>> ALL RIGHT, WELCOME EVERYBODY.
THANK YO ORGANIZ
FOR THIS WONDERFUL DAY OF
RESEARCH.
SO I'M SILL SILVIALOPEZ-GUZMAN
IT'S MY PLEASURE TO BE THE
MODERATOR.
WE HAVE DR. YUKIKO ASADA FROM
THE CLINICAL CENTER TO TALK TO
US ABOUT FAIR LAB A F WHAT MAKEM
A GOOD LIFE STUDY.
>> OKAY.
THANK YOU VERY MUCH.
USUAL DISCLAIMER.
I WANT TO START WITH THE BAD
NEWS THAT I HOPE MOST OF YOU ARE
FAMILIAR WITH.
SO HOUSING EQUALITIES ALSO OFTEN
CALLED HEALTH DISPARITIES ARE
EVERYWHERE AND SOCIAL PATTERN
AND PERSISTENCE.
INEQUALITY IN LIFE EXPECTANCY,
HOW LONG PEOPLE ARE EXPECTED TO
LIVE.
THE LEFT BOTTOM IS THE LIFE
EXPECTANCY DIFFERENCE BY RACE
AND ETHNICITY.
AND WHEN YOU LOOK AT THE TOP
RIGHT THAT'S BY INCOME.
THE BOTTOM RIGHT IS MAPPED TO
WASHINGTON, D.C.
THE BOTTOM LINE MESSAGE IS
HOWEVER, WE CUT IT LIFE
EXPECTANCY DIFFERENCE BY SOCIAL
GROUPS CAN BE 10 YEARS, WHICH IS
QUITE SUBSTANTIAL.
AND IT'S ACTUALLY INCREASING.
SO WHEN WE THINK ABOUT HEALTH
INEQUITIES AND TRY TO MEASURE IT
WE THINK ABOUT SOCIAL GROUPS AND
WE HAVE RACE AND ETHNICITY,
INCOME AND IN THE COUNTIES OF
RESIDENCE LOOK AT SEXUAL
ORIENTATION, NEIGHBORHOOD,
SINGLE PARENTHOOD, LIST GOES ON
AND ON.
THOSE ARE THE DESCRIPTION OF THE
GRAY DOTS ARE SOCIAL GROUPS.
THE CORE OF WHY WE CARE ABOUT
THOSE SOCIAL GROUPS IS THE
CONCEPT OF SOCIAL DISADVANTAGE.
WHAT THAT SOCIAL DISADVANTAGE
ACTUALLY MEANS?
TRADITIONALLY RESEARCHERS HAVE
ARTICULATED SUCH A CONCEPT.
FOR EXAMPLE RESEARCHERS GOT
TOGETHER AND DECIDED WHAT WE
SHOULD COUNT FOR SOCIAL
VULNERABILITY INDEX DEVELOPED
FOR THE DISASTER MANAGEMENT IN
THE UNITED STATES.
AND FOR EXAMPLE FOR THE COVID
VACCINE ALLOCATION WE'LL USE
THAT.
OF COURSE PHILOSOPHERS HAVE A
LOT TO SAY ABOUT THE CONCEPT OF
SOCIAL DISADVANTAGE.
WE NEED TO LOOK AT THOSE
AFFECTED MOST.
HERE I'M NOT INTERESTED IN THE
GUT FEELINGS OF THE PUBLIC BUT
THE WELL THOUGHT OUT VIEWS OF
THE PUBLIC.
IF YOU'RE INTERESTED HOW WE
SHOULD ASK THEM, I THINK WE NEED
TO ASK TWO QUESTIONS.
HOW BEST TO FRAME THE QUESTION
AND HOW BEST TO DRAW REFLECTIVE,
WELL THOUGHT OUT ANSWERS.
WE CAN THINK THIS WAY.
THERE IS A LABEL WE ACADEMICS
USE, SOCIAL DISADVANTAGE.
KNOW WE'RE INTERESTED IN HOW LAY
PEOPLE THINK OF THE CONSTRUCT.
ONE WAY TO FRAME THE QUESTION IS
TO GIVE THE DEFINITION OF SOCIAL
DISADVANTAGE WE USE IN ACADEMIA
AND HOW THE GENERAL PUBLIC
REACT.
MANY DO THIS KIND OF RESEARCH.
NOTHING WRONG WITH IT BUT THE
PUBLIC MIGHT GIVE US THE ANSWER
THEY THINK WE WANT TO HEAR FROM
THEM AND WE ASK THE HARDSHIPS
AND PREVENTS GOOD LIFE.
WE'LL TAKE THE BOTTOM UP
APPROACH BECAUSE THAT'S MOST
INFLEXIBLE AND NON PRESCRIPTIVE.
SO NOW WE KNOW HOW WE WANT TO
FRAME THE QUESTION BUT THEN HOW
BEST TO DRAW RECOLLECTIVE
ANSWERS.
THE VALUE LADEN QUESTIONS ARE
DIFFICULT.
SO IT'S NOT REALLY IDEAL TO JUST
GET PEOPLE TOGETHER AND TALK
ABOUT IT.
THEY DON'T WANT TO DO THAT.
SO WE NEED SOME INNOVATIVE
APPROACH TO ENABLE OPEN
REFLECTIVE DISCUSSION.
SO TRADITIONAL GO-TO METHOD IS
THE PUBLIC WELL DEVELOPED
ENDORSED APPROACH IN POLITICAL
SCIENCE AND WE HAVE TONS OF
EXAMPLE.
CLIMATE CHANGE IS ONE EXAMPLE
OFTEN USED.
IN HEALTH POLICY THE PRIORITY
SETTING IS ONE OF THEM AND IN
THE TYPICAL PUBLIC IS LIKE THIS,
LET IDEAL CITIZENS DISCUSS IN AN
IDEAL SETTING.
HERE IDEAL CITIZENS ARE WELL
INFORMED AND BIASSED.
SO WE GIVE A BUNCH OF
INFORMATION IN AN UNBIASSED WAY
TO THE PARTICIPANTS AND LET THEM
DISCUSS IN AN IDEAL SETTING
WHICH IS LIKE A DOMINATION AND
PEOPLE ARE OPEN TO THE NEW IDEAS
AND WE SET THE CONDITION.
THAT'S THE DISCUSSION BASED BUT
WE THINK THERE'S MAYBE ANOTHER
WAY.
SO HERE'S A SERIOUS PLAY.
MAYBE THIS IS AN ABOUT TWEAK FOR
THE PUBLIC EVALUATION.
SO THIS METHOD IS THE SMALL
GROUP FACILITATED THINKING
TECHNIQUE DEVELOPED IN BUSINESS
ABOUT 20 YEARS AGO.
IT'S BEEN USED A LOT IN BUSINESS
AND EDUCATION.
AND NOW BEGINNING TO BE USED IN
OTHER ACADEMIC RESEARCH.
SO USE OF LEGO INVITES THE PLAY.
SO THERE'S IMAGINATION, USE OF
METAPHOR AND STORY TELLING AND
IT OVERCOMES A DEFENSE MECHANISM
WE MIGHT HAVE WHEN WE TRY TO
TALK ABOUT SOMETHING DIFFICULT
LIKE SOCIAL DISADVANTAGE.
THAT'S THE IDEA.
BECAUSE IT'S A LEGO, YOU TOUCH
IT SO THERE'S A CONNECTION OF
THE HAND AND THE BRAIN SO IT'S A
CONSTRUCTIONISM AND THAT OPENS
UP THE KNOWN VERBAL
COMMUNICATION.
SO STRUCTURE OF LEGO SERIOUS
PLAY IS A SMALL GROUP BUT EACH
PERSON WAS MAKING THE ANSWER FOR
THE QUESTION WE OPPOSED.
AND AFTER THAT THEY SHARED THEIR
STORY.
SO THAT STRUCTURE IS SET TO BE
QUITE DEMOCRATIC.
SO WE START THE OBJECTIVE OF THE
STUDY WITH WHAT MAKES A GOOD
LIFE STUDY IS THAT TO DRAW
INSIGHTS FROM THE GENERAL PUBLIC
ABOUT THE CONCEPT OF SOCIAL
DISADVANTAGE, SPECIFIC AIMS ARE
WE WANT TO EXAMINE LAY PERSON'S
VIEWS ON A GOOD LIFE AND
HARDSHIPS THAT PREVENT GOOD
LIFE.
THE FIRST PLOT THEY MAKE
INDIVIDUALLY.
WE KNOW INDIVIDUAL IDEAS AND
LATER WE ASK SHARE THE MODEL
COLLECTIVELY AS A GROUP MAKE THE
MODEL OF HARDSHIP TO EXAMINE THE
SHARED VIEW THERE AND THEN WE
CAN EXAMINE, INVESTIGATE WHAT
DIALOGUE IS ASKED TO INDIVIDUAL
USE BY CONTRASTING INDIVIDUAL
GROUP IDEAS AND THEN ASSESS IN
WHAT WAY LAY PERSON'S VIEW ON
GOOD LIFE AND ALERT HARDSHIP
ALIGNS WITH OR DIFFER FROM THE
PHILOSOPHICAL THEORIES AND THE
UNDERPINNINGS OF THE EXISTING
HEALTH POLICIES.
FINALLY WE WANT TO EVALUATE
ADVANTAGE AND DISADVANTAGE OF
LEGO SERIOUS PLAY AS A METHOD TO
EXPLORE LAY PERSON'S VIEW ON
CONCEPTS.
STUDY DESIGN USING LEGO SERIOUS
PLAY.
THE ONE SESSION TAKES ABOUT FIVE
TO SIX HOURS AND WE'LL ASK THE
SURVEY TO LEARN ABOUT THE
CHARACTERISTICS AND THE SAMPLE
SIZE, WE WANT TO RUN THREE
GROUPS NINE TOTAL IN THREE
COUNTIES BECAUSE WE DEVELOPED
RELATIONSHIPS OVER THE PAST YEAR
AND THEY'RE WILLING TO HELP US
RUN THE STUDY.
IN EACH GROUP THERE'S SIX TO
EIGHT PARTICIPANTS.
TOTAL WE'RE EXPECTING SIX TO 70
SAMPLE SIZE.
RECRUITMENT IS TYPICAL AS NOBEL
METHODS CONSIDER THE NETWORKS OF
OUR WONDERFUL COMMUNITY CONTACTS
AND ALSO WE PUT THE FLYERS
EVERYWHERE IN PUBLIC LOCATIONS.
AND ANALYSIS IS A QUALITATIVE
AND WE AUDIO RECORD AND
TRANSCRIBE THE STORY PEOPLE TELL
ABOUT THEIR MODEL.
THAT'S THE ANSWER TO OUR
QUESTION OF GOOD LIFE AND
HARDSHIP.
SO THIS SUMMER I HAD A GREAT
SUMMER OF RUNNING FIVE COMMUNITY
PILO
PILOTS AND WE HAVE COMMUNITY
MEMBERS NOT JUST IN THE NIH
COLLEAGUES AND THERE WAS A PILOT
STUDY.
SO WE DIDN'T COLLECT DATA.
SO I CAN'T TELL YOU WHAT I CAN
FIND BUT I HAD A VERY
INTERESTING OBSERVATION.
I WANT TO TALK ABOUT IT A LITTLE
BIT BEFORE I END AND THEN TALK
ABOUT EXPECTED CONTRIBUTIONS OF
THE STUDY.
WHAT WE WANT TO KNOW IS THE
SOCIAL DISADVANTAGE THE CONCEPT
OF IT AND I HEARD DIFFERENT
THINGS FROM THE GENERAL PUBLIC
TO THE ACADEMIC DISCUSSION.
SO ACADEMICS AND TALK ABOUT
CHARACTERISTICS SHOULD ACCOUNT
FOR SOCIAL DISADVANTAGE.
WHEN I TALK TO PEOPLE THEY
REALLY DIDN'T CARE WHAT'S IN IT
BUT IT'S MORE COLLECTIVELY A
CLUSTER OR CASCADE OF HARDSHIPS
SO WHEN IT'S A CLUSTER THING
THEY DON'T HAVE SO MUCH A
RESERVOIR MEANING ONE LITTLE
TRIVIAL THING CAN MAKE LIFE VERY
DIFFICULT.
I THINK OF THIS IF I GET THIS
RESULT IN ACTUAL STUDY I WILL
RUN LATER THIS YEAR PUT IN
POTENTIALLY IMPORTANT
IMPLICATIONS HOW WE MEASURE
SOCIAL DISADVANTAGE.
AND THE SECOND IS THE
METHODOLOGICAL.
WE'RE INTERESTED IN EXPLORING
VALUES WITH THE PUBLIC.
THERE'S TWO FIELDS WE COULD MAKE
SOME INTERESTING CONTRIBUTION.
ONE IS THE POLITICAL SCIENCE
WHERE THE STUDIES ARE OFTEN
DONE.
MAYBE OUR WAY OF DOING IT IS AN
ALTERNATIVE APPROACH TO CREATE
AN IDEAL CONDITION IN PUBLIC AND
ALSO THEY STARTED TO TALK ABOUT
MAYBE WE SHOULD INVOLVE THE
PUBLIC TO DISCUSS SOCIAL ISSUES.
SO IT'S QUITE EXCITING THEY
THEMSELVES HAVE STARTED TO TALK
ABOUT WHAT'S MISSING SO MAYBE WE
CAN COME IN AND SAY THERE'S ONE
WAY TO DO IT.
OF COURSE THE STUDY I CAN'T RUN
BY MYSELF AND I HAVE A WONDERFUL
COLLABORATORS AND ADD VIEWSERS
AND QUITE GENEROUS AND TALENTED
AND BENEFIT FROM THEIR INPUTS
QUITE A BIT.
THESE ARE MY INSIDE AND OUTSIDE
NIH COLLABORATORS.
THANK YOU VERY MUCH.
>> ARE THERE ANY QUESTIONS?
IF NOT I MIGHT ADD A QUESTION IF
THAT'S OKAY.
I THINK THIS IS FASCINATING AND
ONE THING I WAS WONDERING IN
YOUR STUDY IS HOW DO YOU TAKE
INTO ACCOUNT DIFFERENT
CULTURAL -- I REPRESENTATION OF
DIFFERENT CULTURES IN TERMS OF
THESE VALUE LADEN CONSTRUCTS
BECAUSE I WOULD IMAGINE
INDIVIDUALS PERHAPS WOULD COME
FROM CULTURES FROM VERY
INDIVIDUALISTIC MAY HAVE
DIFFERENT IDEAS OF WHAT
DISADVANTAGE MIGHT BE WHETHER
IT'S A THING OR GOOD THING AND
MAYBE THAT ENERGIZES YOU.
CAN YOU SAY MORE HOW YOU ENSURE
THAT IN YOUR STUDY?
>> YEAH, SO THAT'S A QUITE RICH
QUESTION.
I'M PROBABLY GET TO THE SURFACE
OF IT.
BASICALLY WE WANT TO HEAR THEM
ALL.
FOR THIS KIND OF STUDY IT COSTS
SO MUCH TIME.
IT'S NOT LIKE A SURVEY AND THEN
PE DO IN 20 MINUTES AND
YOU CAN HAVE REPRESENTATIVE
SAMPLE.
IT'S NOT REPRESENTATIVE.
AND IT'S OKAY.
THE WAY I THINK ABOUT IT IS IF
IT MAKES SENSE TO SOME OF YOU
IT'S LIKE A BAYESIAN.
YOU GET THE DATA POINTS
INCREASED AND BECAUSE THAT'S A
GOOD DATA POINT YOU WILL REVISE
YOUR ASSUMPTION AND YOU JUST
HAVE TO DO MANY TIMES.
ALSO MY GUESS IS IT'S WHAT KIND
OF LEVEL YOU ASK THE QUESTION IT
MAY NOT BE THAT DIFFERENT
FROM -- IT'S QUITE AN EMPIRICAL
QUESTION THAT IT'S A STRONG
FACTOR THAT PREDICTS THE VIEW OF
HARDSHIP AND A GOOD LIFE.
AND THEN IN THE PILE OF
COMMUNICATION STUDIES WE RUN WE
HAD DIFFERENT KINDS OF PEOPLE.D
DIFFERENCES BUT A LOT THEY COULD
SHARE.
SO THAT'S PART OF WHAT I WANT TO
SEE HOW MUCH BECAUSE NOW IS A
DIVISIVE TIME, CAN WE TALK AND
MY UNDERNEATH DESIRE IS YES, WE
CAN TALK IF WE CAN ASK IN A
CERTAIN WAY.
THAT'S WHERE I WANT TO CONNECT.
>> NICOLE FARMER CLINICAL
CENTER.
ABOUT THE LABEL AND CONSTRUCTS
YOU PRESENTED HAVE YOU SEEN THIS
WORK USED OR APPLIED TO WHAT WE
OFTEN DESCRIBE RACE WHICH IS AS
A PRIMARY SOCIAL CONSTRUCT WHERE
YOU BRING PEOPLE TOGETHER TO
ACTUALLY THINK ABOUT CHANGES OR
NARRATIVES ABOUT WHAT RACE IS?
I DON'T KNOW IF THIS METHOD HAS
BEEN USED WITH A DIFFERENT TYPE
OF TOPIC OR IF IT'S SO NEW IT'S
SOMETHING YOU'RE THINKING OF
DOING.
>> NO, IT'S FROM MY HEAD FOR NOW
BUT I WOULDN'T BE SURPRISED.
THAT'S THE KIND OF SUMMARY HOW I
MAKE SENSE OF HOW OTHER PEOPLE
DO SO IN A SOCIAL DISADVANTAGE
CONTEXT SOME PEOPLE HAD A
CAPABILITY APPROACH AND
RESEARCHERS SHOWED THE LIST AND
THE REACTION, WOULD YOU LIKE TO
ADD SOMETHING.ME
THAT'S THE KIND OF QUESTION.
AND SEE LESS IACH WE
WANT TO TAKE BECAUSE IT'S RISKY
BUT DESERVES A TRY IF YOU KNOW
OTHER PEOPLE THINKING AHEAD I'D
LOVE TO KNOW.
>> WE CAN TALK.
IT'D BE INTERESTING WITH
INVESTIGATORS AND SCIENTIST TO
CONSTRUCTS TOGETHER.
>> THANK YOU.
>> ALL RIGHT.
I THINK WOE CAN MOVE ON.
THIS IS DR. RAMYA RAMASWAMI FROM
NCI.
SHE'LL BE TALKING ABOUT
BROADENING HORIZONS, A BREAST
CANCER DRUG DEMONST
ACTIVITY IN KAPOSI SARCOMA.
>> THANK YOU FOR THIS INVITATION
TO SPEAK AT THE NIH RESEARCH
FESTIVAL AND I HOPE WE HIGHLIGHT
THE WORK BEING DONE AT THE NIH
RESEARCH PROGRAM AND EXCITED TO
TALK ABOUT A CLINICAL TRIAL I
LEAD HERE AT THE NCI.
JUST TO BRING US TO WHERE WE ARE
RIGHT NOW I NEED TO TAKE US TO A
LITTLE JOURNEY IN THE PAST AND
ABOUT 100 YEARS AGO, KAPOSI
SARCOMA OR KS WAS SEEN AMONG
OLDER MEN OF MEDITERRANEAN
ORIGIN.
IT WAS VERY SURPRISING IN THE
'80s YOUNG MEN WHO IDENTIFIED
MSM MEN, MEN HAVING SEX WITH
MEN, WERE DYING OF CANCER THAT
WAS PREVIOUSLY RARE AND IT WAS A
HARBINGER OF ANOTHER VIRUS, HIV
AND KS ITSELF WAS ASSOCIATED
WITH IMMUNOSUPPRESSION ASSOCIATE
WITH HIV.
IN 1987 THANKS TO THE
INVESTIGATORS HERE AT THE NIH
AND NCI, AZT BECAME ONE OF THE
FIRST DRUGS APPROVED BY HIV BY
THE FDA IN 1987.
WE SUDDENLY HAVE TO PLAY THE
ROLE OF THE ACTIVISTS AND
ADVOCACY GROUPS THAT HELPED US
TO BETTER UNDERSTAND THIS VIRUS
AND WHAT IT DOES AND ALSO ALLOW
FOR DISSEMINATION OF INFORMATION
ON THE THERAPIES THEMSELVES.
IN FACT WHEN IT COMES TO KS IT
WAS ONLY IN 1994 WE IDENTIFIED
THE VIRUD HAT CAUSES KAPOSI
SARCOMA AND THE HERPES VIRUS AND
YOU'LL IN 199 R5 THE FIRST
CHEMOTHERAPY WAS APPROVED FOR KS
AND KNOWN AS A DRUG STILL VERY
MUCH USED TODAY IN THE UNITED
STATES.
AND THIS WAS FOLLOWED BY 1997
AND THE SECOND CHEMOTHERAPY DRUG
USED FOR KS.
AND OVER TIME WITH THE USE OF
ADVANCED ANTIVIRAL THERAPY TO
TREAT HIV THOUGH WE SAW A STEEP
INCLINE WITH THE INCIDENTS OF KS
WE SKWEBTLY SAW A DECLINE OF
INCIDENTS IN THE UNITED STATES.
BUT WE RECOGNIZED WITH HIV AND
KS IT IS NOT JUST THE UNITED
STATES ISSUE THAT MORE PEOPLE
WERE DYING OF HIV AND KS
GLOBALLY.
WE'RE GRATEFUL TO MANY PROGRAMS
ESTABLISHED WITHIN THE COUNTRY
TO DISSEMINATE INFORMATION AND
THERAPIES FOR HIV WORLDWIDE.
SO WHERE DO WE STAND RIGHT NOW?
CURRENTLY THERE ARE THREE
APPROVED WIDELY USED THERAPIES
FOR KS.
TWO OF THE ONES I SPOKE ABOUT
AND A THIRD WHICH IS AN ORAL
FORMER OF AN IMMUNOMODULATORY
PROGRAM.
WHAT WE KNOW ABOUT THE CONDITION
AND VIRUS, THE VIRUS IS A DNA
VIRUS.
IT HAS TWO PROGRAMS AND EXISTS
PREDOMINANTLY IN HUMANS IN A
LATENCY PHASE AND TENDS TO
REPLICATE AND CAUSE A LOT OF
HAVOC IN THE PATIENT.
USUALLY THE VIRUS IS ACTUALLY
VERY SMART.
IT HAS IT'S OWN MECHANISMS FOR
MOLECULAR MIMICRY YOU CAN SAY
FIVE TIMES FAST BUT BASICALLY IT
EVADES THE IMMUNE SYSTEM AND CAN
PROPAGATE ANGIOGENESIS AND HAS
ITS OWN CELL CYCLE AND IS A
FASCINATING VIRUS.
IN BLUE AND RED IS WHERE WE SEE
THE HIGHEST PREVALENCE IN
SUB-SAHARAN AFRICA WHERE WITH HE
SEE HIGH RATES OF HIV.
THAT'S WHAT WE TO THE ABOUT THE
CONDITION AND VIRUS IT'S CAUSED
BY SO FAR BRIEFLY.
BUT WHEN IT COMES TO THE DAY TO
DAY MANAGE OF KS OFTEN WHEN I GO
TO ONCOLOGY CONFERENCES WITH MY
COLLEAGUES THEY'LL SAY YOU TREAT
KS I DIDN'T KNOW IT STILL EXISTS
BUT THE PICTURES ON THE SCREEN
ARE PATIENTS WE SEE UP ON THE
12th FLOOR OF THIS BUILDING.
THESE ARE PATIENTS WITH SEVERE
KS OFTEN DIAGNOSED WITH HIV
EARLY ON.
THERE'S PATIENTS WHO ARE KS.
THE PARADIGM IS YOU CAN LIVE A
NORMAL LIFE EXPECTANCY WITH THE
AVAILABLE THERAPIES WITH HIV BUT
KS IS A CONDITION THAT COMES AND
GOES A LOT OF THE TIME AND THIS
CAN BE DESPITE ADHERENCE TO HIV
THERAPIES AS WELL AS WELL
CONTROLLED HIV THE VIRUS CAN
KEEP HAVING KS COME BACK AND GO
AND COME BACK AND GO.
SO A LOT OF THE PATIENTS CAN GET
SEVERAL COURSES OF CHEMO
THERAPIES IN THEIR LIFE TIME AND
TEND TO GET THEM YOUNG.
THAT CAN IMPACT THE T CELLS AND
PROPAGATE MORE KS SARCOMA.
A LOT OF THESE TREATMENTS DON'T
ADDRESS THE VIRAL ETIOLOGY OF KS
SO WE'RE ALWAYS LEARNING MORE AS
WE'RE DEVELOPING THE IMMUNE
THERAPIES FOR THIS CONDITION.
SO AS WE THINK ABOUT NEW
THERAPEUTIC APPROACHES WE WERE
PARTICULARLY EXCITED ABOUT
AVAILABLE THERAPIES THAT WE
COULD EXPLORE FOR THIS
CONDITION.
I WANT TO TALK TO YOU ABOUT THE
CD46 BLOCKING THE TUMOR
EXPRESSIVE PROTEIN AND DOES SO
AND THUS INHIBITS THE
PROLIFERATION OF CANCER CELLS BY
CAUSING CELL CYCLE ARREST AND
BECAUSE WE DO NOT HAVE AN ANIMAL
MODEL FOR KS, A LOT OF THE DATA
HAS BEEN DEVELOPED FROM KCH CELL
LINES AND BECAUSE OF THIS CLASS
OF AGENTS THERE ARE ACTUALLY
THREE DRUGS OF CDK INHIBITORS
ANOW APPROVED FOR BREAST CANCER
WHERE WE SEE THE ISSUE OF
UPREGULATION MORE COMMON IN THIS
POPULATION.
SO THREE OF THESE DRUGS ARE
APPROVED IN EARLY AND METASTATIC
BREAST CANCER AMONG PATIENTS
WITH ER POSITIVE BREAST CANCER.
WE KNOW THERE'S INCREASED ENCE
ON THE GENE THAT REGULATES
CYCLIN G AND WORK FROM OUR LAB
WITH DR. WU HAS SHOWN IN THE
ENDOTHELIAL CELLS HAVE LED TO
THE UP REGULATION OF IMMUNE CELL
SURFACE MARKERS AND THAT ITSELF
IS PROMISING BECAUSE THAT MAY
ALLUDE TO THE IMMUNE SYSTEM
ITSELF TRYING TO BETTER CONTROL
THE VIRUS-INFECTED CELLS AND
THUS TREAT THE CANCER.
SO BASED ON ON THE APPROPRIATE
OF THE DRUG IN BREAST CANCER AND
THE AVAILABLE EVIDENCE IN CDC
INFECTED CELL LINES WE DEVELOPED
A PROTOCOL LAUNCHED IN 2021
USING APE ORAL DRUG GIVEN ONCE
EVERY DAY, TWICE EVERY DAY FOR
28 DAYS OF A CYCLE AND SO
PATIENTS RECEIVE THE STANDARD
DOSE THAT PATIENTS WITH BREAST
CANCER CAN RECEIVE.
THERE'S TWO STUDIES.
PATIENTS WHO HAD PRIOR TREATMENT
FOR KS.
IF YOU HAVE HIV AND KS THE MOST
IMPORTANT THING IS GETTING YOUR
HIV THERAPY BUT IN ADDITION YOU
GET SYSTEMIC THERAPY FOR KS.
ALL THE PATIENTS HAD HAD PRIOR
THERAPY.
IN THE PHASE 2 COMPONENT WE HAD
10 OF 15 PATIENTS SO FAR WHO
HAVE BEEN ENROLLED IN A
PREVIOUSLY TREATED PARADIGM FOR
KS.
AND SEVEN OF 10 PATIENTS HAVE
BEEN ENROLLED SO FAR WHO HAVE
HAD NO PRIOR THERAPY.
THAT INCLUDES PEOPLE WHO HAVE
JUST HAD HIV THERAPY FOR THEIR
HIV IN KS OR HAD NO OTHER
TREATMENT AND HAVE A NEW
DIAGNOSIS OF KS.
SO I WANT TO TALK A LITTLE BIT
ABOUT THE RESPONSES THAT WE'VE
SEEN AMONG THESE PATIENTS.
SO THIS PATIENT IS WELL KNOWN TO
US.
WE'VE KNOWN HIM SINCE 2018 AND
HE'S LAD FIVE LINES OF PREVIOUS
CHEMOTHERAPY AND HAS HIV.
HE'S BEEN DOING REALLY WELL FROM
THE HIV SAMPLING BUT I DON'T
KNOW HOW WELL IT PROJECTS ON THE
SCREEN BUT YOU CAN SEE VERY
BUMPY LESIONS ON THE LEGS.
THESE PATIENTS HAVE PAIN AND
SWELLING ASSOCIATED WITH
LESIONS.
THANKFULLY AFTER STARTING THE
THERAPY YOU CAN SEE SIGNIFICANT
FLATTENING OF THE KS LESIONS
HIGHLIGHTED AND THE PATIENT HAD
ABOUT 10 MONTHS OF TREATMENT
WITH RESPONSE.
SIMILARLY KS CAN AFFECT ANY PART
OF THE BODY.
AND THIS PATIENT WE SEE KS
AFFECTING THEIR FOOT.
SO HE COULDN'T WALK AROUND AND
THIS AT BASELINE HIS FEET WERE
VERY WEEPY AND SWOLLEN.
YOU CAN SEE IMPROVEMENT OF THE
LESIONS IN THE PATIENT WHO DOES
NOT HAVE HIV IN FACT.
AND YOU CAN SEE CRUSTING OF THE
LESIONS THE AND IMPROVEMENT AND
SYMPTOMATICALLY HAS BEEN DOING
BETTER AND THESE WHEN WE LOOK AT
THE OVER ALL RESPONSE AMONG ALL
PARTICIPANTS WITH HE SEE A 78%
RESPONSE RATE.
STANDARD CHEMO THERAPIES ARE 50%
TO 70% RESPONSE RATE.
THAT WAS ALL DURING THE INITIAL
PHASES OF DEVELOPING HIV THERAPY
BACK IN THE LATE '90s.
THIS IS ACTUALLY A VERY GOOD
RESPONSE RATE.
WE'VE SEEN A 50% TO 80% RATE AND
AMONG PATIENTS WHO HAD NOT HAD
ANY SYSTEMIC PRIOR TREATMENT FOR
KS WE SEE ALL OF THEM RESPOND TO
THE DRUG SO IT'S BEEN VERY
EXCITING.
SPECIFICALLY AMONG PEOPLE WITH
HIV WE'VE SEEN SIMILAR TRENDS
WITH RESPONSE RATES OF 72% AMONG
UNTREATED WE HAVE SEEN 100%
RESPONSE RATES.
SO THE BIG QUESTION START TO BE
WELL, HOW DOES IT IMPACT THE
PATIENT AND WHEN WE THINK BACK
ABOUT HOW KS AFFECTS OUR PATIENT
POPULATION ESPECIALLY IN OUR
PEOPLE WITH HIV HOW DOES IT
AFFECT THE CD4 ACCOUNT AND WILL
WE HELP IN THE SHORT TERM AND
KEEP HAVING KS IN THE LONG TERM?
WHEN WE LOOK AT THE CD4 COUNTS
IN THESE PATIENTS OVER TIME WE
DON'T SEE A DECREASE IN CD4 AND
THAT BODE WELL IN TERMS OF THE
TYPE OF OPTION FOR PATIENTS WHO
DO HAVE IT.
A
AND ARE NOW USING SPATIAL
TRANSCRIPTOMICS METHODS TO LOOK
AND SEE HOW THE HOST AND VIRUS
CHANGES OVER THE COURSE OF
TREATMENT.
AND PRELIMINARILY YOU CAN SEE A
SECTION FROM THE FIRST PATIENT
THAT I SHOWED YOU HAD A RESPONSE
AND YOU CAN START IT SEE IN THE
GREEN THAT THERE'S SOME LINE OF
POSITIVITY IN THE INFECTION.
SO THE STORY WILL CONTINUE AND
WE'RE EXCITED ABOUT THE
DEVELOPMENTS WE'VE BEEN MAKING
IN THE STUDY.
SO I WANT TO THANK OUR AMAZING
CLINICAL TEAM AND PARTICIPANTS
AND THEIR FAMILIES AND OUR
RESEARCHERS AND MANY OF MY
COLLEAGUES HERE WHO ARE PART OF
THE BRANCH.
I REALLY APPRECIATE YOUR HELP
AND THANK YOU FOR LISTENING.
>> WE CAN TAKE A COUPLE
QUESTIONS.
>> MANU PLATT.
THIS IS SOMETHING AND A
THROWBACK TO MY TEEN A YEARS.
THE WAY I LEARNED ABOUT IT WAY
BACK WHEN AND IF A PATIENT HAD
UNTREATED HIV AND KAPOSI SARCOMA
IS THIS SOMEONE WHO NEVER
DEVELOPED IT AND ARE THEY
DEVELOPING ITNG LATER EVEN WITH
MANAGED HIV?
>> WE'RE SEEING A BROAD
SPECTRUM, THANK YOU FOR THE
QUESTION IT'S VERY INTERESTING.
I CAN SPEND A LONG TIME TALKING
ABOUT IT.
WE SEE A SPECTRUM OF PATIENTS.
WE SEE PATIENTS WHO HAVE NEWLY
PRESENTED AND THERE ARE BUCKETS
OF PEOPLE WHO UNFORTUNATELY HAVE
DISADVANTAGES THAT PRECLUDE THEM
FROM GETTING ACCESS TO THEIR
ARTs TO FALL OUT OF GETTING CAL4
COUNTS AND KNEW SEE AN AGING
POPULATION WHO HAVE HAD HIV FOR
DECADES AND THEIR FRIENDS AND
LOVERS AND PARTNERS DIED OF KS
BACK IN THE '80s AND '90s.
SO THEY SEE KS EMERGE AS THEY
GET OLDER AND SEE
IMMUNOSENESCENCE.
WE'RE SEEING A SPECTRUM OF CASES
AMONG BOTH PEOPLE WITH AND
WITHOUT HIV YOUNG MSM AND OTHERS
AS WELL.
>> OKAY.
>> ANY OTHER QUESTIONS?
THANK YOU, DR. RAMASWAMI.
OKAY, NEXT UP WE HAVE DR. SARAH
JACK NCI TOO WHO WILL
TALK TALK ABOUT CANCER AMONG
TRANSGENDER AND GENDER EXPANSIVE
INDIVIDUALS.
DR. JACKSON.
>> THANK YOU, EVERYONE.
I'M HAPPY TO GO AFTER RAMYA AND
PUT IN A PLUG FOR THE DSP.
RAMYA AND I MET THROUGH THE DSP
AND FOUND COMMON AREAS OF
INTEREST AND WILL START
COLLABORATING.
SO I'M AT THE DIVISION OF CANCER
EPIDEMIOLOGY AND GENETICS WHERE
MY RESEARCH FOCUSES ON SEX
DIFFERENCES IN CANCER INCIDENTS
AND CANCER AMONG TRANSGENDER AND
GENDER EXPANSIVE INDIVIDUALS AND
I WANT TO START WITH
DEFINITIONS.
CISGENDER IS A PERSON WHO'S
GENDER IDENTITY MAXES THEIR SEX
ADESIGNED AT BIRTH AND
TRANSGENDER IDENTITY DIFFERS
FROM THE SEX ASSIGNED AT BIRTH
AND THESE ARE PEOPLE WHO
CONSIDER THEMSELVES TO BE NON
BINARY OR GENDER DIVERSE AND
PEOPLE MAY NOT IDENTIFIED WITH A
TRADITIONAL BINARY GENDER.
THEY CAN FEEL BOTH, NEITHER OR
SOMETHING IN BETWEEN.
AND THROUGHOUT THE PRESENTATION
I'M GOING TO USE OTHER TERMS
LIKE TRANS MEN OR TRANS
MASCULINE ADULT AND A GENDER
IDENTITY AND I MIGHT USE THE
TERMS TRANS WOMAN OR TRANS
FEMININE ADULT WHICH REFERS TO A
PERSON ASSIGNED MALE AT BIRTH
WITH A FEMALE OR FEMININE GENDER
IDENTITY.
WHY DO WE THINK THERE ARE CANCER
HEALTH DISPARITIES AMONG TRANS
PEOPLE?
I THINK THERE ARE FOUR MAIN
REASONS THAT HAVE TO DO WITH
THESE ON THE SCREEN SO GENDER
ATERMING HORMONE THERAPY,
SITUATIONAL FACTORS.
THESE ARE RISK FACTORS LIKE
SMOKING OR ALCOHOL USE USED AS A
COPING MECHANISM.
WE THINK THESE MIGHT BE HIGHER
DUE TO MINORITY STRESS OF THE
POPULATION FAILSES AND EXPOSURE
TO VIRAL INFECTIONS AND THEN
BARRIERS TO HEALTH CARE.
I'LL START WITH HARM AND USE.
I ALSO WANT TO MENTION WE DON'T
HAVE THAT MUCH DATA ON THESE
CANCER RISK FACTORS, CANCER
INCIDENTS OR SURVIVAL IN THE
POPULATION.
LARGELY BECAUSE WE DON'T COLLECT
GENDER IDENTITY IN OUR COHORT
STUDIES OR CANCER REGISTRIES.
SO IF YOU WERE STARTING A COHORT
STUDY OR WORKED FOR A CANCER
REGISTRY, I IMPLORE YOU TO ASKED
SEX ORIENTATION IN THE STUDY.
END OF SOAPBOX.
NOT A LOT OF RESEARCH HAS BEEN
CONDUCTED ON THE AFFECTS OF
LONG-TERM HORMONE USE AND ONE
STUDY CAME FROM AMSTERDAM THAT
SHOWED BREAST CANCER WAS
ELEVATED AMONG TRANS WOMEN
COMPARED TO CIS MEN AND WE THINK
IT HAS TO DO WITH ESTROGEN
THERAPY.
WE SUSPECT ESTROGEN WILL
INFECTIOUS THE RISK OF
TESTICULAR CANCERS THIS IS BASED
ON STUDIES ON CIS PEOPLE AND THE
SAME COHORT FOUND BREAST CANCER
IS DECREASED LIKELY DUE TO
SURGERY.
WE THINK BUT DON'T KNOW YET
CERVICAL, ENDOMETRIAL AND
CERVICAL CANCERS MAY BE
INFECTIOU
INCREASED AMONG THIS POPULATION.
THERE'S A QUESTION MARK NEXT TO
NON-REPRODUCTIVE CANCER AND
LOOKING AT THIS IN CIS GENDER
PEOPLE AND NEED TO TURN OUR
ATTENTION HOW THEY AFFECT RISK
IN THESE INDIVIDUALS.
SOME OF THE RESEARCH WE HAVE ON
CANCER RISK FACTORS THAT ARE
NON-HORMONAL SUCH AS SITUATIONAL
AND VIRAL INFECTIONS COME OUT OF
THE GROUP I PUT TOGETHER A
COHORT OF TRANS PEOPLE IN THE
UNITED KINGDOM AND WHEN YOU SEE
A QR CODE IT'S MORE INFORMATION
ON RESEARCH AND YOU CAN SCAN IT
AND WE LOOKED AT ALCOHOL AND
SMOKING AND OTHER GROUPS ON
TRANSGENDER AND TRANS FEMININE
ADULT IN PINK AND YOU ARE
LOOKING AT GRAPHS LIKE THIS
BECAUSE YOU'RE NOT AN
EPIDEMIOLOGIST I WILL JUST TELL
YOU ANYTHING ABOVE THE ONE LINE
MEANS THAT RISK FACTOR IS
INCREASED IN TRANS PEOPLE AND
ANYTHING BELOW THAT LINE MEANS
IT'S DECREASED.
SO WE FOUND THAT OBESITY, HIV
INFECTION AND MAYBE HCV
INFECTION WAS INCREASED IN TRANS
MASCULINE ADULTS WHILE HIV AND
HCV WAS INCREASED IN TRANS
FEMININE ADULTS COMPARED TO
CITES CISGENDER MEN AND COMPARED
IT TO CISGENDER WOMEN AND HIV
INFECTION AND HCV INFECTION WERE
INFECTIOUSED IN BOTH POPULATIONS
AS WITH SMOKING.
CURRENT ALCOHOL USE IS ON PAR,
OBESITY IS INCREASED AMONG TRANS
MASCULINE ADULTS BUT DECREASED
AMONG TRANS FEMININE ADULTS.
I WANT TO TURN MY ATTENTION TO
HIV INFECTION.
IT'S ESTIMATED WORLDWIDE TRANS
WOMEN HAVE THE HIGHEST
PREVALENCE OF HIV AT ABOUT 19%.
AND WHILE HIV ITSELF DOES NOT
CAUSE CANCER IT'S ASSOCIATED
WITH A HIGHER RISK OF A NUMBER
OF CANCERS DUE TO
IMMUNOEXPRESSION EVEN AMONG
THOSE WHO HAVE ACCESS TO
ANTIVIRAL THERAPY.
IT'S ASSOCIATED WITH KAPOSI
SARCOMA AND NON HODGKIN'S AND
AAL CANCER AND LUNG CANCER AND
VIRAL ETIOLOGY LIKE HPV AND
HEPATITIS ARE IMPORTANT
INFECTIONS FOR THIS POPULATION
AS WELL.
THEN HIV ALSO INCREASES THE RISK
OF CANCER MORTALITY.
THERE'S BEEN GREAT STUDIES
LOOKING AT THE CANCERS BUT WE
WERE MISSING ESTIMATE OF RISK
ACCORDING TO GENDER UNTIL NOW.
THIS IS NOT PRELIMINARY DATA WE
HAVE NOT WRITTEN THIS UP YET SO
DON'T TAKE PICTURES OR QUOTE
THIS AND THERE'S A CLOSE
COLLABORATOR THAT USE THE
HIV/AIDS CANCER MATCH STUDY AND
THE RISK OF BREAST, COLORECTAL
AND LUNG CANCERS ARE DECREASED
AMONG TRANS MEN COMPARED TO BOTH
CISGENDER GROUPS AND DEPENDING
ON THE COMPARISON GROUP BREAST
CANCER INCIDENTS IS INCREASED OR
DECREASED AMONG TRANS FEMININE
AND PROSTATE AND LUNG CANCERS
ARE DECREASED BUT COLORECTAL AND
KIDNEY CANCERS INCREASED.
SO TURNING TO THE VIRALLY
RELATED CANCERS, TRANS MEN HAVE
AN INCREASED INCIDENT OF NON
HODGKIN'S LYMPHOMA AND DECREASED
CANCERS WHEN COMPARED TO BOTH
GROUPS.
TRANS WOMEN HAVE DECREASED
INCIDENTS OF NON-HODGKINS
LYMPHOMA AND CERVICAL CANCER
INCIDENT IS ABOUT THE SAME IN
TRANS MEN AS CISGENDER WOMEN
WITH HIV.
HOWEVER, THERE'S BARRIERS TO
SCREENING FOR WITH A CERVIX.
THIS IS A SCHEMATIC OF THE
BARRIERS TO CERVICAL CANCER
SCREENING THEY MAY ENCOUNTER.
THE FIRST IS PROVIDERS HAVING A
POOR UNDERSTANDING OF TRANS
HEALTH AND THE NEXT IS PEOPLE
EXPERIENCING GENDER DYSPHORIA OR
THE SCREENING OR EVEN GETTING
CORRESPONDENCE ABOUT THE
SCREENING.
MANY PEOPLE REPORT THEY'VE
EXPERIENCED STIGMA AND
DISCRIMINATION IN THE CLINIC.
HAVING A FEMALE CENTERED CLINIC
CAN BE A HUGE BARRIER TO
SOMEBODY WHO PRESENTS AS MALE.
FURTHER OUR SYSTEMS OR PROVIDER
MIGHT NOT CALL THAT PERSON FOR
SCREENING IF THEY HAVE A MALE
GENDER MARKER.
AND THEN THE AFFECTS OF ANDROGEN
THERAPY CAN ATROPHY THE VAGINA
MAKING EXAMINES AND MIMIC
DYSPLASIA.
AND THEY'RE 10 TIMES MORE LIKELY
TO HAVE AN INADEQUATE SAMPLE
MEANING THE PROCEDURE HAS TO BE
DONE AGAIN.
THERE'S FACILITATORS WE
RECOGNIZED.
ONE IS HAVING A CLINIC THAT'S
NOT INGENDERED AND HAVING
PAMPHLETS AND OTHER MATERIALS
TAR GUESTED TO TRANS
INDIVIDUALS.
TARTAR GET AND HAVING ACCESS TO
TRANS SPECIALIST SERVICES AND
CULTURALLY COMPETENT PROVIDERS
AS WELL.
AND THEN ALSO HAVING THE OPTION
OF HPV SELF-SWAB.
I'LL TALK ABOUT THE PILOT STUDY
I LAUNCHED EARLIER THIS YEAR.
WE DID PUBLISH THE PROTOCOL AND
IF YOU WANT TO SCAN THE QR CODE
YOU CAN LEARN AND DR. BURNER IS
MY COP.I.
WE CALLED IT SELF-TI AND
ENROLLING PEOPLE WITH A CERVIX
WITH A HISTORY OF TESTOSTERONE
THERAPY AND THEY'LL DO
SELF-COLLECTION IN THE CLINIC
AND TAKE A SURVEY ON
ACCEPTABLEABILITY.
THE TRANS FEMININE GROUP ARE
ASSIGNED MALE AT BIRTH AND OVER
THE AGE OF 18 WILL DO
SELF-COLLECTION IN THE CLINIC
AND THEN TAKE THE KIT HOME AND
DO IT AT HOME AND MAIL IT IN AND
TAKE A SURVEY ON ACCEPTABLITY.
THE ORAL RINSE, URINE, VAGINAL
SWABS AND AA -- ANAL SWAB AND
DEVELOPED IN COLLABORATION WITH
THE COMMUNITY.
I HAD A COMMUNITY ADVISORY BOARD
RAN BY THE EXECUTIVE OF OUT
PATIENTS WHICH IS A CANCER
ORGANIZATION FOR LGBTQ+ PEOPLE
IN ENGLAND AND IN THE INTEREST
OF TIME I WILL SAY THEY HELPED
US DEVELOP ADVERTISEMENT
MATERIALS FOR THE STUDY.
THEY INTRODUCED US TO FOX FISHER
WHO IS A FAMOUS TRANSACTION
TRANS-ACTIVIST AND THIS IS FROM
INSTAGRAM AND YOU SEE HOW MUCH
ENGAGEMENT WE GOT ON THE FIRST
DAY IT WAS POSTED.
A LOT OF OUR RECRUITMENT IS
BECAUSE OF THIS INSTAGRAM.
THEY ALSO SUGGESTED WE CREATE AN
INSTRUCTIONAL VIDEO THAT WE HAD
NARRATED BY FOX.
SO WHEN THE PATIENTS COLLECT
THEIR SAMPLES THEY CAN SCAN THE
QR CODE AND HAVE THE
INSTRUCTIONAL VIDEO WALKING
THROUGH THE STEPS AND SEE THE
ADVERTISEMENT MATERIAL HERE AND
THE QR CODE SCANS TO OUR STUDY'S
WEBSITE SO IF YOU ARE INTERESTED
YOU CAN LOOK AT IT.
I WANT TO THANK MY COLLABORATORS
AT SELF-TI AND THE NIH FOR THE
PROJECTS.
THANK YOU VERY MUCH.
>> QUESTIONS
>> SO, AS A QUEER PERSON WITH OF
A FRIENDS WHO ARE NON BINARY IT
WAS SAD AND INTERESTING TO SEE
THE STUDIES CARRYING OUT ARE
BEING CARRIED OUT IN THE U.K.
AND WOULD LIKE TO LEARN A LITTLE
BIT MORE WHY THAT IS THE CASE
AND WHETHER ARE YOU FINDING
BARRIERS TO USING CERTAIN
STUDIES HERE IN THE U.S. AND THE
U.S. COMMUNITY IS ACTIVE SO WE
SHOULD BE ABLE TO HAVE VERY GOOD
ENGAGEMENT.
SO WHAT IS THE BARRIER?
>> THAT'S A GREAT QUESTION.
AND I DON'T MEAN TO FOCUS MOSTLY
INTERNATIONALLY.
WE ARE GOING TO BE LOOKING AT
USING FULL MEDICAID IN THE
FUTURE WHICH IS A GREAT
RESOURCE.
ONE OF THE REASONS THAT I HAVE
LOOKED IN THE U.K. IS TWOFOLD.
ONE, THEY HAVE GOOD PRIMARY DATA
COLLECTION.
THEIR POPULATION REGISTRIES ARE
NOT ON PAR WITH THE NORDIC
COUNTRIES OR A LITTLE BIT MORE
COMPLETE THAN WE HAVE IN THE
U.S.
OUR HEALTH INSURANCE AND HEALTH
CARE SYSTEMS WE HAVEY
COMPLEX AND IT'S REALLY HARD TO
FOLLOW PEOPLE OVER TIME.
I START THE SELF-TI STUDY A A
POSTDOC AND MY FUNDS WERE
LIMITED AND THE U.K. WAS AN
EASIER PLACE TO DO THAT.
I HAVE PLANS TO EXPAND IN THE
UNITED STATES.
>> WONDERFUL.
ALL RIGHT COMING UP WE HAVE AV
DR. TIJANATI IVANOVIC TALKING
ABOUT PHENOTYPIC DIVERSITY IN
VIRAL EVOLUTION.
L
>> HI, EVERYONE.
THANK YOU FOR THE OPPORTUNITY
AND ALL TO COME IN THE
SUBSEQUENT YEARS AND THE REST OF
THE DAY TODAY.
I'M EXCITED TO SHARE WITH YOU
SOME OF MY LAB'S RESEARCH.
ONE OF OUR BIG PICTURE QUESTIONS
IS TO UNDERSTAND RELATIONSHIP
BETWEEN VIRAL POPULATION
DIVERSITY AND ADAPTABILITY.
AND IN THE CONTEXT WE'RE EXCITED
ABOUT THE CHALLENGE OF
UNDERSTANDING PHENOTYPIC
DIVERSITY AND THE EXAMPLE OF THE
MISSHAPED VIRUSES.
INFLUENZA VIRUS IS ONE SUCH
VIRUS.
AND INFECTIONS OF CELLS BY
INFLUENZA YIELD A MIXTURE OF
SHAPES FROM SMALL SPHERICAL
PARTIC
PARTICLES AND AN INFECTION OF
CELLS WITH EITHER PARTICLE FORM
YIELD THE SAME MIXTURE OF SLAP.
AND IT SPECIFY THE PROS
PROBABILITY AND NOT ONE IN
SPECIFIC.
IT MEANS YOU'RE ALWAYS DEALING
WITH MIXTURES AND IT MAKES IT
DIFFICULT TO TACKLE.
I WAS WITHIN OF THE CHALLENGES
WHERE WE THOUGHT METHODS WOULD
HAVE A GREAT ADVANTAGE.
I COULDN'T DO THE POINTERS SO
SOMETHING SEEMS FROZ
SORRY.
ALL RIGHT.
THANKS SO MUCH.
SO THE VIRUS IS SHARED AMONG
DIFFERENT VIRAL FAMILIES AND
INCLUDES SOME VERY DANGEROUS
PATHOGENS AND SOME LISTED ON THE
RIGHT CIRCULATING AND EMERGING
VIRUSES.
SO THE WAY WE TACKLE THE PROBLEM
IS BY CONSIDERING VIRUS
STRUCTURE AT DIFFERENT SKAELZ
FROM THE POPULATION LEVEL TO THE
PARTICLE LEVEL TO PROTEINS AND
THEN APPLY METHODS TO ALLOW TO
DEVELOP MODELS OF VIRAL FUNCTION
IN EACH CALLS FROM THE PROTEIN
TO PARTICLE TO POPULATION.
SO WHAT ARE FUNCTIONS OF VIRUS
PARTICLES?
THEY ENCLOSE THE GENOME AND HAVE
TO PROTECT IT AND INTERFACE
CELLULAR PRESSURES AND ADAPTIVE
IMMUNITY AND HAVE TO ENCOUNTER
NEW HOSTS AND RECOGNIZE SPECIFIC
SECTOR AND MEDIATE ENTRY.
THE LAST STEP IS FUSION BETWEEN
THE VIRAL ENVELOPE AND ENDOSOMAL
COMPARTMENTS AND I'LL LOOK AT
THE PARTICLES AND TALK ABOUT
VIRUS ASSEMBLY THE PROCESS THAT
GENERATES THE DIVERSITY.
SO HOW DO WE LOOK AT AND LOOK AT
THZED MICROSCOPES THAT
ARE CAPABLE OF SINGLE MOLECULE
IMAGING.
WE LOOK AND THE MEMBRANES
INCORPORATE FLUORESCENT DYES AND
INCORPORATE SPECIFIC RECEPTORS.
WHAT YOU'RE SEEING IS A MOVIE OF
MEMBRANE S LAYER BY LAYER AND
VIRUS PARTICLES AND WHEN YOU SEE
THE BURSTS OF CLOUD THAT'S THE
DYE BEING DEPOSITED AS THEY FUSE
THE MEMBRANE.
SINCE WE USED THE FULL CELL
SYSTEM WHICH ALLOWS US TO
TRIGGER FUSION IT ALSO INITIALLY
INDUCE THE ROLLING OF RECEPTORS
AND THE PROCESS THEN REPORTS ON
THE INTERACTION.
I'LL REPEAT THIS HERE AND SEE
THE VIRUS PARTICLES MERGE.
THE MOVIES LEAVE DETAIL ABOUT
THE UNDERLYING MECHANISMS OF
MEMBRANE FUSION AND ALLOWS US TO
BUILD DETAILED MODELS.
THEY ALSO ALLOW US TO ASK
QUESTIONS HOW DO ANTIBODIES
BLOCK THE PROCESSES AND
ANTIBODIES THAT BLOCK VIRUS
ATTACHMENT OR THOSE THAT BLOCK
VIRUS FUSION OR SPIKE FUSION
ASSOCIATED CONFIRMATIONAL
CHANGES AND THEN CAN ASK THE
CONTEXT ON A SMALLER VERSUS
LARGE VIRION TO VIRUSES TO
ACTIVATION SINCE WE CAN RESOLVE
LARGE PARTICLES WE CAN ASK
QUESTIONS HOW DIFFERENT PARTICLE
TYPES ARE AFFECTED.
WE CONCLUDE THEY RESIST EXTRA
CELLULAR CHALLENGES AT THE LEVEL
OF ATTACHMENT AND MEMBRANE
FUSION AND WE FIND THE ABSENCE
OF PRESSURE THEY'RE MORE
EFFICIENT AND USE LESS RESOURCES
TO BUILD.
AND SO QUE THINK THE MIXTURES
ARE IMPORTANT AND THERE'S A
DIFFERENT PARTICLE TYPE THEY MAY
ENCOUNTER IN THE EXTRA CELLULAR
SPACE.
BUT HOW IS VIRION SHAPE
REGULATED?
IT HASN'T BEEN EXPLORED IN GREAT
DETAIL.
THE ASSUMPTION IS THAT THERE'S A
GENETIC CHANGE TO SWITCH
DISTRIBUTION TO CHANGE FROM
FILAMENT TO SPHERE AND A RED
PARTICLE RESULTS IN MORE
FILAMENTS AND THE BLUE PARTICLE
MAY HAVE A MUTATION THAT RESULTS
IN MORE SPHERE S.
THE SHAPE CAN BE PHENOTYPICALLY
AND IT CAN SENSE THE PRESSURE OF
AND RESPOND WITHOUT REQUIRING
GENETIC CHANGE BY PRODUCING MORE
FILAMENTS OR SPHERES DEPENDING
ON THE PARTICULAR NEED.
THE TWO SCENARIOS WE HAVE
DIFFERENT CONSEQUENCES AS IT
RELATES TO VIRUS ADAPTABILITY.
THE FORMER IS ASSUMED BUT THE
LETTER IS MORE POWERFUL FOR THE
VIRUS AND THIS IS ILLUSTRATE.
THIS IS HOW A GENETIC MODEL
PLAYS OUT.
UNDER ATTENUATING PRESSURES THE
VIRUS POPULATION IS TSHRINK AND
VARIANT WOULD GENERATE A
BOTTLENECK AND REDUCE DIVERSITY
HAVING TO ACCUMULATE TO PER
CIVILITY LONG ENOUGH AND LEAD TO
TRUE RESISTANCE AND COULD EXPAND
AND EXPAND TO FILAMENTS FIRST
AND WOULD NEED ANOTHER SELECTION
TO REVERT TO MORE EFFICIENT
SPHERES.
IF A VIRUS CAN CHANGE IT SHAPE
PHENOTYPICALLY IT CAN BE
PACKAGED INTO I A -- A FILAMENT
AND IF THE POPULATIONS EXIST YOU
MAY ARISE TO RESISTANCE BUT
IMMEDIATELY THE FORMS COULD
EXPAND INTO MORE SPHERES.
THE LATTER WOULD BE MORE
EFFICIENT MECHANISM FOR THE
VIRUS TO NAVIGATE A CHANGE IN
EXTERNAL ENVIRONMENT BUT WHICH
ONE IS TRUE?
WE NEED A BETTER WAY TO STUDY
SHAPE.
THE GOLD STANDARD IS
ELECTROSCOPY AND YOU SEE VIRUS
PARTICLES AND KNOW WHAT YOU'RE
COUNTING BUT COUNT ON PURIFIED
SAMPLES AND LABORIOUS AND WE
INTERROGATE SCATTERED OF LASER
LIGHT SO 4 OR 5 NANO METER AND
LARGER PARTICLES AND YOU CAN SEE
IN THE POPULATION YOU SEE THIS
CHARACTERISTIC AND IF YOU HAVE
MORE FILAMENTS YOU GET THE
SECOND PEAK.
NOW WE HAVE A WAY OF QUICKLY
GETTING INFORMATION FOR MANY
VIRUS PARTICLES AND WE ACHIEVE A
HUNDRED THOUSAND TIMES AND WE
HAVE TO MANIPULATE AND
CONCENTRATE THEM IN ANYWAY AND
HAVE TO DILUTE THEM AND
INTERROGATE AND IT'S A PROCESS
TO MEASURE MANY SAMPLES IN
PARALLEL.
WE WANTED TO ASK COULD THE
PRESSURES BE SENSED IN SOME WAY
AND COULD THE VIRUS RESPOND BY
CHANGING THE OUTPUT SHAPE OF
VIRUSES.
SO IN THIS EXPERIMENT WE TREATED
A VIRUS WITH NEUTRALIZING
ANTIBODIES FOR THE FIRST FOUR
HOURS TO ALLOW THE PRESSURE AND
MEASURED THE SHAPE OF PARTICLES
24 HOURS LATER AND WE OBSERVED
AS WE INFECTIOUSED THE
CONCENTRATION IN ANTIBODY --
INCREASED THE CONCENTRATION OF
ANTIBODY THE RESULT PARTICLE
SHANE RESPONDED BY INCREASING
THE PROPORTION OF FILAMENTS.
THIS IS LIMITED TO NEUTRALIZING
ANTIBODIES SO THOSE THAT BIND
VIRUS PARTICLES BUT DON'T
ATTENUATE INFECTION.
DID NOT RESULT IN INCREASED
FILAMENTS THIS IS EXPECTED OF A
METHOD FOR VIRUS RESPONSE TO THE
PRESENCE OF PRESSURES.
WE THEN ASKED ABOUT ANTIBODIES
SOME CAN INHIBIT THE ASSEMBLY.
AS ANTIBODIES INHIBIT ASSEMBLING
THEY PRODUCE MORE FILAMENT.
IN THIS CASE THIS WAS TRUE ALSO
FOR ANTIBODIES THAT BIND
AFFECTED CELLS BUT DON'T
INTERFERE SUGGESTING THE VIRUS
RESPONDS TO MOUNTING PRESSURE
BEFORE IT BECOMES POTENT AND THE
POPULATIONS PREPARE FOR WHAT'S
TO COME.
THESE EFFECTS ARE FAST AND
MEASURE SHAPE CHANGES AS SOON AS
10 MINUTES AND ADDITION TO AN
ALREADY ESTABLISHED INFECTION
AND VIRUSES CAN IMMEDIATELY
RESPOND TO THE PRESENCE OF
PRESSURES.
AND WE THINK THAT SHAPE TUNING
IS A POWERFUL ADAPTATION
STRATEGY.
SO WITH THIS I'D LIKE TO THANK
PEOPLE HERE ED AND ANNA THE
FIRST AND SECOND AUTHOR ON THE
PAPER I TOLD YOU A LITTLE BIT
ABOUT AND THE SECOND ROUND OF
REVISIONS WHO CONTRIBUTED
IMPORTANT EXPERIMENT FOR THE
WORK.
I ALSO WANT TO BRIEFLY INTRODUCE
NEW MEMBERS IN THE LAB AND OTHER
EXCITING PROJECTS AND WE'LL BE
STUDYING BIO PHYSICS OF CELL
ENTRY IN OTHER VIRUSES LIKE
EBOLA AND AVIAN INFLUENZA.
WE'RE WORKING ON THE ASSEMBLY OF
MECHANISMS AND OTHER PHENOTYPIC
AFFINITY SUCH AS VIRUS
ABROGATION IN A SHAPE THAT CAN
DELIVER MORE GENOMES AND AND
FINALLY KELLY AND ANTONIO ARE
ASKING ABOUT DISCUSSIONS IN THE
CONTEXT OF THE HOST AND HOW DO
CELLS RECOGNIZE DIFFERENT
PARTICLE SHAPES OR ORGANIZATIONS
AND WITH THIS I'D LIKE TO THANK
OUR COLLABORATORS AND FUNDING
SOURCES PAST AND PRESENT AND THE
DSP FOR THEIR SUPPORT.
THANK YOU.
I DON'T KNOW IF WE HAVE TIME FOR
QUESTIONS.
>> WE HAVE TIME FOR QUESTIONS.
>> CAN I ASK A QUESTION IN THE
MEANTIME, I WAS OF WAS WONDERING
IF YOU HAVE ANY IDEA OF HOW
VIRAL SHAPE MIGHT INTERACT WITH
THE HOST CELL FUNCTION?
IS THERE ANY REASON WHY ONE
SHAPE MIGHT BE FAVORS IN SOME
INFECTED CELLS VERSUS OTHERS?
>> UNDER DIFFERENT TYPE OF
AFFILIATION FILAMENTS ARE LIKELY
TO ENTER BUT THERE'S A
DIFFERENCE.
SO DIFFERENT PARTICLES ENTER
USING DIFFERENT PATHWAYS.
SOME ENTER BYCYTOSIS AND OTHERS
BY MACRO PHENOCYTOSIS AND THEY
MUST BIND AND THIS IS ONE OF THE
GREAT INTERESTS IN UNDERSTANDING
WHAT IS SENSED BECAUSE WE THINK
ABOUT THE PARTICLES AS BEING
SMALLER OR BIGGER SAME THING,
RIGHT.
LIKE THE SCALE SURFACE PROTEINS
WITH SIZE IS.
IT'S BASICALLY SAME INTERACTIONS
AND MULTI-VALENT INTERACTIONS.
SO WHAT IS PERCEIVED AS THE
DIFFERENCE IS A VERY IMPORTANT
FUNDAMENTAL QUESTION WE'RE
EXCITED ABOUT ANSWERING.
>> COULD YOU USE YOUR FLOW
VIROMETRY METHOD TO ANSWER OR A
QUESTION OF TWO POPULATIONS
VERSUS NON-GENETIC?
>> SO HERE'S THE THING, YES, WE
CAN SORT.
NOT THE SAME LEVEL OF
DEVELOPMENT AS ALICE'S.'S A TRI
INSTRUMENTS CAN DO BUT WANT TO
SORT AND SEQUENCE.
BUT TO ADDRESS YOUR QUESTION,
WE'VE GOTTEN TO THE QUESTION OF
GENETIC CHANGES THAT CAN CHANGE
SHAPE BUT ANY CHANGE THAT
ATTENUATE THE FUNCTION,
ENCODING, REPLICATION,
TRANSCRIPTION WILL HAVE A RESULT
OF INCREASING FILAMENTS BUT IT'S
NOT NECESSARILY A DIRECT EFFECT
ON ASSEMBLY.
AND SO NOW WE'RE TRYING TO
FIGURE OUT WHAT ARE TRUE GENETIC
CHANGES.
N BE ENRICHED FOR ONE FORM
AND SEE THE EXACT SAME SF
PARTICLES.
THE OUTPUT IS IDENTICAL IN SHAPE
AND-YEAR- YIELD AND EVERYTHING.
THERE'S NO INDICATION -- AT
LEAST IN A MIXED POPULATION
DIFFERENT TYPES BUT OTHER
MUTATIONS PROBABLY THERE ARE BUT
IT'S A TRICKY THING TO GET AT.
THANK YOU.
E'RE TO TAKE A
SHORT BREAK AND START AGAINTA
PROMPTLY AT 2:20.
THANK YOU.
>> OKAY.
WELCOME BACK, EVERYBODY.
WE'RE GOING TO CONTINUE OUR
SESSION OF 2023 DSP SCHOLARS
WITH-DR. JULIETA LISCHINSKY AND
TALKING ABOUT THE HARD WIRED TO
ATTACK UNCOVERING THE
DEVELOPMENT AND CELLULAR
MECHANISM AND SOCIAL PE HAFRZ AF
AND LIMBIC SYSTEM.
>> A BEHAVIOR IS MATING.
WHEN ONE WANTS TO START A FAMILY
AND HAVE CHILDREN AND THE
OPPOSITE IS AGGRESSION ESSENTIAL
FOR PROTECTING ONE'S SELF AND
ONE'S FAMILY AS WELL AS SECURING
RESOURCES.
WE SEE AN EXAMPLE OF THE
AGGRESSION DURING THE SUPER BOWL
WHEN TRAVIS KELCE PUSHED THE
HEAD COACH.
WE CAN SEE HOW THIS IS SHARED
ACROSS SPECIES.
WHAT'S MOST INTERESTING ABOUT
THE INNATE SOCIAL BEHAVIORS IS
THEY'RE UNLEARNED AN CAN TAKE
PLACE WITHOUT PRIOR EXPERIENCE.
OUR MAIN GOAL IS TO UNDERSTAND
HOW THE BRAIN IS PROCESSING
SOCIAL INFORMATION AS WELL AS
SOCIAL BEHAVIORS.
SO TO TACKLE THE QUESTION WE
TAKE THE MULTI-LEVEL APPROACH.
WE FIRST LOOK AT THE CELLS AND
IDENTIFY WHAT IS THE MOLECULAR
IDENTITY AND THE NEURAL
RESPONSES OF TRANSCRIPTIONAL
POPULATIONS ACROSS THE LIMBIC
SYSTEMS AND WE'RE SEEING TO THE
MECHANISMS FOR THE PROCESSING OF
THESE SOCIAL INFORMATION AS WELL
AS SOCIAL BEHAVIORS BOTH IN
DEVELOPMENT AND IN ADULTHOOD.
AND THE CIRCUITS REGULATE
BEHAVIOR AND INTERESTED IN
ELUCIDATING THE FUNCTIONAL
RELEVANCE OF POPULATIONS AN
CIRCUITS FOR INFANT AND ADULT
SOCIAL BEHAVIORS AND ALSO
INTERESTED IN UNDERSTANDING HOW
IS THE ENVIRONMENT SUCH AS
ENVIRONMENTAL INSULTS GOING TO
DISRUPT THE SOCIAL BEHAVIORS
ACROSS THE LIFE TIME.
STO TO
TO INVESTIGATE WE CAN LOOK AT
DIFFERENT INTRUDERS INTO THE
ANIMAL CAGE AND THE MALE MOUSE
WILL TRY TO DETERMINE IF THIS IS
GOING TO BE A FRIEND OR FOE AND
THEN PERFORM THE APPROPRIATE
MODEL RESPONSE.
IF WE INTRODUCE A FEMALE INTO
THE MALE MOUSE'S CAGE THEY'LL
TRY TO MATE.
IF WE INTRODUCE THE MALE HE'LL
TRY TO ATTACK THE OTHER MALE.
IN ORDER TO STUDY HOW THESE
SENSORY INFORMATION IS ITERATE
AS THE RESPONSE WE LOOK AT THE
AMYGDALA.
WE ABBREVIATE AS AND -- MEA
AND WE HAVE THE MOTOR RESPONSE.
IT CAN BE DIVIDED INTO SECTIONS
AND THE DORSAL PORTION IS
COMPRISED OF GABAERGIC CELLS.
THESE CELLS ARE RESPONSIBLE FOR
THE GENERATION OF MATING AS WELL
AS AGGRESSION AND IN AN
INTENSITY DEVELOPED FASHION.
HOW HAVE THE CELLS IMPLICATED IN
THE PRODUCTION OF THESE VERY
DIVERSE SOCIAL BEHAVIORS TO HAVE
SPECIFIC SENSORY TRIGGERS AND
DEFINED STEREOTYPE OUTPUTS.
AND THE POPULATIONS WITHIN THE
GABAERGIC CELLS IMPLICATED AND I
WANTED TO TAKE A DEVELOPMENT
APPROACH TO UNDERSTAND WHETHER
THE SUBSTRATES FOR THE SOCIAL
BEHAVIORS COULD BE
DEVELOPMENTALLY DEFINED.
SO THIS END I LOOKED AT TWO
DISTINCT POPULATIONS EXPRESSING
THE TRANSCRIPTION FACTORS AND
DURING THE BRAND OF DEVELOPMENT
WE SEE THE AREA THAT GIVES RIGS
TO THE AMYGDALA AND THEY'RE PARS
LA
ELATED AND THEIR
NON-OVERLAPPING.
DURING MY Ph.D. AND POSTDOC I
OBSERVED THE POPULATIONS WERE
SPATIALLY POPULATED AND HAD
DISTINCT MOLECULAR IDENTITIES
AND PROFILES.
AND THIS IS IN THE IN VIVO
RESPONSES DURING SOCIAL
BEHAVIORS AS WELL AS IN THEIR
CIRCUIT CONNECTIVITY.
I'M GOING TO FOCUS ON SHARE SOME
OF THE PAST AND CURRENT WORK
WE'RE PERFORMING.
FIRST WE WANTED TO UNDERSTAND
WHETHER THEY HAVE INCREASES IN
NEURAL ACTIVITY DURING DISTINCT
BEHAVIORS IN FREELY MOVING MALE
MICE.
IN ORDER TO MEASURE ACTIVITY WE
INJECT THE CALCIUM INDICATOR
INTO THE AMYGDALA AND THEN
RECORD AFTER PLACING AN OPTIC
FIBER CHANGES AND THE CHANGES
SERVE AS A PROXY FOR NEURONAL
ACTIVITY.
HERE A VIDEO OF OUR THIS IS A
VIDEO FROM OUR MALE YOU CAN SEE
HAS A BLACK FUR AND IN THE Y
AXIS WE SEE THE CHANGES IN
DYNAMICS AND NEURONAL ACTIVITY
ON THE X AXIS WE CAN SEE HOW THE
MALE RESIDENT MOUSE IS
INVESTIGATING AND NOW HE'S GOING
TO INVESTIGATE THE MOUSE IN THE
CAGE AND WE SEE NICE INCREASES
IN ACTIVITY ESPECIALLY NOW THE
MOUSE IS DIFFERENT.
HE JUST ATTACKED OUR INTRUDER
AND SEE ROBUST DIFFERENCES IN
ACTIVITY AND NOW THE MICE IS
SNIFFING AGAIN AND SEE THIS VERY
NICE ACTIVITY.
WE CAN ALSO INVESTIGATE WHETHER
THE CELLS ARE RESPONDING DURING
SEXUAL BEHAVIORS.
WE CAN INTRODUCE THE FEMALE IN
THE CAGE OF THE MALE MOUSE AND
HOUR MALE IS INVESTIGATING AND
WE CAN SEE HERE THERE'S NO
CHANGES IN THE NEURAL ACTIVITY
OF THE CELLS DURING THE SEXUAL
BEHAVIORS.
THIS IS IN DIRE CONTRAST TO THE
NEURAL RESPONSES DURING THE
PRESENTATION OF A MALE.
THERE'S ROBUST INCREASES IN
NEURAL ACTIVITY BUT NO CHANGES
DURING MALE UNDERGOING SEXUAL
BEHAVIOR WITH THE FEMALE.
WE HAVE SPECIFIC BEHAVIOR TIMES
0 OVER THE Y AXIS THE CHANGES IN
NEURONAL ACTIVITY.
WE SEE DURING THE PRESENTATION
OF A MALE MOUSE THERE'S
INCREASES IN THE NEURAL ACTIVITY
OF THE AMYGDALA FOX P2 CELLS
DURING INVESTIGATION AND ATTACK.
HOWEVER WHOEVER WHEN WE
INTRODUCE THE FEMALE THERE'S NO
CHANGES IN NEURONAL ACTIVITY AND
THIS IS DONE IN MICE WITH NO
SEXUAL EXPERIENCE AND WHAT ARE
THE RESPONSES?
SO TO THIS END WE LOOKED AT THE
DIFFERENT GROUPS AND A GROUP
WITH NO SOCIAL EXPERIENCE AND A
GROUP WITH SOCIAL EXPERIENCE BUT
WAS NOT AGGRESSIVE AND AN
EXPERIENCED GROUP THAT HAD
SOCIAL EXPERIENCE AND WAS ALSO
AGGRESSIVE.
SO WE CAN AGAIN SEE THEHISTO
GRAMS WE SEE THE RESPONSES OF
THE NAIVE MOUSE INCREASED DURING
THE INVESTIGATION OF A MALE
HOWEVER, AFTER THE REPEATED
SOCIAL EXPERIENCES WE SEE THE
RESPONSES TO THE MALE
INVESTIGATION BECOME VERY
ROBUST.
THERE'S AN INCREASE IN RESPONSE
IN EXPERIENCE IS AGGRESSIVE MICE
AND SEE THERE'S A DECREASE IN
THE LATENCY FOR THE CELLS TO
RESPOND.
IT APPEARS WITH THE REPEATED
SOCIAL ENCOUNTERS THE AMYGDALA
CELLS ARE BECOMING MORE REFINED.
THE NEXT QUESTION WE HAVE IS ARE
THE CELLS GOING TO BE
FUNCTIONALLY RELEVANT FOR SOCIAL
BEHAVIORS?
SO TO THIS END WE USED TOOLS TO
INJECT A RECEPTOR EXCLUSIVELY AC
ACTIVATED BY A DESIGNER DRUG TO
ACT VEIL THE CNL.
WE SEE IN PINK THE MICE DO NOT
HAVE SOCIAL EXPERIENCE AFTER
REACTIVATE THE FOX P2 CELLS ALL
THE MALE MICE BECOME AGGRESSIVE
AND THERE'S AN INCREASED TIME
THEY SPEND ATTACK.
ON THE OTHER HAND WE CAN TRAIN
MICE TO BE VERY AGGRESSIVE AND
THEN SILENCE THE FOX P2 CELLS.
WHEN WE SILENCE THE CELLS WE SEE
MICE THAT WERE PREVIOUSLY
ATTACKING SHOW LITTLE OR NO
ATTACK BEHAVIOR.
IT APPEARS THE CELLS ARE
BI-DIRECTIONALLY MODULATING
AGGRESSION AND ANOTHER QUESTION
WE'RE INVESTIGATING ARE THE
RESPONSES GOING TO BE SEXUALLY
DIMORPHIC?
HOW ABOUT IN FEMALE MICE?
WE HAVE DATA LIKE WE'VE DONE IN
FEMALES AND MALES AND THE MICE
ARE RUNNING ON A WHEEL AND WE
CAN PRESENT DIFFERENT SOCIAL
CUES.
HERE'S THE RESPONSES FROM
FEMALES AND WE CAN SEE THERE'S
AN INCREASE IN THE RESPONSES OF
A MALE AS WELL AS INCREASES IN
THE RESPONSES TOWARDS A MALE.
SO WE WANTED TO TAKE THIS A STEP
FURTHER AND BE ABLE TO
UNDERSTAND WHETHER THE SAME
CELLS ARE RESPONDING TO BOTH
MALE AND FEMALE QUEUE OR WHETHER
WE CAN HAVE DISTINCT WITHIN THE
POPULATION SOME RESPOND TO MALES
AND SOME TO FEMALES.
TO THIS END VERY TALENTED
POSTDOC IN THE LAB HAS BEEN
PERFORMING SINGLE CELL IMAGING
IN FREELY MOVING MICE WHERE WE
CAN RECORD FROM THE AMYGDALA
CELLS AT THE SINGLE CELL LEVEL
AND SEE AN IMAGE OF OUR FEMALE
MOUSE WITH THE SCOPE AND WE'RE
REPORTING.
I'LL SHOW YOU A SNEAK PEEK OF
WHAT THESE LOOK LIKE AND WE'RE
ACTIVITY COLLECTING THE DATA.
WE CA IN SEE IN THE TOP LEFT WE
HAVE OUR FIELD OF VIEW WITH ALL
THE CELLS OF INTEREST AND THE
ROIs AND TO THE TOP RIGHT CELL
TRACES FROM EACH CELL.
AND AND WE SEE WHAT IS
INVESTIGATING A JUVENILE
INTRUDER PLACED IN THE CAGE.
SHE'S INVESTIGATING AND SEEING
HOW THE KRE CELLS ARE RESPONDIN
DURING THE INVESTIGATION.
WE SEE OTHERS ARE NOT.
WE CAN BETTER INFORMATION THE
NEURAL RESPONSES OF THIS CELLS
DURING THE PRESENTATION OF THE
DIFFERENT SOCIAL CUES AS THE
MOUSE IS FREELY MOVING.
IN SUMMARY THE AMYGDALA FOX P2
CELLS IN MICE APPEAR TO RESPOND
DURING MALE INVESTIGATION AND
ATTACK AND HAVE SPECIFIC CIR
CIRCUITRY AND MODULATING
AGGRESSIONS ESSENTIAL FOR
TERRITORIAL AGGRESSION EVEN IN
MICE WITH MINIMAL OR NO SOCIAL
EXPERIENCE AND THINK IT WILL BE
PREDICTIVE OF BEHAVIORAL
RESPONSES EVEN WITH NO OR
MINIMAL EXPERIENCE.
THANK YOU FOR LISTENING AND I'D
LIKE TO GIVE A BIG THANK YOU TO
OUR GROUP ESPECIALLY TO THE
FINDING MEMBERS OF OUR LAB AND
IT'S BEEN SO GREAT TO SET UP THE
LAB WITH THE TALENTED AN
MOTIVATED SCIENTISTS AND I'D
LIKE TO THANK OUR COLLABORATORS
AND OUR FUNDING SOURCES.
WE'RE RECRUITING FOR MEMBERS TO
JOIN OUR GROUP SO FEEL FREE TO
REACH OUT.
WE HAVE POSTDOC AND POST-BAC
POSITIONS AVAILABLE LOOKING AT
SOCIAL BEHAVIORS.
THANK YOU.
>> SAY HOW THE CIRCUITS MIGHT BE
RELEVANT IN HUMANS?
HOW DO WE KNOW THAT THESE INNATE
BEHAVIORS DON'T NECESSARY
TRANSLATE EXACTLY TO HOW IT
WORKS IN HUMANS BUT THERE MIGHT
BE SOME PARALLELS THERE.
>> YES SO THAT'S A GREAT
QUESTION.
SO ON THE AMYGDALA ANOTHER
STRUCTURE SUCH AS THE
HYPOTHALAMUS ARE HIGHLY
CONSERVED ACROSS SPECIES.
THE AMYGDALA HAS BEEN OBSERVED
IN LESION STUDIES IN NON HUMAN
PRIMATES TO BE RELEVANT FOR
AGGRESSION.
WE ALSO HAVE FOXP 2 SEEN IN
HUMAN PATIENTS THAT HAVE SPEECH
AND LANGUAGE DISORDERS OF FOX
P2K FAMILY FOR EXAMPLE AND THESE
ARE VERY TRANSLATION AS THE
REGIONS ARE HIGHLY CONSERVED
ACROSS SPECIES.
THERE'S INANS THERE'S GOING
TO BE DTOORTICAL CONTROL
THAT'S GOING TO BE HINDERING
SOME OF OUR IMPULSES TO ATTACK
FOR EXAMPLE THAT ARE NOT SEEN.
THERE'S LESS CORTICAL CONTROL IN
THE RODENTS.
>> GREAT TALK.
VERY FASCINATIFASCINATING.
VALERIE DARCY NIDDK.
THERE'S NO NEURONAL SIGNAL IS
THERE A SOCIAL HIERARCHY IN THE
MOUSE OR ANIMAL COLONY?
I KNOW IN NON HUMAN PRIMATES
THEY'RE ESTABLISHED AS DOMINANCE
HIERARCHIES AND WONDER IF YOU
MAY BE ABLE TO SPECULATE IN
THOSE COMMUNAL ANIMAL GROUP IF
THERE MIGHT BE SOME MECHANISTIC
HIGHER GABA LEVELS AND HOW THEY
MAY BE REFINED TO ESTABLISH THE
DOMINANT VERSUS THE PASSIVE
ANIMAL IN THE GROUP.
>> GREAT QUESTION.
WE DO SEE THERE'S RESPONSES WITH
SOCIAL EXPERIENCE AND THE MEDIAD
AMYGDALA SHOWS A MARKER OF
NEURAL ACTIVITY DURING SOCIAL
HIERARCHIES OF STRONGERAR
OPPONENTS.
THERE'S BEEN WORK DONE AND I
HAVEN'T LOOKED SPECIFICALLY IN
THE POPULATION BUT I WOULD BE
INTERESTED TO SEE IF THE FOX P2
CELLS ARELL RELEVANT IN NTABLIS.
THERE'S WORK IN THE AMYGDALA
PREFRONTAL CORTEXES AND WHERE IN
THE HI THE
E TBE.
THERE'S INTERESTING WORK ON
THAT.
>>
>> THAT'S THANK DR. LIS CLIN
SKI.
-- DLISCHINSKY.
>> TO CONCLUDE THE SESSION THE
2023 DISTINGUISHED SCHOLARS
SEASON WE HAVE DR. AUGUSTIN LUNA
TALKING ABOUT INTEGRATIVE MODEL
OF DRUG RESPONSE AND RESISTANCE
USING BIG DATA AND NETWORK
PHARMACOLOGY.
>> SO WITH THIS PRESENTATION I
WANT TO GIVE YOU AN OVERVIEW OF
THE WORK I DO WITH MY GROUP AND
LARGER SET OF COLLABORATORS.
SO THE WORK IN THEHE GROUP IS
FOCUSSED IN ONE ASPECT BUILDING
OUT DATA RESOURCES.
SO THESE ARE AROUND CANCER
PHARMACO GENOMICS AND DATABASES
FOR PATHWAY INFORMATION AND
EXCHANGE INFORMATION ABOUT
SYSTEMS BIOLOGY ACROSS DIFFERENT
SETS OF TOOLS IN A FAIR MANNER
AND REOPERABLE FASHION.
WITH THE DATA RESOURCES THAT
BECOMES THE INPUT TO VARIOUS
ANALYSIS TOOLS OF WHICH I'M
GOING IT TALK ABOUT A COUPLE.
THEY ANSWER PARTICULAR QUESTIONS
OF INTEREST BEING IN CANCER,
DRUG RESPONSE PREDICTION AND
ALSO D
RESISTANCE AND
BIOMARKERS IDENTIFIED FOR
CANCER.
SO THE FIRST TOOL I'M GOING TO
MENTION IS A LOT OF WORK WITH
DEVELOPMENT THERAPEUTICS BRANCH
AT THE NCI.
THIS IS A WEB APPLICATION
PLATFORM WHERE WE'RE PULLING IN
TOGETHER DATA FROM A LOT OF
DIFFERENT INSTITUTES AND THE
BROAD INSTITUTE AND OTHERS AND
WE HAVE PHARMACO GENOMICS AND
PROTEOMICS AND GENETIC
INFORMATION ALL FOR CELL LINES.
WITH THIS AND IN THE PLATFORM
USERS CAN EXPLORE THE DATA AND
PREDICTIVE PROGRESSION ANALYSIS
WITH THE CONTENT WE HAVE.
THE RESULTS ARE ANNOTATED WITH
GENE SETS AND PATHWAY
INFORMATION AND WE DO A LOT TO
DO DRUG IDENTIFIER CONVERSION.
THERE'S NOT REALLY ONE STANDARD
NOMENCLATURE FOR DRUGS OUT
THERE.
WE ALLOW TEAM TO PUT DIFFERENT
ALIASES IN.
OVER ALL WE HAVE A LARGE PART
FROM DRUG SCREENING HAPPENING AT
THE NCI.
AND THE PORTAL WE INVITE PEOPLE
TO COME AND USE BUT IT'S ALSO
KIND OF A WORK SPACE FOR US TO
DO INDIVIDUAL PROJECTS.
SO THE FIRST PROJECT THAT WE PUB
HISH BACK IN -- PUBLISHED WE
IDENTIFIED A DRUG THAT WE ARE
MOVING FORWARD WITH FOR THE
TREATMENT OF TRIPLE NEGATIVE
BREAST CANCER AND HIGHLIGHTING
THAT HERE WITH PDX EXAMPLES AND
A COUPLE OTHER PROJECTS WE'VE
WORKED ON IS IN SMALL CELL LUNG
CANCER, SARCOMA AND MORE RECENT
IS ADENO CORTICO CARCINOMA A
RARER FORM OF CANCER AND PUTTING
TOGETHER A TECHNICAL PEOPLE FOR
PEOPLE TO BE ABLE TO LEARN HOW
TO INSTALL CELL MINER CDB AND
CUSTOMIZE THE PORTAL.
THE LAST THING I WANT TO MENTION
WITH THIS IS TUMOR MINER AND
WE'RE MOVING INTO MORE PATIENT
FOCUSSED COLLECTING OF DATA.
A LOT OF THAT DATA IS THROUGH
CLINICIANS PART OF THE
THERAPEUTICS BRANCH AT THE NCI
FOCUSSED ON ADENO CORTICAL
CARCINOMA AND WANT TO FIND MORE
PREDICTIVE MODELS FOR TREATMENT
OF THOSE PATIENTS IN COMPARISON
TO WHAT WE'VE ALREADY DONE WITH
THE CELL LINES.
THE SECOND PROJECT I'LL QUICKLY
BRING UP IS DR. GAT.
SO THIS IS FOR DRUG RESPONSE
PREDICTION AND IT IS DEEP
LEARNING METHOD AND IT'S BY A
LARGE PART OF THE EFFORT BY A
RECENT HIRE INTO THE GROUP AS A
DOCTORAL STUDENT.
SO WITH A LOT OF THE WORK DONE
THEY'VE FOCUSSED ON ONE DRUG AND
ONE PREDICTION.
SO WITH THE HELP OF HIS EFFORTS
WE ARE MOVING TOWARDS MORE OF A
HOLISTIC MODEL THAT'S ABLE TO
TAKE IN INFORMATION FROM MANY
DRUGS AT ONCE TO BUILD ONE MODEL
THAT IS PREDICTIVE OF THESE MANY
DRUGS ACROSS DIFFERENT TYPES OF
SAMPLES.
HERE WITH THIS WORK FLOW THIS
HAS BEEN A DEEP LEARNING
ALGORITHM.
WE TAKE INFORMATION FROM DRUGS
AND THEIR STRUCTURES AND CAN
MOVE THEM TO A NUMERICAL
FINGERPRINT AND ALSO HAVE CELLS
AND THEIR RESPONSE TO A LARGE
COLLECTION OF DRUGS HERE.
IT'S ABOUT 270 DNA DAMAGING
COMPOUND AND HAVE 2,000 GENES
AND VARIOUS TRANSFORMATIONS TO
GET US INTO A NUMBER OF MATRIX
AND FEATURES TO MOVE FORWARD.
IN TERMS OF A GRAPH AS THIS IS A
GRAPH-BASED METHOD WE TAKE THE
DRUG RESPONSES AND THE GENE
EXPRESSION AND WE'RE ABLE TO
CONVERT THAT TO A RICH GRAPH
KNOWLEDGE BASE IN ADDITION TO A
DRUG AND TARGET INTERACTION
NETWORK AND SO THOSE TWO THINGS
COMBINED AND HERE'S THIS LAYER
HERE THIS THING LABELLED AS GAT.
THIS IS THE CRUX OF THE
ALGORITHM.
THIS IS A GRAPH ATTENTION LAYER,
DEEP LEARNING LAYER WHERE WHAT
WE'RE TRYING TO DO IS PRODUCE A
SET OF FEATURES THAT WHERE
EVERYWHERE HAS A FEATURE THAT IA
INFORMED BY ITS NEIGHBORS.
SO WITH THESE NEW FEATURES, WE
CAN THEN DO OUR DRUG PREDICTION.
BUT BECAUSE WE ALSO HAVE THIS
NETWORK WE CAN ALSO MAKE USE OF
THAT NETWORK FOR THE SAKE OF
INTEROPERABILITY OF THE RESULTS
WE GET.
IN THAT SENSE WE ARE USING THE
RELATIONSHIPS AND THESE ARE
WEIGHTED RELATIONSHIPS FOR DOING
THINGS LIKE ENRICHMENT ANALYSES
TO KNOW WHAT KIND OF PATHWAYS
MIGHT BE MOST RESPONDENT TO
PARTICULAR DRUGS AND BE
PREDICTIVE OF THAT RESPONSE.
THE OTHER THING WE DO IS A LOT
OF COMPARISON TO LITERATURE AND
WHAT'S KNOWN AND WHAT IS NEW IN
THE PREDICTIONS WE MAKE.
HERE WITH THIS SLIDE WHAT I'M
SHOWING IS A SURVEY OVERVIEW OF
THE RESULTS OF DR. GAT IN
COMPARISON TO OTHER BASELINE
METHODS.
SOME OF THE METHODS THAT WE'RE
COMPARING ARE MORE TRADITIONAL
METHODS SUCH AS RANDOM FOREST OR
GRADIENT BOOSTING AND SOME
METHODS THAT USE GRAPHS AND ARE
ALSO DEEP LEARNING.
FOR US WITH DR. GAT WE TRIED
DIFFERENT VARIATIONS OF THE
GRAPH ATTENTION EXTREME.
I HIGHLIGHTED WHAT WORKS BEST
FOR US AND YOU CAN SEE IT DOES
WELL IN COMPARISON TO OTHER
METHODS INCLUDING THE BASELINE
METHODS AND THE VARIATIONS FOR
DR. GAT.
DOWN HERE JUST TO DRAW YOUR
ATTENTION TO FIGURE
FIGURE B THIS IS WHERE IN
ORANGE NODES WE HAVE DIFFERENT
DRUGS AND WE HAVE THE TOP FIVE
PREDICTIVE FEATURES AND THIS IS
A SOLID LINE KNOWN DRUG TARGET
INTERACTION FROM THAT DRUG TO A
PARTICULAR GENE BEING USED AS
PART OF THE PREDICTION.
BUT ALSO WITH THE LONGER DASH
LINES IS WHERE IT IS A KNOWN
ASSOCIATIONS NOT NECESSARILY A
TARGET INTERACTION AND THEN WITH
THE SMALLER DASH LINES THESE ARE
NOVEL PREDICTED INTERACTIONS
THAT MIGHT EXIST AND FOLLOWED UP
EXPERIMENTALLY.
WITH THIS PROJECT WE'RE ALSO
EXPANDING TO NOT JUST DNA
DAMAGING DRUGS BUT THE LARGER
COLLECTION OF DRUGS AS PART OF
THE NCI 60 AND CELL MINER
COLLECTION.
THE THIRD PROJECT I BRIEFLY WANT
TO MENTION IS MORE COMMUNITY
EFFORT IN RESOURCE SHARING AND
BIO GRAPHICAL NOTATION.
PATHWAYS AND PATHWAY DIAGRAMS
ARE A WAY THAT WE HAVE SEEN
LOOKED ACROSS MANY PAPERS WHERE
IT SUMMARIZES THE RESULTS FOR
MANY PUBLICATIONS.
AND WHAT SBGN IS TRYING TO DO IS
A COMMUNITY STANDARD WHERE WE
WANT TO PRODUCE AN UNAMBIGUOUS
FASHION AND HAVE PATHWAYS HUMAN
READABLE AND MACHINE READABLE
AND THAT MEANING THAT WE CAN
EXCHANGE THE PATHWAY INFORMATION
BETWEEN TOOLS AND KEEP IMAGES
NOT JUST LIKE A PICTURE OF A CAT
BUT WITH SEMANTICS BEING
EXCHANGED BETWEEN DIFFERENT
TOOLS.
SBGN IS USED IN PATHWAYS AND
MATHEMATICAL MODELLING AND SOME
CURRENT EFFORTS WITH A RECENT
HIRE FROM THE SUMMER A POSTDOC
ONE OF THE EFFORTS WE'RE TRYING
TO DO IS HOW DO WE MAKE IT
EASIER FOR PEOPLE TO WORK WITH
THE FORMALISM AND SO THIS IS UFK
ARTIFICIAL IN TETELLIGENCE TO T
VERSION OF SBGN AND WE'RE
WORKING ON ARTIFICIAL
INTELLIGENCE FOR AUTOMATIC
ANNOTATION OF THE PATHWAYS AND
LAST REFINEMENT OF A SPECIFIC SO
UNDERLYING SBGN AND THE
COMMUNITY EFFORT WE'VE HAD
CONTRIBUTIONS FROM AROUND 80
AUTHORS IN PREVIOUS
SPECIFICATIONS.
WE HAVE A LOT OF ISSUES THAT
HAVE ARISEN EXACTLY HOW YOU
VISUALIZE A PARTICULAR THING.
SO WE'RE WORKING THROUGH THOSE
ISSUES AND HAVE A SET OF 42
ISSUES BEFORE THE NEXT RELEASE
FROM OUR PREVIOUS SPECIFICATION
THAT WAS RELEASED FIVE YEARS
AGO.
THE LAST PROJECT I BRIEFLY WANT
TO MENTION IS TARGET SCORE AND
SO THIS IS COLLABORATION WITH MD
ANDERSON LOOKING AT CANCER DRUG
RESISTANCE AND SO WITH THIS
PROJECT THE MAIN ALGORITHM OF
TARGETS IS WHERE WE'VE GOT A SET
OF WE NEED TWO PIECES OF DATA
NETWORK AND PROFILING
INFORMATION AND SO WITH THE DRUG
TREATMENT INFORMATION YOU'VE GOT
A SET OF SAMPLES SOME SENSITIVE
TO A DRUG OR RESISTANT TO A DRUG
AND WITH IT WE TREAT THE SAMPLES
AND COLLECT PROFILING
INFORMATION AFTER THE FACT IN
THIS CASE PHOSPHO PROTEOMICS AND
WE HAVE A REFERENCE NETWORK THAT
CAN BE PULLED IN FROM PATHWAY
DATABASES, LITERATURE MANUALLY
CURATED DATABASES OR ALSO
CREATED FROM NETWORK INFERENCE
ALGORITHMS.
IN OUR CASE WE'RE MERGING THE
TWO CONCEPTS TOGETHER TO GET US
A REFERENCE NETWORK THAT IS
CONTEXT SPECIFIC.
THE THIRD AND THIS IS THE TARGET
SCORE FORMULA.
FOR EACH PROTEIN MEASURED WHAT
WE'RE TRYING TO GET A SENSE OF
IS HOW MUCH AN INDIVIDUAL
PROTEIN IS GOING UP OR DOWN.
AND ALSO HOW MUCH IN THE NETWORK
AROUND IT IS GOING UP OR DOWN.
AND THEN THAT IS ALSO PAIRED
WITH THIS FUNCTION SCORE SO THIS
IS MAINLY CURATED SCORE THAT IS
TELLING US WHETHER OR NOT A
PARTICULAR PROTEINS ARE MORE PRO
CANCER OR TUMOR SUPPRESSER OR
ONCOGENES AND WHERE IT'S
AMBIGUOUS WE HAVE A ZERO.
ONCE WE HAVE THE TARGET SCORE
VALUES FOR THE PROTEINS WE'RE
ABLE TO MAP THEM TO THE
REFERENCE NETWORK AND THEN TRY
TO IDENTIFY PATHWAYS AND MODULES
THAT ARE GOING UP OR DOWN TO A
PARTICULAR TREATMENT.
THEN FROM THERE WE CAN FORM
HYPOTHESIS OF WHAT SHOULD BE
COMPLEMENT THE ORIGINAL DRUG AND
THEN START DOING EXPERIMENTS.
THIS IS QUICKLY AN ONGOING
PROJECT THAT MAKES USE OF TARGET
SCORE AND THE HYPOTHESIS
GENERATED THERE AND IT'S
FOCUSSED AROUND BREAST CANCER
AND THE RESISTANCE OF MCL1.
IT'S ALTERED IN A LOT OF BREAST
CANCER PATIENTS AND ALSO RELATED
TO APOPTOSIS WITH THE TARGET
SCORE ALGORITHM THE HYPOTHESIS
GENERATED FROM IT WAS MAKING USE
OF AN INHIBITOR RESPONSE AND
INHIBIT GROWTH AND TO NOT GO
OVER THE DENSE RESPONSE CURVES
BUT THE SUMMARY FIGURE IS THE
DOSE RESPONSES.
WHAT WE'RE ABLE TO SEE WITH THE
EXPERIMENTS IS THAT MCL1 IN
COMBINATION WITH THE MCL1 IN THE
PRESENTAL CELL LINE SENSITIVE TO
MCL1 WORKS MORE SYNERGISTICALLY
AND YOU SEE THE CELL LINE
RESISTANT TO MCL1 AND THERE WE
SAW SYNERGY WITH THE INHIBITOR
ALONE.
THUSZ THIS
THIS FIRST NOT OF A THIS IS JUST
SHOWING THAT WE HAVE A PDX
RESISTANT TO MCL1 INHIBITION AND
WITH B THE, GREEN LINE IS THE
MAIN HIGHLIGHT IS THAT THE
COMBINATION IS ABLE TO KEEP
TUMOR VOLUME LOW IN THE PDXs AND
THEN D AND E IS A COMPLETELY
SEPARATE SET OF PDX EXPERIMENTS
DONE BY A DIFFERENT GROUP OF
COLLABORATORS AT HARVARD WHERE
WE ALSO SEE A SIMILAR RESULT
WHERE THE COMBINATION OF PART
AND SHIP TO INHIBITION IS ABLE
TO KEEP THE MICE SURVIVING THE
LONGEST.
AND THEN THAT'S IT.
SO JUST ACKNOWLEDGEMENTS ON
THESE PROJECTS AND OTHER
PROJECTS.
A GREAT SET OF COLLABORATORS
I'VE HAD THE FORTUNE TO WORK
WITH AND THAT'S IT.
>> ANY QUESTIONS FOR DR. LUNA?
IN YOUR PROCESS OF DEVELOPING
THESE TOOLS HOW MUCH DO FIGURE
USABILITY?
DO YOU BRING IN DIFFERENT GROUPS
TO SEE HOW THEY CAN IMPLEMENT IT
OR TARGETINGC QUESTIONSIO IO
AND CUSTOMIZING THE TOOL?
>> SOME TOOLS LIKE SPM IS WHERE
WE INVITE AS MANY USERS AS
POSSIBLE BECAUSE WE WANT THE
PATHWAYS UNDERSTAND BY A WIDE
SWATH OF BIOMEDICAL RESEARCHERS.
ALSO WITH THE CELL MINER C D
DID -- CDB IS DIRECTED AT CANCER
RESEARCHERS BUT WANT A WIDE
SWATH OF RESEARCHERS BE ABLE TO
ANSWER THE QUESTIONS THEY'RE
MOST INTERESTED IN.
THE WAY IT WORKS AND SOME
FEATURES ARE AS MODULES THAT CAN
BE ADDED IN OR REMOVED DEPENDING
ON THE USE CASE.
WITH THE CELL LINE WORK THAT
REQUIRES A CERTAIN SET OF
MODULES.
KNOW THAT WE'RE MOVING INTO
PATIENT FOCUSSED MATERIAL AND WE
WANT CLINICIANS TO BE ABLE TO
MAKE USE OF THE RESOURCES, THAT
REQUIRES A DIFFERENT SET OF
QUESTIONS AND WE'RE ASKING
CLINICIANS WHAT THE THINK OF THE
TOOL.
>>
>> LET'S THANK DR. LUNA.
THAT CONCLUDES OUR 2023 DSP
SCHOLARS PRESENTATION.
>> WE'RE GOING TO G TAKEER
SHORT BREAK AND BACK AT 3:00 FOR OUR 2024 DSP INTRODUCTIONS.
I'VE BEEN PART OF THE PROGRAM
THE LAST THREERS AND IT'S
FABULOUS AND FEEL HUMBLED TO
INTRODUCE THE LINEUP OF SCHOLARS
THIS YEAR.
WELCOME TO THE LARGE FAMILY.
I HOPE YOU WILL ENJOY AND WILL
BE HERE THE NEXT 40 YEARS.
I'M OPTIMISTIC ABOUT THE
PROCESS.
THE FIRST IS DR. VICTORIA
ACOSTA-RODRIGUEZ FROM THE NIA. F
>> GOOD AFTERNOON.
I'M VICKY.
I JOINED THE TRANSLATIONAL
GERONTOLOGY BRANCH THIS YEAR
2024.
THE NUMBER 24 HAS SPECIAL
MEANING FOR ME I'M A CIRCADIAN
BIOLOGIST BECAUSE WE KNOW WE
HAVE DEVELOPED A 24 HOURS TIME
KEEPING MECHANISM THAT ALLOWSLLS
PREDICT AND ANTICIPATE
CHANGES IN THE ENVIRONMENT.
AS SUCH WE KNOW FROM THE SIR --
CIRCADIAN CHANGE MOLECULAR AND
THE MOST KNOWN CIRCADIAN RHYTHM
IS THE 24 HOURS CYCLES INS
AWAKE CYCLES.
AS WE KNOW MANY BIOLOGICAL
FUNCTIONS DECLINE WITH AGE AND
CIRCADIAN RHYTHMS.
IN OUR UNIT WE ARE TRYING TO
UNDERSTAND HOW THE CIRCADIAN
CLOCKS AGE AND LOSE THEIR
ABILITY TO TELL TIME.WE ARE ALS
PROMOTE INTERVENTIONS THAT CAN
PROMOTE THE RHYTHMS AT OLDER
AGES TO PROMOTE H LIFE L
SPAN.
THE TWO AREAS WE'RE TRYING TO
UNDERSTAND IS HOW THE CIRCADIAN
CLOCKS CHANGE AND THE DAMPENING
MECHANISMS AND LOOKING AT
INFLAMMATION AND SENESCENT CELLS
AS A DAMPENING FOR THE CIRCADIAN
RHYTHMS AND TAKING ADVANTAGE OF
THE POTENTIAL NIH OFFERS US TO
DO LONGITUDINAL STUDIES IN MICE
AND TRACK HOW CIRCADIAN CLOCKS
WORK THROUGHOUT THE ENTIREHEE G
DIFFERENT TISSUES.
AND THE GOAL OF THIS VERY HIGH
RISK PROJECT IS TO TRY TO
IDENTIFY MARKERS OF CIRCADIAN
ETHNICITY TO PREDICT AGINGRE
PROGRESSION.
WE CANNOT DO THIS TYPE OF
RESEARCH OURSELF.
WE HAVE THIS AMAZING TEAM WITH
SCIENTISTS THAT WERE BRAVE
ENOUGH TO JOIN A LAB THAT JUST
STARTED.
AND THIS IS OUR WORKING
HYPOTHESIS IS THAT IF WE CAN
PROMOTE CIRCADIAN RHYTHMS WE CAN
LIVE HEALTHIER FOR LONGER IN ALL
OF US.
AND THE SECRET WEAPON THAT WE
ARE TRYING TO USE IS ACTUALLY
NOT VERY EXPEN THERAPIES BUT
USING TIME OF DAY AS A SIMPLE V
HEALTHIER LIFE SPAN.
THANK YOU.
>> SO DON'T HAVE TIME FOR
QUESTIONS GOING TO THE NEXT
SCHOLAR IS PHILLIP ADAMS FROM
THE NIAID.
>> I'M EXCITED TO BE HERE.
I WAS HERE PRESENTING AS AN
INDEPENDENT RESEARCH SCHOLAR
LAST YEAR SO IT'S NICE TO
PRESENT HERE AS AN INCOMING
DISTINGUISHED SCHOLAR.
MY GROUP IS STARTING IN NIAID
AND WE STUDY GENE REGULATION IN
PATHOGENIC SPIROKETE AND YOU SEE
IT DEPICTED IN THE MICROGRAPH.
THESE CELLS ARE VERY LONG,
SLENDER CELLS AND YOU PROBABLY
KNOW THEM FROM THE CONTEXT IN
LOOICHL DISEASE.
IT EXISTS IN A MOUSE OR SMALL
MAMMAL RESERVOIR AND ACQUIRE THE
BACTERIUM.
IF YOU ENCOUNTER AN INFECTED
TICK IT CAN DEVELOP TO LYME
DISEASE.
SO A TICK IS 23 DEGREES A MAMMAL
IS 37 DEGREES.
THERE'S DIFFERENT PROPERTIES IN
THE ORGANISM AND NUTRIENTS AND
BORRELIA USE GLUCOSE IN MAMMALS
AND DIFFERENT IMMUNE DIFFERENCES
AN FACTORS, ETCETERA.
SOMETHING MY LAB HAS BEEN
FOCUSSED ON IS THE STUDY OF
MOTILITY.
SO BOAR -- BORRELIA AND IT
BECOMES MOTILE.
IT CHANGES THE OUTER SURFACE
PROTEINS AND MOVES INTO THE
SALIVARY GLAND INTO THE HOST.
WHAT PREDICTS THAT IS UNKNOWN
AND ONE BARRIER OF ASKING THE
QUESTION IS THERE'S LOW INPUTS
IN THE NUMBER OF BACTERIA IN
TICKS AND ALSO IN MAMMALS.
SO WE'VE BEEN USING SOME NEW
SEQUENCING APPROACHES IN
COMBINATION WITH PEOPLE IN NIAID
TO ENRICH FOR THE BORRELIA
TRANSCRIPTOME AND I'LL LEAVE IT
AT THAT AN ME THANK YOU SO
MUCH.
.
>> THANK YOU.
THE NEXT SPEAKER IS FARRAN
BRIGGS FROM THE NIH.
THANK YOU.
>> THIS IS A SURPRISE BECAUSE I
DON'T REMEMBER WHAT I PUT ON THE
SLIDE.
SO I'VE HAD AN ESTABLISHED
LABORATORY A NUMBER OF YEARS NOW
RECENTLY COMING FROM THE
UNIVERSITY OF ROCHESTER.
AND I'M A VISION SCIENTIST AND
SO AT THE CORE THE GOAL OF MY
RESEARCH IS TO TRY TO FIGURE OUT
HOW TO REHABILITATE VISION IN
CASES OF VISION L
UT ALSO
JUST TO TRY TO UNDERSTAND THE
VERY BASICS OF HOW OUR BRAINS
PROCESS THE VISUAL STIMULI OUT
IN THE WORLD.
AND SO WE ACTUALLY HAVE A NUMBER
OF DIFFERENT RESEARCH PROJECTS
THAT ARE ONGOING AND THOSE ARE
LISTED DOWN BELOW.
AND I'M NOT GOING TO GO THROUGH
THEM BUT SOME OF THE THEMES THAT
FOLLOW THROUGH ALL OF MY
RESEARCH WHICH I THINK I
HIGHLIGHTED AT THE TOP IS I'M S
ALWAYS INTERESTED IN FINDING
LINK BETWEEN STRUCTURE AND
FUNCTION.
SO PART OF ME IS PHYSIOLOGIST
AND REALLY AT THE CORE OF WHAT I
DO IS TRYING TO UNDER OF
UNDERSTAND HOW PARTICULAR CELLS
AND CIRCUITS ARE CONNECTIONS
BETWEEN CELLS GIVE RISE TO THE
PERCEPTIVE VISION.
MOST OF WHAT I'M STUDYING IS
VERY LOW LEVEL.
YOU SEE ON THE TOP HERE THE
RETINA AND THE VISUAL THALAMUS
AND THE VISUAL CORTEX.
AT THE EARLY STAGES WE DON'T
HAVE MUCH OF A CONSCIOUS PERCEPT
OF THE EARLY STAGES YET IF
THERE'S DAMAGE IT'S
DEBILITATING.
SO AGAIN THE CORE OF MY RESEARCH
THEN IS TO TRY TO UNDERSTAND HOW
THESE PATHWAYS ARE FUNCTIONING
IN HEALTHY INDIVIDUALS AND WHAT
GOES WRONG IN CASES OF LOW
VISION.
THIS PICTURE IS NOT JUST MY LAB.
IT'S MY LAB AND FRIENDS SO I'M
NOT THAT IMPORTANT.
BUT WE HAVE GROWN TO QUITE A
LARGE GROUP AT ROCHESTER.
SOME OF THOSE PEOPLE I WILL BE
CONTINUING TO COLLABORATE WITH.
A FEW MAY END UP COMING HERE IN
THE FUTUREE I'M EXCITED TO
CONTINUE MY ONGOING COMMITMENT
TO MENTORING AND ESPECIALLY TO
DEIA AND SO I'M EXCITED TO BE
PART OF THE PROGRAM.
RTYOU VERY MUCH.
>> THANK YOU.
THE NEXT SCHOLAR IS DR. LEAH
COOK.
SHE'S A SENIOR INVESTIGATOR AT
THE NCI.
I GOT TO KNOW HER RECENTLY.
WELCOME.
THANKS SO MUCH.
THANKS SO MUCH FOR THIS PROGRAM.
IT'S BEEN REALLY NICE HEARING SO
MUCH COOL SCIENCE GOING ON HERE.
I'M LEAH COOK.
I RECENTLY CAME HERE FROM
UNIVERSITY OF NEBRASKA MEDICAL
CENTER WHERE I STARTED MY LAB
AND INTERESTED IN THE MECHANISMS
OF BONE METASTATIC PROSTATE
CANCER AND HOW THE TUMOR CAN
GROW AND THRIVE LARGELY DUE TO
THE INTERACTIONS OF PROSTATE
CANCER CELLS WITH BONE STROMAL
CELLS THAT HIJACK THE PROCESSES.
YOU CAN SEE IT IN THE PATIENT'S
SPINE WHERE THERE'S MILKY WHITE
REGIONS AN AN INDICATION OF
TUMOR OSTEOGENESIS AND THOUGH WE
KNOW A LOT ABOUT THE
INTERACTIONS THE MORE ABUNDANT
POPULATIONS OF CELLS ARE
NEUTROPHIL PRE CURSORS AND
HEMATOPOIETIC CELLS AND TRYING
TO UNDERSTAND HOW IT ADVANCES
PROGRESSION AND IT CAN SHUT DOWN
THE TUMOR RESPONSE.
WE'RE INVESTIGATING THE
MECHANISMS AND HOW NEUTROPHILS
INDUCE DEATH AND HAVE SPECIES IN
RESPONSE TO THE TUMOR CELLS AND
THEY LOVE IT.
WE'RE TRYING TO UNDERSTAND HOW
WE CAN UTILIZE THAT INFORMATION
TO TARGET PROSTATE CANCER
PROGRESSION BY FATTY ACID
METABOLISM.
AND FROM CLINICAL DATA WE
ACQUIRE FROM PERIPHERAL BLOOD
NEUTROPHILS I WAS EXCITED TO
FIND WE ACTUALLY SHOWED THAT
ANDROGEN THERAPY CAN SHUT DOWN
RESPONSE BY TURNING ON TGF BETA
SIGNALLING AND TRYING TO
INFORMATION TO RESCUE THE
NEUTROPHILS AND I BECAUSE I
NEVER GET TIRED OF TALKING ABOUT
NEUTROPHILS OR BONE AND LOOK AT
THE BONE STROMAL CELLS TO
REGULATE CELLS THROUGH
PROINFLAMMATORY CYTOKINES
THROUGH THAT INTERACT
WITH THAT I'LL STOP.
THANK YOU SO MUCH.
>> THANK YOU.
OUR NEXT SCHOLAR IS VA I
DARCEY FROM THE NIDDK.
WELCOME.
>> HI, EVERYONE.
I'LL VALERIE DARCEY.
I AM A NEW STADTMAN TRACK
ADVOCATOR AT NIDDK LEADING THE
ACTION ON NUTRITION AND
METABOLIC NEURO LIIMAGIN
I WANT TO START WITH MAKING YOU
THINK WHAT IF YOUR STATUS CAN
ESTABLISH COULD LEAD TO YOUR
DIET OR SMOKING S CESSATION.
THE TWO MAIN BRAIN REGIONS OF
INTEREST ARE THE PREFRONTAL
CORTEX WHICH I SHOULD START WITH
THE STRIATUM WHICH E E BASICALLY
DRIVES OUR MOTIVATIONS AN
IMPULSES THINK OF IT AS THE GAS
PEDAL AND THE PREFRONTAL CORTEX
AS THE BRAKES CAN CONTROL THE
DRIVES AND IMPULSES.
SO MY EARLY WORK I SHARED
HEALTHY ADOLESCENCE WHEN WE
LOOKED AT THE OMEGA 3 FATTY ACID
INTAKE IF WE DON'T CONSUME ITS
IN OUR DIET WE'LL BECOME
DEFICIENT THEIR INTAKE AND BLOOD
LEVELS WERE NOT ONLY RELATED TO
THEIR IMPULSE CONTROL BUT ALSO
TO THEIR BRAIN STRUCTURE, THEIR
PREFRONTAL DEVELOPMENT AND
IMPULSE CONTROL.
FROM A POSTDOCTORAL STANCE I
SWITCHED AT LOOKING AT THE
STRIATUM OF IMPULSE CONTROL BY
LOOKING AT HEALTHY ADULTS.
I LOOK AT THE STRIATUM WITH
RESPECT TO DOPAMINE.
I USED MULTI-MODAL NEURAL
IMAGING AND TOMOGRAB OGRAPHY AN
PROTON SPECTROSCOPY LOOKING AT
NEURAL FUNCTION AND PHYSIOLOGY.
SOME MAY BE THINKING I CAN'T
REMEMBER WHAT I ATE FOR DINNER
HOW CAN YOU BE SURE YOUR
PARTICIPANTS ARE REPORTING WHAT
THEY ATE ACCURATELY.
TO CIRCUMVENT THAT WE DO
CONTROLLED FEEDING STUDIES AND
HAVE PRECISE CONTROL OVER WHAT
THEY'RE PUTTING IN THEIR BODIES
AND HOW IT MAY CHANGE THEIR
BRAIN CHEMISTRY.
CONTRARY TO POPULAR BELIEF AN
ACUTE HIGH FAT, HIGH SUGAR MILK
SHAKE DOESN'T CHANGE SO MUCH IN
TERMS MUCH DOPAMINE RESPONSE AND
WITH REDUCED CARBOHYDRATE
INCREASED BASIL DOPAMINE TONE
AND HIGH FAT FOODS AFTER DIETS
WERE COMPLETED IN PEOPLE WITH
OBESITY AND PEOPLE WHO HAVE
OBESITY MAY BE STARTING AT A
HIGHER LEVEL OF DOPAMINE TONE
COMPARED TO COUNTER PARTS
WITHOUT OBESITY.
ONE BIG QUESTION I'M INTERESTED
IN DIVING INTO FIRST WHILE
STARTING MY LAB AT NIDDK IS
FIGURING OUT WHETHER ULTRA
PROCESSED FOODS MAY CHANGE OUR
CHEMISTRY AND INCREASING
POTENTIALLY INFLAMMATION IN
BRAIN CENTERS THAT CONTROL
APPETITE LIKE THE HIPE --
HYPOTHALAMUS AND IMPULSE.
THAT'S WHAT I PLAN TO DO.
>> THANK YOU.
OUR NEXT SCHOLAR IS IFECHUKWUDE
EBENUWA FROM THE NIDDK.
WELCOME.
>> HELLO.
NICE TO BE HERE.
SO OUR LAB OF RESEARCH GOALS THE
TWO MAIN RESEARCH GOALS ONE IS
TO UNDERSTAND THE
PATHOPHYSIOLOGICAL HAPPENING IN
CHRONIC DISEASE LIKE DIABETES.
WE USE VITAMIN C AND THE SECOND
GOAL IS IT TO EXPLORE
INTERVENTIONS IN THE MITIGATING
DISEASE PROGRESSION.
AND VITAMIN C IS AN IMPORTANT
NUTRIENT AND INVOLVED IN THE
BODY'S FUNCTIONS.
AND SOME OF THE WORK WE'VE DONE
HAS SHOWN VITAMINS
DYSREGULATED IN HIV AND WHAT IS
SHOWN IN THE PRESENTATION WE
FOUND INDIVIDUALS WITH HIV AND
DIABETES HAVE ABNORMALLY
INCREASED LOWS CONTRIBUTING TO
LOW VITAMIN C CONCENTRATION.
ONE BUCKET IS UNDERSTANDING THE
MECHANISMS IN DISEASE AND HOW
VITAMIN C CANS REGULATION IS
BUILT UP IN DECEASE AND LOOKING
AT THE -- DISEASE AND HOW
VITAMIN C IS UTILIZED AND THE
BIO AVAILABILITY OF VITAMIN C IS
DIFFERENT IN DISEASE AND LOOKING
AT FACTORS THAT CONTRIBUTE.
IT'S NOT JUST CLINICAL AND
DIETARY AND DEMOGRAPHIC
DIFFERENCES BUT THE SOCIO
ECONOMIC FACTORS THAT PREDISPOSE
SOME OF THREES DYSREGULATION
WE'VE OBSERVED AND THE THIRD
BUCKET IS LOOKING AT THE HEALTH
IMPLICATIONS AND VITAMIN C IS
DYSREGULATED SO WHO CARES.
AS AN ENDOCRINOLOGIST I'M
FOCUSSED ON THE EFFECT ON
ENDOCRINE STRESS REGULATION AND
UNDERSTANDING THE IMPACT IT HAS
ON PSYCHIATRIC FUNCTIONING.
THANK YOU.
>> OUR NEXT SCHOLAR IS RAJULA
ELANGO.
>> THANK YOU FOR BEING HERE.
MY NAME IS RAJULA ELANGO AND I'M
A NEW TENURE TRAFFIC
INVESTIGATOR AT THE NIE HS IN I
NORTH CAROLINA AND AFFILIATED
WITH THE LABORATORIES AND LEAD
THE STALLED REPLICATION REPAIR
GROUP AND INTERESTED IN
UNDERSTANDING HOW DNA DAMAGE IS
FORMED, DIAGNOSED AND REPAIRED
IN MAMMALIAN CELLS.
ONE SUCH TYPE OF DNA LESION
WE'RE INTEN IS CALLEDTETE
THE DNA PROTEIN PROS -- CROSS
LINK.
THESE ARE ROUTINELY FORMED IN
RESPONSE TO CHEMOTHERAPY.
IN ADDITION THESE LESIONS WERE
OFTEN FORMED IN RESPONSE TO
ENVIRONMENTAL EXPOSURE LIKE
RADIATION AND OXIDATIVE STRESS.
SO IT BECOMES IMPORTANT TO
UNDERSTAND WHAT HAPPENS WHEN THE
REPLICATION ARRIVES AND BUMPS
INTO THIS DNA LESION BEFORE IT
BEGINS TO DISRUPT ALL THE OTHER
PROCESSES LIKE REPLICATION AND
TRANSCRIPTION.
SO MY LAB HAS SET UP PROJECTS TO
ADDRESS SOME OF THESE QUESTIONS.
FIRST, WE'RE INTERESTED IN
UNDERSTANDING HOW THESE DPCs ARE
DETECTED AND PROCESSED IN
MAMMALIAN CELLS AND INTERESTED
IN UNDERSTANDING THE DNA
INTERMEDIATES ARE FORMED IN
RESPONSE TO THESE DBCs.
AND MOST IMPORTANTLY WHERE ARE
THE IMPLICATIONS OF THE ARE PAIR
OR LACK OF REPAIR OF THE DPCs IN
DISEASES LIKE CANCER AND WHAT
ARE THE EFFECTS IN HUMAN HEALTH.
WE DEVELOPED ASSAYS IN OUR LAB
AND ESTABLISHED STATE OF THE ART
TECHNIQUES THAT ARE NEXT
GENERATION SEQUENCING.
WE HAVE HIGH THROUGHPUT
SEQUENCING TECHNIQUES AND N SEQ
TO VISUALIZE INTERMEDIATE TO THE
NUCLEOTIDE LEVEL WITH HIGH
PRECISION.
SO IF WE CAN ADDRESS ALL OF
THESE QUESTIONS WE WILL NOT ONLY
UNDERSTAND HOW DNA PROTEIN CROSS
LINKS OUR REPAIR IN MAMMALIAN
CELLS AND TARGET THE PATHWAYS
FOR THERAPY.
THANK YOU.
>> THANK YOU. OUR NEXT SPE IS N
FARMER FROM THE CLINICAL CENTER.
>> I'M PLEASED TO BE HERE.
THREW TO THE DSP COMMITTEE FOR
THE WORK WE DO AND I WANT TO SAY
IT'S GREAT TO HAVE SO MANY
DIFFERENT INVESTIGATORS IN THIS
COHORT THAT ARE FOCUSSED ON
NUTRITION.
I'M VERY EXCITED TO SEE SHOUT
OUT TO THE NUTRITION PEOPLE WHAT
WE COME UP WITH.
SO MY SECTION IS ENTITLED
DIETARY BEHAVIORS IN BIO
PSYCHOSOCIAL HEALTH.
I KNOW THAT'S A MOUTHFUL SO I'LL
DO EXPLANATION WHAT OUR RESEARCH
GOALS ARE AND OUR RESEARCH
APPROACHES.
SO ONE, LET ME GIVE A BASIC
FACTOR ABOUT BEHAVIORS IN
POPULATION HEALTH.
GLOBALLY 1 IN 5 DEATHS ARE
RELATED TO POOR DIETARY INTAKE.
THE LAST 20 YEARS WE'VE HAD
ADVANCES IN RESEARCH WITH
DIETARY APPROACHES TO
HYPERTENSION AND THE
MEDITERRANEAN DIET IN TERMS OF
LEARNING THE IMPORTANCENG OF
DIETARY PATTERNS FOR DISEASE
RISK PREVENTION.
BUT LESS ABOUT 80% OF AMERICANS
DO NOT FOLLOW CURRENT FRUIT AND
VEGETABLE AND WHOLE GRAIN
RECOMMENDATIONS WHICH ARE THE
MAINSTAYS OF THESE PATTERNS AND
THINKING ABOUT THIS
IMPLEMENTATION SIDE OF NUTRITION
AND HOW TO DESIGN EFFECTIVE AND
EQUITABLE INTERVENTIONS THAT
REACH COMMUNITIES MOST AT RISK
FOR DIET-RELATED DISEASES?
SO TO DO THIS WE USING A
PHILOSOPHICAL MODEL CALLED THE
BIO PSYCHOSOCIAL HEALTH MODEL
LOOKING AT BIOLOGICAL OUTCOMES
AND SOCIAL DETERMINATES IN A
DIETARY PATTERN.
AND WE LOOK AT ENVIRONMENT AND
DIET INTERACTIONS AND SO THAT
ENVIRONMENT CAN BE THE FOOD
ENVIRONMENT AS WELL AS ONE'S
HOUSEHOLD SOCIAL ENVIRONMENT AND
AN EXAMPLE OF THE RESEARCH
FINDINGS I DID AS A POSTDOC A
COUPLE YEARS AGO WAS LOOKING AT
THE ROLE OF FOOD ENVIRONMENT AND
NEIGHBORHOOD ENVIRONMENT ON A
DIETARY METABOLITE LINKED TO
INFLAMMATION AND CARDIOVASCULAR
RISK FACTORS AND LINK
ENVIRONMENT TO INFLAMMATION AND
METABOLITE DISORDERS.
OUR RESEARCH APPROACHES
CONSISTENT OF THREE MAIN PARTS,
COMMUNITY ENGAGEMENT SO WE GO
INTO SOUTHEAST D.C. AND DO
COMMUNITY ENGAGEMENT IN OUR
DIETARY INTERVENTIONS AND HAVE A
BIO BEHAVIORAL COMPONENT WHERE
WE'RE SEEKING TO ANSWER WHAT
SEEMS LIKE TWO OPPOSING
QUESTION.
THE FIRST IS HOW CAN WE MODULATE
COOKING TASK TO LOWER
ANTICIPATORY STRESS FOR THOSE
NEW TO COOKING OR DIET
INTERVENTIONS AND A FILL SO --
PHILOSOPHICAL QUESTION AND WHAT
DRIVES US TO COOK WITH SO MANY
FOOD AROUND US AND WE USE MOBIL
BL EEG IN A COOKING LAB
AND ARE TRYING TO LOOK AT
LOCALIZATION TO THE PREFRONTAL
CORTEX LOCATIONS AND WE HAVE A
TRANSLATIONAL ARM TO OUR
RESEARCH WHERE WE PHENOTYPE BY
ENVIRONMENT, DIET AND CLINICAL
OUTCOMES AND LOOK AT STRESS
PROFILE METABOLOMIC PROFILING IN
THE IMMUNE CELL FUNCTION AND
PROFILES.
WE HOPE WITH THE START OF THIS
LAB OUR IMPACT WILL BE THAT
WE'LL HAVE TO CREATE A RESEARCH
FRAMEWORK FOR INCORPORATING BIO,
PSYCHOSOCIAL OUTCOMES RELATED TO
DIETARY BEHAVIOR TO IMPROVE THE
IMPLEMENTATION SCIENCE WHEN IT
COMES TO THE FIELD OF NUTRITION.
WE'RE ALSO INTERESTED IN SPECIAL
PATIENT POPULATIONS LIKE THOSE
WHO HAVE SUBSTANCE DISORDERS OR
SICKLE CELL DISEASE AND LOOKING
AT DIETARY INTERVENTIONS FOR
THEM AND CONTINUING OUR LOCAL
NEIGHBORHOOD ENVIRONMENT WORK
AND I'D LIKE TO THANK THE
MEMBERS OF MY TEAM IN THE
AUDIENCE AND REPRESENTED ON THE
SLIDE.
THANK YOU.
>> OUR NEXT SCHOLAR IS CARLOS
FERREIRA FROM THE NIMHD.
----NICHD.
>> I'M EXCITED TO BE HERE.
MY LAB I'M A CLINICAL TRACK
INVESTIGATOR AS OF TODAY IN FACT
AND MY LAB STUDIES SKE
DISORDERS.
WE BASICALLY HAVE THREE GOALS.
ONE IS TO UNDERSTAND THE NATURAL
VISIT OF THE DISORDERS AND FOCUS
ON TWO GROUPS OF DISORDERS.
ONE IS DISORDERS OF BIOLOGY AND
THE OTHER IS SKELETAL DYSPLASIA
IDENTIFYING NEW GENES TO NEW
DISEASE AND WE BRING THEM TO THE
CLINICAL CENTER AND PERFORM DEEP
PHENOTYPING.
WHAT I MEAN IS NOT JUST SKELETAL
PHENOTYPING BUT MANY PATIENTS WE
SEE HAVE INVOLVEMENT AND
COLLABORATE WITH COLLEAGUES AT
NEA AND SOME HAVE HEARING LOSS
AND WITH SCHOLARS AT NIDCD AND
ONE ASSOCIATED WITH
CARDIOVASCULAR DISEASE.
AND LOOKING AT CARDIAL
INFARCTION AND STROKE IN THE
FIRST YEAR OF LIFE AND WE
COLLABORATE WITH EXPERTS.
WE DON'T JUST COLLECT CLINICAL
DATA BUT RNA AND DNA SAMPLES
FROM BLOOD OR AFFECTED BONE
LESIONS, PERFORMING GENOMIC
STUDIES TRYING TO IDENTIFY GENES
LEADING TO SKELETAL DISEASE AND
COLLECT URINE AND PLASMA AND
SERUM SAMPLES TRYING TO IDENTIFY
NEW BIOMARKERS OF THE DISORDERS
WE STUDY AND STARTING TO DEVELOP
A LARGE IMAGING DATA.
ALL THE DATA SET WE TRIED TO
DEVELOP EN POINTS FOR FUTURE
CLINICAL TRIAL.
THE SECOND AIM OF THE SKELETAL
GENOMICS IS TO UNDERSTAND
MECHANISMS OF THE DISORDERS WE
STUDY AND FOR THAT WE USE CELL
AND ANIMAL MODELS.
FOR CELLS WE WORK WITH PRIMARY
CELL LINES FROM STROMAL CELLS
FROM BONE BIOPSY AND BONE AND
CARTILAGE AND WORK WITH MOUSE
MODELS ON DEVELOPING NEW MODELS
OF THE DISORDERS AND RIGHT NOW
WE'RE TRYING TO EXPAND TO
ZEBRAFISH MODELS AND THE LAST
AIM OF THE UNIT IS TO DEVELOP
NEW THERAPEUTIC TARGETS FOR THE
DISORDERS WE STUDY AND TRY THAT
FIRST IN THE CELL MODELS IN
VITRO AND EVENTUALLY IN OUR
PRECLINICAL MOUSE MODELS.
AND IF THEY SHOW PROMISE IN THE
IN VITRO AND IN VIVO MODELS WE
WRING TO CLINICAL TRIALS.
SO THANK YOU TO NICHD AND DSP
FOR SUPPORTING THIS WORK.
>> THE NEXT SPEAKER ISN
HERMAN BUT COULDN'T MAKE IT
TODAY AND HOPEFULLY NEXT YEAR
WE'LL GET TO KNOW HER AND SO
NEXT IS RAS ICA MATHIAS.
>> I'M A GENETIC EPIDEMIOLOGIST
BY TRAINING.
AND I AM A SENIOR INVESTIGATOR
AT NIAID AND CHIEF OF THE
GENETICS AND PRECISION HEALTH
SECTION.
WE STARTED THIS SIX MONTHS AGO
AND IT DOESN'T FEEL LIKE I'VE
CHANGED SO MUCH BECAUSE I'VE
COME BACK HOME HONESTLY.
THIS IS 20 YEARS SINCE I STARTED
MY POSTDOC AT NIH.
THAT WAS IN NHGRI AND SPENT
ALMOST TWO DECADES AS HOPKINS AT
FACULTY.
PRECISION HEALTH AIMS TO
INTEGRATE AN INDIVIDUAL'S
GENETIC CODE TO THEIR HEALTH
CARE.
I WORK IN COMPLEX DISEASE.
THE COMMON DISEASE, COMMON
VARIANT HYPOTHESIS IS WHERE WE
STARTED.
THE MOST COMMONLY USED TOOL WE
TALK ABOUT IS THE POLY GENIC
RISK SCORE WHERE WE SUM UP AN
INDIVIDUAL'S RISK ACROSS
MILLIONS OF POINTS ACROSS THE
HUMAN GENOME AND POLY GENIC
SCORES FOR ASTHMA NOW HAVE 2
MILLION VARIANTS.
ONE OF THE CHALLENGES WE'RE DEAL
WITH IS NOT ONE OF VARIANT
ACQUISITION AND I'M PART OF
CONSORTIA STUDYING WITH WHOLE
GENOME SEQUENCING AND WE HAVE
GWAS.
ACQUIRING THE VARIATION IS NOT
THE CHALLENGE.
UNDER STANDING THE VARIATION IS
THE CHALLENGE.
FOR ME IN THE SPACE OF ASTHMA
USING THE GENETIC PRE DIRECTORS
TO UNDERSTAND AND PREDICT ENDO
TYPES OF ASTHMA WOULD BE ALMOST
AS USEFUL AS UNDERSTAND ASTHMA
RISK AND CONNECTING TO CLINICAL
SETTINGS AN USE THIS TO
UNDERSTAND THE BIOLOGY OF
DISEASE.
GOING BACK TO THE CHALLENGE I
BRING TOGETHER PROTEOMICS AND
TRANSCRIPTOMICS AN GENETICS IN
ORDER TO DO THIS.
AND WE STUDY A COMPLEX OF
DISEASES AND ASTHMA IS AN
OPERATOR AND AGING BECAUSE
COMPLEX DISEASES ARE CONNECTED
TO HEALTHY AGING AND THE OUTCOME
AND TALKING ABOUT NUTRITION.
WE HAVE ANOTHER WAY TO CONNECT.
ONE PIVOTAL PIECE MY LAB HAS
DONE IS SHOW POLY UNSATURATED
METABOLISM CAN DIFFER BETWEEN
POPULATIONS.
I LOVE HEARING THE CONNECTIVITY.
THE PART THAT'S IMPORTANT IS
HEALTH DISPARITIES.
WE REACHED A POINT IN GENOMICS
RESEARCH WHERE WE'VE RECOGNIZED
THE CLINICAL TRANSLATIONAL
ASPECT WE COMPOUNDED HEALTH
DISPARITIES BECAUSE OF THE UNDER
REPRESENTATION OF MINORITY
POPULATIONS IN OUR WORK.
SO ALMOST IF NOT EVERY PROJECT I
DO PAYS ATTENTION NOT INCLUSION
OF MINORITY POPULATIONS IN OUR
RESEARCH BODY.
THE FOURTH PILLAR IS CLINICAL
TRANSLATION.
OBVIOUSLY I WANT TO UNDERSTAND
DISEASE BUT WANT TO TAKE IN POLY
GENIC RISK SCORES AND RARELY IS
ANYTHING DONE IN ONE
COMPARTMENT.
I'M EXCITED TO BE PART OF THE
DSP.
I'M A TENURED INVESTIGATOR BUT
THERE'S ALWAYS MORE TO LEARN
FROM COLLEAGUES AND PEERS.
THIS IS SUPER EXCITING TO ME
BECAUSE THE WORK WE DO IS
FOCUSSED ON DIVERSITY IN THE
SCIENCE AND TO BEST ADDRESS THE
INEQUALITIES WE NEED IT PAY
ATTENTION TO DIVERSITY AND
INCLUSION IN THE NEXT GENERATION
OF LEADERS.
I'M TRYING TO GET MORE PEOPLE TO
DO WHAT I DO AND BETTER THAN I
DO.
THIS IS AN IMPORTANT PART OF MY
MISSION IN THE LAST SIX MONTHS
LED ME ON RESEARCH OPPORTUNITIES
BUT TAKING ADVANTAGE OF THE
PROGRAM.
I'M EXCITED TO MEET AND WORK
WITH THE OTHER DSP COHORTS.
THANKS.
>> THANK YOU.
OUR NEXT SCHOLAR IS FROM NINDS.
>> THANK YOU.
I'M AMREEN MUGHAL.
I'M THE ACTING CHIEF OF
RESEARCH.
IN THE RESEARCH UNIT OUR GOAL IS
TO STUDY NEUROVASCULAR COUPLING
WIN THE NEURONS AND BLOOD
VESSELS AND INTERESTED IN
STUDYING THESE MECHANISMS IN THE
BRAIN HOMEOSTASIS AND INTERESTED
TO EXPAND THE KNOWLEDGE TO BRAIN
AND OUR GOAL IS TO EXTEND THIS
TO THE DEMENTIA LOOKING AT
AMYLOID ANGIOPATHY.
THE MORE WE'RE LEARNING IN THE
MODELS IT'S NOT THE SUPPLY OF
GLUCOSE BUT MORE METABOLIC
FACTOR SUCH AS AMYLOID BETA AND
TAU PROTEIN.
WE'RE USING A VARIETY OF
APPROACHES FROM SINGLE CELL TO
WHOLE ANIMAL PROVIDING A
PERSPECTIVE OF COUPLING
MECHANISMS IN THE BRAIN.
WE USE IMAGING AND CREATE A
SMALL WINDOW OVER THE CORTEX AND
CAN CREATE IT OVER ANY BRAIN
REGION.
WE STUDY THE DYNAMIC CHANGES.
AND ONE EXAMPLE IS SHOWN HERE IS
WHERE THE FLUORESCENCE INDICATED
THE BRAIN CORTICAL VASCULATURE
AND THE SIGNALS GENERATED IN THE
ENDOTHELIAL CELLS.
WE COMBINED IT WITH EX VIVO
APPROACHES AND STUDY ION
EXPRESSION WITHOUT CONTRIBUTE
TOE THIS COUPLING MECHANISM.
AND WE ALSO COMBINE THIS WITH EX
VIVO EXPERIMENTS WHERE WE
ISOLATE THE VESSELS FROM THE
BRAIN AND THE VESSELS ARE CLOSE
TO 20 MICRONS THE DIAMETER OF
THE HUMAN HAIR.
YOU CAN SEE HOW TINY THE VESSELS
ARE AND PERFORM ACTIVITY TO
UNDERSTAND WHAT MAY BE
CONTRIBUTING TO THE DIFFERENT
COUPLING MECHANISMS.
SO OUR GOAL IS TO PROVIDE
DETAILED PERSPECTIVE ON COUPLING
AND HOMEOSTASIS.
LIKE MANY I'M A NEW INVESTIGATOR
AS WELL.
I STARTED SIX MONTHS AGO.
SO WE ARE A GROWING TEAM AND ON
THIS CORNER YOU CAN SEE OUR
CURRENT GROUP SOME PEOPLE ARE
MISSING FROM THE PICTURE.
AND WITH THAT I WOULD LIKE TO
THANK THE NIH AND DSP PROGRAM
SUPPORTING OUR MISSION.
THANK YOU.
>> THANK YOU.
THE NEXT DSP SCHOLAR IS JOE
NGUYEN FROM CANCER RESEARCH.
WELCOME, JOE.
>> OKAY.
THANKS FOR HAVING ME HERE.
I'M EXCITED TO BE PART OF THE
DSP.
MY NAME IS JOE NGUYEN A DENTIST
SCIENTIST AND I HAVE BEEN
WORKING WITH NCI SINCE A JOINED
AS A POSTDOC.
IT'S FINALLY TO BE IN A POSITION
TO WORK WITH DIFFERENT TRAINEES
AT DIFFERENT LEVELS.
THE PHOTO IS OUR SUMMER CREW.
THEY'RE ONLY THERE FOR THE
SUMMER BUT IT WAS A GREAT AND
FUN EXPERIENCE FOR ALL OF US.
I'M INTERESTED IN UNDERSTANDING
THE MECHANISMS OF CANCER
RESEARCH.
WE'RE UTILIZING TECHNOLOGIES
WITH TRANSCRIPTOME TECHNOLOGIES
AND WE LOOK AND THE
COLLABORATORS WITH THE
UNIVERSITY OF BALTIMORE AND
COLLEGE PARK.
WHAT'S INTERESTING FOR OUR
FUTURE WORK IS TO UNDERSTAND WHY
SOME CELLS WITHIN THE DISPLASTIC
EPITHELIUM DIFFER FROM THE
CANCER SAMPLES.
WE THINK BY HONING IN ON THE
ASPECT OF THE BIOLOGY WE CAN
MAKE SPECIFIC GENE TO
MOUSE MODELS OF HEAD AND NECK
CANCER AND STUDY IT IN AN IMMUNE
COMPETENT FASHION.
OUR GROUP HAS BEEN ABLE TO
UTILIZE THE BIOLOGY SAMPLES FROM
DIVERSE GROUPS BUT ALSO TAKE
MOUSE MODELSED IN HOUSE
THAT EXPRESS KAS 9 AND WE CAN
GROW TUMORS IN VIVO AND STUDY
THE ROLE OF THESE GENES
SPECIFICALLY ENHANCED IN WHAT WE
CALL THE MALIGNANT TUMOR OR
TRANSFORMATION ZONE.
THAT'S WHAT I DO NOW.
HAPPY TO MEET YOU ALL.
THANK YOU.
>> OUR NEXT DSP SCHOLAR IS CAMI
LA ODIO FROM NIAID.>>CAMILA ODI
HONORED TO BE HERE AND AN
ASSISTANT CLINICAL INVESTIGATOR
IN NIAID AND I'LL TELL YOU ABOUT
MY INTEREST IN SEVERE DENGUE.
THERE'S FOUR TYPES TRANSMITTED
BETWEEN HUMANS BY MOSQUITOS.
THIS HALF OF THE WORLD'S
POPULATION IS AT RISK FOR DENGUE
AND THE INCIDENCE IS RISING AND
ONE OF THE FEW INFECTIOUS
DISEASES HAVING A HUGE OUTBREAK
THIS YEAR AND INTERESTINGLY
ABOUT DENGUE THE SECOND
INFECTION IS ACTUALLY THE HIGHER
RISK FOR SEVERE DISEASE.
SO WITH THE FIRST INFECTION HERE
THE CLEAR BAR TYPICALLY YOU HAVE
JUST THE DENGUE FEVER BUT WITH
THE SECOND INFECTION WITH THE
DIFFERENT SEROTYPE YOU GET THE
BLACK BAR OR HIGHER AMOUNT OF
SEVERE DISEASE.
TO TRY TO UNDERSTAND THIS BETTER
MY MENTOR AND I LAUNCHED A
VACCINE TRIAL HERE.
WE'VE ENROLLED 40 OF OUR 45
PARTICIPANTS HOPING TO FINISH
ENROLLMENT THIS MONTH AND HAVE
TAKEN 15 INDIVIDUALS WHO HAVE
NEVER SEEN DENGUE BEFORE.
15 WITH ONE PRIOR EXPOSURE TO
DENGUE TYPE 1, 2 OR 4 AND 15
WITH MULTIPLE EXPOSURES AND A
LIVE ATTENUATED DENGUE VACCINE
AND LOOKING CLOSELY AT THEIR
IMMUNE RESPONSE AND HOW THEIR
VIREMIA TRACKS.
THROUGH THIS HETEROGENEOUS GROUP
THIS IS THE GROUP MOST AT RISK
FOR SEVERE DISEASE.
SO UNDERSTAND THE IMMUNE
RESPONSES BETTER WE'RE
COLLECTING BLOOD AT MULTIPLE
TIME POINTS AND PARTICIPANTS ARE
VERY GRACIOUS AND COME VERY
OFTEN GET A LOT OF BLOOD TAKEN.
TO UNDERSTAND THE EARLY RESPONSE
WHICH IS IMPOSSIBLE TO CAPTURE
IN NATURAL INFECTION STUDIES
PAUSE THE VIRUS DOES NOT INDUCE
SYMPTOMS UNTIL ABOUT SEVEN DAYS
AFTER EXPOSURE.
BY A CONTROLLED EXPOSURE WE CAN
LOOK AT THE IMMUNE RESPONSE
EARLY ON.
WE'RE ALSO PIONEERING LYMPH NODE
COLLECTION AND ASPIRATIONS WITH
HEALTHY KOL -- VOLUNTEERS AND
OVER TIME WE CAN SEE WHAT CELLS
ARE GOING IN AND COMING OUT AND
HOW DOES PRIOR EXPOSURE
INFLUENCE THE IMMUNE SYSTEM.
FROM ANIA CI I'M SETTING UP A
HOSPITALIZED COHORT IN CAMBODIA
TO LOOK AT MILD VERSUS SEVERE
DENGUE AND VALIDATE SOME
FINDINGS FROM THE VACCINE STUDY
IN A NATIONAL INFECTION SETTING.
FINALLY I'M VERY INTERESTED IN
POTENTIAL TREATMENTS FOR SEVERE
DENGUE.
SO DENGUE CAN CAUSE SEVERE
DISEASE WITH SHOCK,
HYPERTENSION, THERE'S NO
TREATMENT.
IT'S ALL CLINICAL MANAGEMENT.
AND SO COVID HAS REVOLUTIONIZED
HOW WE THINK OF SEVERE VIRAL
INFECTION AND USE HOST DIRECTED
IMMUNE TARGETS TO TREAT SEVERE
DISEASE AND IMMUNE OPERATIONS
THAT MAY BE ASSOCIATED.
I'M LOOKING AT THE DRUG THAT'S
AN INHIBITOR.
IT SHOWED IMPROVED OUTCOMES AND
MORTALITY BENEFIT IN COVID-19
PATIENT AND THE FAMILY OF DRUGS
IN DENGUE HAS SHOWN ANTI-DENGUE
ACTIVITY AND INFECTION AND A
RELATED DRUG AS YOU INCREASE THE
AMOUNT THE DENGUE GOES DOWN.
IN THE MOUSE MODEL IN BLUE ALL
THE MICE THAT HAVE SEVERE DENGUE
DIED AND INCREASED DOSES IN THE
SAME FAMILY LED TO IMPROPOSALS
IN MORTALITY.
SO THE STUDY I'M SETTING UP WITH
THE DIVISION OF CLINICAL
RESEARCH IS A PHASE II TRIAL
FROM MODERATE TO SEVERE DENGUE
AND TAKE INDIVIDUALS AND
RANDOMIZED THEM IN A DOUBLE
BLINDED FASHION TO PLACEBO AND
MEDICATION AND CLINICAL EFFICACY
AND THE MODIFIED SCORE FOCUSSED
ON DENGUE.
.
THANK YOU SO M
>> THANK YOU.
OUR LAST SCHOLAR IS INDIRA
TURNEY FROM THE NIA.
>> THANK YOU FOR STICKING IT
OUT.
AND I'M A TENURE TRACK EVALUATOR
I BELIEVE I'M THE YOUNGEST DSP
SCHOLAR HERE TODAY AND MY WORK
IS ON UNDERSTANDING BRAIN HEALTH
DISPARITIES ACROSS MID LIFE AND
OLDER ADULTS IN THE COMMUNITY
AND USE A MIX OF NEURAL IMAGE
AND MRIs AND EPIGENETIC FACTORS
AFFECT THE BRAIN ACROSS A
DIVERSE GROUP OF PEOPLE.
AS WE TALK ABOUT HEALTH
DISPARITIES WE'RE TALKING ABOUT
MODIFIABLE RISK FOR INDIVIDUALS
WHO ARE AT SOCIAL DISADVANTAGED
POPULATIONS.
THEY'RE AVOIDABLE AND MODIFIABLE
TO MAKE CHANGES TO THIS.
I'M TAKING A BROAD
INTERDISCIPLINARY APPROACH AND
LOOKING AT THE PSYCHOSOCIAL
FART
FACTORS AND GET A SENSE AS TO
WHAT'S DRIVING THE DISPARITIES
IN THE INDIVIDUALS.
AND TRYING TO DEVELOP THESE
BIOMARKERS FROM DIFFERENT S
WHETHER THEY'RE CARDIOVASCULAR,
INFLAMMATORY PATHWAYS AND NEURAL
REGENERATION AS IT RELATE TO
DEMENTIA ACROSS THESE PEOPLE AND
THE GOAL IS TO UNDERSTAND IN A
CROSS CONTEXT AND TIME AND MAYBE
IN CHILDHOOD SOME FACTORS MAY BE
MORE PREVALENT VERSUS MID LIFE
AND LATER IN LIFE AND THE
FRAMEWORK GUIDES MY WORK.
USING FIVE SETS BUT
REITERATIVELY AND EXAMINING
PERFECT THE DISPARITIES YOUR AND
SOME WORK HAS SHOWN THAT AND
WE'VE SEEN MID LIFE BLACK ADULTS
SHOW ACCELERATED BRAIN AGING
COMPARED TO THEIR LATER LIFE
COUNTER PARTS AND LOOKING AT
IDENTIFYING THE FACTORS THAT
EXACERBATE SOME OF THESE
DISPARITIES.
SHOWING SES MAY PLAY A ROLE
ACROSS DIFFERENT GROUPS AND
THIRD WOULD BE TO LOOK AT THE
DIFFERENT PATHWAYS AND TRYING TO
UNDERSTAND WITH A MIX OF DNA
METHYLATION AND WITH PROTEOMICS
TO SEE WHERE THEY'RE FALLING
SHORT WITHIN THE BODY TO GET AT
WHAT IS CAUSING THESE
DISPARITIES IN THE BRAIN AND
THERE'S DIFFERENT TIME POINTS
AND BIOMARKERS THAT GIVE US
DIFFERENT INFORMATION.
I'M TAKING A HOLISTIC APPROACH
AND ALSO ACKNOWLEDGING THE ROLE
OF RACISM IN OUR WORK.
WE'RE TRYING TO INFORMATION
PEOPLE IN THE COMMUNITY AND
THEY'RE LIVED EXPERIENCES AND A
LOT OF THAT IS TIED TO RACISM
TRYING TO UNDERSTAND HOW THAT
PLAYED A ROLE TO EXACERBATE SOME
OF THE INEQUALITIES BY STUDYING
THE PEOPLE MOST AFFECTED
FOCUSSING ON BLACK AND HISPANIC
INDIVIDUALS WHO ARE TWO TO THREE
TIMES GREATER RISK FOR DEMENTIA.
AND SO OF COURSE LASTLY USING
THE BIOMARKERS AND DEVELOPING
INTERVENTIONS THAT CAN REDUCE
SOME OF THESE DISPARITY AND
AGAIN REITERATIVELY WE NEED TO
TEST TO SEE IF THEY'RE REDUCING
THE DISPARITIES WE THINK THEY'RE
REDUCING.
SO THE END GOAL IS MY HOPE BY
PINPOINTING SOME OF THESE
BIOMARKERS AND THEIR
RELATIONSHIPS WITH THE SOCIAL
AND STRUCTURAL DEVELOPMENTS IS
THE RIGHT INTERVENTION FOR THE
RIGHT PEOPLE AT THE RIGHT TIME.
ONE THE BIG TASKS I HOPE TO DO
HERE IS DEVELOP A MIDDLE ABLED
COHORT OF BLACK INDIVIDUALS 20
TO 45 IN BALTIMORE AND I SEE
EXPERTISE IN THE ROOM SO I'M
CURRENTLY JUST ONE I SEE
EVERYBODY ELSE HAS A TEAM BUT IF
IF YOU KNOW ANYONE INTERESTED IN
THIS EXCITING WORK SEND THEM MY
WAY.
THANK YOU.
>> THANK YOU SO MUCH.
WE'LL END THE SESSION WITH THE
CLOSING REMARKS BY DR. MARIE
BERNARD THE CHIEF OFFICER F
SCIENTIFIC DIVERSITY WORKFORCE
AT THE NIH.
YOU'LL SEE HER FOR MANY YEARS TO
COME.
>> THANK YOU.
SO IT'S ALWAYS A PLEASURE TO
HEAR DISTINGUISHED KOL SCHOLARS
AND THE WORK YOU'RE DOING.
IT'S A MARVELOUS MIXTURE.
YOU HAVE DIFFERENT BACKGROUND
AND SCIENCE.
THE UNIFYING THING BEING YOU
HAVE BEEN SELECTED BECAUSE OF
YOUR INTEREST IN TRACK RECORD
AND PROMOTING DIVERSITY, EQUITY
AND INCLUSION.
I THINK THAT'S MARVELOUS.
SO IF YOU DO THAT AS PART OF
YOUR RESEARCH, ALL OOU DO IT
ADDS PART OF YOUR MENTORING.
SOME DO IT IN FORMAL THINGS LIKT
THE UNITE INITIATIVE AT NIH AND
THE FAN GROUP OR THE
DISABILITIES WORKING GROUP BUT
HOWEVER, YOU CONTRIBUTE IT IS SO
IMPORTANT AND SO APPRECIATE
AND I ALWAYS LIKE TO REMIND YOU
THAT THE SUCCESS OF THE
DISTINGUISHED SCHOLARS PROGRAM
HAS LED NIH TO INVEST IN TRYING
TO REPLICATE THIS WITHI THE
EXTERNAL SCIENTIFIC COMMUNITY.
THERE'S SOMETHING CALLED THE
FIRST INITIATIVE RECRUITMENT FOR
SUSTAINABILITY TRANSFORMATION
THAT HAS ABOUT $250 MILLION
ANTICIPATED TO BE SPENT OVER THE
NEXT NINE YEARS.
THERE'S 15 COHORTS OF FACULTY
ACROSS THE COUNTRY WHO ARE EARLY
IN THEIR SEEKING TENURE.
I KNOW THERE'S A FEW SENIOR
DISTINGUISHED SCHOLARS AMONG THE
GROUP BUT THE INTENT IS TO
SUPPORT THE INDIVIDUALS WHO
YOU HAVE AN INTEREST AND TRACK
RECORD IN DIVERSITY, EQUITY AND
INCLUSION.
IT'S NOT NECESSARILY THEIR AREA
OF RESEARCH BUT HAVE THAT TRACK
RECORD AND SUPPORT THEM TO
BECOMING TENURED SCIENTISTS ONE
THE THEORY, THEY, LIKE YOU, WILL
IMPACT THE CLIMATES THEY'RE IN
AND THAT THAT WILL LEAD US, NIH,
TO HAVE BROADER DIVERSITY OF
PERSPECTIVES IN THOSE WHO GET
GRANT FUNDING FROM US.
KUDOS TO YOU ALL.
KEEP UP THE GREAT WORK AND I'M
NOT GOING TO HOLD YOU ANY LONGER
BECAUSE I KNOW YOU'VE BEEN HERE
ALL DAY.
SO, THANK YOU.
>> THAT CONCLUDES THE SYMPOSIUM.
WE HAVE A REFLECTION UP THERE
FOR EVERYONE INVITED.
I'D LIKE TO ASK THE DSP SCHOLARS
TO TAKE A GROUP PHOTO AND WE'LL
MAKE OUR WAY THERE THEO
RECEPTION.
THANK YOU, EVERYONE.