>> TO THE REGULAR ADMINISTRATIVE
ANNOUNCEMENTS.
WE'RE CURRENTLY AWAITING
DEPARTMENTAL APPROVAL OF OUR
2023 COUNCIL -- FOR ALL OF YOU
ALL TO KNOW AND WE'VE BEGUN THE
PROCESS TO IDENTIFY NOMINEES FOR
THE 2024 VACANCY.
WE FINALLY GOT A BUDGET.
AND OBVIOUSLY YOU'VE SEEN THAT
CURVE GOING UP FOR THE PRECEDING
FIVE YEARS, BUT WE'VE ENTERED
INTO A PHASE WHERE THINGS ARE A
BIT MORE CHALLENGING, AND IN
ESSENCE, WE HAVE A RELATIVELY
FLAT BUDGET FOR THE NIH, AND FOR
NHLBI, AND AS YOU ARE ALL AWARE,
GIVEN THE SORT OF GENERAL
INFLATIONARY PRESSURES ON
EVERYTHING, INCLUDING BIOMEDICAL
SCIENCES THAT YOU'RE ALL AWARE
OF, IN THE CONTEXT OF THAT
INFLATION, A FLAT BUDGET MEANS
THAT INEVITABLY THERE ARE GOING
TO BE CONSTRAINTS AND
TIGHTENING.
SO THIS WILL BE A CHALLENGE FOR
FY 24, AND AT THE BEGINNING OF
THE PROCESS FOR FY 25, THINGS
ARE LOOKING LIKE THE SPACE WILL
BE VERY SIMILAR.
SO WE HAVE A CHALLENGING COUPLE
OF YEARS TO WORK THROUGH.
WE HAD THE PRIVILEGE OF JOINING
THE NIH DIRECTOR AT THE SENATE
APPROPRIATIONS HEARING, WHERE
DR. BERTAGNOLLI OUTLINED A
NUMBER OF PRIORITIES AS WELL AS
WE HEARD FROM OUR APPROPRIATORS
AND SOME OF THE TOPICS MENTIONED
IN THE CONTEXT OF THAT HEARING
ARE ADDRESSED HERE.
RURAL HEALTH, WOMEN'S HEALTH,
MATERNAL MORBIDITY AND
MORTALITY, HEART DISEASE WAS
MENTIONED.
AS WAS A SENSE OF WHAT THESE
AUSTERE BUDGETS MAY HAVE FOR THE
NEXT GENERATION.
BY SOME OF OUR MEMBERS OF
CONGRESS.
SIMILARLY, THERE WAS NOTEWORTHY
QUESTIONS AND DIALOGUE ABOUT
CERTAIN POPULATIONS, TYPICALLY
ASIAN AMERICANS, NATIVE
HAWAIIANS, PACIFIC ISLANDERS, A
LOT OF INTEREST AND EXCITEMENT
AROUND ARTIFICIAL INTELLIGENCE,
MACHINE LEARNING AND ITS
IMPLICATIONS FOR BIOMEDICAL
SCIENCE, AS WELL AS LONG COVID.
SO ALTHOUGH THERE ARE A NUMBER
OF GREAT PRIORITIES THAT ARE
EXCITING, WE'RE GOING TO HAVE TO
WORK THROUGH THAT AT THIS POINT
WITH A RELATIVELY FLAT BUDGET.
THAT OBVIOUSLY HAS IMPLICATIONS
ON HOW WE'VE BEEN ABLE TO
NAVIGATE THIS.
WE'VE TRIED TO MAINTAIN THOSE
OPERATING PRINCIPLES,
RECOGNIZING THAT PROBABLY THE
GROUP THAT PAYS THE GREATEST
COST IN THESE AUSTERE TIMES
TENDS TO BE OUR NEXT GENERATION.
IT'S ALWAYS HARD TO GET A
FOOTHOLD WHEN THE PAYLINES ARE
FALLING.
THE SENIOR INVESTIGATORS ARE
ABLE TO ADAPT, HAVE MORE GRANTS,
ET CETERA, SO WE'VE TRIED TO
STRIVE TO MAINTAIN THOSE
PAYLINES.
THAT HAS MEANT THAT WE DID
SOMETHING WE TYPICALLY DON'T DO
AT THE NHLBI, DONE AT OTHER
INSTITUTES, WHERE WE GIVE A HAIR
CUT, A 2% REDUCTION IN THE
NONCOMPETING AWARDS, SINCE WHAT
WE HAD TO DO THIS YEAR, IN ORDER
TO HAVE THE CORPUS TO TRY TO
MAINTAIN AT LEAST OUR 14TH
PERCENTILE.
IF WE HAD NOT DONE THAT,
OBVIOUSLY THIS WOULD HAVE BEEN
COMPROMISED IN TERMS OF NUMBER
OF R01s AND SUCCESS RATES
WE'RE ABLE TO MAINTAIN.
SO YOU CAN SEE THERE, DESPITE
THE FACT THAT WE HAVE ACTUALLY
MORE APPLICATIONS COMING IN,
WITH THAT HAIR CUT ACROSS THE
BOARD, THAT HAS ENABLED US TO
TRY TO MAINTAIN AT LEAST HEAD
ABOVE WATER.
AND WE'RE HOPEFUL THAT WE CAN
STILL MAINTAIN OUR TARGET FOR
EARLY STAGE INVESTIGATORS AS
PART OF THAT.
WE'VE ALSO TRIED TO MAINTAIN OUR
TARGETS FOR CAREER DEVELOPMENT
AWARDS AND OTHER ELEMENTS
RELATED TO TRAINEES.
IN ADDITION, AS YOU'RE PROBABLY
AWARE, WE DID I THINK ABOUT AN
8% INCREASE, FAIRLY SUBSTANTIAL
JUMP FOR ONE YEAR OF OUR
STIPENDS AND SO FORTH FOR
POSTDOCS.
SO DESPITE THE AUSTERE BUDGET,
WE'VE TRIED TO FOCUS ON THE NEXT
GENERATION, ENSURING THAT THEY
KIND OF GET THROUGH THIS AND
WEATHER THIS PERIOD OF TIME.
BUT IT DOES CAUSE CONSTRAINTS
THAT WILL HAVE IMPLICATIONS.
TO SOME MORE POSITIVE NEWS, JUST
WANT TO GIVE YOU A SENSE OF SOME
OF THE TRANSITIONS IN LEADERSHIP
THAT WE HAVE, THIS IS ALSO VERY
EXCITING BECAUSE THIS IS AN
OPPORTUNITY FOR THE INSTITUTION,
THE ORGANIZATION TO CONTINUE TO
RENEW ITSELF AND ACTUALLY HAVE A
NEW GENERATION OF LEADERS COMING
THROUGH, WHICH IS EXCITING, AND
HOPEFULLY YOU CAN SEE THE
INCLUSIVE EXCELLENCE OF THESE
FOLKS AS THEY TRANSITION INTO
LEADERSHIP ROLES.
TRACI IN DBDR, MICHELLE IN DCDS
AND COURTNEY ALSO IN DBDR.
SO WE'RE EXCITED TO HAVE THEM AS
NEW LEADERS.
SIMILARLY, WE'RE ALWAYS EXCITED,
JIM WILL TELL YOU THAT THE LUNG
DIVISION IS THE GREATEST
DIVISION IN THE NHLBI.
HE SAYS THAT UNABASHEDLY, I SEE
HIM SMILING BACK THERE, AND HE'S
LED AN ADAPTIVE CHANGE IN
PURSUIT INVOLVING SCIENTIFIC
OPPORTUNITIES, MOVE FROM THE
TWO-BRANCH STRUCTURE TO ONE THAT
DLD BELIEVES IS CAPTURING THE
SPECTRUM OF SCIENCE.
DLD HAS ALSO EXPANDED UNDER HIS
LEADERSHIP, AND I THINK THIS
PUTS DLD IN A VERY GOOD POSITION
TO ALIGN THE EXPERTISE AND
CAPABILITIES AND REALLY THE
SCIENTIFIC OPPORTUNITIES THAT
ARE EMERGING IN LUNG DISEASE
THAT WE'LL TOUCH ON AS WELL.
SIMILARLY, IT GIVES AN
OPPORTUNITY FOR ALL THOSE YOUNG
LEADERS TO EMERGE AND HELP US
DRIVE THE ORGANIZATION.
TOWARD THAT END, THIS IS
PROBABLY A LITTLE OF A PREVIEW,
BUT COMING ATTRACTIONS, NEW
DIVISION LEADERSHIP ALSO IN DLD
IS EMERGING, AND THERE'S SOME
FINALISTS HERE.
SO WE'RE VERY EXCITED ABOUT THE
DIRECTION OF OUR LUNG DIVISION.
I'D BE REMISS IF I ALSO DIDN'T
ACKNOWLEDGE THE SUPERLATIVE
LEADERSHIP THE DIVISION OF LUNG
DISEASE HAS HAD, IN PARTICULAR,
A MILESTONE.
IT WAS 1984 WHEN DR. KILEY
JOINED THE ORGANIZATION AS A
YOUNG PUP.
I WON'T SAY HOW YOUNG HE WAS.
AND HAS REALLY BLAZED A PATHWAY
AS A PROGRAM OFFICER, WHO WAS
SEEN AS AN EMERGING STAR,
INCREASING OPPORTUNITIES OF
LEADERSHIP TO THE POINT WHERE HE
BECAME DIRECTOR OF DIVISION OF
LUNG DISEASES.
AND HE'S LED A VARIETY OF
PROGRAMS, I CAN'T EVEN LIST ALL
THE THINGS THAT DR. KILEY HAS
DONE OVER HIS 40 YEARS OF
SERVICE.
DOING A LOT OF THE PIONEERING
WORK WITH DEVELOPING CLINICAL
TRIAL NETWORKS, HERE'S JUST
LISTING CADET, THE THINGS
THEY'VE DONE, OXYGEN, HE
ACTUALLY WAS THE FIRST DIRECTOR
OF THE NATIONAL CENTER ON SLEEP
DISORDER RESEARCH, AND SO I JUST
WANTED TO TAKE A MOMENT TO JUST
GIVE A VERY SPECIAL SHOUT OUT TO
A DEDICATED SERVANT.
JIM AND I SOMETIMES GET INTO
DEBATES IN OUR EXECUTIVE
LEADERSHIP TEAM MEETINGS, AND I
LOVE HIS PERSPECTIVE.
HE HAS A LOT OF HISTORY AND
EXPERIENCE, SO I HAVE GREAT
RESPECT FOR THAT PERSPECTIVE, AS
HOPEFULLY MY EXECUTIVE TEAM
WOULD ACKNOWLEDGE.
I LIKE THE BACK AND FORTH, THE
DIALOGUE.
I THINK THAT MAKES US BETTER AS
AN ORGANIZATION.
AND ALTHOUGH WE MAY NOT ALWAYS
AGREE ON TACTICAL APPROACHES,
ONE THING I DO KNOW ABOUT JIM
KILEY IS THAT HE WOULD DO
ANYTHING IF HE THINKS IT'S THE
BEST FOR THE INSTITUTE, AND IN
FULFILLING OUR MISSION.
SO I HAVE NO DOUBT ABOUT HIS
DEDICATION TO THE NHLBI AND ALL
THAT IT DOES.
SO JIM, WE JUST WANT TO
ACKNOWLEDGE YOU IN YOUR 40 YEARS
OF SERVICE.
[APPLAUSE]
I CAN TELL YOU I PROBABLY WON'T
MAKE TO THE 40-YEAR MARK, THAT'S
FOR SURE.
SO WE THANK JIM FOR THAT.
I ALSO WANTED TO GIVE AN
ACKNOWLEDGMENT TO ANOTHER PART
OF OUR EXECUTIVE LEADERSHIP, DRW
SCIENTIFIC DIRECTOR OF OUR
INTRAMURAL PROGRAM,
PARTICIPATING IN THE OVERSIGHT
OF OUR BOARD OF SCIENTIFIC
COUNSELOR MEETING AND
EVALUATIONS, THAT WAS PART OF
THE CLOSED SESSION.
AND SO WE'RE DELIGHTED TO HAVE
DR. CHILDS AS THE LEADER OF THE
INTRAMURAL PROGRAM, EXCITED
ABOUT HIS GREAT VISION, HAVING
BEEN THE DIRECTOR -- THE
CLINICAL DIRECTOR OF THE DIR,
NOW TAKING THE HELM FROM BOB
BALABAN AFTER BOB'S 25 YEARS AS
SD, SO WE'RE VERY EXCITED ABOUT
THE DIRECTION OF THE INTRAMURAL
PROGRAM IN THE NHLBI.
A KEY PART OF DR. CHILDS, QUITE
FRANKLY, RESPONSIBILITY AND
STEWARDSHIP IS, AGAIN, FOR THE
NEXT GENERATION, AND WE'RE VERY
EXCITED ABOUT THIS INCREDIBLE
GROUP OF TENURED TRACKERS THAT
HE WILL BE MENTORING AND
SHEPHERDING IN THEIR CAREER
TRAJECTORY.
AND WE'RE DELIGHTED THAT TODAY
AS PART OF OUR OVERALL VIEW OF
THE INTRAMURAL PROGRAM, WE'LL
HAVE DR. COURTNEY FITZHUGH WHO
WILL BE PRESENTING SOME OF HER
WORK TO GIVE YOU A GLIMPSE OF
SOME OF THE SCIENCE THAT'S BEING
DONE IN THE NHLBI INTRAMURAL
PROGRAM.
SO LET ME PIVOT FROM THE
STEWARDSHIP TO WHERE WE'RE GOING
IN TERMS OF OUR SCIENTIFIC
OPPORTUNITIES, OF WHICH THE
FIRST PART RELATES TO THE
STRATEGIC VISION REFRESH THAT
BOTH COUNCIL AND BOARD OF
EXTERNAL EXPERTS HAS BEEN
INSTRUMENTAL IN HELPING US TO
DEVELOP AND SHAPE SINCE THE LAST
STRATEGIC VISION, AND THIS IS AN
OPPORTUNITY FOR US TO HEAR FROM
THE COMMUNITY, GET YOUR EXPERT
INPUT AS WE SHAPE THE DIRECTION
FOR THE NEXT FIVE TO 10 YEARS.
AND TOWARD THAT END, WE'RE
MAKING PROGRESS.
THANKS TO DR. LAURA JOHNSON AND
OUR OSPEAK GROUP ALONG WITH
PROGRAM STAFF ARE WORKING
DILIGENTLY TO DO THE OUTREACH TO
THE COMMUNITY TO START TO GET A
SENSE OF IDEAS THAT ARE BUBBLING
UP, STRATEGIC DIRECTIONS WE
MIGHT TAKE OVER THE NEXT FIVE TO
10 YEARS OF THIS REFRESH, SO
LOOKING AT OUR COMPELLING
QUESTIONS AND CRITICAL
CHALLENGES TO SEE IF THOSE HAVE
CHANGED OR EVOLVED DURING THIS
PERIOD, AND NOTABLY THIS IS SOME
OF THE PROGRESS THAT'S BEEN MADE
IN THAT PROCESS.
STAFF HAS DONE AN INCREDIBLE
AMOUNT OF WORK TO KIND OF REVIEW
ALL THOSE, AND IT'S BECOMING
NOTABLE THAT THERE'S CERTAIN
THEMES THAT APPEAR TO BE
EMERGING.
SOME OF IT RELATES TO
OPPORTUNITIES IN WOMEN'S HEALTH
IN PARTICULAR SEEMS TO COME UP.
OBVIOUSLY DATA SCIENCE AND AI/ML
BEING A KEY ONE, BUT ALSO OTHER
AREAS OF IMPLEMENTATION SCIENCE,
SOCIAL DETERMINANT OF HEALTH,
THE MOTION OF MULTILEVEL
INTERVENTIONS, ACTUALLY
INTERSECTIONS LIKE WITH HIV.
SO WE'RE VERY INTRIGUED BY THAT
REQUEST FOR INFORMATION AND A
LOT OF THINGS THAT CAME FROM THE
INTRAMURAL COMMUNITY ABOUT OUR
FUTURE DIRECTIONS.
NOW, JUST AS PART OF THAT
STRATEGIC VISION REFRESH, ONE OF
THE THINGS THAT WE'LL JUST TOUCH
UPON ARE A COUPLE THEMATIC
OPPORTUNITIES THAT ALIGN WITH A
LOT OF THE INPUT WE RECEIVE THAT
WE HOPE CAN CONTINUE TO LEVERAGE
THIS VIRTUAL CYCLE OF DISCOVERY
SCIENCE THAT WE HOPE TO
TRANSLATE INTO THE HEALTH OF ALL
COMMUNITIES.
AND WANTED TO GIVE A PARTICULAR
SHOUT OUT TO BLOOD DIVISION IN
THIS REGARD, AS WE'RE EXCITED
ABOUT THE TWO FDA-APPROVED GENE
THERAPY FOR SICKLE CELL DISEASE.
IT CAME THIS YEAR AS A MAJOR
MILESTONE THAT I THINK REFLECTS
A LOT OF THE INSTITUTE'S
PORTFOLIO, PARTICULARLY IN THE
BLOOD DIVISION THAT SPANS A
BASIC FIRST IN HUMAN CLINICAL
TRANSLATION, AS WELL AS
IMPLEMENTATION SCIENCE NA WE
BELIEVE HAS MADE A DRAMATIC
IMPACT, TRANSFORMATIVE IMPACT ON
SOME OF THE PATIENTS RECEIVING
THESE THERAPIES.
A PICTURE OF JANELLE DOWN THERE
IN THE CORNER IN WHICH IN MANY
WAYS EMBODIES THE PROUD LEGACY
OF THE NHLBI IN MAKING A
DIFFERENCE FOR RARE DISEASES.
IT'S ALSO ONE WHERE IT'S BEEN A
KEY PART OF COLLABORATIVE
PARTNERSHIPS WITH PATIENTS AT
THE CENTER.
AS WELL AS SISTER AGENCIES LIKE
FDA AND CMS TO MAKE SURE THAT
THESE CURATIVE THERAPIES AND
DRAMATIC TRANSFORMATIONAL
TECHNOLOGIES ACTUALLY MEET
PATIENTS WHERE THEY ARE AND ARE
ACCESSIBLE TO ALL OF THEM.
INDEED THAT ABILITY TO TRANSLATE
DISCOVERY SCIENCE IN A WAY THAT
DISSEMINATES AND IS TAKEN UP AT
SCALE OFTEN INVOLVES
COMMERCIALIZATION IN OUR FREE
MARKET SOCIETY.
AND SO WE WANT TO BE SURE THAT
WE CONTINUE THAT ENGINE OF
ACCELERATED TRANSLATION, AND AS
PART OF COUNCIL'S DELIBERATIONS,
WE'RE EXCITED ABOUT THE RENEWAL
OF THE CATALYZE SUITE OF
INITIATIVES THAT'S ALL ABOUT
THAT TRANSLATIONAL SPACE AND
ENABLING THE SUCCESS AND IDEAS
OF INVESTIGATORS LIKE
YOURSELVES.
ALSO WANTED TO, IN THAT SAME
WAY, GIVE A SHOUT OUT TO THE
CURE SICKLE CELL INITIATIVE,
WHICH IS AGAIN SORT OF
EMBLEMATIC OF WHAT WE THINK IS
GOING TO CONTINUE OVER THE NEXT
FIVE TO 10 YEARS WITH THESE NEW
TOOLS AND TECHNOLOGIES, SIMILAR
ACTUALLY TO WHAT WAS USED IN THE
VACCINES AND OTHER FORMS OF IN
VIVO GENE TRANSFER ARE, WE
THINK, GOING TO GO ON AN
EXPONENTIAL OR INFLECTION AT
LEAST IN THE NEXT FIVE TO 10
YEARS.
IN MANY WAYS, THE SICKLE CELL
INITIATIVE IS PRESUMABLY A
FORELONGER OF THAT AND IS IN
MANY WAYS INVESTMENTS IN BASIC
SCIENCE, DISCOVERY SCIENCE TO
APPRECIATE STRATEGIES BY WHICH
WE COULD CURE SICKLE CELL
DISEASE, AND APPLYING THOSE
TECHNOLOGIES.
FURTHER TECHNOLOGY DEVELOPMENT
IS GOING TO BE NECESSARY TO SEE
IF WE COULD DO THIS IN VIVO AND
LEAPFROG TECHNOLOGIES TO TURN
THAT EX VIVO BONE MARROW
TRANSPLANT DRIVEN APPROACH TO
SOMETHING THAT IS CLOSER TO A
BLOOD TRANSFUSION.
SO THAT'S THE NEXT TARGET TO
CURE SICKLE CELL.
I JUST WANTED TO GIVE A SHOUT
OUT AGAIN TO THAT ECOSYSTEM
THAT'S EVOLVED IN THE PRIVATE
SECTOR IN THIS SPACE.
THERE'S ALSO A NICE INTERSECTION
APROPOS TO TODAY WHERE WE SEE
THE COMPLEMENTARITY BETWEEN THE
INTRAMURAL AND EXTRAMURAL
PROGRAM.
HOPEFULLY SOME OF YOU ARE AWARE,
OUR BRANCH CHIEF IN THE
INTRAMURAL PROGRAM IS AN AWARDEE
OF THE SHAW PRIZE, INCREDIBLY
PRESTIGIOUS AWARD.
FOR THEIR
INCREDIBLE WORK RELATED TO
SICKLE CELL DISEASE.
AGAIN, THAT FUNDAMENTAL
DISCOVERY SCIENCE, INDEED ONE OF
THE PROTOCOLS THAT IS BEING
FUNDED THROUGH CURE SICKLE CELL
TO ACTUALLY TAKE ARLEN TEE VIRUS
SHORT HAIRPIN TO KNOCK DOWN
BC11A AS A MEANS OF POTENTIALLY
TREATING SICKLE CELL DISEASE.
AND IT'S COME THROUGH THAT WHOLE
VIRTUOUS CYCLE.
WANT TO ACKNOWLEDGE THE
EXTRAMURAL TEAMS THAT HAVE
REALLY DRIVEN THAT WHOLE
PROCESS, TRACI MONDORO, JULIE
PANEPINTO, COMPLEMENTING THE
WORK OF JOHN TISDALE, AGAIN
YOU'LL HEAR FROM COURTNEY IN HER
TALK.
I THINK IT'S A NICE BLENDING OF
THE EXTRAMURAL AND EXTRAMURAL TO
DO SOMETHING TRANSFORMATIONAL
THAT WE HOPE TO CONTINUE TO
EXPAND UPON.
ANOTHER SORT OF UPDATE AND
OPPORTUNITY RELATES TO WOMEN'S
HEALTH.
AND THAT PICTURE THERE IS A
CEREMONY THAT WAS HELD WHEN
PRESIDENT BIDEN SIGNED AN
EXECUTIVE ORDER RELATED TO
WOMEN'S HEALTH RESEARCH
INITIATIVE AT THE WHITE HOUSE.
WE HAD THE PRIVILEGE OF BEING
INVITE TO THAT CEREMONY, WHERE
HE OUTLINED A BOLD VISION FOR
WOMEN'S HEALTH.
ACTUALLY TALKING ABOUT THE
BILLION DOLLARS A YEAR FOR ABOUT
10 YEARS ABOVE WHAT WE ALREADY
ARE INVESTING.
WHETHER THAT WILL TRANSLATE INTO
ACTUAL APPROPRIATION STILL
REMAINS TO BE SEEN, BUT AGAIN
NEVERTHELESS A BOLD AND
IMPORTANT VISION.
AND TOWARD THAT END, THIS IS
CERTAINLY SOMETHING THAT
REFLECTS THE SCIENTIFIC
OPPORTUNITY RELEVANT TO THE
NHLBI.
ONE OF THE THINGS THAT I THINK
WE'RE ALL AWARE OF AS CLINICIANS
IS THE SEX-BASED DIFFERENCES IN
MALE AND FEMALES IN TERMS OF
THAT CARDIOVASCULAR RISK
PROFILE, AND HOW THERE'S BEEN
ALL THIS WORKING HYPOTHESIS
SINCE PROBABLY I WAS A MEDICAL
STUDENT THAT WOMEN ARE PROTECTED
IN SOME WAY FROM THAT RISK UNTIL
MID LIFE AND MENOPAUSE AND
PRESUMABLY THE LOSS OF SOME OF
THOSE -- THAT PROTECTIVE EFFECTS
OF ESTROGEN, AT LEAST THAT WAS
THE HYPOTHESIS, SUCH THAT THAT
PROTECTIVE EFFECT IS LOST.
BUT I NEVER WAS CONVINCED WE
REALLY HAD A GOOD MECHANISTIC
UNDERSTANDING OF WHY THAT
ACTUALLY IS.
INDEED, IN SOME WAYS, THE FIRST
WOMEN'S HEALTH INITIATIVE NOW,
WHAT, ALMOST 30 YEARS AGO,
LOOKED AT THE INFLUENCE OF
PROVIDING HORMONE REPLACEMENT
THERAPY, PRESUMABLY ON THAT
HYPOTHESIS.
WELL, IF WE GIVE BACK THE
ESTROGEN AND PROGESTERONE IN A
COMBINATION, PERHAPS THAT WOULD
BE A GOOD THING.
AS EVERYONE IN THIS AUDIENCE
KNOWS, IT DIDN'T QUITE WORK OUT
LIKE THAT HYPOTHESIS THOUGHT.
INDEED, THERE APPEARED TO BE A
LOT OF HARM POTENTIALLY TO THE
HORMONE REPLACEMENT THERAPY
REGIMES THAT WERE USED IN THE
90s.
AND SO I THINK THAT SENT US BACK
TO THE DRAWS BOARD ON SOME OF
THOSE HYPOTHESES.
AND RELATED TO THAT,
EPIDEMIOLOGIC STUDIES HAVE ALSO
STARTED TO DIG A LITTLE FURTHER
INTO WHAT THAT MEANS TO HAVE
THAT MID LIFE TRANSITION INTO
MENOPAUSE.
I ALWAYS FEE K FEEL KIND OF AWKS
AN OLD MALE GUY TALKING ABOUT
MENOPAUSE, CERTAINLY NOT
SOMETHING THAT I'M EXPERT IN,
BUT CLEARLY, THERE'S A
RELATIONSHIP BETWEEN A LOT OF
THOSE SYMPTOMS THAT RELATE TO
THAT TRANSITION AND RISK.
AND SO THAT WAS ALREADY A CLUE
THAT THAT TRANSITION IS
INFLUENCING THESE PROCESSES BUT
MECHANISTICALLY STILL REMAIN A
BIT UNCLEAR.
AND TOWARD THAT END AS PART OF
THIS VIRTUOUS CYCLE, I ALWAYS
FOUND IT INTRIGUING THAT IF THAT
FIRST CLINICAL TRIAL WHERE WE
JUST TOOK A SIMPLE HYPOTHESIS
DIDN'T KIND OF WORK OUT, WE NEED
TO GO BACK TO THE BENCH AND
REALLY START TO DIG DEEPER AND
UNDERSTAND WHAT'S GOING ON IN
TERMS OF THE MOLECULAR PATHWAYS
THAT MAY BE DRIVING SOME OF
THESE THINGS.
AND CLEARLY ALL THAT
SYMPTOMATOLOGY, THE HOT FLASHES,
THE NIGHT SWEATS, ALL THESE
THINGS WERE SUGGESTIVE OF A
PERTURBATION OF THERMAL
REGULATORY CONTROL THAT THEN
SPEAKS TO BLOOD VESSELS AS
THERMAL REGULATION HAS EVOLVED
TO DO.
AND HOW THAT'S PERTURBED IN THE
CONTEXT OF HORMONAL TRANSITIONS.
THERE ARE CERTAIN MOLECULES THAT
MEDIATE SOME OF THOSE, AND SOME
OF THOSE HAVE BEEN OBSERVED NOW
WITH NEUROKININ 3, AND
DEMONSTRATING THE LINKAGES OF
THE WHOLE HYPOTHAT LA MACK BY
TEU TERRY GONADAL AXIS THAT
IDENTIFIES THOSE PATHWAYS, A KEY
MEDIATOR OF SOME OF THOSE
FACTORS.
WITH THAT BASIC SCIENCE
UNDERSTANDING AND TARGETING OF
THAT AS A KEY MEDIATOR,
FDA-APPROVED THERAPIES FOR
NON-HORMONAL AGENTS THAT ARE
NOVEL THAT MAY ACTUALLY MODULATE
THOSE VASOMOTOR SYMPTOMS.
SO IT'S NOT CLEAR TO ME WHETHER
THAT HAS IMPLICATIONS BEYOND THE
VASOMOTOR SYMPTOMS AND AFFECTS
OTHER FORMS OF THE DISEASE, BUT
AT LEAST THERE ARE NOW SAFE AND
EFFECTIVE THERAPIES THAT ARE
EMERGING AS WELL AS MORE
APPROPRIATE WAYS OF DELIVERING
ESTROGEN THAT WE HOPE ARE
ADDRESSING THE NEEDS OF WOMEN.
SO THOSE THEMES OF ADDRESSING
WOMEN'S HEALTH ACROSS THE
LIFESPAN THAT ARE OUTLINED IN
THAT VISION IN THE EXECUTIVE
ORDER, I THINK ARE QUITE
RELEVANT TO OUR PORTFOLIO.
I BELIEVE WE CAN START TO PROBE
EVEN FURTHER ABOUT WHAT THOSE
TRANSITION POINTS ARE, AND
AGAIN, HOW WE CAN BEST ADDRESS
THE NEEDS OF WOMEN IN MID LIFE.
AND TOWARD THAT END, IT'S CLEAR
THAT THERE IS THIS RELATIONSHIP
BETWEEN PARTICULARLY EARLY
MENOPAUSE AND RISK THAT AGAIN
SUGGESTS ITS CRITICAL ROLE.
AND INDEED, THAT SEEMS TO
CORRESPOND TO CHANGES IN
VASCULAR FUNCTION AS A HARBINGER
THAT THERE IS SOMETHING GOING ON
WITH VASCULAR DISEASE DURING
THAT TRANSITION.
AND INDEED MAY EVEN INTERSECT
WITH SOME OF THE RACIAL
DISPARITIES WE SEE AS WELL THAT
AMPLIFIES SOME OF THESE
ELEMENTS.
AND INDEED SOME OF THE MOLECULAR
FINGERPRINTS APPEAR TO BE
EMERGING IN WHICH THESE
TRANSITIONS MIGHT AFFECT BOTH
THE EPIGENOME AND THE
TRANSCRIPTOME.
PERHAPS NOT TOO SURPRISING,
GIVEN THE HORMONES -- BASICALLY
LIGANDS CAPABLE OF MODULATING
THE GENOME.
AND TOWARD THAT END, AGAIN,
THESE FACTORS ARE STARTING TO
EMERGE AS MOLECULAR PATHWAYS
DURING THIS TRANSITION.
INDEED, SOME SENSE THAT THIS
COULD INTERFACE WITH ACCELERATED
AND BIOLOGICAL AGING RELATED TO
THESE TRANSITIONS, INDEED EVEN
INCLUDING TELEMERE LENGTH.
SO CLEARLY THE BIOLOGY, SYSTEMS
BIOLOGY IS BEING MODULATED IN
THE CONTEXT OF THIS TRANSITION.
AND I THINK W WE'RE JUST TIPPING
THE ICEBERG IN REALLY
UNDERSTANDING THE MAGNITUDE OF
THESE CHANGES ON SYSTEMS.
THAT
AFFECT WOMEN AND WE HAD THE
CAPABILITY NOW TO CHARACTERIZE
THAT IN A MORE PROFOUND AND
DEEPER WAY.
AND AGAIN, THERE ARE HINTS THERE
AS WELL, AS WE THINK ABOUT THIS
POTENTIALLY FROM A MULTI-OMIC
AND SYSTEMS BIOLOGY APPROACH TO
UNDERSTANDING THAT TRANSITION
ACROSS THE LIFESPAN THAT COULD
HAVE IMPLICATIONS AND IS
STARTING TO REVEAL CERTAIN
MOLECULAR PATHWAYS THAT MAY BE
ALTERED IN THAT CONTEXT.
AGAIN, GIVEN SEX-SPECIFIC
DIFFERENCES THAT ARE PART OF
THAT TRAJECTORY THAT WOMEN HAVE
THAT ARE CLEARLY DISTINCT FROM
MEN.
AND THAT MAY HAVE LONG TERM
IMPLICATIONS.
AND SO THAT WOMEN'S HEALTH
INITIATIVE, WE THINK COULD BE A
GREAT OPPORTUNITY TO START TO
THINK ABOUT HUMAN SYSTEMS
BIOLOGY IN A VERY DEEP WAY AT
SCALE IN WAYS THAT WE THINK
COULD CONTRIBUTE TO ENHANCING
WOMEN'S HEALTH.
LET ME NOW PIVOT FROM WOMEN'S
HEALTH TO ANOTHER AREA THAT WE
THINK IS A GROWING OPPORTUNITY.
WE ALLUDED TO THE ADVANCES OF
THE LUNG DIVISION UNDER
DR. KILEY'S LEADERSHIP, AND ONE
OF THE AREAS THAT WE'VE BEEN
DIALOGUING ABOUT AS THE LUNG
DIVISION DOES ITS STRATEGIC
VISION REFRESH IS REALLY DRIVING
GREATER DEPTH IN THE MOLECULAR
BASIS OF CHRONIC LUNG DISEASE,
AND MOVING THROUGH THAT SAME
VIRTUAL CYCLE.
AND TOWARD THAT END, ONE OF THE
AREAS THAT WE'VE BEEN TRYING TO
HIGH LIGLIGHT RELATES TO IDIOPAC
PULMONARY FIBROSIS.
SOME OF YOU HAVE HEARD ME TALK
ABOUT PREVIOUSLY WHERE IT'S ONE
OF THOSE SORT OF VEXING
CHALLENGES THAT WE'VE HAD FOR
SOME TIME WHERE THESE
INDIVIDUALS, BY THE TIME THEY'RE
DIAGNOSED, ON OXYGEN, HAVE THE
HORRIBLE PROGNOSIS, AND THAT
PROGNOSIS HASN'T CHANGED MUCH
OVER TIME, AND SO THIS IS REALLY
AN AREA THAT'S INCREDIBLE AND I
THINK WE HAVE TO REDOUBLE OUR
EFFORTS.
TOWARD THAT END, WE'RE INTRIGUED
BY, AGAIN, EMERGING BASIC
SCIENCE, AND SOME OF THE THINGS
THAT COUNCIL HAS ALREADY
REVIEWED A BIT IN TERMS OF THE
LUNG MAP AND APPRECIATING HOW
MANY DIFFERENT KINDS OF CELLS
ARE IN THE LUNG.
AND INCLUDING PROGENITOR CELLS
AND A GREAT REPARATIVE CAPACITY,
INTERACTION WITH THE IMMUNE
SYSTEM, AND ONE OF THE THINGS
THAT WAS VERY INTRIGUING WAS
THIS EXPERIMENT IN WHICH IT
TARGETED SELECTIVELY CELL NE
SENESCENCE, AND THIS WAS A MODEL
THAT RESULTED IN ENHANCED LUNG
FIBROSIS.
AGAIN, INTRIGUING AS TO HOW WE
GET TO THAT END STAGE OF IPF AND
HOW THAT MAY RELATE TO THE
ABILITY OF THE LUNG, WHICH IS
REALLY AT THE FRONT LINE OF
EXPOSURES OF A LOT OF THINGS
THAT ARE INJURIOUS IN ITS
CAPACITY TO REPAIR ITSELF.
OVER
TIME.
AND AS WE TRY TO UNDERSTAND
THESE PROCESSES AND
SUSCEPTIBILITIES AND TRY TO
UNDERSTAND THINGS AT THE
EARLIEST ONSET, THE FAMILIAL
MODELS SEEMS TO HOLD A LOT OF
PROMISE, GIVEN THOSE
PREDISPOSITIONS.
AND IT'S INTRIGUING THAT MUCH OF
THE EARLY WORK RELATES TO
POTENTIAL VARIANTS IN GENES THAT
ARE INVOLVED IN SENESCENCE AND
TELOMERE LENGTH LIKE TERT, IN
WHICH THESE VARIANTS ARE
ASSOCIATED WITH RISK IN THESE
PATIENT POPULATIONS, AGAIN
CONSISTENT PERHAPS WITH SOME
ACCELERATED AGING.
SO REALLY WE DO HAVE THAT
OPPORTUNITY POTENTIALLY
SUGGESTED BY THOSE FAMILIAL
CASES, PERHAPS FIND FOLKS WHO
ARE SUSCEPTIBLE AND GETTING AN
EARLIER ONSET OF THE DISEASE TO
GET UPSTREAM TO REALLY START TO
SEE WHAT MIGHT BE PRE-CLINICAL
AND UNDERSTAND THOSE MEDIATOR
PATHWAYS IN A WAY THAT WE MIGHT
BE ABLE TO INTERRUPT OR PREEMPT
OR MODIFY DISEASE COURSE.
IN THIS REGARD, INTRIGUED BY
EMERGING OPPORTUNITIES WHERE
EVERYTHING HAS GOT TO BE AN OMIC
THESE DAYS, SO THE RADIOLOGIST
DIDN'T WANT TO BE LEFT OUT SO
NOW THERE'S RADIOMICS, MACHINE
LEARNING, ARTIFICIAL
INTELLIGENCE, TO BE ABLE TO
DISCERN FEATURES FROM VARIOUS
TESTS RAID YO LI RADIOLOGIC TES,
WHETHER THAT CAN HELP US GET
UPSTREAM TO IT.
IT WOULD SEEM THAT THIS IS A
SUBSTANTIAL OPPORTUNITY AS WE
LOOK TO THE STRATEGIC VISION
OVER THE NEXT FIVE TO 10 YEARS,
THE APPLICATION OF AI TO IMAGING
AND ITS IMPLICATIONS FOR
CLINICAL MEDICINE, WE THINK ARE
GOING TO BE PROFOUND, AND I
BELIEVE THAT NHLBI NEEDS TO MAKE
INVESTMENTS IN THAT SPACE, NIH
NEEDS TO MAKE INVESTMENTS IN
THAT SPACE APPLICABLE TO OUR
PORTFOLIO.
INDEED SOME INVESTIGATORS AGAIN
RELATED -- FUNDED BY NHLBI,
THEY'RE STARTING TO EXPLORE THE
SPACE AND TRYING TO IDENTIFY
SOME OF THESE EARLY CHANGES,
RADIOGRAPHICALLY, INTERSTITIAL
LUNG ABNORMALITIES, TRYING TO
CHARACTERIZE IT IN WAYS THAT WE
HOPE ARE PRIOR TO A FINAL
DIAGNOSIS OF PULMONARY FIBROSIS,
WOULD GIVE US MORE OF A SENSE OF
THOSE EARLY CHANGES IN WHICH WE
MIGHT BE ABLE TO INTERVENE AND
MAKE A DIFFERENCE.
AND AGAIN, SOME OF THOSE SAME
AREAS OF CONVERGENCE, OLDER AGE,
EXPOSURES, THINGS LIKE SMOKING,
SHORTER TELOMERE LENGTHS, INDEED
SOME OF THE CANDIDATES GENES
APPEAR TO BE PLAYING A ROLE, ALL
SUGGESTING THAT WE'RE GETTING
CLOSER AND CLOSER TO STARTING TO
GET UPSTREAM AND GET TOWARD
FACTORS THAT MAY BE PREDISPOSING
AND IDENTIFYING THOSE AT RISK AS
WELL AS MEDIATORS.
THIS IS MOVING FORWARD IN WAYS
THAT ARE INTRIGUING IN WHICH
PICKING UP SOME OF THESE IMAGING
BIOMARKERS START TO BE RELATED
TO SOME OF THESE MEDIATING
PATHWAYS, CERTAINLY INFLAMMATION
AND OTHERS.
AND THESE ARE COMING FROM OUR
OBSERVATIONAL COHORTS, ARIC,
FRAMINGHAM, MESA, WHERE WE HAVE
THOSE PROSPECTIVE RADIOLOGICAL
CHARACTERIZATION OF POPULATIONS
RELATED TO THEIR EXPOSURES AND
STARTING TO SEE THESE IN A
PRE-CLINICAL CONTEXT IN THE
COHORTS, AND THAT GIVES US AN
OPPORTUNITY TO THEN APPLY
GENOMICS AND START TO IDENTIFY
GWAS LOCI OR EVEN POLYGENIC RISK
SCORES, AND AGAIN, SOME OF THESE
ARE POPPING UP WITH MEDIATOR
PATHWAYS THAT, AGAIN, MIGHT
RELATE TO REPLICATION AND
SENESCENCE.
AS WELL AS OTHER LOCI.
AND INDEED, THIS IS ANOTHER
COLLECTION OF THE VARIOUS COHORT
STUDIES AND SEGMENTS, INCLUDING
PROGRAMS LIKE COPDGEEP,
SPIROMICS, WHEN WE PUT THAT ALL
TOGETHER IT STARTS TO ENABLE
INVESTIGATORS TO PUT TOGETHER
POLYGENIC RISK SCORES THAT AGAIN
APPEAR TO BE PREDICTIVE IN
HELPING US IDENTIFY WHO'S MOST
AT RISK, WHO WE MIGHT STUDY AND
INTERVENE ON EARLIER IN THE
COURSE OF DISEASE.
AND TOWARD THAT END,
COMPLEMENTING THOSE POPULATION
STUDIES IN THE RADIOMICS WITH IN
DEIN-DEPTH MOLECULAR
CHARACTERIZATION OF TISSUES,
COUNCIL ALSO REVIEWED TODAY A
LUNG MAP AS ONE OF THE SIGNATURE
PROGRAMS OF THE LUNG DIVISION,
STARTING TO GET TO THIS POINT OF
MOLECULAR CHARACTERIZATION OF
TISSUES IN DEPTH IN WAYS THAT
AGAIN ARE STARTING TO IDENTIFY
MEDIATOR PATHWAYS AS SHOWN ON
THE RIGHT, YOU SEE CYTOKINES AND
PROTEINASES AND COLLAGEN,
GIVING, AGAIN, A SENSE OF A
PATHOBIOLOGY.
THAT COULD BE AMENABLE TO
TARGETING, AND SO HOPEFULLY,
OVER THIS NEXT FIVE YEARS, WE
CAN START TO REALLY GET DEEPER
AND GET EARLIER IN UNDERSTANDING
THE PATHOGENESIS OF THIS DISEASE
IN WAYS THAT WE ARE STARTING TO
BE ABLE TO CHARACTERIZE AT
SINGLE CELL RESOLUTION HOPEFULLY
SOME OF THESE MEDIATORS IN THESE
PATHWAYS THAT I HOPE WILL BE
TARGETS FOR DISEASE MODIFYING
THERAPIES OF A NEW GENERATION.
IN A WAY THAT WE HOPE CAN
TRANSFORM THE LIVES OF THOSE
PATIENTS AS WELL.
WITH THESE
PROGRAMS.
SO WE THINK THAT A LOT OF THIS
HOPEFULLY WILL CONVERGE AND COME
TOGETHER AS WE LEVERAGE THESE
VARIOUS RESOURCES, THE MOLECULAR
ATLASES LIKE LUNG MAP, THE
TISSUE REPOSITORIES, ALONG WITH
TOPMED AND THE APPLICATION OF
THE RADIOMICS OF IMAGING
TECHNOLOGIES WE HAVE IN BDC, ALL
DRIVEN IN AN AI/ML ANALYTICS
THAT'S REALLY COME TOGETHER IN
WAYS OF INTEGRATING ALL THIS
INFORMATION.
PRESUMABLY AND HOPEFULLY IN A
PRE-CLINICAL CONTEXT TO REALLY
MOVE THIS AREA FORWARD IN A WAY
THAT SERVES THESE PATIENTS MUCH
BETTER.
SO I JUST TRIED TO OUTLINE AT
LEAST A COUPLE OF EMERGING
OPPORTUNITIES THAT FRANKLY I
HOPE WE CAN START TO MOVE ON IN
THE NEXT YEAR OR TWO RELATED TO
WOMEN'S HEALTH, AND CHRONIC LUNG
DISEASE AND MOLECULAR
CHARACTERIZATION, RADIOMICS,
LEVERAGING OUR TOP MED RESOURCES
AND OUR BIODATA CATALYSTS,
PARTNERING WITH DATA SCIENTISTS
CAN HELP US APPLY AI/ML
GENERATED TOOLS ALONG WITH
DISCOVERY SCIENTISTS IN HEART,
LUNG AND BLOOD SLEEP SCIENCE IN
WAYS THAT WE THINK COULD HAVE A
DRAMATIC IMPACT FOR BOTH THOSE
TWO DOMAINS OF WOMEN'S HEALTH.
IN
CHRONIC LUNG DISEASE.
AND WITH THAT, I WILL SIT DOWN.
SO THANK YOU VERY MUCH FOR YOUR
ATTENTION.
[APPLAUSE]
>> THANK YOU VERY MUCH,
DR. GIBBONS.
DOES ANYONE HAVE ANY QUESTIONS,
COMMENTS FOR DR. G GIBBONS?
HEARING NONE, OUR NEXT SPEAKER
IS DR. COURTNEY FITZHUGH.
SHE RECEIVED HER B.S. MAGNA CUM
LAUDE FROM LOS ANGELES IN
1996 --
>> CAN I -- HOLD ON, COURTNEY?
IF YOU DON'T MIND, I'D LIKE TO
MAKE A PROVIZATIONAL
INTERJECTION HERE, I THINK I
HAVE THAT PREROGATIVE.
WE'LL GET TO YOU, COURTNEY.
AS AN EXTENSION OF OUR
ACKNOWLEDGMENT OF DR. KILEY'S 40
YEARS OF SERVICE, DR. CHILDS,
WOULD YOU BE SO KIND AS TO COME
TO THE FRONT OF THE PODIUM AND
DO THE HONORS O TO DESCRIBE WHAT
YOU'D LIKE DR. KILEY TO ENGAGE
IN?
[LAUGHTER]
>> I'VE HEARD DR. KILEY LOVES
SURPRISES.
SO HE'S GOING TO LOVE THIS.
BUT -- SO I'M A MEMBER OF THE
UNIFORMED SERVICE, THERE'S EIGHT
UNIFORMED SERVICES, ARMY, NAVY,
AIR FORCE, MARINES, PEACE CORPS,
NOAA AND THE PUBLIC HEALTH
SERVICE.
ONE OF TWO SERVICES THAT WE
DON'T CARRY GUNS.
WE CARRY STETHOSCOPES IN THE
PUBLIC HEALTH SERVICE.
AND ONE OF OUR TRADITIONS IS
THAT WHEN YOU HIT A BENCHMARK
THAT'S IMPORTANT AND NOTEWORTHY,
YOU MAY BE A CANDIDATE FOR
GETTING A COIN.
AND IT'S HARD TO HIT THAT
BENCHMARK.
SOMETIMES GARY AND I WERE
TALKING AND HE'S LIKE, IS THAT
COIN-WORTHY?
I'M LIKE, NO, GARY, THAT'S NOT
COIN-WORTHY.
BUT I JUST WANT TO -- ON BEHALF
OF THE UNITED STATES PUBL PUBLIC
HEALTH SERVICE, RECOGNIZE
DR. KILEY FOR ALL HIS WORK THAT
HAS IMPACTED PUBLIC HEALTH AS IT
APPLIES TO PULMONARY DISEASE AND
RECOGNIZE HIM BY GIVING HIM MY
CHALLENGE COIN, WHICH HAS ON
IT -- HOPEFULLY HE CAN SHOW YOU
LATER -- HEART, LUNG AND BLOOD.
HE MIGHT BE A LITTLE
DISAPPOINTED THAT IT'S NOT LUNG,
HEART AND BLOOD, BUT I WANT TO
PRESENT THIS TO YOU TODAY IN
RECOGNITION.
THIS IS -- OF ALL THE WORK THAT
HE'S DONE.
[APPLAUSE]
>> THANK YOU SO MUCH.
>> YOU'RE WELCOME.
>> THANK YOU ALL VERY MUCH.
SUCH A SPECIAL RECOGNITION,
PARTICULARLY FROM MY COLLEAGUES.
A CARRIES A HUGE AMOUNT OF
WEIGHT, SO IT'S REALLY WONDERFUL
TO BE RECOGNIZED.
[APPLAUSE]
>> HEY, JIM, HOLD ON A SECOND.
RICK, DOES THIS REQUIRE A VOTE?
>> YOU'LL ALL HAVE TO RECUSE
YOURSELVES.
>> I THINK IF JIM JUST TAKES THE
COIN AND MOVES IT, IT COULD B
BE --
[LAUGHTER]
>> BACK TO THE AGENDA.
WE HAVE DR. COURTNEY FITZHUGH TO
SPEAK TO US ABOUT HEMATOPOI -- E
PARTICIPATED IN THE NIH CLINICAL
RESEARCH TRAINING PROGRAM, WHERE
SHE STUDIED WITH DR. JOHN
TISDALE IN NIDDK AND NHLBI AFTER
RECEIVING HER M.D., DR. FITZHUGH
COMPLETED A JOINT RESIDENCY IN
INTERNAL MEDICINE AND PEDIATRICS
AT DUKE UNIVERSITY MEDICAL
CENTER AND IN 2005 SHE DID A
COMBINED HEMATOLOGY ONCOLOGY
FELLOWSHIP AT THE NIH AND JOHNS
HOPKINS HOSPITAL.
IN 2007, DR. FITZHUGH RETURNED
TO THE NHLBI AND WAS APPOINTED
AS ASSISTANT CLINICAL
INVESTIGATOR IN 2012 AND LASKER
CLINICAL RESEARCH SCHOLAR AS A
CLINICAL TENURE TRACK
INVESTIGATOR IN 2016.
HER CURRENT RESEARCH INCLUDES
EXPLORING NEW AVENUES OF
HEMATOPOIETIC CELL
TRANSPLANTATION FOR SICKLE CELL
DISEASE, AND STUDYING THE LONG
TERM HEALTH EFFECTS OF KERATIN
THERAPIES FOR SICKLE CELL
DISEASE.
HER TEAM HAS BEEN DEVELOPING AN
ALTERNATIVE APPROACH WHERE
PATIENTS RECEIVE AGENTS FOCUSED
OND ERADICATING THE IMMUNE
SYSTEM AND MAKING SPACE IN THE
BONE MARROW WHILE AVOIDING HIGH
DOSE CHEMOTHERAPY.
SHE HAS DEMONSTRATED THE
EFFICACY OF THIS
NON-MYELOABLATIVE PROCEDURE IN
BOTH MICE AND HUMAN VOLUNTEERS,
AND IS CURRENTLY PARTICIPATING
IN A LONG-TERM FOLLOW-UP STUDY
WITH PATIENTS TO SEE IF THEY
REMAIN FREE OF SICKLE CELL
DISEASE.
ADDITIONALLY, SHE IS ALSO
INTERESTED IN LEARNING MORE
ABOUT THE LONG TERM HEALTH
EFFECTS OF CURATIVE THERAPIES IN
PATIENTS WITH SICKLE CELL
DISEASE.
SHE'S A MEMBER OF THE AMERICAN
SOCIETY OF HEMATOLOGY AND THE
AMERICAN SOCIETY OF
TRANSPLANTATION AND CELLULAR
THERAPY.
AND MOST RECENTLY SHE WAS ONE OF
ONLY SEVEN NIH INVESTIGATORS
ELECTED TO THE AMERICAN SOCIETY
FOR CLINICAL INVESTIGATION.
THIS YEAR.
WELCOME, DR. FITZHUGH.
>> THANK YOU SO MUCH FOR THE --
[APPLAUSE]
>> THANK YOU FOR THE
INTRODUCTION AND FOR INVITING ME
TO GIVE THIS PRESENTATION.
SO MY TALK IS ENTITLED CLONAL
HEMATOPOE CYST FOLLOWING
CURATIVE THERAPIES FOR SICKLE
CELL DISEASE.
I'M GOING TO START BY
INTRODUCING YOU TO ONE OF MY
PATIENTS I'M GOING TO REFER TO
AS MR. SMITH.
HE WAS A 36-YEAR-OLD AFRICAN
AMERICAN GENTLEMAN WITH SICKLE
CELL DISEASE.
HE ALSO HAD CHRONIC RENAL
INSUFFICIENCY WITH BASELINE
CREATININE OF 2.5 MG PER DL.
SICKLE CELL DISEASE IS CAUSED BY
MUTATION THAT LEADS TO THE
TRANSFORMATION OF RED BLOOD
CELLS FROM CONCAVE -- THAT
EASILY MOVE THROUGHOUT THE MICRO
VASCULATURE TO A RIGID --
ASSOCIATED WITH DAMAGE TO THE
BONE MARROW MICROENVIRONMENT,
INFLAMMATION AND OXIDATIVE
STRESS.
IN THIS FIGURE YOU SEE THE --
SURVIVAL -- THESE ARE IN 25
PATIENTS MOSTLY WITH HOMOZYGOUS
SICKLE CELL DISEASE MEDIAN OF
6 1/2 YEARS.
YOU SEE 60% OF THE PATIENTS WERE
TAKEN -- HYDROXYUREA -- AT LEAST
20 YEARS EARLIER THAN THE
GENERAL AFRICAN AMERICAN
POPULATION.
-- WANTED TO KNOW WHETHER
HAVING MORE THAN ONE ORGAN
IMPAIRED LEADS TO FURTHER
INCREASE IN MORTALITY.
LUNG IMPAIRMENT LESS THAN 70%
AND KIDNEY IMPAIRMENT HAD
MULTIPLE DEFINITIONS INCLUDING
ESTIMATED GFR OF LESS THAN 60.
YOU SEE PATIENTS WHO HAD ZERO OR
ONE ORGAN IMPAIRED HAD A
MEANTIME TO DEATH OF 14 YEARS,
WHILE PATIENTS WITH MORE THAN
ONE ORGAN IMPAIRED HAD A
MEANTIME TO DEATH OF ONLY
7.8 YEARS.
AND BECAUSE MR. SMITH HAD BOTH
HEART AND KIDNEY IMPAIRMENT, HIS
RISK OF EARLY MORTALITY WAS EVEN
GREATER.
PATIENTS WITH SICKLE CELL
DISEASE HAVE INCREASED RISK FOR
AGGRESSIVE MYELOID LIG M MALIGN.
IDENTIFIED BETWEEN 1991 AND
2014, AND THEY WERE FOLLOWED FOR
OVER 140,000 PERSON YEARS AND
COMPARED TO THE GENERAL
POPULATION.
THEY DID NOT FIND AN INCREA
INCREASED -- 3.6 FOLD
INCREASE -- OR AML.
THEY ALSO FOUND PATIENTS WITH
SICKLE CELL DISEASE WHO ARE
OLDER AND THOSE WITH MORE SEVERE
DISEASE HAD A HIGHER RISK OF
LEUKEMIA, BUT THEY ALSO COMPARED
THE PREVALENCE OF LEUKEMIA
BEFORE AND AFTER HYDROXYUREA WAS
FDA-APPROVED IN 1998 AND THEY
DID NOT FIND INCREASED
PREVALENCE OF LEUKEMIA AFTER
HYDROXYUREA WAS FDA-APPROVED.
IF YOU LOOK CLOSELY AT THE DATA,
YOU SEE AGAIN THAT OVER 6400
PATIENTS WITH SICKLE CELL
DISEASE WERE FOLLOWED FOR OVER
27 YEARS.
DURING THAT TIME, ONLY SIX
PATIENTS DEVELOPED AML WITH OVER
140,000 PERSON YEARS OF
FOLLOW-UP, OR 0.004 PER 100
PERSON YEARS.
THIS COMPARES TO IS .67
INDIVIDUALS WITHOUT SICKLE CELL
DISEASE WHO ARE EXPECTED TO
DEVELOP AML OVER THAT TIME FRAME
WHEN CONTROLLED FOR AGE, SEX,
RACE AND ETHNICITY OR 0.001 PER
100 PERSON-YEARS.
SO WHILE THERE'S AN INCREASED
RELATIVE RISK FOR LEUKEMIA IN
PATIENTS WITH SICKLE CELL
DISEASE OR AML SPECIFICALLY, THE
ABSOLUTE RISK IS LOW.
THERE ARE MULTIPLE RISK FACTORS
FOR MYELOID -- INFLAMMATION,
HYPOXIA AND ACIDOSIS,
TRANSFUSION-RELATED
IMMUNOMODULATION, COMPROMISED
APOPTOSIS, ENDOTHELIAL DAMAGE,
INCREASED AGE, AND CLONAL
HEMATOPOESIS.
-- OFFERS A POTENTIAL CURE FOR
PATIENT WITH SICKLE CELL
DISEASE.
IN ORDER TO COMPLETELY WIPE OUT
THEIR BONE MAY OTHER AND REPLACE
IT WITH THAT OF THE DONOR.
93% OF THE PATIENTS WERE ALIVE,
AND EVENT-FREE SURVIVAL OF 91%,
MEANING AT FIVE YEARS, 91% WERE
ALIVE AND FREE OF SICKLE CELL
DISEASE.
THE FIVE-YEAR OVERALL SURVIVAL
AND EVENT-FREE SURVIVAL WERE A
LITTLE HIGHER AN 95 AND 93%
RESPECTIVELY FOR PATIENTS
YOUNGER THAN 16 YEARS OF AGE,
AND THAT WASN'T SURPRISING SINCE
MANY OF THE PATIENTS RECEIVED
MYELOABLATIVE DOSES OF
CHEMOTHERAPY.
THEY ALSO REPORT THE A
CUMULATIVE INCIDENCE OF
GRAFT-VERSUS-HOST DISEASE OF 15%
AND CHRONIC OF 14%.
IT'S WHEN IT RECOGNIZES IT AS
BEING FOREIGN AND ATTACKS THE
PATIENT, CAN BE DEADLY, SO YOU D
BECAUSE THERE'S NO BENEFIT -- SO
THE FIRST MAJOR OBSTACLE IS THAT
MANY ADULTS WITH SICKLE CELL
DISEASE WHO RECEIVE THE STANDARD
CURATIVE THERAPY WHICH INCLUDES
MYELOABLATIVE CONDITIONING WILL
DIE.
WE WANTED TO DEVELOP A NON-MILE
MYELOABLATIVE APPROACH WHERE
INSTEAD OF GIVING HIGH DOSE
CHEMOTHERAPY WE WOULD SUPPRESS
THE IMMUNE SYSTEM IN ORDER TO
REDUCE THE RISK FOR GRAFT
REJECTION OR GRAFT-VERSUS-HOST
DISEASE.
PATIENTS RECEIVE O ALEMTUZUMAB.
-- ALSO MAKES SPACE FOR THE
DONOR CELLS.
AND WE GIVE SIROLIMUS, SO THE
DONOR AND RECIPIENT CELLS NO
LONGER RECOGNIZE THIS THING AS
FOREIGN.
SO NIH AND COLLEAGUES AT THE
UNIVERSITY OF ILLINOIS AT
CHICAGO RECENTLY DESCRIBED
PATIENTS USING THIS APROA. THE
MEDIAN FOLLOW-UP WAS FOUR YEARS
AND THE OVERALL SURVIVAL WAS
93%, THE EVENT-FREE SURVIVAL WAS
85%.
NONE OF THE PATIENTS HAD GRADE D
CHRONIC GVHD.
THE SECOND MAJOR OBSTACLE FROM
CURING MR. SMITH IS -- OF
PATIENTS WITH SICKLE CELL
DISEASE HAVE A FULLY HLA
MAST-RELATED DONOR.
ON THE OTHER HAND, 90% OR AT
LEAST 90% OF PATIENTS WILL HAVE
A PARENT, A CHILD OR -- MATCHED
SIBLING -- THIS GREATLY EXPANDS
THE DONOR POOL, ALLOWING
ENROLLMENT OF PATIENTS WHO HAVE
ORGAN DAMAGE.
SO NON-MYELOABLATIVE
HAPLOIDENTICAL TRANSPLANT
EXPANDS THE DONOR POOL AND
ALLOWS PATIENTS WITH
COMORBIDITIES TO UNDER GS
TRANSPLANT.
WHEN THE ORIGINAL PROTOCOL WAS
WRITTEN, ONLY THE NIH AND
HOPKINS WERE PERFORMING
HAPLOIDENTICAL TRANS PL TRANSPLN
ADULTS WITH SICKLE CELL DISEASE
SO -- WE EFFICACY AND TOXICITY
ASSOCIATED WITH TRANSPLANT WERE
NOT KNOWN.
IT WAS WRITTEN AS A DOSE
ESCALATION OF POST TRANSPLANT --
BASED ON -- DATA.
YOU SEE THE PATIENTS RECEIVED AL
ALE MTUZUMAB.
IN THE FIRST COHORT, PATIENTS
DIDN'T RECEIVE ANY POST
TRANSPLANT CYCLOPHOSPHAMIDE.
-- WE MOVED TO THE SECOND
COHORT, WHERE PATIENTS RECEIVED
50MG PER KG.
WE MOVED TO THE THIRD AND FINAL
COHORT, WHERE PATIENTS WOULD
RECEIVE 100MG PER KG IN DIVIDED
DOSES.
SO 23 PATIENTS WERE TRANSPLANTED
ON THIS STUDY.
THE MEDIAN AGE WAS 36 YEARS WITH
A RANGE OF 20 TO 506 YEARS.
20 TO 56 YEARS.
MOST OF THE PATIENTS HAD
HOMOZYGOUS SICKLE CELL DISEASE,
TWO HAD TRANSPLANT DEPENDENT
THALASSEMIA.
-- HEART FAILURE, AND PULMONARY
HYPERTENSION, AND THAT'S BECAUSE
THE EXPECTED BENEFITS WERE
THOUGHT TO OUTWEIGH THE RISKS.
SO THESE ARE THE RESULTS OF THE
STUDY.
IN THE FIRST COHORT, PATIENTS
DIDN'T RECEIVE ANY PT -- THREE
PATIENTS WERE TRANSPLANTED, ONE
OF THEM INITIALLY ENGRAFTED BUT
THEN SHE LOST HER GRAFT AT SEVEN
MONTHS POST TRANSPLANT.
SO WE -- MOVED TO THE SECOND
COHORT, WHERE PATIENTS RECEIVED
ONE DOSE, 15, EIGHT PATIENTS
WERE TRANSPLANTED, FIVE OF THEM
INITIALLY -- OR EIGHT OF THEM
INITIALLY -- FIVE OF THEM
INITIALLY ENGRAFTED BUT ONLY TWO
REMAINED FREE OF SICKLE CELL
DISEASE.
SO AGAIN WE MOVED TO THE THIRD
AND FINAL COHORT, WHERE PATIENTS
RECEIVED 100MG PER KG.
12 PATIENTS WERE TRANSPLANTED,
10 INITIALLY ENGRAFTED BUT ONLY
SIX REMAIN FREE OF SICKLE CELL
DISEASE.
SO WITH THE PT -- THE
ENGRAFTMENT RATE GOT BETTER AND
THE EVENT-FREE SURVIVAL IMPROVED
BUT EVEN WITH THE THIRD COHORT,
THE REJECTION RATE WAS
UNACCEPTABLY HIGH AND -- SO
MR. SMITH UNDERWENT
HAPLOIDENTICAL TRANSPLANT.
HIS MOTHER WAS THE DONOR.
UNFORTUNATELY HE REJECTED HIS
GRAFT WITH SUBSEQUENT RETURN OF
HIS SICKLE CELL DISEASE.
WHY DID MR. SMITH'S ATTEMPTED
CURE FAIL?
WITH THE TRANSPLANT -- WHILE
MINIMIZING GRAFT REJECTION AND
GVHD.
WITH THE FIRST PROTOCOL, WE HAD
A LOT OF GRAFT REJECTION AND
REALLY NO SIGNIFICANT GVHD, SO
WE HYPOTHESIZED THAT ADDITIONAL
UP FRONT IMMUNOSUPPRESSION WOULD
DECREASE THE GRAFT REJECTION
RATE WHILE AVOIDING UNACCEPTABLE
GVHC OR VIRAL DISEASE.
SO THESE ARE TWO NEWER STUDIES
WHERE WE ATTEMPTED TO DECREASE
THE RATE OF GRAFT REJECTION
ESPECIALLY IN A HAPLOIDENTICAL
SETTING AND BOTH STUDIES INCLUDE
UP FRONT PRECONDITIONING TO
PROVIDE MORE IMMUNOSUPPRESSION
AND WE CHOSE INTRAVENOUS
PENTOSTA TIB AND DAILY ORAL
CYCLOPHOSPHAMIDE FOR 14 DAYS.
BEFORE MOVING ON I WANT TO
INTRODUCE AUTOLOGOUS GENE
THERAPY AS A CURATIVE STRATEGY
FOR PATIENTS WITH SICKLE CELL
DISEASE.
I BORROWED THIS SLIDE, THIS IS
OUR MULTICENTER STUDY AND YOU
CAN SEE THAT ALL OF THE PATIENTS
RECEIVED MYELOABLATIVE
CONDITIONING.
PATIENTS WERE DIVIDED INTO THREE
DIFFERENT GROUPS.
A PRECOLLECTION -- WAS OPTION
NAND IN GROUP A PATIENTS AND WAS
REQUIRED FOR GROUPS B AND C
PATIENTS.
THE -- BONE MARROW IN GROUP A
AND B PATIENTS AND MOBILIZED
PERIPHERAL BLOOD IN GROUP C
PATIENTS.
THE ORIGINAL MANUFACTURING
PROCESS IS GIVEN TO GROUP A AND
SOME GROUP B PATIENTS AND A MORE
REFINED PROCESS FOR THE REST OF
GROUP B AND ALL OF GROUP C
PATIENTS.
AND WITH THESE CHANGES, THE CELL
DOSE THAT RECEIVED BY PATIENTS
IN GROUP C WAS HIGHER AND
THERE'S ALSO A LOWER RATE OF
GRAFT FAILURE.
SO A TWO-YEAR POST TRANSPLANT,
MR. SMITH WAS FOUND TO BE
NEUTROPENIC.
-- AND PATHOGENIC TP53
MUTATION.
HE WAS TREATED WITH DECITABINE
FOLLOWED BY AZACYTIDINE.
-- AT THE NIH BETWEEN SEPTEMBE
DECEMBER 2020.
18 PATIENTS RECEIVED HLA MATCHED
SIBLING TRANSPLANT WITH A MEDIAN
AGE OF 31 YEARS.
39 PATIENTS UNDERWENT
HAPLOIDENTICAL TRANSPLANT WITH A
MEDIAN AGE OF 32 YEARS AND A
RANGE OF 19 TO 501 YEARS.
FIVE PATIENTS DEVELOPED EITHER
MDS OR AML POST TRANSPLANT.
ALL FIVE PATIENTS HAD HOMOZYGOUS
SICKLE CELL DISEASE WITH AGE
RANGING FROM 20 TO 44 YEARS AT
THE TIME OF TRANSPLANT.
TWO OF THE PATIENTS UNDERWENT --
THE REMAINDER HAPLOIDENTICAL
TRANSPLANT.
ONE PATIENT -- FAILURE RANGED
FROM 73 DAYS TO 7 MONTHS POST
TRANSPLANT.
REMAINING THREE AML.
TIME OF DIAGNOSIS RANGED FROM
FOUR MONTHS TO 5 1/2 YEARS POST
TRANSPLANT.
AND WHEN WE GOT BONE MARROWS AT
THE TIME OF THE DIAGNOSIS,
THE -- WERE COMPLEX IN FOUR OF
THE PATIENTS, THE FIFTH PATIENT
HAD A SUDDEN ACUTE LESION.
FOUR OF THE PATIENTS COMPLETELY
REJECTED THEIR GRAFT.
THE FIFTH PATIENT HAD IMPENDING
FAILURE AND -- OF 18% AT THE
TIME OF AML DIAGNOSIS.
AND ALL OF THE PATIENTS ARE
DECEASED.
SO THIS TABLE SHOWS THE
INCIDENCE OF MDS OR AML ACROSS
PROTOCOL OR ACROSS STUDIES.
THESE FIRST THREE COLUMBUS SHOW
PATIENTS UNDERGOING HLA --
EITHER AT THE NIH OR CHICAGO
OR -- YOU SEE THAT AT RISK TIME
RANGED FROM 87.5 TO 518 PERSON
YEARS WITH THE INCIDENCE OF MDS
OR AML RANGING FROM ZERO TO 0.8
PER 100 PERSON YEARS.
WITH THE STUDY THAT INCLUDED
PRECONDITIONING, AT RISK TIME IS
96 YEARS WITH THE INCIDENCE OF
MKM DS OR AML -- THIS FIRST COLN
SHOWS THE STUDY WHICH INCLUDES A
ESCALATION OF PT5, AS RISK TIME
WAS -- WITH INCIDENCE BEING
1.7 PER 100 PERSON YEARS.
THE STUDY THAT WE HAVE THAT
INCLUDES PENTOSTATIN/AM TEUZ
MAN -- WITH ALL FIVE OF THESE
STUDIES, THE THERAPEUTIC GOAL IS
MIXED DONOR AND RECIPIENT
CHIMERISM.
I'D LIKE TO THANK BLUEBIRD BIO,
THEY PROVIDED DATA ON THE NUMBER
OF PATIENTS AND PERSON YEARS AND
YOU CAN SEE THAT THEIR AT RISK
TIME WAS 112 PERSON YEARS AND
THE INCIDENCE OF AML WAS 1.79
PER 100 PERSON YEARS, WHICH IS
SIMILAR TO WHAT WE SEE IN OUR
STUDIES AT THE NIH.
BOTH WERE GROUP A PATIENTS AN
AND -- THIS COMPARES TO TWO
LARGER STUDIES WHICH IS MOSTLY
PEDIATRIC PATIENTS AND WHERE
BOTH OF THE PATIENTS UNDERWENT
MYELOBLAITIVE TRANSPLANT.
AT RISK TIME AGES FROM OVER 1600
TO 1800 PERSON YEARS, AND NONE
OF THE PATIENTS WERE REPORTED TO
DEVELOP MBS OR AML.
THE THERAPEUTIC GOAL OF THESE
STUDIES IS FULL DONOR CHIMERISM.
SO THE INCIDENCE IS HIGHEST IN
ADULTS WITH GRAFT FAILURE --
GENE THERAPY FOR SICKLE CELL
DISEASE.
I MENTIONED EARLIER THAT THE
ABSOLUTE RISK OF AML IS LOW IN
PATIENTS WITH SICKLE CELL WHO
DON'T UNDERGO CURATIVE THAIMPLET
WE REPORTED THREE OF OUR
PATIENTS DEVELOPING AML -- SO
THE RATE OF AML IS APPROXIMATELY
89 TIMES HIGHER IN ADULTS
FOLLOWING TRANSPLANT FOR SICKLE
CELL DISEASE, RESULTING IN GRAFT
FAILURE COMPARED TO THOSE WITH
SICKLE CELL DISEASE WHO DO NOT
RECEIVE CURATIVE THERAPY.
WHY IS THE INCIDENCE OF
AGGRESSIVE MYELOID MALIGNANCIES
HIGHER IN ADULTS AFTER GRAFT
FAILURE AND GENE THERAPY FOR
SICKLE CELL DISEASE?
THERE'S MULTIPLE POSSIBLE
REASONS THAT NEED FURTHER
EX-PARTICULARRATION.
I SAID EARLIER THAT PATIENTS
WITH SICKLE CELL DISEASE WHO ARE
OLDER AND WHO HAD MORE SEVERE
DISEASE WERE MORE LIKELY TO
DEVELOP LEUKEMIA.
AT THE NIH, WE TRANSPLANT OLDER
PATIENTS THAT ARE TYPICAL AND
PATIENTS WITH MORE SEVERE
DISEASE THAT ARE -- COMPARED TO
THE PEDIATRIC POPULATION, WE USE
TOTAL BODY RADIATION VERSUS
CHEMOTHERAPY-BASED CONDITIONING,
AND IN THE SETTING OF GRAFT
FAILURE AND ALSO WITH GENE
THERAPY, THERE'S A REQUIREMENT
OF REGENERATIVE HEMATOPOEISIS.
SO BEFORE GOING ON, I WANT TO
TALK ABOUT THE HEALTHY
POPULATION AND IMPORTANT TO NOTE
THAT IN THIS STUDY, CLONAL
HEMATOPOEISIS -- FREQUENCY OF
AROUND -- MUTATIONS THAT HAD A
GRANULAR FREQUENCY OF 3-POINT --
PERCENT OR HIGHER.
YOU CAN SEE THAT THE PREVALENCE
OF CLONAL HEMATOPOEISIS IS RARE
IN PEOPLE LESS THAN 40 YEARS OF
AGE AND IT INCREASES 10% AND
HIGHER IN THOSE WHO WERE 7 YEARS
OF AGE AND OLDER.
ALSO IN THE HEALTHY POPULATION,
THE GENES MOST COMMONLY IMPACTED
ARE DNMT3A, ASXL1 AND TET2.
SO I'VE SAID WE'VE HAD FIVE
PATIENTS DEVELOP MDS OR AML
AFTER OUR TRANSPLANT, AND FOUR
OF THE PATIENTS HAD NEXT
GENERATION SEQUENCING DONE AT
THE TIME OF THE DIAGNOSIS, AND
ALL FOUR PATIENTS HAD PATHOGENIC
TP53 MUTATIONS.
SO WASN'TED TO KNOW IF THEY WERE
CAUSED BY RADIATION WE GAVE THE
PATIENTS OR AS A RESULT OF
SICKLE CELL DISEASE, THE STRESS
AND INFLAMMATION OR IF THEY WERE
ALREADY PRESENT AT BASELINE.
THIS FIGURE ACTUALLY SHOWS
MR. SMITH'S DATA.
YOU CAN SEE AT THE TIME OF HIS
MDS DIAGNOSIS, HE HAD A TP53
MUTATION WITH A -- FREQUENCY OF
24%.
WHEN WE WENT BACK TO HIS
BASELINE BLOOD SAMPLES THAT WE
COLLECTED BEFORE WE DID
ANYTHING, THAT SAME MUTATION WAS
PRESENT WITH THE GRANULAR
FREQUENCY MUCH LOWER AT 0.3%.
AFTER GRAFT REJECTION, THE
PATIENT SUBSEQUENTLY DEVELOPED
MDS.
IN THE SECOND FIGURE, YOU SEE
OUR SECOND PATIENT WHO DEVELOPED
MDS AND HIS TP53 MUTATION WAS
DIFFERENT AND IT HAD A VERY LOW
FREQUENCY OF JUST ABOUT 3% AT
THE TIME OF HIS MDS DIAGNOSIS,
AND WHEN WE WENT BACK TO
BASELINE SAMPLES, THAT SAME
MUTATION WAS PRESENT, MUCH
LOWER, VERY LOW FREQUENCY, AS
WELL AS 0.03%.
GRAFFITI AFTER GRAFT REJECTION
IT EXPANDED AND THE PATIENT
DEVELOPED MDS.
SO THESE ARE THE RESULTS I JUST
TOLD YOU ABOUT THE OTHER TWO
PATIENTS.
A THIRD PATIENT HAD A TP53
MUTATION WITH A FREQUENCY OF 58%
AND AGAIN WE WENT BACK TO THE
SAME BASELINE SAMPLE, THE SAME
MUTATION WAS PRESENT, AND THE
FOURTH PATIENT HAD A TP53
MUTATION WITH A DIF OF 79% OF
AML DIAGNOSIS AND WHEN WE WENT
BACK TO THE BASELINE EXAMPLE, WE
WERE NOT ABLE TO DETECT, --
0.06%, AND INCREASE ONE YEAR
LATER TO 0.34% AND SIX MONTHS
LATER IT INCREASED TO THE 79%
AND SHE DEVELOPED AML.
SO AT BASELINE, EITHER THE
MUTATION WAS AT SUCH A LEVEL WE
WEREN'T ABLE TO DETECT IT OR IT
WASN'T PRESENT.
SO WHAT ABOUT OUR PATIENTS WHO
ARE NOT DEVELOPING LEUKEMIA?
WE WANTED TO LOOK AT THE TP53
MUTATION FIRST IN A SET OF
PATIENTS WHO HAD BROAD FAILURE.
SO ALL OF THE CASES EXCEPT ONE
HAD HOMOZYGOUS SICKLE CELL
DISEASE.
ALL OF THEM HAPLOIDENTICAL
TRANSPLANT.
THE AGE AT THE TIME OF
TRANSPLANT RANGED FROM 20 TO 506
YEARS.
NONE OF THEM WERE FOUND TO HAVE
TP53 MUTATIONS BEFORE THE
TRANSPLANT.
THREE OF THE PATIENTS ARE
DECEASED AND FOLLOW-UP RANGED
FROM 40 1/2 TO 12 YEARS.
THE EIGHT PATIENTS REMAINING
GRAFTED, ALL HAD HOMOZYGOUS
SICKLE CELL DISEASE, HALF
UNDERWENT HAPLOIDENTICAL
TRANSPLANT, AGE RANGE FROM 10 TO
50 YEARS AT THE TIME OF
TRANSPLANT AND AGAIN, WE DID NOT
DETECT ANY TP53 MUTATIONS AT
BASELINE WITH FOLLOW-UP RANGING
FROM 4 YEARS TO 9 YEARS POST
TRANSPLANT.
WHAT ABOUT THE BASELINE
PREVALENCE IN PATIENTS WITH
SICKLE CELL DISEASE WHO HAVE NOT
RECEIVED CURATIVE THERAPY?
A VERY LOW FREQUENCY OF 10% IS
ASSOCIATED WITH A PREDISPOSITION
TO MYELOID MALIGNANCY
DEVELOPMENT, SO -- AND
COLLEAGUES ANALYZED WHOLE GENOME
SEQUENCING DATA AND 71,000
UNAFFECTED CONTROLS.
WE WERE ABLE TO RELIABLY DETECT
MOST MUTATIONS ABOVE 5% AND AT
THIS LEVEL, THEY WERE NOT ABLE
TO DETECT A DIFFERENCE IN THE
PREVALENCE OF CLONAL
HEMATOPOEISIS BETWEEN GROUPS.
-- AND COLLEAGUES ANALYZED
SEQUENCING DATA IN 1400
INDIVIDUALS WITH SICKLE CELL
DISEASE AND JUST UNDER 7,000
UNAFFECTED CONTROLS.
THEY WERE ABLE TO DETECT THE
AMOUNT OF -- AS WELL AS 2 1/2%.
THE MEAN AGE OF THE PATIENTS
WITH SICKLE CELL DISEASE WAS
YOUNGER, AT 24 YEARS VERSUS 50
YEARS, AND DESPITE THEM BEING
YUN GER, THEY FOUND 15 --
MUTATIONS AND -- WITH SICKLE
CELL DISEASE WITH YOUNGEST BEING
17 YEARS AND 199 MUTATIONS AND
189 CONTROLS WITH THE YOUNGEST
BEING 34 YEARS.
THEY ALSO FOUND TWO PATIENTS
BETWEEN 23 AND 36 YEARS OF AGE
WHO HAD TP53 MUTATIONS WITH A
VAF RANGING FROM 7% TO 26%, AND
THIS IS DEFINITELY HIGHER
FREQUENCY THAN WE WOULD HAVE
EXPECTED.
SICKLE CELL DISEASE STATUS WAS
INDEPENDENTLY ASSOCIATED WITH
THE INCREASE IN CH, AND AT THE
AGE OF 50 YEARS, THE PROBABILITY
TO DETECT THE CH MUTATION WAS 7%
IN SICKLE CELL DISEASE AND 0.7%
IN CONTROLS.
IT'S ALSO IMPORTANT TO REMEMBER
THAT THE TRUE PREVALENCE OF
ULTRA DEEP HEMATOPOEISIS IN
PATIENTS WITH SICKLE CELL
DISEASE MAY BE HIGHER AND
CLINICALLY RELEVANT IN THE
SETTING OF -- I'M WORKING ON A
MULTICENTER COLLABORATION
THROUGH A U01 AWARD WITH
INVESTIGATORS AT HOPKINS AND
VANDERBILT AND OTHER SITES
CALLED COALESCE, AND WE'RE
LOOKING AT THE LONG TERM HEALTH
EFFECTS OF CURATIVE THERAPIES IN
PATIENTS WITH SICKLE CELL
DISEASE AND WE HIGH POTASSIUM
SEISE THAT AFTER GRAFT FAILURE
OR GENE THERAPY, THE STRESS OF
SWITCHING FROM HOMEOSTATIC TO
REGENERATIVE HEMATOPOEISIS BY
AUTOLOGOUS CELLS DRIVES CLONAL
EXPANSION AND TRANSFORMATION OF
PRE-EXISTING PRELIG NANT CLONES
EVENTUALLY RESULTING IN AML/MDS.
HOW TO POTENTIALLY MITIGATE THE
RISK.
SO THIS REPRESENTS -- AGING AND
COMORBIDITIES THEY MAY DEVELOP
THIS LOW LEVEL SOMATIC MUTATION
THAT IF THEY DON'T RECEIVE
CURATIVE THERAPY, THEY DON'T
EXPAND SO THAT MOST PATIENTS
WITH SICKLE CELL DISEASE DON'T
DEVELOP MYELOID MALIGNANCIES.
HOWEVER, IN THE SETTING OF GRAFT
REJECTION OR GENE THERAPY, A
PERIPHERAL STRESS INVOLVED LEADS
TO CLONAL EXPANSION AND FUTURE
MYELOID MALIGNANCY DEVELOPMENT.
I MENTIONED THAT BOTH OF THE
GENE THERAPY PATIENTS ARE IN
GROUP A, SO THE CELL DOSE THEY
RECEIVED WAS LOWER AND THEY
POTENTIALLY HAD TO UNDERGO
MORE -- STRESS, SO THAT'S A
POSSIBLE REASON WE'VE ONLY SEE
AML IN GROUP A PATIENTS TO DATE.
IF THERE WAS A GENETIC RISK
FACTOR WE'RE ABLE TO IDENTIFY
AND THE PATIENT HAD IT, WE COULD
RECOMMEND ALLOGENEIC -- THAT'S
BECAUSE MOST DONORS ARE YOUNG SO
THEY'RE NOT LIKELY TO HAVE
CLONAL HEMATOPEE HEMATOPOEISIS-
EXTREMELY RARE.
IF THEY DIDN'T HAVE A GENETIC
RISK FACTOR, WE COULD RECOMMEND
ANY KIND OF CURATIVE THERAPY
INCLUDING GENE THERAPY OND GENE
EDITING BUT UNFORTUNATELY
THERE'S NO -- THAT ACTUALLY
EXIST -- IN MY LAB OR OUTSIDE
THE NIH.
SO HOW DO WE COUNSEL PATIENTS
ABOUT THE BASELINE RISK -- I
WROTE THIS WILL MANUSCRIPT AND
THIS REPRESENTS OUR OPINION.
THE PRESENCE OF CH MAY GUIDE THE
THERAPEUTIC DECISIONS IN
PATIENTS WITH SICKLE CELL
DISEASE.
INDIVIDUALS WITH HIGH RISK SUCH
AS TP53 MUTATIONS SHOULD BE
OFFERED CURATIVE THERAPIES
INTENDED TO INDUCE FULL DONOR
CHIMERISM.
ALTERNATIVELY, PATIENTS WITHOUT
DETECTABLE CH OR HEREDITARY
CANCER PREDISPOSITION SYNDROMES
COULD BE OFFERED GENE
THERAPY/GENE EDITING.
NO RELIABLE BASELINE SCREENING
STUDIES ARE CURRENTLY AVAILABLE
TO ASSESS THE RISK OF MYELOID
MALIGNANCY DEVELOPMENT AFTER
CURATIVE THERAPY FOR SICKLE CELL
DISEASE.
SO IN SUMMARY, HLA MATCHED --
OFFER CURATIVE OPTIONS FOR
CHILDREN AND ACUL ADULTS WITH SE
CELL DISEASE.
WHILE -- THE ABSOLUTE RISK IS
LOW.
THE INCIDENCE OF MYELOID
MALIGNANCY DEVELOPMENT IS HIGHER
THAN EXPECTED AFTER GRAFT
FAILURE AND GHEEN THE GENE THERR
SICKLE CELL DISEASE.
WHILE WE DON'T KNOW WHY OUR
PATIENTS HAVE A HIGHER RISK OF
MALIGNANT MYELOID MALIGNANCIES,
FUTURE PROTOCOLS HAVE SHIFTED
FROM -- TO FULL DONOR CHIMERISM.
NO RELIABLE BASELINE SCREENING
STUDIES ARE CURRENTLY AVAILABLE
TO ASSESS THE RISK OF MYELOID
MALIGNANCY DEVELOPMENT AFTER
CURATIVE THERAPY FOR SICKLE CELL
DISEASE.
THE RISK OF MYELOID MALIGNANCY
DEVELOPMENT AFTER CURATIVE
THERAPY FOR SICKLE CELL DISEASE
SHOULD BE CONSIDERED IN THE
CONTEXT OF THE RISK OF EARLY
MORTALITY IN ADULTS WITH SICKLE
CELL DISEASE.
AND THE LONG-TERM FOLLOW-UP IS
CRUCIAL TO EVALUATE THE
LONG-TERM HEALTH EFFECT OF
CURATIVE THERAPY IN PATIENTS
WITH SICKLE CELL DISEASE.
AND I WANT US TO END BY TALKING
ABOUT THE DIRECTION THE -- IS
GOING IN ORDER TO TRY TO
INCREASE THE CHANCE OF --
CHIMERISM.
SO I'VE TOLD YOU WE'VE HAD TWO
DIFFERENT -- PROTOCOLS TO DATE.
THE Y AXIS SHOWS THE PROPORTION
OF PATIENTS WHO HAVE NOT
EXPERIENCED REJECTION, AND YOU
CAN SEE WITH THE SECOND PHOTO WE
ADDED -- WITH A SIGNIFICANTLY
HIGHER PROPORTION -- GRAFT
REJECTION SO THAT'S THE GOOD
NEWS.
THE BAD NEWS IS THAT TWO
PATIENTS DEVELOPED -- FIVE --
PROLIFERATIVE DISEASE WITH ONE
OF THEM DYING, SO THE PROTOCOL
CLOSED TO A COOL IN NOVEMBER OF
2023.
SO WITH OUR FIRST HAPLOIDENTICAL
PROTOCOL, THERE WAS A HIGH RATE
OF GRAPH REJECTION AND
AGGRESSIVE MYELOID MALIGNANCY.
SO WE HYPOTHESIZED WE DIDN'T
GIVE THEM ENOUGH
IMMUNOSUPPRESSION.
WITH THE SECOND PROTOCOL, THERE
WAS A HIGH RATE OF VIRAL DISEASE
AND HYPERINFLAMMATORY
COMPLICATIONS, SO WE HAD
HYPOTHESIZED WE GAVE THEM TOO
MUCH IMMUNOSUPPRESSION.
SO WE NOW HYPOTHESIZE THAT A
MODERATE AMOUNT OF AMINO -- AND
INCREASED MILE LOW SUPPRESSION
WILL MAINTAIN A LOW RATE OF
GRAFT REJECTION WHILE AVOIDING
UNACCEPTABLE TOXICITIES.
SO THIS FIGURE HERE SHOWS THE
ANTIGEN ENGAGING THE T-CELL
RECEPTOR.
THIS IS KNOWN AS SIGNAL ONE.
AND IN THE SETTING OF
CO-STIMULATION OR SIGNAL TWO,
THERE'S A NORMAL IMMUNE
RESPONSE.
THE -- ALLOWS -- SO THE T-CELL
ENTERS AN ANERGIC STATE AND
WE'RE -- SO WITH THIS NEW
PROTOCOL, DETAILING FOR IG, AND
IT ALSO -- TO OCCUR BUT IT
BLOCKS SIGNAL TWO, SO --
IMMUNOLOGIC TOLERANCE.
SO THE PROTOCOL -- MODERATE
AMOUNT OF IMMUNOSUPPRESSION.
THE INCREASING AMOUNT OF
MYELOSUPPRESSION, WE'VE INCLUDED
AN UNCONJUGATED ANTIBODY THAT
FUNCTIONALLY BLOCKS INTERACTION
WITH STEM CELL FACTOR, LEADING
TO STEM CELL DEATH.
SO THIS IS OUR NEW PROTOCOL THAT
JUST OPENED THIS YEAR.
THIS IS THE FIRST COHORT AND
THIS PROTOCOL IS TARGETING
PATIENTS WHO HAVE HEART, LUNG
AND KIDNEY IMPAIRMENT, INCLUDING
PATIENTS ON DIALYSIS, WHO ARE
NOT ABLE TO UNDERGO TRANSPLANT
OUTSIDE THE NIH.
SO WITH THE FIRST COHORT,
PATIENTS RECEIVED BRIQU LI.
LIMAB, ALEMTUZUMAB, AS WELL AS .
IF TOO MANY PATIENTS EXPERIENCE
REJECTION -- WHERE EVERYTHING
REMAINS THE SAME EXCEPT WE ADDED
A SECOND DOSE OF PT5.
WE TRANSPLANTED TWO PATIENTS AND
TO DATE, BOTH OF THEM ARE FREE
OF SICKLE CELL DISEASE.
SO I'D LIKE TO THANK THE
PATIENTS AND THEIR FAMILIES, I'D
LIKE TO THANK ALL MY LAB
MEMBERS, ESPECIALLY EMILY, THE
TISDALE LAB, THE HOURIGAN LAB
DID ALL THE TP53 SEQUENCING.
I'D LIKE TO THANK THE PROTOCOL
SUPPORT TEAM, THE ALESCE, NHLBI
FOR BEING AN ADVOCATE FOR ME AND
FOR PROVIDING FUNDING NOW THAT
WE'RE DOING SOME WORK ON GENETIC
RISK FACTORS, AND THE CLINICAL
STAFF OF THE CRC.
SO THANK YOU, I'M HAPPY TO TAKE
ANY QUESTIONS.
[APPLAUSE]
>> COURTNEY, THAT WAS BRILLIANT.
SO MANY QUESTIONS.
BUT JUST ONE.
AS YOU KNOW, THE CLINICAL
EXPRESSION AND THE GENETIC
ARCHITECTURE OF SICKLE CELL
DISEASE VARIES ACROSS SO MANY
DIFFERENT POPULATIONS.
THE QUESTION I HAVE WITH THE CH
MUTATION, THE PREVALENCE YOU
SHOWED, WHAT SICKLE CELL
POPULATIONS WERE STUDIED?
>> SO WE TRANSPLANT PATIENTS
FROM ALL OVER THE WORLD HERE, SO
WE HAVE TRANSPLANTED PATIENTS
FROM DIFFERENT COUNTRIES IN
AFRICA, SOME FROM THE CARIBBEAN,
FROM SOUTH AFRICA, FROM ALL
OVER.
THAT'S THE THING I REALLY LOVE
ABOUT NIH IS WE CAN TRANSPLANT
ANYBODY WE WANT.
SO OUR POPULATION IS VERY
DIVERSE.
IT'S MOSTLY AFRICAN AMERICANS
BUT THERE ARE PEOPLE FROM -- OF
THE COUNTRY.
WHEN YOU LOOK AT THE LARGER
STUDIES, IT'S ALL AMERICAN-BASED
STUDIES, MOSTLY AMERICANS.
>> RIGHT, SO OF THOSE PATIENTS S
WERE RESIDENTS IN THE UNITED
STATES?
>> IN THE LARGER STUDY BUT NOT
OUR STUDY.
>> OKAY, WE CAN TALK MORE ABOUT
THAT.
>> FIRST CONGRATULATIONS ON A
WONDERFUL TALK AND A GREAT BODY
OF WORK AND EXCITING TO SEE
WHERE THIS LEADS.
>> THANK YOU.
>> I HAD A QUESTION ON ONE OF
YOUR EARLIER SLIDES.
YOU MENTIONED THE POPULATION OF
SICKLE CELL PATIENTS, ONLY 60%
WERE ON HYDROXYCHLOROQUINE --
HYDROXYUREA.
SORRY.
I'M WONDERING, THIS IS A LITTLE
OFF TARGET FROM WHERE YOUR WORK
IS, BUT HOW DO WE GET MORE OF
OUR PATIENTS WITH SICKLE CELL TO
GET WHAT THE STANDARD OF CARE
THERAPY SHOULD BE AT THE
PRESENT?
>> THAT'S A GREAT QUESTION, AND
I THINK THERE'S SOME FEAR
ASSOCIATED WITH HYDROXYUREA IN
PATIENTS AND EVEN IN PHYSICIANS
WHERE THERE IS A CONCERN, SO I
ALWAYS WANT TO MAKE THE POINT --
ASSOCIATED WITH LEUKEMIA, SO I
THINK IT'S REALLY ABOUT
INCREASING AWARENESS.
I KNOW NHLBI IS PUTTING A LOT OF
FUNDING INTO TRYING TO DO THAT,
TO REALLY TRY TO -- ONE PATIENT,
HE WOULDN'T TAKE HYDROXYUREA --
STARTED IT RIGHT AWAY.
SO I THINK IT'S REALLY ABOUT
EDUCATION NOT ONLY OF THE
PATIENTS BUT ALSO THE PROVIDERS
AND GETTING THE -- GETTING MORE
PEOPLE INTERESTED IN SICKLE
CELL --.
>> ANY OTHER QUESTIONS FOR
DR. FITZHUGH?
>> CAN I ASK A QUICK QUESTION, I
APOLOGIZE IF THIS WAS MY
IGNORANCE.
THIS WAS REALLY INTERESTING, A
GREAT BO DEAL BODY OF WORK.
THANK YOU.
SO THE MOST COMMON DRIVERS OF,
YOU KNOW, HEMATOPOEISIS ARE --
AND DOSE THREE.
AND IT SEEMS LIKE THE HYPOTHESIS
IS THAT THE STRESS OF
HEMATOPOEISIS, YOU KNOW, YOU
WOULD HAVE TO -- ADVANTAGEOUS
PROLIFERATION, BUT WHY IS IT,
YOU KNOW, A DIFFERENT DRIVER IN
SICKLE CELL DISEASE?
WHAWHY IS IT NOT WHAT IS IN THE
COMMON POPULATION?
>> I SHOWED YOU THE TWO PATIENTS
I HAD TP53 MUTATIONS, MOTORS
COMMON WE FOUND WAS -- IT IS
STILL COMMON IN SICKLE CELL BUT
THE FREQUENCY OF TNA DAMAGE
RESPONSE GENES CAUSING TP53,
TP1MD IS MORE COMMON IN PATIENTS
WITH SICKLE CELL DISEASE AND WE
DON'T KNOW EXACTLY WHY.
IT'S ALMOST LIKE -- EVEN
PATIENTS THAT AREN'T GETTING
TRANSPLANTED, THEY CAN
DEVELOP -- LOOKS LIKE
THERAPY-ASSOCIATED LEUKEMIA.
SO THERE'S SOMETHING ABOUT THEIR
BONE MARROW -- THERE'S SOMETHING
ABOUT -- INFLAMMATION OR
WHATEVER THAT'S LEADING TO
THE -- SOMETHING THAT WE'RE
STUDYING NOW.
>> SO TP53 IS MORE COMMON IN THE
SICKLE CELL MUTATION AND SICKLE
CELL POPULATION THAN BEFORE?
>> MORE COMMON THAN WE EXPECTED,
THAT'S RIGHT.
>> OKAY, THANK YOU.
>> ANY OTHER QUESTIONS FOR
DR. FITZHUGH?
I DON'T SEE ANY.
THANK YOU VERY MUCH FOR A
WONDERFUL TALK.
[APPLAUSE]
WE'LL NOW TAKE A 30-MINUTE BREAK
SO YOU CAN WALK ACROSS THE HALL
AND GET SOME LUNCH.
WE'LL RECONVENE AT ABOUT 10:01.
>> ALL RIGHTY.
WELCOME BACK.
HOPE YOU ENJOYED THAT BREAK.
WE NOW MOVE TO THE FINAL AGENDA
ITEM ON TODAY'S MEETING, FOR
TODAY'S MEETING, VOTING ON THE
CONCEPTS FOR THIS ROUND.
HOWEVER, BEFORE WE PROCEED, I
HAVE SOME REMINDERS.
FOR DECISION LENS TECHNICAL
ISSUES, WHEN YOU'RE LOOKING AT
THE CONCEPTS AND VOTING, FOR ANY
TECHNICAL ISSUES, WE HAVE KAANAN
HERE FROM DECISION LENS AND
AFTER HE PERFORMS THE LIVE DEMO,
HE WILL BE HERE TO LEND
ASSISTANCE SHOULD YOU NEED THAT.
BRIAN GLEASON WILL PROVIDE
BACKUP SUPPORT AND FOR MORE
TECHNICAL SUPPORT WHICH IS
ONLINE, SO YOU SHOULD HAVE THOSE
EMAIL ADDRESSES.
THEY WILL BE DISPLAYED ON THE
SCREEN WHEN YOU PULL UP THE
APPLICATION, SO IF YOU NEED
TECHNICAL SUPPORT, YOU CAN TRY
CANAAN AND IF HE CAN'T HELP YOU,
THEN THEY'LL FORWARD ON TO THE
TECH ONLINE.
WITH THAT, I'LL TURN IT OVER TO
CANAAN FOR THE DEMO.
>> ALL RIGHT, GREAT.
HI, EVERYBODY.
I'M CANAAN GABLEY FROM DECISION
LENS.
THANK YOU ALL FOR HAVING YOU US
BACK.
WI'LL BE TAKING YOU THROUGH THE
DEMONSTRATION OF DECISION LENS.
WE'LL ALSO BE HERE ALL DAY IN
CASE YOU HAVE ANY QUESTIONS OR
RUN INTO ANY TECHNICAL ISSUES.
SO FOR THOSE THAT WILL BE
PARTICIPATING IN THE VOTING, YOU
SHOULD HAVE RECEIVED AN EMAIL
FROM
ADMINISTRATOR@DECISIONLENS.COM.
YOU CAN USE THE INSTRUCTIONS IN
THAT EMAIL TO DIRECTLY ACCESS
DECISION LENS AND GET LOGGED IN.
SO ONCE YOU ACCESS DECISION
LENS, YOU'LL COME TO A LOGIN
PAGE, YOU NEED YOUR EMAIL AND
PASSWORD IN ORDER TO GET IN.
THERE IS A FORGOT PASSWORD
OPTION ON THE SCREEN TO MANUALLY
RESET IT OR IF YOU NEED MORE
HELP, LET US KNOW AND WE'LL COME
HELP.
ONCE YOU GET LOGGED IN, YOU'LL
SEE WHAT IS DISPLAYED ON THE
ZOOM AND ALSO ON THE TOP OF THE
SCREEN HERE, THERE'S GOING TO BE
ONE TASK CALLED RATE
ALTERNATIVES FOR THE PORTFOLIO
TITLED IDP JUNE 2024 COUNCIL.
ALL YOU'LL NEED TO DO IS CLICK
ON THE TASK AT THE TOP.
YOU'LL SEE THAT WE ARE RATING 15
CONCEPTS HERE, AND YOU'LL SEE
THEM IN ORDER ON THE MIDDLE OF
THE SCREEN.
SO TO BEGIN, WE'LL JUST HAVE YOU
CLICK ON 3938, WHICH IS THE
FIRST ONE.
AND THIS WILL BRING UP THE
CONCEPT.
SO YOU'LL SEE THE BLUE TEXT AT
THE TOP IS THE CONCEPT.
YOU WANT TO GET A LITTLE BIT
MORE INFORMATION ON THE CONCEPT,
AND THE DETAILS BEHIND IT, YOU
CAN DO THAT BY CLICKING AT THE
BLUE TEXT ON THE TOP, THE
CONCEPT TITLE.
YOU'LL SEE THAT WILL OPEN UP THE
SIDECAR HERE.
YOU CAN SCROLL, READ ALL YOU
NEED.
THEN YOU'LL PROCEED TO WORK DOWN
THE PAGE.
SO THE PURPLE TEXT ARE THE
CRITERIA THAT YOU'LL BE
EVALUATING THE CONCEPT AGAINST.
SO THE FIRST ONE BEING
IMPORTANCE OF THE SCIENTIFIC,
MEDICAL, PUBLIC HEALTH OR
RESEARCH-RELATED QUESTIONS
OPPORTUNITY.
IF YOU CLICK ON THE PURPLE TEXT,
YOU'LL SEE THE DESCRIPTION ON
THE RIGHT-HAND SIDE.
IF YOU WANT TO READ A LITTLE BIT
MORE, JUST CLICK THE "MORE"
OPTION AND YOU'LL SEE THAT
EXPANDS.
THEN FOR EACH OF THE RATING
SCALE OPTIONS FROM EXTREMELY
IMPORTANT TO NOT IMPORTANT,
YOU'LL SEE THE DEFINITIONS FOR
EACH ON THE RIGHT-HAND SIDE.
SO NOW THAT YOU'VE READ
EVERYTHING YOU NEED TO EVALUATE
THE CONCEPT AGAINST THIS
SPECIFIC CRITERION, YOU CAN GO
AHEAD AND MAKE YOUR JUDGMENT.
I THINK IT WOULD BE VERY -- IF
FOR WHATEVER REASON YOU LOSE
INTERNET, GET LOGGED OUT,
EVERYTHING WILL BE AUTO SAVED
AND YOUR PROGRESS WILL BE
TRACKED.
SO GO DOWN THE PAGE FOR EACH
CRITERION, MAKING YOUR
ASSESSMENT.
THEN ONCE YOU REACH THE BOTTOM
OF THE PAGE, YOU WILL SEE A
"NEXT" BUTTON ON THE SCREEN.
ONCE YOU'VE COMPLETED ALL SIX
EVALUATIONS FOR THE CONCEPT,
THAT WILL LIGHT UP IN ORANGE.
AND YOU CAN CLICK THE NEXT
BUTTON AND IT WILL BRING UP THE
NEXT CONCEPT.
ONE OTHER PIECE I DO WANT TO
POINT OUT, IF YOU HAVE ANY
COMMENTS THAT YOU WOULD LIKE TO
LEAVE IN THE TOOL, THIS IS VERY
HELPFUL AFTER THE FACT, SO YOU
CAN LOOK AT THEM IN A SINGLE
OUTPUT.
IF YOU HAD A COMMENT, A
QUESTION, A CONCERN, ANYTHING
THAT YOU WOULD LIKE TO RECORD IN
THE TOOL, YOU CAN USE THE SPEECH
BUBBLE OR THIS COMMENT BUBBLE
THAT'S LOCATED RIGHT NEXT TO THE
CRITERIA NAME.
WHEN YOU CLICK THAT, THE SIDEBAR
WILL OPEN UP AND YOU'LL BE ABLE
TO ENTER IN YOUR COMMENTS HERE.
SO I'M JUST GOING TO TYPE IN A
TEST COMMENT.
ONCE YOU'RE READY TO PUBLISH AND
ENTER THIS COMMENT INTO THE
TOOL, ENTER THE -- PRESS THE
ORANGE "ADD COMMENT" BUTTON AND
YOU'LL SEE THAT.
YOU WILL BE ABLE TO SEE YOUR
PROGRESS IN THE TOP RIGHT, SO AS
WE WORK OUR WAY THROUGH, YOU'LL
SEE THE PROGRESS IN THE TOP
RIGHT.
MARA AND I WILL ALSO BE
MONITORING THAT TO MAKE SURE
THAT EVERYONE IS STAYING ON
PACE.
BUT THAT SHOULD BE -- ANY
QUESTIONS OR ANYTHING THAT YOU'D
LIKE ME TO RE-EMPHASIZE?
OKAY.
WE'LL BE OVER HERE, SO IF YOU
HAVE ANY ISSUES GETTING IN,
PLEASE LET US KNOW.
AND WE'LL COME BY AND ASSIST.
THANK YOU.
>> OKAY.
THE LUNG DIVISION IS GOING TO
START US OFF.
JIM, ANY TIME YOU'RE READY.
>> OKAY, VERY GOOD.
SO SOUNDS LIKE YOU ALREADY DID
THE FIRST ONE, SO WE CAN MOVE
ON.
NO, WE'RE GOING TO START WITH --
WE HAVE FOUR.
THE FIRST TWO ARE A PACKAGE SO
REALLY THREE.
WE'RE GOING TO DO INITIATIVE
NUMBER 3938 AND 3940.
THIS IS ENTITLED VIRAL
INFECTIONS IN YOUNG -- IN THE
YOUNG LUNG.
THE FINAL CLINICAL CONSORTIUM
AND THE DATA COORDINATING
CENTER.
SO AS I SAID, THESE ARE A
PACKAGE, TWO GO TOGETHER, IT'S
THE COORDINATING CENTER AND THE
CLINICAL COORDINATING CENTERS.
SO THIS WOULD BE A NEW
CONSORTIUM THAT WE ARE PROPOSING
THAT WE BUILD THAT WILL
ELUCIDATE THE VIRAL LOWER
RESPIRATORY TRACT INFECTIONS IN
THE YOUNG LUNG, OTHERWISE KNOWN
AS VINYL.
THIS IS A DEEP PHENOTYPING
EFFORT TO UNDERSTAND BOTH THE
CLINICAL, CELLULAR AND MOLECULAR
LEVEL OF WHAT IS GOING ON IN
ABOUT 1500 KIDS, NOT QUITE A
BIRTH COHORT BUT CLOSE TO IT,
ZERO TO 2-YEAR-OLD
INFANTS/CHILDREN WHO ARE
HOSPITALIZED WITH VIRAL LOWER
RESPIRATORY TRACT INFECTIONS.
AND TO FOLLOW THESE YOUNG
CHILDREN UNTIL PRESCHOOL AGE TO
LOOK AT PULMONARY SEQUELAE.
SO I DON'T HAVE TO TELL THIS
GROUP THAT VIRAL LOWER
RESPIRATORY TRACT INFECTIONS
SUCH AS BRONG BRO -- THIS LEAD,
MANY HOSPITALIZATIONS IN THE
UNITED STATES.
ALSO THIS POPULATION
DISPROPORTIONATELY AFFECTS YOUNG
CHILDREN, THOSE BORN SOMETIMES
PREMATURE, ALSO THOSE IN LOW
SOCIOECONOMIC CIRCUMSTANCES.
SO I THINK THIS IS A VERY
IMPORTANT INITIATIVE TO BEGIN TO
LOOK AT THE PROBLEM BECAUSE
RIGHT NOW, THERE ARE NO NEW
THERAPIES TO TREAT.
MOST OF THE MANIFESTATIONS,
WHETHER IT'S BRONCHIOLITIS OR
OTHER THINGS THAT RESULT FROM
THESE LOWER RESPIRATORY TRACT
INFECTIONS -- FOR MANY, MANY
YEARS.
THE CLINICAL COURSE IS VERY
VARIED, THE RESPONSE TO THERAPY
IS ALSO QUITE VARIED, AND
PARTICULARLY WHERE THERE'S
SEVERE INFECTION, AND THESE
CERTAINLY HAVE A POWERFUL IMPACT
ON EARLY INSULTS TO THE YOUNG
LUNG, AND THEN ON TO AUTOGENY OF
THE RESPIRATORY AMINO PHENOTYPE
THAT MAY IMPACT ON FUTURE LUNG
AND AIRWAY HEALTH.
AND AGAIN, THAT SORT OF ROLLS ON
INTO ALL OF THE ISSUES WE SEE
WITH THE PEDIATRIC POPULATION,
WHETHER IT'S PEDIATRIC ASTHMA OR
OTHER KINDS OF ALLERGIC AND
IMMUNOLOGICAL CONDITIONS
AFFECTING THE YOUNG LUNG.
AND THIS CONTINUES SORT OF
UNABATED, REALLY, IN MANY WAYS
BECAUSE OF THE LACK OF REAL GOOD
WAYS TO MITIGATE AT THE EARLIEST
STAGE.
SO THIS PARTICULAR INITIATIVE
WILL ESTABLISH CLINICAL CENTERS,
COORDINATING CENTERS.
IT WILL ESSENTIALLY ENROLL THIS
COHORT THAT WE HOPE THAT WE CAN
DO HAVE, VERY EXTENSIVE DEPUTY
KNOW TYPING ON, PARTICULARLY THE
IMMUNOPHENOTYPING WHICH WE
BELIEVE IS SOMEWHAT LACKING
RIGHT NOW.
NOT ONLY WILL WE UNDERSTAND A
BIT MORE ABOUT BEST THERAPIES
AND HOW TO BEST INTERVENE IN
THESE KIDS, BUT ALSO TO BEGIN TO
REALLY PUT THE PIECES TOGETHER
THAT GO FROM INITIAL INSULT,
PATHOLOGY, TO POTENTIAL
COMPROMISE IN THAT LUNG AS THEY
AGE, AND AS THEY DEVELOP.
AND THIS KIND OF PULLS ALL OF
THAT TOGETHER IN A WAY THAT WE
HOPE, OVER TIME, THAT WE'LL
BEGIN TO LOOK -- AND YOU HEARD
EARLY, HOW CAN WE INTERVENE
EARLY?
WE CAN'T GET MUCH EARLIER THAN
THIS POPULATION, SO THIS IS A
WAY IN WHICH WE CAN REALLY START
TO REALLY PUT THE PIECES
TOGETHER.
WE THINK THIS WOULD BE REALLY A
GREAT START TO NOT ONLY
UNDERSTAND BETTER THIS CONDITION
IN YOUNG CHILDREN, ALSO
UNDERSTAND VIRAL RESPIRATORY
DISEASE, WHICH ALSO HAS, AS YOU
KNOW, RAMIFICATIONS OR
IMPLICATIONS FOR OTHER KINDS OF
RESPIRATORY INSULTS, WHETHER
IT'S VIRAL, BACTERIAL OR
OTHERWISE.
SO THIS IS A LARGE PROGRAM, IT'S
AMBITIOUS, IT'S ONE THAT TARGETS
A FRAGILE AND SOMEWHAT
UNDERREPRESENTED POPULATION.
IT'S AN IMPORTANT ONE FOR, I
THINK, US TO UNDERSTAND NOT ONLY
THE CLINICAL PROBLEM BUT ALSO
TRY TO UNTANGLE THE BIOLOGY AND
THE BASIC UNDERSTANDING OF HOW
THE YOUNG LUNG RESPONDS TO THESE
INSULTS AND HOW WE CAN GET IN,
UNDERSTAND IT BETTER AND LOOK
FOR WAYS TO BETTER TREAT IT.
SO WITH THAT, I'LL STOP.
HAPPY TO TRY TO TAKE QUESTIONS.
WE HAVE A NUMBER OF STAFF IN THE
DIVISION THAT HAVE BEEN INVOLVED
IN DEVELOPMENT OF THIS
INITIATIVE.
DRR NATAJARAN, OUR RESIDENT
PEDIATRIC INTENSIVIST, HAS BEEN
LEADING THIS EFFORT, CERTAINLY
CAN HELP ANSWER QUESTIONS IF I
CAN'T.
I'LL STOP THERE.
>> VERY IMPORTANT INITIATIVE.
OBVIOUSLY WE'LL BE STARTING
AFTER THE START OF RSV
PREVENTION, WHICH IS VERY LIKELY
TO CHANGE EPIDEMIOLOGY
TREMENDOUSLY, AND THE SECOND
COMMENT, I THINK IT'S GREAT AND
REALLY IMPORTANT THAT THE LONG
TERM OUTCOME OF ASTHMA BEING
FOLLOWED, BUT ONE OF THE THINGS
WE DON'T KNOW, THIS ASSOCIATION
HAS BEEN ESTABLISHED IN LIKE A
HUNDRED STUDIES, BUT ONE OF THE
THINGS WE REALLY DON'T KNOW THAT
I DIDN'T SEE SPECIFICALLY
ADDRESSED BUT I THINK COULD BE
VERY IMPORTANT IS REALLY
UNDERSTANDING THE SHARED GENETIC
PREDISPOSITION TO THESE TWO
DISEASES.
SEVERE BRONCHIOLITIS AND ASTHMA.
>> AGAIN, THESE ARE GREAT
COMMENTS AND CERTAINLY WE CAN
KIND OF BUILD THIS INTO IT, I
THINK IT LENDS ITSELF FOR DOING
THAT, FOR SURE.
YES.
>> I'M NOT A PEDIATRICIAN, BUT
AS AN ADULT PULMONOLOGIST, I
THINK IT IS INCREASINGLY
APPARENT HOW IMPORTANT CHILDHOOD
LUNG DISEASES ARE FOR THE
DEVELOPMENT OF CHRONIC LUNG
DISEASES.
AND UNDERSTANDING THE BASIC
MECHANISMS AND BEING ABLE TO
FOLLOW A COHORT OVER TIME IS
GOING TO BE CRITICALLY IMPORTANT
FOR INSIGHTS INTO COPD, ASTHMA
AND OTHER LUNG DISEASES.
SO I THINK THIS IS REALLY
IMPORTANT, AND I ALSO WOULD LOVE
TO SEE IT CONTINUE BEYOND THE
NEXT FIVE YEARS AND ONWARD.
>> YEAH, IT HAS TO.
I SAY THAT JOKINGLY, BUT WE
CAN'T EVEN PICK UP THAT ASTHMA
SIGNAL THAT IS SIGNIFICANT --
CAN SPEAK TO THIS MUCH BETTER
THAN I CAN, UNTIL PROBABLY
THEY'RE PRESCHOOL AGE, 5, 7,
SOMETHING LIKE THAT, SO THIS HAS
TO GO A LITTLE BIT FURTHER IF
WE'RE GOING TO TRY TO PICK UP
SOME OF THOSE LONG-TERM SIGNALS
THAT I THINK ARE CRITICAL ALSO
FOR REALLY NAILING THIS DOWN,
WHAT DOES THAT INSULT DO TO THAT
DEVELOPMENT OF THAT LATER
SEQUELLA.
>> AND I DIDN'T READ CLOSE
ENOUGH, IS THERE ANY HEALTHY
COHORT CONTROL AS PART OF THIS?
>> WELL, THAT'S AN INCREDIBLY
IMPORTANT QUESTION, AND WE HAVE
BEEN WRESTLING WITH THAT ONE.
THE BOARD OF EXTERNAL EXPERTS
BROUGHT THAT UP TOO, A
CONTEMPORARY CONTROL FOR THESE
KIDS.
AND WE DO HAVE SOME LEAPS.
IT'S NOT BUILT IN TO HAVE A
CONTROL GROUP HERE.
THAT, WE'RE LOOKING AT BUT
OBVIOUSLY IT WOULD ADD A LOT
MORE TO IT.
BUT WE DO THINK THERE MAY BE
SOME OTHER COHORTS THAT EXIST
THAT COULD POTENTIALLY ALIGN,
PARTICULARLY THOSE THAT ARE
FUNDED BY THE NIAID, EVEN THOUGH
THEY ARE NOT IN-HOSPITAL-ROW
LATED E-RELATEDEVENTS OR KIDS TG
HOSPITALIZED.
THERE IS OUTPATIENT WORK THEY'RE
DOING THAT MIGHT ALSO GIVE US
SOME -- ECHO MIGHT BE ANOTHER
PLACE THAT WE CAN LOOK AT FOR
CONTROLS THAT AGAIN MAY ALIGN.
WE HEAR YOU, WE KNOW THAT'S A
PROBLEM, AN ISSUE, AND WE'RE
TRYING TO DO WHAT WE CAN TO MAKE
SURE WE HAVE SOMETHING TO
COMPARE TO.
>> I HAVE A QUESTION, ALIGNED
EXACTLY WITH THE CONTROL ISSUE.
I SAW THE PLAN IS TO USE OTHER
COHORTS WITH LESS SEVERE
DISEASE, WHICH I THINK WOULD BE
FINE, BUT ARE THEY EQUALLY AS
TYPICALLY CHARACTERIZED AS THIS
COHORT IS OR WOULD THEY BE
ESPECIALLY IN TERMS OF LIKE
GENETIC PREDISPOSITION AND
THINGS LIKE THAT?
>> WE KNOW THAT IF WE CAN GRAB
SOME THINGS FROM ALLERGY, FROM
NIAID, WE'LL GET GOOD
IMMUNOPHENOTYPING.
BECAUSE THEY'VE ACTUALLY BEEN
INVOLVED IN HELPING US DEVELOP
THIS PROGRAM, SO WE'VE MODELED
IT AND WE'VE MADE SURE THAT THE
TYPE OF THE TYPE OF PHENOTYPING
BEING DONE HERE IS CONSISTENT
WITH WHAT THEY THINK IS
IMPORTANT AND WHAT THEY'RE DOING
IN THEIR PROGRAM.
SO THIS WILL LINE YOU PRETTY
WELL.
NOW THERE MAY NOT BE QUITE AS
MUCH PULMONARY FUNCTION
MEASUREMENTS OR OTHER THINGS WE
MIGHT DO WITH THESE KIDS THAT
THEY'RE NOT DOING, BUT WE'LL TRY
TO GET THE ALIGNMENT AS BEST WE
CAN.
IT'S NEVER GOING TO BE TOTALLY
HARMONIZED OR PERFECT, GIVEN
THAT WE'RE TRYING TO GRAB THEM
FROM DIFFERENT SOURCES AT
DIFFERENT TIMES, BUT WE'LL SEE
WHAT WE CAN DO TO GET THIS
CORRECT.
>> AND THE OTHER QUESTION I HAD
OR COMMENT IS ABOUT NEONATOLOGY
INPUT, JUST BECAUSE PRETERM
BIRTH IS SUCH A RISK FACTOR FOR
ALL OF THIS, AND I DON'T KNOW IF
THAT'S GOING TO BE JUST PART OF
THE COHORT OR YOU WILL EXCLUDE,
OBVIOUSLY BPD IS AN UNDERLYING
DISEASE AND MAJOR RISK FACTOR
FOR ANY OF THEM.
SO JUST TO MAKE SURE THAT THIS
UNIQUE NEONATAL -- PARTICULARLY
PREMATURITY WITH OR WITHOUT LUNG
DISEASE IS CONSIDERED IN THE
EQUATION.
IT WOULD BE GREAT TO INCLUDE
THEM, BUT THEY'RE SEPARATE,
DIFFERENT SUBTYPES.
>> WELL, AGAIN, THIS HAS A LOT
OF BREADTH TO IF YOU WANT TO TRY
TO CONTINUE TO EXPAND, AND WE'LL
TRY TO WRAP IN AS MUCH AS WE
CAN.
APPRECIATE THESE COMMENTS,
THOUGH.
THEY'RE VERY HELPFUL AS WE THINK
ABOUT HOW TO BEST STRUCTURE THIS
GOING FORWARD, WHAT WE CAN
COLLECT, HOW WE CAN DO IT WITHIN
A PROJECT THAT WE THINK WE CAN
MAYBE HANDLE IF THIS GOES
FORWARD.
SO APPRECIATE THAT.
IT'S VERY HELPFUL.
YES.
OTHER COMMENTS ON VINYLS?
IF NOT, IF YOU COULD GO IN TO
THE SYSTEM AND RATE EACH OF
THESE ELEMENTS.
BEFORE WE MOVE ON TO THE NEXT
ONE.
>> WE HAVE A FEW PEOPLE THAT ARE
STILL VOTING.
OR RATING.
>> GIVE US THE SIGNAL.
OH, YOU HAVE TO DO EACH ONE OF
THEM SEPARATELY.
I'M SORRY, I SHOULD HAVE
MENTIONED THAT TO BEGIN WITH.
DO THE FIRST, AND THEN GO TO THE
SECOND.
>> THEY'RE GOING TO VOTE FOR
3938 AND 3940.
>> MAYBE JUST ANOTHER MINUTE OR
SO, OR 30 SECONDS.
OKAY, I THINK YOU CAN MOVE ALONG
NOW.
>> OKAY, THANK YOU.
SO THE NEXT ONE IS CONCEPT
NUMBER 5019.
THIS IS A CONTRACT PROPOSAL, AND
THIS IS THE RENEWAL OF THE
NATIONAL SLEEP RESEARCH
RESOURCE, THE NSRR.
THIS IS A CONTRACT, THIS IS THE
RENEWAL TO CONTINUE THAT PROGRAM
AND HERE WE PROPOSE TO EXPAND
THIS VERY, VERY HIGHLY UTILIZED
SLEEP-SPECIFIC PHENOTYPE AND
PHYSIOLOGICAL SIGNAL DATA
RESOURCE TO FACILITATE PROPER
INGESTION OF NEW DATA TYPES,
MOST NOTABLY THE HUMAN CIRCADIAN
DATA, AS WELL AS THE ANNOTATION
AND ENRICHMENT OF THE SLEEP AND
CIRCADIAN MODEL ORGANISM DATA
THAT WE'D ALSO LIKE TO
INCORPORATE INTO THIS RESOURCE
AND MAKE ALL OF THAT USABLE AND
ACCESSIBLE TO THE BROADER
AUDIENCE AND COMMUNITY.
SO JUST AS A LITTLE BACKGROUND,
THE NSRR WAS STARTED A NUMBER OF
YEARS AGO.
IT WAS ACTUALLY A RESOURCE GRANT
THAT WAS SUBMITTED BY AN
INVESTIGATOR THAT THEN GOT
CONVERTED TO A CONTRACT, BUT
OVER THE YEARS, IT'S REALLY
GAINED AND EARNED GLOBAL
RECOGNITION AS THE PREMIERE DATA
SHARING REPOSITORY FOR THE SLEEP
RESEARCH COMMUNITY.
IN FACT, IT'S EVEN EXPANDED
BEYOND THE SLEEP COMMUNITY NOW.
IT'S ACCELERATED THE
FACILITATION OF RELIABLE AND
WELL ANNOTATED DATA SHARING
ACROSS MANY WELL CHARACTERIZED
COHORT STUDIES AND CLINICAL
TRIALS, BRINGS THEM ALL IN AND
ADJUSTS FOR THOSE, IT HARMONIZES
IT THE BEST THEY CAN AND MAKES
ALL OF THAT DATA AVAILABLE.
I DON'T HAVE TO TELL THIS GROUP,
SOME OF THE POLYGRAPHIC DATA IS
ENORMOUS, HUGE AMOUNTS OF DATA
CONTAINED IN SOME OF THOSE SLEEP
STUDIES, SO NSRR HAS DONE A
GREAT JOB AS AN NIH-WIDE
RESOURCE, AND IT HAS NOT ONLY
ALLOWED THAT TO HAPPEN BUT IT IS
INCORPORATED -- IT HAS
INCORPORATED NHLBI CLINICAL
TRIAL COHORTS, IT'S EVEN NOW
HOUSING INTERNATIONAL ASSETS SO
IT'S A GLOBAL RESOURCE.
IT HAS ABOUT 11,000 USERS
WORLDWIDE, HAS ABOUT 5,000 DATA
USE AGREEMENTS.
THERE ARE CURRENTLY 18 FUNDED
U.S. PROJECTS FROM ACROSS NIH
THAT FOCUS ON SLEEP AND
CIRCADIAN RESEARCH AND CLOSE TO
400 PUBLICATIONS THAT ARE COMING
OUT OF THIS RESOURCE.
SO THIS WAS ALSO REVIEWED BY THE
BOARD OF EXTERNAL EXPERTS.
THEY ALSO HAD SOME ENTHUSIASM
FOR THIS.
THE NEXT FUNDING PERIOD, THE
NSRR AS I MENTIONED, WE'D LIKE
TO EXPAND AND BRING IN SOME NEW
DATASETS, AND I MENTIONED THE
HUMAN CIRCADIAN DATA AND MODEL
ORGANISM, SLEEP AND CIRCADIAN
DATA, AND I THINK THAT GIVEN THE
SUCCESS THAT THEY'VE HAD THE
WITH THE HUMAN SLEEP DATA, THIS
SHOULD BE VERY DOABLE.
THEY THEN HAVE A PLAN TO
TRANSFORM ALL OF THAT DATA AND
THE RELATED FIELDS INTO A
RESOURCE THAT WILL ULTIMATELY
LIVE AND RESIDE WITHIN OUR OWN
DATASET, BDC, HERE AT NHLBI.
THIS IS ALSO A TIME WHERE I
THINK THEY CAN ALSO GENERATE AND
HELP ADVANCE NEW HYPOTHESES
USING ARTIFICIAL INTELLIGENCE,
MACHINE LEARNING APPROACHES, AND
REALLY MINE ALL OF THAT DATA IN
A MUCH MORE ROBUST AND
SOPHISTICATED WAY THAN MAYBE
WHAT'S BEEN DONE HERETOFORE.
SO THIS WILL OPEN UP THE
POSSIBILITY OF MAYBE NOVEL
SCIENTIFIC QUESTIONS IN SLEEP
AND CIRCADIAN, AND THEN
HOPEFULLY PROMPT SOME ADDITIONAL
RESEARCH THAT WOULD BE COMING
FROM THIS HYPOTHESIS GENERATING
KINDS OF A RESOURCE.
IT ALIGNS VERY WELL WITH THE NIH
SLEEP RESEARCH PLAN, WITH THE
NHLBI STRATEGIC REFRESH, AND WE
THINK THIS IS A VALUABLE
RESOURCE TO CONTINUE SUPPORTING.
SO WITH THAT, I'LL STOP AND I'LL
BE HAPPY TO TRY TO ANSWER
QUESTIONS HERE AS WELL.
THIS COMES FROM OUR NATIONAL
CENTER ON SLEEP DISORDERS
RESEARCH, LED BY MARISHKA BROWN
AND STAFF IN THE SLEEP CENTER,
AND THEY'VE DONE A GOOD JOB OF
REALLY TRYING TO LOOK AT THIS
LONG TERM TO MAKE SURE THIS IS
THE BEST THEY CAN BE AND WELL
UTILIZED BY THE BROADEST
COMMUNITY AS POSSIBLE.
OPEN IT UP FOR QUESTIONS.
GLL HOW M
>> HOW MUCH PEDIATRIC DATA IS
THERE OR FOCUS ON PEDIATRIC
POPULATIONS?
>> OH, BOY, THAT'S A GOOD
QUESTION.
I DON'T KNOW IF I HAVE AN ANSWER
TO THAT.
MARISHKA, ARE YOU THERE WITH US?
>> YES, I AM HERE.
>> DID YOU HEAR THE QUESTION?
WE CAN HEAR YOU.
>> YEAH, SO THANK YOU, THAT'S A
GREAT QUESTION.
WE DO HAVE QUITE A BIT OF
PEDIATRIC DATA, AND WE'RE
CONTINUING TO ACTUALLY INGEST
MORE, SO RIGHT NOW I CAN'T TELL
YOU THE EXACT NUMBER BUT NSRR
INGESTS DATA FROM ACROSS THE
LIFESPAN.
SO PEDIATRIC DATA DOES EXIST AND
SOME OF THE MOST POPULAR
PUBLICATIONS THAT HAVE COME OUT
OF NSRR HAVE COME OUT OF
PEDIATRICS AND SLEEP DISORDERED
BREATHING.
>> THANK YOU.
>> OTHER QUESTIONS ON THE SLEEP
RESEARCH RESOURCE?
THANK YOU, M MAR ISHKA.
OKAY, AS WITH THE PREVIOUS ONE,
IF YOU COULD RATE EACH OF THESE
ELEMENTS.
THIS IS 5019.
THERE'S JUST ONE HERE.
>> DR. KI
>> THE LAST ONE I'M GOING TO
PRESENT TO YOU TODAY IS NUMBER
5403.
THIS IS ACTUALLY AN NHLBI-WIDE,
IN FACT ALMOST -- NOW IT'S GOING
TO BECOME AN NIH-WIDE
INITIATIVE, AND WE WOULD LIKE TO
PARTICIPATE AS A SECONDARY
SIGN-ON WITH THE NATIONAL
INSTITUTE ON DIABETES AND
DIGESTIVE AND KIDNEY DISEASES,
AS THEY REISSUE A PROGRAM CALLED
STEP-UP, WHICH IS A SHORT-TERM
RESEARCH EXPERIENCE PROGRAM TO
UNLOCK POTENTIAL.
AS I SAID, THIS IS A
CROSS-INSTITUTE EFFORT WHERE WE
WANT TO JOIN NIDDK IN THEIR
PROGRAM THAT THEY'RE GOING TO
RENEW.
SO THIS IS A FIRST-TIME
PARTICIPATION FOR US.
THIS IS A -- THE STEP-UP PROGRAM
IS REALLY TARGETING HIGH
SCHOOL-LEVEL INDIVIDUALS THAT
WE'RE TRYING TO ATTRACT INTO
RESEARCH CAREERS.
IT WAS FORMALLY ESTABLISHED IN
2002, AS A RESEARCH EDUCATION
PROGRAM TO FUND A COORDINATING
CENTER THAT WOULD ORGANIZE THE
RECRUITMENT MENTORING AND
HANDS-ON RESEARCH EXPERIENCE FOR
HIGH SCHOOL AND PERHAPS
UNDERGRADUATE STUDENTS IN
DIVERSE GEOGRAPHIC LOCATIONS
ACROSS THE U.S. -- ACROSS THE
UNITED STATES AND U.S.
TERRITORIES.
ONE OF ITS GOALS IS TO GROW A
DIVERSE BIOMEDICAL RESEARCH
WORKFORCE THAT WOULD HELP
ADVANCE STUDENTS TO ADDITIONAL
CAREER LEVELS IN SCIENCE.
THIS IS A CRITICAL NEED, I DON'T
HAVE TO SPEAK TO THIS GROUP
ABOUT THAT.
IN FACT, WE'RE VERY EXCITED
ABOUT THIS BECAUSE IT'S ONE OF
THE FIRST TIMES THAT WE IN THIS
INSTITUTE ARE REALLY BEGINNING
TO NOW MEANINGFULLY ENGAGE WITH
HIGH SCHOOL STUDENTS FROM
DIVERSE BACKGROUNDS IN
GEOGRAPHIC LOCATIONS WHO
HISTORICALLY HAVE INADEQUATE
ACCESS TO SIGNIFICANT SCIENTIFIC
RESEARCH OPPORTUNITIES AND WE
THINK THIS STEP-UP PROGRAM IS
DESIGNED TO ADDRESS A BARRIER
AND A CHALLENGE THAT IS FACED BY
HIGH SCHOOL STUDENTS, AND THIS
PROGRAM THEN GIVES IT A BOOST TO
TRY TO ATTRACT, RETAIN AND THEN
HOPEFULLY ADVANCE THOSE STUDENTS
THROUGH TYPICAL CAREERS IN
SCIENCE.
IT'S NOVEL BECAUSE THE
COORDINATING CENTERS ARE
DISTRIBUTED GEOGRAPHICALLY
ACROSS THE COUNTRY, SO THEY
FACILITATE SORT OF A STREAMLINED
SUBMISSION, THEY REVIEW THE
APPLICATIONS IN HOUSE, THEY
MATCH THE MENTORS AND THE
STUDENTS, AND THEN THEY ENSURE
TIMELY RESEARCH INTERNSHIP.
RIGHT NOW THE HIGH SCHOOL
COORDINATING CENTERS SUPPORT 25
PARTICIPANTS ANNUALLY, AND THE
STUDENTS ENGAGE IN HANDS-ON
EXPERIENCE IN THEIR COMMUNITIES,
MOSTLY WITHIN COMMUTING DISTANCE
OF THEIR HOMES FOR EIGHT WEEKS
IN THE SUMMER.
AT THE END OF THE SUMMER, THEY
COME BACK AND -- SORRY -- THEY
ATTEND AN ANNUAL SYMPOSIUM AT
NIH HERE ON THE CAMPUS, WHERE
THEY PRESENT THEIR PROJECTS AND
THEY INTERACT WITH EACH OTHER.
SO WE THINK THIS IS A MODEST
INVESTMENT TO ADD ADDITIONAL
COORDINATING CENTERS FROM NHLBI
TO THE NIDDY COLLECTION THAT
WOULD THEN ALLOW US TO ALSO
TARGET THESE STUDENTS AND
HOPEFULLY CONVINCE THEM THAT
CARDIOVASCULAR, PULMONARY,
HEMATOLOGY AND SLEEP ARE ALSO
GOOD CAREER OPPORTUNITIES FOR
THEM TO CONSIDER AS THEY ADVANCE
IN SCIENCE.
SO I WILL STOP THERE AND ANSWER
QUESTIONS ON THIS ONE.
SORRY, WAS THERE A QUESTION?
YES, TINA.
YOU TAKE THE PRIZE HERE SO FAR.
>> I REALLY LIKE THIS.
I THINK IT'S IMPORTANT,
HOPEFULLY IMPACTFUL.
ONE IDEA THAT I'D LOVE TO SEE
ADDED TO THIS IS WE'RE TRYING TO
FIGURE OUT HOW DO THIS ON OUR
OWN BECAUSE THERE'S SO MANY
NIH-FUNDED STUDIES THAT ALREADY
ENGAGE THIS AGE POPULATION.
ONE OF THE THINGS WE'RE TRYING
TO DO IS MAKE OUR RESEARCH
PARTICIPANTS FEEL LIKE CITIZEN
SIGNISCIENTISTS SO WE'RE KIND OF
DOING THIS ON OUR OWN.
I JUST REALIZED THE AMOUNT OF
RESEARCH POTENTIAL -- THAT WE
COULD ALSO REACH WITH AN
INITIATIVE LIKE THIS TO HELP
INVESTIGATORS, THOSE OF US
TRYING TO FIGURE OUT ON OUR OWN
HOW TO MAKE OUR RESEARCH
PARTICIPANTS NOT FEEL JUST LIKE
RESEARCH PARTICIPANTS BUT
CITIZEN SCIENTISTS WOULD BE
SOMETHING REALLY NICE TO ADD TO
THIS.
>> CAN DO.
I THINK THAT'S A GREAT POINT.
I'M SURE -- WE'LL WORK WITH D.K.
ON THIS SINCE THEY'RE DRIVING
WITH BUT I THINK THEY WOULD
ABSOLUTELY CONCUR WITH YOUR
POINTS.
OKAY.
LYNN?
>> I ALSO REALLY LIKE THIS
PROGRAM AND THE CONCEPT AND THE
FACT THAT IT'S BEEN AROUND FOR A
NUMBER OF YEARS AND THERE IS
METRICS OF SUCCESS.
MY QUESTION IS, HOW LONG ARE
THOSE PARTICIPANTS FOLLOWED
AFTERWARDS, AND ARE THERE
ANOTHER MECHANISM AFTER GOING
THROUGH THIS PROGRAM TO CAPTURE
THOSE INDIVIDUALS AND CONTINUE
TO FOSTER THEIR INTEREST IN
SCIENCE?
>> I THINK THAT CAME UP WITH THE
B2 AS WELL.
CAN YOU HELP WITH THAT ONE?
BECAUSE YOU PROBABLY KNOW THE
ANSWER.
[INAUDIBLE]
>> BECAUSE ALL OF US ARE ALSO
TRYING TO INCREASE ENROLLMENT IN
MEDICAL SCHOOL OR IN OUR T -- ET
CETERA, SO WE CAN I'D -- IF WE
CAN IDENTIFY A COHORT TO
CONTINUE TO TAP INTO WOULD BE
AWESOME.
>> GOOD POINT TOO.
>> DOES THE MECHANISM PROVIDE
ANY SUPPORT FOR THE MENTORS WHO
ARE HOSTING THEM?
>> I DO NOT THINK SO.
DO YOU KNOW THE ANSWER TO THAT
ONE, MARISOL?
THEY DON'T GET A SALARY OR ANY
KIND OF COMPENSATION, DO THEY?
NO.
>> THE ONE CHALLENGE I WOULD SAY
WITH THAT IS, IT'S ONE THING FOR
RESEARCH ONE INSTITUTIONS THAT
ARE VERY WELL-FUNDED THAT HAVE
LAYERS OF PEOPLE WHO ARE ABLE TO
ENGAGE AND PROVIDE A STRUCTURED
EXPERIENCE, BUT A LOT OF
UNDERREPRESENTED INDIVIDUALS
DON'T LIVE WITHIN A CLOSE
DISTANCE TO THOSE TYPES OF
INSTITUTIONS, AND IT CAN BE
QUITE -- IT CAN TAKE A LOT OF
TIME, PARTICULARLY FOR STUDENTS
WHO ARE NOT COMING IN WITH THE
SAME SKILLSET AS VERY PRIVILEGED
STUDENTS.
IT CAN TAKE A LOT MORE TIME TO
MENTOR THAT MANY MAY NOT BE ABLE
TO SPARE, AND A LOT OF
TEACHING-INTENSIVE INSTITUTIONS,
I UNDERSTAND MAYBE THAT'S NOT
WHERE THESE ARE BASED BUT THEY
PROVIDE A GREAT ENTREE INTO
EDUCATION AND BEING ABLE TO
PROVIDE SUPPORT FOR THEM WHERE
THEY DON'T HAVE SUMMER SALARY
COVERAGE OR OTHER THINGS TO
PROVIDE A COMPREHENSIVE TRAINING
EXPERIENCE, I THINK WOULD BE
VERY IMPORTANT AND EXPAND THE
IMPACT.
>> ALL RIGHT.
WELL, THAT'S AN IMPORTANT POINT.
IT'S ONE THAT WE'LL HAVE TO TALK
TO D.K. ABOUT, GARY.
>> IT IS AN EXCELLENT POINT, AND
IT MIGHT EVEN HAVE COME UP IN IF
IN THE SENSE THAT THERE'S
CLEARLY A GOOD TRACK RECORD, BUT
THEY PROBABLY COULD USE A
BROADER DIVERSITY OF THOSE HUBS,
AND SO ACTUALLY THAT WAS ONE OF
THE THINGS ABOUT US JOINING IN.
THEY BUILD UP THE CRITICAL MASS
OF ICs THAT WOULD ENABLE TO
SEE AND THEN AS YOU SAY, HAVE
GREATER OUTREACH.
SO GREAT POINT AND SOMETHING WE
CAN WORK WITH D.K. ON.
>> ANY OTHER COMMENTS ON THIS
ONE?
IF NOT, 5043, YOU'RE RATING
THOSE ELEMENTS AS WELL.
WHERE DO WE GO NEXT?
CARDIOVASCULAR?
>> CARDIOVASCULAR.
>> WITH THAT, I'M GOING TO TURN
IT OVER TO DR. GOFF.
I THINK THEY'RE NEXT, DAVID,
CARDIOVASCULAR DIVISION?
>> ARE YOU SURE YOU'RE THROUGH?
OKAY.
SO WE HAVE FIVE CONCEPTS TO
PRESENT FROM THE TI VIS DIVISIOF
CARDIOVASCULAR SCIENCES TODAY.
WE'RE STARTING I BELIEVE WITH
CONCEPT 5027?
YES.
THAT'S ON THE SCREEN.
IT'S THE BENCH TO -- CONGENITAL
HEART DISEASE ADVANCING NEW
UNDERSTANDING IN GENOMICS
COHORT, B2B CHANGE COHORT.
IT'S A RENEWAL OF AN EXISTING
INITIATIVE BUT IT'S REALLY A
TRANSFORMATION OF AN EXISTING
INITIATIVE AND IT WOULD BE
FUNDED THROUGH A U01 MECHANISM
IF WE GO FORWARD.
IT'S A TRANSFORMATION OF
PEDIATRICS -- REFERRED TO AS THE
PCGC THAT'S HAD 15 YEARS OF
SUPPORT FROM NHLBI.
IT'S REALLY CHANGED THE
LANDSCAPE OF WHAT WE KNOW ABOUT
CONGENITAL HEART DISEASE
GENETICS.
WE NOW UNDERSTAND AN ADDITIONAL
25% OF WHAT WAS PREVIOUSLY
UNEXPLAINED IN TERMS OF JEK
DETERMINANGENETICDETERMINANTS OS
PRIMARILY NEWBORNS TO 35 YEARS
OLD AND OVER 18,000 RELATIVES,
MAKING IT ONE OF THE LARGEST
CONGENITAL HEART DISEASE COHORTS
WITH GENOMIC AND CLINICAL DATA
EVER ASSEMBLED.
SO WE PROPOSE TO LEVERAGE THESE
PREVIOUS INVESTMENTS TO
TRANSFORM THE PCGC INTO WHAT
WE'RE CALLING THE B2B CHANGE
COHORT.
THE COHORT WOULD ENHANCE THE
VALUE OF OUR EXISTING
INVESTMENTS THROUGH LONG-TERM
FOLLOW-UP OF ABOUT 6,000 CURRENT
PCGC PARTICIPANTS, AND ALLOWING
US TO ASSESS MANY CLINICAL
OUTCOMES OF INTEREST SUCH AS
HEART FAILURE AND ARRHYTHMIAS
THAT HAVE NOT YET OCCURRED BUT
WILL LIKELY OCCUR IN COHORT
MEMBERS, MANY OF WHOM AS I
MENTIONED WERE ENROLLED AS
INFANTS.
NOW THE COHORT WILL ALLOW A
UNIQUE OPPORTUNITY TO UNDERSTAND
LONG TERM CLINICAL OUTCOMES AND
HOW THEY RELATE TO A PERSON'S
UNDERLYING GENETICS.
IT WILL ALSO PROVIDE A PLATFORM
FOR MECHANISTIC STUDIES TO
ADVANCE THE CONGENITAL HEART
DISEASE FIELD TOWARD THE
DEVELOPMENT OF PRECISION BASED
CLINICAL TRIALS AND TARGETED
THERAPEUTICS.
SO WITH THE RECENT RENEWAL OF
THE PEDIATRIC HEART NETWORK,
WHICH IS KIND OF A COMPLEMENTARY
EFFORT OF THE INSTITUTE, THERE
WILL BE AN OPPORTUNITY FOR
CONTINUED COLLABORATION ACROSS
THE TRANSLATIONAL SPECTRUM.
SO THIS INITIATIVE WOULD SUPPORT
A COHORT INCLUDING COLLECTING
DATA ON LONGITUDAL CLINICAL
OUTCOMES, COMMUNITY ENGAGEMENT
TO OBTAIN A REPRESENTATIVE
COHORT, IMPORTANT PHENOTYPIC AND
SOCIAL DETERMINANTS DATA,
LEVERAGING PHENOTYPIC DATA IN
RELEVANT CONGENITAL HEART
DISEASE IN PEDIATRIC REGISTRIES
AND WOULD FACILITATE AN
IN-PERSON VISIT DURING YEAR FOUR
OR FIVE TO SUPPORT ANCILLARY
STUDIES THAT COULD BE FUNDED
THROUGH INVESTIGATOR-INITIATED
GRANT APPLICATIONS, R01, SIMILAR
TO OUR CONTRACT PLATFORM
COHORTS.
ALTHOUGH THIS WOULD BE SUPPORTED
THROUGH A COOPERATIVE AGREEMENT.
THE INITIATIVE PROPOSES A BUDGET
OF ABOUT 5 1/2 MILLION PER YEAR
FOR SEVEN YEARS, WHICH IS ABOUT
20% REDUCTION FROM THE CURRENT
PCGC BUDGET.
WE THINK THIS IS A REALLY GREAT
WAY TO LEVERAGE THE INVESTMENTS
WE'VE MADE TO DATE, AND LOOK
FORWARD TO YOUR QUESTIONS AND
COMMENTS.
>> YOU WERE VERY CLEAR.
>> APPARENTLY.
WONDERFUL!
WELL THEN -- EVERY NOW AND THEN,
RIGHT?
WHAT DO THEY SAY ABOUT SQUIRRELS
AND NUTS?
PLEASE GO AHEAD AND RATE THIS
ONE AND WE'LL MOVE ON.
YOU LET ME KNOW WHEN IT'S TIME
TO MOVE ON.
>> OKAY.
LOOKS LIKE EVERYONE IS STILL
VOTING, OR RATING.
THANK YOU, YOU CAN MOVE ON.
>> NEXT CONCEPT IS 5024, THE
GLOABL CARDIOVASCULAR FORUM,
WOMEN'S CARDIOVASCULAR HEALTH
INITIATIVE.
THIS IS A INITIATIVE THAT WOULD
BE FUNDED THROUGH SORT OF AN
OTHER OR M.O.U. TYPE OF FUNDING
ARRANGEMENT.
SO THE GCRFF, IF YOU'LL LET ME
USE THAT ACRONYM, THE GLOBAL
CARDIOVASCULAR RESEARCH FUNDERS
FORUM, IS A PARTNERSHIP MADE UP
OF 12 MAJOR CARDIOVASCULAR
RESEARCH FUNDERS INCLUDING
NHLBI, THE AMERICAN HEART
ASSOCIATION, AND OTHER FUNDERS
ACROSS CANADA, EUROPE, AUSTRALIA
AND NEW ZEALAND, THAT WAS
ESTABLISHED IN 2018 TO SUPPORT
AND PROMOTE CARDIOVASCULAR
RESEARCH.
THIS IS A SIGNIFICANT SCIENTIFIC
AREA FOR THE GCRFF BECAUSE CBD
I -- BECAUSECVD IS THE REMAININF
DEATH IN WOMEN, IT REMAINS UNDER
DID YOU STUDIED, UNDERDIAGNOSED
AND UNDERTREATED, AND MANY
UNDERSTUDIED AREAS FROM A
LIFESPAN PERSPECTIVE.
THE FUNDING AND STRUCTURE OF
THIS IS THAT WE'RE BEING ASKED
AS A PARTICIPANT IN THE GCRFF
WITH OTHER FUNDING AGENCIES TO
CONTRIBUTE $1.9 MILLION, WHICH
IS THE SAME AS THE OTHER LARGER
FUNDING ORGANIZATIONS IN THIS
CONSORTIUM, INCLUDING THE HEART
ASSOCIATION, THE LE DUKE
FOUNDATION AND BRITISH HEART
FOUNDATION.
SO $1.9 MILLION WOULD BE OUR
SHARE OF THE TOTAL OF
$10 MILLION TO FUND THIS INITIAL
FIVE-YEAR RESEARCH PROJECT ON
WOMEN'S CARDIOVASCULAR HEL.
HEALTH.
THE INTENT OF THE INITIATIVE IS
TO FUND A COHESIVE RESEARCH
PROGRAM THAT WOULD TAP INTO
EXPERTS FROM AROUND THE WORLD
AND DELIVER THE TYPE OF IMPACT
THAT NO SINGLE INSTITUTION OR
COUNTRY CAN DELIVER ON ITS OWN.
ONE RESEARCH GRANT WILL BE
AWARDED IN FISCAL YEAR 26, THE
HIGHEST RATED INTERNATIONAL
RESEARCH NETWORK APPLICATION.
ALTHOUGH IT'S BEING REFERRED TO
AS A NETWORK, IT'S REALLY MORE
OF WHAT WE WOULD PROBABLY CALL A
CONSORTIUM.
FUNDING WILL BE OPEN TO LEAD
INSTITUTIONS FROM A GCRFF
COUNTRY.
IT'S EXPECTED THAT THE AWARD
WOULD BE MULTIDISCIPLINARY,
MULTI-INSTITUTIONAL AND
MULTI-COUNTRY AND STRUCTURE, AND
THE LEAD INSTITUTION CAN PARTNER
WITH INVESTIGATORS FROM
NON-GCRFF COUNTRIES.
THIS IS AN ASPECT THAT WAS
REALLY IMPORTANT TO US AS AN
INSTITUTE TO MAKE SURE THAT THE
IMPACT OF THIS RESEARCH WOULD GO
BEYOND HIGH-INCOME COUNTRIES AND
REALLY ADDRESS ISSUES OF
IMPORTANCE TO WOMEN'S
CARDIOVASCULAR HEALTH GLOBALLY,
WHERE 80% OF CARDIOVASCULAR
CONDITIONS AND DISEASES OCCUR IN
LOW AND MIDDLE INCOME COUNTRIES.
SO SOME OF THE POTENTIAL
RESEARCH TOPICS EXAMPLES INCLUDE
ADVANCING EFFECTIVE PREVENTION
AND TREATMENT OF CVD IN WOMEN
ACROSS DIFFERENT COUNTRIES AND
SOCIAL SETTINGS, UNDERSTANDING
WHY HEART OWE TACK IS OCCURRING
AT AN INCREASING RATE IN YOUNGER
WOMEN GLOBALLY, PROVIDING
INSIGHT ON PATHOLOGY AND
TREATMENT OF PERIPARTUM
CARDIOMYOPATHY, WHICH IS MORE
PREVALENT IN WOMEN OF AFRICAN
HISTORY AND WOMEN IN SUB-SAHARAN
AFRICA.
TESTING STRATEGIES TO ADVANCE
THE IMPLEMENTATION OF
EVIDENCE-BASED PRACTICES RELATED
TO CARDIOVASCULAR DISEASE IN
WOMEN ACROSS DIFFERENT SECTORS.
SO WE BELIEVE THE GCRFF IS
QUALIFIED TO LEAD THIS EFFORT
BECAUSE THE MEMBERS HAVE LONG
TRACK RECORDS OF SUPPORTING
MERITORIOUS RESEARCH AND HAVE
DEVELOPED A COLLABORATIVE
CULTURE THROUGH THE
MULTI-NATIONAL CLINICAL TRIALS
INITIATIVE, WHICH WAS THE FIRST
INITIATIVE OF THIS CONSORTIUM.
THERE'S ALSO A RESEARCH FUNDING
DATA SHARING INITIATIVE THAT IS
THE SECOND WORK STREAM.
THIS WILL BE THE FIRST TIME THAT
THE MEMBERS WILL ACTUALLY BE
POOLING RESOURCES TO AWARD AN
INDIVIDUAL RESEARCH PROJECT.
AND IF SUCCESSFUL WITH THIS
MODEL OF POOLING FUNDS TO
SUPPORT A RESEARCH PROJECT, IT
REALLY SETS THE STAGE FOR OTHER
POTENTIALLY LARGER INITIATIVES
DOWN THE ROAD THAT MAY MAKE MORE
SUBSTANTIAL IMPACT ON WOMEN'S
CARDIOVASCULAR HEALTH AND OTHER
CARDIOVASCULAR CONDITIONS.
SO WITH THAT, I'LL BE HEANS TO
ANSWER QUESTIONS OR GET YOUR
FEEDBACK.
>> AS I UNDERSTAND IT, THIS IS
$10 MILLION IN TOTAL FOR ONE
GRANT THAT CAN BE AWARDED?
>> YES.
>> AND IN RANDOM -- IN A RANDOM
COUNTRY?
>> YEAH, SO THE LEAD INSTITUTION
MUST BE IN ONE OF THE MEMBER
COUNTRIES, BUT IT'S EXPECTED TO
BE A PARTNERSHIP ACROSS
COUNTRIES AND AT LEAST WE ARE
HOPEFUL AND HAVE MADE IT CLEAR
WE THINK IT WOULD BE PREFERABLE
TO HAVE PARTNERSHIP WITH
INVESTIGATORS FROM LOW AND
MIDDLE INCOME COUNTRIES.
>> AND YOU SAID THE GROUP HAS
WORKED TOGETHER BUT THIS IS A
NEW MECHANISM FOR THE DIFFERENT
FOUNDATIONS TO WORK TOGETHER?
>> THAT'S RIGHT.
SO THE FIRST WORK STREAM IS A
MULTI-NATIONAL CLINICAL TRIALS
EFFORT, AND WHAT THAT HAS BEEN,
JUST TO BROAFL SUMMARIZE, IS
THERE IS A LETTER OF INTENT
PROCESS WHERE INVESTIGATORS WHO
WANT TO DO A MULTI-NATIONAL
CARDIOVASCULAR TRIAL SUBMIT A
LETTER OF INTENT, AND THAT GETS
REVIEWED BY A PANEL OF EXPERTS
WHO HAVE BEEN PUT TOGETHER
ACROSS THE MEMBER COUNTRIES, AND
THEN IT IS EVALUATED AND THE
GCRFF EITHER ENDORSES IT OR NOT.
AN ENDORSEMENT MEANS WE THINK
IT'S A GOOD IDEA, BUT YOU STILL
HAVE TO SUBMIT FOR FUNDING FROM
THE DIFFERENT MEMBER
ORGANIZATIONS AND MEMBER FUNDERS
FROM THE COUNTRIES YOU WANT TO
DO THE TRIAL IN.
AND EACH COUNTRY IS RESPONSIBLE
FOR THEIR OWN FUNDING, AND WE
HAVE NOW FUNDED A COUPLE OF
TRIALS THAT WAY IN PARTNERSHIP,
AND THAT'S BEEN REALLY EFFECTIVE
FOR US BECAUSE IT MEANS THE
TRIALS WE FUND ARE MORE LIKELY
TO BE HIGH IMPACT, REALLY AFFECT
GUIDELINES BECAUSE THEY'RE OF
MAJOR IMPORTANCE TO MORE THAN
ONE COUNTRY, AND WE'RE ALSO
SHARING THE FINANCIAL
RESPONSIBILITIES, SO WE GET A
LITTLE BIT BETTER BREAK IN TERMS
OF THE RETURN ON OUR INVESTMENT.
THAT'S BEEN EFFECTIVE, ALTHOUGH
THE DOWNSIDE HAS BEEN MULTIPLE
DIFFERENT REVIEW GROUPS,
DECISION PROCESSES, AND THAT HAS
SLOWED DOWN SOME OF THE PROGRESS
BECAUSE SOME ORGANIZATIONS ARE
MORE NIMBLE THAN OTHERS.
I WON'T NAME NAMES.
THE SECOND WORK STREAM, WE'VE
PULLED MONEY TOGETHER TO FUND A
SMALL KA DATA CHALLENGE PRIZE,
WHICH IS -- WE ARE SHARING OUR
DATA ON OUR RESEARCH FUNDING,
AND SO THIS WAY BY DOING THAT,
WE'RE ABLE TO GET AN IDEA
GLOBALLY WHAT ARE WE FUNDING,
BECAUSE WE KNOW WHAT WE'RE
FUNDING AND THEY KNOW WHAT
THEY'RE FUNDING BUT NOBODY HAS
REALLY TAKEN A LOOK AT THE TOTAL
PORTFOLIO OF THESE 13 DIFFERENT
FUNDERS.
SO WE'VE FUNDED A SMALL DATA
CHALLENGE PRIZE IN THAT SPACE.
THIS IS THE FIRST TIME WE'VE
TRIED TO DO SOMETHING RELATIVELY
BIG, AND EVEN $2 MILLION ISN'T
ALL THAT BIG, BUT RELATIVELY BIG
TO SEE IF WE CAN ACTUALLY WORK
THROUGH THE PROCESSES OF WORKING
TOGETHER AROUND A SINGLE REVIEW,
SHARED DECISION-MAKING, SHARED
FUNDING AND KABILITY.
ACCOUNTABILITY.
OTHER QUESTIONS, COMMENTS?
>> I THINK YOU ANSWERED.
I WAS JUST GOING TO ASK HOW THIS
IS REVIEWED, SO IS NIH JUST
FEEDING TO AN OUTSIDE REVIEW
COMMITTEE OR HOW DOES THAT WORK?
>> SO THERE IS A LEAD
ORGANIZATION, THE HEART AND
STROKE FOUNDATION OF CANADA HAS
AGREED TO BE THE LEAD
ORGANIZATION FOR THIS
INITIATIVE, AND SO THEY WILL BE
IMPANELING A REVIEW GROUP THAT
WOULD INCLUDE PEOPLE NOMINATED
BY THE MEMBER ORGANIZATION.
SO WE'LL BE NOMINATING REVIEWERS
TO BE ON THE PANEL THAT WILL BE
REVIEWING A PERSON WHO INTENDS
TO APPLY, THEY HAVE TO MANAGE
CONFLICTS AND ALL THAT, BUT TO
HAVE A SINGLE REVIEW GROUP
COMPRISECOMPRISED OF INTERNATIOL
EXPERTS IN CARDIOVASCULAR
WOMEN'S HEALTH.
AND THE HEART ASSOCIATION WILL
MANAGE THE MONEY.
BECAUSE THEY'RE ABLE TO TAKE
MONEY FROM MULTIPLE DIFFERENT
FOLKS.
WE WOULD HAVE DIFFICULTY AND
SOME OF THE OTHER FUNDERS WOULD
HAVE DIFFICULTY TAKING MONEY
FROM MULTIPLE DIFFERENT PEOPLE.
DIFFERENT ORGANIZATIONS.
IF NO OTHER COMMENTS -- HEART
ASSOCIATION IS REALLY GOOD AT
TAKING MONEY.
[LAUGHTER]
AND THEY DO GOOD THINGS WITH IT,
RIGHT, MERCEDES?
YEAH.
SO LET ME KNOW WHEN THE RATING
IS OVER AND WE'LL MOVE ON.
I THINK WE'RE PROBABLY DONE WITH
ALL THE QUESTIONS AND COMMENTS.
>> JUST A FEW PEOPLE ARE STILL
WORKING THEIR WAY THROUGH.
I THINK YOU CAN MOVE FORWARD,
DR. GOFF.
>> THANK YOU.
THE NEXT CONCEPT IS NUMBER 5038,
RENEWAL OF THE MAX WISE COMBINED
COHORT STUDY OF HIV IN THE
UNITED STATES.
THIS IS A RENEWAL RFA THAT WOULD
BE FUNDED THROUGH THE
U01 MECHANISM.
SO THIS INITIATIVE CALLS FOR
RENEWAL OF NHLBI SUPPORT FOR THE
MACS/WIHS COMBINED COHORT STUDY.
IN 2019 UNDER NHLBI LEADERSHIP,
NIH MERGED TWO LONGSTANDING
U.S.-BASED HIV COHORTS, THE
MULTICENTER AIDS COHORT STUDY OF
MEN AND THE WOMEN'S INTERAGENCY
HIV STUDY, I THINK IS WHAT THAT
WAS.
AND WE ORIENTED THEM ON A
PRIMARY FOCUS OF COMORBIDITIES
IN THE CONTEXT OF LONG-TERM
SURVIVAL WITH TREATED HIV.
BOTH OF THESE COHORT STUDIES
WERE STARTED IN THE ERA WHEN HIV
HAD MUCH FEWER EFFECTIVE
THERAPIES.
SO THIS LONGITUDINAL COHORT IS
CURRENTLY COMPRISED OF OVER 5300
LONG-TERM OR NEWLY ENROLLED
PARTICIPANTS AGED 35 AND OLDER,
HALF OF THEM ARE WOMEN AND THE
MAJORITY OF WHOM ARE GROUPS FROM
UNDERREPRESENTED IN MEDICAL
RESEARCH.
WE SEEK TO CONTINUE FOR AN
ADDITIONAL SEVEN YEARS AND
SEVERAL KEY AREAS OF SCIENCE
WILL BE EXPANDED IN RESPONSE TO
BOTH THE EVOLVING HIV KNOWLEDGE
BASE AND THE AGING OF THE
COHORT.
SO THE RENEWAL WILL EMPLOY A
LIMITED COMPETITION TO RETAIN A
GEOGRAPHICALLY DIVERSE GROUP OF
UP TO 13 CLINICAL RESEARCH SITE,
A LIMITED COMPETITION FOR A
SHARPLY REFOCUSED DATA ANALYSIS
AND DATA SHARING CENTER, AND AN
OPEN COMPETITION FOR A NEW
LEADERSHIP AND COORDINATING
CENTER.
THE NEW LEADERSHIP CENTER WILL
IMPROVE SCIENCE OF THE COHORT
AND CREATE AN ENHANCED STRUCTURE
FOR ANCILLARY STUDIES, WORK
GROUPS, OPERATIONAL -- AND
COMMUNITY IN PARTICIPANT
ENGAGEMENT.
WE ACTUALLY FOUND THAT WHEN WE
WERE MERGING THESE TWO COHORTS,
THERE WAS QUITE A BIT OF CULTURE
CHANGE AND A BUNCH OF CHANGE
MANAGEMENT, AND I THINK WE WISH
WE HAD STARTED A NEW LEADERSHIP
CENTER LAST ROUND, BUT HAVING
LEARNED THAT, WE WANT TO START
IT THIS ROUND.
THE MAX WISE HAS BEEN DESCRIBED
AS THE -- OF TH -- 40-YEAR
INVESTMENT IN ONE OF THE WORLD'S
MOST IMPORTANT SOURCES OF
RIGOROUS SCIENTIFIC KNOWLEDGE
ABOUT EVOLVING IMPACT OF HIV
INFECTION AND ITS COMORBIDITIES
ON HUMAN HEALTH.
SUSTAINING NHLBI'S LEADERSHIP OF
THE STUDY WILL CONTRIBUTE TO OUR
INFLUENCE ON THE GROWING FIELD
OF INTEGRATED SCIENCE, SEEKING
TO UNDERSTAND AND CONTROL HEART,
LUNG, BLOOD AND SLEEP CONDITIONS
OF VIRAL INFECTIONS.
AND WITH THAT, I'LL BE HAPPY TO
TAKE QUESTIONS AND COMMENTS.
>> I THINK IT'S REALLY IMPORTANT
THAT NHLBI CONTINUE INVOLVEMENT
IN THIS, PULMONARY AND
CARDIOVASCULAR COMPLICATIONS ARE
THE MAJOR COMORBIDITIES AND
SOURCES OF MORBIDITY AND
MORTALITY IN PEOPLE LIVING WITH
AIDS, WITH HIV, AND THE TOBACCO
EPIDEMIC, PEOPLE WITH HIV, IT'S
A MAJOR ISSUE.
I THINK IT'S A REALLY IMPORTANT
EA ONE THAT'S UNDERSTUDIED.
>> THANK YOU.
WE CERTAINLY AGREE, AND
APPRECIATE THE OPPORTUNITY AND
TRUST, REALLY, THAT NIH HAS
GIVEN IN US TO TAKE ON
STEWARDSHIP OF THIS RESOURCE.
WE THINK IT'S REALLY IMPORTANT.
WE HAVE A LOT OF IDEAS ABOUT HOW
TO LEVERAGE IT.
WE'RE BEGINNING TO DO
MULTI-OMICS IN MACS/WIHS,
CONTINUE TO DO MORE OF THAT AS
WE GO FORWARD, WE'LL HAVE SOME
COMPARATORS BETWEEN FOLKS IN
MACS/WIHS AND OUR OTHER COHORTS,
SO THERE'S JUST SO MANY
OPPORTUNITIES HERE TO SUPPORT
DISCOVERY SCIENCE.
PLEASE LET ME KNOW WHEN WE'RE
READY TO MOVE ON.
>> I THINK YOU CAN MOVE ON.
>> OKAY, THANK YOU.
THE NEXT CONCEPT IS 5042,
EMULATING ACCESS TO RESEARCH IN
RESIDENCY OR S STARR.
THIS RENEWAL OF WHICH NHLBI IS
THE LEAD INSTITUTE WITH
PARTICIPATION FROM NIAID, NCI,
NIA, AND NEI AND OTHER
PARTICIPATING INSTITUTES.
SO THE R38 IS AN INSTITUTIONAL
AWARD TO SUPPORT MENTORED
RESEARCH ACTIVITIES FOR
RESIDENTS WHO ARE EXPECTED TO
THEN PURSUE CAREERS AS PHYSICIAN
SCIENTISTS.
THE R38 SUPPORTS SPECIFIC
RESEARCH TOPICS WITHIN EACH
PARTICIPATING INSTIT INSTITUTE'S
INDIVIDUAL MISSIONS.
LESS THAN 5% OF ALL PHYSICIANS
HOLD AN MD PH.D., AND ALTHOUGH
MOST MD PH.D.s ARE ENGAGED IN
RESEARCH IN THEIR CAREERS, THE
MAJORITY OF SIT 10 SCIENTISTS IN
THE WORKFORCE ARE MADE UP OF
M.D.s WITHOUT A PH.D.
IT HIGHLIGHTED WHAT WE CALL AN
M.D. ONLY, ALTHOUGH IT'S NOT
JUST AN M.D., BUT AN M.D. ONLY
POOL ARE THE ONES THAT ARE
ENTERING ACADEMIC CAREERS AT A
DIMINISHING RATE.
YOU STILL SEE THAT PEOPLE WHO GO
TO THE POINT OF GETTING THE M.D.
PH.D., THEY TEND MOSTLY TO DO
RESEARCH, BUT THIS -- SHRINK IT.
THERE ARE A NUMBER OF
RECOMMENDATIONS THAT RESULTED
FROM THE WORKING GROUP THAT LED
TO THE CREATION OF THE R38 STARR
PROGRAM, INCLUDING THAT NIH'S
PILOT IDEAS TO TEST NOVEL
APPROACHES TO INPROVE SHORTING
RESEARCH TRAINING AND INTENSIFY
EFFORTS TO INCREASE DIVERSITY IN
THE WORKFORCE.
FOR RESIDENTS WHO ARE IN THE
STARR PROGRAM, THEY'RE SUPPORTED
AND MENTORED RESEARCH FOR
BETWEEN 12 AND 24 MONTHS AT 80%
EFFORT.
NHLBI HAS BEEN FUNDING R38
PROGRAMS SINCE ABOUT 2018.
AT PRESENT, WE SUPPORT
21 PROGRAMS FOR WHICH 158
RESIDENTS HAVE RECEIVED OR ARE
CURRENTLY RECEIVING RESEARCH
SUPPORT OF THESE 158 RESIDENTS,
47% ARE WOMEN, AND ABOUT 15% ARE
FROM UNDERREPRESENTED GROUPS.
BY SPECIALTY, THE MAJORITY ARE
IN INTERNAL MEDICINE, ABOUT
HALF, 42 IN PEDIATRICS, 23
SURGEONS, 12 FROM PATHOLOGY, AND
A SMALL NUMBER FROM FAMILY
MEDICINE AND EMERGENCY MEDICINE.
IN TERMS OF FUTURE SUCCESS, 42
OF THE RESIDENTS HAVE COMPLETED
THEIR R38 PROGRAM FOR AT LEAST
THREE YEARS.
AMONG THOSE 42, ABOUT HALF ARE
STILL IN CLINICAL TRAINING,
MOSTLY IN CLINICAL FELLOWSHIPS.
11 OR 26% HAVE RECEIVED AN NIH
AWARD SUCH AS A T32 OR K AWARD,
AND 9 OR 21% ARE CURRENTLY
ACADEMIC FACULTY AND PURSUING A
RESEARCH CAREER.
SO WE THINK THE EARLY RESULTS
ARE VERY PROMISING FOR THIS
PROGRAM.
WE ARE INTERESTED IN CONTINUING
TO SUPPORT TO SEE WHAT THE
LONGER TERM OUTCOMES WILL BE AND
LOOK FORWARD TO YOUR QUESTIONS
AND COMMENTS.
>> CAN I ASK A COUPLE QUESTIONS?
>> YES, PLEASE.
>> SO THE PROGRAM -- ADDITIONAL
18 MONTHS IS NOT -- [INAUDIBLE]
>> SO DIFFERENT PROGRAMS HAVE
DECIDED TO DO THAT DIFFERENTLY.
SOME ADD A YEAR, SOME INTEGRATE.
THE ONES THAT ADD A YEAR TEND TO
HAVE LONGER PERIODS OF RESEARCH.
THIS PROGRAM SUPPORTS 12 TO 24
MONTHS.
SO FOR THE PROGRAMS THAT ADD A
YEAR, THEY'RE TYPICALLY
INTEGRATING SOME RESEARCH TIME
AND ADDING RESEARCH TIME.
FOR THOSE THAT INTEGRATE, THEY
MOSTLY DON'T GET FAR BEYOND 12
MONTHS.
>> AND --
>> THAT'S MY UNDERSTANDING, BUT
DAVID MAY BE OUT THERE, IF
YOU'RE ONLINE OR IN THE ROOM AND
I'M MISSTATING, PLEASE HOLLER
OUT.
>> I AM HERE.
THANK YOU, AND NO, YOU SAID THAT
EXACTLY RIGHT.
PROGRAMS -- ALL KIND OF
STRUCTURED SLIGHTLY DIFFERENTLY
AND AS YOU SAID, SOME ARE ABLE
TO DO ONE YEAR OF RESEARCH WB A
THREE-YEAR RESIDENCY.
IT COMPACTS THE REST OF THEIR
CLINICAL TIME INTO THEIR TWO
YEARS.
BUT SOME DO, ESPECIALLY IF THEY
DO 18 OR 24 MONTHS, WILL ADD ON
A FOURTH YEAR TO A THREE-YEAR
RESIDENCY, FOR EXAMPLE IF WE'RE
TALKING ABOUT MEDICINE AND
PEDIATRICS, WHICH MAKE UP THE
BULK OF THE PROGRAMS.
>> ONE MORE QUESTION.
JUST IN TERMS OF DIVERSITY, ARE
INTERNATIONAL GRADUATES ELIGIBLE
OR DOES THIS HAVE A U.S.
CITIZENSHIP REQUIREMENT?
>> DAVID, DO YOU KNOW THE ANSWER
TO THAT?
I DON'T KNOW THE ANSWER TO THAT.
>> I DON'T BELIEVE THERE IS --
THAT WE PUT A U.S. CITIZENSHIP
REQUIREMENT ON IT.
NO.
NO, JUST THAT THEY'RE IN
RESIDENCY, BUT WE DON'T
STIPULATE RESIDENCY STATUS FOR
THIS, I'M PRETTY SURE.
I CAN ALWAYS CONFIRM, BUT NO, IT
WAS NOT OUR INTENTION TO DO
THAT, AT LEAST.
>> THAT'S WONDERFUL.
THANK YOU SO MUCH.
>> ANY OTHER QUESTIONS OR
COMMENTS OR WE CAN MOVE ON TO
RATINGS?
>> MAYBE JUST ANOTHER
30 SECONDS, WE'LL BE ABLE TO
MOVE ON.
OKAY, DR. GOFF.
YOU CAN MOVE ON.
>> THANK YOU.
THE FINAL CONCEPT WE HAVE FROM
DCBS IS NUMBER 5044 TITLED WHOLE
PERSON RESEARCH AND COORDINATION
CENTER.
THIS IS SECONDARY PARTICIPATION
AND THEN TRANS-NIH RFA TO FUND A
U24 MECHANISM LED BY NCCIH.
SO THE GOAL OF THIS INITIATIVE
IS TO BUILD AN INTEGRATED
FRAMEWORK WITH MOLECULAR STUDIES
AT ONE END OF THE SPECTRUM TO
PATIENT AND SOCIETAL LEVEL DATA,
INCLUDING SOCIAL DETERMINANTS OF
HEALTH AND CULTURAL FACTORS AT
THE OTHER END OF THE SPECTRUM.
STARTING IN THE MIDDLE
PHYSIOLOGICAL LAYER OR ORGAN AND
SYSTEM-LEVEL FUNCTIONING.
THE NOTICE OF FUNDING
OPPORTUNITY WILL INCLUDE FOUR
BASIC SCIENCE COMPONENTS OR FOUR
BASIC CORE COMPONENTS, I SHOULD
SAY, SCIENTIFIC LEADERSHIP,
DOMAIN MAPPING AND COMMON DATA
ELEMENTS, DATA SCIENCE AND
MODELING, AND A COORDINATION
CORE.
SO FAR, 15 INSTITUTES, CENTERS
AND OFFICES ACROSS NIH HAVE
AGREED TO PARTICIPATE IN THIS
NEW EFFORT.
THE U24 MECHANISM IS PLANNED TO
BE DEPLOYED IN TWO PHASES.
ONE COORDINATING CENTER WILL BE
FUNDED.
THE GOAL OF THE FIRST PHASE,
YEARS ONE AND TWO OF THE AWARD,
IS TO BUILD A HUMAN WHOLE PERSON
CONCEPT MAP OF WHAT WE ALREADY
KNOW ABOUT MAJOR PHYSIOLOGICAL
FUNCTIONS.
IT WILL BE BUILT BY A TEAM OF
EXPERTS REPRESENTING VARIOUS
PHYSIOLOGICAL SYSTEMS.
THE NEXT STEP IN PHASE ONE WILL
BE TO IDENTIFY COMMON DATA
ELEMENTS FOR EACH PHYSIOLOGICAL
FUNCTION.
IN PHASE TWO, WHICH IS
ENVISIONED AS YEARS THREE
THROUGH FIVE, THE CONCEPT MAP
WILL BE POPULATED WITH DATA FROM
EXISTING INITIATIVES AND COHORT
STUDIES SUCH AS ALL-OF-US AND
OUR TOP MED PROGRAM.
THIS DATA POPULATED NETWORK
WOULD THEN BE USED TO BUILD AND
TEST INSILICO OR COMPUTER
GENERATED MODELS, FOCUSING ON
LIFESTYLE INTERVENTIONS TO
SUPPORT WHOLE PERSON HEALTH.
IN FUTURE PROJECTS, THIS CAN BE
USED TO MODEL DISEASE
PATHOPHYSIOLOGY AND THE EFFECTS
OF TREATMENTS.
THIS NOFO WOULD PROVIDE
OPPORTUNITY TO INCREASE OUR
RETURN ON INVESTMENT AND OUR
BIODATA CATALYST PROGRAM, TOP
MED, LUNG MAP, THE NATIONAL
SLEEP RESEARCH RESOURCES
PROGRAM, THE -- AND OUR SEAL
PROGRAM AMONG OUR OTHER NHLBI
INVESTMENTS.
THERE WILL ALSO BE OPPORTUNITIES
FOR US TO BRING NHLBI RESEARCH
PRIORITIES INTO THIS NIH-WIDE
INITIATIVE AND OUR INVESTIGATORS
WILL BE ABLE TO UTILIZE THE
RESOURCES AND BE ABLE TO JOIN
THIS WHOLE PERSON RESEARCH
COMMUNITY.
NCCIH WILL PROVIDE MORE THAN
HALF OF THE OVERALL FUNDING,
PROPOSED CONTRIBUTION OF 100,000
PER YEAR FOR FIVE YEARS OR A
TOTAL OF $500,000 WOULD
CONSTITUTE ABOUT 4% OF THE
PROJECT'S OVERALL BUDGET.
IF SUCCESSFUL WITH THIS REALLY
MODEST INVESTMENT, YO WE THINK Y
SCIENTIFIC DISCOVERIES ARE
POSSIBLE WITH COLLABORATION FROM
NCCIH AND OTHER INSTITUTES.
AT THIS POINT, I'D BE HAPPY TO
TAKE YOUR QUESTIONS AND
COMMENTS.
OR WE CAN MOVE TO RATINGS.
AND I'LL PASS THE BATON BACK TO
DR. PRENGER.
>> THANK YOU VERY MUCH.
WHILE YOU FINISH, WE'LL MOVE ON
TO -- DR. MENSAH CAN BEGIN THAT.
>> OKAY, DR. MENSAH, IT'S ALL
YOURS.
>> THANK YOU VERY MUCH.
WE'RE ALMOST AT THE END HERE.
IT'S MY PLEASURE TO REPRESENT
THE DIVISION OF EXTRAMURAL
RESEARCH ACTIVITIES IN
PRESENTING THE LAST SEVEN
CONCEPTS.
THE FIRST TWO CONCEPT MEMBERS
5028 5028 AND 5029 ARE RENEWAL
RFAs.
THEY'RE INTENDED TO ACCELERATE
COMMERCIALIZATION OF
TECHNOLOGIES FOR HEART, LUNG,
BLOOD AND SLEEP DISORDERS AND
DISEASES.
THEY USE THE R24 MECHANISM.
I'D LIKE TO BEGIN BY GIVING
CREDIT TO DR. JANE -- FROM THE
DIVISION OF EXTRAMURAL RESEARCH
ACTIVITY, WHO HAS SHEPHERDED
THESE PROGRAMS THROUGH OUR --
THAN NORMAL PROCESSES.
CONCEPT 5028 SUPPORTS THE BRIDGE
AWARDS WHIEK 5029 PROVIDES SMALL
MARKET AWARDS.
I'LL PRESENT BOTH OF THEM
TOGETHER BUT THEN GIVE YOU TIME
TO RATE THEM INDEPENDENTLY.
THE PHASE 2B PROGRAM AS YOU KNOW
IS DESIGNED TO -- TECHNOLOGY
FUNDING BETWEEN THE EAND OF AN
SBIR AWARD AND ACQUISITION OF
THIRD PARTY -- NEEDED TO
ACCOMPLISH REGULATORY MILESTONES
AND ADDITIONAL DE-RISKING AS
SMALL BUSINESS ORGANIZATIONS
COMMERCIALIZE THEIR PRODUCTS.
THE TWO KEY GOALS OF THE PROGRAM
ARE TO PROVIDE FUNDING FOR
CAPITAL-INTENSIVE STAGE PRODUCT
DEVELOPMENT ACTIVITIES THAT ARE
REQUIRED TO ADVANCE PROJECTS TO
REGULATORY APPROVAL AND
COMMERCIALIZATION.
THE SECOND IS TO ENCOURAGE
PUBLIC PRIVATE PARTNERSHIPS THAT
ENHANCE THE RETURN ON
INVESTMENTS WE MAKE IN
PREVIOUSLY FUNDED TECHNOLOGIES.
SINCE ITS RELEASE BACK IN 2013,
THE PROGRAM HAS FUNDED 44 AWARDS
OUT OF A TOTAL OF 117
APPLICATIONS SUBMITTED.
THIS FUNDING IS PARTICULARLY
CRUCIAL IN TODAY'S INVESTMENT
LANDSCAPE WHERE EXTERNAL FUNDERS
HAVE BECOME INCREASINGLY
RISK-AVERSE.
PROGRAM EVALUATION SHOWS THAT
THE FUNDED PHASE 2B BRIDGE
AWARDEES HAVE ACTUALLY BEEN MORE
SUCCESSFUL AT ACHIEVING
MILESTONES AND ATTRACTING
INVESTMENT COMPARED TO THEIR
UNFUNDED COUNTERPARTS.
FOR EXAMPLE, THE EVALUATION
SHOWS THAT ABOUT A THIRD OF THE
PHASE 2B FUNDED PROJECTS HAVE
REACHED THE COMMERCIAL STAGE.
ANOTHER 20% HAVE SUCCESSFULLY
BEEN ACQUIRED BY OTHER
COMPANIES.
OUT OF 31 TECHNOLOGIES THAT ARE
IN DEVELOPMENT, ABOUT 40% OF
THEM ARE IN CLINICAL SETTINGS.
SO BASED ON THE RESULTS OF THESE
EVALUATIONS, WE REMAIN VERY
ENTHUSIASTIC ABOUT THE PROGRAM,
AND LOOK FORWARD TO COUNCIL'S
SUPPORT FOR THE RENEWAL.
LET ME TELL YOU ABOUT A SECOND,
5029.
NOW WHILE THE BRIDGE AWARD YOU
JUST HEARD ABOUT SUPPORTS SMALL
BUSINESSES WORKING IN ALL OF
NHLBI'S MISSION AREAS, A SMALL
MARKET RFA IS SPECIFICALLY
DESIGNED TO SUPPORT COMPANIES
DEVELOPING TECHNOLOGIES WITH
SMALL COMMERCIAL MARKETS OR
THOSE DEVELOPING TECHNOLOGIES
FOR PEDIATRIC IMPLICATIONS.
COMPANIES FOCUSED ON
TECHNOLOGIES WITH SMALL
COMMERCIAL MARKETS FILL A VERY
IMPORTANT CLINICAL NEED AND,
VERY OFTEN, THEY ARE THE FIRST
AND HARDEST HIT WHEN INVESTORS
DOUBLE DOWN ON BIG WINNERS IN
THE PORTFOLIO.
ADDITIONALLY, COMPANIES FOCUSING
ON -- DRUG DEVELOPMENT AND
PEDIATRIC DEVICE MANUFACTURERS
OFTEN NEGATIVELY AFFECTED BY THE
TENDENCY TO AVOID RISKY
INVESTMENTS.
HOWEVER, -- VALUABLE CLINICAL
NEED, DESIGNED FOR I A DULT
PATIENTS AND VERY ILL SUITED FOR
NEONATAL AND PEDIATRIC PATIENTS.
ADDITIONALLY, SMALL MARKET
AWARDEES ARE REQUIRED TO
SECURE -- THEY'RE REQUIRED TO
MAKE A ONE TO THREE MATCH RATHER
THAN A ONE TO ONE MATCH, SO THE
BRIDGE AWARDS.
FOR INSTANCE, IF A COMPANY
RECEIVES $3 MILLION AWARD FROM
NHLBI, THEY MUST BRING IN AT
LEAST A MILLION FROM OTHER
PRIVATE INVESTORS OR SOURCES
OF -- FUNDING.
SINCE ITS INCEPTION IN 2014, THE
PROGRAM HAS YIELDED 14 AWARDS
FROM A TOTAL OF 49 APPLICATIONS.
2023 EVALUATION SHOWS THAT -- AT
ACHIEVING CONVENTIONAL
MILESTONES AND -- INVESTMENTS
COMPARED TO THE UNFUNDED
COUNTERPARTS.
IMPORTANTLY, THE ANALYSIS SHOWS
THAT FOR EVERY DOLLAR OF PHASE
2B FUNDS THAT NHLBI INVESTED IN
THE PROGRAM, THE AWARDED
COMPANIES RAISED 11 MILLION --
I'M SORRY -- THAT WOULD HAVE
BEEN GREAT RETURN ON INVESTMENT.
$11 FOR EVERY DOLLAR WE INVESTED
IN TERMS OF FULL-ON FUNDING
DURING AND AFTER AWARD TO
DEVELOP THEIR TECHNOLOGIES.
BASED ON THESE RESULTS AND THESE
EVALUATIONS, WE'RE VERY
ENTHUSIASTIC OF THIS M PRA, AND
WEPROGRAM ANDWE LOOK FORWARD TOS
SUPPORT OF THE RENEWAL OF THE
SMALL MARKET RFA TO HELP
COMPANIES BRING THEIR PRODUCTS
TO PEDIATRIC PATIENTS AND TO
THOSE WITH RARE DISEASES.
I'LL PAUSE HERE FOR YOUR
QUESTIONS, YOUR COMMENTS, AND
THEN RATE THE TWO PROGRAMS.
AGAIN, THE NUMBERS ARE 5028 AND
5029.
PLEASE.
>> YOU TALK ABOUT HOW SUCCESSFUL
THESE APPLICANTS ARE IN GETTING
FUNDING, AND I'M JUST CURIOUS
HOW THAT FITS WITH WHY IS
INDUSTRY SO RISK-AVERSE IF THESE
PEOPLE ARE DOING SO WELL?
AND HOW DOES THAT WORK?
IS THERE ANY CONCERN THAT THE
COMPANIES ARE RISK-AVERSE
BECAUSE THIS FUNDING IS
AVAILABLE?
>> THAT'S A VERY IMPORTANT
QUESTION AND IT'S EASIER FOR US
TO CONCEPTUALIZE PARTICULARLY
FOR THE PEDIATRIC AND NEONATAL
POPULATION.
LET ME CALL ON DR. CRUX.
>> DR. MENSAH, CAN YOU HEAR ME?
>> YES, WE CAN.
>> OKAY, GREAT.
THANK YOU.
THANK YOU FOR THAT QUESTION.
SORE THIS RISK-AVERSE NATURE OF
INVESTORS, AND I WANT TO START
WITH SAYING THE SUCCESS OF OUR
SMALL BUSINESS PROGRAM ALMOST
EXCLUSIVELY DEPENDS ON THE
COMPANIES THAT -- TO BRING IN
ADDITIONAL CAPITAL FROM PRIVATE
SOURCES LIKE INVESTORS AND
PARTNERS, AND THE FACT THAT WE
MENTIONED, AS DR. MENSAH
MENTIONED, INVESTORS ARE
RISK-AVERSE AND THAT'S ALMOST A
PLANGT STATABLANKET STATEMENT, T
FACT, ESPECIALLY BECAUSE THESE
DAYS, THERE ARE A LOT OF
TECHNOLOGIES THAT HAVE ADVANCED
TO LATER STAGES OF DEVELOPMENT,
SO INVESTORS HAVE A LOT MORE
OPTIONS, SO THE SMALL BUSINESS
PROGRAM, BY THE TIME OUR
COMPANIES FINISH A PHASE TWO
PROGRAM, THEY ARE NOT AS
ADVANCED AS MOST INVESTORS LIKE
THEM TO BE.
AND THAT'S WHERE THAT RISK
FACTOR COMES IN.
SO PROVIDING THIS ADDITIONAL
PHASE 2B FUNDING ALLOWS OUR
COMPANIES TO DO THIS NEEDED TO
CROSS THAT VALLEY OF DEATH, TO
COMPLETE SOME REALLY CRITICAL
DE-RISKING ASK YOU STUDIES SO
THEY CAN GET TO A STAGE WHERE
THEY CAN ATTRACT INVESTORS AND
PARTNERS.
DOES THAT ANSWER THE QUESTION?
>> I SEE HEAD NODDING, JANE.
ALL RIGHT.
IF THERE AREN'T ANY OTHER
QUESTIONS, IF YOU COULD GO AHEAD
AND PLEASE RATE THEM SEPARATELY.
5028 AND 5029.
>> I THINK WE'RE GOOD TO GO.
>> THANK YOU.
WE NOW HAVE THE LAST FIVE
CONCEPTS FOR YOUR CONSIDERATION.
THEY ARE ALL PART OF OUR
CATALYZE SUITE OF PROGRAMS.
YOU HEARD ABOUT THEM THIS
MORNING FROM DR. PECK AND ALSO
FROM DR. GIBBONS' REPORT.
I'D LIKE TO GIVE CREDIT TO
DR. MIKE PECK, WHO'S THE PROGRAM
DIRECTOR FOR THE ENTIRE SUITE OF
PROGRAMS.
THE CATALYZE PROGRAM WAS
LAUNCHED FIVE YEARS AGO TO
PROVIDE NHLBI WITH A
COMPREHENSIVE SUITE OF PROGRAMS,
SUPPORTS, AND SERVICES TO
EFFICIENTLY AND EFFECTIVELY HELP
INVESTIGATORS BRING THE HLBS
RELATED INNOVATIONS FROM THE
PRODUCT DEFINITION STAGE THROUGH
RESEARCH AND REGULATORY
SUBMISSIONS.
WE ARE ASKING COUNCIL'S SUPPORT
FOR THE RENEWAL OF FIVE
UNDERLYING RFAs.
EACH CONCEPT NEEDS TO BE RATED
SEPARATELY.
TO QUOTE JIM KILEY, IT'S NOT AS
BAD AS IT SOUNDS.
YOU'RE NOT GOING TO HEAR FIVE
REPEATED PRESENTATIONS.
AT THE END, I'LL REMIND YOU WHAT
THE TITLES ARE TO MAKE IT A
LITTLE BIT EASIER FOR YOU TO
RATE THEM SEPARATELY.
ONE RFA, THE FIRST ONE I'LL TALK
ABOUT, ADDRESSES THE ENABLING
TECHNOLOGIES AND TRANSFORMATIVE
PLATFORMS.
THAT'S WHEN YOU HAVE THE REALLY
CRAZY IDEA, THAT'S WHERE YOU GO.
TWO ADDRESSES SMALL MOLECULES
AND BIOLOGICS, AND THE LAST TWO
ADDRESS MEDICAL DEVICE
PROTOTYPES AND OTHER
THERAPEUTICS.
THE GRANTS THAT ARE FUNDED BY
THESE FIVE RFAs ARE
SUPPLEMENTED BY TECHNICAL AND
BUSINESSES SERVICES FROM THE
CATALYZE COORDINATING CENTER.
LET ME GIVE A BRIEF DESCRIPTION
OF WHAT EACH RFA IS DOUGH S DESO
DO AND THEN SHARE WITH YOU WHAT
IMPACT THE PROGRAMS HAVE HAD AND
WHY WE ARE ENTHUSIASTIC ABOUT
THEM.
THE CONCEPT 5030 IS A RENEWAL
NOFO FOR THE ENABLING
TECHNOLOGIES AND TRANSFORMATIVE
PLATFORMS THAT WILL SUPPORT THE
DEVELOPMENT OF THE NEXT
GENERATION OF PREDICTIVE
DIAGNOSTIC AND THERAPEUTIC
PRODUCTS OR MODEL SYSTEMS
RELEVANT TO THE NHLBI MISSION
AREAS.
THAT'S 5030.
5031 AND 5032 ADDRESS SMALL MOL
MOL KEULS AND BIOLOGICS AND HERE
THE FOCUS IS ON TARGET
IDENTIFICATION AND VALIDATION
FOR THE FIRST ONE, AND THEN
PRELIMINARY PRODUCT AND LEAD
SERIES IDENTIFICATION.
THE LAST TWO ARE CONCEPTS
5033 AND 5034, AND THEY ADDRESS
MEDICAL DEVICE PROTOTYPES
DEVELOPMENT AND TESTING, AND
VALIDATION.
I'LL TELL YOU ABOUT THE IMPACT
OF THESE PROGRAMS.
SINCE THE CATALYZE PROGRAM
LAUNCHED BACK IN FISCAL YEAR
2019, THE CATALYZE SUITE OF
NOFOs THAT RESULTED IN
253 APPLICATIONS AND 51 FUNDED
AWARDS.
THE 51 FUNDED AWARDS HAVE
RESULTED IN 60 PUBLICATIONS, 23
U.S. PATENT APPLICATIONS, AND
SIX INTERNATIONAL PATENT
APPLICATIONS.
THREE OF THE U.S. PATENTS HAVE
ALREADY BEEN AWARDED.
THERE HAVE BEEN SEVERAL FDA FI
FILINGS FOR PREIND AND Q
SUBMISSIONS.
IN ADDITION, OF THE 22 COMPLETED
PROJECTS WHICH WERE FUNDED IN
COHORT 1 AND COHORT 2, 2019 AND
2020, 3 PROJECTS HAVE ALREADY
ADVANCED TO THE CATALYZE
PRE-CLINICAL PHASE.
THREE PROJECTS WERE PROACTIVELY
TERMINATED BY THE INSTITUTE DUE
TO TECHNICAL FEASIBILITY ISSUES.
16 PROJECTS HAVE CONTINUED ALONG
THEIR PRODUCT DEVELOPMENT
PATHWAY, AND MOST IMPORTANTLY,
12 OF THE 16 PROJECTS HAVE
RECEIVED NEARLY $15 MILLION IN
FULL-ON FUNDING, INCLUDING FOUR
ADDITIONAL NHLBI SBIR AWARDS,
THREE R01 AWARD, AND FUNDING
FROM OTHER ORGANIZATIONS.
ONE OF THE GOALS OF THE CATALYZE
PROGRAM IS TO ATTRACT
GEOGRAPHICALLY AND
DEMOGRAPHICALLY DIVERSE
INNOVATORS FROM BOTH ACADEMIC
AND FOR-PRO FIPROFIT INSTITUTIO.
WE'VE ACTUALLY BEEN MODESTLY
SUCCESSFUL ON THE GEOGRAPHIC
DIVERSITY FRONT.
THE PROGRAM HAS RECEIVED
APPLICATIONS FROM ORGANIZATIONS
IN 30 U.S. STATES, AND WE'VE
FUNDED ORGANIZATIONS IN 19 OF
THESE STATES.
THE 51 AWARDS REPRESENT A
DIVERSE MIX OF INSTITUTIONS,
ABOUT TWO THIRDS OF THEM
ACADEMIC, 15% SMALL BUSINESSES,
8% BEING NON-PROFIT RESEARCH
ORGANIZATIONS.
I MUST ADMIT WE HAVE MORE WORK
TO DO TO ADVANCE OUR DIVERSITY
BY RACE AND ETHNICITY AND ALSO
DIVERSITY BY GENDER.
WE ANTICIPATE THAT THE RENEWAL
OF THE CATALYZE PROGRAM WILL
CONTINUE TO ATTRACT A DIVERSE
POOL OF INNOVATORS AND
NON-FEDERAL COST SHARING AND
ALSO ENABLE US TO GENERATE MORE
INTELLECTUAL PROPERTY BUT ALSO
TO DIVERSIFY THE PROGRAM.
SO LET ME BRIEFLY SUMMARIZE BY
TELLING YOU ABOUT -- IF I CAN
SEE MY CHEAT SHEET HERE.
SO 5030 IS THE ENABLING
TECHNOLOGIES PLATFORM.
5031 IS THE DEFINITION FOR SMALL
MOLECULES AND BIOLOGICS, THAT'S
FOR TARGET IDENTIFICATION AND
VALIDATION.
5032 IS THE PRODUCT DEFINITION
FOR SMALL MOLECULES AND
BIOLOGICS AS A PRELIMINARY AND
LEAD SERIES IDENTIFICATION, AND
5033 IS MEDICAL DEVICE PROTOTYPE
DESIGN AND TESTING.
AND THEN THE LAST ONE, 5034, IS
MEDICAL DEVICE PROTOTYPE TESTING
CHARACTERIZATION AND VALIDATION.
SO THE WHOLE COMPREHENSIVE
SUITE.
THANK YOU VERY MUCH.
LET ME PAUSE HERE TO SEE IF YOU
HAVE ANY QUESTIONS AND I KNOW
DR. PECK IS ONLINE TO HELP ME
OUT IF THERE ARE QUESTIONS THAT
I CAN'T ANSWER RIGHT HERE IN
PERSON.
>> PLEASE.
>> SO I REALLY DO LIKE THE
SUPPORT THAT'S BUILT INTO THESE
PROGRAMS AND TO HELP THE P.I.s
AND -- THE PROGRAM.
MY QUESTION IS EVERY TIME I
REVIEW GRANTS FOR THESE
MECHANISMS, THERE ALWAYS SEEMS
TO BE A VERY LIMITED NUMBER OF
APPLICATIONS PER CALL, AND I'M
WONDERING WHETHER, ONE, IS IT
WORTH FOLDING ALL FIVE INTO ONE
AND RE-LOOKING AT HOW THAT
PROGRAM IS STRUCTURED?
TWO, IS THERE OPPORTUNITY TO
CONTINUE TO INCREASE THE POOL OF
APPLICATIONS THAT COME IN, GET
MORE DIVERSITY, BECAUSE IT'S
LIKE -- OFTEN IT'S ONE OR THREE
APPLICATIONS PER FUNDING CYCLE
APPLYING FOR EACH OF THESE, SO
COMMENT ON THAT?
>> I'M GLAD TO SEE MY
[INAUDIBLE], BUT MY SHORTEST
ANSWER TO YOU IS YES, DEFINITELY
VERY THOUGHT-PROVOKING AND WE
SHOULD CONSIDER ALL OPTIONS.
WHAT DO YOU THINK?
>> IN TERMS OF EVALUATION PANEL,
COME UP WITH THE SAME STATEMENT
FOR HOW YOU'RE DOING THIS.
ONE WAY WE'RE TRYING TO ADDRESS
THIS IS BY IMPROVING OUR
MARKETING OUTREACH, AND THEN
ALSO ADDRESSING MAYBE -- THESE
ARE VERY CHALLENGING, LIKE YOU
HAVE TO COME IN WITH A --
MATCHING FUND -- SO IT'S
TRACKING THE DIFFERENT NAWD
NA -- SOAGAIN THERE'S THAT CHALE
OF -- BUT GREAT QUESTIONS AND I
THIITHINK WE'LL TAKE THOSE BACK.
>> THANK YOU.
ANY OTHER ADDITIONAL QUESTIONS
OR SUGGESTIONS FOR THE
INSTITUTE?
ALL RIGHT.
THE EASIEST ONE TO REMEMBER IS
THE CRAZY IDEAS PLATFORM, THE
FIRST ONE.
AND THEN MAYBE THINK OF THEM IN
TERMS OF THE SMALL MOLECULES AND
BIOLOGICS FOR THE SECOND TWO.
AND THE MEDICAL DEVICE
PROTOTYPES.
AND IN EACH OF THE TWO, THERE'S
THE EARLY PHASE PRODUCT
DEFINITION AND THEN THERE'S THE
LATER PHASE FOR VALIDATION
AND -- THAT'S HOW I THINK ABOUT
IT.
THAT'S A GOOD WAY TO THINK ABOUT
IT.
>> THANKS, MIKE.
>> ALL RIGHT.
IF YOU COULD GO AHEAD AND
COMPLETE YOUR RATING.
PLEASE.
>> HOW ARE WE DOING ON THE
VOTING?
>> WE JUST HAVE THREE MORE
PEOPLE WE'RE WAITING ON, AND
THEN I CAN SEE THE SENSITIVITY
ANALYSIS.
>> ALL RIGHT.
WITH THREE MORE TO GO, I'LL TURN
IT OVER TO DR. PRENGER.
THANK YOU VERY MUCH.
>> WHILE YOU FINISH VOTING, WE
WILL BE ABLE TO TABULATE THE
RESULTS AND PUT IT UP.
>> WE'RE ALMOST THERE.
JUST A FEW VOTES AWAY.
JUST A FEW RATES AWAY.
AND I CAN PUT THAT UP FOR YOU.
OKAY.
>> WE'LL PUT THOSE UP AFTER WE
CLOSE THE SESSION.
>> OKAY.
EVERYONE'S FINISHED THEN.
>> OKAY.
THANK YOU VERY MUCH, EVERYONE.
THAT CONCLUDES THE OPEN SESSION
OF OUR COUNCIL TODAY.
SO DR. GIBBONS, WOULD YOU LIKE
TO CLOSE US OUT?
>> THANK YOU FOR YOUR SERVICE.
WE STAND ADJOURNED.
GREAT JOB.
>> THANK YOU VERY MUCH.
[RECORDING STOPPED]