1 00:00:11,440 --> 00:00:13,640 Welcome to the Clinical Center Grand Rounds, 2 00:00:13,640 --> 00:00:17,440 a weekly series of educational lectures for physicians and 3 00:00:17,440 --> 00:00:20,080 health care professionals broadcast from the Clinical 4 00:00:20,080 --> 00:00:23,040 Center at the National Institutes of Health in 5 00:00:23,040 --> 00:00:24,840 Bethesda, MD. 6 00:00:24,840 --> 00:00:28,400 The NIH Clinical Center is the world's largest hospital totally 7 00:00:28,400 --> 00:00:32,080 dedicated to investigational research and leads the global 8 00:00:32,080 --> 00:00:35,040 effort in training today's investigators and discovering 9 00:00:35,040 --> 00:00:37,200 tomorrow's cures. 10 00:00:37,200 --> 00:00:46,080 Learn more by visiting us online at http://clinicalcenter.nih.gov 11 00:00:46,080 --> 00:00:48,240 >>OUR SPEAKERS TODAY ARE 12 00:00:48,240 --> 00:00:51,680 LASKER CLINICAL RESEARCH 13 00:00:51,680 --> 00:00:55,000 SCHOLARS DOCTORS COURTNEY 14 00:00:55,000 --> 00:00:56,840 FITZHUGH AND DR. ANISHTHOMAS. 15 00:00:56,840 --> 00:01:00,520 I WILL START WITH DR. FITZHUGH, 16 00:01:00,520 --> 00:01:02,160 SHE IS A INVESTIGATOR IN THE 17 00:01:02,160 --> 00:01:03,880 SICKLE CELL ON MORTALITY 18 00:01:03,880 --> 00:01:07,480 PREVENTION AS A NHLBI. 19 00:01:07,480 --> 00:01:10,160 SHE RECEIVED HER BS MAGNA CUM 20 00:01:10,160 --> 00:01:12,920 LAUDE, FROM THE UNIVERSITY OF 21 00:01:12,920 --> 00:01:14,400 CALIFORNIA LOS ANGELES AND THEN 22 00:01:14,400 --> 00:01:16,720 EARNED HER M. D. FROM THE 23 00:01:16,720 --> 00:01:17,760 UNIVERSITY OF CALIFORNIA 24 00:01:17,760 --> 00:01:20,040 SAN FRANCISCO. 25 00:01:20,040 --> 00:01:22,040 DURING MEDICAL SCHOOL, 26 00:01:22,040 --> 00:01:23,360 DR. FITZHUGH PARTICIPATE INDEED 27 00:01:23,360 --> 00:01:25,120 THE NIH CLINICAL TRAINING 28 00:01:25,120 --> 00:01:28,920 PROGRAM, WHERE SHE STUDIED 29 00:01:28,920 --> 00:01:31,360 SICKLE CELL DISEASE UNDER 30 00:01:31,360 --> 00:01:33,120 DR. JOHN TISDALE, AND AFTER THAT 31 00:01:33,120 --> 00:01:34,640 SHE ENJOYED A PEDIATRIC 32 00:01:34,640 --> 00:01:36,760 RESIDENCY AT DUKE AND THEN 33 00:01:36,760 --> 00:01:39,080 STARTED A COMBINED ADULT 34 00:01:39,080 --> 00:01:40,680 HEMEATOLOGY AND PEDIATRIC 35 00:01:40,680 --> 00:01:41,840 HEMEATOLOGY ONCOLOGY FELLOWSHIP 36 00:01:41,840 --> 00:01:44,800 AT THE NIH AND JOHNS HOPKINS. 37 00:01:44,800 --> 00:01:47,480 SHE RETURNED TO NHLBI WHERE SHE 38 00:01:47,480 --> 00:01:50,360 WAS APPOINTED AS AN ASSISTANT 39 00:01:50,360 --> 00:01:51,160 CLINICAL INVESTIGATOR IN 2012 40 00:01:51,160 --> 00:01:52,800 AND BECAME A LASKER CLINICAL 41 00:01:52,800 --> 00:01:56,800 RESEARCH SCHOLAR AND A TENURED 42 00:01:56,800 --> 00:02:00,240 TRACK INVESTIGATOR IN 2016. 43 00:02:00,240 --> 00:02:02,920 DR. FITZHUGH IS BOARD CERTIFIED 44 00:02:02,920 --> 00:02:03,760 IN PEDIATRIC HEMEATOLOGY, 45 00:02:03,760 --> 00:02:05,440 ONCOLOGY, ERNE TURNOVERRAL 46 00:02:05,440 --> 00:02:06,280 MEDICINE AND PEDIATRICS. 47 00:02:06,280 --> 00:02:09,480 IN 2022 SHE WAS AWARDED THE NIH 48 00:02:09,480 --> 00:02:10,920 DIRECTOR'S AWARD FOR HER EFFORTS 49 00:02:10,920 --> 00:02:12,360 ON THE IGNITE INITIATIVE. 50 00:02:12,360 --> 00:02:15,720 SHE IS A VIEW EDITOR FOR BLAD 51 00:02:15,720 --> 00:02:16,920 ADVANCES AND PREVIOUSLY REVIEW 52 00:02:16,920 --> 00:02:22,920 FOR FRONTIERS IN GENOME EDITING. 53 00:02:22,920 --> 00:02:24,600 SHE'S A MEMBER OF THE AMERICAN 54 00:02:24,600 --> 00:02:26,000 SOCIETY OF HEMEATOLOGY AND 55 00:02:26,000 --> 00:02:29,360 AMERICAN SOCIETY OF 56 00:02:29,360 --> 00:02:30,240 TRANSPLANTATION CELLULAR 57 00:02:30,240 --> 00:02:30,480 THERAPY. 58 00:02:30,480 --> 00:02:34,320 I WILL ALSO INTRODUCE OUR NEXT 59 00:02:34,320 --> 00:02:36,840 SPEAKER THIS IS ALSO DR. ANISH 60 00:02:36,840 --> 00:02:38,840 THOMAS IN THE DEVELOPMENT 61 00:02:38,840 --> 00:02:40,800 THERAPEUTIC BRANCH OF THE 62 00:02:40,800 --> 00:02:41,320 NATIONAL CANCER INSTITUTE. 63 00:02:41,320 --> 00:02:42,680 DR. THOMAS IS A MEDICAL 64 00:02:42,680 --> 00:02:43,400 ONCOLOGIST WHO SPECIALIZES IN 65 00:02:43,400 --> 00:02:46,240 THE TREATMENT OF THORACIC 66 00:02:46,240 --> 00:02:46,600 CANCERS. 67 00:02:46,600 --> 00:02:48,920 HE EARNED HIS MEDICAL DEGREE AND 68 00:02:48,920 --> 00:02:50,360 COMPLETED POST GRADUATE TRAINING 69 00:02:50,360 --> 00:02:53,560 IN INTERNAL MEDICINE FROM 70 00:02:53,560 --> 00:02:54,960 ST. JOHN'S MEDICAL COLLEGE IN 71 00:02:54,960 --> 00:02:58,120 INDICATORSIA AND FOLLOWED BY A 72 00:02:58,120 --> 00:03:01,320 RESIDENCY IN NEW YORK UPSTATE 73 00:03:01,320 --> 00:03:02,760 MEDICAL UNIVERSITY IN SYRACUSE. 74 00:03:02,760 --> 00:03:05,880 HE THEN CAME TO NIH TO TRAIN IN 75 00:03:05,880 --> 00:03:07,920 MEDICAL ONCOLOGY AND HEMEATOLOGY 76 00:03:07,920 --> 00:03:09,840 ANDLET MEDICAL ONCOLOGY BRANCH 77 00:03:09,840 --> 00:03:12,600 OF THE NIH AND NCI RESPECTIVELY. 78 00:03:12,600 --> 00:03:17,040 IN 2023 HE WAS AWARDED TRECTOR'S 79 00:03:17,040 --> 00:03:18,240 AWARD FOR TRANSLATIONAL SCIENCE 80 00:03:18,240 --> 00:03:19,160 FOR TRANSLATIONAL STUDIES 81 00:03:19,160 --> 00:03:20,680 LEADING TO SUBGROUPS OF SMALL 82 00:03:20,680 --> 00:03:22,560 CELL LUNG CANCER PAVING THE WAY 83 00:03:22,560 --> 00:03:24,080 FOR PRECISION MEDICINE 84 00:03:24,080 --> 00:03:25,040 APPROACHES. 85 00:03:25,040 --> 00:03:27,120 HE IS BOARD CERTIFIED IN 86 00:03:27,120 --> 00:03:28,360 ONCOLOGY AND HEMEATOLOGY AND 87 00:03:28,360 --> 00:03:29,720 ELECTED MEMBER OF AMERICAN 88 00:03:29,720 --> 00:03:31,960 SOCIETY FOR CLINICAL 89 00:03:31,960 --> 00:03:32,320 INVESTIGATION. 90 00:03:32,320 --> 00:03:33,800 THE TITLE OF TODAY'S 91 00:03:33,800 --> 00:03:37,120 PRESENTATION IS: HOW TO BECOME 92 00:03:37,120 --> 00:03:40,800 A SUCCESSFUL CLINICIAN 93 00:03:40,800 --> 00:03:41,360 SCIENTIST, NIHLASKER SCHOLAR 94 00:03:41,360 --> 00:03:41,560 PANEL. 95 00:03:41,560 --> 00:03:43,800 PLEASE JOIN ME IN WELCOMING 96 00:03:43,800 --> 00:03:46,600 TODAY'S GRADUATE SPEAKERS 97 00:03:46,600 --> 00:03:51,080 DR. COURTNEY FITZHUGH AND 98 00:03:51,080 --> 00:03:52,280 DR. ANISH THOMAS. 99 00:03:52,280 --> 00:03:52,560 [ APPLAUSE ] 100 00:03:52,560 --> 00:03:54,680 >>SO TO GIVE YOU A SENSE OF THE 101 00:03:54,680 --> 00:03:56,080 AGENDA, BOTH INVESTIGATORS WILL 102 00:03:56,080 --> 00:03:58,280 GIVE A BRIEF RESEARCH 103 00:03:58,280 --> 00:03:59,480 PRESENTATION AND I DIDN'T GO 104 00:03:59,480 --> 00:04:00,640 INTO THE DEAILS OF THEIR 105 00:04:00,640 --> 00:04:02,000 RESEARCH AND THEN WE WILL 106 00:04:02,000 --> 00:04:03,760 TRANSITION OVER AND DO A PANEL 107 00:04:03,760 --> 00:04:04,080 DISCUSSION. 108 00:04:04,080 --> 00:04:05,080 I HOPE HAVE YOU QUESTIONS IF ARE 109 00:04:05,080 --> 00:04:08,080 THEM LATER. 110 00:04:08,080 --> 00:04:08,800 THANK YOU. 111 00:04:08,800 --> 00:04:11,000 >>GOOD AFTERNOON, AND THANK YOU 112 00:04:11,000 --> 00:04:13,640 FOR INVITING ME TO BE 113 00:04:13,640 --> 00:04:14,840 PART THIS PANEL, SO MY TALK IS 114 00:04:14,840 --> 00:04:16,920 ENTITLED LEUKEMIA THERAPY FOR 115 00:04:16,920 --> 00:04:17,360 SICKLE CELL DISEASE. 116 00:04:17,360 --> 00:04:20,000 I DO NOT HAVE ANY FINANCIAL 117 00:04:20,000 --> 00:04:21,200 DISCLOSURES TO REPORT AND MY 118 00:04:21,200 --> 00:04:24,960 OBJECTIVE IS TO DESCRIBE THE 119 00:04:24,960 --> 00:04:26,200 INCREASED RISK OF LEUKEMIA 120 00:04:26,200 --> 00:04:27,640 FOLLOWING CARE FOR CERTAIN 121 00:04:27,640 --> 00:04:28,080 SICKLE CELL DISEASE. 122 00:04:28,080 --> 00:04:29,800 SICKLE SEIZE DISEASE IS POINT 123 00:04:29,800 --> 00:04:30,960 MUTATION FROM RED BLOOD CELLS 124 00:04:30,960 --> 00:04:33,480 FROM A EASILY DRIVABLE CONCAVE 125 00:04:33,480 --> 00:04:36,400 DISK TO A RIGID SICKLE SHAPE 126 00:04:36,400 --> 00:04:37,800 CELL WHICH INCLUDES 127 00:04:37,800 --> 00:04:38,720 MICROVASCULATURE, SICKLE CELL 128 00:04:38,720 --> 00:04:40,960 DISEASE IS ASSOCIATE 129 00:04:40,960 --> 00:04:42,040 WIDEOXIDATIVE STRESS, 130 00:04:42,040 --> 00:04:43,360 INFLAMMATION, SHORT AND RED CELL 131 00:04:43,360 --> 00:04:45,760 SURVIVAL WHICH LEADS TO THE 132 00:04:45,760 --> 00:04:47,280 STRESS, HYPOXIA AND DAMAGE TO 133 00:04:47,280 --> 00:04:52,280 THE BONE MARROW 134 00:04:52,280 --> 00:04:52,960 MICROENVIRONMENT. 135 00:04:52,960 --> 00:04:55,000 THE MAIN COMPLICATION THAT 136 00:04:55,000 --> 00:04:57,040 PATIENTS WITH SICKLE CELL 137 00:04:57,040 --> 00:04:58,480 DISEASE EXPERIENCE IS 138 00:04:58,480 --> 00:04:59,960 DEBILITATING PAIN AND CAN IMPACT 139 00:04:59,960 --> 00:05:01,720 ANY ORGAN OF THE BODY LEADING TO 140 00:05:01,720 --> 00:05:03,360 DAMAGE AND IT'S KNOWN THAT ADULT 141 00:05:03,360 --> 00:05:04,680 WHO HAVE DAMAGE TO THE LIVER, 142 00:05:04,680 --> 00:05:10,560 HEART, LUNG AND KIDNEYS, DIE 143 00:05:10,560 --> 00:05:12,280 PREMATURELY. 144 00:05:12,280 --> 00:05:15,000 SO ON THE Y-AXIS THE CUMULATIVE 145 00:05:15,000 --> 00:05:17,200 SURVIVAL AND ON THE X-ACIS THE 146 00:05:17,200 --> 00:05:20,320 AGE OR DEATH AND 60% OF THE 147 00:05:20,320 --> 00:05:22,120 PATIENTS ARE ON HYDROXY URIA 148 00:05:22,120 --> 00:05:23,440 WHICH IS STILL THE BEST MEDICINE 149 00:05:23,440 --> 00:05:24,960 FOR PATIENTS WITH SICKLE CELL 150 00:05:24,960 --> 00:05:26,680 DISEASE. 151 00:05:26,680 --> 00:05:29,640 YOU SEE THAT 2225 PATIENTS HAD 152 00:05:29,640 --> 00:05:30,280 MOSTLY HOMOZYGOUS SICKLE SEAL 153 00:05:30,280 --> 00:05:32,800 DISEASE AND THIS IS THE MOST 154 00:05:32,800 --> 00:05:34,240 SEVERE TIME AND THE FOLLOW UP IS 155 00:05:34,240 --> 00:05:37,240 6 AND HALF YEARS AND THE MEAN 156 00:05:37,240 --> 00:05:38,160 SURVIVAL IS ONLY 48 YEARS WHICH 157 00:05:38,160 --> 00:05:40,680 HAS NOT CHANGE INDEED THE LAST 158 00:05:40,680 --> 00:05:42,320 2-3 DECADES AND STILL 20 YEARS 159 00:05:42,320 --> 00:05:44,240 EARLIER THAN THE GENERAL AFRICAN 160 00:05:44,240 --> 00:05:45,040 AMERICAN POPULATION. 161 00:05:45,040 --> 00:05:46,440 THERE HAVE BEEN 2 LARGE 162 00:05:46,440 --> 00:05:47,840 POPULATION STUDIES TO SHOW THAT 163 00:05:47,840 --> 00:05:49,240 PATIENTS WITH SICKLE CELL 164 00:05:49,240 --> 00:05:50,880 DISEASE HAVE INCREASED RISK FOR 165 00:05:50,880 --> 00:05:52,320 LEUKEMIA, I WILL GO THROUGH 1 166 00:05:52,320 --> 00:05:53,960 FORT ARTICLES PUBLISHED BY UC 167 00:05:53,960 --> 00:05:55,720 DAVIS WHERE THEY IDENTIFY OVER 168 00:05:55,720 --> 00:05:57,960 6400 PATIENTS WITH SICKLE CELL 169 00:05:57,960 --> 00:06:00,320 DISEASE, WHO ARE IDENTIFIED 170 00:06:00,320 --> 00:06:03,280 BETWEEN 19 NONE AND 2014, THEY 171 00:06:03,280 --> 00:06:04,360 ARE FOLLOWED AND COMPARED TOO 172 00:06:04,360 --> 00:06:05,200 THE GENERAL POPULATION AND THEY 173 00:06:05,200 --> 00:06:06,520 FOUND THAT PATIENTS WITH SICKLE 174 00:06:06,520 --> 00:06:08,840 CELL DISEASE HAD A 2.3 FOLD 175 00:06:08,840 --> 00:06:11,080 INCREASED RISK FOR LEUKEMIA AND 176 00:06:11,080 --> 00:06:15,480 A 3.6 INCREASED RISK FOR MYELOID 177 00:06:15,480 --> 00:06:16,600 LEUKEMIA OR AML. 178 00:06:16,600 --> 00:06:18,560 WHEN YOU LOOK MORE CLOSELY AT 179 00:06:18,560 --> 00:06:21,360 THE DATA YOU WILL SEE THAT THEY 180 00:06:21,360 --> 00:06:23,200 WILL FOLLOWED OVER 27 YEARS BUT 181 00:06:23,200 --> 00:06:26,360 ONLY 31 PATIENTS DEVELOPED A 182 00:06:26,360 --> 00:06:29,680 HEMEAT O LOGIC MALIGNANCY OR 183 00:06:29,680 --> 00:06:31,680 0.21 PER 100 YEARS OF FOLLOW UP. 184 00:06:31,680 --> 00:06:32,840 EIGHTEEN INDIVIDUALS WITHOUT 185 00:06:32,840 --> 00:06:34,680 SICKLE CELL DISEASE WERE 186 00:06:34,680 --> 00:06:37,000 EXPECTED TO DEVELOP HEMEAT O 187 00:06:37,000 --> 00:06:38,400 LOGIC MALIGNANCIES DURING THAT 188 00:06:38,400 --> 00:06:40,960 TRIEM FRAME WHEN CONTROLLING FOR 189 00:06:40,960 --> 00:06:43,160 AGE, RACE, SEX, ETHNICITY AND SO 190 00:06:43,160 --> 00:06:44,680 YOU SEE WHILE THERE'S INCREASE 191 00:06:44,680 --> 00:06:46,760 RELATIVE RISK FOR PATIENTS WITH 192 00:06:46,760 --> 00:06:48,280 SICKLE CELL DISEASE DEVELOPING 193 00:06:48,280 --> 00:06:55,160 LEUKEMIA, THE ABSOLUTE RISK IS 194 00:06:55,160 --> 00:06:56,080 LOW. 195 00:06:56,080 --> 00:06:58,720 SO THIS OFFERS CARE WITH WHEN I 196 00:06:58,720 --> 00:07:01,600 SAY MILE ON ABLATIVE THAT MEANS 197 00:07:01,600 --> 00:07:03,840 HIGH DOSE CHEMO THERAPY AND WIPE 198 00:07:03,840 --> 00:07:05,880 OUT THE BONE MARROW AND REPLACE 199 00:07:05,880 --> 00:07:07,760 IT WITH THE BLOOD OF THE DONOR. 200 00:07:07,760 --> 00:07:10,840 SO THIS WAS A STUDY WHERE 1000 201 00:07:10,840 --> 00:07:13,840 PATIENTS WITH SICKLE CELL 202 00:07:13,840 --> 00:07:14,920 DISEASE UNDERWENT THE TRANSPLANT 203 00:07:14,920 --> 00:07:17,800 O PLANT AND YOU SEE THE 5 YEAR 204 00:07:17,800 --> 00:07:21,680 OVERALL SURVIVAL IS 93%, MEANING 205 00:07:21,680 --> 00:07:24,960 93% OF THE PATIENTS WERE ALIVE, 206 00:07:24,960 --> 00:07:27,200 AFTER 5 YEARS AND THEN 91% WERE 207 00:07:27,200 --> 00:07:28,720 ALIVE AND FREE OF SICKLE CELL 208 00:07:28,720 --> 00:07:29,000 DISEASE. 209 00:07:29,000 --> 00:07:30,040 SO YOU HEARD IN THE INTRODUCTION 210 00:07:30,040 --> 00:07:31,800 THAT I CAME TO THE NIH AS A 211 00:07:31,800 --> 00:07:34,560 MEDICAL STUDENT AND I WORKED 212 00:07:34,560 --> 00:07:36,560 WITH JOHN TISDALE WHO IS AN 213 00:07:36,560 --> 00:07:38,400 ADULT HEMEATOLOGYIST AND MOST 214 00:07:38,400 --> 00:07:39,840 ADULTS CANNOT TOLERATE HIGH DOSE 215 00:07:39,840 --> 00:07:42,080 CHEMO THERAPY SO WE WANTED TO 216 00:07:42,080 --> 00:07:43,840 APPLY THIS CURATIVE APPROACH TO 217 00:07:43,840 --> 00:07:46,800 ASULTS SO INSTEAD OF HIGH ON 218 00:07:46,800 --> 00:07:47,240 DOSE CHEMO THERAPY AND 219 00:07:47,240 --> 00:07:47,840 ACTIVITIES AND PROJECTS WE 220 00:07:47,840 --> 00:07:56,680 WANTED TO USE A NONMILE ABLATIVE 221 00:07:56,680 --> 00:08:03,080 THERAPY WHERE YOU USE A MIXTURE 222 00:08:03,080 --> 00:08:04,600 EVER DONOR AND RECIPIENT CELLS. 223 00:08:04,600 --> 00:08:06,720 SO IN ORDER TO CREATE THIS 224 00:08:06,720 --> 00:08:08,200 MIXTURE, IT'S LIKE YOU HAVE TO 225 00:08:08,200 --> 00:08:09,360 REEDUCATE THE IMMUNE SYSTEM SO 226 00:08:09,360 --> 00:08:11,240 THAT THE DONOR AND RECIPIENT 227 00:08:11,240 --> 00:08:12,520 CELLS NO LONGER RECOGNIZE EACH 228 00:08:12,520 --> 00:08:16,760 OTHER AS BEING FOREIGN. 229 00:08:16,760 --> 00:08:19,600 SO, THE INVITRO DATA SUGGEST 230 00:08:19,600 --> 00:08:21,840 THAD CYCLOSPORIN WOULD NOT 231 00:08:21,840 --> 00:08:24,360 INDUCE TOLERANCE WHERE RAPAMYCIN 232 00:08:24,360 --> 00:08:24,880 WOULD INDUCE TOLERANCE. 233 00:08:24,880 --> 00:08:27,240 SO THIS WAS A MOUSE MODEL WHERE 234 00:08:27,240 --> 00:08:29,080 I GAVE THEM EITHER--I WILL CALL 235 00:08:29,080 --> 00:08:31,320 IT RAP O MICEIN, BUT THIS IS ALL 236 00:08:31,320 --> 00:08:31,680 [INDISCERNIBLE]. 237 00:08:31,680 --> 00:08:33,480 BUT I GAVE THE RAP O MICEIN FOR 238 00:08:33,480 --> 00:08:38,200 30 DAYS AND YOU SEE THAT THE 239 00:08:38,200 --> 00:08:43,320 MICE RECEIVED CYCLOSPORIN 240 00:08:43,320 --> 00:08:44,240 INITIALLY ACHIEVED REGRESSION 241 00:08:44,240 --> 00:08:49,680 BUT REJECTED THE GRAPHS AND THEN 242 00:08:49,680 --> 00:08:51,440 THEY RECEIVED RAPAMYCIN, AND 243 00:08:51,440 --> 00:08:53,440 THEN THE INCREASE 8 MONTHS AFTER 244 00:08:53,440 --> 00:08:54,080 THE RAPAMYCIN WAS DISCONTINUED 245 00:08:54,080 --> 00:08:55,960 SO IT LOOKS LIKE WE WERE ABLE TO 246 00:08:55,960 --> 00:08:59,240 INDUCE THIS TOLERANCE STATE IN 247 00:08:59,240 --> 00:09:00,120 THE MICE. 248 00:09:00,120 --> 00:09:05,280 SO BASED ON THESE DATA, THEY 249 00:09:05,280 --> 00:09:06,080 WROTE THIS PROTOCOL TO--WHICH 250 00:09:06,080 --> 00:09:08,000 WAS VERY SIMILAR TO WHAT WE DID 251 00:09:08,000 --> 00:09:08,800 WITH THE MICE. 252 00:09:08,800 --> 00:09:12,720 SO THE MICE RECEIVE 3 CENTIGRADE 253 00:09:12,720 --> 00:09:19,480 OF RADIATION AND WE ADD 254 00:09:19,480 --> 00:09:21,920 ALETMUZUMAB, SO NOT ONLY ARE YOU 255 00:09:21,920 --> 00:09:23,800 DEPLETING THIS WITH THE 256 00:09:23,800 --> 00:09:26,200 RECIPIENTS BUT THE DONORS, SO WE 257 00:09:26,200 --> 00:09:27,640 GET 3 CENTIGRADE RADIATION TO 258 00:09:27,640 --> 00:09:29,800 MAKE SPACE IN THE BONE MARROW 259 00:09:29,800 --> 00:09:31,440 AND PROVIDE ARK DITIONAL 260 00:09:31,440 --> 00:09:33,400 SUPPRESSION AND THEN WHEN THE 261 00:09:33,400 --> 00:09:35,280 LIESMEE SIGHTS GROW BACK, SO CAN 262 00:09:35,280 --> 00:09:38,360 YOU INDUCE TOLERANCE O MATT SHAY 263 00:09:38,360 --> 00:09:39,280 AND INVESTIGATORS AT THE 264 00:09:39,280 --> 00:09:42,440 UNIVERSITY OF ILLINOIS AND SAUDI 265 00:09:42,440 --> 00:09:44,040 ARABIA RECENTLY REPORTED 122 266 00:09:44,040 --> 00:09:45,320 PATIENTS TRANSPLANTED USING 267 00:09:45,320 --> 00:09:47,760 THIS,A PROACH, THE OVERALL 268 00:09:47,760 --> 00:09:50,160 SURVIVAL WAS 93% AFTER NIEF 269 00:09:50,160 --> 00:09:55,080 QUEERS, WITH AN 8385%, AND NONE 270 00:09:55,080 --> 00:09:57,000 OF PATIENTS DEVELOPED SEVERE 271 00:09:57,000 --> 00:09:57,840 MODERATE GRAFT VERSUS HOST 272 00:09:57,840 --> 00:09:58,080 DISEASE. 273 00:09:58,080 --> 00:09:59,440 SO WHILE THIS WAS EXCITING DATA, 274 00:09:59,440 --> 00:10:01,520 THE PROBLEM AT THE TIME WAS THAT 275 00:10:01,520 --> 00:10:03,640 ONLY LESS THAN 15% OF THE PATES 276 00:10:03,640 --> 00:10:05,480 HAVE A SIBLING DONOR HOWEVER 90% 277 00:10:05,480 --> 00:10:09,760 OF THE PATIENTS HAVE A HAPPEN LO 278 00:10:09,760 --> 00:10:11,320 IDENTICAL DONOR SO PARENTS, 279 00:10:11,320 --> 00:10:14,320 CHILDREN AND ALPHMASH SIBLINGS 280 00:10:14,320 --> 00:10:15,600 CAN SERVE AS DONORS. 281 00:10:15,600 --> 00:10:17,320 SO WE WANTED TO DEVELOP A 282 00:10:17,320 --> 00:10:19,440 PROTOCOL WE'VE SEEN IN THE MATCH 283 00:10:19,440 --> 00:10:21,000 SIBLING STUDY AND BASED ON 284 00:10:21,000 --> 00:10:21,960 MURINE BATTA I WROTE THIS 285 00:10:21,960 --> 00:10:24,240 PROTOCOL AND I WAS ABLE TO BE A 286 00:10:24,240 --> 00:10:25,320 PRINCIPLE INVESTIGATOR AS A 287 00:10:25,320 --> 00:10:28,120 FELLOW SOY WANT TO THANK 288 00:10:28,120 --> 00:10:28,720 DR. TISDALE FOR THAT. 289 00:10:28,720 --> 00:10:33,200 SO ALL OF THE PATIENTS GOT 290 00:10:33,200 --> 00:10:34,640 ALATUZUMAB, WE INCREASED 291 00:10:34,640 --> 00:10:37,040 RADIATION TO 400 CENTIGRADE, AND 292 00:10:37,040 --> 00:10:39,480 ALL THE PATIENTS RECEIVE 293 00:10:39,480 --> 00:10:41,760 SEROLMUS, AND IT WAS AICOSE 294 00:10:41,760 --> 00:10:42,680 ESCALATION OF THE FIEK SO FOSTER 295 00:10:42,680 --> 00:10:44,480 NURSED FOCUSED ON MID, SO THE 296 00:10:44,480 --> 00:10:47,240 FIRST COHORT OF PATIENTS DIDN'T 297 00:10:47,240 --> 00:10:47,880 RECEIVE AND CYCLOFOSTER NURSED 298 00:10:47,880 --> 00:10:51,160 FOCUSED ON MID, SO TOO MANY 299 00:10:51,160 --> 00:10:53,440 PATIENTS REJECTED GRAFS OR 300 00:10:53,440 --> 00:10:54,880 DEVELOPED GROF THE VERSUS HOST 301 00:10:54,880 --> 00:10:57,200 DISEASE, WE MOVED TO THE SECOND 302 00:10:57,200 --> 00:10:59,600 COHORT WHERE PATIENTS AREY 303 00:10:59,600 --> 00:11:00,240 CEIVED MORE CYCLOFOSTER NURSED 304 00:11:00,240 --> 00:11:03,200 FOCUSED ON MADE, AND WE MOVED TO 305 00:11:03,200 --> 00:11:06,200 THE FINAL COHORT WHICH IS A 306 00:11:06,200 --> 00:11:08,320 HUNDRED MILLIGRAM IN DOSES AND 307 00:11:08,320 --> 00:11:11,280 WE IMPROVE THE ENGRAPHMENT RATE 308 00:11:11,280 --> 00:11:12,800 AND WE DID IMPROVE THE EVENT 309 00:11:12,800 --> 00:11:14,480 FREE SURVIVAL BUT EVEN WITH THE 310 00:11:14,480 --> 00:11:16,440 COHORT, 50% OF THE PASHTS 311 00:11:16,440 --> 00:11:18,560 REJECTED THE GRAF AND THE STUDY 312 00:11:18,560 --> 00:11:22,520 WAS CLOSED TO ACCRUAL. 313 00:11:22,520 --> 00:11:25,680 SO BECAUSE OF THIS INCREASE THE 314 00:11:25,680 --> 00:11:26,520 RISK REJECTION WITH THE HAPPEN 315 00:11:26,520 --> 00:11:31,760 LO STUDY, WE HAD NEW PROTOCOLS, 316 00:11:31,760 --> 00:11:33,400 WHICH ADDS PEBT STATUS 317 00:11:33,400 --> 00:11:34,400 PRECONDITIONING BECAUSE THOSE 318 00:11:34,400 --> 00:11:37,000 AGENTS WORK TOGETHER TO DEPLETE 319 00:11:37,000 --> 00:11:38,040 LYMPHOCYTES AND TO DATE BOTH 320 00:11:38,040 --> 00:11:38,880 PROTOCOLS HAVE BEEN ASSOCIATED 321 00:11:38,880 --> 00:11:42,360 WITH THE LOWER RISK OF GRAPH 322 00:11:42,360 --> 00:11:42,760 REJECTION. 323 00:11:42,760 --> 00:11:44,880 AND I JUST WANTED TO MENTION 324 00:11:44,880 --> 00:11:46,640 SOMETHING ABOUT GENE THERAPY 325 00:11:46,640 --> 00:11:49,000 WHICH IS A NEWER PROCESS TO USE 326 00:11:49,000 --> 00:11:50,600 AS A CURATIVE OPTION FOR 327 00:11:50,600 --> 00:11:51,120 PATIENTS WITH SICKLE CELL 328 00:11:51,120 --> 00:11:52,400 DISEASE AND I WANT TO MENTION 329 00:11:52,400 --> 00:11:53,480 THERE ARE 3 DIFFERENT GROUPS, 330 00:11:53,480 --> 00:11:56,440 PATIENTS THAT HAVE RECEIVED THIS 331 00:11:56,440 --> 00:11:59,720 GENE THERAPY, GROUPS A, B, C, 332 00:11:59,720 --> 00:12:01,760 WITH GROUP AIAN PRECOLLECTION OF 333 00:12:01,760 --> 00:12:03,280 BLOOD CELL TRANSFUSION IS 334 00:12:03,280 --> 00:12:06,320 REQUIRED FOR GROUPS B AND C 335 00:12:06,320 --> 00:12:07,560 PATIENTS, THE HEMEAT O POET STEM 336 00:12:07,560 --> 00:12:11,000 CELL SOURCE WAS BONE MARROW IN B 337 00:12:11,000 --> 00:12:12,040 ANDA PATIENTS AND MOBILIZED IN 338 00:12:12,040 --> 00:12:13,720 GROUP C AND THE ORIGINAL 339 00:12:13,720 --> 00:12:14,880 MANUFACTURING DRUG AND PROCESS 340 00:12:14,880 --> 00:12:16,280 WAS USING SOME GROUP A AND B 341 00:12:16,280 --> 00:12:17,720 PATIENTS IN A MORE REFINED 342 00:12:17,720 --> 00:12:19,360 PROCESS IN GROUP B AND C PATIENT 343 00:12:19,360 --> 00:12:22,480 ANDS IMPORTANTLY ALL OF THE 344 00:12:22,480 --> 00:12:25,280 PATIENTS RECEIVE MILE ABLATIVE 345 00:12:25,280 --> 00:12:25,880 CONDITIONING WITH B-CELL, SO 346 00:12:25,880 --> 00:12:28,920 THIS IS A FELLOW IN MY LAB AND 347 00:12:28,920 --> 00:12:32,440 WE RECENTLY REPORTED 120 348 00:12:32,440 --> 00:12:33,960 PATIENTS, NONALLO BRAIT BLAITIVE 349 00:12:33,960 --> 00:12:34,760 TRANSPLANT FOR SICKLE CELL 350 00:12:34,760 --> 00:12:40,720 DISEASE HERE AT THE IN, IH 351 00:12:40,720 --> 00:12:41,320 SEPTEMBER 2004 AND 352 00:12:41,320 --> 00:12:42,680 DECEMBER 2020. 353 00:12:42,680 --> 00:12:43,480 EIGHTY-ONE PATIENTS RECEIVED THE 354 00:12:43,480 --> 00:12:47,600 TRANSPLANT WITH THE MEDIAN AGE 355 00:12:47,600 --> 00:12:51,840 OF 31 YEARS, 39 PATIENTS 356 00:12:51,840 --> 00:12:53,120 UNDERWENT HAPPEN LO IDENTICAL 357 00:12:53,120 --> 00:12:56,280 HCT AT 32 YEARS, AND BETWEEN 4 358 00:12:56,280 --> 00:12:58,920 MONTHS AND 9 YEARS POST 359 00:12:58,920 --> 00:13:00,320 TRANSPLANT, DEVELOPED MALIGNANCY 360 00:13:00,320 --> 00:13:03,480 SO 5 PATIENTS DEVELOPED A MORE 361 00:13:03,480 --> 00:13:05,480 AGGRESSIVE TYPE OF AML IN THE 362 00:13:05,480 --> 00:13:07,600 SETTING OF GRAPH FAILURE, 3 363 00:13:07,600 --> 00:13:10,360 DEVELOPED MEL AN OHM, MYELOID 364 00:13:10,360 --> 00:13:16,480 ALEUKEMIA AND A SETTING OF MIXED 365 00:13:16,480 --> 00:13:16,800 CHIMERISM. 366 00:13:16,800 --> 00:13:19,040 SO WHEN YOU LOOK AT THE DATA 367 00:13:19,040 --> 00:13:20,840 ACARDING TO THE PROTOCOL THEY 368 00:13:20,840 --> 00:13:27,640 WERE TRANSPLANTED ON, IN THE 369 00:13:27,640 --> 00:13:28,800 FIRST COLLUM,--YOU SEE THAT 1 370 00:13:28,800 --> 00:13:32,520 HADN'T 8% OF THE PATES DEVELOPED 371 00:13:32,520 --> 00:13:35,800 MDS OR AML, 5.3% DEVELOPED ALL 372 00:13:35,800 --> 00:13:37,880 HEMEAT O LOGIC MALIGNANCIES AND 373 00:13:37,880 --> 00:13:39,640 A MEDIAN OF 3 AND HALF YEARS 374 00:13:39,640 --> 00:13:40,960 POST TRANSPLANT, WHEN THE SAME 375 00:13:40,960 --> 00:13:44,640 APPROACH WAS USED IN CHICAGO OR 376 00:13:44,640 --> 00:13:47,040 RIOT, 1.6% OF THE PATIENTS 377 00:13:47,040 --> 00:13:50,200 GEPPED MDS OR AML AT 3 YEARS 378 00:13:50,200 --> 00:13:53,200 TRANSPLANT AND WE ADD THE 379 00:13:53,200 --> 00:13:54,840 [INDISCERNIBLE] PRECONDITIONING, 380 00:13:54,840 --> 00:13:59,560 4.2% DEVELOPED AMDS OR AML AND 381 00:13:59,560 --> 00:14:01,440 4.3 PERCENT WITH THE MALIGNANCY. 382 00:14:01,440 --> 00:14:03,280 THERE ARE THE 2 PROTOCOLS WHERE 383 00:14:03,280 --> 00:14:05,480 YOU SEE WITH THE ORIGINAL 384 00:14:05,480 --> 00:14:07,680 DECLARATION OF THE PROT COL, WE 385 00:14:07,680 --> 00:14:13,080 HAD 14% DEVELOP M, IT DS OR AML, 386 00:14:13,080 --> 00:14:19,400 THIS IS A NEWER PROTOCOL AND SO 387 00:14:19,400 --> 00:14:22,600 FAR TO DATE WE HAVE NONE SEE 388 00:14:22,600 --> 00:14:24,160 DEVELOPMENT OF MALIGNANCY. 389 00:14:24,160 --> 00:14:26,000 THIS IS COMPARATIVE WITH 2 390 00:14:26,000 --> 00:14:28,080 STUDIES, WHERE 44% OF THEM 391 00:14:28,080 --> 00:14:30,560 DEVELOPED MDS OR AML ANDY SEE 392 00:14:30,560 --> 00:14:31,640 THE INCIDENCE IS SIMILAR TO WHAT 393 00:14:31,640 --> 00:14:33,960 WE'VE SEEN AT THE NIH. 394 00:14:33,960 --> 00:14:34,800 IMPORTANTLY BOTH OF THESE 395 00:14:34,800 --> 00:14:35,760 PATIENTS WERE IN GROUP A AND 396 00:14:35,760 --> 00:14:37,960 THEY WERE IN A LOWER CELL DOSE 397 00:14:37,960 --> 00:14:41,320 IN THE PATIENTS MORE RECENTLY. 398 00:14:41,320 --> 00:14:44,640 BY RECEIVING THE GENE THERAPY. 399 00:14:44,640 --> 00:14:46,280 THIS COMPARES TO LARGER STUDIES, 400 00:14:46,280 --> 00:14:48,520 THIS IS MOSTLY PEDIATRIC 401 00:14:48,520 --> 00:14:51,280 PATIENTS, MOSTLY HLA MATCHED 402 00:14:51,280 --> 00:14:51,920 SIBLING, USING CONDITIONING AND 403 00:14:51,920 --> 00:14:54,600 YOU CAN SEE THAT THE INCIDENTS 404 00:14:54,600 --> 00:14:56,080 OF HEMEAT O LOGIC IS MUCH LOWER 405 00:14:56,080 --> 00:14:59,040 COMPARED TO WHAT WE'VE SEEN. 406 00:14:59,040 --> 00:15:05,640 I WANT TO MAKE SURE I DON'T GO 407 00:15:05,640 --> 00:15:06,600 TOO FAR. 408 00:15:06,600 --> 00:15:09,880 SO WHAT ARE PONL REASONS THESE 409 00:15:09,880 --> 00:15:10,480 PATIENTS HAVE MYELOID 410 00:15:10,480 --> 00:15:11,040 MALIGNANCIES HERE? 411 00:15:11,040 --> 00:15:13,840 THIS IS THE UC DAVIS STUDY I 412 00:15:13,840 --> 00:15:14,680 PREPORTED EARLIER, WE LOOK AT 413 00:15:14,680 --> 00:15:15,880 ALL PATIENTS WITH SICKLE CELL 414 00:15:15,880 --> 00:15:16,520 DISEASE, THEY FOUND THAT ISHT 415 00:15:16,520 --> 00:15:17,760 PATHWAY GIVESS WHO WERE OLDER 416 00:15:17,760 --> 00:15:19,280 AND THOSE WITH MORE SEVERE 417 00:15:19,280 --> 00:15:21,160 DISEASE WERE MORE LIKELY TO 418 00:15:21,160 --> 00:15:21,960 DEVELOP LEUKEMIA, WE TRANSPLANT 419 00:15:21,960 --> 00:15:24,200 PATIENTS HERE AT THE NIH WHEN 420 00:15:24,200 --> 00:15:25,480 ARE HOLDER THAN TYPICAL AND MORE 421 00:15:25,480 --> 00:15:26,320 SEVERE DISEASE THAN TYPICAL AND 422 00:15:26,320 --> 00:15:28,080 WE ALSO HAVE A LONGER DURATION 423 00:15:28,080 --> 00:15:29,280 OF FOLLOW UP AND A HIGHER 424 00:15:29,280 --> 00:15:31,800 PROPORTION OF PATIENT WHO IS ARE 425 00:15:31,800 --> 00:15:34,920 FOLLOWING LONG-TERM, WE ALSO USE 426 00:15:34,920 --> 00:15:37,480 TOTAL BODY IRRADIATION, AND 427 00:15:37,480 --> 00:15:38,720 SIMILAR, TO GENE THERAPY, 428 00:15:38,720 --> 00:15:41,680 PATIENTS THAT HAVE GRAPH FAILURE 429 00:15:41,680 --> 00:15:44,680 HAVE A REQUIREMENT OF 430 00:15:44,680 --> 00:15:53,440 REGENERATIVE HEMEAT O 431 00:15:53,440 --> 00:15:54,560 POETICESIS. 432 00:15:54,560 --> 00:15:55,880 SO I'M GOING TO END HERE. 433 00:15:55,880 --> 00:16:03,600 SO WE'VE HAD 2 PATIENTS WHO HAVE 434 00:16:03,600 --> 00:16:05,760 QUEPED MYELOID MALIGNANCIES AND 435 00:16:05,760 --> 00:16:06,480 HAD TP53 MUTATIONS AT THE 436 00:16:06,480 --> 00:16:07,880 DIAGNOSE AND WE WANT TO KNOW 437 00:16:07,880 --> 00:16:09,440 WHETHER WE CAUSED THESE 438 00:16:09,440 --> 00:16:10,960 MUTATIONS WITH THE CHEMO THERAPY 439 00:16:10,960 --> 00:16:12,480 OR RADIATION THAT WE GAVE OR 440 00:16:12,480 --> 00:16:13,880 BECAUSE OF SICKLE CELL DISEASE 441 00:16:13,880 --> 00:16:16,200 AND THE LIFETIME OF INFLAMMATION 442 00:16:16,200 --> 00:16:18,080 AND STRESS, THESE PATIENTS HAD 443 00:16:18,080 --> 00:16:21,560 THE MUTATIONS AT BASE LINE SO WE 444 00:16:21,560 --> 00:16:23,480 WORK WITH RISK ASSESSMENTS 445 00:16:23,480 --> 00:16:24,720 HORGANNA'S LAB AND THEY FOUND 446 00:16:24,720 --> 00:16:29,960 THESE WERE IN A FREE RADICALS 447 00:16:29,960 --> 00:16:33,000 FERENCEY OF SMR PBT 3 IN THISSA 448 00:16:33,000 --> 00:16:34,680 PATIENT AND 0.06% IN THIS 449 00:16:34,680 --> 00:16:37,360 PATIENT AND AFTER INJECTION, IT 450 00:16:37,360 --> 00:16:39,800 LOW FREQUENCY UNTIL THEY 451 00:16:39,800 --> 00:16:41,720 DEVELOPED THESE MYELOID 452 00:16:41,720 --> 00:16:42,040 FREQUENCIES. 453 00:16:42,040 --> 00:16:44,000 SO MY LAB IS LOOKING AT LARGER 454 00:16:44,000 --> 00:16:44,960 POPULATION OF TRANSPLANTS TO 455 00:16:44,960 --> 00:16:46,240 LOOK THEA THE PREVALENCE OF 456 00:16:46,240 --> 00:16:49,680 THESE CLONES, WE ARE WORKING 457 00:16:49,680 --> 00:16:51,880 WITH DANA FARBER TO SEE IF THESE 458 00:16:51,880 --> 00:16:53,280 CLONES ARE OCCURRING AT BASE 459 00:16:53,280 --> 00:16:54,320 LINE AND WHETHER THEY'RE 460 00:16:54,320 --> 00:16:55,840 EXPANDING OVER TIME AND THEN WE 461 00:16:55,840 --> 00:16:58,400 WILL LOOK AT THE SINGLE CELL 462 00:16:58,400 --> 00:17:00,400 LEVEL TO SEE IF THERE ARE DRIVER 463 00:17:00,400 --> 00:17:02,560 MUTATIONS THAT MAKE THEM MORE 464 00:17:02,560 --> 00:17:05,280 PRONE TO DEVELOPING THOSE 465 00:17:05,280 --> 00:17:05,640 MALIGNANCIES. 466 00:17:05,640 --> 00:17:06,040 I WILL END THERE. 467 00:17:06,040 --> 00:17:10,680 THANK YOU VERY MUCH. 468 00:17:10,680 --> 00:17:14,400 [ APPLAUSE ] 469 00:17:14,400 --> 00:17:15,680 >>THANK YOU SO MUCH FOR BEING 470 00:17:15,680 --> 00:17:18,320 HERE, I STUDY SMALL CELL LUNG 471 00:17:18,320 --> 00:17:18,800 CANCER. 472 00:17:18,800 --> 00:17:20,880 I HAVE NO DISCLOSURES IF YOU'RE 473 00:17:20,880 --> 00:17:22,600 NOT FAMILIAR WITH SMALL CELL 474 00:17:22,600 --> 00:17:24,120 LUNG CANCERS IT'S PROBABLY 1 OF 475 00:17:24,120 --> 00:17:27,320 THE MOST HIGHLY METASTATIC 476 00:17:27,320 --> 00:17:28,480 CANCERS MOST PATIENTS PRESENT 477 00:17:28,480 --> 00:17:30,000 WITH WIDE SPREAD DISEASE AND 478 00:17:30,000 --> 00:17:32,120 THESE TUMORS TEND TO BE 479 00:17:32,120 --> 00:17:33,040 EXCEPTIONALLY RESPONSIVE TO 480 00:17:33,040 --> 00:17:33,640 CHEMO THERAPY. 481 00:17:33,640 --> 00:17:36,680 YOU CAN SEE THIS IS A CT SCAN OF 482 00:17:36,680 --> 00:17:39,560 A PATIENT, THIS IS A TUMOR IN 483 00:17:39,560 --> 00:17:42,040 THE RIGHT LOBE MELTING AWAY 484 00:17:42,040 --> 00:17:43,960 FOLLOWING CHEMO THERAPY. 485 00:17:43,960 --> 00:17:44,880 THESE RESPONSES ARE VERY 486 00:17:44,880 --> 00:17:47,760 TRANSIENT WHICH IS FOLLOWED BY 487 00:17:47,760 --> 00:17:48,840 SYSTEM TEMMIC RELAPSE AND HERE 488 00:17:48,840 --> 00:17:49,800 YOU CAN SEE RELAPSE IN THE LIVER 489 00:17:49,800 --> 00:17:52,280 AS WELL AS IN THE ADRENAL. 490 00:17:52,280 --> 00:17:54,760 AND AT THE TIME OF RELAPSE, MOST 491 00:17:54,760 --> 00:17:57,880 OF THE STANDARD TREATMENTS ARE 492 00:17:57,880 --> 00:18:01,680 LARGELY INEFFECTIVE AND PATIENTS 493 00:18:01,680 --> 00:18:03,120 DIE--MOST PATIENTS DIE WITHIN A 494 00:18:03,120 --> 00:18:05,160 YEAR OF THEIR DIAGNOSE. 495 00:18:05,160 --> 00:18:07,160 IT'S AN EXCEPTIONALLY SEVERE 496 00:18:07,160 --> 00:18:08,360 DISEASE, IT'S A STANDARD 497 00:18:08,360 --> 00:18:12,720 TREATMENT OF THESE, MORE CHEMO 498 00:18:12,720 --> 00:18:13,840 THERAPY, MORE RECENTLY, IMMUNO 499 00:18:13,840 --> 00:18:15,960 THERAPY IS ADD BUT IT ONLY 500 00:18:15,960 --> 00:18:17,160 BENEFITS A SMALL SUBSET OF 501 00:18:17,160 --> 00:18:17,400 PATIENTS. 502 00:18:17,400 --> 00:18:19,360 AND IT'S NOT AN UNCOMMON 503 00:18:19,360 --> 00:18:19,600 DISEASE. 504 00:18:19,600 --> 00:18:21,800 IT AFFECTS A LOT OF PEOPLE. 505 00:18:21,800 --> 00:18:22,920 IT AFFECTS 250,000 INDIVIDUALS 506 00:18:22,920 --> 00:18:25,040 WORLD WIDE EVERY YEAR. 507 00:18:25,040 --> 00:18:28,280 AND IN THE U.S. IT KILLS AT 508 00:18:28,280 --> 00:18:29,480 LEAST 30,000 PEOPLE EVERY YEAR 509 00:18:29,480 --> 00:18:32,280 SO IT'S AN EXCEPTIONALLY LETHAL 510 00:18:32,280 --> 00:18:33,400 CANCER, BUT IT'S ALSO 511 00:18:33,400 --> 00:18:36,080 EXCEPTIONALLY COMMON AND AS I 512 00:18:36,080 --> 00:18:37,240 SAID, MEDIAN SURVIVAL IN MOST 513 00:18:37,240 --> 00:18:42,040 PATIENT SYSTEM LESS THAN A YEAR. 514 00:18:42,040 --> 00:18:43,720 AND RECENT STUDY VS SHOWN IT'S 515 00:18:43,720 --> 00:18:45,320 NOT 1 DISEASE, IT CONSISTS OF 516 00:18:45,320 --> 00:18:46,840 MANY DISEASES AND MANY SUBTYPES 517 00:18:46,840 --> 00:18:49,280 AND BROADLY YOU COULD UNDERSTAND 518 00:18:49,280 --> 00:18:50,800 THE HETEROGENEITY IN SMALL CELL 519 00:18:50,800 --> 00:18:56,040 LUNG DANCER INTO TUMORS THAT 520 00:18:56,040 --> 00:18:57,520 HARBOR INDO KRIN PHENOTYPE AND 521 00:18:57,520 --> 00:19:01,960 TUMORS WHO HAVE NEW EXPRESSION 522 00:19:01,960 --> 00:19:02,880 OF NONNEW ENDOCRINE PHENOTYPE 523 00:19:02,880 --> 00:19:05,040 AND THIS IS DETERMINED BY THE 524 00:19:05,040 --> 00:19:05,800 DEFINING TRANSCRIPTION FACTORS 525 00:19:05,800 --> 00:19:09,160 THAT ARE LISTED HERE. 526 00:19:09,160 --> 00:19:10,520 THEY CHARACTERIZE FURTHER 527 00:19:10,520 --> 00:19:11,920 SUBTYPES WITHIN SMALL LUNG 528 00:19:11,920 --> 00:19:12,160 CANCER. 529 00:19:12,160 --> 00:19:15,200 SO DESPITE US KNOWING THERE IS 530 00:19:15,200 --> 00:19:17,360 HETEROGENEITY BASED ON THE 531 00:19:17,360 --> 00:19:19,200 LINEAGE OF DEFINING FACTORS WE 532 00:19:19,200 --> 00:19:20,760 TREAT SMALL CELL LUNG FACT OR AS 533 00:19:20,760 --> 00:19:22,720 A SINGLE DISEASE, AND EVERYBODY 534 00:19:22,720 --> 00:19:24,480 WITH SMALL CELL LUNG CANCER GETS 535 00:19:24,480 --> 00:19:26,480 THE SAME TREATMENTS AND AS A 536 00:19:26,480 --> 00:19:29,360 RESULT, THE SMALL CELL OUTCOME 537 00:19:29,360 --> 00:19:31,320 VS NOT CHANGED SUBSTANTIALLY IN 538 00:19:31,320 --> 00:19:32,880 THE LAST MANY, MANY DECADES, 539 00:19:32,880 --> 00:19:34,640 THIS IS DATA GOING BACK TO 2001, 540 00:19:34,640 --> 00:19:38,440 CAN YOU SEE THE 2 YEAR SURVIVAL 541 00:19:38,440 --> 00:19:40,320 FOR MEN IS 10% AND FOR WOMEN, 542 00:19:40,320 --> 00:19:46,880 IT'S A BIT HIGHER MAYBE 15%. 543 00:19:46,880 --> 00:19:49,280 SO WHAT MAKES SMALL CELL SUCH AN 544 00:19:49,280 --> 00:19:50,160 AGGRESSIVE CANCER? 545 00:19:50,160 --> 00:19:51,040 THE BIG CHALLENGE IS THAT WE 546 00:19:51,040 --> 00:19:53,240 KNOW VERY LITTLE ABOUT THE 547 00:19:53,240 --> 00:19:54,440 MOLECULAR BASIS OF HUMAN SMALL 548 00:19:54,440 --> 00:19:56,200 CELL LUNG CANCER AND YOU CAN 549 00:19:56,200 --> 00:19:57,280 CHARACTERIZE THE AGGRESSIVE 550 00:19:57,280 --> 00:19:58,400 FEATURES OF SMALL CELL AND USE 551 00:19:58,400 --> 00:20:01,040 IT AS A MODEL DISEASE TO STUDY 552 00:20:01,040 --> 00:20:04,040 METASTASIS, CHEMO RESISTANCE AND 553 00:20:04,040 --> 00:20:04,720 HETEROGENEITY. 554 00:20:04,720 --> 00:20:06,800 AND THE BIG CHALLENGE IS THAT 555 00:20:06,800 --> 00:20:07,880 THERE'S VERY LIMITED 556 00:20:07,880 --> 00:20:09,880 AVAILABILITY OF CLINICAL SAMPLES 557 00:20:09,880 --> 00:20:10,920 OR HUMAN TUMOR SAMPLES FOR 558 00:20:10,920 --> 00:20:13,480 RESEARCH AND BECAUSE THERE'S 559 00:20:13,480 --> 00:20:15,080 LIMITED AVAILABILITY OF CLINICAL 560 00:20:15,080 --> 00:20:17,040 SAMPLES, SMELL CELL IS NOT 561 00:20:17,040 --> 00:20:19,640 INCLUDED IN MANY OF THE CANCER 562 00:20:19,640 --> 00:20:20,920 STUDIES INCLUDING TCGA AND 563 00:20:20,920 --> 00:20:22,560 BECAUSE OF THE CLINICAL SAMPLES, 564 00:20:22,560 --> 00:20:24,480 ALMOST EVERYTHING THAT WE KNOW 565 00:20:24,480 --> 00:20:26,400 ABOUT SMALL CELL, IS BASICALLY 566 00:20:26,400 --> 00:20:27,600 DERIVED FROM THE CELL CULTURES 567 00:20:27,600 --> 00:20:31,880 AS WELL AS MOUSE MODELS. 568 00:20:31,880 --> 00:20:33,440 AND WHAT WE HAVE TRIED TO DO NOW 569 00:20:33,440 --> 00:20:35,200 OVER THE LAST CLOSE TO 10 YEAR 570 00:20:35,200 --> 00:20:37,040 SYSTEM TO TRY TO CHANGE THAT AND 571 00:20:37,040 --> 00:20:39,520 THIS IS REALLY THE MOTIVATION 572 00:20:39,520 --> 00:20:40,760 WHICH GOT ME STARTED THINKING 573 00:20:40,760 --> 00:20:42,920 ABOUT SMALL CELL WAS THIS 574 00:20:42,920 --> 00:20:44,720 DOCUMENT WHICH WAS PUT OUT BY 575 00:20:44,720 --> 00:20:47,480 NCI IN RESPONSE TO THE 576 00:20:47,480 --> 00:20:48,720 RECALCITRANT CANCER RESEARCH ACT 577 00:20:48,720 --> 00:20:50,880 OF 2012 AND THIS WAS PUBLISH 578 00:20:50,880 --> 00:20:54,440 INDEED JUNE 2014. 579 00:20:54,440 --> 00:20:56,840 AND IT HIGHLIGHTED BASICALLY THE 580 00:20:56,840 --> 00:20:57,880 SCARCE AMOUNT OF RESEARCH GOING 581 00:20:57,880 --> 00:20:59,360 ON IN SMALL CELL AS WELL AS THE 582 00:20:59,360 --> 00:21:02,520 LACK OF CLINICAL TRIALS. 583 00:21:02,520 --> 00:21:04,640 IN PARTICULAR WHAT STRUCK ME 584 00:21:04,640 --> 00:21:06,640 THERE WAS NO INTRAMURAL TRIALS 585 00:21:06,640 --> 00:21:08,720 FOR SMALL CELLS AT THAT TIME, SO 586 00:21:08,720 --> 00:21:10,320 WE TRIED TO ADDRESS SMALL CELL 587 00:21:10,320 --> 00:21:12,120 FROM A VERY PATIENT-CENTERED 588 00:21:12,120 --> 00:21:13,480 APPROACH AND OUR GOAL IS TO 589 00:21:13,480 --> 00:21:14,680 PROVIDE THE BEST POSSIBLE CARE 590 00:21:14,680 --> 00:21:16,040 FOR EVERY PATIENT AND LEARN FROM 591 00:21:16,040 --> 00:21:18,600 EVERY PATIENT AND USING THIS 592 00:21:18,600 --> 00:21:20,880 APPROACH WE HAVE NOW BUILT A 593 00:21:20,880 --> 00:21:21,920 ROBUST CLINICAL PROGRAM FOR 594 00:21:21,920 --> 00:21:23,960 SMALL CELL LUNG CANCER HERE, WE 595 00:21:23,960 --> 00:21:25,560 LAUNCHED OVER 15 CLINICAL TRIALS 596 00:21:25,560 --> 00:21:27,960 IN THE LAST 9 YEARS OR SO AND 597 00:21:27,960 --> 00:21:29,760 ROLLED OVER 400 PATIENTS 598 00:21:29,760 --> 00:21:32,920 CONDUCTED NUMEROUS RESEARCH 599 00:21:32,920 --> 00:21:35,640 BIOPSIES, AND ABOUT 20 RESEARCH 600 00:21:35,640 --> 00:21:36,320 AUTOPSIESS THAT HAVE FORMED THE 601 00:21:36,320 --> 00:21:37,320 TREATMENT OF THE DISEASE AND THE 602 00:21:37,320 --> 00:21:40,400 BIOLOGY OF THE DISEASE. 603 00:21:40,400 --> 00:21:43,360 SO I WILL FOCUS ON 1 PARTICULAR 604 00:21:43,360 --> 00:21:44,480 ASPECT WHICH IS REPLICATION 605 00:21:44,480 --> 00:21:47,840 STRESS SO EARLY ON WE HYPOTHESIS 606 00:21:47,840 --> 00:21:53,080 THAT WE HAVE SMALL CELL DRIVING 607 00:21:53,080 --> 00:21:56,520 TUMOR SUPPRESS, 253 AND RB AND 608 00:21:56,520 --> 00:22:04,560 HIGH FREQUENCY OF MYC 609 00:22:04,560 --> 00:22:06,400 AMPLIFICATION, AND STRIKING 610 00:22:06,400 --> 00:22:08,040 RESPONSES TO DNA REPRECATION AND 611 00:22:08,040 --> 00:22:09,840 IT ALSO RESPONDS VERY WELL TO 612 00:22:09,840 --> 00:22:12,400 DNA DAMAGING THERAPY AS WELL AS 613 00:22:12,400 --> 00:22:14,120 HIGH GENOMIC INSTABILITY 614 00:22:14,120 --> 00:22:17,040 CHARACTERIZED BY MUTATIONAL LOAD 615 00:22:17,040 --> 00:22:18,240 AND ANUE EMPLOYEDY. 616 00:22:18,240 --> 00:22:20,600 SO THIS IS DRIVEN BY HIGH 617 00:22:20,600 --> 00:22:21,080 REPLICATION STRESS AND 1 618 00:22:21,080 --> 00:22:23,280 APPROACH TO OTHER TAKEN--THEYET 619 00:22:23,280 --> 00:22:24,480 REPLICATION STRESS IS TO TARGET 620 00:22:24,480 --> 00:22:27,200 THE MEDIATION OF STRESS AND 1 621 00:22:27,200 --> 00:22:28,360 IMPORTANT REPLICATION STRESS WE 622 00:22:28,360 --> 00:22:33,160 FOCUS ON WAS ATR. 623 00:22:33,160 --> 00:22:36,080 AND ESSENTIALLY WE HAVE FOCUS ON 624 00:22:36,080 --> 00:22:38,120 ATR SINCE ABOUT 2014, 2015 AND 625 00:22:38,120 --> 00:22:39,080 WE'VE DISCOVERED THAT 626 00:22:39,080 --> 00:22:40,800 REPLICATION STRESS IS A SMALL 627 00:22:40,800 --> 00:22:42,200 CELL LUNG CANCER VULNERABILITY, 628 00:22:42,200 --> 00:22:44,800 AND OUR STUDIES HAVE PAVED THE 629 00:22:44,800 --> 00:22:45,840 WAY FOR RATIONAL PATIENT 630 00:22:45,840 --> 00:22:47,280 SELECTION IN A DISEASE THAT'S 631 00:22:47,280 --> 00:22:51,160 TREATED WITH A SINGLE TREATMENT 632 00:22:51,160 --> 00:22:51,760 FOR--SAME TREATMENT FOR 633 00:22:51,760 --> 00:22:52,160 EVERYBODY. 634 00:22:52,160 --> 00:22:54,320 SO 1 OF OUR FIRST CLINICAL TRIAL 635 00:22:54,320 --> 00:22:56,240 WAS A PHASE 1 CLINICAL TRIAL, SO 636 00:22:56,240 --> 00:22:57,960 THIS WAS A FIRST IN CLASS 637 00:22:57,960 --> 00:22:58,640 INHIBITOR AND BEFORE THAT THERE 638 00:22:58,640 --> 00:23:00,520 WERE A LOT OF CONCERNS ABOUT 639 00:23:00,520 --> 00:23:02,760 TARGETING ATR BECAUSE IT'S AN 640 00:23:02,760 --> 00:23:05,760 ESSENTIAL PROTEIN. 641 00:23:05,760 --> 00:23:06,800 WE CHARACTERIZED SAFETY AND SO 642 00:23:06,800 --> 00:23:09,240 THIS IS ANOTHER DNA DAMAGING 643 00:23:09,240 --> 00:23:11,240 AGENT WHICH FORMS THE BASIS OF 644 00:23:11,240 --> 00:23:12,080 STANDARD CHEMO THERAPY OF SMALL 645 00:23:12,080 --> 00:23:12,800 CELL. 646 00:23:12,800 --> 00:23:14,680 SO THIS WAS A FIRST PUBLISHED 647 00:23:14,680 --> 00:23:16,680 CLINICAL TRIAL OF AN ATR 648 00:23:16,680 --> 00:23:18,320 INHIBITOR, WE THEN CONDUCTED THE 649 00:23:18,320 --> 00:23:19,760 PHASE 2 CLIN DALLASCOWBOYS.COM 650 00:23:19,760 --> 00:23:22,720 TRIAL OF THIS COMBINATION WHICH 651 00:23:22,720 --> 00:23:24,240 RESULTED IN RESPONSES IN ABOUT 652 00:23:24,240 --> 00:23:26,680 36% OF 25 OR SO PATIENTS THAT WE 653 00:23:26,680 --> 00:23:26,920 TREATED. 654 00:23:26,920 --> 00:23:31,680 AND THEN WE EXTENDED THE STUDY 655 00:23:31,680 --> 00:23:33,280 TO EXTRA PULMONARY SMALL CELL 656 00:23:33,280 --> 00:23:35,120 CANCER, THESE ARE SMALL CELL 657 00:23:35,120 --> 00:23:37,800 CANCERS THAT ARISE FROM NONLUNG 658 00:23:37,800 --> 00:23:38,920 SITES BUT CELL MORPHOLOGIC 659 00:23:38,920 --> 00:23:41,280 FEATURES AND AS WELL AS SOME 660 00:23:41,280 --> 00:23:42,160 WITH SMALL CELL. 661 00:23:42,160 --> 00:23:47,800 AND MORE RECENTLY WE COMPLETED A 662 00:23:47,800 --> 00:23:53,480 MULTICENTER NATIONAL RANDOMIZED 663 00:23:53,480 --> 00:23:55,440 TRIAL WITH TOPOTICAN AND WITHOUT 664 00:23:55,440 --> 00:23:57,520 AND FOLLOWED UP ON THESE 665 00:23:57,520 --> 00:23:57,760 STUDIES. 666 00:23:57,760 --> 00:23:59,560 WE NOW HEAVILY INVESTED IN 667 00:23:59,560 --> 00:24:02,520 IDENTIFYING DETERMINE NABTS OF 668 00:24:02,520 --> 00:24:04,400 RESPONSE, WHERE SOME PATIENTS 669 00:24:04,400 --> 00:24:06,240 RESPOND AND WHY SOME DON'T 670 00:24:06,240 --> 00:24:06,520 RESPOND. 671 00:24:06,520 --> 00:24:08,560 WE INTERESTED IN UNDERSTANDING 672 00:24:08,560 --> 00:24:10,520 THE REPLICATION STRESS, THE 673 00:24:10,520 --> 00:24:11,320 MOTIVATION THAT REPLICATION 674 00:24:11,320 --> 00:24:13,360 STRESS IS NOT UNIQUE TO OTHER 675 00:24:13,360 --> 00:24:15,000 CANCERS, IT'S FOUND IN A LOT OF 676 00:24:15,000 --> 00:24:17,680 OTHER CANCERS WE WANT TO IMPROVE 677 00:24:17,680 --> 00:24:19,120 INDEX OF THE TARGETED THERAPIES 678 00:24:19,120 --> 00:24:21,360 AND OFTEN TYPES THESE STREEMENTS 679 00:24:21,360 --> 00:24:23,040 CAN CAUSE MILE O SUPPRESSION AND 680 00:24:23,040 --> 00:24:24,680 WE WANT TO IMPROVE THE ROUTINE 681 00:24:24,680 --> 00:24:26,720 OF THOSE EAMENTS AND WE TRY TO 682 00:24:26,720 --> 00:24:28,960 HAPPENED THE SMALL CELL LUNG 683 00:24:28,960 --> 00:24:29,880 CANCER REPLICATION, SO VERY 684 00:24:29,880 --> 00:24:32,520 QUICKLY I WILL GO OVER THE PHASE 685 00:24:32,520 --> 00:24:35,480 2 CLIN TRIAL, SOME OF THE 686 00:24:35,480 --> 00:24:36,560 CORRELATIVE STUDIES WHICH HAVE 687 00:24:36,560 --> 00:24:37,680 DWIF PATIENTS. 688 00:24:37,680 --> 00:24:38,480 WE DETERMINED THE COMBINATION 689 00:24:38,480 --> 00:24:39,800 HERE, WE ARE LOOKING AT EFFICACY 690 00:24:39,800 --> 00:24:42,600 AND WE WERE ABLE TO OBTAIN 691 00:24:42,600 --> 00:24:43,320 PRETREATMENT TUMOR BIOPSIES FROM 692 00:24:43,320 --> 00:24:45,600 MOST OF THE PATIENTS AND AGAIN 693 00:24:45,600 --> 00:24:46,600 IT'S A UNIQUELY SOURCED HERE AT 694 00:24:46,600 --> 00:24:48,000 THE CLINICAL CENTER THAT ALLOWS 695 00:24:48,000 --> 00:24:50,920 US TO BRING PATIENTS IN, QUICKLY 696 00:24:50,920 --> 00:24:52,440 GET BIOPSIES AND GET STARTED ON 697 00:24:52,440 --> 00:24:53,840 TREATMENT QUICKLY BECAUSE THESE 698 00:24:53,840 --> 00:24:55,200 ARE AGGRESSIVE CANCERS AND 699 00:24:55,200 --> 00:24:56,400 PATIENTINGS PROGRESS VERY 700 00:24:56,400 --> 00:24:56,640 QUICKLY. 701 00:24:56,640 --> 00:24:59,440 SO WE PROFRIEL FILE THE 702 00:24:59,440 --> 00:25:00,480 PRETREATMENT TUMORS, WITH THE 703 00:25:00,480 --> 00:25:02,360 GOAL OF IDENTIFYING WHAT ARE THE 704 00:25:02,360 --> 00:25:04,240 FEATURES THAT YOU KNOW PREDICT 705 00:25:04,240 --> 00:25:05,560 RESPONSE TO TREATMENT AND WE 706 00:25:05,560 --> 00:25:08,320 FOUND THAT RESPONDING TUMORS HAD 707 00:25:08,320 --> 00:25:10,880 2 UNIQUE FEATURES, AND THEY WERE 708 00:25:10,880 --> 00:25:12,400 RELATED TO CELL CYCLE CHOIK 709 00:25:12,400 --> 00:25:14,720 POINTS AND DNA REPAIR GENES AND 710 00:25:14,720 --> 00:25:17,200 THIS SUGGESTS THAT TUMORS IN 711 00:25:17,200 --> 00:25:18,120 HIGHER REPLICATION STRESS, AND 712 00:25:18,120 --> 00:25:20,440 MORE INTERESTING WAS THESE WERE 713 00:25:20,440 --> 00:25:22,640 RESPONDING HAD INCREASED MURINE 714 00:25:22,640 --> 00:25:23,600 ENDOCRINE GENE EXPRESSION, IF 715 00:25:23,600 --> 00:25:27,040 YOU MPLE 1 OF MY FIRST SLIDES, 716 00:25:27,040 --> 00:25:28,440 THERE'S MARKED HETEROGENEITY IN 717 00:25:28,440 --> 00:25:30,880 SMALL CELL, WITH SOME HAVING 718 00:25:30,880 --> 00:25:32,400 HIGHER ENDOCRINE FEATURES AND 719 00:25:32,400 --> 00:25:34,840 SOME TUMORS HAVING LOWER 720 00:25:34,840 --> 00:25:36,480 ENDOCRINE FEATURES, SO THESE 721 00:25:36,480 --> 00:25:38,880 WITH THE HIGHER 1S RESPOND TO 722 00:25:38,880 --> 00:25:41,160 TREATMENT AND THIS IS A 723 00:25:41,160 --> 00:25:42,160 NEUROENDOCRINE MARKER. 724 00:25:42,160 --> 00:25:44,480 IT'S NOT A HUNDRED% BIOMARKERS 725 00:25:44,480 --> 00:25:46,280 NOT ALL PATIENTS WITH THE 726 00:25:46,280 --> 00:25:47,280 FEATURES RESPOND. 727 00:25:47,280 --> 00:25:50,400 FIFTY% OF THEM DO, BUT 728 00:25:50,400 --> 00:25:51,920 COMPARATIVELY NONE ALONE RESPOND 729 00:25:51,920 --> 00:25:52,320 TO TREATMENT. 730 00:25:52,320 --> 00:25:54,640 APPROXIMATE WE FIND THAT THE 731 00:25:54,640 --> 00:25:56,880 DURATION RESPONSE AS WELL AS 732 00:25:56,880 --> 00:25:57,640 PROGRESSION FREE RADICALS 733 00:25:57,640 --> 00:25:59,440 SURVIVAL IS MUCH LOWER IN THE 734 00:25:59,440 --> 00:26:02,320 COMBINATION WITH PATIENTS WITH 735 00:26:02,320 --> 00:26:03,360 HIGHER ENDOCRINE FEATURE. 736 00:26:03,360 --> 00:26:06,560 SO WE'RE FINDING THAT SMALL CELL 737 00:26:06,560 --> 00:26:08,760 HETEROGENEITY AND WE'RE FINDING 738 00:26:08,760 --> 00:26:11,000 THAT THE TUMORS WITH HIGH 739 00:26:11,000 --> 00:26:12,160 NEUROENDOCRINE FEATURES HAVE 740 00:26:12,160 --> 00:26:15,080 MORE LIKELIHOOD OF RESPONDING 741 00:26:15,080 --> 00:26:16,920 AND TOPOICE ORDER OF MICRONSER 742 00:26:16,920 --> 00:26:17,320 ACE INHIBITION. 743 00:26:17,320 --> 00:26:18,520 AND WE USED A SIMILAR APPROACH 744 00:26:18,520 --> 00:26:20,720 THIS IS IS A DIFFERENT CLINICAL 745 00:26:20,720 --> 00:26:20,920 TRIAL. 746 00:26:20,920 --> 00:26:23,920 INSTEAD OF USING A DNA REPAIR 747 00:26:23,920 --> 00:26:24,520 INHIBITOR WE USE IMMUNO THR 748 00:26:24,520 --> 00:26:26,400 ACTIVITIES AND PROJECTS EXPE 749 00:26:26,400 --> 00:26:29,760 AGAIN THE PRETREATMENT, RNA 750 00:26:29,760 --> 00:26:30,720 SEQUENCING, DCR SEQUENCING AND 751 00:26:30,720 --> 00:26:32,600 WE FIND THAT THEY ENRICH FOR 752 00:26:32,600 --> 00:26:36,040 IMMUNE SYSTEM, RELATED PATHWAYS 753 00:26:36,040 --> 00:26:37,200 BUT ALSO NEUROLOGICAL PATHWAYS 754 00:26:37,200 --> 00:26:40,800 SO IT IS A LOW NEUROENDOCRINE 755 00:26:40,800 --> 00:26:42,560 TUMOR THAT RESPOND TO 756 00:26:42,560 --> 00:26:44,040 IMMUNOTHERAPY HERE AND WE'VE 757 00:26:44,040 --> 00:26:44,880 DONE MECHANISTIC STUDIES TO 758 00:26:44,880 --> 00:26:46,560 FOLLOW UP ON THIS BUT THE BOTTOM 759 00:26:46,560 --> 00:26:48,200 LIEB IS THAT SMALL CELL WHICH IS 760 00:26:48,200 --> 00:26:49,800 CURRENTLY THROUGH A SINGLE 761 00:26:49,800 --> 00:26:51,440 DISEASE, WE FIND IT IS 762 00:26:51,440 --> 00:26:52,360 HETEROGENEOUS ORY GENIUS AND WE 763 00:26:52,360 --> 00:26:56,880 FIND THAT THE TUMORS AND THE 764 00:26:56,880 --> 00:26:57,440 HETEROGENEITY OF TREATMENT 765 00:26:57,440 --> 00:26:59,600 RESPONSE IS BASED ON THE 766 00:26:59,600 --> 00:27:00,480 NEUROENDOCRINE GENE EXPRESSION 767 00:27:00,480 --> 00:27:02,280 PATTERN WITH SOME TUMORS 768 00:27:02,280 --> 00:27:03,600 RESPONDING TO DNA REPAIR 769 00:27:03,600 --> 00:27:05,480 TARGETED THERAPIES AND OTHER 770 00:27:05,480 --> 00:27:09,120 TUMORS RESPONDING TO 771 00:27:09,120 --> 00:27:09,640 IMMUNOTHERAPIES. 772 00:27:09,640 --> 00:27:12,440 SO IN FOLLOW UP STUDIES WE TRIED 773 00:27:12,440 --> 00:27:14,200 TO UNDERSTAND, YOU KNOW WHAT IS 774 00:27:14,200 --> 00:27:16,760 DRIVING IN THE TUMOR 775 00:27:16,760 --> 00:27:18,080 HETEROGENEITY, AS YOU CAN 776 00:27:18,080 --> 00:27:19,880 IMAGINE, THESE TUMORS ARE 777 00:27:19,880 --> 00:27:20,960 HETEROGENEOUS ORY GENIUS AND 778 00:27:20,960 --> 00:27:22,240 LIKELY PLASTIC AND PROBABLY MOVE 779 00:27:22,240 --> 00:27:23,640 FROM 1 CELL STATE TO ANOTHER AND 780 00:27:23,640 --> 00:27:28,320 WE ARE TRYING TO UNDERSTAND WHAT 781 00:27:28,320 --> 00:27:33,160 DOES DRIVING THE TUMOR FOR INTRA 782 00:27:33,160 --> 00:27:33,760 TUMOR HETEROGENEITY AND AS CAN 783 00:27:33,760 --> 00:27:35,560 YOU IMAGINE IT COULD BE 784 00:27:35,560 --> 00:27:36,280 UNDERLYING TREATMENT FAIL NUR 785 00:27:36,280 --> 00:27:37,360 MANY OF THESE PATIENTS. 786 00:27:37,360 --> 00:27:41,200 SO WE TRY TO UNDERSTAND AND IN 787 00:27:41,200 --> 00:27:43,200 THE HETEROGENERATED AITY, IN A 788 00:27:43,200 --> 00:27:44,960 SIMPLE FRAMEWORK, TRYING TO 789 00:27:44,960 --> 00:27:46,560 UNDERSTAND THE DETERMINANTS OF 790 00:27:46,560 --> 00:27:52,240 HETEROGENEITY AND FOCUSING ON 791 00:27:52,240 --> 00:27:53,880 THE DETERMINANTS, IT IS KNOWN 792 00:27:53,880 --> 00:27:55,680 THAT SMALL CELL LUNG CANCER 793 00:27:55,680 --> 00:27:57,080 EVOLVES FROM A NEUROEND COKRIN 794 00:27:57,080 --> 00:27:58,600 STATE AND WITH TIME AND 795 00:27:58,600 --> 00:28:00,800 TREATMENT, IT EVOLVES INTO A 796 00:28:00,800 --> 00:28:04,880 NIEWN NEUROENDOCRINE CELL STATE 797 00:28:04,880 --> 00:28:09,560 AND MYC STARTED TO MEDIATE THIS 798 00:28:09,560 --> 00:28:11,000 BY REPROGRAMMING THE 799 00:28:11,000 --> 00:28:11,960 NEUROENDOCRINE FATE BUT IT DOES 800 00:28:11,960 --> 00:28:15,280 NOT KNOW WHAT THIS LEVEL ENABLES 801 00:28:15,280 --> 00:28:16,120 ACTIVATION WHICH ENABLES SMALL 802 00:28:16,120 --> 00:28:19,120 CELL LUNG CANCER TO BE PLASTIC 803 00:28:19,120 --> 00:28:19,960 AND TRANSFORM FROM 1 CELL STATE 804 00:28:19,960 --> 00:28:21,000 TO ANOTHER. 805 00:28:21,000 --> 00:28:23,040 WE FOCUSED ON EXTRA CHROMOSOMAL 806 00:28:23,040 --> 00:28:25,160 DNA SO THESE ARE ELEMENTS THAT 807 00:28:25,160 --> 00:28:29,880 ARE FOUND OUTSIDE OF THE 808 00:28:29,880 --> 00:28:31,280 CHROMOSOME WHICH ARE BASICALLY, 809 00:28:31,280 --> 00:28:32,920 THEY'RE OWN SEGREGATED AND THEY 810 00:28:32,920 --> 00:28:35,320 CAN ACCUMULATE IN LARGE NUMBERS 811 00:28:35,320 --> 00:28:36,120 WITHIN SINGLE--WITHIN SINGLE 812 00:28:36,120 --> 00:28:39,160 CELLS AND THUS DRIVING HUGE 813 00:28:39,160 --> 00:28:40,960 AMOUNTS OF EPITHELIAL RAMIEWROR 814 00:28:40,960 --> 00:28:43,160 HETEROGENEITY, AND WE ALSO 815 00:28:43,160 --> 00:28:43,880 FOCUSED ON THE DETERMINANTS AND 816 00:28:43,880 --> 00:28:45,360 WE FOUND THAT THE TUMOR 817 00:28:45,360 --> 00:28:47,560 MICROENVIRONMENT CAN SHAPE THE 818 00:28:47,560 --> 00:28:49,200 SMALL CELL LUNG CANCER SUBTYPES 819 00:28:49,200 --> 00:28:52,000 BUT I KOANT GO INTO THE DETAILS 820 00:28:52,000 --> 00:28:56,040 BUT BOTTOM LINE THIS IS TUMOR 821 00:28:56,040 --> 00:28:56,640 INTRINSIC DEEMERGINGINANTS OF 822 00:28:56,640 --> 00:28:58,320 HETEROGENEITY AND SO HERE'S THE 823 00:28:58,320 --> 00:29:02,080 DNA LOOKS AND SO THESE ARE MYC 824 00:29:02,080 --> 00:29:12,520 CHROME SOLEAL DNA HERE AND 825 00:29:12,920 --> 00:29:15,520 EDCNA, AND WE FIND THAT THE 826 00:29:15,520 --> 00:29:16,960 MECHANISM OF MYC AMPLIFICATION 827 00:29:16,960 --> 00:29:21,880 BY THE EXTRA CHROME SOLEAL DNA 828 00:29:21,880 --> 00:29:23,640 AND IT REALLY MATTERS BECAUSE IN 829 00:29:23,640 --> 00:29:25,640 PATIENTS WITH COMPLEX EXTRA 830 00:29:25,640 --> 00:29:27,000 CHROMOSOMAL DNA THEY SURVIVE 831 00:29:27,000 --> 00:29:28,280 MUCH LESS TO PATIENTS WITH 832 00:29:28,280 --> 00:29:30,200 TUMORS THAT DON'T HAVE EXTRA 833 00:29:30,200 --> 00:29:30,600 CHROMOSOMAL DNA. 834 00:29:30,600 --> 00:29:33,240 AND THIS IS A PATIENT WHO WE 835 00:29:33,240 --> 00:29:34,480 PERFORMED RAPID AUTOPSIES AND WE 836 00:29:34,480 --> 00:29:38,600 FIND THAT WITHIN THIS PATIENT 837 00:29:38,600 --> 00:29:40,760 MULTIPLE METASTATIC SITES HAD 838 00:29:40,760 --> 00:29:44,320 DISTINCT MECHANISMS OF EXTRA 839 00:29:44,320 --> 00:29:45,040 CHROMOSOMAL DNA AMPLIFICATION 840 00:29:45,040 --> 00:29:47,800 AND, YOU CAN SEE THAT IT'S EXTRA 841 00:29:47,800 --> 00:29:49,200 CHROMOSOMAL AND THAT HAS 842 00:29:49,200 --> 00:29:50,640 CONSEQUENCES IN TERMS OF 843 00:29:50,640 --> 00:29:52,240 TRANSCRIPTIONAL PHENOTYPE AND WE 844 00:29:52,240 --> 00:29:53,320 FIND THAT THERE ARE APPROACHES 845 00:29:53,320 --> 00:29:55,520 THAT YOU CAN USE TO 846 00:29:55,520 --> 00:29:57,800 NONINVASIVELY DETECT THESE SMALL 847 00:29:57,800 --> 00:30:00,760 CELL LUNG CANCER TRANSCRIPTIONAL 848 00:30:00,760 --> 00:30:01,880 SUBTYPES FROM PLASMA. 849 00:30:01,880 --> 00:30:02,960 AGAIN IT'S A CHALLENGE TO GET 850 00:30:02,960 --> 00:30:05,680 THESE PATIENTS BIOPSIES SO WE'RE 851 00:30:05,680 --> 00:30:09,280 LOOKING AT TRANSCRIPTION START 852 00:30:09,280 --> 00:30:11,600 SITE, HISTONE MARKS INSERTING 3 853 00:30:11,600 --> 00:30:14,080 DNA AND WE FIND COMPARED TO 854 00:30:14,080 --> 00:30:15,920 TUMOR RNA SEQUENCING WE FIND 855 00:30:15,920 --> 00:30:16,720 THERE'S GOOD CORRELATION BETWEEN 856 00:30:16,720 --> 00:30:19,600 INFORMATION WE DEVELOP FROM THE 857 00:30:19,600 --> 00:30:21,920 TUMOR RNA SEQ, FOR THE 858 00:30:21,920 --> 00:30:22,960 TRANSCRIPTION FACTORS, D1 AS 859 00:30:22,960 --> 00:30:30,400 WELL AS PLASMA CIRCULATING DNA 860 00:30:30,400 --> 00:30:30,920 IN CHIP-SEQ. 861 00:30:30,920 --> 00:30:33,000 SO WE FIND THIS IS A SINGLE 862 00:30:33,000 --> 00:30:35,200 STATE TEASE NOW BUT IT'S 863 00:30:35,200 --> 00:30:37,640 MULTIPLE DISEASES, THERE ARE 864 00:30:37,640 --> 00:30:38,880 MULTIPLE VULNERABILITIES, WE 865 00:30:38,880 --> 00:30:40,200 IDENTIFIED GERM LINE SMALL CELL 866 00:30:40,200 --> 00:30:43,080 LUNG CANCER WHICH IS UNIQUE 867 00:30:43,080 --> 00:30:44,960 VULNERABLES AND WE FOCUS ON 868 00:30:44,960 --> 00:30:48,800 NOVEL SUBSETS, THE DRIVERS OF 869 00:30:48,800 --> 00:30:49,640 HETEROGENEITY AND NONINVASIVELY 870 00:30:49,640 --> 00:30:51,720 IDENTIFYING THESE IN PLASMA, 871 00:30:51,720 --> 00:30:56,960 AGAIN, THANK YOU FOR YOUR 872 00:30:56,960 --> 00:30:58,600 ATTENTION. 873 00:30:58,600 --> 00:30:59,960 YEAH, THIS IS PEOPLE FROM MY 874 00:30:59,960 --> 00:31:01,280 CLINICAL GROUP AND MY LAB AND A 875 00:31:01,280 --> 00:31:03,720 BIG THANKS TO THEM AND ALL OF 876 00:31:03,720 --> 00:31:04,880 YOU. 877 00:31:04,880 --> 00:31:13,360 [ APPLAUSE ] 878 00:31:13,360 --> 00:31:17,440 >>SO OBVIOUSLY 879 00:31:17,440 --> 00:31:21,520 WE HAVE 2 INCREDIBLE TENURE 880 00:31:21,520 --> 00:31:23,040 TRACK SCHOLARS HERE TO REAL HE 881 00:31:23,040 --> 00:31:24,680 HELP ANSWER YOUR QUESTIONS ABOUT 882 00:31:24,680 --> 00:31:26,280 WHAT THEIR PATH WAS LIKE GOING 883 00:31:26,280 --> 00:31:28,680 FROM BEING A FELLOW JUST LIKE 884 00:31:28,680 --> 00:31:30,320 YOU IN THE NIH FELLOWSHIP 885 00:31:30,320 --> 00:31:32,640 PROGRAMS AND THEN MOVING ON TO 886 00:31:32,640 --> 00:31:33,400 THESE INCREDIBLE RESEARCH 887 00:31:33,400 --> 00:31:34,560 CAREERS SO I WANT TO THANK YOU 888 00:31:34,560 --> 00:31:35,600 BOTH FIRST FOR SHARING YOUR 889 00:31:35,600 --> 00:31:37,360 RESEARCH AND THE SCIENCE BEHIND 890 00:31:37,360 --> 00:31:37,720 YOUR WORK. 891 00:31:37,720 --> 00:31:39,880 YOU BOTH HAVE DEVELOPED RESEARCH 892 00:31:39,880 --> 00:31:42,600 LABS THAT SPAN BASIC TO CLINICAL 893 00:31:42,600 --> 00:31:45,160 INTERVENTIONS, SO I REALLY THINK 894 00:31:45,160 --> 00:31:47,040 YOUR EXAMPLES OF WHAT WE JUST 895 00:31:47,040 --> 00:31:47,800 CALL TRUE TRANSLATIONAL 896 00:31:47,800 --> 00:31:49,160 RESEARCHERS AND I THINK THAT'S A 897 00:31:49,160 --> 00:31:50,520 WONDERFUL THING THAT YOU 898 00:31:50,520 --> 00:31:51,080 ACCOMPLISHED. 899 00:31:51,080 --> 00:31:53,720 AND IT IS NOTABLE THAT YOU BOTH 900 00:31:53,720 --> 00:31:54,760 COMPLETED YOUR FELLOWSHIPS HERE 901 00:31:54,760 --> 00:31:57,520 AND HAVE GONE ON TO CONTINUE 902 00:31:57,520 --> 00:32:00,440 YOUR RESEARCH CAREER IN THE 903 00:32:00,440 --> 00:32:03,520 INTRAMURAL PROGRAM AND THEY 904 00:32:03,520 --> 00:32:04,560 MIGHT--THE NEW FELLOWS MIGHT 905 00:32:04,560 --> 00:32:07,960 KNOW WHAT A LASKER OR CLINICAL 906 00:32:07,960 --> 00:32:09,120 FELLOWS SCHOLAR IS, SOMETHING WE 907 00:32:09,120 --> 00:32:10,840 MIGHT TALK ABOUT BUT I'M SURE 908 00:32:10,840 --> 00:32:11,920 THE FELLOWS WILL WANT TO KNOW 909 00:32:11,920 --> 00:32:14,400 MORE ABOUT YOU AND YOUR GABBING 910 00:32:14,400 --> 00:32:16,800 GROUND SO WE CAN START THE PANEL 911 00:32:16,800 --> 00:32:17,080 DISCUSSION. 912 00:32:17,080 --> 00:32:18,920 OKAY, SO FIRST OF ALL, YOU GO IN 913 00:32:18,920 --> 00:32:19,840 WHATEVER ORDER YOU WANT BUT 914 00:32:19,840 --> 00:32:22,040 PLEASE TELL US A LITTLE BIT 915 00:32:22,040 --> 00:32:23,800 YOURSELF, YOUR BACKGROUND, 916 00:32:23,800 --> 00:32:25,440 PERHAPS YOUR FAMILY, WHERE YOU 917 00:32:25,440 --> 00:32:35,800 WERE BORN AND GREW UP. 918 00:32:44,520 --> 00:32:46,520 >>YEAH, SO I GREW UP IN INDIA, 919 00:32:46,520 --> 00:32:48,520 I WAS BORN AND RAISED IN THE 920 00:32:48,520 --> 00:32:58,720 SOUTH OF INDIA IN A PLACE KAWED 921 00:32:58,720 --> 00:33:02,560 [INAUDIBLE ], I STARTED MEDICAL 922 00:33:02,560 --> 00:33:03,400 SCHOOL IN 96. 923 00:33:03,400 --> 00:33:06,600 AND I COMPLETED A POST GRADUATE 924 00:33:06,600 --> 00:33:07,760 TRAINING IN INTERNAL MEDICINE AT 925 00:33:07,760 --> 00:33:09,960 THE SAME INSTITUTE I DID MY 926 00:33:09,960 --> 00:33:12,960 MEDICAL SCHOOL SO FOR 10 YEAR I 927 00:33:12,960 --> 00:33:14,760 WAS IN BANG LOR, I CAME TO THE 928 00:33:14,760 --> 00:33:16,960 U.S., I DID MY RESIDENCY IN 929 00:33:16,960 --> 00:33:18,240 UPSTATE NEW YORK AND SYRACUSE 930 00:33:18,240 --> 00:33:20,800 AND THEN I CAME HERE IN 2010. 931 00:33:20,800 --> 00:33:22,560 SO BEEN A BIT ALL OVER THE PLACE 932 00:33:22,560 --> 00:33:23,960 AND HERE I AM. 933 00:33:23,960 --> 00:33:26,440 >>I AM CURIOUS WHAT MOTIVATED 934 00:33:26,440 --> 00:33:28,480 YOU TO MOVE FROM INDIA TO THE 935 00:33:28,480 --> 00:33:28,800 U.S.? 936 00:33:28,800 --> 00:33:30,240 >>YEAH, THE BIG MOTIVATION WAS 937 00:33:30,240 --> 00:33:35,680 TO TRY TO DO SOMETHING JUST 938 00:33:35,680 --> 00:33:36,440 BEYOND CLINICAL MEDICINE. 939 00:33:36,440 --> 00:33:39,120 SO WE DEVELOPED A LOT OF 940 00:33:39,120 --> 00:33:39,960 OUTSTANDING CLINICAL SKILLS AND 941 00:33:39,960 --> 00:33:41,960 THAT WAS MOSTLY BECAUSE OF LACK 942 00:33:41,960 --> 00:33:44,360 OF DIAGNOSTIC EQUIPMENT WHICH 943 00:33:44,360 --> 00:33:46,680 WAS NOT, YOU KNOW--THINGS HAVE 944 00:33:46,680 --> 00:33:51,800 IMPROVED NOW BUT IT WAS NOT AS 945 00:33:51,800 --> 00:33:52,200 GREAT. 946 00:33:52,200 --> 00:33:54,680 WE WERE VERY GREAT AT DIAGNOSING 947 00:33:54,680 --> 00:33:56,080 SYMPTOMS AND THINGS BUT NOT 948 00:33:56,080 --> 00:33:57,240 REALLY GREAT ABOUT DOING MUCH 949 00:33:57,240 --> 00:33:59,840 ABOUT IT AND I THINK THERE WAS 950 00:33:59,840 --> 00:34:00,760 ALWAYS THIS MOTIVATION TO TRY 951 00:34:00,760 --> 00:34:02,720 AND DO SOMETHING MORE THAN JUST 952 00:34:02,720 --> 00:34:03,600 CLINICAL MEDICINE AND I THOUGHT, 953 00:34:03,600 --> 00:34:06,400 YOU KNOW THIS WAS REALLY A GREAT 954 00:34:06,400 --> 00:34:07,440 PLACE, ACTUALLY THE FIRST TIME I 955 00:34:07,440 --> 00:34:10,200 CAME TO THE U.S. WAS IN 2005. 956 00:34:10,200 --> 00:34:14,960 IT WAS ACTUALLY FOR APLASTIC 957 00:34:14,960 --> 00:34:17,080 ANEMIA AND MDS CONFERENCE WHICH 958 00:34:17,080 --> 00:34:18,440 DR. NEAL YOUNG ORGANIZED DOWN IN 959 00:34:18,440 --> 00:34:20,560 D. C. SO I COME WITH MY POSTER 960 00:34:20,560 --> 00:34:24,000 BASICALLY WHICH WAS LOOKING AT 961 00:34:24,000 --> 00:34:26,200 LOW DOSE OF CYCLOSPORIN FOR 962 00:34:26,200 --> 00:34:27,200 PATIENTS WITH APLASTIC ANEMIA 963 00:34:27,200 --> 00:34:29,240 AND YOU KNOW I THOUGHT IT WAS 964 00:34:29,240 --> 00:34:30,800 GREAT STUFF BUT WHEN I CAME HERE 965 00:34:30,800 --> 00:34:32,200 I REALIZED JUST THE AMOUNT OF 966 00:34:32,200 --> 00:34:36,840 WORK THAT WAS BEING DONE AND SO 967 00:34:36,840 --> 00:34:38,360 FORTH, SO, 15, THE REAL 968 00:34:38,360 --> 00:34:39,440 MOTIVATION WAS TO TRY TO DO 969 00:34:39,440 --> 00:34:40,600 SOMETHING MORE AND YOU KNOW TRY 970 00:34:40,600 --> 00:34:41,680 TO LEARN SOMETHING MORE ABOUT 971 00:34:41,680 --> 00:34:45,800 THE DISEASE AND DO SOMETHING 972 00:34:45,800 --> 00:34:46,000 MORE. 973 00:34:46,000 --> 00:34:47,720 >>OKAY, SO WOULD YOU LIKE TO 974 00:34:47,720 --> 00:34:49,240 SPEAK TO THAT TOO? 975 00:34:49,240 --> 00:34:50,680 >>SURE, I GREW UP IN SAN JOSE, 976 00:34:50,680 --> 00:34:52,560 MY FATHER WAS A DOCTOR SO I 977 00:34:52,560 --> 00:34:55,720 PRETTY MUCH ALWAYS KNEW I WANTED 978 00:34:55,720 --> 00:34:57,040 TO BE A DOCTOR, I WORKED WITH 979 00:34:57,040 --> 00:34:59,520 HIM IN HIS CLINIC AND I GOT 980 00:34:59,520 --> 00:35:00,800 INTERESTED IN SICKLE CELL 981 00:35:00,800 --> 00:35:01,600 DISEASE IN COLLEGE. 982 00:35:01,600 --> 00:35:03,240 SO I KNEW PRETTY MUCH EARLY ON, 983 00:35:03,240 --> 00:35:05,320 MOST PEOPLE ARE NOT LIKELY BUT I 984 00:35:05,320 --> 00:35:07,240 PRETTY MUCH NEW EARLY ON I WAS 985 00:35:07,240 --> 00:35:08,280 INTERESTED IN SICKLE CELL JUST 986 00:35:08,280 --> 00:35:11,560 BECAUSE I READ ABOUT IT AND I 987 00:35:11,560 --> 00:35:12,720 SAW IT AS SOMEWHERE WHERE I 988 00:35:12,720 --> 00:35:14,480 COULD MAKE A DIFFERENCE. 989 00:35:14,480 --> 00:35:16,840 FROM WHAT I READ, IT SEEMED LIKE 990 00:35:16,840 --> 00:35:19,320 THE PATIENTS WEREN'T BEING 991 00:35:19,320 --> 00:35:20,920 TREATED PROPERLY AND I--SO AFTER 992 00:35:20,920 --> 00:35:24,920 MY FIRST YEAR OF MEDICAL SCHOOL, 993 00:35:24,920 --> 00:35:26,680 I WORKED IN A LAB AND REALIZED 994 00:35:26,680 --> 00:35:29,760 THE LAB WAS NOT THE PLACE FOR ME 995 00:35:29,760 --> 00:35:31,360 BUT I REALLY LOVE SEEING THE 996 00:35:31,360 --> 00:35:32,640 PATIENTS WITH THEM IN CLINIC SO 997 00:35:32,640 --> 00:35:36,080 I WENT TO A MEDICAL SCHOOL 998 00:35:36,080 --> 00:35:36,800 CONFERENCE, I GUESS DURING MY 999 00:35:36,800 --> 00:35:38,320 THIRD YEAR OF MEDICAL SCHOOL AND 1000 00:35:38,320 --> 00:35:40,040 I MET KENNY WILLIAMS AND HE TOLD 1001 00:35:40,040 --> 00:35:41,720 ME ABOUT THE NIH AND TOLD ME 1002 00:35:41,720 --> 00:35:43,960 ABOUT THE CLINICAL RESEARCH 1003 00:35:43,960 --> 00:35:44,800 TRAINING PROGRAM AND THE 1004 00:35:44,800 --> 00:35:46,280 CLINICAL RESEARCH WAS IN THE 1005 00:35:46,280 --> 00:35:50,000 NAME, I WAS REALLY INTRIGUED SO 1006 00:35:50,000 --> 00:35:52,240 I CAME HERE AND YOU SEE 1 OF THE 1007 00:35:52,240 --> 00:35:53,720 PROJECTS I WORKED ON, IT WAS 1008 00:35:53,720 --> 00:35:55,520 FROM A CAREER STANDPOINT 1 OF 1009 00:35:55,520 --> 00:35:57,760 THE MOST LIFE TRANSFORMING YEARS 1010 00:35:57,760 --> 00:35:58,720 FOR ME. 1011 00:35:58,720 --> 00:36:00,960 I REALLY LOVED BEING AT THE NIH, 1012 00:36:00,960 --> 00:36:03,960 I LOVED WORKING WITH JOHN 1013 00:36:03,960 --> 00:36:06,400 TISDALE, AND JUST, IT WAS JUST 1014 00:36:06,400 --> 00:36:08,240 AN INCREDIBLE EXPERIENCE. 1015 00:36:08,240 --> 00:36:10,840 SO I WENT, FINISHED MEDICAL 1016 00:36:10,840 --> 00:36:12,840 SCHOOL, DID MED PEDS AND WHEN I 1017 00:36:12,840 --> 00:36:14,840 CAME BACK AND FINISHED MY 2 1018 00:36:14,840 --> 00:36:18,480 CLINICAL YEARS ON AN ADULT 1019 00:36:18,480 --> 00:36:19,880 HEMEATOLOGY AND PEDEIAT 1020 00:36:19,880 --> 00:36:20,480 HEMEATOLOGY AND ONCOLOGY I 1021 00:36:20,480 --> 00:36:22,280 LOOKED BA BEING TO JOHNS LAB AND 1022 00:36:22,280 --> 00:36:23,360 THE PROTOCOL WAS WORKING REALLY 1023 00:36:23,360 --> 00:36:24,560 WELL AND IT WAS EXCITING BUT 1024 00:36:24,560 --> 00:36:25,760 THERE WERE A LOT OF PATIENTS WE 1025 00:36:25,760 --> 00:36:27,080 WERE HAVING TO TURN AWAY BECAUSE 1026 00:36:27,080 --> 00:36:30,120 THEY DIDN'T HAVE A DONOR. 1027 00:36:30,120 --> 00:36:32,360 SO, JOHN SAID WHY DON'T YOU WORK 1028 00:36:32,360 --> 00:36:34,160 ON DEVELOPING THIS HAPPEN LO 1029 00:36:34,160 --> 00:36:35,560 IDENTICAL APPROACH. 1030 00:36:35,560 --> 00:36:37,920 SO AS I SAID, I WAS A PI ON THE 1031 00:36:37,920 --> 00:36:39,720 PROT COLAND WITH HIM AS A FELLOW 1032 00:36:39,720 --> 00:36:41,240 FOR 5 YEARS AND I CAME TO THE 1033 00:36:41,240 --> 00:36:42,840 NIH BECAUSE I WANTED TO WORK 1034 00:36:42,840 --> 00:36:44,840 WITH JOHN, I WANTED TO BE HIS 1035 00:36:44,840 --> 00:36:46,280 STAFF CLINICIAN BUT WHEN I 1036 00:36:46,280 --> 00:36:48,160 FINISHED MY 5 YEARS THAT WAS THE 1037 00:36:48,160 --> 00:36:49,000 MAXIMUM TIME YOU CHRONIC LIVER 1038 00:36:49,000 --> 00:36:50,040 DISEASE DO THAT, HE DIDN'T HAVE 1039 00:36:50,040 --> 00:36:51,480 I POSITION FOR ME SO THATTA WHEN 1040 00:36:51,480 --> 00:36:53,080 I LEARNED ABOUT THE ASSISTED 1041 00:36:53,080 --> 00:36:53,840 CLINICAL INVESTIGATOR AND THAT 1042 00:36:53,840 --> 00:36:55,400 WAS HOW THE DOOR OPENED FOR ME. 1043 00:36:55,400 --> 00:36:56,480 I NEVER WOULD HAVE THOUGHT I 1044 00:36:56,480 --> 00:36:58,080 WOULD HAVE HAD MY OWN LAB, THAT 1045 00:36:58,080 --> 00:37:01,680 WAS NOT ON MYRA DART--DARTH AT 1046 00:37:01,680 --> 00:37:03,320 ALL, SO, YEAH, BUT I REALLY 1047 00:37:03,320 --> 00:37:04,720 LOVED BEING IN ACI AND BEING 1048 00:37:04,720 --> 00:37:06,160 ABLING TO MAKE DECISIONS ON MY 1049 00:37:06,160 --> 00:37:08,000 OWN AND BE RESPONSIBLE FOR THE 1050 00:37:08,000 --> 00:37:11,000 TRAJECTORY AND GROW TO REALLY 1051 00:37:11,000 --> 00:37:13,200 LOVE MENTORING STUDENTS, SO 1052 00:37:13,200 --> 00:37:18,080 THAT'S WHY I WENT ON TO THE 1053 00:37:18,080 --> 00:37:18,320 LASKER. 1054 00:37:18,320 --> 00:37:20,440 >>YOU KNOW, CAN YOU REFLECT A 1055 00:37:20,440 --> 00:37:21,800 BIT ON YOUR SUBSPECIALTY 1056 00:37:21,800 --> 00:37:27,480 TRAINING HERE AT NIH AND COULD 1057 00:37:27,480 --> 00:37:29,200 YOU REFLECT ON HOW IT MIGHT HAVE 1058 00:37:29,200 --> 00:37:31,160 SET YOU UP TO BE A RESEARCHER 1059 00:37:31,160 --> 00:37:32,720 LIKE YOU ARE, NOW DID THAT WORK 1060 00:37:32,720 --> 00:37:33,680 FOR YOU AND MORE DETAILS ABOUT 1061 00:37:33,680 --> 00:37:37,000 WHAT YOU DID EACH YEAR AND 1062 00:37:37,000 --> 00:37:38,760 PERHAPS LIKE TURNING POINTS? 1063 00:37:38,760 --> 00:37:41,160 >>YEAH, YOU KNOW WHEN I WAS 1064 00:37:41,160 --> 00:37:43,440 DOING MY RESIDENCY IN SYRACUSE I 1065 00:37:43,440 --> 00:37:44,840 HAD KNOWN ABOUT NIH AND THE 1066 00:37:44,840 --> 00:37:45,600 TRAINING PROGRAM HERE. 1067 00:37:45,600 --> 00:37:49,720 I WORKED IN A LAB, AND A MENTOR 1068 00:37:49,720 --> 00:37:51,480 AT THAT TIME HERE HAD HIS 1069 00:37:51,480 --> 00:37:56,440 FELLOWSHIP AT NIH IN THE LATE 1070 00:37:56,440 --> 00:37:59,280 1970S. 1071 00:37:59,280 --> 00:38:02,480 HE WAS ACTUALLY A BIG PLAYER IN 1072 00:38:02,480 --> 00:38:04,520 THE DISCOVERY OF HDLB1 AND HE 1073 00:38:04,520 --> 00:38:06,520 HAD A PAPER IN 1981 ON THE 1074 00:38:06,520 --> 00:38:09,520 SECOND DAY OF HIS FELLOWSHIP 1075 00:38:09,520 --> 00:38:12,720 WHERE HE DISCOVERED HDLB1, IN A 1076 00:38:12,720 --> 00:38:16,160 NEW VIRUS IN PATIENTS WITH 1077 00:38:16,160 --> 00:38:19,760 [INDISCERNIBLE] SYNDROME, CUE 1078 00:38:19,760 --> 00:38:20,960 TAINIOUS T-CELL, BUT WHEN I DID 1079 00:38:20,960 --> 00:38:21,800 COME, I HAD THE EXPERIENCE IN 1080 00:38:21,800 --> 00:38:23,480 THE LAB AND I HAD ALL THE 1081 00:38:23,480 --> 00:38:24,960 CLINICAL EXPERIENCE BUT REALLY 1082 00:38:24,960 --> 00:38:25,880 NO EXPERIENCE ABOUT CLINICAL 1083 00:38:25,880 --> 00:38:30,440 TRIALS OR WHAT CLINICAL RESEARCH 1084 00:38:30,440 --> 00:38:33,880 IS, REALLY A TOTAL NEWBIE IN 1085 00:38:33,880 --> 00:38:35,200 THAT AREA, BUT REALLY THE 3 1086 00:38:35,200 --> 00:38:38,280 YEARS AT NIH AND I DID 6 MONTHS 1087 00:38:38,280 --> 00:38:40,760 OF MY HEMEATOLOGY TRAINING, TOO, 1088 00:38:40,760 --> 00:38:42,120 REALLY TRANSFORMED BY VIEW OF 1089 00:38:42,120 --> 00:38:44,440 CLINICAL RESEARCH AND I GOT AN 1090 00:38:44,440 --> 00:38:46,200 OPPORTUNITY TO WRITE A LOT OF 1091 00:38:46,200 --> 00:38:47,280 CLINICAL PROTOCOLS, AND I THINK 1092 00:38:47,280 --> 00:38:48,560 THAT WAS REALLY THE BASIC 1093 00:38:48,560 --> 00:38:49,760 TRAINING THAT I HAD WRITING A 1094 00:38:49,760 --> 00:38:52,200 LOT OF CLINICAL TRIALS. 1095 00:38:52,200 --> 00:38:54,160 I WAS INVOLVED IN A LOT OF 1096 00:38:54,160 --> 00:38:57,640 TRANSLATIONAL STUDIES, SO I FEEL 1097 00:38:57,640 --> 00:38:58,720 LIKE THE 3 YEARS WERE CRITICAL 1098 00:38:58,720 --> 00:39:00,280 AND WE HAD A LOT OF IMPORTANT 1099 00:39:00,280 --> 00:39:01,240 STUDIES SOPHISTICATEDY WOO HAD 1 1100 00:39:01,240 --> 00:39:02,720 OF THE FIRST PRECISION ONCOLOGY 1101 00:39:02,720 --> 00:39:05,880 STUDIES WHERE WE LOOK ATA BIOPSY 1102 00:39:05,880 --> 00:39:07,160 PATIENT, LOOK AT PATIENTS 1103 00:39:07,160 --> 00:39:08,520 MUTATION AND ASSIGN THEM A 1104 00:39:08,520 --> 00:39:09,720 PARTICULAR TREATMENT AND EVEN 1105 00:39:09,720 --> 00:39:11,560 NOW THOSE CLINICAL TRIALS HAVE 1106 00:39:11,560 --> 00:39:13,240 BEEN DONE, THOSE LARGE NCI 1107 00:39:13,240 --> 00:39:14,320 CLINICAL TRIALS BUT WE WERE 1 OF 1108 00:39:14,320 --> 00:39:16,400 THE FIRST TO DO A CLINICAL 1109 00:39:16,400 --> 00:39:17,960 TRIALS AND WE ENROLLED OVER 350 1110 00:39:17,960 --> 00:39:20,000 PATIENTINGS IN A 2 YORE TIME 1111 00:39:20,000 --> 00:39:23,200 FRAME IN A CLINICAL TRIAL, DISP 1112 00:39:23,200 --> 00:39:24,880 THIS WAS--YOU KNOW SO I GOT 1113 00:39:24,880 --> 00:39:26,480 REALLY COMFORTABLE WITH DOING 1114 00:39:26,480 --> 00:39:26,920 CLINICAL TRIALS. 1115 00:39:26,920 --> 00:39:29,200 TAKING CARE OF PATIENTS AND 1116 00:39:29,200 --> 00:39:30,240 ANOTHER IMPORTANT TRIAL WE DID 1117 00:39:30,240 --> 00:39:35,880 WAS, YOU KNOW LOOKING AT THYMIC 1118 00:39:35,880 --> 00:39:37,160 CARCINOMAS, THORACIC CANCERS 1119 00:39:37,160 --> 00:39:39,320 ORPHAN CANCERS BUT NOT MUCH 1120 00:39:39,320 --> 00:39:40,280 OPTION THERAPY AFTER CANCER 1121 00:39:40,280 --> 00:39:42,080 RELAPSE AND WE DID 1 OF THE 1122 00:39:42,080 --> 00:39:46,360 FIRST TRIALS OF KINASE 1123 00:39:46,360 --> 00:39:46,880 INHIBITORS PARTICULARLY 1124 00:39:46,880 --> 00:39:47,120 SEROTINIB. 1125 00:39:47,120 --> 00:39:49,680 I WAS VERY HAPPY BECAUSE OUR 1126 00:39:49,680 --> 00:39:52,800 TRIAL LED TO THAT BEING INCLUDED 1127 00:39:52,800 --> 00:39:54,760 IN THE NCC GUIDELINES TO TREAT 1128 00:39:54,760 --> 00:39:57,240 PATIENTS SO VERY HAPPY THAT THAT 1129 00:39:57,240 --> 00:39:59,600 LED TO, YOU KNOW A PRACTICE 1130 00:39:59,600 --> 00:40:00,400 CHANGING CLINICAL TRIAL THAT I 1131 00:40:00,400 --> 00:40:01,960 WAS ABLE TO BE PART OF THAT. 1132 00:40:01,960 --> 00:40:05,440 SO, AGAIN, IT WAS A REAL, YOU 1133 00:40:05,440 --> 00:40:07,480 KNOW WONDERFUL PERIOD, A LOT OF 1134 00:40:07,480 --> 00:40:08,840 WORK, BUT YOU ARE INVOFFED WITH 1135 00:40:08,840 --> 00:40:10,400 A LOT OF EXCITING PROJECTS AND 1136 00:40:10,400 --> 00:40:12,680 DOG A LOT OF INTERESTING STUFF. 1137 00:40:12,680 --> 00:40:14,160 >>AND YOU'RE SAYING THIS IS 1138 00:40:14,160 --> 00:40:16,880 WHILE YOU'RE STILL A FELLOW. 1139 00:40:16,880 --> 00:40:17,280 >>INCREDIBLE. 1140 00:40:17,280 --> 00:40:18,480 >>YEAH, IT JUST SPEAKS TO THE 1141 00:40:18,480 --> 00:40:21,920 OPPORTUNITIES THAT ARE AVAILABLE 1142 00:40:21,920 --> 00:40:23,760 HERE LIKE I SAID EARLIER, THE 1143 00:40:23,760 --> 00:40:25,320 ABILITY TO DO BIOPSIES IN 1144 00:40:25,320 --> 00:40:28,720 PATIENTS THAT YOU CANNOT BIOPSY 1145 00:40:28,720 --> 00:40:33,400 ANYWHERE ELSE BECAUSE OF THE 1146 00:40:33,400 --> 00:40:38,320 INFRASTRUCTURE AND SO I THINK 1147 00:40:38,320 --> 00:40:38,760 IT'S, YEAH. 1148 00:40:38,760 --> 00:40:40,800 >>SO FOR ME IT WAS FUNNY 1149 00:40:40,800 --> 00:40:42,440 BECAUSE I NEVER--IT WAS NEVER ON 1150 00:40:42,440 --> 00:40:44,240 MYRA DART--DARTH TO HAVE A LAB 1151 00:40:44,240 --> 00:40:45,400 HERE, THINGS WERE HAPPENING THAT 1152 00:40:45,400 --> 00:40:47,040 WERE TRAINING ME, EVEN WHEN I 1153 00:40:47,040 --> 00:40:49,240 WAS A SUBMITTAL STUDENT WOB OF 1154 00:40:49,240 --> 00:40:51,080 MY OTHER PROJECTS WAS A WROTE A 1155 00:40:51,080 --> 00:40:55,280 BIG CLINICAL PROTEIN COMPLEX C 1156 00:40:55,280 --> 00:40:56,480 OT--PROTOCOL AND I WAS ABLE TO 1157 00:40:56,480 --> 00:40:58,120 PRESENTED TO THE VERMEN INFECTED 1158 00:40:58,120 --> 00:40:59,960 VIEW BIEWRD, CONTACTED THE FDA, 1159 00:40:59,960 --> 00:41:01,280 GOD PERMISSION TO MOVE FORWARD 1160 00:41:01,280 --> 00:41:02,360 AND STARTED RECRUITING PATIENTS 1161 00:41:02,360 --> 00:41:03,560 AND UNFORT MATILY THE DRUG WE 1162 00:41:03,560 --> 00:41:08,120 WERE GOING IT USE IN OUR DRUG 1163 00:41:08,120 --> 00:41:08,800 POPULATION, CAUSED ANNA FLACKSIC 1164 00:41:08,800 --> 00:41:10,320 REACTION IN ANOTHER POPULATION 1165 00:41:10,320 --> 00:41:11,760 SO I WASN'T ABLE TO DO IT BUT I 1166 00:41:11,760 --> 00:41:12,680 HAD THAT EXPERIENCE AND THEN 1167 00:41:12,680 --> 00:41:14,680 WHEN I CAME BACK AS A FELLOW, MY 1168 00:41:14,680 --> 00:41:16,640 FIRST 2 YEAR CLINICAL YEARS 1169 00:41:16,640 --> 00:41:20,520 BECAUSE I DID ADULT HEMEATOLOGY 1170 00:41:20,520 --> 00:41:22,960 AND PEDIATRIC HEME ONC, I THINK 1171 00:41:22,960 --> 00:41:25,160 MY FELLOWSHIP WAS BUZZIER, 1172 00:41:25,160 --> 00:41:27,840 DEFINITELY THE OTHER HEMEATOLOGY 1173 00:41:27,840 --> 00:41:28,680 FELLOWS, I WAS ROTATING IN 1174 00:41:28,680 --> 00:41:30,120 DIFFERENT PLACES AND THE SECOND 1175 00:41:30,120 --> 00:41:31,640 YEARA AT HOPKINS FOR THE 1176 00:41:31,640 --> 00:41:33,760 PEDIATRIC YEAR WAS REALLY BUSY 1177 00:41:33,760 --> 00:41:35,160 SO I WASN'TA TO A LOT OF 1178 00:41:35,160 --> 00:41:36,360 RESEARCH DURING THAT TIME BUT 1179 00:41:36,360 --> 00:41:38,480 WHEN I GOT TOWARDS THE END AND I 1180 00:41:38,480 --> 00:41:40,960 KNEW I WAS--I WANTED TO GO BACK 1181 00:41:40,960 --> 00:41:44,200 TO JOHNS LAB, MY MAIN GOAL WAS 1182 00:41:44,200 --> 00:41:46,320 TO DEVELOP THIS HAPPEN LO 1183 00:41:46,320 --> 00:41:47,160 IDENTICAL TRANSPLANT APPROACH 1184 00:41:47,160 --> 00:41:48,320 BUT I ALSO WORKED ON A PROJECT 1185 00:41:48,320 --> 00:41:49,840 THAT WAS GOING TO BE ABLE TO BE 1186 00:41:49,840 --> 00:41:51,400 DONE IN A SHORTER PERIOD OF 1187 00:41:51,400 --> 00:41:51,640 TIME. 1188 00:41:51,640 --> 00:41:55,400 SO I ACTUALLY STARTED PREPARING 1189 00:41:55,400 --> 00:41:58,160 FOR IT AS A SECOND YEAR FELLOW 1190 00:41:58,160 --> 00:41:59,560 SO TOWARDS THE END OF MY 1191 00:41:59,560 --> 00:42:00,680 CLINICAL YEAR, DOG THE 1192 00:42:00,680 --> 00:42:01,760 BACKGROUND READING AND WRITING 1193 00:42:01,760 --> 00:42:02,800 THE PROTOCOL BECAUSE THE 1194 00:42:02,800 --> 00:42:03,720 PROTOCOL TAKES SO LONG TO GO 1195 00:42:03,720 --> 00:42:05,400 THROUGH THE SYSTEM AND I DIDN'T 1196 00:42:05,400 --> 00:42:07,760 WANT TO USE UP A LOT OF MY 1197 00:42:07,760 --> 00:42:08,840 FELLOW TIME WAITING FOR A 1198 00:42:08,840 --> 00:42:09,680 PROTOCOL TO GO THROUGH SO THAT 1199 00:42:09,680 --> 00:42:11,200 WAS 1 THING THAT WAS HELPFUL AND 1200 00:42:11,200 --> 00:42:13,440 THEN AS I SAID, JOHN ALLOWED ME 1201 00:42:13,440 --> 00:42:15,880 TO BE THE PI ON THE HAPPEN LO 1202 00:42:15,880 --> 00:42:16,720 IESHES DENTICAL PROTOCOL SO 1203 00:42:16,720 --> 00:42:18,160 THEREYA A LOT OF 1204 00:42:18,160 --> 00:42:19,840 RESPONSIBILITIES AS A PI AND 1205 00:42:19,840 --> 00:42:22,880 ESPECIALLY AT 1 TIME HOPKINS 1206 00:42:22,880 --> 00:42:24,440 DOING HAPPEN LO IDENTICAL 1207 00:42:24,440 --> 00:42:25,480 TRANSPLANTS IN ADULTS WITH 1208 00:42:25,480 --> 00:42:26,280 SICKLE CELL DISEASE AND WE 1209 00:42:26,280 --> 00:42:28,480 DIDN'T KNOW WHAT THE TOXICITY OR 1210 00:42:28,480 --> 00:42:29,040 EFFICACY COULD BE. 1211 00:42:29,040 --> 00:42:30,320 AND THE GUY THAT HAD THE 1212 00:42:30,320 --> 00:42:34,120 TRANSPLANT AT THE TIME HAD 1213 00:42:34,120 --> 00:42:36,040 TRANSPLAIPTED 10 PATIENT WITH 1214 00:42:36,040 --> 00:42:36,880 LEUKEMIA USE THE HAPPEN LO 1215 00:42:36,880 --> 00:42:38,880 APPROACH AND THEY ALL DIED AND I 1216 00:42:38,880 --> 00:42:41,200 WAS SHOCKED THAT HE ALLOWED ME 1217 00:42:41,200 --> 00:42:43,160 TO BE THE PI BUT I HAD A LOT OF 1218 00:42:43,160 --> 00:42:45,040 SPENCE OF RESPONSIBILITY, I WAS 1219 00:42:45,040 --> 00:42:47,000 THE 1 THAT HAD TO REPORTOT 1220 00:42:47,000 --> 00:42:51,280 PATIENTS AND I HAD TO REPORT THE 1221 00:42:51,280 --> 00:42:52,880 SEs AND AEs, SO THIS 1222 00:42:52,880 --> 00:42:55,320 DEVELOPED ME TO RUN MY OWN LAB 1223 00:42:55,320 --> 00:42:57,240 AND RUNNING THE TRANSLATIONAL 1224 00:42:57,240 --> 00:42:57,560 PROGRAM. 1225 00:42:57,560 --> 00:42:59,840 >>SO I THINK YOU BOTH SPOKE TO 1226 00:42:59,840 --> 00:43:00,600 THE HIGH RISK-HIGH REWARD TRIALS 1227 00:43:00,600 --> 00:43:02,440 THAT I DO HERE, CORRECT AND ALSO 1228 00:43:02,440 --> 00:43:03,760 YOU MENTIONED LIKE THE 1229 00:43:03,760 --> 00:43:04,600 INFRASTRUCTURE HERE, CAN YOU SAY 1230 00:43:04,600 --> 00:43:06,720 A BIT ABOUT HOW THE CLINICAL 1231 00:43:06,720 --> 00:43:07,920 CENTER AND THIS INTRAMURAL 1232 00:43:07,920 --> 00:43:10,120 PROGRAM AND HOW IT RUNS MAYBE 1233 00:43:10,120 --> 00:43:11,520 DIFFERENTLY FROM AN OUTSIDE 1234 00:43:11,520 --> 00:43:12,760 INSTITUTION, HOW DID THAT 1235 00:43:12,760 --> 00:43:14,480 FACILITATE YOUR BEING ABLE TO DO 1236 00:43:14,480 --> 00:43:16,760 YOUR RESEARCH? 1237 00:43:16,760 --> 00:43:18,520 >>I THINK A BIG CRITICAL FACTOR 1238 00:43:18,520 --> 00:43:20,720 IS THE ABILITY TO TAKE CARE OF 1239 00:43:20,720 --> 00:43:22,560 PATIENTS LIKE WITHOUT HAVING TO 1240 00:43:22,560 --> 00:43:24,800 WORRY ABOUT, YOU KNOW THE SOCIAL 1241 00:43:24,800 --> 00:43:26,320 ISSUES OR INSURANCE ISSUES OR 1242 00:43:26,320 --> 00:43:28,200 THINGS LIKE THAT, AND FOR US, 1243 00:43:28,200 --> 00:43:29,600 FOR THE CANCER, LIKE SMALL CELL 1244 00:43:29,600 --> 00:43:32,360 WHICH IS REALLY AGGRESSIVE THAT, 1245 00:43:32,360 --> 00:43:34,240 YOU KNOW TO GIVE THE RESOURCES 1246 00:43:34,240 --> 00:43:36,280 TO THE PATIENTS, SO THAT THEY 1247 00:43:36,280 --> 00:43:38,520 CAN COME HERE QUICKLY, YOU KNOW 1248 00:43:38,520 --> 00:43:40,040 PAYING THEIR COST OF 1249 00:43:40,040 --> 00:43:41,200 TRANSPORTATION AND STUFF LIKE, 1250 00:43:41,200 --> 00:43:42,480 THAT'S FROM THE PATIENT SIDE, 1251 00:43:42,480 --> 00:43:53,000 AND I FEEL LIKE FROM THE FROM A 1252 00:43:53,320 --> 00:43:54,280 MORE BAIVENG AND SCIENTIFIC 1253 00:43:54,280 --> 00:43:55,520 SITE, THAT'S A LOT OF 1254 00:43:55,520 --> 00:43:56,440 COLLABORATION, AND I FEEL LIKE 1255 00:43:56,440 --> 00:43:59,000 THERE ARE LOTS OF UNIVERSITIES 1256 00:43:59,000 --> 00:44:00,280 WHERE THAT HAPPENS BUT I FEEL 1257 00:44:00,280 --> 00:44:01,680 LIKE THERE'S LESS OF A BEIGIER 1258 00:44:01,680 --> 00:44:07,760 TO BRIDGE THESE GAPS BECAUSE YOU 1259 00:44:07,760 --> 00:44:09,760 KNOW PEOPLE ARE NOT STRESSED 1260 00:44:09,760 --> 00:44:10,800 ABOUT THEIR NEXT GRANT. 1261 00:44:10,800 --> 00:44:12,320 THOSE 2 FROM THE PATIENT ANGLE 1262 00:44:12,320 --> 00:44:14,160 AND AS WELL AS FROM THE SCIENCE 1263 00:44:14,160 --> 00:44:16,480 ANGLE IS JUST A LOT OF 1264 00:44:16,480 --> 00:44:16,920 OPPORTUNITIES. 1265 00:44:16,920 --> 00:44:18,000 >>YEAH, THATY A HUGE POINT HE 1266 00:44:18,000 --> 00:44:19,560 MADE, NOT HAVING TO DEAL WITH 1267 00:44:19,560 --> 00:44:20,520 INSURANCE, I THINK ANOTHER THING 1268 00:44:20,520 --> 00:44:24,520 THAT WAS VERY ATTRACTIVE TO ME 1269 00:44:24,520 --> 00:44:25,960 IS THAT IT'S BUSY THE FIRST 2 1270 00:44:25,960 --> 00:44:27,320 CLINICAL YEARS BUT ON THE THIRD 1271 00:44:27,320 --> 00:44:28,960 AND FOURTH YEAR I HAD TIME TO 1272 00:44:28,960 --> 00:44:30,320 FOCUS ON RESEARCH SO THAT WAS A 1273 00:44:30,320 --> 00:44:31,000 HUGE PLUS. 1274 00:44:31,000 --> 00:44:36,800 AS FAR AS RESOURCES AND I CAN 1275 00:44:36,800 --> 00:44:39,600 ONLY SPEAK TO NHLBI, AS FAR AS 1276 00:44:39,600 --> 00:44:40,800 WE'VE GONE, THEY WANT TO GIVE 1277 00:44:40,800 --> 00:44:42,200 YOU THE RESOURCES TO SUCCEED. 1278 00:44:42,200 --> 00:44:44,960 SO I HAVE AND I'VE GOTTEN BUSIER 1279 00:44:44,960 --> 00:44:47,080 I'VE KNOTTEN MORE 1280 00:44:47,080 --> 00:44:47,920 RESEARCH--GOTTEN MORE RESOURCES 1281 00:44:47,920 --> 00:44:49,760 SO I HAVE 2 RESOURCE NURSES, 1282 00:44:49,760 --> 00:44:56,680 ACCESS TO A STATISTICIAN, DATA 1283 00:44:56,680 --> 00:44:57,600 MANAGER, PROTOCOL NAVIGATOR AND 1284 00:44:57,600 --> 00:44:59,600 THEY HELP WITH ANY RESOURCE 1285 00:44:59,600 --> 00:45:05,640 STRESS WTION WRIETDING THE 1286 00:45:05,640 --> 00:45:06,240 PROTOCOL WHAT ELSE? 1287 00:45:06,240 --> 00:45:08,080 THE PEOPLE IN MY LAB BUT AS FAR 1288 00:45:08,080 --> 00:45:10,800 AS THE CLINICAL EXPART GETTING 1289 00:45:10,800 --> 00:45:11,720 THE PROTOCOL THROUGH, THEY 1290 00:45:11,720 --> 00:45:12,680 MONITOR YOUR NEEDS AND GIVE YOU 1291 00:45:12,680 --> 00:45:17,200 THE SUPPORT YOU NEED TO BE 1292 00:45:17,200 --> 00:45:17,480 SUCCESSFUL. 1293 00:45:17,480 --> 00:45:19,520 >>CAN YOU TALK ABOUT THE ROLE 1294 00:45:19,520 --> 00:45:20,800 OF MENTORS IN YOUR TRAINING AND 1295 00:45:20,800 --> 00:45:22,840 ANY ADVICE YOU WOULD GIVE TO THE 1296 00:45:22,840 --> 00:45:25,000 FELLOWS ABOUT MENTORING. 1297 00:45:25,000 --> 00:45:27,360 >>YOU KNOW I HAD MENTORS OVER 1298 00:45:27,360 --> 00:45:28,520 THE COURSE OF MY CAREER, LIKE 1299 00:45:28,520 --> 00:45:30,960 EVEN WHEN I STARTED IN 1300 00:45:30,960 --> 00:45:35,400 INDICATORSIA, AND THEN IN 1301 00:45:35,400 --> 00:45:38,240 UPSTATE NEW YORK, I HAD MENTORS 1302 00:45:38,240 --> 00:45:39,520 DURING MY FELLOWSHIPS. 1303 00:45:39,520 --> 00:45:41,680 OBVIOUSLY THEY HAVE A VERY 1304 00:45:41,680 --> 00:45:42,840 CRITICAL AND CRUCIAL ROLE. 1305 00:45:42,840 --> 00:45:44,920 AND I TRIED TO TAKE THE BEST OF 1306 00:45:44,920 --> 00:45:46,760 ALL OF THESE MENTORS, I THINK 1307 00:45:46,760 --> 00:45:48,280 IT'S EVERYBODY'S WORKING ON 1308 00:45:48,280 --> 00:45:49,480 THEIR MENTORING SKILLS, YOU KNOW 1309 00:45:49,480 --> 00:45:51,240 I DON'T THINK ANYBODY'S PERFECT 1310 00:45:51,240 --> 00:45:56,920 IN ALL ASPECTS, I REALLY TRIED 1311 00:45:56,920 --> 00:45:59,480 TO IMPROVE OR INCORPORATE THESE 1312 00:45:59,480 --> 00:46:02,080 POSITIVE THINGS THAT ARE IN MY 1313 00:46:02,080 --> 00:46:03,800 MENTORING APPROACHES AND I WOULD 1314 00:46:03,800 --> 00:46:05,560 SAY, IN TERMS OF CHOOSING A 1315 00:46:05,560 --> 00:46:07,640 MENTOR, I THINK IT'S IMPORTANT 1316 00:46:07,640 --> 00:46:09,200 TO HAVE, YOU KNOW SOMEONE WHO'S 1317 00:46:09,200 --> 00:46:14,160 ADDRESSING A BIG PROBLEM OR AN 1318 00:46:14,160 --> 00:46:15,360 IMPORTANT PROBLEM. 1319 00:46:15,360 --> 00:46:17,440 AND THAT MAY SEEM TRIVIAL BUT 1320 00:46:17,440 --> 00:46:18,040 IT'S IMPORTANT BECAUSE 1 IT'S 1321 00:46:18,040 --> 00:46:19,240 IMPORTANT TO GET YOU MOTIVATED 1322 00:46:19,240 --> 00:46:22,440 TO DO THE WORK, AND 2 IS, YOU 1323 00:46:22,440 --> 00:46:25,200 KNOW IT MIGHT HELP YOU GET MORE 1324 00:46:25,200 --> 00:46:26,120 OPPORTUNITIES LATER ON, BUT I 1325 00:46:26,120 --> 00:46:28,240 THINK THE QUESTION IS VERY 1326 00:46:28,240 --> 00:46:30,320 IMPORTANT, THAT THE LAB IS 1327 00:46:30,320 --> 00:46:32,440 STUDYING AND IT COULD BE BIG IN 1328 00:46:32,440 --> 00:46:34,320 TERMS OF PATIENTS AFFECTED SO 1329 00:46:34,320 --> 00:46:36,960 FOR EXAMPLE, LUNG CANCER IS A 1330 00:46:36,960 --> 00:46:38,680 COMMON PROBLEM OR PANCREATIC 1331 00:46:38,680 --> 00:46:40,200 CANCER, NOT AS COMMON AS LUNG 1332 00:46:40,200 --> 00:46:41,040 CANCER BUT A BAD PROBLEM. 1333 00:46:41,040 --> 00:46:43,280 SO YOU WANT TO PICK A PROBLEM 1334 00:46:43,280 --> 00:46:44,360 THAT HAS--AT LEAST MY OPINION 1335 00:46:44,360 --> 00:46:46,040 AND MY FEELING IS THAT, YOU KNOW 1336 00:46:46,040 --> 00:46:48,200 THAT AFFECTS A LOT OF PEOPLE 1337 00:46:48,200 --> 00:46:49,440 THAT HAS REALLY AFFECTING 1338 00:46:49,440 --> 00:46:52,120 PATIENTS IN TERMS OF THEIR 1339 00:46:52,120 --> 00:46:53,480 LETHALITY OR MORTALITY, AND I 1340 00:46:53,480 --> 00:46:56,480 THINK IT'S ALSO IMPORTANT TO 1341 00:46:56,480 --> 00:46:58,400 HAVE MENTORS WHO ARE ACCESSIBLE 1342 00:46:58,400 --> 00:47:00,040 BUT AT THE SAME TIME WHO GIVE 1343 00:47:00,040 --> 00:47:01,240 YOU A LOT OF FREEDOM. 1344 00:47:01,240 --> 00:47:03,640 SO YOU DON'T WANT TO BE LIKE A 1345 00:47:03,640 --> 00:47:04,720 CLONE OF YOUR MENTOR, YOU WANT 1346 00:47:04,720 --> 00:47:07,000 TO BE INDEPENDENT, SO I THINK 1347 00:47:07,000 --> 00:47:10,560 BOTH ARE IMPORTANT AND I THINK 1348 00:47:10,560 --> 00:47:13,200 YOU KNOW ALWAYS THINK BEYOND THE 1349 00:47:13,200 --> 00:47:16,000 MENTOR, ALSO TO OTHER PREME IN 1350 00:47:16,000 --> 00:47:16,800 THE LAB BECAUSE YOU'RE NOT 1351 00:47:16,800 --> 00:47:18,200 ALWAYS TALKING TO THE MENTOR, I 1352 00:47:18,200 --> 00:47:19,160 THINK IT'S GOOD TO HAVE 1353 00:47:19,160 --> 00:47:19,800 RELATIONSHIPS WITH OTHER PEOPLE 1354 00:47:19,800 --> 00:47:21,280 IN THE LAB TO MAKE SURE THEY'RE 1355 00:47:21,280 --> 00:47:29,760 EASY TO WORK WITH AND THINGS 1356 00:47:29,760 --> 00:47:31,080 LIKE THAT. 1357 00:47:31,080 --> 00:47:33,040 SO LAB, ACCESSIBILITY, FREEDOM, 1358 00:47:33,040 --> 00:47:34,720 AND THE GENERAL LAB ENVIRONMENT 1359 00:47:34,720 --> 00:47:36,240 OR CLINICAL ENVIRONMENT, I 1360 00:47:36,240 --> 00:47:38,320 THINK, I'M SURE THERE ARE OTHERS 1361 00:47:38,320 --> 00:47:39,960 BUT AT LEAST IN MY MIND THESE 1362 00:47:39,960 --> 00:47:41,000 ARE THINGS THAT ARE IMPORTANT. 1363 00:47:41,000 --> 00:47:43,960 >>YEAH AND I KNOW YOU HAD A 1364 00:47:43,960 --> 00:47:45,200 PRIMARY MENTOR DR. TISDALE FOR 1365 00:47:45,200 --> 00:47:46,800 QUITE A WHILE BUT THE ISSUE IN 1366 00:47:46,800 --> 00:47:47,800 SOME WAYS WAS HOW TO 1367 00:47:47,800 --> 00:47:48,520 DEVELOPMENTAL ENDOCRINOLOGY 1368 00:47:48,520 --> 00:47:49,440 REBTIATE AND MAKE YOUR OWN PATH 1369 00:47:49,440 --> 00:47:52,880 IS THAT SOMETHING THAT WAS 1370 00:47:52,880 --> 00:47:53,240 DIFFICULT? 1371 00:47:53,240 --> 00:47:54,640 >>YEAH, SO, THAT'S GOING TO 1372 00:47:54,640 --> 00:47:56,200 OTHER QUESTIONS, I THINK 1 OF 1373 00:47:56,200 --> 00:47:57,440 THE BIGGEST CHALLENGES I'VE HAD 1374 00:47:57,440 --> 00:47:59,320 SINCE I'VE BEEN AT THE NIH FOR 1375 00:47:59,320 --> 00:48:03,120 SO LONG IS FIGURING OUT HOW TO 1376 00:48:03,120 --> 00:48:03,800 DIFFERENTIATE YOURSELF FROM YOUR 1377 00:48:03,800 --> 00:48:05,480 MENTOR AND IT CAN BE HARD, IT'S 1378 00:48:05,480 --> 00:48:06,720 NOT JUST LOOKING OR BEING LIKE A 1379 00:48:06,720 --> 00:48:08,240 CLONE BUT IT'S ALSO ON PAPER, 1380 00:48:08,240 --> 00:48:10,920 LIKE IF YOU WANT TO BE A TENURED 1381 00:48:10,920 --> 00:48:12,360 TRACK INVESTIGATOR HERE YOU HAVE 1382 00:48:12,360 --> 00:48:18,160 TO HAVE YOUR OWN NICHE AND THAT 1383 00:48:18,160 --> 00:48:20,240 WAS CHALLENGING FOR ME BUT HE 1384 00:48:20,240 --> 00:48:22,560 GAVE ME THE HAPPEN LO IDENTICAL 1385 00:48:22,560 --> 00:48:25,000 PROGRAM WHEN I WAS--INITIALLYIVE 1386 00:48:25,000 --> 00:48:26,720 WASN'T WHEN I WAS BE ABLE TO 1387 00:48:26,720 --> 00:48:28,840 FOCUS ON, AND HE WAS A SICKLE 1388 00:48:28,840 --> 00:48:30,240 CELL TRANSPLANT PERSON, I DIDN'T 1389 00:48:30,240 --> 00:48:31,760 THINK HE WOULD ALLOW ME TO THAT 1390 00:48:31,760 --> 00:48:34,200 I CAN TAKE THAT ON BUT THAT 1391 00:48:34,200 --> 00:48:35,360 SHOWS AGAIN THE PERSON THAT HE 1392 00:48:35,360 --> 00:48:37,320 IS AND SO I HAD TO FIGURE OUT 1393 00:48:37,320 --> 00:48:39,320 WHAT IS MY NICHE, WHAT AM I 1394 00:48:39,320 --> 00:48:40,280 PASSIONATE ABOUT AND MY 1395 00:48:40,280 --> 00:48:42,560 EXPERTISE AND I WAS ABLE TO DO 1396 00:48:42,560 --> 00:48:45,560 THAT BUT MORE ABOUT WHAT YOU 1397 00:48:45,560 --> 00:48:46,960 WERE SAYING, IT'S REALLY 1398 00:48:46,960 --> 00:48:48,160 IMPORTANT HOW MULTIPLE MENTORS, 1399 00:48:48,160 --> 00:48:49,800 SO I HAVE MENTORS IN DIFFERENT 1400 00:48:49,800 --> 00:48:51,280 AREAS SO I HAVE SPOKEN A LOT 1401 00:48:51,280 --> 00:48:53,600 ABOUT JOHN BUT I HAVE MENTORS 1402 00:48:53,600 --> 00:48:55,440 OUTSIDE OF NIH, 1403 00:48:55,440 --> 00:48:56,400 M-TEBURKEULOSEISORS FOR WORK 1404 00:48:56,400 --> 00:48:57,360 LIFE BALONS OR COLLEAGUES THAT I 1405 00:48:57,360 --> 00:48:59,360 LOOKED UP TO WAS THE YEAR AHEAD 1406 00:48:59,360 --> 00:49:02,040 OF ME WHO WAS A TENURED TRACK 1407 00:49:02,040 --> 00:49:03,080 INVESTIGATOR WHO I THINK WAS 1408 00:49:03,080 --> 00:49:04,040 REALLY IMPORTANT TO HAVE 1409 00:49:04,040 --> 00:49:05,640 MULTIPLE PEOPLE THAT YOU GO TO 1410 00:49:05,640 --> 00:49:06,480 AND IT'S ALSO VERY IMPORTANT FOR 1411 00:49:06,480 --> 00:49:08,920 YOU TO BE THE 1S TO INITIATE AND 1412 00:49:08,920 --> 00:49:10,080 CONTINUE THE RELATIONSHIP AND 1413 00:49:10,080 --> 00:49:12,400 NOT WAIT FOR YOUR MENTOR TO 1414 00:49:12,400 --> 00:49:16,040 REACH OUT TO YOU TO BE VERY 1415 00:49:16,040 --> 00:49:17,920 CLEAR WHAT YOU LIKE FROM THAT 1416 00:49:17,920 --> 00:49:21,720 MENTOR AND TO FOLLOW UP IS VERY, 1417 00:49:21,720 --> 00:49:22,760 VERY CRUCIAL. 1418 00:49:22,760 --> 00:49:24,360 >>OKAY, SO CAN I ASK YOU IF YOU 1419 00:49:24,360 --> 00:49:26,000 HAVE SOMETHING YOU WANT TO SAY, 1420 00:49:26,000 --> 00:49:28,840 CAN YOU DESCRIBE ANY BARRIERS OR 1421 00:49:28,840 --> 00:49:29,720 CRITICAL TURNING POINTS IN YOUR 1422 00:49:29,720 --> 00:49:32,120 CAREER AND HOW YOU DEALT WITH 1423 00:49:32,120 --> 00:49:32,360 THEM? 1424 00:49:32,360 --> 00:49:34,400 SO THINGS THAT WERE JUST--COULD 1425 00:49:34,400 --> 00:49:35,880 HAVE BEEN A MAKE OR BREAK MOMENT 1426 00:49:35,880 --> 00:49:41,280 FOR YOU IN TERMS WHERE YOU ARE 1427 00:49:41,280 --> 00:49:41,640 NOW. 1428 00:49:41,640 --> 00:49:42,840 >>I WAS JUST TALKING ABOUT IT, 1429 00:49:42,840 --> 00:49:46,720 I MEAN THAT WAS--SO WHEN I WAS 1430 00:49:46,720 --> 00:49:47,560 AN ASSISTANT CLINICAL 1431 00:49:47,560 --> 00:49:48,800 INVESTIGATOR, I WAS ACTUALLY 1432 00:49:48,800 --> 00:49:50,280 HAD--I DEPARTMENT WANT TO DO 1433 00:49:50,280 --> 00:49:52,360 MORE WITH TRANSPLANT WHEN I WAS 1434 00:49:52,360 --> 00:49:53,240 TAKING ANOTHER TRAJECTORY AND 1435 00:49:53,240 --> 00:49:55,080 WHEN I WAS IN THE SICKLE CELL 1436 00:49:55,080 --> 00:49:57,240 BRANCH AT THE TIME AND SO MANY 1437 00:49:57,240 --> 00:49:58,760 THINGS THAT THE BRANCH CHIEF AND 1438 00:49:58,760 --> 00:50:00,200 SHE SAID COURTNEY THIS IS NOT SO 1439 00:50:00,200 --> 00:50:02,160 INTERESTING, THRANS PLANT IS 1440 00:50:02,160 --> 00:50:03,200 WHAT YOU HF-TRANSPLANT IS WHAT 1441 00:50:03,200 --> 00:50:05,520 YOU MEDE TO DO, STHEE HELP MEDE 1442 00:50:05,520 --> 00:50:07,280 GO AND TALK TO JOHN AND BE 1443 00:50:07,280 --> 00:50:08,560 A--BITS ADVOCATE AND TELL HOW 1444 00:50:08,560 --> 00:50:10,200 IMPORTANT IT WAS FOR HIM TO LET 1445 00:50:10,200 --> 00:50:13,800 GO OF THE HAPPEN LO IDENTICAL, 1446 00:50:13,800 --> 00:50:15,320 THE GOOD THING FOR ME IS THAT 1447 00:50:15,320 --> 00:50:16,760 HE'S EXCITED AND INTERESTED IN 1448 00:50:16,760 --> 00:50:19,080 GENE THERAPY AND EDITING WHICH 1449 00:50:19,080 --> 00:50:21,680 IS DIFFERENT, SO HE HAD PLENTY 1450 00:50:21,680 --> 00:50:25,800 TO DO OUTSIDE OF HAPPEN LO 1451 00:50:25,800 --> 00:50:29,240 IDENTICAL TRANSPLANT, IT WAS 1452 00:50:29,240 --> 00:50:30,640 HAVING THE UMBILICAL CORD CUT, 1453 00:50:30,640 --> 00:50:32,520 AND SINCE I WAS A TRANSLATIONAL 1454 00:50:32,520 --> 00:50:34,240 STUDY AND FELLOW HE LOOKED AT ME 1455 00:50:34,240 --> 00:50:35,840 AND IT TOOK A BIT OF TRANSLATION 1456 00:50:35,840 --> 00:50:38,000 TIME FOR HYM TO SEE ME AS A 1457 00:50:38,000 --> 00:50:39,160 COLLEAGUE AND I THINK THAT'S 1458 00:50:39,160 --> 00:50:40,600 BEEN 1 OF THE BIGGEST CHALLENGES 1459 00:50:40,600 --> 00:50:45,200 BUT WE'RE IN A REALLY, REALLY 1460 00:50:45,200 --> 00:50:45,840 GOOD PLACE NOW. 1461 00:50:45,840 --> 00:50:48,080 >>YEAH, YOU KNOW I THINK I'VE 1462 00:50:48,080 --> 00:50:49,360 HAD SEVERAL TURNING POINTS, I 1463 00:50:49,360 --> 00:50:51,040 WOULD SAY, I THINK--I DIDN'T PUT 1464 00:50:51,040 --> 00:50:52,720 A LOT OF THOUGHT BO CHOOSING A 1465 00:50:52,720 --> 00:50:54,560 MENTOR BUT I THINK I ENDED UP 1466 00:50:54,560 --> 00:50:56,720 WITH A GREAT MENTOR DO DURING MY 1467 00:50:56,720 --> 00:50:58,640 FELLOWSHIP PROGRAM, SO I THINK 1468 00:50:58,640 --> 00:51:00,080 THAT WAS GREAT, THAT LOOKS BACK 1469 00:51:00,080 --> 00:51:02,880 AND SEEMS TO BE AN IMPORTANT 1470 00:51:02,880 --> 00:51:05,360 DECISION, I COULD BE DOING 1471 00:51:05,360 --> 00:51:07,320 SOMETHING ELSE, MAYBE IT'S NOT 1472 00:51:07,320 --> 00:51:09,520 REALLY A BAD AREA BUT IT'S A 1473 00:51:09,520 --> 00:51:11,360 TURNING POINT IS JUST SORT OF 1474 00:51:11,360 --> 00:51:13,680 HOW I VIEW MYSELF AS A MENTOR 1475 00:51:13,680 --> 00:51:18,000 AND MENTORING MY MENTORING 1476 00:51:18,000 --> 00:51:19,400 APPROACHES THAT CHANGED 1477 00:51:19,400 --> 00:51:22,600 DRAMATICALLY, SO WORKING WITH 1478 00:51:22,600 --> 00:51:23,680 OUTSTANDING CLINICAL FELLOWS WHO 1479 00:51:23,680 --> 00:51:27,880 CHANGED MY VIEW OF THINKING AND 1480 00:51:27,880 --> 00:51:29,040 REALLY, YOU KNOW REALLY CHANGE 1481 00:51:29,040 --> 00:51:33,160 THE WAY I VIEW MENTOR-MENTEE 1482 00:51:33,160 --> 00:51:33,480 RELATIONSHIPS. 1483 00:51:33,480 --> 00:51:34,880 I THINK THAT'S SOMETHING THAT 1484 00:51:34,880 --> 00:51:37,560 WAS LIKE TOTALLY UNEXPECTED. 1485 00:51:37,560 --> 00:51:40,720 I THINK THAT AGAIN IS NOT A BAD 1486 00:51:40,720 --> 00:51:44,600 AREA BUT IT'S SORT OF A CHANGE. 1487 00:51:44,600 --> 00:51:46,640 I WAS INITIALLY A STAFF 1488 00:51:46,640 --> 00:51:47,680 CLINICIAN POST FELLOWSHIP FOR 1489 00:51:47,680 --> 00:51:49,640 ABOUT 4 OR 5 YEARS OR SO BEFORE 1490 00:51:49,640 --> 00:51:52,040 I MOVED TO DEVELOPING AN 1491 00:51:52,040 --> 00:51:53,200 INDEPENDENT PROGRAM IN SMALL 1492 00:51:53,200 --> 00:51:53,400 CELL. 1493 00:51:53,400 --> 00:51:56,480 YOU KNOW, AGAIN IT WAS NOT LIKE 1494 00:51:56,480 --> 00:51:58,080 A 1 MOMENT SWITCH FROM WHAT I 1495 00:51:58,080 --> 00:51:59,560 WAS DOING PREVIOUSLY TO SORT OF 1496 00:51:59,560 --> 00:52:02,000 ORGANIC AND IT HAPPENED OVER A 1497 00:52:02,000 --> 00:52:05,040 PERIOD OF TIME AND AGAIN, 1498 00:52:05,040 --> 00:52:06,560 LOOKING BACK, I THINK THAT WAS 1499 00:52:06,560 --> 00:52:08,320 AN IMPORTANT DECISION TO SORT OF 1500 00:52:08,320 --> 00:52:11,360 RECOGNIZE THAT IS AN UNMET NEED 1501 00:52:11,360 --> 00:52:14,040 AND REALLY NO PROGRAM FOR NIH 1502 00:52:14,040 --> 00:52:15,320 FOR SMALL CELL, THIS IS 1503 00:52:15,320 --> 00:52:16,400 SOMETHING I COULD BUILD ON AND 1504 00:52:16,400 --> 00:52:18,520 AGAIN ISSUES YOU KNOW I HAD 1505 00:52:18,520 --> 00:52:20,320 WONDERFUL PEOPLE IN THE CLINIC 1506 00:52:20,320 --> 00:52:21,480 TO, YOU KNOW TO BUILD THE 1507 00:52:21,480 --> 00:52:24,600 PROGRAM ALONG WITH ME SO IT'S 1508 00:52:24,600 --> 00:52:27,120 NOT A 1-MAN EXERCISE AND ALSO ON 1509 00:52:27,120 --> 00:52:28,320 THE BASIC SIDE I WAS FORTUNATE 1510 00:52:28,320 --> 00:52:30,960 TO FIND A LOT OF WONDERFUL 1511 00:52:30,960 --> 00:52:33,840 CLINICAL COLLABORATORS WITHIN MY 1512 00:52:33,840 --> 00:52:35,400 CURRENT BRANCH, DEVELOPMENTAL 1513 00:52:35,400 --> 00:52:36,600 THERAPEUTICS BRANCH SO IT WAS 1514 00:52:36,600 --> 00:52:38,560 WELL SUPPORTED FROM THE CLINICAL 1515 00:52:38,560 --> 00:52:42,160 CENTER AS A PLACE WHERE WE SEE 1516 00:52:42,160 --> 00:52:44,560 PATIENTS FROM NCI AS WELL AS 1517 00:52:44,560 --> 00:52:46,040 COLLABORATIONS WITHIN THE BRANCH 1518 00:52:46,040 --> 00:52:49,480 AS WELL AS WONDERFUL CLINICAL 1519 00:52:49,480 --> 00:52:51,760 COLLEAGUES AND RESEARCHERS AND 1520 00:52:51,760 --> 00:52:52,720 OTHERS TO BUILD THE PROGRAM. 1521 00:52:52,720 --> 00:52:56,600 SO AGAIN, THIS IS NOT SOMETHING 1522 00:52:56,600 --> 00:52:57,440 THAT HAPPENED OVERNIGHT, I THINK 1523 00:52:57,440 --> 00:52:59,520 IT WAS A PROCESS THAT TOOK 1524 00:52:59,520 --> 00:53:01,080 SEVERAL MONTHS OR OVER A YEAR TO 1525 00:53:01,080 --> 00:53:03,600 RECOGNIZE THAT THIS WAS MY GOAL 1526 00:53:03,600 --> 00:53:05,680 AND THIS IS WHERE I SHOULD GO. 1527 00:53:05,680 --> 00:53:06,600 >>YEAH, WELL, THANK YOU. 1528 00:53:06,600 --> 00:53:09,440 I DON'T KNOW IF THE FELLOWS 1529 00:53:09,440 --> 00:53:10,880 KNOW, BUT BECOMING A LASKER 1530 00:53:10,880 --> 00:53:13,960 CLINICAL SCHOLAR IS A 1531 00:53:13,960 --> 00:53:14,640 COMPETITIVE APPLICATION. 1532 00:53:14,640 --> 00:53:16,360 YOU DON'T JUST GO OUT, TO BE A 1533 00:53:16,360 --> 00:53:21,640 FELLOW YOU HAVE TO REALLY IT'S 1534 00:53:21,640 --> 00:53:23,200 ADVERTISED, IT'S A VERY RIGOROUS 1535 00:53:23,200 --> 00:53:25,600 PROCESS TO GET 1 OF THESE 1536 00:53:25,600 --> 00:53:26,960 TENURED TRACK POSITIONS. 1537 00:53:26,960 --> 00:53:29,840 AND I IMAGINE THAT YOU'RE KIND 1538 00:53:29,840 --> 00:53:31,320 OF HOT COMMODITIES IN THE FIELD 1539 00:53:31,320 --> 00:53:32,960 EMPLOY SO HAVE YOU HAD OUTSIDE 1540 00:53:32,960 --> 00:53:35,400 OFFERS FROM OTHER INSTITUTIONS, 1541 00:53:35,400 --> 00:53:36,800 HAVE PEOPLE TRIED TO LURE YOU 1542 00:53:36,800 --> 00:53:39,720 AWAY AND IF SO, WHAT WERE YOU 1543 00:53:39,720 --> 00:53:41,120 BALANCING THERE AND DECIDING TO 1544 00:53:41,120 --> 00:53:43,560 STAY VERSUS LEAVING, CAN YOU 1545 00:53:43,560 --> 00:53:44,240 TALK ABOUT THAT? 1546 00:53:44,240 --> 00:53:47,520 MOST PEOPLE DO LEAVE HERE, SO 1547 00:53:47,520 --> 00:53:49,680 IT'S NOT--THERE'S A THE RULE 1548 00:53:49,680 --> 00:53:52,760 THAT MORE PEOPLE LEAVE THAN 1549 00:53:52,760 --> 00:53:52,960 STAY. 1550 00:53:52,960 --> 00:53:54,000 SO CAN YOU TALK ABOUT THAT FOR 1551 00:53:54,000 --> 00:53:55,960 YOURSELF AND WHAT YOU 1552 00:53:55,960 --> 00:53:56,560 EXPERIENCED? 1553 00:53:56,560 --> 00:53:57,960 >>YEAH, I'VE INTERVIEWED RIGHT 1554 00:53:57,960 --> 00:53:59,920 OUTSIDE OF FELLOWSHIP, I 1555 00:53:59,920 --> 00:54:01,520 INTERVIEWED QUITE WIDELY TO GET 1556 00:54:01,520 --> 00:54:03,600 A POSITION AND THEN, YOU KNOW 1557 00:54:03,600 --> 00:54:08,240 MAYBE ABOUT 5 YEARS INTO MY, 1558 00:54:08,240 --> 00:54:10,320 RIGHT AROUND THE TIME I WAS 1559 00:54:10,320 --> 00:54:11,880 APPLYING FOR LASKER TENURED 1560 00:54:11,880 --> 00:54:12,720 POSITION I APPLIED TO DIFFERENT 1561 00:54:12,720 --> 00:54:15,400 PLACES AND I THINK, REALLY WHAT 1562 00:54:15,400 --> 00:54:17,120 SETS THIS PLACE APART IS WHAT 1563 00:54:17,120 --> 00:54:19,000 HAS REALLY, YOU KNOW HELPED ME 1564 00:54:19,000 --> 00:54:24,440 HERE IS REALLY THE ABILITY TO DO 1565 00:54:24,440 --> 00:54:28,000 RESEARCH AND PATIENT CENTERED 1566 00:54:28,000 --> 00:54:29,560 RESEARCH AND ABILITY TO WITH 1567 00:54:29,560 --> 00:54:31,320 GREAT PEOPLE, ACCESS TO 1568 00:54:31,320 --> 00:54:32,520 RESOURCES LET'S ALL MAKE THIS A 1569 00:54:32,520 --> 00:54:35,640 REALLY NICE PLACE AND YOU KNOW, 1570 00:54:35,640 --> 00:54:36,440 YEAH. 1571 00:54:36,440 --> 00:54:36,720 >>OKAY. 1572 00:54:36,720 --> 00:54:39,560 >>YEAH, THERE'S A LOT OF ADULT 1573 00:54:39,560 --> 00:54:40,760 SICKLE CELL PROVIDERS ESPECIALLY 1574 00:54:40,760 --> 00:54:41,840 THAT DO TRANSPLANTS SO I'VE 1575 00:54:41,840 --> 00:54:44,320 GOTTEN A LOT OF REQUESTS BUT 1576 00:54:44,320 --> 00:54:45,720 I'VE ALWAYS WANTED TO STAY HERE 1577 00:54:45,720 --> 00:54:47,880 JUST LIKE YOU SAID, I LOVE THE 1578 00:54:47,880 --> 00:54:49,000 RESOURCES THAT ARE AVAILABLE, I 1579 00:54:49,000 --> 00:54:51,440 LOVE HAVING A LAB WHICH IS 1580 00:54:51,440 --> 00:54:53,040 TRANSLATIONAL, I CAN SEE 1581 00:54:53,040 --> 00:54:54,680 PROBLEMS GOING ON WITH MY 1582 00:54:54,680 --> 00:54:56,400 PATIENTS, BRING IT INTO THE LAB 1583 00:54:56,400 --> 00:54:59,280 AND TAKE IT BACK TO PATIENTS SO 1584 00:54:59,280 --> 00:55:00,800 THERE'S' NOT A LOT OF 1585 00:55:00,800 --> 00:55:01,720 OPPORTUNITY OUTSIDE OF HERE TO 1586 00:55:01,720 --> 00:55:02,640 DO THAT. 1587 00:55:02,640 --> 00:55:05,200 >>WELL, I WOULD LIKE TO END 1588 00:55:05,200 --> 00:55:08,560 WITH A QUESTION ABOUT HOW DO YOU 1589 00:55:08,560 --> 00:55:09,920 ACHIEVE WORK-LIFE BALANCE AND 1590 00:55:09,920 --> 00:55:12,160 WHAT ARE THE CHALLENGES YOU FACE 1591 00:55:12,160 --> 00:55:13,440 IN DOING SO? 1592 00:55:13,440 --> 00:55:15,400 >>YEAH, SO I GOT MARRIED AS A 1593 00:55:15,400 --> 00:55:16,800 TENURED TRACK INVESTIGATOR SO I 1594 00:55:16,800 --> 00:55:18,200 THINK IT'S BEEN MORE RECENTLY 1595 00:55:18,200 --> 00:55:19,600 TRYING TO FIGURE OUT HOW TO 1596 00:55:19,600 --> 00:55:21,480 BALANCE THAT AND THE WAY WE DO 1597 00:55:21,480 --> 00:55:23,920 IT, FIRST OF ALL MARRY SOMEBODY 1598 00:55:23,920 --> 00:55:26,560 WHO IS VERY SUPPORTIVE OF MY 1599 00:55:26,560 --> 00:55:28,080 CAREER, WE HAVE TIMES THAT I 1600 00:55:28,080 --> 00:55:29,160 FOCUS ON HIM AND I HAVE TIMES 1601 00:55:29,160 --> 00:55:32,800 THAT I FOCUS ON THE LAB, SO JUST 1602 00:55:32,800 --> 00:55:34,360 BEING VERY CLEAR, MAKING SURE 1603 00:55:34,360 --> 00:55:36,480 THEY GIVE HIM THE TIME BECAUSE 1604 00:55:36,480 --> 00:55:37,760 HIS LOVE LANGUAGE IS QUALITY 1605 00:55:37,760 --> 00:55:39,600 TIME BUT HE ALLOWS ME THE TIME I 1606 00:55:39,600 --> 00:55:41,040 NEED TO BE SUCCESSFUL AND FOCUS 1607 00:55:41,040 --> 00:55:45,560 ON MY WORK AND THAT'S HOW WE DO 1608 00:55:45,560 --> 00:55:45,960 IT. 1609 00:55:45,960 --> 00:55:47,480 >>YEAH, I THINK SIMILAR, YOU 1610 00:55:47,480 --> 00:55:49,480 KNOW TRY TO FOCUS WHEN I'M AT 1611 00:55:49,480 --> 00:55:52,000 HOME, FOCUS ON THINGSA THE HOME, 1612 00:55:52,000 --> 00:55:53,600 WHEN I'M HERE, I THINK THE MOST 1613 00:55:53,600 --> 00:55:54,920 PRECIOUS THING YOU CAN GIVE A 1614 00:55:54,920 --> 00:55:57,600 PARTNER OR A CHILD IS YOUR FULL 1615 00:55:57,600 --> 00:56:00,960 SELF, BODY AND MIND. 1616 00:56:00,960 --> 00:56:07,400 WITHOUT THAT THERE I'M UNHAPPY 1617 00:56:07,400 --> 00:56:09,400 AND WOUTR THAT YOU'RE UNHAPPY SO 1618 00:56:09,400 --> 00:56:11,720 IT'S MINDFUL TO BE PRESENT. 1619 00:56:11,720 --> 00:56:13,600 >>IS IT WORKING, IS IT A 1620 00:56:13,600 --> 00:56:15,040 PROCESS? 1621 00:56:15,040 --> 00:56:16,160 >>SOME DAYS IT'S EASY, ON A DAY 1622 00:56:16,160 --> 00:56:17,880 WHEN YOU HAVE A PRESENTATION, 1623 00:56:17,880 --> 00:56:20,880 NEXT DAY IT'S NOT THAT EASY, 1624 00:56:20,880 --> 00:56:21,240 YEAH. 1625 00:56:21,240 --> 00:56:21,480 >>OKAY. 1626 00:56:21,480 --> 00:56:22,680 SO ABOUT TO OPEN IT UP FOR 1627 00:56:22,680 --> 00:56:24,560 QUESTIONS IF ANYONE HAS, THERE'S 1628 00:56:24,560 --> 00:56:25,640 MICs HERE IF ANYONE IN THE 1629 00:56:25,640 --> 00:56:28,320 AUDIENCE HAS A QUESTION FOR YOUR 1630 00:56:28,320 --> 00:56:29,840 PANELISTS, FEEL FREE TO CUM UP 1631 00:56:29,840 --> 00:56:39,160 AND ASK YOUR QUESTION. 1632 00:56:39,160 --> 00:56:40,240 >>HI, THANKS BOTH FOR SHARING 1633 00:56:40,240 --> 00:56:42,200 YOUR TIME AND EXPERIENCE, SO MY 1634 00:56:42,200 --> 00:56:44,320 NAME IS KRISTI AND I JUST 1635 00:56:44,320 --> 00:56:46,520 STARTED IN ACI, I CAME HERE FOR 1636 00:56:46,520 --> 00:56:48,400 AN INFECTIOUS DISEASE FELLOWSHIP 1637 00:56:48,400 --> 00:56:51,240 AND CLINICAL TRIALS, PEDS, I 1638 00:56:51,240 --> 00:56:52,680 HAVE A DESCENT CLINICAL 1639 00:56:52,680 --> 00:56:55,120 STANDPOINT BUT THIS IDEA OF 1640 00:56:55,120 --> 00:56:55,720 BEING THE TRANSLATIONAL 1641 00:56:55,720 --> 00:56:56,920 RESEARCHERS, THE DESIRE TO BUILD 1642 00:56:56,920 --> 00:56:58,680 THE CLINICAL SIDE BUT YOU ALSO 1643 00:56:58,680 --> 00:57:01,320 NEED A LAB COMPONENT AND SO THE 1644 00:57:01,320 --> 00:57:02,960 CLINICAL SIDE TAKES SO MUCH TIME 1645 00:57:02,960 --> 00:57:03,720 AND GETTING THE PATIENTS THAT 1646 00:57:03,720 --> 00:57:07,440 YOU WANT TO WORK WITH CAN FEEL 1647 00:57:07,440 --> 00:57:10,360 LIKE A FULL-TIME JOB BUT TO BE 1648 00:57:10,360 --> 00:57:11,840 ABLE TO BE COMPETITIVE FOR A 1649 00:57:11,840 --> 00:57:12,840 LASKER YOU NEED A LAB 1650 00:57:12,840 --> 00:57:13,360 COMOPPOSITE BEHAVIORIAL 1651 00:57:13,360 --> 00:57:14,640 PHENOTYPE AND THEN THE YOU NEED 1652 00:57:14,640 --> 00:57:16,720 TO BUILD THAT CAPACITY TO BRING 1653 00:57:16,720 --> 00:57:19,400 IN A TRAINEE OR TRAINEES TO HAVE 1654 00:57:19,400 --> 00:57:20,600 A BIOLOGIST, CAN YOU REFLECT ON 1655 00:57:20,600 --> 00:57:23,360 WHAT IT WAS LIKE FOR YOU ON HOW 1656 00:57:23,360 --> 00:57:24,160 YOU BUILT THAT? 1657 00:57:24,160 --> 00:57:26,760 HOW YOU MANAGED THE TIME? 1658 00:57:26,760 --> 00:57:27,480 AND ARE THERE THOUGHTS ON THE 1659 00:57:27,480 --> 00:57:30,000 BEST WAY TO BUILD YOUR RESEARCH 1660 00:57:30,000 --> 00:57:30,880 TEAM WHEN YOU KNOW YOU'RE 1661 00:57:30,880 --> 00:57:33,040 LOOKING TO BUILD A TEAM THAT 1662 00:57:33,040 --> 00:57:34,720 PROBABLY AS STRENGTHS AND SKILL 1663 00:57:34,720 --> 00:57:36,320 SETS THAT YOU DIDN'T EVEN 1664 00:57:36,320 --> 00:57:38,840 INDIVIDUALLY HAVE IF THAT MAKES 1665 00:57:38,840 --> 00:57:39,080 SENSE? 1666 00:57:39,080 --> 00:57:40,760 >>YOU WANT TO TAKE IT? 1667 00:57:40,760 --> 00:57:41,600 >>YEAH, GO AHEAD. 1668 00:57:41,600 --> 00:57:43,680 >>YEAH, I MEAN I THINK THAT WAS 1669 00:57:43,680 --> 00:57:45,760 CHALLENGING AS AN ACI, AND I'VE 1670 00:57:45,760 --> 00:57:46,760 GOTTEN BET WE--WE--YOU THAT OVER 1671 00:57:46,760 --> 00:57:49,000 TIME. 1672 00:57:49,000 --> 00:57:50,400 I THINK I HAVE BEEN ABLE TO 1673 00:57:50,400 --> 00:57:52,160 FOCUS AS I'VE GOTTEN MORE 1674 00:57:52,160 --> 00:57:52,400 RESOURCES. 1675 00:57:52,400 --> 00:57:54,760 I THINK AS AN ACI, I HAD A POST 1676 00:57:54,760 --> 00:57:57,360 BACK AND I HAD LIKE A LAB 1677 00:57:57,360 --> 00:57:59,000 MANAGER BUT I WASN'T ABLE TO DO 1678 00:57:59,000 --> 00:58:00,480 A LOT OF THE LAB BASED RESEARCH 1679 00:58:00,480 --> 00:58:01,800 BUT I HAD PLANS FOR WHAT I WANT 1680 00:58:01,800 --> 00:58:03,960 TO DO FOR THE FUTURE SO THE WAY 1681 00:58:03,960 --> 00:58:06,200 I WAS ABLE TO MANAGE THAT WAS 1682 00:58:06,200 --> 00:58:07,960 WHEN I APPLIED, I GOT THE 1683 00:58:07,960 --> 00:58:09,920 TENURED TRACK POSITION I GOT A 1684 00:58:09,920 --> 00:58:11,160 STAFF SCIENTIST WHO WAS ABLE TO, 1685 00:58:11,160 --> 00:58:13,320 SO I THINK I DIDN'T HAVE--I MEAN 1686 00:58:13,320 --> 00:58:14,160 I HAD THE PREVIOUS EXPERIENCE 1687 00:58:14,160 --> 00:58:16,280 BUT I DIDN'T HAVE A LOT AS AN 1688 00:58:16,280 --> 00:58:17,800 ACI BUT I BUILT IT INTO MY PLACE 1689 00:58:17,800 --> 00:58:19,960 FOR THE FUTURE AND THAT'S--AND I 1690 00:58:19,960 --> 00:58:21,000 HIRED SOMEBODY THAT HAD THE 1691 00:58:21,000 --> 00:58:23,560 EXPERTISE I NEEDED TO BE 1692 00:58:23,560 --> 00:58:23,960 SUCCESSFUL. 1693 00:58:23,960 --> 00:58:24,760 >>SO, THANK YOU. 1694 00:58:24,760 --> 00:58:25,800 I THINK WE'RE OUT OF TIME. 1695 00:58:25,800 --> 00:58:27,240 THANK YOU ALL FOR COMING, IT'S 1696 00:58:27,240 --> 00:58:28,640 GREAT TO SEE YOU ALL IN PERSON 1697 00:58:28,640 --> 00:58:32,040 AND WE WILL SEE YOU HERE NEXT 1698 00:58:32,040 --> 00:58:33,280 WEEK FOR THIS SECOND OF OUR 3 1699 00:58:33,280 --> 00:58:34,080 LECTURES, DR. NIA SHORE WILL BE 1700 00:58:34,080 --> 00:58:35,880 HERE. 1701 00:58:35,880 --> 00:58:40,120 THANK YOU. 1702 00:58:40,120 --> 00:58:50,360 [ APPLAUSE ]