT 1865 01:27:15,026 --> 01:27:17,629 ABOUT MY WORK AND SHOW HOW 1866 01:27:17,629 --> 01:27:19,664 ENGINEERING PRINCIPLES CAN BE 1867 01:27:19,664 --> 01:27:23,235 USED TO ASK BIOLOGICAL AND 1868 01:27:23,235 --> 01:27:24,269 CLINICAL QUESTIONS. 1869 01:27:24,269 --> 01:27:31,543 AND I LOVE PROTEASES MORE THAN 1870 01:27:31,543 --> 01:27:31,810 ANYTHING. 1871 01:27:31,810 --> 01:27:42,354 THIS IS ME AT THE GIC ON BE ON 1872 01:28:02,474 --> 01:28:04,342 THIS AND SS HAS SICKLE CELL AND 1873 01:28:04,342 --> 01:28:12,684 IT'S A HEALTH DISPARITY ONE IN 1874 01:28:12,684 --> 01:28:16,655 12 HAS SICKLE CELL TRAITOR 1875 01:28:16,655 --> 01:28:19,591 CARRIERS AND IT'S A GLOBAL 1876 01:28:19,591 --> 01:28:20,191 DISEASE. 1877 01:28:20,191 --> 01:28:24,429 I GOT INTO IT WITH THE 1878 01:28:24,429 --> 01:28:26,665 CARDIOVASCULAR COMPONENTS. 1879 01:28:26,665 --> 01:28:29,067 A LOT OF WORK IN THE MICRO 1880 01:28:29,067 --> 01:28:30,368 CIRCULATION AND I WAS TOLD 1881 01:28:30,368 --> 01:28:31,770 CHILDREN WITH SICKLE CELLS ARE 1882 01:28:31,770 --> 01:28:35,040 HAVING STROKE. 1883 01:28:35,040 --> 01:28:37,942 Ph.D. TRAINING WAS TALKING ABOUT 1884 01:28:37,942 --> 01:28:39,044 CARDIOVASCULAR DISEASE THAT 1885 01:28:39,044 --> 01:28:45,950 DEVELOP OVER 60, 70 YEARS AND 1886 01:28:45,950 --> 01:28:50,322 THE CELLS SICKLE UNDER THE 1887 01:28:50,322 --> 01:28:53,725 CONDITIONS AND 11% OF CHILDREN 1888 01:28:53,725 --> 01:28:55,794 WITH SICKLE CELL HAVE A STROKE 1889 01:28:55,794 --> 01:29:02,067 BY 16 AND GREATEST RISK IS 2 AND 1890 01:29:02,067 --> 01:29:03,968 6 YEARS OLD AND THERE'S A 1891 01:29:03,968 --> 01:29:06,504 COGNITIVE RESULT WHERE THEY LOOK 1892 01:29:06,504 --> 01:29:08,673 AT THE MRI AND REALIZE THE 1893 01:29:08,673 --> 01:29:10,642 CHALLENGES. 1894 01:29:10,642 --> 01:29:13,144 THERE'S AN AMAZING CLINICAL 1895 01:29:13,144 --> 01:29:21,286 TRIAL IN THE '90s SHOWING 1896 01:29:21,286 --> 01:29:23,054 INCREASED VELOCITIES ARE AT 1897 01:29:23,054 --> 01:29:25,457 GREATER RISK OF STROKE. 1898 01:29:25,457 --> 01:29:26,825 ONE CLINICAL TRIAL STOPPED EARLY 1899 01:29:26,825 --> 01:29:28,660 BECAUSE THOSE NOT RECEIVING 1900 01:29:28,660 --> 01:29:29,861 TRANSFUSIONS WERE RECEIVING 1901 01:29:29,861 --> 01:29:31,596 STROKES OR DIAG. 1902 01:29:31,596 --> 01:29:33,932 THIS IS STILL THE CURRENT STATE 1903 01:29:33,932 --> 01:29:35,033 OF CARE. 1904 01:29:35,033 --> 01:29:38,703 WHY ARE THE VELOCITIES INCREASED 1905 01:29:38,703 --> 01:29:42,607 IN WHEN YOU GET STENOSIS YOU CAN 1906 01:29:42,607 --> 01:29:46,644 GET INCREASED VELOCITY AND POST 1907 01:29:46,644 --> 01:29:49,981 STENOSIS YOU GET DECREASED FLOW 1908 01:29:49,981 --> 01:29:51,816 IN THE VASCULATURE AND THOSE ARE 1909 01:29:51,816 --> 01:29:53,718 SITES WHERE ATHEROSCLEROTIC 1910 01:29:53,718 --> 01:29:55,653 PLAQUES WERE FORMING. 1911 01:29:55,653 --> 01:30:00,058 YOU CAN SEE A PATHOLOGIST 1912 01:30:00,058 --> 01:30:01,726 STARTED TO SEE THESE AND TALKED 1913 01:30:01,726 --> 01:30:06,698 TO HIS BUDDY WHO SAID WE KNOW 1914 01:30:06,698 --> 01:30:11,136 WITH A BIFURCATION YOU GET FLOW 1915 01:30:11,136 --> 01:30:13,171 REVERSAL OVER THE CARDIAC CYCLE 1916 01:30:13,171 --> 01:30:16,641 AND WHERE YOU GET THE REGIONS IS 1917 01:30:16,641 --> 01:30:26,651 WHERE WE'RE SEEING THE PLAQUE 1918 01:30:26,651 --> 01:30:27,652 AND INCREASED DISEASE. 1919 01:30:27,652 --> 01:30:33,124 I SAID WHY ARE WE NOT LOOKING AT 1920 01:30:33,124 --> 01:30:33,792 THIS IN SECOND HALF. 1921 01:30:33,792 --> 01:30:42,434 SO WE -- SICKLE CELL AND WE 1922 01:30:42,434 --> 01:30:45,370 RECREATED THIS IN THE COMPUTER 1923 01:30:45,370 --> 01:30:46,704 TO USE COMPUTATIONAL FLUID 1924 01:30:46,704 --> 01:30:50,041 DYNAMICS TO SEE HOW IT CAN LEAD 1925 01:30:50,041 --> 01:30:55,046 TO DISTURBED FLOW THAT MIGHT BE 1926 01:30:55,046 --> 01:30:58,483 SUSCEPTIBLE TO THE REMODELLING 1927 01:30:58,483 --> 01:31:00,618 OF CHILDREN WITH SICKLE CELL AND 1928 01:31:00,618 --> 01:31:02,520 THEY HAD REGIONS OF FLOW 1929 01:31:02,520 --> 01:31:03,888 RECIRCULATION IN HUMANS. 1930 01:31:03,888 --> 01:31:07,025 NOW AS AN ENGINEER WE CAN 1931 01:31:07,025 --> 01:31:12,030 RECREATE THE FLUID PROFILES IN 1932 01:31:12,030 --> 01:31:14,332 VITRO AND HAVE A REACTOR AND NOW 1933 01:31:14,332 --> 01:31:20,505 YOU CAN PUT IN VASO PROTECTIVE 1934 01:31:20,505 --> 01:31:23,975 PROFILES OR ONE LIKE SEEN ON THE 1935 01:31:23,975 --> 01:31:27,045 OUTSIDE OF THE CAROTID ARTERY 1936 01:31:27,045 --> 01:31:32,484 WALL AND THE ENDOTHELIAL CELLS 1937 01:31:32,484 --> 01:31:34,652 THAT ELONGATE FLOW SHOW IT'S 1938 01:31:34,652 --> 01:31:39,057 WORKING AND THE THERE'S BIO M 1939 01:31:39,057 --> 01:31:44,929 MECHANICS AND THERE'S DIFFERENT 1940 01:31:44,929 --> 01:31:50,502 FLOW PROFILES AND BIO CHEMISTRY 1941 01:31:50,502 --> 01:31:51,035 RESPONSES. 1942 01:31:51,035 --> 01:31:53,671 THERE'S A MOUSE MODEL AND WE 1943 01:31:53,671 --> 01:31:55,640 KNOCKED OUT THE MOUSE HEME 1944 01:31:55,640 --> 01:32:06,150 SFLOEB -- HEMOGLOBINS AND WE 1945 01:32:06,417 --> 01:32:11,022 LOOKED AT THE MICE ACTIVATED WAS 1946 01:32:11,022 --> 01:32:12,257 ELEVATED IN THE CAROTID ARTERIES 1947 01:32:12,257 --> 01:32:18,530 OF THE MOUSE AND IN WHY HIBTING 1948 01:32:18,530 --> 01:32:22,166 CAN STOP IT FROM BEING TURNED UP 1949 01:32:22,166 --> 01:32:23,801 AND THEN LOOKED AT 5-MONTH-OLD 1950 01:32:23,801 --> 01:32:25,203 MICE AND THIS SHOCKED US. 1951 01:32:25,203 --> 01:32:26,938 WE WERE FOCUSSED ON THE 1952 01:32:26,938 --> 01:32:28,640 DEGRADATION BUT BY FIVE MONTHS 1953 01:32:28,640 --> 01:32:30,775 WE SAW THIS INCREDIBLE LOSS OF 1954 01:32:30,775 --> 01:32:34,646 COLLAGEN IN THE ARTERY WALL AND 1955 01:32:34,646 --> 01:32:36,748 CONFIRMED STIFFNESS AND YOU SEE 1956 01:32:36,748 --> 01:32:38,816 THE BLOWN OUT ARTERY. 1957 01:32:38,816 --> 01:32:43,821 ONCE THE CHILDREN GET PAST THE 1958 01:32:43,821 --> 01:32:47,458 OF STROKE THEY'RE AT RISK OF 1959 01:32:47,458 --> 01:32:49,027 HEMORRHAGIC STROKE AND LOSS OF 1960 01:32:49,027 --> 01:32:51,462 THE ARTERY WALL THAT PREDISPOSED 1961 01:32:51,462 --> 01:32:55,033 THEM TO THAT BUT THERE'S A 1962 01:32:55,033 --> 01:32:57,101 VARIABILITY. 1963 01:32:57,101 --> 01:32:58,770 THE SAME VARIABILITY GOES TO OUR 1964 01:32:58,770 --> 01:33:01,639 MASS MODEL. 1965 01:33:01,639 --> 01:33:04,208 MY SENIOR STAFF AND STAFF 1966 01:33:04,208 --> 01:33:06,077 SCIENTISTS IDENTIFIED A PROTOCOL 1967 01:33:06,077 --> 01:33:07,845 WE COULD MONITOR THE SAME MOUSE 1968 01:33:07,845 --> 01:33:10,848 AS THEY AGE TO REDUCE THAT 1969 01:33:10,848 --> 01:33:11,950 SUBJECT TO SUBJECT VARIABILITY. 1970 01:33:11,950 --> 01:33:13,885 SO WE'VE BEEN DOING THAT AND 1971 01:33:13,885 --> 01:33:17,622 OVER TIME FROM ONE TO FIVE MONTH 1972 01:33:17,622 --> 01:33:19,057 MONITORING THE CHANGES IN THE 1973 01:33:19,057 --> 01:33:23,494 DIAMETERS OFF THE ARTERIES OF 1974 01:33:23,494 --> 01:33:27,899 THE MICE AND HETEROGOUS AND WITH 1975 01:33:27,899 --> 01:33:30,668 LIVING MICE WE'RE ABLE TO SEE 1976 01:33:30,668 --> 01:33:31,970 THIS LUMINAL EXPANSION AS THE 1977 01:33:31,970 --> 01:33:33,304 MICE AGE WHICH MATCHES WHAT WE 1978 01:33:33,304 --> 01:33:34,639 WERE SEEING BEFORE BUT THEN THE 1979 01:33:34,639 --> 01:33:36,474 QUESTION IS HOW DOES THAT CHANGE 1980 01:33:36,474 --> 01:33:40,645 THE BIO MECHANICS OR BLOOD FLOW 1981 01:33:40,645 --> 01:33:40,912 PROFILES. 1982 01:33:40,912 --> 01:33:43,014 HERE I HAVE TALENTED POST-BACS 1983 01:33:43,014 --> 01:33:46,651 AND ALONG THE LENGTH OF THE 1984 01:33:46,651 --> 01:33:49,087 ARTERY THE FLUID PROFILE 1985 01:33:49,087 --> 01:33:51,022 CHANGING AND WE CAN LOOK AT THE 1986 01:33:51,022 --> 01:33:53,524 DISTRIBUTION VERSUS THE OTHERS. 1987 01:33:53,524 --> 01:33:56,427 AND WHAT'S INTERESTING IS YOU 1988 01:33:56,427 --> 01:33:59,464 SEE GREATER AREAS IN THE SS AND 1989 01:33:59,464 --> 01:34:04,636 IN THE STRAIGHT PARTS OF THE 1990 01:34:04,636 --> 01:34:05,637 ARTERY AND THAT BECOMES THE 1991 01:34:05,637 --> 01:34:06,471 DISTINCTION BETWEEN 1992 01:34:06,471 --> 01:34:07,038 CARDIOVASCULAR DISEASE AND 1993 01:34:07,038 --> 01:34:09,207 OTHERS AND NOW TRYING TO 1994 01:34:09,207 --> 01:34:11,209 REGISTER WHERE WE SEE THOSE WITH 1995 01:34:11,209 --> 01:34:14,512 THE BIOLOGICAL CHANGES WITH 1996 01:34:14,512 --> 01:34:17,615 HISTOLOGY AND IMMUNOHISTORIC 1997 01:34:17,615 --> 01:34:19,951 CHEMISTRY AND FINALLY THE GENE 1998 01:34:19,951 --> 01:34:21,285 THERAPY WORKED BUT STILL 1999 01:34:21,285 --> 01:34:23,554 REQUIRES A BONE MARROW 2000 01:34:23,554 --> 01:34:24,622 TRANSPLANT. 2001 01:34:24,622 --> 01:34:25,923 EVEN PATIENTS WITH TRANSPLANT 2002 01:34:25,923 --> 01:34:28,593 STILL ARE AT RISK SO WE WANT TO 2003 01:34:28,593 --> 01:34:29,994 UNDERSTAND IF THERE'S ADJUVANT 2004 01:34:29,994 --> 01:34:33,131 THERAPIES OR TIMING COULD BE 2005 01:34:33,131 --> 01:34:33,531 HELPFUL. 2006 01:34:33,531 --> 01:34:36,334 WE TRANSPLANTED AND THE EARLIER 2007 01:34:36,334 --> 01:34:39,170 WE DID THE TRANSPLANT WE COULD 2008 01:34:39,170 --> 01:34:41,439 PROTECT THE VASCULATURE FROM THE 2009 01:34:41,439 --> 01:34:43,174 INSULT AND WORKS OUT FOR THE 2010 01:34:43,174 --> 01:34:45,777 MICE LATER. 2011 01:34:45,777 --> 01:34:47,045 SO, ANATOMICAL CHANGES ARE 2012 01:34:47,045 --> 01:34:50,348 IMPORTANT AND THINKING ABOUT THE 2013 01:34:50,348 --> 01:34:52,650 MECHANICS OF THE BLOOD FLOW AND 2014 01:34:52,650 --> 01:34:54,018 BIOLOGY AND PATIENT TO PATIENT 2015 01:34:54,018 --> 01:34:56,421 BIOLOGY AND LOOK AT ADJUVANT 2016 01:34:56,421 --> 01:34:58,656 THERAPIES TO PROTECT THE 2017 01:34:58,656 --> 01:35:01,159 VASCULATURE AFTERWARDS IF THAT'S 2018 01:35:01,159 --> 01:35:01,826 NOT SUFFICIENT. 2019 01:35:01,826 --> 01:35:02,093 THANK YOU. 2020 01:35:02,093 --> 01:35:06,164 LOVE MY TEAM AND I WANT TO THANK 2021 01:35:06,164 --> 01:35:10,635 THE PROGRAM AND DR. MARIE 2022 01:35:10,635 --> 01:35:14,572 BERNARD VERY SUPPORTIVE AND I 2023 01:35:14,572 --> 01:35:15,973 WANT TO THANK DR. TROMBERG. 2024 01:35:15,973 --> 01:35:17,241 IT'S BEEN WONDERFUL TO BE HERE 2025 01:35:17,241 --> 01:35:18,209 AT NIH. 2026 01:35:18,209 --> 01:35:19,077 THANK YOU ALL. 2027 01:35:19,077 --> 01:35:20,878 COME SEE US SOON. 2028 01:35:20,878 --> 01:35:22,880 >> THANK YOU, DR. PLATT. 2029 01:35:22,880 --> 01:35:25,850 THAT WAS A TOUR DEFORCE AND 2030 01:35:25,850 --> 01:35:27,452 THANK YOU FOR THE ADVERTISING 2031 01:35:27,452 --> 01:35:28,419 FOR THE BETA CENTER. 2032 01:35:28,419 --> 01:35:29,454 WE HAVE TO CONNECT. 2033 01:35:29,454 --> 01:35:35,026 ARE THERE ANY QUESTIONS? 2034 01:35:35,026 --> 01:35:38,129 >> THANK YOU FOR THE WONDERFUL 2035 01:35:38,129 --> 01:35:39,030 TALK. 2036 01:35:39,030 --> 01:35:42,900 I'M AN ENDOCRINOLOGIST AND 2037 01:35:42,900 --> 01:35:47,038 LOOKING IF THE WORK YOU DO IS 2038 01:35:47,038 --> 01:35:51,042 APPLICABLE TO TO DIABETES WITH 2039 01:35:51,042 --> 01:35:51,809 CARDIOVASCULAR COMPLICATIONS. 2040 01:35:51,809 --> 01:35:54,612 YOU KNOW YOU FOCUS ON THE BIGGER 2041 01:35:54,612 --> 01:35:57,648 BLOOD VESSELS BUT IF WHAT YOU DO 2042 01:35:57,648 --> 01:36:00,551 CAN APPLY TO SMALLER VESSELS AND 2043 01:36:00,551 --> 01:36:01,519 COMPLICATIONS IN DIABETES. 2044 01:36:01,519 --> 01:36:04,222 >> ABSOLUTELY. 2045 01:36:04,222 --> 01:36:08,726 WE DO MRAs AND CAN EUTHANIZE 2046 01:36:08,726 --> 01:36:14,198 THEM AND GET THE VOLUME AND 2047 01:36:14,198 --> 01:36:15,399 ANATOMY OF THE MICROVESSELS AND 2048 01:36:15,399 --> 01:36:16,634 HAPPY TO TALK AFTER. 2049 01:36:16,634 --> 01:36:18,970 >> YOU'RE OPEN TO STUDYING 2050 01:36:18,970 --> 01:36:22,640 PEOPLE WITH DIABETES IN ADDITION 2051 01:36:22,640 --> 01:36:25,576 TO SICKLE CELL? 2052 01:36:25,576 --> 01:36:27,879 >> YES. 2053 01:36:27,879 --> 01:36:29,881 AND THE BETA CENTER CAN HELP 2054 01:36:29,881 --> 01:36:30,882 YOUR TEAM. 2055 01:36:30,882 --> 01:36:34,485 >> I CUT MY TEETH AS A POSTDOC 2056 01:36:34,485 --> 01:36:36,888 IN THE SAME LAB YOU DID YOUR 2057 01:36:36,888 --> 01:36:37,955 STUDY. 2058 01:36:37,955 --> 01:36:40,158 I WONDER WHEN WE THINK OF BLOOD 2059 01:36:40,158 --> 01:36:41,859 VESSELS WE THINK OF THEM MOSTLY 2060 01:36:41,859 --> 01:36:42,927 IN TERMS OF THE FLOW GOING 2061 01:36:42,927 --> 01:36:47,331 THROUGH IN ONE DIRECTION BUT YOU 2062 01:36:47,331 --> 01:36:51,035 DESCRIBE THERE'S AN AXIAL 2063 01:36:51,035 --> 01:36:51,636 STRETCH. 2064 01:36:51,636 --> 01:36:55,039 DO YOU THINK THERE ARE WAYS TO 2065 01:36:55,039 --> 01:36:56,574 POTENTIALLY REVERSE THIS 2066 01:36:56,574 --> 01:36:59,510 PHENOTYPE ONES IT SETS IN. 2067 01:36:59,510 --> 01:37:01,078 GETTING BACK TO THE AGING THING 2068 01:37:01,078 --> 01:37:03,614 BECAUSE AS YOU GET OLDER THEY 2069 01:37:03,614 --> 01:37:04,182 GET STIFFER. 2070 01:37:04,182 --> 01:37:14,592 >> WE LOOK AT ARTERIAL 2071 01:37:16,460 --> 01:37:16,661 STIFFNESS. 2072 01:37:16,661 --> 01:37:20,031 WE CANNOT CORRECT DAMAGE TO THE 2073 01:37:20,031 --> 01:37:22,500 ARTERIES AND PROVIDE THE 2074 01:37:22,500 --> 01:37:25,136 ELASTICITY BUT YOU CAN MODULATE 2075 01:37:25,136 --> 01:37:27,038 SOME COLLAGEN SO IT'S NOT TOO 2076 01:37:27,038 --> 01:37:28,639 STIFF BUT IF YOU REDUCE IT TOO 2077 01:37:28,639 --> 01:37:32,109 MUCH YOU'RE AT RISK OF BLOWING 2078 01:37:32,109 --> 01:37:34,512 IT OUT BUT I THINK THERE'S 2079 01:37:34,512 --> 01:37:35,112 REGENERATIVE PRINCIPLES AND 2080 01:37:35,112 --> 01:37:37,248 WE'RE TRYING TO FIND NEW WAYS 2081 01:37:37,248 --> 01:37:38,816 BUT I THINK THE NATIVE BODY 2082 01:37:38,816 --> 01:37:43,020 DOESN'T REPAIR ON ITS OWN. 2083 01:37:43,020 --> 01:37:43,688 >> AND SICKLE CELL DISEASE BEING 2084 01:37:43,688 --> 01:37:49,560 A HEMOGLOBINOPATHY TO YOU THINK 2085 01:37:49,560 --> 01:37:51,462 IT APPLIES TO OTHERS? 2086 01:37:51,462 --> 01:37:54,131 >> WE THINK THERE'S THINGS 2087 01:37:54,131 --> 01:37:55,766 HAPPENING IN THE ALPHA TAU AND 2088 01:37:55,766 --> 01:37:58,769 BETA TAU AND WE'RE FOCUSSING ON 2089 01:37:58,769 --> 01:38:01,439 SICKLE CELL BUT NOW GETTING INTO 2090 01:38:01,439 --> 01:38:02,440 SD AND THERE'S INTERESTING 2091 01:38:02,440 --> 01:38:05,343 THINGS AND TO THE ENCRINOLOGIST 2092 01:38:05,343 --> 01:38:08,412 I WAS HOPING YOU'D SAY 2093 01:38:08,412 --> 01:38:09,614 OSTEOPOROSIS BECAUSE THERE'S 2094 01:38:09,614 --> 01:38:10,648 BONE COMPLICATIONS BY LAB IS 2095 01:38:10,648 --> 01:38:17,755 ALSO LOOKING AT SO IT'S A 2096 01:38:17,755 --> 01:38:19,991 MULTI-FACTORIAL EFFECT AND 2097 01:38:19,991 --> 01:38:22,660 MULTI-ORGAN SYSTEMS. 2098 01:38:22,660 --> 01:38:25,396 >> THANK YOU. 2099 01:38:25,396 --> 01:38:29,300 OUR NEXT SPEAKER IS 2100 01:38:29,300 --> 01:38:31,602 DR. FLORENCIA PRATTO TALKING 2101 01:38:31,602 --> 01:38:33,404 ABOUT MULTI-LAYERED CON FREE 2102 01:38:33,404 --> 01:38:37,308 THROW LINE OF THE RECOMBINATION 2103 01:38:37,308 --> 01:38:38,910 AND DIVERSITY IN THE MAMMALIAL 2104 01:38:38,910 --> 01:38:43,014 GERM LINE. 2105 01:38:43,014 --> 01:38:46,717 >> SO I'M GOING TO TRY TO FOLLOW 2106 01:38:46,717 --> 01:38:53,391 AND TALK ABOUT THE MULTIPLE LAY 2107 01:38:53,391 --> 01:38:58,663 YEARS OF CONTROL IN THE 2108 01:38:58,663 --> 01:39:04,635 MAMMALIAN GERM LINE AND WE LOOK 2109 01:39:04,635 --> 01:39:15,079 AT REPLICATION. 2110 01:39:15,079 --> 01:39:25,556 AND ONE GOAL OF RECOMBINATION IS 2111 01:39:43,341 --> 01:39:50,548 TO LINK THE CHROMOSOMES TO 2112 01:39:50,548 --> 01:39:54,652 ORIENT AND SECOND IT CREATES NEW 2113 01:39:54,652 --> 01:39:56,253 ALLELE COMBINATIONS THEREFORE 2114 01:39:56,253 --> 01:40:00,157 HAS GENETIC DIVERSITY. 2115 01:40:00,157 --> 01:40:02,793 THE DOUBLE STRAND BREAKS ARE 2116 01:40:02,793 --> 01:40:07,765 IMPORTANT FOR SUCCESSFUL MIOS 2117 01:40:07,765 --> 01:40:09,333 IS. 2118 01:40:09,333 --> 01:40:13,104 THE CELL HAS TO MAKE THE RIGHT 2119 01:40:13,104 --> 01:40:14,405 AMOUNT IN THE RIGHT TIME AT THE 2120 01:40:14,405 --> 01:40:19,710 RIGHT PLACE AND THOUGH THERE'S 2121 01:40:19,710 --> 01:40:21,579 GOOD CONTROL IT'S BEEN ESTIMATED 2122 01:40:21,579 --> 01:40:28,652 UP TO 60% OF HUMAN HAVE THE 2123 01:40:28,652 --> 01:40:30,721 CHROMOSOMAL ABNORMALITY TO THE 2124 01:40:30,721 --> 01:40:34,091 ERRORS DUE TO MANY CASES ARE A 2125 01:40:34,091 --> 01:40:39,930 LEADING CAUSE OF MISCARRIAGES 2126 01:40:39,930 --> 01:40:40,598 INFERTILITY. 2127 01:40:40,598 --> 01:40:41,732 THERE'S BEEN TIME TRYING TO 2128 01:40:41,732 --> 01:40:42,633 UNDERSTAND HOW THE EVENTS ARE 2129 01:40:42,633 --> 01:40:46,871 MADE AND HOW TO CONTROL THE 2130 01:40:46,871 --> 01:40:50,875 OUTCOMES. 2131 01:40:50,875 --> 01:40:55,046 THESE ARE MADE BY CONSERVED 2132 01:40:55,046 --> 01:41:05,156 PROTEIN THAT MAKES THE DOUBLE 2133 01:41:05,156 --> 01:41:08,626 STRAND BREAK AND WE LOOK AT THE 2134 01:41:08,626 --> 01:41:14,098 BACTERIA AND COVERS THE FILAMENT 2135 01:41:14,098 --> 01:41:18,769 AND CELL MYOSIS AND ONCE IT'S 2136 01:41:18,769 --> 01:41:21,105 ENGAGED THE BREAKS ARE REPAIRED 2137 01:41:21,105 --> 01:41:28,946 AND IN MAMMALIANS THERE'S A 2138 01:41:28,946 --> 01:41:32,817 SHORT OUTCOME BUT DOESN'T HAVE 2139 01:41:32,817 --> 01:41:38,789 THE HAPLOTYPE SWITCH. 2140 01:41:38,789 --> 01:41:43,027 SO THE DOUBLE STRAND BREAKS 2141 01:41:43,027 --> 01:41:47,031 OCCUR AT HOT SPOTS. 2142 01:41:47,031 --> 01:41:49,467 AND THEN IT WAS DISCOVERED IT'S 2143 01:41:49,467 --> 01:41:54,338 A VERY INTERESTING PROTEIN AND 2144 01:41:54,338 --> 01:42:00,544 DERMINATE OF THE LOCATION AND 2145 01:42:00,544 --> 01:42:05,683 MYOTIC TRANSFERASE AND IT BINDS 2146 01:42:05,683 --> 01:42:07,751 TO THE GENOME AND THEREFORE 2147 01:42:07,751 --> 01:42:08,319 CHANGES THE LANDSCAPE AMONG 2148 01:42:08,319 --> 01:42:10,087 INDIVIDUALS. 2149 01:42:10,087 --> 01:42:16,127 IT IS THE FASTEST IN MAMMALS AND 2150 01:42:16,127 --> 01:42:17,027 WE FOUND HUNDREDS FROM HUMANS 2151 01:42:17,027 --> 01:42:21,265 AND MICE. 2152 01:42:21,265 --> 01:42:24,969 SO THERE WERE HOT SPOTS AND 2153 01:42:24,969 --> 01:42:26,237 LOOKED AT WHERE THEY WERE 2154 01:42:26,237 --> 01:42:27,171 LOCATED IN MAMMALS. 2155 01:42:27,171 --> 01:42:35,012 WE DEVELOPED A TECHNIQUE WHICH 2156 01:42:35,012 --> 01:42:37,047 IS WHERE WE PULL THIS DOWN AND 2157 01:42:37,047 --> 01:42:39,617 LOOK AT THE DNA ASSOCIATED WITH 2158 01:42:39,617 --> 01:42:39,850 IT. 2159 01:42:39,850 --> 01:42:41,118 WE KEEP THE FORMATION. 2160 01:42:41,118 --> 01:42:46,657 WE HAVE A STEREOTYPICAL PATTERN 2161 01:42:46,657 --> 01:42:49,393 OF STRAND TO THE BREAK AND TO 2162 01:42:49,393 --> 01:42:50,995 THE RIGHT OF THE BREAK. 2163 01:42:50,995 --> 01:42:52,663 THIS GIVES US A LOT OF 2164 01:42:52,663 --> 01:42:56,000 SENSITIVITY AND SPECIFICITY SO 2165 01:42:56,000 --> 01:42:56,634 WE WERE ABLE TO DO THIS FROM 2166 01:42:56,634 --> 01:43:04,642 HUMAN INDIVIDUALS. 2167 01:43:04,642 --> 01:43:08,646 THIS IS A SNAPSHOT FROM HUMAN 2168 01:43:08,646 --> 01:43:09,313 INDIVIDUALS. 2169 01:43:09,313 --> 01:43:10,648 THE POSITIONS OF THE HOT SPOTS 2170 01:43:10,648 --> 01:43:18,322 ARE DETERMINED BY THE TYPE OF 2171 01:43:18,322 --> 01:43:24,495 ALLELES THE INDIVIDUAL CARRIES 2172 01:43:24,495 --> 01:43:27,932 AND THERE'S A HUGE RECOMBINATION 2173 01:43:27,932 --> 01:43:29,166 AT THE CHROMOSOME. 2174 01:43:29,166 --> 01:43:31,635 THIS IS THE PART AND THERE'S 2175 01:43:31,635 --> 01:43:37,441 MORE HOT SPOTS AND THEY'RE MORE 2176 01:43:37,441 --> 01:43:37,708 FREQUENT. 2177 01:43:37,708 --> 01:43:40,644 THE PAST WORK UNCOVERED TWO 2178 01:43:40,644 --> 01:43:45,649 PROCESSES THAT OPERATE ON BROAD 2179 01:43:45,649 --> 01:43:46,650 SCALES. 2180 01:43:46,650 --> 01:43:53,857 ONE WHAT IS ILLUSTRATED HERE AND 2181 01:43:53,857 --> 01:43:58,729 TWO THE CONCENTRATION OF THE 2182 01:43:58,729 --> 01:43:59,997 RECOMBINATION. 2183 01:43:59,997 --> 01:44:02,132 SO WE THOUGHT TO UNDERSTAND WHAT 2184 01:44:02,132 --> 01:44:05,502 IS UNDERLYING THIS BROAD SCALE 2185 01:44:05,502 --> 01:44:08,439 CONTROL OF RECOMBINATION AND 2186 01:44:08,439 --> 01:44:13,978 THOUGHT TO LOOK TO THE 2187 01:44:13,978 --> 01:44:18,215 REPLICATION AND THIS IS LINKED 2188 01:44:18,215 --> 01:44:21,285 FOR REPLICATION MECHANISTICALLY 2189 01:44:21,285 --> 01:44:26,890 AND WE CANNOT STUDY MAMMALIAN 2190 01:44:26,890 --> 01:44:30,561 MYOSIS IN VIVO. 2191 01:44:30,561 --> 01:44:33,597 THIS IS HAPPENING IN THE MALES 2192 01:44:33,597 --> 01:44:35,799 IN THE TISSUE WHERE 1% OF THE 2193 01:44:35,799 --> 01:44:38,469 CELLS ARE UNDERGOING MYOTIC 2194 01:44:38,469 --> 01:44:39,003 REPLICATION. 2195 01:44:39,003 --> 01:44:41,972 THIS POSES MANY CHALLENGES AND 2196 01:44:41,972 --> 01:44:46,410 WE CAME UP WITH THIS METHOD TO 2197 01:44:46,410 --> 01:44:52,650 CHARACTERIZE FOR REPLICATION IN 2198 01:44:52,650 --> 01:44:53,817 MEIOSIS AND LOOK AT DOUBLE 2199 01:44:53,817 --> 01:44:59,590 STRAND DNA TO THE ORIGIN 2200 01:44:59,590 --> 01:45:03,027 DETECTION AND ISOLATED 2201 01:45:03,027 --> 01:45:12,202 REPLICATING THE NUCLEI AND HAVE 2202 01:45:12,202 --> 01:45:15,005 A MODEL TO UNDERSTAND WHAT'S 2203 01:45:15,005 --> 01:45:18,175 GOING ON IN MEIOSIS. 2204 01:45:18,175 --> 01:45:19,376 WE LEARNED MOUSE REPLICATION IS 2205 01:45:19,376 --> 01:45:24,515 SLOWER THAN THAT OF THE CELLS IN 2206 01:45:24,515 --> 01:45:29,553 THE TESTES AND ANY OTHER CELL 2207 01:45:29,553 --> 01:45:30,287 TYPE WE LOOKED. 2208 01:45:30,287 --> 01:45:32,956 THIS WAS NOT SURPRISING. 2209 01:45:32,956 --> 01:45:33,957 . 2210 01:45:33,957 --> 01:45:35,893 EVERYWHERE PEOPLE LOOKED THE 2211 01:45:35,893 --> 01:45:40,698 REPLICATION WAS SLOWER AND TAKES 2212 01:45:40,698 --> 01:45:46,370 TWICE THE TIME AND WHAT WE 2213 01:45:46,370 --> 01:45:49,773 LEARNED FROM OUR MODEL IS THE 2214 01:45:49,773 --> 01:45:51,008 SLOWER REPLICATION IS DUE TO 2215 01:45:51,008 --> 01:45:52,643 LOWER RATES. 2216 01:45:52,643 --> 01:45:57,247 THERE'S FEWER WHEN CELLS DO 2217 01:45:57,247 --> 01:45:58,649 MYOTIC REPLICATION AND TRYING TO 2218 01:45:58,649 --> 01:46:01,552 UNDERSTAND WHY AND WHAT'S THE 2219 01:46:01,552 --> 01:46:04,655 CONSEQUENCES OF HAVING SLIGHTLY 2220 01:46:04,655 --> 01:46:10,327 FASTER REPLICATION IN MEIOSIS. 2221 01:46:10,327 --> 01:46:12,262 WE LOOKED AT METRIC OF 2222 01:46:12,262 --> 01:46:14,998 RECOMBINATION WE HAD IN THE LAB 2223 01:46:14,998 --> 01:46:19,303 AND CAN FIND THE HOT SPOTS ARE 2224 01:46:19,303 --> 01:46:23,574 HIGHLY ENRICHED IN THE GENOME 2225 01:46:23,574 --> 01:46:26,143 THEREFORE CORRELATING THIS TO 2226 01:46:26,143 --> 01:46:26,910 THE PROCESS. 2227 01:46:26,910 --> 01:46:31,382 BUT WHEN WE LOOKED AT THE HUMAN 2228 01:46:31,382 --> 01:46:34,685 TIMING WE SEE THERE'S A VERY 2229 01:46:34,685 --> 01:46:37,454 DISTINCT PATTERN AND IT'S GERM 2230 01:46:37,454 --> 01:46:39,356 LINE SPECIFIC SEEING REPLICATION 2231 01:46:39,356 --> 01:46:43,026 AT THE ENDS OF THE CHROMOSOMES 2232 01:46:43,026 --> 01:46:43,227 EARLY. 2233 01:46:43,227 --> 01:46:44,862 THIS HIGHLY DIFFERENT PATTERN 2234 01:46:44,862 --> 01:46:47,998 MIRRORS THE DISTRIBUTION OF THE 2235 01:46:47,998 --> 01:46:52,403 BROAD SCALE OF DOUBLE-STRAND 2236 01:46:52,403 --> 01:46:54,638 BREAKS SUGGESTING THE EARLY 2237 01:46:54,638 --> 01:46:56,106 REPLICATION UNDERLYING THE 2238 01:46:56,106 --> 01:47:01,145 PATTERNS WE SEE IN BREAKS. 2239 01:47:01,145 --> 01:47:03,013 SO SINCE THEN WE HAVE APPLIED 2240 01:47:03,013 --> 01:47:07,017 THE METHOD TO STUDY REPLICATION 2241 01:47:07,017 --> 01:47:09,853 TO HUMAN TESTES. 2242 01:47:09,853 --> 01:47:16,093 WE HAD DETECTED ORIGINS AND HAVE 2243 01:47:16,093 --> 01:47:20,164 A NICE REPLICATION. 2244 01:47:20,164 --> 01:47:22,699 SO I TOLD YOU THE RELATION 2245 01:47:22,699 --> 01:47:25,269 BETWEEN BREAKS AND EARLY 2246 01:47:25,269 --> 01:47:28,672 REPLICATION AND NOW WITH THE 2247 01:47:28,672 --> 01:47:30,073 VERY FINE RESOLUTION WE CAN 2248 01:47:30,073 --> 01:47:32,176 START ASKING DIFFERENT 2249 01:47:32,176 --> 01:47:34,211 QUESTIONS. 2250 01:47:34,211 --> 01:47:37,448 AND WHEN WE LOOK AT DIFFERENT 2251 01:47:37,448 --> 01:47:40,384 REGIONS OF THE GENOME OR 2252 01:47:40,384 --> 01:47:41,652 INTERSTITIAL PARTS SEPARATELY WE 2253 01:47:41,652 --> 01:47:46,657 SEE A DIFFERENT STORY. 2254 01:47:46,657 --> 01:47:52,663 IN THE INTERSTITIAL PART THERE'S 2255 01:47:52,663 --> 01:47:58,602 MORE BREAKS AND THIS SUGGESTS 2256 01:47:58,602 --> 01:48:02,940 THE CHROMOSOMAL CONTEXT MODIFIES 2257 01:48:02,940 --> 01:48:05,342 THE PATHWAY USED TO RESOLVE THE 2258 01:48:05,342 --> 01:48:07,010 DOUBLE STRAND BREAKS. 2259 01:48:07,010 --> 01:48:09,046 AND THIS IS VERY IMPORTANT 2260 01:48:09,046 --> 01:48:10,981 BECAUSE WHEN WE HAVE HUNDREDS OF 2261 01:48:10,981 --> 01:48:16,653 BREAKS AND ONLY 10% RESULT AS A 2262 01:48:16,653 --> 01:48:19,022 CROSSOVER AND HOW THEY'RE 2263 01:48:19,022 --> 01:48:23,060 DETERMINED IS A FUNDAMENTAL 2264 01:48:23,060 --> 01:48:26,330 QUESTION ON MEIOSIS AND WE HAVE 2265 01:48:26,330 --> 01:48:28,198 TO START UNDERSTANDING THE 2266 01:48:28,198 --> 01:48:29,833 THINGS AND TO FINISH AND I 2267 01:48:29,833 --> 01:48:34,671 DIDN'T TELL YOU THIS IN HUMANS 2268 01:48:34,671 --> 01:48:40,677 REMEMBER I TOLD YOU THERE'S A 2269 01:48:40,677 --> 01:48:51,221 FEMALE MEIOSIS IS DIMORPHIC AND 2270 01:48:56,393 --> 01:48:57,928 ONE OF RISK FOR CHROMOSOME 21 2271 01:48:57,928 --> 01:49:02,299 AND DOWN SYNDROME IS HAVING THE 2272 01:49:02,299 --> 01:49:03,267 CROSSOVER TO THIS IN THE 2273 01:49:03,267 --> 01:49:03,567 CHROMOSOME. 2274 01:49:03,567 --> 01:49:05,536 THE SYSTEM IS ALLOWING US TO TRY 2275 01:49:05,536 --> 01:49:09,907 TO UNDERSTAND HOW THE PROCESSES 2276 01:49:09,907 --> 01:49:13,043 ARE CONTROLLED AND WILL HAVE 2277 01:49:13,043 --> 01:49:14,111 MORE ANSWERS IN A LITTLE WHILE. 2278 01:49:14,111 --> 01:49:20,317 SO JUST TO FINISH, I'D LIKE TO 2279 01:49:20,317 --> 01:49:24,988 THANK THE CURRENT MEMBERS OF MY 2280 01:49:24,988 --> 01:49:28,659 LAB AND MY LAB AT NIDDK AND ALL 2281 01:49:28,659 --> 01:49:30,394 THE COLLABORATORS PAST AND 2282 01:49:30,394 --> 01:49:31,528 PARENT AND THE DISTINGUISHED 2283 01:49:31,528 --> 01:49:31,895 SCHOLAR PROGRAM. 2284 01:49:31,895 --> 01:49:38,402 THANK YOU. 2285 01:49:38,402 --> 01:49:39,002 >> THANK YOU VERY MUCH. 2286 01:49:39,002 --> 01:49:44,908 THAT'S A FASCINATING TALK. 2287 01:49:44,908 --> 01:49:50,314 >> 2288 01:49:50,314 --> 01:49:51,982 >> THIS IS ROSE AGAIN. 2289 01:49:51,982 --> 01:49:53,383 I THOUGHT IT WAS ALSO A 2290 01:49:53,383 --> 01:49:54,117 FASCINATING TALK. 2291 01:49:54,117 --> 01:49:57,621 I HAVE A QUESTION ABOUT THE PRD 2292 01:49:57,621 --> 01:50:00,991 AND 9 REGIONS. 2293 01:50:00,991 --> 01:50:04,661 IN CHILDHOOD CANCER THERE ARE 2294 01:50:04,661 --> 01:50:07,030 RECURRENT FUSIONS AND THAT 2295 01:50:07,030 --> 01:50:10,233 PRECISELY RECUR IN DIFFERENT 2296 01:50:10,233 --> 01:50:10,500 PATIENTS. 2297 01:50:10,500 --> 01:50:13,770 SO AT THE REGIONS THAT LEAD TO 2298 01:50:13,770 --> 01:50:18,108 DOUBLE STRAND BREAKAGE DO THEY 2299 01:50:18,108 --> 01:50:19,843 CONTRIBUTE TO THAT PATHOGENESIS. 2300 01:50:19,843 --> 01:50:25,248 >> PEOPLE HAVE BEEN LOOKING INTO 2301 01:50:25,248 --> 01:50:30,120 THAT BECAUSE THERE'S A FIELD OF 2302 01:50:30,120 --> 01:50:37,194 ANTIGEN THAT IS MEIOTIC GENES IN 2303 01:50:37,194 --> 01:50:39,663 CANCER AND ONE STUDY LOOKED AT 2304 01:50:39,663 --> 01:50:45,636 CHILDREN WITH LEUKEMIA AND HAVE 2305 01:50:45,636 --> 01:50:56,179 EXCESS OF SOME OF THESE AND HAVE 2306 01:50:56,480 --> 01:50:58,715 THE TARGET BUT IT COULD 2307 01:50:58,715 --> 01:51:03,020 DEFINITELY MAKE AN IMPACT. 2308 01:51:03,020 --> 01:51:12,796 IT DOES NOT SO WE HAVE DIFFERENT 2309 01:51:12,796 --> 01:51:16,700 REPLICATION SIZE AND FUSIONS WE 2310 01:51:16,700 --> 01:51:20,537 DON'T SEE EXACT SAME POSITION 2311 01:51:20,537 --> 01:51:21,972 BUT IN CANCERS THEY'RE OVER 2312 01:51:21,972 --> 01:51:25,075 EXPRESSED AND UNREGULATED. 2313 01:51:25,075 --> 01:51:28,679 >> I LOVE THAT YOUR TALK STARTED 2314 01:51:28,679 --> 01:51:30,714 WITH PHYSIOLOGICAL PRINCIPLES 2315 01:51:30,714 --> 01:51:34,451 AND THEN MOVED TO DISEASE 2316 01:51:34,451 --> 01:51:34,685 STATES. 2317 01:51:34,685 --> 01:51:36,787 DURING MEIOSIS IS THE 2318 01:51:36,787 --> 01:51:37,788 SEGREGATION OF CHROMOSOMES 2319 01:51:37,788 --> 01:51:45,062 RANDOM ERR OR DO YOU HAVE HOT SS 2320 01:51:45,062 --> 01:51:46,263 THAT SEGREGATE TOGETHER? 2321 01:51:46,263 --> 01:51:50,500 >> THE MAJOR ASSORTMENT IS DUE 2322 01:51:50,500 --> 01:51:54,805 TO THE INDEPENDENT ASSORTMENT OF 2323 01:51:54,805 --> 01:51:56,139 CHROMOSOMES AND THEN WITH 2324 01:51:56,139 --> 01:51:58,408 CROSSOVERS YOU DO THE 2325 01:51:58,408 --> 01:51:58,709 INTERACTION. 2326 01:51:58,709 --> 01:52:02,546 IT'S NOT ONLY FEMALES THAT ARE 2327 01:52:02,546 --> 01:52:09,653 RECOMBINANT CHROMOSOME TENDS TO 2328 01:52:09,653 --> 01:52:13,190 STAY SO THERE'S SOMETHING THAT 2329 01:52:13,190 --> 01:52:16,693 SENSES RECOMBINANT IS BETTER AND 2330 01:52:16,693 --> 01:52:21,998 ONE HAS A RECOMBINATION EVENT 2331 01:52:21,998 --> 01:52:25,635 AND IF THERE'S SMALLER BIASSED 2332 01:52:25,635 --> 01:52:26,169 IN FEMALES. 2333 01:52:26,169 --> 01:52:28,138 >> IS THERE A THOUGHT ON WHAT 2334 01:52:28,138 --> 01:52:29,406 THE MECHANISM MIGHT BE? 2335 01:52:29,406 --> 01:52:31,608 >> NO, IT MUST BE A PROTEASE 2336 01:52:31,608 --> 01:52:36,113 THAT MARKS THE CROSSOVERS. 2337 01:52:36,113 --> 01:52:37,681 >> LOUIS. 2338 01:52:37,681 --> 01:52:38,749 >> GREAT TALK. 2339 01:52:38,749 --> 01:52:43,019 WHY DO YOU THINK SUCH AN 2340 01:52:43,019 --> 01:52:45,822 ERROR-PRONE MECHANISM WOULD HAVE 2341 01:52:45,822 --> 01:52:48,558 SURVIVED EVOLUTION? 2342 01:52:48,558 --> 01:52:51,795 THE CLASSIC GENETIC TEXTBOOKS 2343 01:52:51,795 --> 01:52:54,631 SAY YOU KEEP ACCUMULATING 2344 01:52:54,631 --> 01:52:56,733 VARIANTS AND YOU NEED SOMETHING 2345 01:52:56,733 --> 01:53:00,337 TO CLUSTER THE GOOD OR BAD ONCE 2346 01:53:00,337 --> 01:53:00,604 TOGETHER. 2347 01:53:00,604 --> 01:53:03,907 I'M NOT SURE THE EXPLANATION IS 2348 01:53:03,907 --> 01:53:08,378 SATISFACTORY BUT WHAT DO YOU 2349 01:53:08,378 --> 01:53:09,012 THINK? 2350 01:53:09,012 --> 01:53:13,116 >> THE FEMALE HORSES ARE JUST 2351 01:53:13,116 --> 01:53:13,583 LIKE HUMANS. 2352 01:53:13,583 --> 01:53:15,118 MANY ORGANISMS HAVE THE ERROR 2353 01:53:15,118 --> 01:53:19,456 RATE HIGH BUT NOT ALL. 2354 01:53:19,456 --> 01:53:22,726 WHAT PEOPLE HAVE PROPOSED IS YOU 2355 01:53:22,726 --> 01:53:25,162 DON'T WANT TO HAVE TOO MANY ONE 2356 01:53:25,162 --> 01:53:29,166 AFTER THE OTHER. 2357 01:53:29,166 --> 01:53:30,767 THAT'S ONE OF THE IDEA WHY IT'S 2358 01:53:30,767 --> 01:53:31,868 BEEN KEPT. 2359 01:53:31,868 --> 01:53:34,371 MAYBE WE'RE AT THE EVOLUTIONARY 2360 01:53:34,371 --> 01:53:37,374 TIME WHERE THIS IS A GLITCH THAT 2361 01:53:37,374 --> 01:53:39,009 IS GOING TO BE FIXED. 2362 01:53:39,009 --> 01:53:49,386 THAT'S NOT AN ANSWER. 2363 01:53:50,554 --> 01:53:55,592 THERE'S HUGE ATTRITION. 2364 01:53:55,592 --> 01:54:01,765 SO ABOUT 10% SURVIVE TO BIRTH. 2365 01:54:01,765 --> 01:54:03,033 SO THERE'S A LOT OF IN THERE. 2366 01:54:03,033 --> 01:54:04,501 >> THANK YOU. 2367 01:54:04,501 --> 01:54:05,802 >> WONDERFUL. 2368 01:54:05,802 --> 01:54:07,537 THANK YOU VERY MUCH. 2369 01:54:07,537 --> 01:54:09,573 THIS IS TO ERROR IS HUMAN. 2370 01:54:09,573 --> 01:54:11,775 >> CAN I USE IT? 2371 01:54:11,775 --> 01:54:13,176 >> WELL, THANK YOU. 2372 01:54:13,176 --> 01:54:14,344 WE'LL CLOSE THE MORNING SESSION 2373 01:54:14,344 --> 01:54:16,713 HERE AND BREAK FOR LUNCH. 2374 01:54:16,713 --> 01:54:17,781 I'LL REMIND YOU THERE ARE 2375 01:54:17,781 --> 01:54:20,450 POSTERS STILL ON THE TERRACE 2376 01:54:20,450 --> 01:54:22,219 UNTIL 12:30 SO IF YOU HAVE A FEW 2377 01:54:22,219 --> 01:54:24,187 MOMENTS GANDER OVER THERE AND 2378 01:54:24,187 --> 01:54:26,456 TAKE A LOOK AND PROVIDE SUPPORT 2379 01:54:26,456 --> 01:54:28,992 TO OUR TRAINEES PRESENTING 2380 01:54:28,992 --> 01:54:31,228 RESEARCH OTHER WISE TAKE A LUNCH 2381 01:54:31,228 --> 01:54:33,263 BREAK AND STRETCH YOUR LEGS AND 2382 01:54:33,263 --> 01:54:35,198 NO DBTs EVERYONE AND WE'LL SEE 2383 01:54:35,198 --> 01:54:35,465 YOU BACK. 2384 01:54:35,465 --> 01:54:45,465 THANK YOU.