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Center at the National Institutes of Health in
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tomorrow's cures.
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>>OUR SPEAKERS TODAY ARE
LASKER CLINICAL RESEARCH
SCHOLARS DOCTORS COURTNEY
FITZHUGH AND DR. ANISHTHOMAS.
I WILL START WITH DR. FITZHUGH,
SHE IS A INVESTIGATOR IN THE
SICKLE CELL ON MORTALITY
PREVENTION AS A NHLBI.
SHE RECEIVED HER BS MAGNA CUM
LAUDE, FROM THE UNIVERSITY OF
CALIFORNIA LOS ANGELES AND THEN
EARNED HER M. D. FROM THE
UNIVERSITY OF CALIFORNIA
SAN FRANCISCO.
DURING MEDICAL SCHOOL,
DR. FITZHUGH PARTICIPATE INDEED
THE NIH CLINICAL TRAINING
PROGRAM, WHERE SHE STUDIED
SICKLE CELL DISEASE UNDER
DR. JOHN TISDALE, AND AFTER THAT
SHE ENJOYED A PEDIATRIC
RESIDENCY AT DUKE AND THEN
STARTED A COMBINED ADULT
HEMEATOLOGY AND PEDIATRIC
HEMEATOLOGY ONCOLOGY FELLOWSHIP
AT THE NIH AND JOHNS HOPKINS.
SHE RETURNED TO NHLBI WHERE SHE
WAS APPOINTED AS AN ASSISTANT
CLINICAL INVESTIGATOR IN 2012
AND BECAME A LASKER CLINICAL
RESEARCH SCHOLAR AND A TENURED
TRACK INVESTIGATOR IN 2016.
DR. FITZHUGH IS BOARD CERTIFIED
IN PEDIATRIC HEMEATOLOGY,
ONCOLOGY, ERNE TURNOVERRAL
MEDICINE AND PEDIATRICS.
IN 2022 SHE WAS AWARDED THE NIH
DIRECTOR'S AWARD FOR HER EFFORTS
ON THE IGNITE INITIATIVE.
SHE IS A VIEW EDITOR FOR BLAD
ADVANCES AND PREVIOUSLY REVIEW
FOR FRONTIERS IN GENOME EDITING.
SHE'S A MEMBER OF THE AMERICAN
SOCIETY OF HEMEATOLOGY AND
AMERICAN SOCIETY OF
TRANSPLANTATION CELLULAR
THERAPY.
I WILL ALSO INTRODUCE OUR NEXT
SPEAKER THIS IS ALSO DR. ANISH
THOMAS IN THE DEVELOPMENT
THERAPEUTIC BRANCH OF THE
NATIONAL CANCER INSTITUTE.
DR. THOMAS IS A MEDICAL
ONCOLOGIST WHO SPECIALIZES IN
THE TREATMENT OF THORACIC
CANCERS.
HE EARNED HIS MEDICAL DEGREE AND
COMPLETED POST GRADUATE TRAINING
IN INTERNAL MEDICINE FROM
ST. JOHN'S MEDICAL COLLEGE IN
INDICATORSIA AND FOLLOWED BY A
RESIDENCY IN NEW YORK UPSTATE
MEDICAL UNIVERSITY IN SYRACUSE.
HE THEN CAME TO NIH TO TRAIN IN
MEDICAL ONCOLOGY AND HEMEATOLOGY
ANDLET MEDICAL ONCOLOGY BRANCH
OF THE NIH AND NCI RESPECTIVELY.
IN 2023 HE WAS AWARDED TRECTOR'S
AWARD FOR TRANSLATIONAL SCIENCE
FOR TRANSLATIONAL STUDIES
LEADING TO SUBGROUPS OF SMALL
CELL LUNG CANCER PAVING THE WAY
FOR PRECISION MEDICINE
APPROACHES.
HE IS BOARD CERTIFIED IN
ONCOLOGY AND HEMEATOLOGY AND
ELECTED MEMBER OF AMERICAN
SOCIETY FOR CLINICAL
INVESTIGATION.
THE TITLE OF TODAY'S
PRESENTATION IS: HOW TO BECOME
A SUCCESSFUL CLINICIAN
SCIENTIST, NIHLASKER SCHOLAR
PANEL.
PLEASE JOIN ME IN WELCOMING
TODAY'S GRADUATE SPEAKERS
DR. COURTNEY FITZHUGH AND
DR. ANISH THOMAS.
[ APPLAUSE ]
>>SO TO GIVE YOU A SENSE OF THE
AGENDA, BOTH INVESTIGATORS WILL
GIVE A BRIEF RESEARCH
PRESENTATION AND I DIDN'T GO
INTO THE DEAILS OF THEIR
RESEARCH AND THEN WE WILL
TRANSITION OVER AND DO A PANEL
DISCUSSION.
I HOPE HAVE YOU QUESTIONS IF ARE
THEM LATER.
THANK YOU.
>>GOOD AFTERNOON, AND THANK YOU
FOR INVITING ME TO BE
PART THIS PANEL, SO MY TALK IS
ENTITLED LEUKEMIA THERAPY FOR
SICKLE CELL DISEASE.
I DO NOT HAVE ANY FINANCIAL
DISCLOSURES TO REPORT AND MY
OBJECTIVE IS TO DESCRIBE THE
INCREASED RISK OF LEUKEMIA
FOLLOWING CARE FOR CERTAIN
SICKLE CELL DISEASE.
SICKLE SEIZE DISEASE IS POINT
MUTATION FROM RED BLOOD CELLS
FROM A EASILY DRIVABLE CONCAVE
DISK TO A RIGID SICKLE SHAPE
CELL WHICH INCLUDES
MICROVASCULATURE, SICKLE CELL
DISEASE IS ASSOCIATE
WIDEOXIDATIVE STRESS,
INFLAMMATION, SHORT AND RED CELL
SURVIVAL WHICH LEADS TO THE
STRESS, HYPOXIA AND DAMAGE TO
THE BONE MARROW
MICROENVIRONMENT.
THE MAIN COMPLICATION THAT
PATIENTS WITH SICKLE CELL
DISEASE EXPERIENCE IS
DEBILITATING PAIN AND CAN IMPACT
ANY ORGAN OF THE BODY LEADING TO
DAMAGE AND IT'S KNOWN THAT ADULT
WHO HAVE DAMAGE TO THE LIVER,
HEART, LUNG AND KIDNEYS, DIE
PREMATURELY.
SO ON THE Y-AXIS THE CUMULATIVE
SURVIVAL AND ON THE X-ACIS THE
AGE OR DEATH AND 60% OF THE
PATIENTS ARE ON HYDROXY URIA
WHICH IS STILL THE BEST MEDICINE
FOR PATIENTS WITH SICKLE CELL
DISEASE.
YOU SEE THAT 2225 PATIENTS HAD
MOSTLY HOMOZYGOUS SICKLE SEAL
DISEASE AND THIS IS THE MOST
SEVERE TIME AND THE FOLLOW UP IS
6 AND HALF YEARS AND THE MEAN
SURVIVAL IS ONLY 48 YEARS WHICH
HAS NOT CHANGE INDEED THE LAST
2-3 DECADES AND STILL 20 YEARS
EARLIER THAN THE GENERAL AFRICAN
AMERICAN POPULATION.
THERE HAVE BEEN 2 LARGE
POPULATION STUDIES TO SHOW THAT
PATIENTS WITH SICKLE CELL
DISEASE HAVE INCREASED RISK FOR
LEUKEMIA, I WILL GO THROUGH 1
FORT ARTICLES PUBLISHED BY UC
DAVIS WHERE THEY IDENTIFY OVER
6400 PATIENTS WITH SICKLE CELL
DISEASE, WHO ARE IDENTIFIED
BETWEEN 19 NONE AND 2014, THEY
ARE FOLLOWED AND COMPARED TOO
THE GENERAL POPULATION AND THEY
FOUND THAT PATIENTS WITH SICKLE
CELL DISEASE HAD A 2.3 FOLD
INCREASED RISK FOR LEUKEMIA AND
A 3.6 INCREASED RISK FOR MYELOID
LEUKEMIA OR AML.
WHEN YOU LOOK MORE CLOSELY AT
THE DATA YOU WILL SEE THAT THEY
WILL FOLLOWED OVER 27 YEARS BUT
ONLY 31 PATIENTS DEVELOPED A
HEMEAT O LOGIC MALIGNANCY OR
0.21 PER 100 YEARS OF FOLLOW UP.
EIGHTEEN INDIVIDUALS WITHOUT
SICKLE CELL DISEASE WERE
EXPECTED TO DEVELOP HEMEAT O
LOGIC MALIGNANCIES DURING THAT
TRIEM FRAME WHEN CONTROLLING FOR
AGE, RACE, SEX, ETHNICITY AND SO
YOU SEE WHILE THERE'S INCREASE
RELATIVE RISK FOR PATIENTS WITH
SICKLE CELL DISEASE DEVELOPING
LEUKEMIA, THE ABSOLUTE RISK IS
LOW.
SO THIS OFFERS CARE WITH WHEN I
SAY MILE ON ABLATIVE THAT MEANS
HIGH DOSE CHEMO THERAPY AND WIPE
OUT THE BONE MARROW AND REPLACE
IT WITH THE BLOOD OF THE DONOR.
SO THIS WAS A STUDY WHERE 1000
PATIENTS WITH SICKLE CELL
DISEASE UNDERWENT THE TRANSPLANT
O PLANT AND YOU SEE THE 5 YEAR
OVERALL SURVIVAL IS 93%, MEANING
93% OF THE PATIENTS WERE ALIVE,
AFTER 5 YEARS AND THEN 91% WERE
ALIVE AND FREE OF SICKLE CELL
DISEASE.
SO YOU HEARD IN THE INTRODUCTION
THAT I CAME TO THE NIH AS A
MEDICAL STUDENT AND I WORKED
WITH JOHN TISDALE WHO IS AN
ADULT HEMEATOLOGYIST AND MOST
ADULTS CANNOT TOLERATE HIGH DOSE
CHEMO THERAPY SO WE WANTED TO
APPLY THIS CURATIVE APPROACH TO
ASULTS SO INSTEAD OF HIGH ON
DOSE CHEMO THERAPY AND
ACTIVITIES AND PROJECTS WE
WANTED TO USE A NONMILE ABLATIVE
THERAPY WHERE YOU USE A MIXTURE
EVER DONOR AND RECIPIENT CELLS.
SO IN ORDER TO CREATE THIS
MIXTURE, IT'S LIKE YOU HAVE TO
REEDUCATE THE IMMUNE SYSTEM SO
THAT THE DONOR AND RECIPIENT
CELLS NO LONGER RECOGNIZE EACH
OTHER AS BEING FOREIGN.
SO, THE INVITRO DATA SUGGEST
THAD CYCLOSPORIN WOULD NOT
INDUCE TOLERANCE WHERE RAPAMYCIN
WOULD INDUCE TOLERANCE.
SO THIS WAS A MOUSE MODEL WHERE
I GAVE THEM EITHER--I WILL CALL
IT RAP O MICEIN, BUT THIS IS ALL
[INDISCERNIBLE].
BUT I GAVE THE RAP O MICEIN FOR
30 DAYS AND YOU SEE THAT THE
MICE RECEIVED CYCLOSPORIN
INITIALLY ACHIEVED REGRESSION
BUT REJECTED THE GRAPHS AND THEN
THEY RECEIVED RAPAMYCIN, AND
THEN THE INCREASE 8 MONTHS AFTER
THE RAPAMYCIN WAS DISCONTINUED
SO IT LOOKS LIKE WE WERE ABLE TO
INDUCE THIS TOLERANCE STATE IN
THE MICE.
SO BASED ON THESE DATA, THEY
WROTE THIS PROTOCOL TO--WHICH
WAS VERY SIMILAR TO WHAT WE DID
WITH THE MICE.
SO THE MICE RECEIVE 3 CENTIGRADE
OF RADIATION AND WE ADD
ALETMUZUMAB, SO NOT ONLY ARE YOU
DEPLETING THIS WITH THE
RECIPIENTS BUT THE DONORS, SO WE
GET 3 CENTIGRADE RADIATION TO
MAKE SPACE IN THE BONE MARROW
AND PROVIDE ARK DITIONAL
SUPPRESSION AND THEN WHEN THE
LIESMEE SIGHTS GROW BACK, SO CAN
YOU INDUCE TOLERANCE O MATT SHAY
AND INVESTIGATORS AT THE
UNIVERSITY OF ILLINOIS AND SAUDI
ARABIA RECENTLY REPORTED 122
PATIENTS TRANSPLANTED USING
THIS,A PROACH, THE OVERALL
SURVIVAL WAS 93% AFTER NIEF
QUEERS, WITH AN 8385%, AND NONE
OF PATIENTS DEVELOPED SEVERE
MODERATE GRAFT VERSUS HOST
DISEASE.
SO WHILE THIS WAS EXCITING DATA,
THE PROBLEM AT THE TIME WAS THAT
ONLY LESS THAN 15% OF THE PATES
HAVE A SIBLING DONOR HOWEVER 90%
OF THE PATIENTS HAVE A HAPPEN LO
IDENTICAL DONOR SO PARENTS,
CHILDREN AND ALPHMASH SIBLINGS
CAN SERVE AS DONORS.
SO WE WANTED TO DEVELOP A
PROTOCOL WE'VE SEEN IN THE MATCH
SIBLING STUDY AND BASED ON
MURINE BATTA I WROTE THIS
PROTOCOL AND I WAS ABLE TO BE A
PRINCIPLE INVESTIGATOR AS A
FELLOW SOY WANT TO THANK
DR. TISDALE FOR THAT.
SO ALL OF THE PATIENTS GOT
ALATUZUMAB, WE INCREASED
RADIATION TO 400 CENTIGRADE, AND
ALL THE PATIENTS RECEIVE
SEROLMUS, AND IT WAS AICOSE
ESCALATION OF THE FIEK SO FOSTER
NURSED FOCUSED ON MID, SO THE
FIRST COHORT OF PATIENTS DIDN'T
RECEIVE AND CYCLOFOSTER NURSED
FOCUSED ON MID, SO TOO MANY
PATIENTS REJECTED GRAFS OR
DEVELOPED GROF THE VERSUS HOST
DISEASE, WE MOVED TO THE SECOND
COHORT WHERE PATIENTS AREY
CEIVED MORE CYCLOFOSTER NURSED
FOCUSED ON MADE, AND WE MOVED TO
THE FINAL COHORT WHICH IS A
HUNDRED MILLIGRAM IN DOSES AND
WE IMPROVE THE ENGRAPHMENT RATE
AND WE DID IMPROVE THE EVENT
FREE SURVIVAL BUT EVEN WITH THE
COHORT, 50% OF THE PASHTS
REJECTED THE GRAF AND THE STUDY
WAS CLOSED TO ACCRUAL.
SO BECAUSE OF THIS INCREASE THE
RISK REJECTION WITH THE HAPPEN
LO STUDY, WE HAD NEW PROTOCOLS,
WHICH ADDS PEBT STATUS
PRECONDITIONING BECAUSE THOSE
AGENTS WORK TOGETHER TO DEPLETE
LYMPHOCYTES AND TO DATE BOTH
PROTOCOLS HAVE BEEN ASSOCIATED
WITH THE LOWER RISK OF GRAPH
REJECTION.
AND I JUST WANTED TO MENTION
SOMETHING ABOUT GENE THERAPY
WHICH IS A NEWER PROCESS TO USE
AS A CURATIVE OPTION FOR
PATIENTS WITH SICKLE CELL
DISEASE AND I WANT TO MENTION
THERE ARE 3 DIFFERENT GROUPS,
PATIENTS THAT HAVE RECEIVED THIS
GENE THERAPY, GROUPS A, B, C,
WITH GROUP AIAN PRECOLLECTION OF
BLOOD CELL TRANSFUSION IS
REQUIRED FOR GROUPS B AND C
PATIENTS, THE HEMEAT O POET STEM
CELL SOURCE WAS BONE MARROW IN B
ANDA PATIENTS AND MOBILIZED IN
GROUP C AND THE ORIGINAL
MANUFACTURING DRUG AND PROCESS
WAS USING SOME GROUP A AND B
PATIENTS IN A MORE REFINED
PROCESS IN GROUP B AND C PATIENT
ANDS IMPORTANTLY ALL OF THE
PATIENTS RECEIVE MILE ABLATIVE
CONDITIONING WITH B-CELL, SO
THIS IS A FELLOW IN MY LAB AND
WE RECENTLY REPORTED 120
PATIENTS, NONALLO BRAIT BLAITIVE
TRANSPLANT FOR SICKLE CELL
DISEASE HERE AT THE IN, IH
SEPTEMBER 2004 AND
DECEMBER 2020.
EIGHTY-ONE PATIENTS RECEIVED THE
TRANSPLANT WITH THE MEDIAN AGE
OF 31 YEARS, 39 PATIENTS
UNDERWENT HAPPEN LO IDENTICAL
HCT AT 32 YEARS, AND BETWEEN 4
MONTHS AND 9 YEARS POST
TRANSPLANT, DEVELOPED MALIGNANCY
SO 5 PATIENTS DEVELOPED A MORE
AGGRESSIVE TYPE OF AML IN THE
SETTING OF GRAPH FAILURE, 3
DEVELOPED MEL AN OHM, MYELOID
ALEUKEMIA AND A SETTING OF MIXED
CHIMERISM.
SO WHEN YOU LOOK AT THE DATA
ACARDING TO THE PROTOCOL THEY
WERE TRANSPLANTED ON, IN THE
FIRST COLLUM,--YOU SEE THAT 1
HADN'T 8% OF THE PATES DEVELOPED
MDS OR AML, 5.3% DEVELOPED ALL
HEMEAT O LOGIC MALIGNANCIES AND
A MEDIAN OF 3 AND HALF YEARS
POST TRANSPLANT, WHEN THE SAME
APPROACH WAS USED IN CHICAGO OR
RIOT, 1.6% OF THE PATIENTS
GEPPED MDS OR AML AT 3 YEARS
TRANSPLANT AND WE ADD THE
[INDISCERNIBLE] PRECONDITIONING,
4.2% DEVELOPED AMDS OR AML AND
4.3 PERCENT WITH THE MALIGNANCY.
THERE ARE THE 2 PROTOCOLS WHERE
YOU SEE WITH THE ORIGINAL
DECLARATION OF THE PROT COL, WE
HAD 14% DEVELOP M, IT DS OR AML,
THIS IS A NEWER PROTOCOL AND SO
FAR TO DATE WE HAVE NONE SEE
DEVELOPMENT OF MALIGNANCY.
THIS IS COMPARATIVE WITH 2
STUDIES, WHERE 44% OF THEM
DEVELOPED MDS OR AML ANDY SEE
THE INCIDENCE IS SIMILAR TO WHAT
WE'VE SEEN AT THE NIH.
IMPORTANTLY BOTH OF THESE
PATIENTS WERE IN GROUP A AND
THEY WERE IN A LOWER CELL DOSE
IN THE PATIENTS MORE RECENTLY.
BY RECEIVING THE GENE THERAPY.
THIS COMPARES TO LARGER STUDIES,
THIS IS MOSTLY PEDIATRIC
PATIENTS, MOSTLY HLA MATCHED
SIBLING, USING CONDITIONING AND
YOU CAN SEE THAT THE INCIDENTS
OF HEMEAT O LOGIC IS MUCH LOWER
COMPARED TO WHAT WE'VE SEEN.
I WANT TO MAKE SURE I DON'T GO
TOO FAR.
SO WHAT ARE PONL REASONS THESE
PATIENTS HAVE MYELOID
MALIGNANCIES HERE?
THIS IS THE UC DAVIS STUDY I
PREPORTED EARLIER, WE LOOK AT
ALL PATIENTS WITH SICKLE CELL
DISEASE, THEY FOUND THAT ISHT
PATHWAY GIVESS WHO WERE OLDER
AND THOSE WITH MORE SEVERE
DISEASE WERE MORE LIKELY TO
DEVELOP LEUKEMIA, WE TRANSPLANT
PATIENTS HERE AT THE NIH WHEN
ARE HOLDER THAN TYPICAL AND MORE
SEVERE DISEASE THAN TYPICAL AND
WE ALSO HAVE A LONGER DURATION
OF FOLLOW UP AND A HIGHER
PROPORTION OF PATIENT WHO IS ARE
FOLLOWING LONG-TERM, WE ALSO USE
TOTAL BODY IRRADIATION, AND
SIMILAR, TO GENE THERAPY,
PATIENTS THAT HAVE GRAPH FAILURE
HAVE A REQUIREMENT OF
REGENERATIVE HEMEAT O
POETICESIS.
SO I'M GOING TO END HERE.
SO WE'VE HAD 2 PATIENTS WHO HAVE
QUEPED MYELOID MALIGNANCIES AND
HAD TP53 MUTATIONS AT THE
DIAGNOSE AND WE WANT TO KNOW
WHETHER WE CAUSED THESE
MUTATIONS WITH THE CHEMO THERAPY
OR RADIATION THAT WE GAVE OR
BECAUSE OF SICKLE CELL DISEASE
AND THE LIFETIME OF INFLAMMATION
AND STRESS, THESE PATIENTS HAD
THE MUTATIONS AT BASE LINE SO WE
WORK WITH RISK ASSESSMENTS
HORGANNA'S LAB AND THEY FOUND
THESE WERE IN A FREE RADICALS
FERENCEY OF SMR PBT 3 IN THISSA
PATIENT AND 0.06% IN THIS
PATIENT AND AFTER INJECTION, IT
LOW FREQUENCY UNTIL THEY
DEVELOPED THESE MYELOID
FREQUENCIES.
SO MY LAB IS LOOKING AT LARGER
POPULATION OF TRANSPLANTS TO
LOOK THEA THE PREVALENCE OF
THESE CLONES, WE ARE WORKING
WITH DANA FARBER TO SEE IF THESE
CLONES ARE OCCURRING AT BASE
LINE AND WHETHER THEY'RE
EXPANDING OVER TIME AND THEN WE
WILL LOOK AT THE SINGLE CELL
LEVEL TO SEE IF THERE ARE DRIVER
MUTATIONS THAT MAKE THEM MORE
PRONE TO DEVELOPING THOSE
MALIGNANCIES.
I WILL END THERE.
THANK YOU VERY MUCH.
[ APPLAUSE ]
>>THANK YOU SO MUCH FOR BEING
HERE, I STUDY SMALL CELL LUNG
CANCER.
I HAVE NO DISCLOSURES IF YOU'RE
NOT FAMILIAR WITH SMALL CELL
LUNG CANCERS IT'S PROBABLY 1 OF
THE MOST HIGHLY METASTATIC
CANCERS MOST PATIENTS PRESENT
WITH WIDE SPREAD DISEASE AND
THESE TUMORS TEND TO BE
EXCEPTIONALLY RESPONSIVE TO
CHEMO THERAPY.
YOU CAN SEE THIS IS A CT SCAN OF
A PATIENT, THIS IS A TUMOR IN
THE RIGHT LOBE MELTING AWAY
FOLLOWING CHEMO THERAPY.
THESE RESPONSES ARE VERY
TRANSIENT WHICH IS FOLLOWED BY
SYSTEM TEMMIC RELAPSE AND HERE
YOU CAN SEE RELAPSE IN THE LIVER
AS WELL AS IN THE ADRENAL.
AND AT THE TIME OF RELAPSE, MOST
OF THE STANDARD TREATMENTS ARE
LARGELY INEFFECTIVE AND PATIENTS
DIE--MOST PATIENTS DIE WITHIN A
YEAR OF THEIR DIAGNOSE.
IT'S AN EXCEPTIONALLY SEVERE
DISEASE, IT'S A STANDARD
TREATMENT OF THESE, MORE CHEMO
THERAPY, MORE RECENTLY, IMMUNO
THERAPY IS ADD BUT IT ONLY
BENEFITS A SMALL SUBSET OF
PATIENTS.
AND IT'S NOT AN UNCOMMON
DISEASE.
IT AFFECTS A LOT OF PEOPLE.
IT AFFECTS 250,000 INDIVIDUALS
WORLD WIDE EVERY YEAR.
AND IN THE U.S. IT KILLS AT
LEAST 30,000 PEOPLE EVERY YEAR
SO IT'S AN EXCEPTIONALLY LETHAL
CANCER, BUT IT'S ALSO
EXCEPTIONALLY COMMON AND AS I
SAID, MEDIAN SURVIVAL IN MOST
PATIENT SYSTEM LESS THAN A YEAR.
AND RECENT STUDY VS SHOWN IT'S
NOT 1 DISEASE, IT CONSISTS OF
MANY DISEASES AND MANY SUBTYPES
AND BROADLY YOU COULD UNDERSTAND
THE HETEROGENEITY IN SMALL CELL
LUNG DANCER INTO TUMORS THAT
HARBOR INDO KRIN PHENOTYPE AND
TUMORS WHO HAVE NEW EXPRESSION
OF NONNEW ENDOCRINE PHENOTYPE
AND THIS IS DETERMINED BY THE
DEFINING TRANSCRIPTION FACTORS
THAT ARE LISTED HERE.
THEY CHARACTERIZE FURTHER
SUBTYPES WITHIN SMALL LUNG
CANCER.
SO DESPITE US KNOWING THERE IS
HETEROGENEITY BASED ON THE
LINEAGE OF DEFINING FACTORS WE
TREAT SMALL CELL LUNG FACT OR AS
A SINGLE DISEASE, AND EVERYBODY
WITH SMALL CELL LUNG CANCER GETS
THE SAME TREATMENTS AND AS A
RESULT, THE SMALL CELL OUTCOME
VS NOT CHANGED SUBSTANTIALLY IN
THE LAST MANY, MANY DECADES,
THIS IS DATA GOING BACK TO 2001,
CAN YOU SEE THE 2 YEAR SURVIVAL
FOR MEN IS 10% AND FOR WOMEN,
IT'S A BIT HIGHER MAYBE 15%.
SO WHAT MAKES SMALL CELL SUCH AN
AGGRESSIVE CANCER?
THE BIG CHALLENGE IS THAT WE
KNOW VERY LITTLE ABOUT THE
MOLECULAR BASIS OF HUMAN SMALL
CELL LUNG CANCER AND YOU CAN
CHARACTERIZE THE AGGRESSIVE
FEATURES OF SMALL CELL AND USE
IT AS A MODEL DISEASE TO STUDY
METASTASIS, CHEMO RESISTANCE AND
HETEROGENEITY.
AND THE BIG CHALLENGE IS THAT
THERE'S VERY LIMITED
AVAILABILITY OF CLINICAL SAMPLES
OR HUMAN TUMOR SAMPLES FOR
RESEARCH AND BECAUSE THERE'S
LIMITED AVAILABILITY OF CLINICAL
SAMPLES, SMELL CELL IS NOT
INCLUDED IN MANY OF THE CANCER
STUDIES INCLUDING TCGA AND
BECAUSE OF THE CLINICAL SAMPLES,
ALMOST EVERYTHING THAT WE KNOW
ABOUT SMALL CELL, IS BASICALLY
DERIVED FROM THE CELL CULTURES
AS WELL AS MOUSE MODELS.
AND WHAT WE HAVE TRIED TO DO NOW
OVER THE LAST CLOSE TO 10 YEAR
SYSTEM TO TRY TO CHANGE THAT AND
THIS IS REALLY THE MOTIVATION
WHICH GOT ME STARTED THINKING
ABOUT SMALL CELL WAS THIS
DOCUMENT WHICH WAS PUT OUT BY
NCI IN RESPONSE TO THE
RECALCITRANT CANCER RESEARCH ACT
OF 2012 AND THIS WAS PUBLISH
INDEED JUNE 2014.
AND IT HIGHLIGHTED BASICALLY THE
SCARCE AMOUNT OF RESEARCH GOING
ON IN SMALL CELL AS WELL AS THE
LACK OF CLINICAL TRIALS.
IN PARTICULAR WHAT STRUCK ME
THERE WAS NO INTRAMURAL TRIALS
FOR SMALL CELLS AT THAT TIME, SO
WE TRIED TO ADDRESS SMALL CELL
FROM A VERY PATIENT-CENTERED
APPROACH AND OUR GOAL IS TO
PROVIDE THE BEST POSSIBLE CARE
FOR EVERY PATIENT AND LEARN FROM
EVERY PATIENT AND USING THIS
APPROACH WE HAVE NOW BUILT A
ROBUST CLINICAL PROGRAM FOR
SMALL CELL LUNG CANCER HERE, WE
LAUNCHED OVER 15 CLINICAL TRIALS
IN THE LAST 9 YEARS OR SO AND
ROLLED OVER 400 PATIENTS
CONDUCTED NUMEROUS RESEARCH
BIOPSIES, AND ABOUT 20 RESEARCH
AUTOPSIESS THAT HAVE FORMED THE
TREATMENT OF THE DISEASE AND THE
BIOLOGY OF THE DISEASE.
SO I WILL FOCUS ON 1 PARTICULAR
ASPECT WHICH IS REPLICATION
STRESS SO EARLY ON WE HYPOTHESIS
THAT WE HAVE SMALL CELL DRIVING
TUMOR SUPPRESS, 253 AND RB AND
HIGH FREQUENCY OF MYC
AMPLIFICATION, AND STRIKING
RESPONSES TO DNA REPRECATION AND
IT ALSO RESPONDS VERY WELL TO
DNA DAMAGING THERAPY AS WELL AS
HIGH GENOMIC INSTABILITY
CHARACTERIZED BY MUTATIONAL LOAD
AND ANUE EMPLOYEDY.
SO THIS IS DRIVEN BY HIGH
REPLICATION STRESS AND 1
APPROACH TO OTHER TAKEN--THEYET
REPLICATION STRESS IS TO TARGET
THE MEDIATION OF STRESS AND 1
IMPORTANT REPLICATION STRESS WE
FOCUS ON WAS ATR.
AND ESSENTIALLY WE HAVE FOCUS ON
ATR SINCE ABOUT 2014, 2015 AND
WE'VE DISCOVERED THAT
REPLICATION STRESS IS A SMALL
CELL LUNG CANCER VULNERABILITY,
AND OUR STUDIES HAVE PAVED THE
WAY FOR RATIONAL PATIENT
SELECTION IN A DISEASE THAT'S
TREATED WITH A SINGLE TREATMENT
FOR--SAME TREATMENT FOR
EVERYBODY.
SO 1 OF OUR FIRST CLINICAL TRIAL
WAS A PHASE 1 CLINICAL TRIAL, SO
THIS WAS A FIRST IN CLASS
INHIBITOR AND BEFORE THAT THERE
WERE A LOT OF CONCERNS ABOUT
TARGETING ATR BECAUSE IT'S AN
ESSENTIAL PROTEIN.
WE CHARACTERIZED SAFETY AND SO
THIS IS ANOTHER DNA DAMAGING
AGENT WHICH FORMS THE BASIS OF
STANDARD CHEMO THERAPY OF SMALL
CELL.
SO THIS WAS A FIRST PUBLISHED
CLINICAL TRIAL OF AN ATR
INHIBITOR, WE THEN CONDUCTED THE
PHASE 2 CLIN DALLASCOWBOYS.COM
TRIAL OF THIS COMBINATION WHICH
RESULTED IN RESPONSES IN ABOUT
36% OF 25 OR SO PATIENTS THAT WE
TREATED.
AND THEN WE EXTENDED THE STUDY
TO EXTRA PULMONARY SMALL CELL
CANCER, THESE ARE SMALL CELL
CANCERS THAT ARISE FROM NONLUNG
SITES BUT CELL MORPHOLOGIC
FEATURES AND AS WELL AS SOME
WITH SMALL CELL.
AND MORE RECENTLY WE COMPLETED A
MULTICENTER NATIONAL RANDOMIZED
TRIAL WITH TOPOTICAN AND WITHOUT
AND FOLLOWED UP ON THESE
STUDIES.
WE NOW HEAVILY INVESTED IN
IDENTIFYING DETERMINE NABTS OF
RESPONSE, WHERE SOME PATIENTS
RESPOND AND WHY SOME DON'T
RESPOND.
WE INTERESTED IN UNDERSTANDING
THE REPLICATION STRESS, THE
MOTIVATION THAT REPLICATION
STRESS IS NOT UNIQUE TO OTHER
CANCERS, IT'S FOUND IN A LOT OF
OTHER CANCERS WE WANT TO IMPROVE
INDEX OF THE TARGETED THERAPIES
AND OFTEN TYPES THESE STREEMENTS
CAN CAUSE MILE O SUPPRESSION AND
WE WANT TO IMPROVE THE ROUTINE
OF THOSE EAMENTS AND WE TRY TO
HAPPENED THE SMALL CELL LUNG
CANCER REPLICATION, SO VERY
QUICKLY I WILL GO OVER THE PHASE
2 CLIN TRIAL, SOME OF THE
CORRELATIVE STUDIES WHICH HAVE
DWIF PATIENTS.
WE DETERMINED THE COMBINATION
HERE, WE ARE LOOKING AT EFFICACY
AND WE WERE ABLE TO OBTAIN
PRETREATMENT TUMOR BIOPSIES FROM
MOST OF THE PATIENTS AND AGAIN
IT'S A UNIQUELY SOURCED HERE AT
THE CLINICAL CENTER THAT ALLOWS
US TO BRING PATIENTS IN, QUICKLY
GET BIOPSIES AND GET STARTED ON
TREATMENT QUICKLY BECAUSE THESE
ARE AGGRESSIVE CANCERS AND
PATIENTINGS PROGRESS VERY
QUICKLY.
SO WE PROFRIEL FILE THE
PRETREATMENT TUMORS, WITH THE
GOAL OF IDENTIFYING WHAT ARE THE
FEATURES THAT YOU KNOW PREDICT
RESPONSE TO TREATMENT AND WE
FOUND THAT RESPONDING TUMORS HAD
2 UNIQUE FEATURES, AND THEY WERE
RELATED TO CELL CYCLE CHOIK
POINTS AND DNA REPAIR GENES AND
THIS SUGGESTS THAT TUMORS IN
HIGHER REPLICATION STRESS, AND
MORE INTERESTING WAS THESE WERE
RESPONDING HAD INCREASED MURINE
ENDOCRINE GENE EXPRESSION, IF
YOU MPLE 1 OF MY FIRST SLIDES,
THERE'S MARKED HETEROGENEITY IN
SMALL CELL, WITH SOME HAVING
HIGHER ENDOCRINE FEATURES AND
SOME TUMORS HAVING LOWER
ENDOCRINE FEATURES, SO THESE
WITH THE HIGHER 1S RESPOND TO
TREATMENT AND THIS IS A
NEUROENDOCRINE MARKER.
IT'S NOT A HUNDRED% BIOMARKERS
NOT ALL PATIENTS WITH THE
FEATURES RESPOND.
FIFTY% OF THEM DO, BUT
COMPARATIVELY NONE ALONE RESPOND
TO TREATMENT.
APPROXIMATE WE FIND THAT THE
DURATION RESPONSE AS WELL AS
PROGRESSION FREE RADICALS
SURVIVAL IS MUCH LOWER IN THE
COMBINATION WITH PATIENTS WITH
HIGHER ENDOCRINE FEATURE.
SO WE'RE FINDING THAT SMALL CELL
HETEROGENEITY AND WE'RE FINDING
THAT THE TUMORS WITH HIGH
NEUROENDOCRINE FEATURES HAVE
MORE LIKELIHOOD OF RESPONDING
AND TOPOICE ORDER OF MICRONSER
ACE INHIBITION.
AND WE USED A SIMILAR APPROACH
THIS IS IS A DIFFERENT CLINICAL
TRIAL.
INSTEAD OF USING A DNA REPAIR
INHIBITOR WE USE IMMUNO THR
ACTIVITIES AND PROJECTS EXPE
AGAIN THE PRETREATMENT, RNA
SEQUENCING, DCR SEQUENCING AND
WE FIND THAT THEY ENRICH FOR
IMMUNE SYSTEM, RELATED PATHWAYS
BUT ALSO NEUROLOGICAL PATHWAYS
SO IT IS A LOW NEUROENDOCRINE
TUMOR THAT RESPOND TO
IMMUNOTHERAPY HERE AND WE'VE
DONE MECHANISTIC STUDIES TO
FOLLOW UP ON THIS BUT THE BOTTOM
LIEB IS THAT SMALL CELL WHICH IS
CURRENTLY THROUGH A SINGLE
DISEASE, WE FIND IT IS
HETEROGENEOUS ORY GENIUS AND WE
FIND THAT THE TUMORS AND THE
HETEROGENEITY OF TREATMENT
RESPONSE IS BASED ON THE
NEUROENDOCRINE GENE EXPRESSION
PATTERN WITH SOME TUMORS
RESPONDING TO DNA REPAIR
TARGETED THERAPIES AND OTHER
TUMORS RESPONDING TO
IMMUNOTHERAPIES.
SO IN FOLLOW UP STUDIES WE TRIED
TO UNDERSTAND, YOU KNOW WHAT IS
DRIVING IN THE TUMOR
HETEROGENEITY, AS YOU CAN
IMAGINE, THESE TUMORS ARE
HETEROGENEOUS ORY GENIUS AND
LIKELY PLASTIC AND PROBABLY MOVE
FROM 1 CELL STATE TO ANOTHER AND
WE ARE TRYING TO UNDERSTAND WHAT
DOES DRIVING THE TUMOR FOR INTRA
TUMOR HETEROGENEITY AND AS CAN
YOU IMAGINE IT COULD BE
UNDERLYING TREATMENT FAIL NUR
MANY OF THESE PATIENTS.
SO WE TRY TO UNDERSTAND AND IN
THE HETEROGENERATED AITY, IN A
SIMPLE FRAMEWORK, TRYING TO
UNDERSTAND THE DETERMINANTS OF
HETEROGENEITY AND FOCUSING ON
THE DETERMINANTS, IT IS KNOWN
THAT SMALL CELL LUNG CANCER
EVOLVES FROM A NEUROEND COKRIN
STATE AND WITH TIME AND
TREATMENT, IT EVOLVES INTO A
NIEWN NEUROENDOCRINE CELL STATE
AND MYC STARTED TO MEDIATE THIS
BY REPROGRAMMING THE
NEUROENDOCRINE FATE BUT IT DOES
NOT KNOW WHAT THIS LEVEL ENABLES
ACTIVATION WHICH ENABLES SMALL
CELL LUNG CANCER TO BE PLASTIC
AND TRANSFORM FROM 1 CELL STATE
TO ANOTHER.
WE FOCUSED ON EXTRA CHROMOSOMAL
DNA SO THESE ARE ELEMENTS THAT
ARE FOUND OUTSIDE OF THE
CHROMOSOME WHICH ARE BASICALLY,
THEY'RE OWN SEGREGATED AND THEY
CAN ACCUMULATE IN LARGE NUMBERS
WITHIN SINGLE--WITHIN SINGLE
CELLS AND THUS DRIVING HUGE
AMOUNTS OF EPITHELIAL RAMIEWROR
HETEROGENEITY, AND WE ALSO
FOCUSED ON THE DETERMINANTS AND
WE FOUND THAT THE TUMOR
MICROENVIRONMENT CAN SHAPE THE
SMALL CELL LUNG CANCER SUBTYPES
BUT I KOANT GO INTO THE DETAILS
BUT BOTTOM LINE THIS IS TUMOR
INTRINSIC DEEMERGINGINANTS OF
HETEROGENEITY AND SO HERE'S THE
DNA LOOKS AND SO THESE ARE MYC
CHROME SOLEAL DNA HERE AND
EDCNA, AND WE FIND THAT THE
MECHANISM OF MYC AMPLIFICATION
BY THE EXTRA CHROME SOLEAL DNA
AND IT REALLY MATTERS BECAUSE IN
PATIENTS WITH COMPLEX EXTRA
CHROMOSOMAL DNA THEY SURVIVE
MUCH LESS TO PATIENTS WITH
TUMORS THAT DON'T HAVE EXTRA
CHROMOSOMAL DNA.
AND THIS IS A PATIENT WHO WE
PERFORMED RAPID AUTOPSIES AND WE
FIND THAT WITHIN THIS PATIENT
MULTIPLE METASTATIC SITES HAD
DISTINCT MECHANISMS OF EXTRA
CHROMOSOMAL DNA AMPLIFICATION
AND, YOU CAN SEE THAT IT'S EXTRA
CHROMOSOMAL AND THAT HAS
CONSEQUENCES IN TERMS OF
TRANSCRIPTIONAL PHENOTYPE AND WE
FIND THAT THERE ARE APPROACHES
THAT YOU CAN USE TO
NONINVASIVELY DETECT THESE SMALL
CELL LUNG CANCER TRANSCRIPTIONAL
SUBTYPES FROM PLASMA.
AGAIN IT'S A CHALLENGE TO GET
THESE PATIENTS BIOPSIES SO WE'RE
LOOKING AT TRANSCRIPTION START
SITE, HISTONE MARKS INSERTING 3
DNA AND WE FIND COMPARED TO
TUMOR RNA SEQUENCING WE FIND
THERE'S GOOD CORRELATION BETWEEN
INFORMATION WE DEVELOP FROM THE
TUMOR RNA SEQ, FOR THE
TRANSCRIPTION FACTORS, D1 AS
WELL AS PLASMA CIRCULATING DNA
IN CHIP-SEQ.
SO WE FIND THIS IS A SINGLE
STATE TEASE NOW BUT IT'S
MULTIPLE DISEASES, THERE ARE
MULTIPLE VULNERABILITIES, WE
IDENTIFIED GERM LINE SMALL CELL
LUNG CANCER WHICH IS UNIQUE
VULNERABLES AND WE FOCUS ON
NOVEL SUBSETS, THE DRIVERS OF
HETEROGENEITY AND NONINVASIVELY
IDENTIFYING THESE IN PLASMA,
AGAIN, THANK YOU FOR YOUR
ATTENTION.
YEAH, THIS IS PEOPLE FROM MY
CLINICAL GROUP AND MY LAB AND A
BIG THANKS TO THEM AND ALL OF
YOU.
[ APPLAUSE ]
>>SO OBVIOUSLY
WE HAVE 2 INCREDIBLE TENURE
TRACK SCHOLARS HERE TO REAL HE
HELP ANSWER YOUR QUESTIONS ABOUT
WHAT THEIR PATH WAS LIKE GOING
FROM BEING A FELLOW JUST LIKE
YOU IN THE NIH FELLOWSHIP
PROGRAMS AND THEN MOVING ON TO
THESE INCREDIBLE RESEARCH
CAREERS SO I WANT TO THANK YOU
BOTH FIRST FOR SHARING YOUR
RESEARCH AND THE SCIENCE BEHIND
YOUR WORK.
YOU BOTH HAVE DEVELOPED RESEARCH
LABS THAT SPAN BASIC TO CLINICAL
INTERVENTIONS, SO I REALLY THINK
YOUR EXAMPLES OF WHAT WE JUST
CALL TRUE TRANSLATIONAL
RESEARCHERS AND I THINK THAT'S A
WONDERFUL THING THAT YOU
ACCOMPLISHED.
AND IT IS NOTABLE THAT YOU BOTH
COMPLETED YOUR FELLOWSHIPS HERE
AND HAVE GONE ON TO CONTINUE
YOUR RESEARCH CAREER IN THE
INTRAMURAL PROGRAM AND THEY
MIGHT--THE NEW FELLOWS MIGHT
KNOW WHAT A LASKER OR CLINICAL
FELLOWS SCHOLAR IS, SOMETHING WE
MIGHT TALK ABOUT BUT I'M SURE
THE FELLOWS WILL WANT TO KNOW
MORE ABOUT YOU AND YOUR GABBING
GROUND SO WE CAN START THE PANEL
DISCUSSION.
OKAY, SO FIRST OF ALL, YOU GO IN
WHATEVER ORDER YOU WANT BUT
PLEASE TELL US A LITTLE BIT
YOURSELF, YOUR BACKGROUND,
PERHAPS YOUR FAMILY, WHERE YOU
WERE BORN AND GREW UP.
>>YEAH, SO I GREW UP IN INDIA,
I WAS BORN AND RAISED IN THE
SOUTH OF INDIA IN A PLACE KAWED
[INAUDIBLE ], I STARTED MEDICAL
SCHOOL IN 96.
AND I COMPLETED A POST GRADUATE
TRAINING IN INTERNAL MEDICINE AT
THE SAME INSTITUTE I DID MY
MEDICAL SCHOOL SO FOR 10 YEAR I
WAS IN BANG LOR, I CAME TO THE
U.S., I DID MY RESIDENCY IN
UPSTATE NEW YORK AND SYRACUSE
AND THEN I CAME HERE IN 2010.
SO BEEN A BIT ALL OVER THE PLACE
AND HERE I AM.
>>I AM CURIOUS WHAT MOTIVATED
YOU TO MOVE FROM INDIA TO THE
U.S.?
>>YEAH, THE BIG MOTIVATION WAS
TO TRY TO DO SOMETHING JUST
BEYOND CLINICAL MEDICINE.
SO WE DEVELOPED A LOT OF
OUTSTANDING CLINICAL SKILLS AND
THAT WAS MOSTLY BECAUSE OF LACK
OF DIAGNOSTIC EQUIPMENT WHICH
WAS NOT, YOU KNOW--THINGS HAVE
IMPROVED NOW BUT IT WAS NOT AS
GREAT.
WE WERE VERY GREAT AT DIAGNOSING
SYMPTOMS AND THINGS BUT NOT
REALLY GREAT ABOUT DOING MUCH
ABOUT IT AND I THINK THERE WAS
ALWAYS THIS MOTIVATION TO TRY
AND DO SOMETHING MORE THAN JUST
CLINICAL MEDICINE AND I THOUGHT,
YOU KNOW THIS WAS REALLY A GREAT
PLACE, ACTUALLY THE FIRST TIME I
CAME TO THE U.S. WAS IN 2005.
IT WAS ACTUALLY FOR APLASTIC
ANEMIA AND MDS CONFERENCE WHICH
DR. NEAL YOUNG ORGANIZED DOWN IN
D. C. SO I COME WITH MY POSTER
BASICALLY WHICH WAS LOOKING AT
LOW DOSE OF CYCLOSPORIN FOR
PATIENTS WITH APLASTIC ANEMIA
AND YOU KNOW I THOUGHT IT WAS
GREAT STUFF BUT WHEN I CAME HERE
I REALIZED JUST THE AMOUNT OF
WORK THAT WAS BEING DONE AND SO
FORTH, SO, 15, THE REAL
MOTIVATION WAS TO TRY TO DO
SOMETHING MORE AND YOU KNOW TRY
TO LEARN SOMETHING MORE ABOUT
THE DISEASE AND DO SOMETHING
MORE.
>>OKAY, SO WOULD YOU LIKE TO
SPEAK TO THAT TOO?
>>SURE, I GREW UP IN SAN JOSE,
MY FATHER WAS A DOCTOR SO I
PRETTY MUCH ALWAYS KNEW I WANTED
TO BE A DOCTOR, I WORKED WITH
HIM IN HIS CLINIC AND I GOT
INTERESTED IN SICKLE CELL
DISEASE IN COLLEGE.
SO I KNEW PRETTY MUCH EARLY ON,
MOST PEOPLE ARE NOT LIKELY BUT I
PRETTY MUCH NEW EARLY ON I WAS
INTERESTED IN SICKLE CELL JUST
BECAUSE I READ ABOUT IT AND I
SAW IT AS SOMEWHERE WHERE I
COULD MAKE A DIFFERENCE.
FROM WHAT I READ, IT SEEMED LIKE
THE PATIENTS WEREN'T BEING
TREATED PROPERLY AND I--SO AFTER
MY FIRST YEAR OF MEDICAL SCHOOL,
I WORKED IN A LAB AND REALIZED
THE LAB WAS NOT THE PLACE FOR ME
BUT I REALLY LOVE SEEING THE
PATIENTS WITH THEM IN CLINIC SO
I WENT TO A MEDICAL SCHOOL
CONFERENCE, I GUESS DURING MY
THIRD YEAR OF MEDICAL SCHOOL AND
I MET KENNY WILLIAMS AND HE TOLD
ME ABOUT THE NIH AND TOLD ME
ABOUT THE CLINICAL RESEARCH
TRAINING PROGRAM AND THE
CLINICAL RESEARCH WAS IN THE
NAME, I WAS REALLY INTRIGUED SO
I CAME HERE AND YOU SEE 1 OF THE
PROJECTS I WORKED ON, IT WAS
FROM A CAREER STANDPOINT 1 OF
THE MOST LIFE TRANSFORMING YEARS
FOR ME.
I REALLY LOVED BEING AT THE NIH,
I LOVED WORKING WITH JOHN
TISDALE, AND JUST, IT WAS JUST
AN INCREDIBLE EXPERIENCE.
SO I WENT, FINISHED MEDICAL
SCHOOL, DID MED PEDS AND WHEN I
CAME BACK AND FINISHED MY 2
CLINICAL YEARS ON AN ADULT
HEMEATOLOGY AND PEDEIAT
HEMEATOLOGY AND ONCOLOGY I
LOOKED BA BEING TO JOHNS LAB AND
THE PROTOCOL WAS WORKING REALLY
WELL AND IT WAS EXCITING BUT
THERE WERE A LOT OF PATIENTS WE
WERE HAVING TO TURN AWAY BECAUSE
THEY DIDN'T HAVE A DONOR.
SO, JOHN SAID WHY DON'T YOU WORK
ON DEVELOPING THIS HAPPEN LO
IDENTICAL APPROACH.
SO AS I SAID, I WAS A PI ON THE
PROT COLAND WITH HIM AS A FELLOW
FOR 5 YEARS AND I CAME TO THE
NIH BECAUSE I WANTED TO WORK
WITH JOHN, I WANTED TO BE HIS
STAFF CLINICIAN BUT WHEN I
FINISHED MY 5 YEARS THAT WAS THE
MAXIMUM TIME YOU CHRONIC LIVER
DISEASE DO THAT, HE DIDN'T HAVE
I POSITION FOR ME SO THATTA WHEN
I LEARNED ABOUT THE ASSISTED
CLINICAL INVESTIGATOR AND THAT
WAS HOW THE DOOR OPENED FOR ME.
I NEVER WOULD HAVE THOUGHT I
WOULD HAVE HAD MY OWN LAB, THAT
WAS NOT ON MYRA DART--DARTH AT
ALL, SO, YEAH, BUT I REALLY
LOVED BEING IN ACI AND BEING
ABLING TO MAKE DECISIONS ON MY
OWN AND BE RESPONSIBLE FOR THE
TRAJECTORY AND GROW TO REALLY
LOVE MENTORING STUDENTS, SO
THAT'S WHY I WENT ON TO THE
LASKER.
>>YOU KNOW, CAN YOU REFLECT A
BIT ON YOUR SUBSPECIALTY
TRAINING HERE AT NIH AND COULD
YOU REFLECT ON HOW IT MIGHT HAVE
SET YOU UP TO BE A RESEARCHER
LIKE YOU ARE, NOW DID THAT WORK
FOR YOU AND MORE DETAILS ABOUT
WHAT YOU DID EACH YEAR AND
PERHAPS LIKE TURNING POINTS?
>>YEAH, YOU KNOW WHEN I WAS
DOING MY RESIDENCY IN SYRACUSE I
HAD KNOWN ABOUT NIH AND THE
TRAINING PROGRAM HERE.
I WORKED IN A LAB, AND A MENTOR
AT THAT TIME HERE HAD HIS
FELLOWSHIP AT NIH IN THE LATE
1970S.
HE WAS ACTUALLY A BIG PLAYER IN
THE DISCOVERY OF HDLB1 AND HE
HAD A PAPER IN 1981 ON THE
SECOND DAY OF HIS FELLOWSHIP
WHERE HE DISCOVERED HDLB1, IN A
NEW VIRUS IN PATIENTS WITH
[INDISCERNIBLE] SYNDROME, CUE
TAINIOUS T-CELL, BUT WHEN I DID
COME, I HAD THE EXPERIENCE IN
THE LAB AND I HAD ALL THE
CLINICAL EXPERIENCE BUT REALLY
NO EXPERIENCE ABOUT CLINICAL
TRIALS OR WHAT CLINICAL RESEARCH
IS, REALLY A TOTAL NEWBIE IN
THAT AREA, BUT REALLY THE 3
YEARS AT NIH AND I DID 6 MONTHS
OF MY HEMEATOLOGY TRAINING, TOO,
REALLY TRANSFORMED BY VIEW OF
CLINICAL RESEARCH AND I GOT AN
OPPORTUNITY TO WRITE A LOT OF
CLINICAL PROTOCOLS, AND I THINK
THAT WAS REALLY THE BASIC
TRAINING THAT I HAD WRITING A
LOT OF CLINICAL TRIALS.
I WAS INVOLVED IN A LOT OF
TRANSLATIONAL STUDIES, SO I FEEL
LIKE THE 3 YEARS WERE CRITICAL
AND WE HAD A LOT OF IMPORTANT
STUDIES SOPHISTICATEDY WOO HAD 1
OF THE FIRST PRECISION ONCOLOGY
STUDIES WHERE WE LOOK ATA BIOPSY
PATIENT, LOOK AT PATIENTS
MUTATION AND ASSIGN THEM A
PARTICULAR TREATMENT AND EVEN
NOW THOSE CLINICAL TRIALS HAVE
BEEN DONE, THOSE LARGE NCI
CLINICAL TRIALS BUT WE WERE 1 OF
THE FIRST TO DO A CLINICAL
TRIALS AND WE ENROLLED OVER 350
PATIENTINGS IN A 2 YORE TIME
FRAME IN A CLINICAL TRIAL, DISP
THIS WAS--YOU KNOW SO I GOT
REALLY COMFORTABLE WITH DOING
CLINICAL TRIALS.
TAKING CARE OF PATIENTS AND
ANOTHER IMPORTANT TRIAL WE DID
WAS, YOU KNOW LOOKING AT THYMIC
CARCINOMAS, THORACIC CANCERS
ORPHAN CANCERS BUT NOT MUCH
OPTION THERAPY AFTER CANCER
RELAPSE AND WE DID 1 OF THE
FIRST TRIALS OF KINASE
INHIBITORS PARTICULARLY
SEROTINIB.
I WAS VERY HAPPY BECAUSE OUR
TRIAL LED TO THAT BEING INCLUDED
IN THE NCC GUIDELINES TO TREAT
PATIENTS SO VERY HAPPY THAT THAT
LED TO, YOU KNOW A PRACTICE
CHANGING CLINICAL TRIAL THAT I
WAS ABLE TO BE PART OF THAT.
SO, AGAIN, IT WAS A REAL, YOU
KNOW WONDERFUL PERIOD, A LOT OF
WORK, BUT YOU ARE INVOFFED WITH
A LOT OF EXCITING PROJECTS AND
DOG A LOT OF INTERESTING STUFF.
>>AND YOU'RE SAYING THIS IS
WHILE YOU'RE STILL A FELLOW.
>>INCREDIBLE.
>>YEAH, IT JUST SPEAKS TO THE
OPPORTUNITIES THAT ARE AVAILABLE
HERE LIKE I SAID EARLIER, THE
ABILITY TO DO BIOPSIES IN
PATIENTS THAT YOU CANNOT BIOPSY
ANYWHERE ELSE BECAUSE OF THE
INFRASTRUCTURE AND SO I THINK
IT'S, YEAH.
>>SO FOR ME IT WAS FUNNY
BECAUSE I NEVER--IT WAS NEVER ON
MYRA DART--DARTH TO HAVE A LAB
HERE, THINGS WERE HAPPENING THAT
WERE TRAINING ME, EVEN WHEN I
WAS A SUBMITTAL STUDENT WOB OF
MY OTHER PROJECTS WAS A WROTE A
BIG CLINICAL PROTEIN COMPLEX C
OT--PROTOCOL AND I WAS ABLE TO
PRESENTED TO THE VERMEN INFECTED
VIEW BIEWRD, CONTACTED THE FDA,
GOD PERMISSION TO MOVE FORWARD
AND STARTED RECRUITING PATIENTS
AND UNFORT MATILY THE DRUG WE
WERE GOING IT USE IN OUR DRUG
POPULATION, CAUSED ANNA FLACKSIC
REACTION IN ANOTHER POPULATION
SO I WASN'T ABLE TO DO IT BUT I
HAD THAT EXPERIENCE AND THEN
WHEN I CAME BACK AS A FELLOW, MY
FIRST 2 YEAR CLINICAL YEARS
BECAUSE I DID ADULT HEMEATOLOGY
AND PEDIATRIC HEME ONC, I THINK
MY FELLOWSHIP WAS BUZZIER,
DEFINITELY THE OTHER HEMEATOLOGY
FELLOWS, I WAS ROTATING IN
DIFFERENT PLACES AND THE SECOND
YEARA AT HOPKINS FOR THE
PEDIATRIC YEAR WAS REALLY BUSY
SO I WASN'TA TO A LOT OF
RESEARCH DURING THAT TIME BUT
WHEN I GOT TOWARDS THE END AND I
KNEW I WAS--I WANTED TO GO BACK
TO JOHNS LAB, MY MAIN GOAL WAS
TO DEVELOP THIS HAPPEN LO
IDENTICAL TRANSPLANT APPROACH
BUT I ALSO WORKED ON A PROJECT
THAT WAS GOING TO BE ABLE TO BE
DONE IN A SHORTER PERIOD OF
TIME.
SO I ACTUALLY STARTED PREPARING
FOR IT AS A SECOND YEAR FELLOW
SO TOWARDS THE END OF MY
CLINICAL YEAR, DOG THE
BACKGROUND READING AND WRITING
THE PROTOCOL BECAUSE THE
PROTOCOL TAKES SO LONG TO GO
THROUGH THE SYSTEM AND I DIDN'T
WANT TO USE UP A LOT OF MY
FELLOW TIME WAITING FOR A
PROTOCOL TO GO THROUGH SO THAT
WAS 1 THING THAT WAS HELPFUL AND
THEN AS I SAID, JOHN ALLOWED ME
TO BE THE PI ON THE HAPPEN LO
IESHES DENTICAL PROTOCOL SO
THEREYA A LOT OF
RESPONSIBILITIES AS A PI AND
ESPECIALLY AT 1 TIME HOPKINS
DOING HAPPEN LO IDENTICAL
TRANSPLANTS IN ADULTS WITH
SICKLE CELL DISEASE AND WE
DIDN'T KNOW WHAT THE TOXICITY OR
EFFICACY COULD BE.
AND THE GUY THAT HAD THE
TRANSPLANT AT THE TIME HAD
TRANSPLAIPTED 10 PATIENT WITH
LEUKEMIA USE THE HAPPEN LO
APPROACH AND THEY ALL DIED AND I
WAS SHOCKED THAT HE ALLOWED ME
TO BE THE PI BUT I HAD A LOT OF
SPENCE OF RESPONSIBILITY, I WAS
THE 1 THAT HAD TO REPORTOT
PATIENTS AND I HAD TO REPORT THE
SEs AND AEs, SO THIS
DEVELOPED ME TO RUN MY OWN LAB
AND RUNNING THE TRANSLATIONAL
PROGRAM.
>>SO I THINK YOU BOTH SPOKE TO
THE HIGH RISK-HIGH REWARD TRIALS
THAT I DO HERE, CORRECT AND ALSO
YOU MENTIONED LIKE THE
INFRASTRUCTURE HERE, CAN YOU SAY
A BIT ABOUT HOW THE CLINICAL
CENTER AND THIS INTRAMURAL
PROGRAM AND HOW IT RUNS MAYBE
DIFFERENTLY FROM AN OUTSIDE
INSTITUTION, HOW DID THAT
FACILITATE YOUR BEING ABLE TO DO
YOUR RESEARCH?
>>I THINK A BIG CRITICAL FACTOR
IS THE ABILITY TO TAKE CARE OF
PATIENTS LIKE WITHOUT HAVING TO
WORRY ABOUT, YOU KNOW THE SOCIAL
ISSUES OR INSURANCE ISSUES OR
THINGS LIKE THAT, AND FOR US,
FOR THE CANCER, LIKE SMALL CELL
WHICH IS REALLY AGGRESSIVE THAT,
YOU KNOW TO GIVE THE RESOURCES
TO THE PATIENTS, SO THAT THEY
CAN COME HERE QUICKLY, YOU KNOW
PAYING THEIR COST OF
TRANSPORTATION AND STUFF LIKE,
THAT'S FROM THE PATIENT SIDE,
AND I FEEL LIKE FROM THE FROM A
MORE BAIVENG AND SCIENTIFIC
SITE, THAT'S A LOT OF
COLLABORATION, AND I FEEL LIKE
THERE ARE LOTS OF UNIVERSITIES
WHERE THAT HAPPENS BUT I FEEL
LIKE THERE'S LESS OF A BEIGIER
TO BRIDGE THESE GAPS BECAUSE YOU
KNOW PEOPLE ARE NOT STRESSED
ABOUT THEIR NEXT GRANT.
THOSE 2 FROM THE PATIENT ANGLE
AND AS WELL AS FROM THE SCIENCE
ANGLE IS JUST A LOT OF
OPPORTUNITIES.
>>YEAH, THATY A HUGE POINT HE
MADE, NOT HAVING TO DEAL WITH
INSURANCE, I THINK ANOTHER THING
THAT WAS VERY ATTRACTIVE TO ME
IS THAT IT'S BUSY THE FIRST 2
CLINICAL YEARS BUT ON THE THIRD
AND FOURTH YEAR I HAD TIME TO
FOCUS ON RESEARCH SO THAT WAS A
HUGE PLUS.
AS FAR AS RESOURCES AND I CAN
ONLY SPEAK TO NHLBI, AS FAR AS
WE'VE GONE, THEY WANT TO GIVE
YOU THE RESOURCES TO SUCCEED.
SO I HAVE AND I'VE GOTTEN BUSIER
I'VE KNOTTEN MORE
RESEARCH--GOTTEN MORE RESOURCES
SO I HAVE 2 RESOURCE NURSES,
ACCESS TO A STATISTICIAN, DATA
MANAGER, PROTOCOL NAVIGATOR AND
THEY HELP WITH ANY RESOURCE
STRESS WTION WRIETDING THE
PROTOCOL WHAT ELSE?
THE PEOPLE IN MY LAB BUT AS FAR
AS THE CLINICAL EXPART GETTING
THE PROTOCOL THROUGH, THEY
MONITOR YOUR NEEDS AND GIVE YOU
THE SUPPORT YOU NEED TO BE
SUCCESSFUL.
>>CAN YOU TALK ABOUT THE ROLE
OF MENTORS IN YOUR TRAINING AND
ANY ADVICE YOU WOULD GIVE TO THE
FELLOWS ABOUT MENTORING.
>>YOU KNOW I HAD MENTORS OVER
THE COURSE OF MY CAREER, LIKE
EVEN WHEN I STARTED IN
INDICATORSIA, AND THEN IN
UPSTATE NEW YORK, I HAD MENTORS
DURING MY FELLOWSHIPS.
OBVIOUSLY THEY HAVE A VERY
CRITICAL AND CRUCIAL ROLE.
AND I TRIED TO TAKE THE BEST OF
ALL OF THESE MENTORS, I THINK
IT'S EVERYBODY'S WORKING ON
THEIR MENTORING SKILLS, YOU KNOW
I DON'T THINK ANYBODY'S PERFECT
IN ALL ASPECTS, I REALLY TRIED
TO IMPROVE OR INCORPORATE THESE
POSITIVE THINGS THAT ARE IN MY
MENTORING APPROACHES AND I WOULD
SAY, IN TERMS OF CHOOSING A
MENTOR, I THINK IT'S IMPORTANT
TO HAVE, YOU KNOW SOMEONE WHO'S
ADDRESSING A BIG PROBLEM OR AN
IMPORTANT PROBLEM.
AND THAT MAY SEEM TRIVIAL BUT
IT'S IMPORTANT BECAUSE 1 IT'S
IMPORTANT TO GET YOU MOTIVATED
TO DO THE WORK, AND 2 IS, YOU
KNOW IT MIGHT HELP YOU GET MORE
OPPORTUNITIES LATER ON, BUT I
THINK THE QUESTION IS VERY
IMPORTANT, THAT THE LAB IS
STUDYING AND IT COULD BE BIG IN
TERMS OF PATIENTS AFFECTED SO
FOR EXAMPLE, LUNG CANCER IS A
COMMON PROBLEM OR PANCREATIC
CANCER, NOT AS COMMON AS LUNG
CANCER BUT A BAD PROBLEM.
SO YOU WANT TO PICK A PROBLEM
THAT HAS--AT LEAST MY OPINION
AND MY FEELING IS THAT, YOU KNOW
THAT AFFECTS A LOT OF PEOPLE
THAT HAS REALLY AFFECTING
PATIENTS IN TERMS OF THEIR
LETHALITY OR MORTALITY, AND I
THINK IT'S ALSO IMPORTANT TO
HAVE MENTORS WHO ARE ACCESSIBLE
BUT AT THE SAME TIME WHO GIVE
YOU A LOT OF FREEDOM.
SO YOU DON'T WANT TO BE LIKE A
CLONE OF YOUR MENTOR, YOU WANT
TO BE INDEPENDENT, SO I THINK
BOTH ARE IMPORTANT AND I THINK
YOU KNOW ALWAYS THINK BEYOND THE
MENTOR, ALSO TO OTHER PREME IN
THE LAB BECAUSE YOU'RE NOT
ALWAYS TALKING TO THE MENTOR, I
THINK IT'S GOOD TO HAVE
RELATIONSHIPS WITH OTHER PEOPLE
IN THE LAB TO MAKE SURE THEY'RE
EASY TO WORK WITH AND THINGS
LIKE THAT.
SO LAB, ACCESSIBILITY, FREEDOM,
AND THE GENERAL LAB ENVIRONMENT
OR CLINICAL ENVIRONMENT, I
THINK, I'M SURE THERE ARE OTHERS
BUT AT LEAST IN MY MIND THESE
ARE THINGS THAT ARE IMPORTANT.
>>YEAH AND I KNOW YOU HAD A
PRIMARY MENTOR DR. TISDALE FOR
QUITE A WHILE BUT THE ISSUE IN
SOME WAYS WAS HOW TO
DEVELOPMENTAL ENDOCRINOLOGY
REBTIATE AND MAKE YOUR OWN PATH
IS THAT SOMETHING THAT WAS
DIFFICULT?
>>YEAH, SO, THAT'S GOING TO
OTHER QUESTIONS, I THINK 1 OF
THE BIGGEST CHALLENGES I'VE HAD
SINCE I'VE BEEN AT THE NIH FOR
SO LONG IS FIGURING OUT HOW TO
DIFFERENTIATE YOURSELF FROM YOUR
MENTOR AND IT CAN BE HARD, IT'S
NOT JUST LOOKING OR BEING LIKE A
CLONE BUT IT'S ALSO ON PAPER,
LIKE IF YOU WANT TO BE A TENURED
TRACK INVESTIGATOR HERE YOU HAVE
TO HAVE YOUR OWN NICHE AND THAT
WAS CHALLENGING FOR ME BUT HE
GAVE ME THE HAPPEN LO IDENTICAL
PROGRAM WHEN I WAS--INITIALLYIVE
WASN'T WHEN I WAS BE ABLE TO
FOCUS ON, AND HE WAS A SICKLE
CELL TRANSPLANT PERSON, I DIDN'T
THINK HE WOULD ALLOW ME TO THAT
I CAN TAKE THAT ON BUT THAT
SHOWS AGAIN THE PERSON THAT HE
IS AND SO I HAD TO FIGURE OUT
WHAT IS MY NICHE, WHAT AM I
PASSIONATE ABOUT AND MY
EXPERTISE AND I WAS ABLE TO DO
THAT BUT MORE ABOUT WHAT YOU
WERE SAYING, IT'S REALLY
IMPORTANT HOW MULTIPLE MENTORS,
SO I HAVE MENTORS IN DIFFERENT
AREAS SO I HAVE SPOKEN A LOT
ABOUT JOHN BUT I HAVE MENTORS
OUTSIDE OF NIH,
M-TEBURKEULOSEISORS FOR WORK
LIFE BALONS OR COLLEAGUES THAT I
LOOKED UP TO WAS THE YEAR AHEAD
OF ME WHO WAS A TENURED TRACK
INVESTIGATOR WHO I THINK WAS
REALLY IMPORTANT TO HAVE
MULTIPLE PEOPLE THAT YOU GO TO
AND IT'S ALSO VERY IMPORTANT FOR
YOU TO BE THE 1S TO INITIATE AND
CONTINUE THE RELATIONSHIP AND
NOT WAIT FOR YOUR MENTOR TO
REACH OUT TO YOU TO BE VERY
CLEAR WHAT YOU LIKE FROM THAT
MENTOR AND TO FOLLOW UP IS VERY,
VERY CRUCIAL.
>>OKAY, SO CAN I ASK YOU IF YOU
HAVE SOMETHING YOU WANT TO SAY,
CAN YOU DESCRIBE ANY BARRIERS OR
CRITICAL TURNING POINTS IN YOUR
CAREER AND HOW YOU DEALT WITH
THEM?
SO THINGS THAT WERE JUST--COULD
HAVE BEEN A MAKE OR BREAK MOMENT
FOR YOU IN TERMS WHERE YOU ARE
NOW.
>>I WAS JUST TALKING ABOUT IT,
I MEAN THAT WAS--SO WHEN I WAS
AN ASSISTANT CLINICAL
INVESTIGATOR, I WAS ACTUALLY
HAD--I DEPARTMENT WANT TO DO
MORE WITH TRANSPLANT WHEN I WAS
TAKING ANOTHER TRAJECTORY AND
WHEN I WAS IN THE SICKLE CELL
BRANCH AT THE TIME AND SO MANY
THINGS THAT THE BRANCH CHIEF AND
SHE SAID COURTNEY THIS IS NOT SO
INTERESTING, THRANS PLANT IS
WHAT YOU HF-TRANSPLANT IS WHAT
YOU MEDE TO DO, STHEE HELP MEDE
GO AND TALK TO JOHN AND BE
A--BITS ADVOCATE AND TELL HOW
IMPORTANT IT WAS FOR HIM TO LET
GO OF THE HAPPEN LO IDENTICAL,
THE GOOD THING FOR ME IS THAT
HE'S EXCITED AND INTERESTED IN
GENE THERAPY AND EDITING WHICH
IS DIFFERENT, SO HE HAD PLENTY
TO DO OUTSIDE OF HAPPEN LO
IDENTICAL TRANSPLANT, IT WAS
HAVING THE UMBILICAL CORD CUT,
AND SINCE I WAS A TRANSLATIONAL
STUDY AND FELLOW HE LOOKED AT ME
AND IT TOOK A BIT OF TRANSLATION
TIME FOR HYM TO SEE ME AS A
COLLEAGUE AND I THINK THAT'S
BEEN 1 OF THE BIGGEST CHALLENGES
BUT WE'RE IN A REALLY, REALLY
GOOD PLACE NOW.
>>YEAH, YOU KNOW I THINK I'VE
HAD SEVERAL TURNING POINTS, I
WOULD SAY, I THINK--I DIDN'T PUT
A LOT OF THOUGHT BO CHOOSING A
MENTOR BUT I THINK I ENDED UP
WITH A GREAT MENTOR DO DURING MY
FELLOWSHIP PROGRAM, SO I THINK
THAT WAS GREAT, THAT LOOKS BACK
AND SEEMS TO BE AN IMPORTANT
DECISION, I COULD BE DOING
SOMETHING ELSE, MAYBE IT'S NOT
REALLY A BAD AREA BUT IT'S A
TURNING POINT IS JUST SORT OF
HOW I VIEW MYSELF AS A MENTOR
AND MENTORING MY MENTORING
APPROACHES THAT CHANGED
DRAMATICALLY, SO WORKING WITH
OUTSTANDING CLINICAL FELLOWS WHO
CHANGED MY VIEW OF THINKING AND
REALLY, YOU KNOW REALLY CHANGE
THE WAY I VIEW MENTOR-MENTEE
RELATIONSHIPS.
I THINK THAT'S SOMETHING THAT
WAS LIKE TOTALLY UNEXPECTED.
I THINK THAT AGAIN IS NOT A BAD
AREA BUT IT'S SORT OF A CHANGE.
I WAS INITIALLY A STAFF
CLINICIAN POST FELLOWSHIP FOR
ABOUT 4 OR 5 YEARS OR SO BEFORE
I MOVED TO DEVELOPING AN
INDEPENDENT PROGRAM IN SMALL
CELL.
YOU KNOW, AGAIN IT WAS NOT LIKE
A 1 MOMENT SWITCH FROM WHAT I
WAS DOING PREVIOUSLY TO SORT OF
ORGANIC AND IT HAPPENED OVER A
PERIOD OF TIME AND AGAIN,
LOOKING BACK, I THINK THAT WAS
AN IMPORTANT DECISION TO SORT OF
RECOGNIZE THAT IS AN UNMET NEED
AND REALLY NO PROGRAM FOR NIH
FOR SMALL CELL, THIS IS
SOMETHING I COULD BUILD ON AND
AGAIN ISSUES YOU KNOW I HAD
WONDERFUL PEOPLE IN THE CLINIC
TO, YOU KNOW TO BUILD THE
PROGRAM ALONG WITH ME SO IT'S
NOT A 1-MAN EXERCISE AND ALSO ON
THE BASIC SIDE I WAS FORTUNATE
TO FIND A LOT OF WONDERFUL
CLINICAL COLLABORATORS WITHIN MY
CURRENT BRANCH, DEVELOPMENTAL
THERAPEUTICS BRANCH SO IT WAS
WELL SUPPORTED FROM THE CLINICAL
CENTER AS A PLACE WHERE WE SEE
PATIENTS FROM NCI AS WELL AS
COLLABORATIONS WITHIN THE BRANCH
AS WELL AS WONDERFUL CLINICAL
COLLEAGUES AND RESEARCHERS AND
OTHERS TO BUILD THE PROGRAM.
SO AGAIN, THIS IS NOT SOMETHING
THAT HAPPENED OVERNIGHT, I THINK
IT WAS A PROCESS THAT TOOK
SEVERAL MONTHS OR OVER A YEAR TO
RECOGNIZE THAT THIS WAS MY GOAL
AND THIS IS WHERE I SHOULD GO.
>>YEAH, WELL, THANK YOU.
I DON'T KNOW IF THE FELLOWS
KNOW, BUT BECOMING A LASKER
CLINICAL SCHOLAR IS A
COMPETITIVE APPLICATION.
YOU DON'T JUST GO OUT, TO BE A
FELLOW YOU HAVE TO REALLY IT'S
ADVERTISED, IT'S A VERY RIGOROUS
PROCESS TO GET 1 OF THESE
TENURED TRACK POSITIONS.
AND I IMAGINE THAT YOU'RE KIND
OF HOT COMMODITIES IN THE FIELD
EMPLOY SO HAVE YOU HAD OUTSIDE
OFFERS FROM OTHER INSTITUTIONS,
HAVE PEOPLE TRIED TO LURE YOU
AWAY AND IF SO, WHAT WERE YOU
BALANCING THERE AND DECIDING TO
STAY VERSUS LEAVING, CAN YOU
TALK ABOUT THAT?
MOST PEOPLE DO LEAVE HERE, SO
IT'S NOT--THERE'S A THE RULE
THAT MORE PEOPLE LEAVE THAN
STAY.
SO CAN YOU TALK ABOUT THAT FOR
YOURSELF AND WHAT YOU
EXPERIENCED?
>>YEAH, I'VE INTERVIEWED RIGHT
OUTSIDE OF FELLOWSHIP, I
INTERVIEWED QUITE WIDELY TO GET
A POSITION AND THEN, YOU KNOW
MAYBE ABOUT 5 YEARS INTO MY,
RIGHT AROUND THE TIME I WAS
APPLYING FOR LASKER TENURED
POSITION I APPLIED TO DIFFERENT
PLACES AND I THINK, REALLY WHAT
SETS THIS PLACE APART IS WHAT
HAS REALLY, YOU KNOW HELPED ME
HERE IS REALLY THE ABILITY TO DO
RESEARCH AND PATIENT CENTERED
RESEARCH AND ABILITY TO WITH
GREAT PEOPLE, ACCESS TO
RESOURCES LET'S ALL MAKE THIS A
REALLY NICE PLACE AND YOU KNOW,
YEAH.
>>OKAY.
>>YEAH, THERE'S A LOT OF ADULT
SICKLE CELL PROVIDERS ESPECIALLY
THAT DO TRANSPLANTS SO I'VE
GOTTEN A LOT OF REQUESTS BUT
I'VE ALWAYS WANTED TO STAY HERE
JUST LIKE YOU SAID, I LOVE THE
RESOURCES THAT ARE AVAILABLE, I
LOVE HAVING A LAB WHICH IS
TRANSLATIONAL, I CAN SEE
PROBLEMS GOING ON WITH MY
PATIENTS, BRING IT INTO THE LAB
AND TAKE IT BACK TO PATIENTS SO
THERE'S' NOT A LOT OF
OPPORTUNITY OUTSIDE OF HERE TO
DO THAT.
>>WELL, I WOULD LIKE TO END
WITH A QUESTION ABOUT HOW DO YOU
ACHIEVE WORK-LIFE BALANCE AND
WHAT ARE THE CHALLENGES YOU FACE
IN DOING SO?
>>YEAH, SO I GOT MARRIED AS A
TENURED TRACK INVESTIGATOR SO I
THINK IT'S BEEN MORE RECENTLY
TRYING TO FIGURE OUT HOW TO
BALANCE THAT AND THE WAY WE DO
IT, FIRST OF ALL MARRY SOMEBODY
WHO IS VERY SUPPORTIVE OF MY
CAREER, WE HAVE TIMES THAT I
FOCUS ON HIM AND I HAVE TIMES
THAT I FOCUS ON THE LAB, SO JUST
BEING VERY CLEAR, MAKING SURE
THEY GIVE HIM THE TIME BECAUSE
HIS LOVE LANGUAGE IS QUALITY
TIME BUT HE ALLOWS ME THE TIME I
NEED TO BE SUCCESSFUL AND FOCUS
ON MY WORK AND THAT'S HOW WE DO
IT.
>>YEAH, I THINK SIMILAR, YOU
KNOW TRY TO FOCUS WHEN I'M AT
HOME, FOCUS ON THINGSA THE HOME,
WHEN I'M HERE, I THINK THE MOST
PRECIOUS THING YOU CAN GIVE A
PARTNER OR A CHILD IS YOUR FULL
SELF, BODY AND MIND.
WITHOUT THAT THERE I'M UNHAPPY
AND WOUTR THAT YOU'RE UNHAPPY SO
IT'S MINDFUL TO BE PRESENT.
>>IS IT WORKING, IS IT A
PROCESS?
>>SOME DAYS IT'S EASY, ON A DAY
WHEN YOU HAVE A PRESENTATION,
NEXT DAY IT'S NOT THAT EASY,
YEAH.
>>OKAY.
SO ABOUT TO OPEN IT UP FOR
QUESTIONS IF ANYONE HAS, THERE'S
MICs HERE IF ANYONE IN THE
AUDIENCE HAS A QUESTION FOR YOUR
PANELISTS, FEEL FREE TO CUM UP
AND ASK YOUR QUESTION.
>>HI, THANKS BOTH FOR SHARING
YOUR TIME AND EXPERIENCE, SO MY
NAME IS KRISTI AND I JUST
STARTED IN ACI, I CAME HERE FOR
AN INFECTIOUS DISEASE FELLOWSHIP
AND CLINICAL TRIALS, PEDS, I
HAVE A DESCENT CLINICAL
STANDPOINT BUT THIS IDEA OF
BEING THE TRANSLATIONAL
RESEARCHERS, THE DESIRE TO BUILD
THE CLINICAL SIDE BUT YOU ALSO
NEED A LAB COMPONENT AND SO THE
CLINICAL SIDE TAKES SO MUCH TIME
AND GETTING THE PATIENTS THAT
YOU WANT TO WORK WITH CAN FEEL
LIKE A FULL-TIME JOB BUT TO BE
ABLE TO BE COMPETITIVE FOR A
LASKER YOU NEED A LAB
COMOPPOSITE BEHAVIORIAL
PHENOTYPE AND THEN THE YOU NEED
TO BUILD THAT CAPACITY TO BRING
IN A TRAINEE OR TRAINEES TO HAVE
A BIOLOGIST, CAN YOU REFLECT ON
WHAT IT WAS LIKE FOR YOU ON HOW
YOU BUILT THAT?
HOW YOU MANAGED THE TIME?
AND ARE THERE THOUGHTS ON THE
BEST WAY TO BUILD YOUR RESEARCH
TEAM WHEN YOU KNOW YOU'RE
LOOKING TO BUILD A TEAM THAT
PROBABLY AS STRENGTHS AND SKILL
SETS THAT YOU DIDN'T EVEN
INDIVIDUALLY HAVE IF THAT MAKES
SENSE?
>>YOU WANT TO TAKE IT?
>>YEAH, GO AHEAD.
>>YEAH, I MEAN I THINK THAT WAS
CHALLENGING AS AN ACI, AND I'VE
GOTTEN BET WE--WE--YOU THAT OVER
TIME.
I THINK I HAVE BEEN ABLE TO
FOCUS AS I'VE GOTTEN MORE
RESOURCES.
I THINK AS AN ACI, I HAD A POST
BACK AND I HAD LIKE A LAB
MANAGER BUT I WASN'T ABLE TO DO
A LOT OF THE LAB BASED RESEARCH
BUT I HAD PLANS FOR WHAT I WANT
TO DO FOR THE FUTURE SO THE WAY
I WAS ABLE TO MANAGE THAT WAS
WHEN I APPLIED, I GOT THE
TENURED TRACK POSITION I GOT A
STAFF SCIENTIST WHO WAS ABLE TO,
SO I THINK I DIDN'T HAVE--I MEAN
I HAD THE PREVIOUS EXPERIENCE
BUT I DIDN'T HAVE A LOT AS AN
ACI BUT I BUILT IT INTO MY PLACE
FOR THE FUTURE AND THAT'S--AND I
HIRED SOMEBODY THAT HAD THE
EXPERTISE I NEEDED TO BE
SUCCESSFUL.
>>SO, THANK YOU.
I THINK WE'RE OUT OF TIME.
THANK YOU ALL FOR COMING, IT'S
GREAT TO SEE YOU ALL IN PERSON
AND WE WILL SEE YOU HERE NEXT
WEEK FOR THIS SECOND OF OUR 3
LECTURES, DR. NIA SHORE WILL BE
HERE.
THANK YOU.
[ APPLAUSE ]