THE NHLBI TO WELCOME YOU TO THIS
311th MEETING OF THE NATIONAL
HEART, LUNG AND BLOOD ADVISORY
COUNCIL AND EXPRESS OUR SINCERE
APPRECIATION TO MEMBERS OF
COUNCIL FOR SHARING THEIR
PRECIOUS TIME AND BRAIN POWER
WITH US AS WE CONDUCT THE
BUSINESS OF NHLBI MISSION AND
WITHOUT FURTHER ADO, LET ME TURN
IT OVER TO OUR EXECUTIVE
SECRETARY DR. CHARISEE LAMAR TO
LEAD US THROUGH THE OPENING
SESSION, AND MY GAVEL IN 1 HAND,
1 HAND ON THE MICROPHONE AND THE
OTHER ON THE GAVEL, THANK YOU.
>> THANK YOU DR. GIBBONS AND
GOOD MORNING AND WELCOME, OR
GOOD AFTERNOON AND WELCOME
DEPENDING ON YOUR TIME ZONE.
WE ARE DELIGHTED TO HAVE YOU
JOIN US TODAY.
SO AS WE GET STARTED I LOOLD
TOIK TO MAKE A FEW
ADMINISTRATIVE ANNOUNCEMENTS.
THE NOTICE OF THIS SCHEDULED
MEETING WAS PUBLISHED IN THE
FEDERAL REGISTER, PLEASE RNL,
THIS IS AN OPEN SESSION TODAY
AND IT IS BEING RECORDED.
THE VIDEO OF THE SESSION WILL BE
ARCHIVED AND REMAIN AVAILABLE TO
THE PUBLIC AND NIH COLLEAGUES.
TO REVIEW BRIEFLY OUR AGENDA FOR
TODAY, WE WILL, AFTER MY
ANNOUNCEMENTS, WE WILL HAVE
DR. GIBBONS GIVE HIS DIRECTOR'S
REPORT.
WE WILL HAVE LUNCH AND THEN WE
WILL HAVE A PRESENTATION BY
DR. MUZUNO FROM THE INTRAMURAL
RESEARCH PROGRAM AND THEN WE
WILL FOLLOW UP WITH A BRIEF
REFRESHER ON THE DECISION LENS
AND THEN REMOVE INTO REVIEW FOR
CONCEPTS FOR COUNSELS AND I WILL
ADJOURN AFTER WE HAVE THOSE
DISCUSSIONS.
SO WITHOUT FURTHER ADO, I WILL
TURN IT OVER TO DR. GIBBONS SO
HE CAN GIVE HIS DIRECTOR'S
REPORT.
DR. GIBBONS?
>> ALL RIGHT.
WELL, THANK YOU, AUDIO'S OKAY,
YOU CAN HEAR?
OKAY, GREAT.
WELL, THANK YOU AND WE CAN GO TO
THE NEXT SLIDE.
THE DIRECTOR'S REPORT, AGAIN IN
OUR USUAL 2 SECTIONS, I WILL
START OFF WITH ACCOUNTABLE
STEWARDSHIP AND MOVE MORE TOWARD
OUR SCIENTIFIC PORTFOLIO
PRIORITIES.
NEXT.
NEXT SLIDE, PLEASE.
FIRST I WANTED TO EXPRESS
APPRECIATION TO OUR BOARD OF
SCIENTIFIC COUNSELORS, SORT OF
AN EXTENSION OF OUR FACA
ACCOUNTABILITY, PARTICULARLY IN
THIS CASE, FOCUSED IN ON OUR
INTRA MAURI OSHEROFFAL PROGRAM
AND INSURING THAT WE'RE
MAINTAINING A HIGH STANDARD AND
CONSTITUTES ABOUT PERHAPS 6 OR
7 PERCENT OF THE OVERALL NHLBI
BUDGET BUT IT IS AN IMPORTANT
AND COMPLIMENTARY COMPONENT TO
OUR SCIENTIFIC PORTFOLIO RELATED
TO THE DISTINKTSIVENESS OF THE
INTRAMURAL PROGRAM IN PART BY
THE CLINICAL CENTER WHICH IS THE
WORLD'S LARGEST RESEARCH
HOSPITAL AND INCLUDES A BREDTH
OF SCIENCE, OF BASIC EARLY
TRANSLATION, CLINICAL POPULATION
SCIENCE AND SO THAT UNDERGOES A
REVIEW AND GENERALLY IN JUNE
COUNCIL WE GET THOSE VERY CYCLES
OF REVIEWS OF OUR VARIOUS
INVESTIGATORS AND THEY UNDERGO A
RIGOROUS EVALUATION BY THIS BSC.
I MIGHT ALSO TAKE THIS MOMENT
NOT ONLY TO THANK THOSE ON THE
BSC WHO HAVE SERVED AND HAVE
BEEN PART OF A CLOSED SESSION
REVIEW OF ALL THE PIs THAT
CAME UP IN THIS CYCLE, WITH OUR
ADVISORY COUNCIL BUT ALSO TO
EXPRESS PUBLICLY, MY
APPRECIATION FOR DR. ALEXIS
THOMPSON WHO HAS BEEN A MEMBER
OF OUR BSC BUT RELATED TO SOME
OF THE ACTIVITIES OF THE NEW
ADMINISTRATION TRANSITION AND
THE REVIEW OF ALL OUR FACA
COMMITTEES WHICH IS THE
PREROGATIVE OF THE
ADMINISTRATION.
THE DECISION WAS MADE TO
TERMINATE HER SERVICE A COUPLE
TIME EARLIER, SHE'S BEEN
EXEMPLARY IN HER SERVICE, SO
THERE'S NO CAUSE THAT WE COULD
DISCERN SO WE EXPRESS OUR
GRATITUDE TO HER AND HER
SERVICE.
I MIGHT JUST POINT OUT
PARENTHETICALLY THAT THIS WAS A
PROCESS THAT OCCURRED THROUGHOUT
A NUMBER OF BSCs WITHIN THE
INTRAMURAL PROGRAM, MANY OF YOU
MAY HAVE SEEN REPORTS AND WE
WANTED TO THANK HER FOR HER
SERVICE.
AND AGAIN AS PART OF THAT REVIEW
OF OUR INTRAMURAL PROGRAM, WE
ALSO LIKE TO TAKE THE
OPPORTUNITY TO SHOWCASE AN
INVESTIGATOR WITHIN THE DIR SO
THAT OVERALL COUNSELS AND I WILL
QUITE FRANKLY OUR EXTRAMURAL
COMMUNITY GETS A WINDOW INTO
SOME OF OUR OUTSTANDING
SCIENTISTS THAT ARE BEING
REVIEWED, AND SO WE LOOK FORWARD
TO THE PRESENTATION TODAY OF
DR. MIZUNO, A WORLD CLASS
EXPERTS IN CRYOEM, AND VERY
EXCITED ABOUT THE CENTER THAT
SHE'S CREATED WITHIN THE
INTRAMURAL PROGRAM.
OKAY, HOPE THAT'S A LITTLE
BETTER.
OKAY, SO WE LOOK FORWARD TO HER
PRESENTATION, AS AGAIN, GIVING
YOU A TASTE OF THE INTRAMURAL
PROGRAM NOW AND ANNUAL WORK
THAT'S BEING DONE THERE.
NEXT SLIDE, PLEASE.
SO WITH THAT, ON THE INTRAMURAL
SIDE, LET ME EXPAND OUT ON THE
EXTRAMURAL ACCOUNTABLE
STEWARDSHIP AND NO SURPRISE TO
ALL OF YOU, YOU ARE AWARE WE'RE
IN WHAT'S CALLED A FULL YEAR
CONTINUING RESOLUTION WHICH IS
IN ESSENCE CONGRESS DIDN'T PUT
TOGETHER AN APPROPRIATION FOR
FY25 THAT GOES THROUGH REGULAR
ORDER AND IT REVIEWS AND
REALLOCATES, BUT RATHER IS
EXTENDING BASICALLY THE FY24
GUIDANCE AND SO THAT KEEPS US
FLAT, IN TERMS OF FY24 TO 25 AND
YOU'VE SEEN OUR PUBLISHED
FUNDING APPROACH WHICH THIS YEAR
WE STRIVE TO MAINTAIN THE PAY
LINE AS MUCH AS WE CAN BUT AS
ALL OF YOU ARE AWARE, EVEN IN A
FLAT BUDGET, GIVEN THE INFLATION
AS PART OF DOING RESEARCH AND
EVERYTHING ELSE THAT YOU'RE
AWARE OF, EVEN WITH A FLAT
BUDGET IT PUTS A LOT OF PRESSURE
SUCH THAT IT'S HARD TO DO THE
SAME AMOUNT OF WORK WITHOUT THE
SAME AMOUNT OF MONEY GIVEN THE
INCREASING COSTS OF DOING
RESEARCH.
WE'RE TRYING TO DO OUR BEST TO
MAINTAIN THAT 12 PERCENTILE AND
THEN A 10-POINT BONUS BUMP FOR
ESIs AND MAKING RECOLLECT
ADJUSTMENTS TO STRETCH THOSE
RESOURCES, THAT'S WHERE WE ARE
WITH 25 AND OBVIOUSLY DESPITE
ALL THE THINGS HAPPENING WITH
THE EXECUTIVE TRANSITION AND A
LOT OF SHIFTS BEING MADE IN HOW
FUNDING IS DONE OR AWARDS ARE
BEING MADE, WE'RE NEVERTHELESS
TRYING TO MAKE PROGRESS IN
GETTING THOSE AWARDS OUT IN
ACCORDANCE WITH THESE
GUIDELINES.
NEXT SLIDE, PLEASE.
AND TOWARD THAT END, I THINK
IT'S ALWAYS IMPORTANT TO
ACKNOWLEDGE WHAT'S HAPPENING AND
ADDRESS THE ELEPHANT IN THE ROOM
OF THE NEW ADMINISTRATION
TRANSITIONS AND HOW THAT'S
AFFECTING OUR OPERATIONS AND HOW
IT'S AFFECTING YOU AS PART OF
THE EXTRAMURAL COMMUNITY.
I'M SURE YOU ARE AWARE THE
PRESIDENT'S BUDGET AS WELL AS
THE ADMINISTRATION'S INTENTION
TO PROPOSE REORGANIZATION OF NIH
IN WAYS YOU HAVE PROBABLY SEEN
MODELS LIKE THIS BEFORE, AS I
RECALL HAROLD VARMIS EVEN
CONSIDERED VARIOUS
ORGANIZATIONAL STRATEGIES, THESE
THINGS SEEM TO COME UP EVERY
5-10 YEARS AND THIS IS THE MOST
RECENT 1.
I SUPPOSE WE'RE BEING FOLDED
INTO SOMETHING CALLED WHAT IS IT
BODY SYSTEMS ALONG WITH MY GOOD
FRIENDS AT DDK AND AMS, BUT
THESE ARE PROPOSALS REMINISCENT
OF THINGS THAT HAVE BEEN OUT
WITH ROGERS IN CONGRESS, IT'S
REMINISCENT OF THINGS THAT ARE
WRITTEN UP IN PROJECT 2025
DOCUMENTS, ET CETERA, SO, THESE
MODELS HAVE BEEN OUT THERE BUT
IT'S IMPORTANT FOR US TO
APPRECIATE THAT IT'S REALLY UP
TO CONGRESS TO AUTHORIZE ANY
RESTRUCTURING OR REORGANIZATION.
THE FACT THAT THERE'S 27 ICs,
IS IN FACT A CREATION OF
CONGRESS, THAT'S ITS WORK AND
THEN IT AUTHORIZED THAT
STRUCTURE AND APPROPRIATES
ACCORDING TO THOSE EXISTING
STRUCTURES SO AGAIN, I KNOW
THERE MIGHT BE A LOT OF CONCERNS
HERE, BUT AT THIS STAGE STILL
JUST A PROPOSAL.
THERE ARE PROCESSES, SOME
INVOLVING STRATEGIC MANAGEMENT
REVIEW BOARD OR SMRB, THAT'S
CONGRESSALLY -- YEAH, I THINK
MANDATED AS A MECHANISM BY WHICH
THESE SORTS OF CONSIDERATIONS
ARE ADJUDICATED AS A SYSTEMATIC
THOUGHTFUL PROCESS BY NIH, AND
SO WE'RE HOPEFUL THEIR NEW NIH
DIRECTOR OF LEVERAGE THAT
MECHANISM TO EVEN CONTEMPLATE
THIS SORT OF CONSIDERATION AND
THAT HAS BEEN DONE BEFORE WITH I
BELIEVE A MERGER OF NIDA AND
NIAAA, IN TERMS OF ALCOHOL AND
DRUG ABUSE THROUGH THAT
MECHANISM.
SO THERE IS PRECEDENT FOR THIS
AND THAT'S WHY I ENCOURAGE US TO
KEEP THE ANXIETY DOWN UNTIL
THOSE SORT OF PROCESSES PLAY
OUT.
NEVERTHELESS, PROBABLY THE MORE
STRIKING PART OF THE PRESIDENT'S
BUDGET WAS THE 40 +% CUT OVER
ALL, A LOSS OF OVER 18 BILLION
DOLLARS, BACK TO A BASE OF 27
FOR NIH.
AND FOR THOSE WHO WATCH THE NIH
DIRECTOR'S HEARING WITH THE
APPROPRIATIONS RECOGNIZE THAT
BOTH SIDES OF THE AISLE QUITE
FRANKLY ARE CONCERNED ABOUT THE
DEPTH OF THOSE CUTS AND THE
IMPLICATIONS OF IT.
SIMILARLY, I DON'T NEED TO TELL
THIS GROUP 1 OF THE EXECUTIVE
ORDERS OF THIS NEW
ADMINISTRATION WAS TO PUT A CAP
ON INDIRECT COSTS AT 15%, THOSE
THINGS ARE BEING CHALLENGED IN
COURT AND IT'S NOTABLE THAT AS
FAR AS I KNOW AND WE'VE GONE
THROUGH THIS BEFORE, THE NIH
DOESN'T HAVE ANY KIND OF
SOLITTORY, STATUTORY AUTHORITY
TO JUST UNILATERALLY CHANGE THE
INDIRECT COST RATE.
AND SO THAT'S PART OF WHAT IS
BEING CHALLENGED.
I DON'T THINK NIH EVEN WORKS
THROUGH THE CALCULATIONS OF ALL
THOSE SORTS OF ELEMENTS AND SO,
THIS IS AN AREA WHERE I WOULDN'T
GET IMMEDIATELY PANICKED.
THIS IS SOMETHING THAT WILL BE
IN PLACE IN THE VERY NEAR TERM
THOUGH IT WILL BE SOMETHING THAT
I SUSPECT WILL BE EXAMINED,
HOPEFULLY IN A MORE THOUGHTFUL
WAY.
AGAIN, WE'RE PERHAPS IT IS TIME
TO STEP BACK AND INSURE WE HAVE
THE BEST MODEL, WE HAVE THE BEST
CRITERIA, WE HAVE THE BEST
PROCESS, AND QUITE FRANKLY FOR
INSTITUTIONS TO THINK HOW THEY
MIGHT BE MORE ACCOUNTABLE
STEWARDS BY TRANSPARENCY ABOUT
WHERE THAT MONEY GOES AND
INSURING THAT IT IS RELATED TO
REAL RESEARCH COSTS THAT ARE
ASSOCIATED WITH THESE PROGRAMS
AND SO, THAT SCENARIO OF I THINK
COLLECTIVE RESPONSIBILITY THAT
THE WHOLE ECOSYSTEM SHOULD BE
LOOKING AT IS HOW DO WE SUSTAIN
THE WORLD'S GREATEST RESEARCH
INFRASTRUCTURE AND PARTNERSHIP
BETWEEN THE GOVERNMENT AND
ACADEMIC INSTITUTIONS AND THEIR
INVESTIGATORS TO FUEL LEADING
EDGE SCIENCE AND SO WE HOPE
THERE WILL BE A THOUGHTFUL
DIALOGUE ABOUT THAT WITH THE
COMMUNITY MOVING FORWARD.
CERTAINLY YOU HAVE ALSO SEEN
WITH THE NEW ADMINISTRATION
TRANSITION, VARIOUS PRIORITIES,
MANY RELATED TO CHRONIC DISEASE
AND THE SLOWING RATE OF INCREASE
OF LIFE EXPECTANCY, AND THAT THE
ADMINISTRATION HAS EXPRESSED
INTEREST IN CERTAIN TOPIC AREAS
LIKE NUTRITION, ENVIRONMENTAL
FACTORS, TOXINS, AND EXPOSURES,
ALL OF WHICH MAY INFLUENCE
CHRONIC CONDITIONS, MANY OF
WHICH ARE IN OUR MISSIONARY, AND
IN OUR PORTFOLIO, SO WE LOOK
FORWARD TO LEARNING MORE ABOUT
THIS ADMINISTRATION'S PRIORITY
AREAS IN PART BECAUSE I THINK WE
MIGHT FIND A GREAT DEAL OF
ALIGNMENT WITH A LOT OF THINGS
WE'VE BEEN PURSUING AT THE NHLBI
RELATED TO PRECISION PREVENTION
AND PREEMPTION OF CHRONIC
DISEASE.
AND SO I REMAIN HOPEFUL AND
OPTIMISTIC THAT AS STAKEHOLDERS
ARE ENGAGED WITH CONGRESS AND WE
FIND OUR APPROPRIATION, THAT
THERE'S A LOT WE CAN DO TO
ADVANCE THAT ASPECT OF THIS
ADMINISTRATION'S AGENDA AND WE
LOOK FORWARD TO THAT.
NEXT SLIDE.
TOWARD THAT END, THE KEY THING
THAT I HOPE WE AS AGAIN A CIRCLE
OF PARTNERS AND AN ECOSYSTEM IS
TO ADDRESS THE VALUE PROPOSITION
FOR THE SHARED SUSTAINABLE
COMMITMENT TO A GROWING
INVESTORMENT IN BIOMEDICAL
RESEARCH THAT OUTPACES INFLATION
IN A WAY THAT CAN MAKE AN IMPACT
SUCH THAT WE CAN REDUCE THE
BURDEN OF DISEASE IN THIS
COUNTRY.
SO IT'S 1 OF THE THINGS THAT
WE'RE HOPING THAT STAKEHOLDERS
WILL PURSUE, WITH CONGRESS IS
HOW TO INDEED ACHIEVE THAT END
AND FOR THOSE OF YOU WHO HEARD
THE HEARING YESTERDAY, THERE'S
BEEN A COMMITMENT, SENATOR
DURBIN ARTICULATED VERY WELL
THAT LED TO THE UPSLOPE DURING
THE LAST OH 7, 8 YEARS AND THE
KEY THING IS REALLY TO MAINTAIN
THAT MOMENTUM AND GET BACK TO IT
AND CERTAINLY NOT GO BACKWARDS
WITH A 40% CUT.
SO I HOPE THAT WE CAN WORK
COLLECTIVELY TO PUT US BACK ON
THAT TRACK.
NEXT SLIDE, PLEASE.
I ALSO WANT TO ADDRESS THE
REALITIES AND THE ELEPHANT IN
THE ROOM IN TERMS OF A LOT OF
THE THINGS RELATED TO CHANGES
OVER LAST 5 MONTHS WHERE YOU HAD
CERTAIN FOLKS WITH CHAIN SAWS
AND EVERYONE HERE BY NOW HAS
HEARD OF DOGE, AND THEIR
APPROACH TO CHANGING THE FEDERAL
GOVERNMENT AND THIS IS RESULTED
IN WHAT'S CALLED REDUCTIONS IN
FORCE IMPLEMENTED BY DOJO THAT
HAS HAD AN IMPACT ON OUR STAFF
AND STAFFING WHERE WE'VE LOST A
NUMBER OF STAFF, OTHER SORTS OF
TERMINATIONS AND THAT'S HAD AN
IMPACT ACROSS OUR ORGANIZATION
AND IS INDEED INCLUDED CERTAIN
SUBUNITS OF OUR INSTITUTE.
THESE ARE THINGS THAT ALSO
INVOLVE A SHIFT IN THE BALANCE
REPORTEDLY BETWEEN FUNCTIONS OF
THE AGENCY THAT WILL BE DONE IN
THE OFFICE OF THE DIRECTOR
RELATIVE TO FUNCTIONS AND
ACTIVITIES THAT ARE DONE IN EACH
OF THE 27 ICs AND OVER TIME
THOSE THINGS -- THERE'S ALSO A
BALANCE INTENTION BUT FOR THE
MOST PART THE ICs HAVE
MAINTAINED AT LEAST SOME
FUNCTIONALITY AND KEY THINGS
CRITICAL TO THE BUSINESS OF
SCIENCE AND EXECUTING ON THAT
AND THAT'S HAD AN EXAMPLE ON OUR
FOIA OFFICE, ETHICS,
COMMUNICATIONS, OUR PLANNING AND
EVALUATION, SO A NUMBER OF
FUNCTIONAL AREAS THAT ARE
IMPORTANT FOR US TO DO THE
BUSINESS OF SCIENCE OF NHLBI OR
BEING MOVED INTO A CENTRAL
SITUATION AND OUR STAFFING HAS
BEEN REDUCED AND THERE WAS A
THREAT FOR THAT TO ALSO HAPPEN
FOR OUR ACQUISITIONS AND IT RUNS
OUR RESEARCH AND DEVELOPMENT
CONTRACTS THAT OFTEN SUPPORTS
ALL OUR COHORT STUDIES, ET
CETERA OF MOVING THAT DOWN TO
GENERAL SERVICES ADMINISTRATION
AS IF, YOU KNOW RUNNING THE ARIC
STUDY WAS SIMILAR TO ORDERING
PENCILS AND PAPER FOR THE AGENCY
AND HOPEFULLY, COMMON SENSE HAS
PREVAILED IN A RECOGNITION THAT
THESE ARE COMPLEX THINGS THAT
REQUIRE CLOSE SCIENTIFIC
EXPERTISE AS WELL AND SO FAR,
WE'VE BEEN ABLE TO SUSTAIN OR
OTHER TRANSACTIONAL AUTHORITY
OFFICE AND ACQUISITION.
THOUGH, AGAIN, HOW THE REPORTING
FUNCTIONS ARE GOING TO WORK
REMAINS TO BE SEEN.
SIMILAR CHANGES ARE HAPPENING IN
OUR INFORMATION TECHNOLOGY.
SO I WON'T BORE YOU WITH ALL THE
SAUSAGE MAKING EXCEPT TO SAY
THAT ALL OF THESE THINGS HAVE AN
EFFECT ON OUR FUNCTIONALITY AS
AN INSTITUTE AND THEREFORE MAY
AFFECT YOU ALL AS WE ENGAGE YOU
AS STAKEHOLDERS AND AWARDEES AND
APPLICANTS AS THESE CHANGES AND
LOSSES IN STAFFING WILL HAVE AN
IMPACT ON OUR OPERATIONS.
THE OTHER THAN I WILL MENTION IS
THE OFFICE OF SCIENTIFIC POLICY
WHERE EDUCATION AND ENGAGEMENT
WHERE A LOT OF OUR STAKEHOLDER
INTERACTIONS MEET AND RESIDE,
THAT'S WHERE A SMALL SICKLE CELL
PROGRAM OR AN ORGANIZATION, ALL
OUR -- OVERA HUNDRED PATIENT
INTEREST GROUPS WERE ENGAGED IN
THE OFFICE AND WE'VE LOST A LOT
OF STAFF THERE AND THAT'S GOING
TO HAVE IMPLICATIONS WITH HOW WE
INTERACT WITH THE VARIOUS
COMMUNITIES WE SERVE.
SO WE'RE HOPEFUL THERE WILL BE A
GREATER RECOGNITION, THE
IMPORTANCE OF SUSTAINING THAT
ACTIVITY AT THE LEVEL OF
INSTITUTE BUT THAT'S AN ONGOING
DISCUSSION.
FINALLY, ON THE OTHER SIDE
THERE, YOU SEE THAT SOME OF THE
EXTRAMURAL PROGRAMS HAD A LOSS,
THAT'S PARTICULARLY BEEN FELT
NOW IN PROGRAM DIVISIONS BUT
ALSO IN OUR DIVISION OF
EXTRAMURAL RESEARCH ACTIVITIES
AND PARTICULARLY OUR SCIENTIFIC
REVIEW SECTION WHICH IS
UNDERGONE A SHIFT OVER TO CSR AS
THAT SCIENTIFIC REVIEW GETS
CENTRALIZED IN CSR.
SO JUST TO HAVE A SENSE OF
SOMEBODY IMPACTING OF THESE
TRANSITIONS AND THE DOGE CUTS
AND RIFTS ON OUR STRUCTURE AND
FUNCTIONALITY FOR YOUR
AWARENESS.
NEXT SLIDE, PLEASE.
SIMILARLY, ANYONE WHO'S BEEN
AWAKE RECOGNIZES THAT THERE HAVE
BEEN A FLURRY OF EXECUTIVE
ORDERS AS PART OF THIS NEW
ADMINISTRATION AND MANY OF THEM
DO RELATE TO OUR RESEARCH
PORTFOLIO.
THIS IS JUST A SAMPLING OF SOME
OF THEM.
HOPEFULLY YOU CAN READ FOR
YOURSELF WHAT THEY'RE FOCUSED IN
ON AND THIS PROVIDES YOU A TEXT
OF THE TERMINATION LETTERS OF
DOGE AND OTHERS HAVE AFFIXED TO
THAT TERMINATION IN ALIGNMENT
WITH THE EXECUTIVE ORDERS.
I WON'T READ THIS TO THE EXTENT
THAT QUITE FRANKLY IT DOESN'T
REFLECT A SENSIBILITY THAT I
HAVE OR THAT I THINK IS
APPROPRIATE FOR A RESEARCH
AGENCY BUT NEVERTHELESS, WE'RE
BEING TRANSPARENT ABOUT WHAT IS
HAPPENING AND WHAT YOU WILL SEE
AS A CONSEQUENCE, NEXT SLIDE,
PLEASE.
NEXT SLIDE.
TOWARD THAT END, THERE'S CERTAIN
CHANGES THAT HAVE BEEN MADE THAT
AGAIN, I THINK THE RESEARCH
COMMUNITY SHOULD BE AWARE OF.
CLEARLY YOU'RE ALREADY FEELING
SOME OF THE GRANT AWARD
TERMINATIONS AND THE PATTERN
RELATED TO SPECIFIC PRIORITIES
OR AREAS OF DEPRIORITIZATION
THAT THE NEW ADMINISTRATION I
THINK ARE FAIRLY MANIFEST TO YOU
AND IN WAYS THAT ARE RAISING
QUESTIONS ABOUT HOW WE PURSUE
RESEARCH AFFECTING CERTAIN
SUBGROUPS AND SPECIAL
POPULATIONS AND GROUPS THAT ARE
DISPROPORTIONATELY AFFECTED AS
AMERICANS IN HEALTH AND DISEASE,
WE THINK THAT'S STILL IMPORTANT
IN FULFILLING OUR MISSION AND
SERVING THE AMERICAN PEOPLE, ALL
THE AMERICAN PEOPLE AND THAT OUR
SCIENCE SHOULD REFLECT THAT
SERVICE TO ALL INCLUDING VARIOUS
GROUPS WHO HAVE DIFFERENT HEALTH
OUTCOMES AND SO THAT'S SOMETHING
WE WILL CONTINUE TO WORK THROUGH
ALONG WITH MANY OTHER AREAS OF
OUR WORKFORCE IN ENSURING WE
HAVE INCLUSIVE EXCELLENCE AS
PART OF WHAT WE DO, RECOGNIZING
THAT TALENT COMES FROM
EVERYWHERE AND WE'RE ABOUT
PROMOTING THAT OPPORTUNITY TO
EVERYONE IN SERVICE TO ALL
COMMUNITIES.
SO REALLY I'VE ALREADY ALLUDED
TO THE CENTRALIZATION OF CSR
REVIEW, IT'S ALWAYS BEEN CSR IS
THE BULK OF PROBABLY LIKE 80% OF
OF
REVIEW, BUT INSTITUTES,
CERTAINLY OURS IS A STATUTORY
AUTHORITY TO DO ITS OWN REVIEWS,
AND WE HAVE WITH OUR OWN SPECIAL
EMPHASIS PANELS SO FOR EXAMPLE,
AN AREA SUCH AS CLINICAL TRIALS,
THAT'S NOW SOMETHING THAT'S GONE
AWAY AND WILL HAVE TO WORK
THROUGH HOW WE MIGHT ADAPT TO
THAT BUT THAT WILL BE A
TRANSITION AND THAT WILL AFFECT
OUR CLINICAL RESEARCH PORTFOLIO
AS WE FIGURE OUT HOW TO WORK
UNDER A CSR SYSTEM RELATIVE TO
AN IC BASED PEER REVIEWED SYSTEM
INSTEAD OF NOFOs.
TOWARD THAT END, YOU SHOULD BE
AWARE OF THE COMMUNICATION
CENTRALIZATION, I'VE ALREADY
KIND OF ALLUDED TO IT THAT HOW
WE DO PUBLIC EDUCATION, HOW WE
DO HIGHLIGHTING, THE ACTIVITIES
OF NHLBI INVESTIGATORS AND
PROBABLY MOST IMPORTANTLY HOW WE
ENGAGE OUR COMMUNITY OR OUR
PROFESSIONAL SOCIETIES AND
PUBLIC INTEREST GROUPS WILL BE
CHANGED BY THESE TRANSITIONS AND
IT WILL HAVE AN IMPACT.
AND FINALLY, AGAIN, I'VE ALREADY
ALLUDED TO IT, SUBSTANTIAL
CHANGES IN HOW WE GO ABOUT
SOLICITING NOFOs, AND
PROVIDING YOU WITH FUNDING
OPPORTUNITY ANNOUNCE ANNOUNCEMD
THERE IS AN EFFORT TO REDUCE THE
NUMBER OF ACTIVE NOFOs BY
HALF, I THINK IT WAS SOMETHING
LIKE 7 OR 800 ARE OUT THERE AND
THEY ARE TRYING TO AIM IT DOWN
TO MAYBE 400, 500.
SO EACH IC MAY HAVE A CAP ON THE
NUMBER OF ACTIVE NOFOs, SO YOU
CAN IMAGINE THAT WILL HAVE AN
IMPACT TO WHAT YOU MAY BE
SEEING, SPECIFICALLY TO IC
NOFO,s.
ONE STRATEGY IS TO DO THIS, OR
MORE COLLABORATION OR CLUSTERING
OF NOFOs IN VARIOUS AREAS OF
CLINICAL TRIALS RATHER THAN EACH
IC HAVE ITS OWN SUITE.
SO THOSE ARE THE THINGS, THE
SAUSAGE MAKING THAT DWELL ON AS
WE ADAPT TO THE NEW
ADMINISTRATION AND SOME OF ITS
CHANGES IN HOW IT WANTS TO
MANAGE THINGS.
NEXT SLIDE, PLEASE.
AND I JUST WANT TO CONVEY OR
WELCOMING TO OUR NEW NIH
DIRECTOR JAY BHATTACHARYA, HE
HAS BEEN HERE I GUESS ALMOST A
COUPLE MONTHS NOW AND WE'RE
HOPEFUL TO GET HIM TO COME TO
OUR COUNCIL.
HE'S A LITTLE BUSY THIS WEEK AND
COULDN'T MAKE THIS GIIVE HE HAD
A SENATE HEARING YESTERDAY BUT
WE'RE HOPEFUL THAT EITHER
OCTOBER OR SOMETIME IN THE NEAR
FUTURE WE COULD HAVE HIM COME
AND ADDRESS THE NHLBI COMMUNITY.
YOU'VE HEARD OF HIS VERY HIGH
LEVEL VISION AND ISSUES, VERY
MUCH INCLINED TOWARD
APPRECIATING AND RECONCILING AND
RECKONING WITH WHAT HE PERCEIVES
AS CERTAIN CHALLENGES RELATED TO
THE COVID PANDEMIC AND ISSUES OF
TRUST THAT HAVE BEEN COMPROMISED
RELATED TO THAT AND THAT'S 1 OF
HIS PRIORITIES IN PART BY
FOCUSING ON SCIENCE THAT MATTERS
TO THE PUBLIC IN THAT WAY
ALIGNING WITH THE FOCUS ON
ADDRESSING CHRONIC DISEASE AND
ADDRESSING ADVANCES IN THAT
SPACE AS PART OF MAKING AMERICA
HEALTHY
I BELIEVE HE WANTS ANY TO FUND
REPLICATION, AND REPLICATION
STUDIES, REPLICATION OF WORK AND
DATA SHARING IN WAYS THAT ARE
MORE TRANSPARENT.
SIMILARLY, WE'VE HEARD HIM
TALKING ABOUT MAKING BIG
ADVANCES.
BY THAT I THINK HE'S ADVANCED A
THESIS WHERE THERE'S MAYBE TOO
MUCH GROUP THINK, INCREMENTALISM
THAT MAY BE PART OF THE PEER
REVIEW AND FUNDING SYSTEM.
THOSE CAMPAIGNS HAVE BEEN
RAISED, ENSURING HIGH RISK, HIGH
REWARD, LEADING EDGE WORK AND WE
LOOK FORWARD TO SEEING HOW HE
FLESHES THAT OUT.
WORKING WITH HIM TO SEE HOW WE
CAN DO THAT.
HIS ANALYSIS BOILS DOWN TO
FUNDING MORE EARLY STAGE
INVESTIGATORS EARLIER, SOMETHING
NOT A PARTICULARLY NOVEL
INTENTION.
BUT ONE WE HAVE TO CONTINUALLY
WORK ON.
INDEED, PROBABLY ONE OF THE BEST
WAYS TO DO THAT IS MAINTAIN A
PAYLINE AND 10-POINT BONUS AND
ENSURE WE GET THEM OFF TO A
START THAT'S SUSTAINABLE.
AND NOT SCARE THEM WITH A 40%
CUT.
BUT THAT'S AN AREA THAT I HOPE
WE CAN, AGAIN, ADDRESS TOGETHER.
AND THEN FINALLY SAFETY AND
TRANSPARENCY, AGAIN TO A CERTAIN
EXTENT RELATES TO DATA AND DATA
SHARING AS WELL AS FINALLY
ACADEMIC FREEDOM.
AND A DIVERSITY OF VIEWPOINTS
AND DEBATE AND DISSENT, AND THAT
SORT OF DIALOGUE THAT ALL
SCIENTISTS ENGAGE IN NATURALLY
AND ONE WHERE I DON'T THINK
THERE WILL BE A LOT OF
DISAGREEMENT ON.
I THINK WHERE THERE'S SOMETIMES
A CHALLENGE IS I DON'T THINK
THAT ANY OF US ARE WELL SERVED
ADVANCING SCIENCE THE MORE WE
POLITICIZE SCIENCE BECAUSE IT'S
ALREADY HYPERPARTISANSHIP THAT'S
GIVING THESE VIEWPOINTS AND I
THINK UNDERGIRDS ISSUES OF TRUST
WITH CERTAIN COMMUNITIES THAT WE
NEED TO ENGAGE BETTER WITH.
AND URGING ACADEMIC FREEDOM IS
REALLY OPENING UP DIALOGUE AS
OPPOSED TO TERMINATING GRANTS
THAT DON'T HAVE THE IDEOLOGY
THAT AN INCUMBENT ADMINISTRATION
MAY HAVE.
I HOPE WE'RE NOT ON A PENDULUM
GOING TO WOKE AND ANTI-WOKE AS
OPPOSED TO JUST FOCUSING ON THE
SCIENCE AND TONING DOWN SOME OF
THE PARTISANSHIP BECAUSE THAT'S
REALLY WHERE SUSTAINED FUNDING
AND SUPPORT OF NIH HAS ALWAYS
BEEN NONPARTISAN, BICAMERAL,
BIPARTISAN IN TERMS OF THAT
STRUCTURE, AND IT'S BECAUSE
SCIENCE AND HEALTH DON'T KNOW
RED STATES OR BLUE STATES,
PATIENTS YOU CARE FOR, YOU DON'T
CARE WHAT POLITICAL AFFILIATION
IS; YOU'RE THERE TO ADDRESS
THEIR SUFFERING.
SCIENCE IS LIKEWISE NOT ABOUT
RED AND BLUE.
I HOPE WE CAN GET TO THAT STAGE.
NEXT SLIDE.
TOWARD THAT END, ONE OF THE
THINGS THAT ACTUALLY JAY
PRESENTED IN ONE OF HIS TALKS
WAS ON THE LEFT-HAND SIDE, WHERE
HE BUILDS IN THAT ARGUMENT THAT
DURING COVID THERE WAS THAT
CLEAR SLIPPAGE IN TERMS OF
SURVEYS OF AN ELEMENT OF THAT
TRUST.
WE DIG A LITTLE BIT DEEPER INTO
THAT SAME STUDY, ALTHOUGH THE
AGGREGATE LOOKS LIKE IT'S A
GENERAL SHIFT DOWN, ACTUALLY
THAT NEXT LAYER OF ANALYSIS
WOULD SUGGEST THAT IT'S STILL
PRETTY HIGH AMONG CERTAIN
SEGMENTS OF OUR POPULATION.
AND, YOU KNOW, HAD A LITTLE BUMP
RELATED TO COVID BUT NOTHING
THAT COULDN'T BE RECOVERED.
AND YOU CAN SEE THE MARKED
DIFFERENCE, AGAIN, BY RED AND
BLUE.
AND SO I THINK THAT'S MORE OF
WHAT WE MAY NEED TO THINK ABOUT
IS HOW WE'RE ENGAGING ALL PARTS
OF THE AMERICAN POPULATION AND
NOT SLIPPING SCIENCE INTO THE
SAME DIVISIVENESS.
ON THE RIGHT YOU CAN SEE AGAIN
PART OF THIS ANALYSIS, CERTAINLY
IN ONE GROUP EDUCATION
ATTAINMENT MIGHT PLAY A ROLE IN
TERMS OF TRUST IN SCIENCE, TRUST
IN SCIENTISTS.
BUT THAT'S NOT UNIFORM.
AND, AGAIN, RAISES SOME QUESTION
HOW WE'RE REACHING ALL
COMMUNITIES AND HOW WE'RE
PERCEIVED AS TRUSTWORTHY BY
VARIOUS COMMUNITIES.
AND WHAT WE MAY NEED TO DO TO
REGAIN THAT SENSE OF
TRUSTWORTHINESS WITH THOSE
COMMUNITIES.
NEXT SLIDE.
AND I THINK THEY ARE TELLING US
SOMETHING ABOUT HOW WE MAY THINK
ABOUT APPROACHING ALL
COMMUNITIES AND ALL THAT WE
SERVE, PERHAPS IN A MORE
EFFECTIVE WAY.
THIS IS SOMETHING WHERE THE
PUBLIC SURVEY ABOUT SCIENTISTS,
THEY TRUST US TO DO THE RIGHT
THING FOR THE PUBLIC, BUT WHAT
DO THEY THINK ABOUT US?
THEY GIVE US PROPS FOR WHAT WE
DO.
WE'RE ALL SMART PEOPLE.
AND THAT'S GREAT.
AND THEY APPRECIATE OUR SKILLS
IN THAT WAY, BUT YOU CAN SEE THE
THINGS WE FALL BELOW 50 THAT
WE'RE TALKING ABOUT THIS
EARLIER, YOU KNOW, I THINK WE
NEED TO GET BETTER AT
COMMUNICATING OUR VALUE
PROPOSITION AND HOW WE CAN BE
HELPFUL TO THE AMERICAN PUBLIC.
AND SO I THINK ALL OF US CAN
BECOME BETTER COMMUNICATORS OF
WHAT WE DO TO ENGENDER THAT
SENSE OF TRUST AND SERVICE TO
THE COMMUNITY.
ANOTHER THING ABOUT US BEING
ALOOF, OLD, UNAPPROACHABLE,
KNOW-IT-ALLS, AND WE ALL ARE
SAGES ON THE STAGE AND WE KNOW
WHAT EVERYONE OUGHT TO DO.
AND WE TELL THEM.
AND SO THOSE ARE THINGS I THINK
WE DEAL WITH THIS CHALLENGE TO
INSTITUTIONS INCLUDING ALL THE
REALLY ACADEMIC INSTITUTIONS
WHICH ARE ALSO UNDER DECLINE IN
TRUST THAT WE DO INTROSPECTION
ABOUT WHAT WE COULD BE DOING
BETTER IN THIS SPACE AS OPPOSED
TO CHANGE, ACKNOWLEDGE WE DO
HAVE A PROBLEM, AND START TO
WORK ON HOW WE CAN BE MORE
EFFECTIVE AT SERVING THE PUBLIC.
AND ENGENDER THEIR TRUST.
AND, AGAIN, YOU CAN SEE SOME
POLARITIES IN THIS REGARD.
NEXT SLIDE.
SO I WANTED TO WALK THROUGH THAT
AS WE TRY TO ADAPT AND NAVIGATE
THIS CHANGE, THAT WE APPROACH IT
WITH A SENSE OF HUMILITY THAT WE
HAVEN'T GOTTEN IT ALL RIGHT ALL
THE TIME.
THERE ARE THINGS THAT I THINK WE
DO NEED TO GET BETTER AT,
PROBABLY HAVE TO LISTEN MORE.
AND AGAIN COME WITH THAT CULTURE
OF HUMILITY IN ADDRESSING A LOT
OF THESE COMMUNITIES THAT DON'T
TRUST US.
AND WHAT WE MAY NEED TO DO TO
ENGENDER MORE TRUST.
AND I THINK THAT WILL BE PART OF
OUR CHALLENGE OVER THESE NEXT
COUPLE YEARS TO EXTEND THAT IT'S
GOING TO BE CRITICAL FOR US TO
FULFILL THE MISSION AND ACTUALLY
THE PRIORITIES OF THIS
ADMINISTRATION BECAUSE IT'S MANY
OF THOSE SAME COMMUNITIES THAT
ARE SUFFERING THE MOST.
I DON'T KNOW THAT THEY ARE
GETTING THE BENEFITS OF THE
SCIENCE WE'RE DOING.
AND IF THEY ARE NOT, AND THAT'S
PART OF THEIR LACK OF TRUST,
AGAIN, I THINK THAT MIGHT BE ON
US AS TO HOW WELL WE'RE
ADDRESSING THEIR NEEDS AND
LISTENING TO THEIR NEEDS AND
BRINGING SCIENCE TO BEAR IN A
WAY THAT BENEFITS THEM AND THEIR
COMMUNITIES.
NEXT SLIDE.
SO, I'LL START TO WRAP UP WITH
WHAT I HOPE IS A RESEARCH AGENDA
THAT ALIGNS WITH WHAT THE NEW
ADMINISTRATION HAS SAID ARE ITS
PRIORITIES, AND ITS CONCERNS.
AND ONE IS THIS LIFE EXPECTANCY
AND HOW IN OUR COMPARABLE
WEALTHY NATIONS IT'S HAD A MORE
RAPID UPSLOPE THAN IN THE U.S.
AND OBVIOUSLY THAT DIP AT THE
END WAS COVID THAT WE'RE STILL
TRYING TO BOUNCE BACK FROM.
I ALSO THOUGHT IT'S IMPORTANT WE
TALK ABOUT LIFE EXPECTANCY
DIFFERENCES THAT THOSE ARE MORE
EXPERT THAN I RECOGNIZE IF
YOU'RE GOING TO CHANGE THAT LIFE
EXPECTANCY CURVE, THE BIGGEST
CHANGES HAPPEN EARLIER ON IN
TERMS OF LOSSES AND PREMATURE
DEATHS, PER SE.
SO I THINK IT IS NOTABLE THAT IF
YOU LOOK AT WHAT HAS ALSO
HAPPENED OVER THAT TIME PERIOD,
THE PREVALENCE OF TWO OR MORE
CHRONIC CONDITIONS AMONGST
RELATIVELY YOUNGER ADULTS IS ON
THE UPSLOPE, PROBABLY IN PART
RELATED TO OBESITY, ET CETERA,
BUT I THINK THIS IS AN AREA OF
CONCERN THAT IS GOING TO
CONTINUE TO DRIVE CHRONIC
DISEASE IN THIS COUNTRY THAT
DOES NEED TO BE ADDRESSED.
NEXT SLIDE.
AND TOWARD THAT END, I THINK
IT'S ALSO IMPORTANT TO
APPRECIATE THE DIVERSITY OF OUR
COUNTRY AND THE VARIOUS
COMMUNITIES.
ALTHOUGH THAT AGGREGATE LIFE
EXPECTANCY CURVE HAS A CERTAIN
SHAPE, IT'S OBVIOUSLY A FAMILY
OF CURVES, AND THERE ARE
SUBPOPULATIONS IN AMERICA THAT
DON'T HAVE THE SAME LEVEL OF
LIFE EXPECTANCY OR EVEN SLOPE.
SOME OF THOSE CURVES ARE GOING
IN THE WRONG DIRECTION ACTUALLY.
AND SO IF WE'RE GOING TO ADDRESS
PANDEMIC OF CHRONIC DISEASE, IF
YOU WILL, I THINK WE HAVE TO
APPRECIATE THE DIFFERENT
POPULATIONS, PARTICULARLY IF
WE'RE GOING TO REDRESS IT.
NEXT SLIDE.
INDEED AS PART OF THAT ANALYSIS
COMPARED TO OTHER WEALTHY
NATIONS, YOU CAN SEE THAT
DECLINE IN CARDIOVASCULAR DEATHS
PARTICULARLY FOR THOSE UNDER AGE
70, YOU CAN SEE OUR SLOPE IS
KIND OF FLATTENED OUT RELATIVE
TO OTHER COUNTRIES, AND IF YOU
PULL OUT THOSE AGED 15 TO 49,
SUBSTANTIAL DIFFERENCE IN CVD
DEATHS, IN THIS REALLY PREMATURE
POPULATION THAT AT LEAST I FOUND
QUITE DISTURBING RELATIVE TO
PEER NATIONS.
IN ADDITION THERE ARE OBVIOUSLY
OTHER FACTORS IN THIS COUNTRY IN
TERMS OF LOSSES FROM GUN
VIOLENCE AND DRUG OVERDOSES THAT
MAY BE VERY DIFFERENT FROM OUR
PEER COUNTRIES THAT AFFECTS LIFE
EXPECTANCY CURVES, BUT GIVEN OUR
PORTFOLIO THIS KEY ONE THAT I
THINK WE SHOULD BE PAYING
ATTENTION TO.
NEXT SLIDE.
AND TOWARD THAT END, I THINK
IT'S, AGAIN, IMPORTANT TO
APPRECIATE THAT, YES, THOSE
CURVES OF THE AGGREGATE FOR OUR
NATION RELATIVE TO WEALTHY
NATIONS HAS THAT DIFFERENT SLOPE
BUT EVEN THE SLOPES WITHIN THIS
COUNTRY ARE DIFFERENT, AND YOU
CAN SEE DIFFERENT PATTERNS AND
HOW IN FACT WITH A LENS OF
SOCIAL DETERMINANTS AND SOCIAL
DEPRIVATION THE RELATIONSHIP
BETWEEN THOSE FACTORS AND
CARDIOVASCULAR MORBIDITY AND
MORTALITY, AND YOU CAN SEE THE
CLEAR GRADIENT RELATED TO SOCIAL
DEPRIVATION AND EVEN SOCIAL
DETERMINANTS YOU CAN SEE, AGAIN,
INTERACTION THERE AS WELL.
SO, CLEARLY IF WE'RE GOING TO
ADDRESS THIS CHRONIC DISEASE
BURDEN, WE HAVE TO BE THINKING
ABOUT THESE SOCIAL, GEOGRAPHIC,
AND PLACE MATTER ISSUES IN
COMBINATION AND AT MULTIPLE
LEVELS.
NEXT SLIDE.
INDEED, DRILLING INTO
HYPERTENSION, THIS IS ONE OF THE
AREAS WHERE THIS MAY BE MOST
CRITICAL, WE'VE LOOKED TOWARD
THOSE YOUNGER ADULTS AND START
TO SEE DIFFERENCES, PARTICULARLY
IN CERTAIN POPULATIONS, AND IN
CERTAIN GEOGRAPHIES, WHERE THIS
PARTICULAR BURDEN OF RISK
FACTORS AMONG THE YOUNGER ADULTS
THAT HAS ALREADY MANIFEST AND
POTENTIALLY DRIVING SOME EARLY
RISK AND PREMATURE DEATHS.
NEXT SLIDE PLEASE.
AND APPRECIATING, AGAIN, THAT
THE INTERACTIONS OF THE VARIOUS
FACTORS, GENETICS, ENVIRONMENTAL
EXPOSURES, VARIOUS LOCAL SOCIAL
DETERMINANTS, NUTRITION,
EXERCISE, ACCESS TO HEALTHY
LIFESTYLE, ALL THESE FACTORS ARE
GOING TO INTERACT IF WE'RE GOING
TO ADDRESS THIS CHRONIC DISEASE
BURDEN IN THIS COUNTRY AND
RECOGNIZE THAT THERE ARE
POPULATIONS WHERE WE HAVE AN
EARLIER ONSET OF A LOT OF THESE
RISK FACTORS AND COMORBID
CONDITIONS PREDISPOSED TO
PREMATURE DEATHS, HYPERTENSION
BEING SHOWN HERE.
NEXT SLIDE PLEASE.
COMBINED WITH OBESITY.
SO THAT'S WHERE WE'RE HOPEFUL
THAT A LOT OF THE APPROACHES
WE'VE BEEN STARTING TO BUILD
TOWARD OF TAKING A HOLISTIC
MULTI-LEVEL SYSTEMS APPROACH TO
REDUCING THE BURDEN OF CHRONIC
DISEASE, TYPICALLY
CARDIOVASCULAR RISK ACROSS THE
LIFE COURSE, HAS BEEN A CORE OF
OUR STRATEGIC VISION AND
CERTAINLY IMPLEMENTATION PLAN,
BUT ALSO LEVERAGING OTHER
ELEMENTS OF THE INSTITUTE LIKE
CTRIS, CEAL, IN WAYS THAT WE CAN
HOPEFULLY DO A HOLISTIC AND
MULTI-LAYERED STRATEGY TO
ADDRESS THAT, BUT LEVERAGE A
SOCIOECOLOGICAL MODEL.
NEXT SLIDE.
AND IN THAT REGARD, I THINK
WE'RE WELL POSITIONED TO ADDRESS
MAKING AMERICA HEALTHY AGAIN IN
MANY WAYS BY LEVERAGING SOME OF
THE PLATFORMS THAT WE CREATED,
INDEED IN THE CONTEXT OF COVID,
WHEN IT WAS REALLY IMPORTANT TO
GET ON THE GROUND IN THESE
COMMUNITIES, MEET THEM WHERE
THEY ARE, LISTEN, CO-CREATE
COMMUNITY-ENGAGED SOLUTIONS TO
THE CHALLENGES THEY SEE, AND
START TO MAKE AN IMPACT ON THOSE
COMMUNITIES, WITH THOSE
COMMUNITIES, WITH THAT STRATEGY.
NEXT SLIDE PLEASE.
INDEED, THERE'S SUGGESTION THAT
PARTICULARLY USING HYPERTENSION
AS A PARADIGM THAT WE'VE MADE
PROGRESS IN SOME OF OUR HEALTH
EDUCATION AND PUBLIC EDUCATION
EFFORTS RAISING AWARENESS, BUT
WE STILL HAVEN'T QUITE GOT THERE
WITH TREATMENT AND CONTROL.
WE'VE DONE GREAT EFFICACY
TRIALS, WITH SPRINT WE NOW KNOW
WE CAN PREVENT HEART ATTACKS,
STROKES, WITH OPTIMAL BLOOD
PRESSURE.
YET WHEN WE LOOK AT WHERE WE
ARE, WITH TREATMENT AND CONTROL,
WE'RE NOT THERE.
AND, AGAIN, THERE'S CERTAIN
COMMUNITIES THAT ARE LAGGING
BEHIND.
SO SOME OF THE BENEFITS OF
GETTING TO THOSE COMMUNITIES
THAT NEED IT THE MOST.
NEXT SLIDE PLEASE.
AND THAT'S WHERE I'M HOPING THAT
WE'LL DOUBLE DOWN ON SOME OF THE
COMMUNITY-ENGAGED RESEARCH AND
IMPLEMENTATION SCIENCE THAT IS
COMMUNITY EMBEDDED IN WAYS THAT
TAKES NOVEL APPROACHES TO
COMMUNICATING WITH FOLKS, AND
LEVERAGING TRUSTED MESSENGERS
WITHIN COMMUNITY TO ENGAGE WITH
PEERS IN WAYS THAT DOES RAISE
AWARENESS, PROMOTES TREATMENT,
PROMOTES CONTROL IN A
COORDINATED SORT OF WAY,
DEMONSTRATED BY RIGOROUS STUDY.
AND SO CAN WE SCALE THESE SORTS
OF ACTIVITIES BECOMES THE
QUESTION.
NEXT SLIDE.
THAT'S WHERE WE'RE HOPEFUL WE'LL
CONTINUE TO BUILD ON THE CEAL
PLATFORM AN ELEMENT LINKED TO
PRIMARY CARE WHICH OBVIOUSLY IS
PART OF RISK FACTOR MANAGEMENT.
IF WE'RE GOING TO MAKE A DENT
MAKING AMERICA HEALTHY AGAIN,
AFFECTING AND ADDRESSING THIS IN
COMMUNITIES THAT LACK AND HAVE
THESE DISPARITIES AND NEED THIS
THE MOST, THEN ENGAGING THESE
COMMUNITIES WHERE THEY ARE AND
COUPLING WITH COMMUNITY EMBEDDED
CLINICAL OPPORTUNITIES AND AREAS
OF RISK FACTOR MANAGEMENT WHERE
HOPEFULLY WE CREATE SCALABLE
MODELS.
NEXT SLIDE.
AND SO, PROGRESS IS BEING MADE
TO BUILD OUT THAT CONNECTION OF
CEAL WITH THE PRIMARY CARE BASED
RESEARCH NETWORKS, AND
DEVELOPING DATA EXCHANGES SUCH
THAT, AGAIN, WE HAVE A SENSE IN
THOSE COMMUNITIES AND THOSE
PRACTICES OF THE CHALLENGES OF
RISK FACTOR AND HEALTHY
LIFESTYLE MANAGEMENT.
NEXT SLIDE.
AND AS WE HAVE THOSE DATA
RESOURCES, WE CAN THEN START TO
ASSESS ARE THERE STRATEGIES WITH
IMPLEMENTATION SCIENCE,
COMMUNITY-ENGAGED RESEARCH WHERE
WE CAN HELP THOSE COMMUNITIES
WHERE THEY HAVE THE HIGHEST
PREVALENCE OF BLOOD PRESSURE,
BUT ALSO BLOOD PRESSURE IS NOT
ADEQUATELY CONTROLLED AND LOOK
AT RISK FACTORS, SO MANY
AFFECTING POPULATIONS, SOCIAL
DETERMINANTS, NEW PROVIDESSERS.
IF WE'RE GOING TO MAKE AN IMPACT
THIS HOLISTIC APPROACH WE THINK
WILL BE CRITICAL.
NEXT SLIDE.
INDEED AS PART OF THE EARLY
PILOT STUDY IN THAT CEAL CARE
NET THEY ARE DOING A RANDOMIZED
CLUSTER DESIGN TRIAL INVOLVING
MULTIPLE CLINICS IN THAT NETWORK
TO TAKE AN APPROACH WHERE
THEYIVELY USING HOPEFULLY EHR
SCREENING WHAT PATIENTS HAVE
UNCONTROLLED HYPERTENSION OR
DIABETES AND LINKING TO SOCIAL
VULNERABILITY AND DOING A SOCIAL
VULNERABILITY SUPPORT WITH
COMMUNITY HEALTH WORKERS AND
HOPING HELPING THEM NAVIGATE
ISSUES OF ACCESS OR ADHERENCE OR
SOCIAL SUPPORT IN OTHER WAYS AND
TO SEE WHETHER THAT COULD BE
DONE AT THAT CLINIC LEVEL IS A
TEST OF THIS.
SO THIS IS KIND OF A TEST OF THE
MODEL, BUT HOPEFULLY STARTS TO
BRING TOGETHER THE COMMUNITY
ENGAGED RESEARCH, PRIMARY CARE
NETWORK, AND HOW WE'RE WRAPPING
AROUND HOLISTICALLY SOCIAL
DETERMINANTS OF HEALTH IN A
HOPEFULLY RIGOROUS AND WAY AND
EVIDENCE-BASED WAY WE HOPE CAN
SCALE.
NEXT SLIDE.
TOWARD THAT END, WE SEE THIS AS
PART OF THAT VIRTUOUS CYCLE OF
DISCOVERY THAT THEN HAS PUBLIC
HEALTH IMPACT IN WHICH THERE'S
THIS INTEGRATION OF COMPONENTS
INCLUDING THE IMPLEMENTATION
SCIENCE TOWARD A HEALTH OUTCOME.
SO I'VE TALKED ABOUT THE
COMMUNITY ENGAGEMENT PART BUT
THERE'S ALSO A POSITION THAT
EVEN CAN OCCUR WITH EARLY
TRANSLATION IN BASIC SCIENCE AS
WELL AS PART OF THE WHOLE CYCLE.
NEXT SLIDE.
AND ONE OF THE EXAMPLES I'LL GO
BACK TO SOME REAL WORLD SCIENCE,
THE AREA I WAS INVOLVED IN, I
STILL REMEMBER OLIVER SMITHIES
PAPER, SHOWING A DOSE DEPENDENT
EFFECT OF EACH COPY ON BLOOD
PRESSURE, HIGHLIGHTING THE
CRITICAL COAL AS PART OF THE
CASCADE, ANGIOTENSEINOGEN,
SETTING THE STAGE OF
FUNDAMENTALLY FOR TRANSLATING
THAT INTO NOVEL THERAPEUTIC, AND
MANY ARE FAMILIAR WITH SOME OF
THE STUDIES WHERE KNOCKING DOWN
ANGIOTENSEINOGEN BY A LIVER
TARGETED THERAPY COULD LOWER
BLOOD PRESSURE AGAIN IN ANIMALS,
NOW IN PHASE 2, MOVING TO PHASE
3 STUDIES, IN AN AGE OF IT TAKES
AN RNA INTERFERON STRATEGY SRNA
AND HOPEFULLY KNOCKS DOWN THE
ANGIOTENSEINOGEN GENE, DELIVERED
BY A GlcNAc POLYMER TO THE
LEVEL WHICH GENERALLY WORKS WELL
AND YOU CAN SEE SIX-MONTH DROP
WITH ONE TREATMENT IN BLOOD
PRESSURE FOR THIS AGENT.
THIS IS ALSO WHERE WE'RE EXCITED
THAT ANOTHER CHAPTER OF
PREEMPTIVE THERAPY MAY BE THE
ABILITY TO TARGET GENE THERAPIES
IN THIS CASE RNA INTERFERONS AS
STRATEGIES TO INFLUENCE PATHWAYS
THAT NOW WE HAVE GREAT MOLECULAR
TARGETS TO, AND WHICH WE CAN
START TO THINK ABOUT PREVENTING
OR PREEMPTING HYPERTENSION.
AND SO WE'RE VERY EXCITED OF
ADVANCING THOSE TECHNOLOGIES,
ACTUALLY WILL BE REVIEWING ONE
OF OUR INNOVATION PLATFORMS
CATALYZE IN WHICH WE'RE LOOKING
FORWARD TO EFFORTS TO BUILD UP
THE CAPABILITIES OF THIS IN VIVO
GENETIC ENGINEERING AND
CELL-BASED THERAPIES REMINISCENT
OF WHAT WE DID WITH SICKLE CELL
AND BONE MARROW TRANSPLANT, IN
SITU, IN CASE THE LIVER FOR
HYPERTENSION AND FRANKLY LDL,
THERE ARE COMPANIES WORKING ON
THESE STRATEGIES BUT DEVELOPING
THE NEXT GENERATION OF VECTORS
AND HOMING VECTORS,
SUFFICIENCIES AND EFFECTIVENESS
OF THESE APPROACHES, WE SEE THIS
AS AN EXCITING AREA FOR
PREEMPTION AND PREVENTION OF
CHRONIC DISEASE.
NEXT SLIDE.
LET ME SHIFT AND CLOSE WITH
MATERNAL HEALTH AS ANOTHER AREA
WHERE AGAIN YOU CAN SEE MAJOR
DISPARITIES WITH OUR COMPARABLE
NATIONS, AND A MAJOR PROBLEM
THAT WE NEED TO ADDRESS IN THIS
COUNTRY, AND THAT I THINK THAT,
AGAIN, IS PART OF MAKING
AMERICAN HEALTHY AGAIN,
RECOGNIZING WOMEN IN THEIR
REPRODUCTIVE YEARS, AND HOW THAT
HAS AN IMPACT PARTICULARLY IN
PREGNANCY ON THE DEVELOPMENTAL
ORIGINS OF CHRONIC DISEASE AS WE
RECOGNIZE THAT IN UTERO
EXPOSURES MAY BE SETTING THE
STAGE FOR CHRONIC DISEASE LATER
IN CHILDHOOD AND IN ADULT LIFE.
NEXT SLIDE.
AND THIS ALSO REPRESENTS AN
OPPORTUNITY TO ADDRESS THAT LIFE
EXPECTANCY AND CHRONIC DISEASE
CURVE BECAUSE WE KNOW THE
LONG-TERM SEQUELAE OF THESE
ADVERSE PREGNANCY OUTCOMES LIKE
PREECLAMPSIA, HYPERTENSION LATER
IN LIFE AND IN THE CHILD, WE CAN
SEE THIS INTERGENERATIONAL
EFFECT IN MANY POPULATIONS.
NEXT SLIDE.
AND THAT MAY BE A VERY RIPE AREA
FOR US TO DO FURTHER STUDY OF
DEFINING WHO IS MOST AT RISK,
AND LEVERAGING SOME OF THE TOOLS
AND TECHNOLOGIES IN GENETICS TO
PREDICT THAT AND BIOMARKERS AS
WELL, WE SEE THAT AS ANOTHER
PROMISING AREA OF RESEARCH ABOUT
WHERE WE CAN, AGAIN, BE MORE
PREDICTIVE AND PRECISE IN
PREVENTING THESE COMPLICATIONS
BY IDENTIFYING WHO IS AT
GREATEST RISK.
NEXT SLIDE.
WITH THAT END, WE SEE AN
OPPORTUNITY TO MAKE
INTERVENTIONS, IN THIS CASE THE
CHAPS TRIAL, LOWERING BLOOD
PRESSURE, REDUCING PRE-ECLAMPSIA
AND OTHER COMPLICATIONS SO
HOPEFULLY WE'RE CHANGING THAT IN
THE HISTORY BOTH FOR MOM AND THE
CHILD BY THOSE INTERVENTIONS.
NEXT SLIDE.
PERHAPS EGGING ON MY COLLEAGUES
TO THINK ABOUT WHAT'S CHAPs
2.0, WHAT WE SHOULD BE DOING
NEXT SYSTOLIC 140 FOR A PREGNANT
WOMAN DOESN'T SOUND THE BEST,
COULD WE DO MORE?
ARE THERE LIFESTYLE CHANGES IN
ADDITION TO THE DRUGS THAT COULD
BE ENHANCING MOM'S HEALTH AND
PERHAPS BABY'S HEALTH AS WELL
THAT MIGHT HAVE LONG-TERM
SEQUELAE.
AND INDEED WE'VE ALREADY CREATED
A DIETARY PATTERN, DASH,
AFFECTED IN THIS CONTEXT.
YET SCRAPED AROUND WITH OUR
TEAM, I DON'T KNOW IN A THERE'S
BEEN A ROBUST DASH-LIKE
INTERVENTION IN WOMEN WHO ARE
PREGNANT GIVEN HOW IMPORTANT
BLOOD PRESSURE IS.
AND SO I'LL LEAVE THAT OUT TO
PROGRAM TO BE THINKING ABOUT
WHAT WE MIGHT BE ABLE TO DO IN
THAT SPACE.
IT'S HARD TO IMAGINE DASH DIET
WOULD DO A LOT OF HARM, PROBABLY
GOOD NOT ONLY FOR MOM BUT BABY
AS WELL, SO THAT MAY BE
IMPORTANT HYPOTHESIS TO TEST.
NEXT SLIDE.
NEXT SLIDE PLEASE.
AND SO WHEN WE TRY TO WALK
THROUGH TODAY, OPPORTUNITIES IN
THAT VIRTUOUS CYCLE THAT WE
THINK COULD BE VERY WELL
ASSIGNED WITH THE NEW
ADMINISTRATION'S MAKE AMERICA
HEALTHY AGAIN AGENDA TO ADDRESS,
PREVENT, IF NOT PREEMPT CHRONIC
DISEASE RELATIVE WITH OUR
PORTFOLIO, AND WE'VE STARTED
WITH THE COMMUNITY TO HAVE
TOOLS, PLATFORMS, WHERE THE
COMMUNITY TO RISE TO THE
CHALLENGE AND MAKE A DIFFERENCE
AND GET CURVES SHIFTED BACK THE
WAY THEY NEED TO BE.
NEXT SLIDE.
ALL THIS WILL BE CRITICAL BUT
ONLY IF WE WORK TOGETHER AS
PARTNERS IN THAT WAY, AND FIRST
OF ALL BE SURE WE GET THE
RESOURCES WE NEED TO PURSUE THAT
AGENDA.
IF WE DO, I THINK THERE'S A LOT
OF EXCITING WORK WE CAN DO
TOGETHER.
WITH THAT, I'LL CLOSE.
THANKS.
>> COMMENTS FROM COUNCIL?
SEEING NO HANDS RAISED
VIRTUALLY, WE'LL BREAK FOR LUNCH.
WE'LL TAKE THE 30 MINUTES AND COME BACK AND RECONVENE THE
PRESENTATION FROM DR. MIZUNO, INTRAMURAL RESEARCH.
WE'RE DELIGHTED TO HAVE WITH US
THE NEXT SPEAKER, DR. MIZUNO,
SENIOR INVESTIGATOR, INTRAMURAL
RESEARCH AT NHLBI.
FROM UNIVERSITY OF TOKYO,
Ph.D. IN BIOPHYSICS THROUGH
JOINT PROGRAM WITH UNIVERSITY OF
TOKYO AND UNIVERSITY OF TEXAS
SOUTHWESTERN MEDICAL CENTER,
PRIOR TO JOINING NHLBI SHE LED
INDEPENDENT GROUP FOR 8 YEARS AT
THE MAX PLANCK INSTITUTE OF
BIOCHEMISTRY IN GERMANY AND ALSO
RECEIVED NUMEROUS EUROPEAN
HONORS INCLUDING EMBO YOUNG
INVESTIGATOR AWARD, AND ERC
CONSOLIDATED GRANT, SERVED AS
EDITOR OF FEB LETTERS AND
EVALUATOR OF THE EUROPEAN UNION
HORIZON 2020 PROGRAM.
WELCOME.
>> THANK YOU VERY MUCH, I'M
NAOKO MIZUNO.
I'M INCREDIBLY HONORED TO BE
HERE TO GIVE MY PRESENTATION TO
YOU ALL FOR THE INTRODUCTION OF
OUR RESEARCH PROGRAM ON EXCITING
FINDS HAPPENING IN MY
LABORATORY.
MY LAB USED TO BE AT MAX PLANCK
INSTITUTE, FIVE YEARS AGO MOVED
TO NIH, STARTED EXPOUNDING
LOOKING AT INTERESTING AND ALSO
IMPORTANT CLINICAL AND MEDICAL
PROGRAMS.
SO I'M GOING TO TELL YOU A
LITTLE BIT OF ONGOING PROGRESS,
ALSO ONE INTERESTING COMPLETE
PROJECT.
JUST A MOMENT, OKAY.
IT WORKS.
SO HERE YOU CAN SEE THIS IS KIND
OF THEME OF MY LABORATORY,
INTEGRATIVE IMAGING, WHICH MEANS
THAT WE ARE USING DIFFERENT TYPE
OF THE MAGNIFYING LENS TO
DESCRIBE THE PHENOMENA WE'RE
INTERESTED IN FOR EXAMPLE
STUDDING MOLECULAR ORGANIZATION,
WE CAN ALSO DESCRIBE NEAR ATOMIC
OR ATOMIC INFORMATION.
YOU CAN SEE IN CELLULAR
ORGANIZATION MORPHOLOGY, TISSUE
ORGANIZATION, USING DIFFERENT
MAGNIFIERS CAN COMBINE
INFORMATION AND FINALLY OUR GOAL
IS TO HAVE A COMPREHENSIVE
UNDERSTANDING OF THE PHENOMENA
THAT WE ARE INTERESTED.
I'M GOING TO TELL YOU A LITTLE
BIT MORE ABOUT THIS LATER.
FOR NOW LET'S MOVE ON.
WHAT I MEAN BY DIFFERENT LENS IS
FOLLOWING.
WE ARE THE IMAGING LAB, LOOK
INTO IMAGING TECHNOLOGIES.
YOU CAN SEE HERE THIS TABLE IS
SHOWING THE LINEUP OF DIFFERENT
TYPE OF MICROSCOPES DEPENDING
WHAT RESOLUTION YOU WANT TO
ACHIEVE OR WHAT KIND OF CONTEXT
FOR THE SIZE OF THE SAMPLE YOU
HAVE.
YOU CAN SEE HERE THIS IS QUITE
NICELY COVERED BUT THIS WAS NOT
THE CASE 10 YEARS AGO.
SO, MY LAB IS WORKING ON
CryoEM, AND MYSELF I HAVE BEEN
WORKING ON CryoEM SINCE 1999.
SO THIS IS REALLY MY EXPERTISE.
BUT IF YOU LOOK AT THIS PORTION,
THIS IS A CryoEM.
WE DID THE TECHNOLOGY.
THIS WAS NOT A VARIABLE OR AT
LEAST WASN'T A PRIME METHOD
UNTIL 2015.
AROUND THAT TIME THERE WAS
TECHNOLOGY BREAKTHROUGH IN THE
FIELD, THAT ALLOWED LARGE
CONTEXTUAL AT NEAR ATOMIC
RESOLUTION CHANGING HOW PEOPLE
LOOK AT STRUCTURE AND
INTERACTIONS ENOUGH WITHIN TWO
YEARS THE PIONEERS IN THE FIELD
GOT NOBEL PRIZE.
SO IT WAS A BIG DEAL.
AFTERWARDS NOW WHAT WE ARE
EXPERIENCING IS THE NEXT PHASE
OF THE REVOLUTION OR BREAK
THROUGH, IN SITU, CryoEM, WE
CAN START LOOKING INTO WHAT'S
GOING ON IN THE CELL, USING
CryoEM METHOD, WE HAVE
POTENTIAL OF INFORMATION.
NOW, LOOKING AT THE FUTURE, I
WANT TO ADD ONE MORE DIMENSION.
THIS IS AN IMAGING DIMENSION BUT
THEN WE CAN ALSO ADD ONE MORE SO
WE CAN START ASKING MORE OF THE
INFORMATION AND COMPREHENSION.
BUT THIS SOMETIMES IS HAPPENING,
NOT ALL THE TIME, BUT IN THE
FUTURE IT'S GOOD TO HAVE AN EYE
ON IT.
FOR EXAMPLE, HOW CAN WE CONNECT
IMAGING INFORMATION WITH
DYNAMICS IN VIVO IMAGING OR GIVE
THE CONTEXT OF THE DISEASE OR
EVEN THE APPLICATION, SO HOW TO
PREVENT THE DISEASE, DEVELOPING
DRUG USING METHOD OF IMAGING.
OKAY.
SO, WHAT WE HAVE BEEN DOING
UNTIL RECENTLY THE PROTEIN
ANALYSIS, YOU CAN SEE HERE THIS
IS PROTEIN COMPLEX, ADHESION
MACHINERY, A MACHINERY THAT IS
PERIPHERY, MAKING A DECISION
WHAT CELLS SHOULD BE DOING,
DEVELOP CANCER, MIGRATE,
POLARIZE, THINGS LIKE THIS
HAPPENING BECAUSE OF THIS
RECEPTOR CALLED INTEGRIN.
IT'S VERY IMPORTANT THAT IT'S
ALSO ON THE ONE TARGET OR THE
TREATMENT.
SO INTEGRIN IS HERE, IT IS DOING
SURVEILLANCE OUTSIDE OF THE
CELL, SO THIS IS ECM, AND YOU
CAN SEE THOSE ARE THE PROTEINS
INSIDE THE CELL, THAT MAKES THIS
COMPLEX.
EVENTUALLY COMPLEX IS INITIATOR
ON DEVELOPING TO HUNDREDS OF
PROTEINS MAKING A DRUG, CHANGED
THE BEHAVIOR OF THE CELL.
SO, WE CAN ADDRESS A LOT OF
THINGS, QUITE NICE THAT WE HAVE
A PRECISE CONTROL AND WE HAVE
PRECISE UNDERSTANDING OF THE
MOLECULES.
BUT THEN THE MAIN CHALLENGE OR
THE CHALLENGE REMAINS WHICH IS
IS IT NOT HAPPENING ALONE, IT IS
HAPPENING IN THE CONTEXT OF THE
CELL, SO CELL HAS A LOT MORE
GOING ON THAN ON OUR LITTLE
COMPLEX SHOWN HERE.
SO QUESTION, ISN'T IT NICE, WE
CAN ADDRESS THE SAME THING IN
THE CONTEXT IN THE LARGER
CONTEXT AND WITHIN THE CONTEXT,
WITHIN THE COMMUNICATION, WITH
THE CELL, BETWEEN THE OUTSIDE,
INSIDE THE CELL, WITHIN THE
CELL, SO THAT'S WHAT WE WANT TO
DO.
THEREFORE, I THINK MORE THAN
FIVE YEARS AGO DECIDED TO MOVE,
JUMP IN THE FIELD OF IN SITU
CryoEM, OR CRYO-ET.
IT LEADS TO UNEXPECTED DISCOVERY
SO IT'S BEEN FUN TO FIND
SOMETHING THAT WE NEVER THOUGHT
WE WOULD FIND.
NOW I'M GOING TO TELL YOU TWO
EXAMPLES OF THE ONGOING
EXPLORATION AND ALSO ONE
COMPLETE EXAMPLE, BUT I THINK
IT'S QUITE AMAZING THAT WE
MANAGED.
SO, I THINK I ALREADY MENTIONED
ABOUT WHAT WE ARE INTERESTED IN,
DECISION-MAKING PROCESS OF CELL,
SO YOU CAN SEE HERE BASICALLY
THE FORMATION, IT SOUNDS LIKE A
SHAPING OF THE CELL, BUT
ACTUALLY THIS MEANS IT'S A
DECISION-MAKING PROCESS OF THE
CELL.
SO, THIS EXAMPLE SHOWS
ACTIVATING
IT'S GOING TO CHANGE THE SHAPE,
SHIELD THE WOUND, DECISION
MAKING, SO DIVIDING, AFTER
DIVIDING PORTION THERE'S A LOT
GOING ON HERE.
SO A LOT OF CONTROL, A LOT OF
SIGNALING HAPPENING.
AND MOST PROMINENT EXAMPLE OF
THE CELL THAT'S CHANGING SHAPE
IS THE NEURONAL CELL OR SHAPING
PROCESS.
SO THE NEURON, ELONGATE, A LOT
OF LOCAL CONTROL IS HAPPENING.
I'M NOT A NEURAL SCIENTIST, BUT
I'M A BASIC SCIENTIST INTERESTED
IN THE SHAPING PROCESS, WE ALSO
LOOK INTO THE NEURONAL CELL
SHAPE PROCESS.
AND NOW BEING AT NIH WE'RE ALSO
FOCUSING ON WHAT IF THE FINE
PROCESS OF THE CELL SHAPE
FORMATION IS NOT WORKING, WHICH
MEANS THAT THE DISEASE IS
HAPPENING QUITE DIRECTLY OUT OF
THE CONTROL, OUT OF THE
HOMEOSTASIS.
FOR EXAMPLE, CANCER CELL, IF YOU
LOOK AT THIS KIND OF LEGS, THE
TIP OF THE LEG WE EXPECT
INTEGRIN TO BE HYPERACTIVATED SO
UPREGULATED SO THAT SHAPE IS
READY TO MIGRATE.
SICKLE CELL FORMATION IS ANOTHER
ONE WE WORK ON ACTIVELY, THAT
THERE IS A SINGLE MUTATION IN
THE HEMOGLOBIN UNDER THE LACK OF
OXYGEN HEMOGLOBIN START MAKING
THE FILAMENT, THE FILAMENT
EVENTUALLY REACHED CELL,
CRESCENT SHAPE, EVENTUALLY TO
BREAK DOWN.
WE WANT ALSO TO HAVE A LOOK AT
HOW THIS CAN HAPPEN AND HOW WE
CAN PREVENT IT.
AND ALSO FINALLY THE NEURONAL
CELL LOSING CONNECTION, THAT
MEANS IT CAN BE INJURED, THAT
MEANS IT'S A BRAIN INJURY, SO WE
TRY TO UNDERSTAND THE PROCESS OF
IT AND HOW WE CAN CONTROL IT OR
AT LEAST TO UNDERSTAND WHAT IS
GOING TO HAPPEN AT THE MOLECULAR
RESOLUTION.
THAT'S WHAT WE'RE TRYING TO
ADDRESS.
OKAY.
SO, NOW THIS IS OUR KIND OF
SHOWCASE EXAMPLE, SHOWING HOW
NEURONAL CELL CHANGING THE SHAPE
SO YOU CAN SEE HERE THIS IS A
NEW NEUROIDE COMING OUT, THIS IS
THE FIRST TIME WE SEE DIRECTLY
WHAT'S HAPPENING WITHOUT
FILTERING FLUORESCENT LEVELING,
WE SEE EVERYTHING HERE.
NOW WHAT WAS QUITE INTERESTING
TO SEE AS MITOCHONDRIA HERE,
YELLOW SHOWN HERE E.R., E.R. IS
HOLDING MITOCHONDRIA SO
MITOCHONDRIA DOESN'T RUN AWAY
FROM THE ROOT OF THE NEURON
PORTION OF THE CELL.
IN ORDER TO MAKE THE PROTEINS
THAT ARE NECESSARY TO MAKE THE
NEURITE, YOU SEE A LOT OF BLUE
DOTS OF THE RIBOSOME, SO THIS
WAS ACTUALLY AN UNEXPECTED
SURPRISE BECAUSE PEOPLE HAVE
NEVER SEEN RIBOSOME IN AXON
BEFORE, THE FIRST EXAMPLE, THIS
IS THE RIBOSOME, IT'S ONLY AT
THE AREA WHERE THE NEW FORMATION
OF THE LIKE MANY CELL PROTRUSIN
TO START HAPPENING SO THIS WAS
FULFILLING EXPERIENCE FOR US,
JUST TO HAVE A LOOK, AND THEN TO
HAVE A SURPRISE OF IT.
SO, WHY DO WE SEE EVERYTHING
USING CryoEM TECHNOLOGY AS
OPPOSED TO NORMAL VOLUME OF EM
AND SO ON?
I WANT TO GIVE A LITTLE BIT OF
EXPLANATION ABOUT IT USING THIS
VIDEO.
SO JUST EMERGING THIS IS YOUR
CELL, THIS IS YOUR TISSUE, YOU
CAN EMBED IT OR GO ON EM GRID,
AND THEN YOU SEE NOW THEY ARE
FROZEN AT MINUS 180 DEGREES AND
THEN THIS IS AN EM GRID,
LITERALLY GOES INSIDE
MICROSCOPE, TO BE COLLECTED SO
THE TOMOGRAPHY IS HAPPENING, NOW
COMBINED, PROJECTED INTO THE 3D
RECONSTRUCTION, YOU SEE DENSITY
BUT THIS DENSITY IS LITERALLY
THE DIFFERENCE OF THE MOLECULE,
SO THIS MEANS THAT YOU WOULD SEE
EVERYTHING, IT IS TRANSPARENT
BECAUSE THERE IS NOTHING
COVERING, NOTHING FIXING, ALSO
IT HAS POTENTIAL OF THE
RESOLUTION OF ATOMIC RESOLUTION,
OF COURSE IF YOU DO GOOD JOB
WITH THE SAMPLE PREPARATION AND
HAVE THE RIGHT SAMPLE.
THIS IS NOT THE EVERYDAY, BUT
POTENTIAL IS VERY HIGH.
I SAID ALREADY IT IS NOT
EVERYBODY'S METHOD BUT WE TRY
OUR BEST TO OPTIMIZE IT.
AND IT IS A DEVELOPING FIELD SO
THIS MEANS THAT EVERY PROJECT
REQUIRES PIPELINE OPTIMIZATION,
SO IT'S NOT GREAT BUT WE TRY OUR
BEST BECAUSE THE FRUIT IS VERY
AMAZING.
SO FAR SAMPLE PREPARATION,
OPTIMIZATION, IDENTIFY AREA OF
INTEREST, COMPOSED OF THICKNESS,
10 OR 20 MICROMETER LENS, THE
SIZE, IF YOU HAVE THE THICKNESS
OF 1 MICRO METER, YOU NEED TO
TRIM NICELY AND TAR GET IT TO
KNOW EXACTLY WHERE YOU'RE
LOOKING AT BECAUSE IT'S GOING TO
BE DIFFICULT TO FIND.
SO WHAT WE TYPICALLY DO FREEZE A
SAMPLE AND THEN WE HAVE A LOOK
USING CREATIVE MICROSCOPE, SO WE
CAN LABEL ONE OF THE FAVORITE
PROTEIN TO THE RIGHT LOCATION
AND THEN YOU DO SOMETHING CALLED
CRYOMEETING.
QUITE A BIT OF MEETING HAPPENING
IN THIS TINY AREA THAT REMAINED,
AND THEN 100-NANOMETER OF THE
FILAMENT THAT'S PRODUCED.
NOW, THIS IS GOING TO BE -- THE
DATA IS COLLECTED USING THIS
LAMINA AND THEN YOU GET
RECONSTRUCTION.
NOW WE NEED TO DO THE ANALYSIS,
ANOTHER SUPER ACTIVE AREA OF
RESEARCH BECAUSE WE NEED TO DO A
LOT OF QUANTIFICATION AND A LOT
OF DATA ANALYSIS TO SQUEEZE OUT
ALL THE INFORMATION.
IF YOU'RE EXTREMELY LUCKY YOU
MIGHT GET NEAR ATOMIC RESOLUTION
OF THE OBJECT THAT YOU ARE
LOOKING BUT IF NOT AT LEAST YOU
GET THE NICE CONTEXT WHICH COULD
ALSO BE EQUALLY INTERESTING.
SO NOW I'M GOING TO TELL YOU TWO
EXAMPLES OF PLOD SYSTEM THAT WE
HAVE -- BLOOD SYSTEM WE'VE BEEN
WORKING ON, REALLY ONGOING
PROJECT, SO WE DON'T HAVE THE
CONCLUSION YET BUT I WANT TO
GIVE YOU THE FLAVOR.
SO, FIRST EXAMPLE I WANT TO TELL
YOU, TO UNDERSTAND THE MECHANISM
OF SICKLE CELL FORMATION.
I ALREADY INTRODUCE YOU ABOUT
THE SICKLE CELL FORMATION, SO
WHAT WE DO, SO THIS IS IN
COLLABORATION WITH NHLBI, SHE'S
A CLINICAL INVESTIGATOR, SHE
KNOWS A LOT ABOUT THE DISEASE
ITSELF AND A LOT ABOUT THE
SICKLE CELL TOGETHER WITH
BIOPHYSICALLIST, EATON, COLLECT
THE SAMPLE FROM PATIENT, THEN WE
HAVE SPECIAL CHAMBER.
SO EVERYTHING IS DONE IN THIS
CHAMBER BECAUSE WE CAN MAKE
DEOXYGENIZATION AND PUT NITROGEN
INTO THE ENVIRONMENT.
SO THEN WE HAVE THE CYCLING
FORMATION MIMICKED HERE, 45
MINUTES, CELLS START BECOMING
SPIKEY.
AFTER 4 HOURS THE COMPLETION OF
SICKLE FORMATION IS HAPPENING.
NOW FREEZING THE SAMPLE, HERE IS
THE FROZEN SAMPLE, HERE YOU CAN
SEE THE FROZEN SAMPLE, THIS AREA
IS EMPTY.
THIS HAPPENS.
LOOKING AT THIS AREA YOU CAN SEE
SOMETHING FROZEN.
THIS IS THE SICKLE CELL.
WE DO THE MEETING, SO TO LOOK
INTO THE INSIDE, TARGETING WITH
THE MILLING, THEN BEAUTIFULLY WE
MANAGED TO GET THE FIRST TIME
VISUALIZATION OF THE FILAMENT.
YEAH, LOOKING LIKE THIS.
SO, NOW YOU CAN SEE IT IS FULL
OF FILAMENT INSIDE THE SICKLE
CELL.
WE NEED TO DO A LOT OF ANALYSIS.
IT TOOK US MORE THAN ONE YEAR TO
GET TO THIS STAGE.
NOW IT'S THE TIME THAT WE DO
ANALYSIS, FOR EXAMPLE, WHAT
WOULD BE THE DISTANCE BETWEEN
TWO FILAMENT OF WHAT WOULD BE
THE MECHANISM OF THE FILAMENT
BUNDLING, WHAT WOULD BE THE
MECHANISM OF THIS FILAMENT
POKING INTO THE INNER MEMBRANE
OF THE PLASMA MEMBRANE ENOUGH
THAT IT IS GETTING FRAGILE, SO
THIS KIND OF INFORMATION WE ARE
GOING TO ASK.
HOW DO I KNOW?
YES, IT'S A GOOD QUESTION.
ONE THING I CAN SAY, TRAINED.
AND SECOND A CONTROL.
IF IT'S NOT SICKLE, IT IS
ABSOLUTELY NOTHING.
SO YOU SEE THE DOTS.
FOR YOU, YOU MIGHT SAY THIS IS
DOTS.
BUT THEN I RECOGNIZE, FOR
EXAMPLE, YEAH, A FILAMENT HERE,
HERE A FILAMENT, HERE A
FILAMENT.
SO, THEN WE CAN INDEPENDENTLY
ALSO RECOGNIZE, THE PROTEIN
STRUCTURE IS KNOWN.
AND STRUCTURE OF THE -- SO
THERE'S CRYSTALGRAPHIC PACKING
THAT ALLOWS US , HOW IT'S
HAPPENING, WE CAN ALSO USE THAT,
WE HAVE EDUCATED GUESS HOW THE
FILAMENT SHOULD LOOK LIKE AND
THIS SEEMS TO BE THE CASE SO WE
CAN VALIDATE THAT AND SO WHAT
WE'RE TRYING TO DO IS NOT JUST
TO LOOK AT IT BUT TRY TO
UNDERSTAND THE MOLECULAR
ORGANIZATION HOW THEY ARE
HAPPENING SO THIS IS ONLY
STARTING TO HAPPEN NOW.
SO MAYBE NEXT YEAR I COME BACK
HERE.
OKAY.
SO THEN THE NEXT EXAMPLE THAT I
WANT TO SHOW YOU, WE FOUND THIS
LIGAND, SO THIS LIGAND IS
RECOGNIZED BY INTEGRIN, VERY
MUCH EXPRESSED ON THE SURFACE OF
THE PLATELET.
SO THIS MEANS YOU MIGHT EXPECT
INTEGRIN IS ACTIVATED SO IF YOU
COMPARE THE PLATELET OF THE
NORMAL CONDITION AND THE TEST
CONDITION, YOU WOULD SEE A LOT
OF PLATELET GETTING ACTIVATED.
NOW WE WANTED TO HAVE A LOOK,
PARTICULARLY INTERESTED IN
INITIATION PROCESS OF ACTIVATION
OF THE PLATELET, AT THE
BEGINNING WHAT WE SAW IS THE
FORMATION OF THE SUPER ELONGATED
PLATELETS, THIS WAY.
SO, BEFORE OPENING UP INTO THE
SHAPE SOME SEE A LOT ELONGATED
PLATELET.
SO WE HAD A LOOK AT THIS ON THE
CryoEM.
YOU CAN SEE HERE THIS IS
ACTUALLY PLATELET.
LIKE THIS.
SO, NOW HAVING, DO TOMOGRAPHY,
APPROXIMATELY ONE MICROMETER IN
SIZE.
THIS IS THE RECONSTRUCTION.
YOU SEE HERE THIS IS THE
MEMBRANE, PLASMA MEMBRANE OF THE
PLATELET AND INSIDE THERE IS A
BUNDLE OF ACTIN WITH PROTEIN
DENSITY WE DON'T KNOW WHAT BUT
TO HAVE FIND IT OUT.
THAT BINDING OF THE LIGAND ON
PLATELET SURFACE, QUITE NICE, I
SHOWED PREVIOUSLY MAYBE 10
MINUTES AGO ABOUT THE ADHESION
MACHINERY THAT WE ARE
RECONSTITUTING, THAT MEANS WE
CAN START TO SEE POTENTIALLY THE
CONNECTION BETWEEN THE ACTIVATED
INTEGRIN COMPLEX, FROM THE IN
SITU, AND COMBINE IT WITH THE
PURIFIED COMPONENTS SO WE CAN
HAVE A COMPREHENSIVE VIEW.
SO, THIS IS AGAIN ONGOING.
OKAY.
FINALLY THE THIRD EXAMPLE I WANT
TO SHOW IS MORE THE COMPLETE
VERSION WHICH IS ABOUT THE
NEURITE.
NOW WHY I WANT TO SHOW YOU THIS
AS AN EXAMPLE IS WE DISCOVERED
SOMETHING BY VISUALIZING IT AND
ALSO ON DIRECT VISUALIZATION OF
NOVEL MECHANISTIC INSIGHTS YOU
CAN SHOWCASE FOR YOU USING THIS
EXAMPLE.
SO, CAN WE DIRECT AGAIN
MECHANISTIC INSIGHT JUST BY
LOOKING IN SITU IMAGES, THE
ANSWER IS YES.
SO, I'M GOING TO SHOW YOU MY
EXAMPLE.
SO WHAT I DID IS ACTUALLY THE
INJURY FORMATION OF AXON, SO
AXON IS THE LONGEST NEURITE OF
THE NEURON, IT IS IMPORTANT TO
SEE THE MOST POLARIZED CELL AS
AN EXAMPLE.
WE WANTED TO CHECK HOW THE
REACTION OF THE INJURY WOULD BE,
HOP REPAIR WOULD HAPPEN, HOW
DECISION MAKING OF THE AXON IS
REGENERATING OR DEGENERATING.
AND THIS IS IMPORTANT
BIOPHYSICALALLY AND CLINICALLY.
AXON INJURY IS ACTUALLY WHICH
MEANS BRAIN INJURY.
SO WHEN THE BRAIN INJURY HAPPENS
IS WHEN YOU HAVE THE CONCUSSION,
WHEN YOU HAVE THE HEAD INJURY,
ESPECIALLY WHEN YOU HAVE THE
BRAIN INJURY IN THE PORTION OF
BRAIN AT THE CENTRAL NERVE
SYSTEM, IT IS KNOWN THAT NEURONS
NEVER REGENERATE.
SO THIS IS A PROGRAM BECAUSE
ONCE YOU HAVE THE INJURY, YOU
GET UNCONSCIOUS, YOU HAVE A
COGNITIVE PROBLEM AND COULD DIE
OUT OF IT SO IT IS IMPORTANT TO
FIND OUT WHAT'S HAPPENING, HOW
WE CAN PREVENT OR HOW WE CAN
EVEN INDUCE THE REGENERATION.
SO WE ARE LOOKING AT INJURY
REACTION OF THE NEURONAL CELLS.
NOW I TELL YOU HOW MOLECULARLY
WHAT'S HAPPENING.
WHEN THE INJURY ON THE AXON
HAPPENS, THAT MEANS MEMBRANE IS
BROKEN, THAT MEANS THAT THE
CYTOSKELETON COMPONENTS LEAK
OUT.
GETS BROKEN.
THE MEMBRANE CLOSES AS YOU CAN
SEE HERE.
CALCIUM GOES IN, MICROTUBULES
SHRINK, THAT'S THE SCIENCE FOR
REGENERATION OF THE AXON.
SOMETIME AGO, 5 YEARS AGO, A
GROUP SHOWED REPAIRING THE
AXONAL INJURY OR REPAIR THE
SPINAL CORD INJURY.
EPO-B IS KNOWN AS ANTI-CANCER
DRUG TO FREEZE THE CELL CYCLE,
BINDING ON MICROTUBAL, CAN BE
REPURPOSED BUT STILL NOT KNOWN
HOW EPO-B CAN ACT FOR THE
REGENERATION.
WE DECIDED TO WORK ON THAT BY
MAKING THE PIPELINE.
SO WE USED THE THALAMUS, TRAIN
TISSUE, DISSECTION.
YOU CAN SEE HERE WE MADE THE
SPECIAL TISSUE, EXPLANT, THE
CENTER BRAIN TISSUE AND THESE
ARE THE NEURITES.
WHAT IS VERY NICE IN THIS SYSTEM
IS THAT EVERYTHING SINGLE
NEURITE WE GET, AXONS, WE CAN
GET EVERYTHING WE LIKE AS
OPPOSED TO NORMAL ISOLATED
NEURON THAT HAS DENDRITE AS
WELL.
WE ALSO CULTIVATE THIS EXPLANT
ONTO EM GRID AND ALSO YOU CAN
SEE THIS IS THE EXPLANT UNDER
LIGHT MICROSCOPE, VISUALIZE AND
MAKE A FUNCTIONAL AND STRUCTURAL
ANALYSIS NOW WHAT WE DO IS
SOMETHING WHICH MEANS WE MAKE
THE INJURY ONTO EM GRID SO WE
DEVELOP THIS SPECIAL METHOD
USING THE NEEDLE, AND THEN TO
MAKE AN INJURY ONTO AXON AND WE
CAN HAVE A LOOK AT THE REACTION
AT A MOLECULAR RESOLUTION USING
CryoEM.
SO, NOW JUST TO TEST, SO
FUNCTIONALLY WHAT'S HAPPENING
YOU CAN SEE HERE INJURY
HAPPENING NOW, HERE IS THE
NEURITE, AND HERE IS ALL THE CUT
AXON, WITHOUT EPO-B, IT GROWS,
WE CAN SEE AT CELLULAR LEVEL
EPO-B IS WORKING.
NOW LET'S HAVE A LOOK AT HOW THE
REGENERATION HAPPENS MORE
CLEARLY.
THIS IS THE CUT AXON, BUT THEN
AFTER SOME TIME IT STARTS THIS.
I DON'T KNOW IF YOU NOTICED,
LIKE THIS, AFTER 90 MINUTES TO
TWO HOURS ACTUALLY, THERE IS
NOTHING HERE.
IT'S ONLY LIKE A STICK THAT IS
REGENERATING.
AND AFTER TWO HOURS THERE'S THIS
MORPHOLOGY COMING OUT, NORMAL
WAY OF AXON GROWING, AND UP TO
TWO HOURS IT'S NOT NORMAL SO
SOMEHOW AXON IS REGENERATING IN
THE ABNORMAL WAY.
SO WE HYPOTHESIS THIS MUST HAVE
SOMETHING TO DO WITH EPO-B,
LIKELY MICROTUBULES.
MAKE THE MICROTUBE TUBULE IS PUG
THE MEMBRANE, SO HERE YOU CAN
ALSO SEE THE SAME THING.
SO TO TEST THIS HYPOTHESIS,
OKAY, WE MEASURED MEMBRANE,
AFTER REGENERATING THE SITE HOW
THE MEMBRANE TENSION IS
CHANGING, SO IF REGENERATION IS
HAPPENING, PUSHING THE MEMBRANE,
MAYBE THE TENSION IS HIGHER SO
WE USED A DYE TO MEASURE THE
MEMBRANE TENSION, REGENERATING
FRONT YOU SEE MEMBRANE TENSION
IS HIGHER AFTER ONE HOUR, BUT
AFTER FOUR HOURS YOU SEE IT GETS
NORMALIZED SO THIS MEANS THAT
MEMBRANE GETS NORMALIZED, WHEN
GROWTH CON CAME BACK.
YOU CAN SEE CONTROL ALSO THE
SAME.
THIS MEANS BETWEEN ONE HOUR TO
FOUR HOURS OF THE REGENERATION,
SOMETHING IS CHANGED, SOMETHING
IS ACTING UP.
SO, WE DECIDED TO HAVE A LOOK
USING CryoEM.
HERE MAYBE YOU CAN SEE A NEURITE
AXON, AND NOW WE WILL PERFORM A
MICROSURGERY ON EM GRID.
YOU CAN SEE THIS DOT, THIS IS
ONE MICROMETER SMALL HOLE
TYPICALLY WE USE FOR THE IMAGING
BUT FOR THE CASE OF AXON WE
DON'T REALLY -- AXON REALLY
DON'T FOLLOW THIS SO WE JUST
COLLECTED DATA -- COLLECT THE
DATA WHEREVER WE CAN FIND.
SURGERY HAPPEN.
THE NEEDLE, THEY CUT THE AXON.
AFTER THE CUT OF THE AXON WHAT
HAPPENS, HERE YOU CAN SEE THIS
IS AXON, THEN YOU CAN SEE THE
GROWTH IS HAPPENING.
SO ON THE EM GRIDDLES WE CAN SEE
REGENERATION REPRODUCED.
NOW CRYOOBSERVATION, HERE IS THE
TISSUE OF THE BRAIN, HERE IS THE
AXON.
SO LET'S LOOK AT THIS AREA.
TWO AXONS, WE CUT BOTH AXONS, ON
THIS ONE DID NOT GROW BACK SO
THIS IS DEGENERATING.
ON THIS ONE SEEMS TO BE
REGENERATING SO SOMETHING IS
HAPPENING HERE SO WE HAD A LOOK
MORE CAREFULLY, SOMETHING THERE.
SO HERE IS THE MONTAGE THAT YOU
CAN SEE.
HERE IS THE CUT SIDE.
AND THERE'S SOMETHING
REGENERATING.
YOU CAN SEE HERE MUCH EASIER, SO
MICROTUBULES, GREEN, AND RED IS
THE ACTIN SHOWN HERE.
SO COMPONENTS COMING OUT.
14 MICROMETER WITHIN ONE HOUR
CAME BACK DRASTICALLY, WE KNOW
THE ANSWER NOW THAT PLASMA
MEMBRANE WAS MISSING, PRECISELY
WHERE THE AX OTOMY HAPPENS, THIS
MEMBRANE WAS SO MUCH PUSHED OR
STRETCHED DURING THE CryoEM
PREPARATION, PLASMA MEMBRANE,
BUT THAT ACTUALLY WAS QUITE AN
ADVANTAGE THING FOR US BECAUSE
WE HAVE A VERY GOOD
SIGNAL-TO-NOISE RATIO KNOWING
WHERE THE CUT HAPPENED AND
DECIDED TO COLLECT THE DATA,
SINGLE PARTICLE ANALYSIS, SPA,
TRYING TO REACH HIGH RESOLUTION
INFORMATION OUT OF IT.
SO HERE YOU CAN SEE THIS IS THE
AXON, ALL THE AXONS ARE GOING TO
THE SAME DIRECTION BECAUSE WE
KNOW WHERE THE SOURCE IS.
IT'S THE TISSUE.
WE DID LARGER AXOTOMY, AND LET
REGENERATION HAPPEN.
WHEN WE DO THE CRYOOPERATION
WHATEVER WE SEE BEYOND THIS
POINT IS REGENERATING POINT OF
THE NEURON.
WE COLLECTED DATA, 3,000 IMAGES
OF THE REGENERATING AXON AND
BOUGHT THIS BEAUTIFUL
TOMOGRAPHY, PLASMA MEMBRANE,
MICROTUBULES.
FROM NOW ON I'M GOING TO FOCUS
ON THE DESCRIPTION OF THE
MICROTUBULES.
NOW YOU CAN SEE HERE THIS IS A
STRUCTURE OF THE MICROTUBULES OF
THE AXONAL MICROTUBULE IN SITU
THAT'S REGENERATING.
WHAT'S AMAZING FOR US, ALL THE
MICROTUBULE HAVE 13 PROTEIN
FILAMENT ARRANGEMENT,
PHYSIOLOGICALLY RELEVANT.
WHEN YOU RECONSTITUTE
MICROTUBEEL YOU GET GET 14, A
STABLE FORM OF THE MICROTUBULE,
THAT MEANS CHAPERONE OR SOME
TEMPLATE IS MAKING REGENERATIVE
MICROTUBULE SO IT IS SET TO 13
PROTEIN FILAMENT.
WE CAN ALSO SEE THIS
REGENERATING PORTION OF THE
AXON, OR THE MICROTUBULE HAVE
SAME DIRECTIONALITY, ALL HAVE,
HALLMARK OF THE AXON.
IT HAS AXONAL IDENTITY.
NOW RESOLUTION WAS 3.6-ANGSTROM,
WE CAN SEE WHAT'S HAPPENING
WITHIN THE MICROTUBULE OF
REGENERATING AXON.
WE MEASURED THE DISTANCE,
83.3-ANGSTROM, SO THIS MEANS
THIS IS AN IN VITRO
RECONSTITUTED MICROTUBULE
PUBLISHED SOMETIME AGO, WHEN IT
IS FORCED TO BE STABILIZED, IT
STRETCHES TO HAVE 84-ANGSTROM,
DYNAMIC, UNSTABLE FORM,
81.8-ANGSTROM WHICH MEANS
REGENERATING IS STABILIZED, WHY
IS THAT?
LIKELY BECAUSE OF THE EPO-B
ENGAGING TO STABILIZE.
HOWEVER WHEN YOU LOOK INTO THE
SKINNIER DENSITY OF THE
MICROTUBULE, THIS IS SUPPOSED TO
BE THE EPO-B DRUG IS SUPPOSED TO
ATTACH.
WE DIDN'T SEE IT.
WHEN WE CHANGE THE DENSITY WE DO
SEE IT SO WE CAN REALLY SEE
EPO-B THE DRUG ENGAGED ON THE
MICROTUBULE REGENERATING AT THE
REGENERATING AXON WHICH IS
EXCITE AMAZING.
EVEN MORE AMAZING, THE
CONCENTRATION IS 20 MICROMOLAR
IN NEURONS, WHICH MEANS 20,000
TIMES LESS AMOUNT OF THE DRUG
THAN ESTIMATED THAT YOU CAN SEE
HERE.
YOU SEE THE DENSITY OF EPO-B,
THERE'S EFFECTIVE CONCENTRATION
OF THE EPO-B AT THE REGENERATING
AXON SO STABILIZATION HAPPEN AND
REGENERATION CAN BE SWITCHED
OFF.
SORRY, SWITCHED ON.
SO NOW WHERE ARE THE
MICROTUBULES COMING FROM?
WE ASKED OURSELVES THREE
HYPOTHESES.
FIRST MAYBE THE TUBULIN IS
SYNTHESIZED AT THE REGENERATING
SITE.
WHY WE THINK SO IS BECAUSE WHEN
WE LOOK NEW NEURITE FORMATION,
RIBOSOMES ARE ACCUMULATED,
LIKELY MAKING THE ACTIN HERE.
SO WE WONDER IF RIBOSOME CAN BE
SHOWN REGENERATING, THE ANSWER
IS KNOW, MICROTUBULES OR TUBULIN
IS NOT SYNTHESIZED AT THE SITE
BUT CARRIED FROM THE DOWNSTREAM
OF THE NEURON.
YOU CAN SEE HERE ACTUALLY THIS
IS REGENERATING AXON, STAINED
TUBULIN YOU SAW, CLUSTER OF
MICROTUBULE TUBULIN TO THE
REGENERATING SITE, IS THIS
MICROTUBULE OR TUBULIN CLUSTER?
SO WE TESTED THAT, TO DO THAT WE
TAKE ADVANTAGE OF THIS MATERIAL,
WE DON'T KNOW THE IDENTITY YET
BUT WE HAVE A LOT INSIGHT.
IF THE MICROTUBULES ARE CARRIED
TO THE REGENERATING SITE WE
EXPECT SPOTS TO BE ALSO PRESENT
AT THE REGENERATING SITE.
NOW YOU CAN SEE HERE THIS IS
REGENERATION, 24 HOUR, YOU SEE
THE DENSITY OF THE INNER LUMEN,
MUCH LESS AT THE BEGINNING OF
THE REGENERATION, YOU EVEN SEE
IT ULTIMATELY AT THE MICROTUBULE
WHERE THE REGENERATION FRONT IS.
YOU SEE NOTHING INSIDE OF THE
MICROTUBULE AS OPPOSED TO
PROXIMAL PORTION, INDICATES THIS
IS A NEWLY POLYMERIZED TUBEIN AT
THE SITE RATHER THAN FROM THE
OTHER SITE OF THE NEURON.
SO THAT MEANS WE SHOULD BE
LOOKING FOR THE CLUSTER TUBULIN
THAT GETS CARRIED TO THE END OF
THE REGENERATING AXON.
ONE MOMENT.
SO THEN WE FOUND IT HERE.
AGAIN WE SEE ALL OLIGOMERS
SHOWING HERE LIKE THIS.
THESE ARE MICROTUBULES.
IF YOU LOOK AT THE SIZE THIS IS
EXACTLY SAME AS WHAT HAS BEEN
OBSERVED IN VITRO, THE CLUSTER
OF TUBULIN AND THAT CAN BE
RECONSTITUTED USING PURIFIED
TUBULIN SO WE HAVE QUITE
CONFIDENT THIS IS THE TUBULIN.
YOU CAN ALSO SEE THE SEGMENTS
AND THEN VISUALIZE EACH OF THE
DOT, LOOKING AT THE SPIRAL,
MEASURING THE SIZE OF THE
SPIRAL, EACH OF THE MOLECULE,
IT'S EXACTLY SAME SIZE AS
TUBULIN YOU SEE IN MICROTUBULES
OR THE SIZE IS DIFFERENT FROM
ACTIN SO THIS IS A VISUALIZATION
METHOD BY LOOKING AT IMAGE WE
CAN DISTINGUISH THE SIZE OF THE
ACTIN, 5-NANOMETER AND TUBULIN
WHICH IS 4-NANOMETER.
NOW YOU CAN SEE IN SITU
MICROTUBULE POLYMERIZATION
HAPPENING, SO SHOWN HERE FOR
EXAMPLE YOU SEE CLUSTER OR THE
SPIRAL OF THE TUBULIN STARTING
TO ATTACH, SOME YOU CAN SEE IT
STARTS STRAIGHTENING, WE CAN
VISUALIZE POLYMERIZATION PROCESS
OF THE MICROTUBULE AS
REGENERATING AXON.
THE CONCLUSION OF THE STUDY,
TUBULIN CLUSTER IS MADE BECAUSE
OF THE EPO-B, AND THEN OLIGOMERS
ARE MADE, THAT WOULD BE
TRANSPARTED.
WE KNOW IT IS TRANSPORTED, WE
DID A STUDY ALREADY, WE DO NOT
KNOW AT THIS POINT WHAT IS THE
TRIGGER OF IT BUT WE DO KNOW IT
GETS CARRIED TO THE TIP OF THE
REGENERATING AXON AND
MICROTUBULES ARE POLYMERIZED, AT
THE REGENERATION, REGENERATING
PORTION, 10 TO 20 MICROMETER OF
THE ELONGATION.
OKAY.
QUALITY CONTROL AFTER 24 HOURS
IT GOT QUITE LONG, CAN YOU SEE
QUALITY CONTROL HOW THE AXON
LOOK LIKE AFTER 24 HOURS OF THE
REGENERATION, THAT SEEMS TO BE A
NORMAL AXON ACTUALLY THAT YOU
CAN ALSO SEE THAT IT ENDS WITH
THE GROWTH CONE.
SO, WITH THAT I'M GOING TO GIVE
YOU A LITTLE SUMMARY.
YEAH, SO WHEN THE MEMBRANE GETS
INJURED ON THE AXON THEN --
FIRST TIME, SORRY.
I HOPE YOU UNDERSTAND BASED ON
MY EXPLANATION WHAT'S HAPPENING
BUT ANYWAY THE MEMBRANE GETS
CUT, TUBULIN CLUSTER THAT'S
HAPPENING, MEMBRANE GETS CLOSED,
AND THEN MICROTUBULE STABILIZED,
SHUTTLING CONTINUOUSLY
HAPPENING.
NOW WE CAN SEE THE MECHANISM OF
IT.
SO THIS WAS AN EXAMPLE IT WAS
QUITE SATISFYING BECAUSE WE SEE
EVERYTHING AND WE CAN ALSO
COMBINE IT WITH THE DYNAMIC, IT
SEEMS TO BE QUITE IMPORTANT FOR
REGENERATION OF THE NEURON.
SO WE ARE WORKING ON DIFFERENT
INTERESTING PROJECTS, SIMILAR
WAY TRYING TO MAKE THE PIPELINE,
TRYING TO MAKE THE MECHANISTIC
UNDERSTANDING, SOMETIMES WE FIND
UNEXPECTED DISCOVERIES,
SOMETIMES WE HAVE A NICE
MECHANISM SHOWING UP SO THIS IS
A VERY NICE METHOD AND IT'S A
VERY NICE TIME FOR THE CryoEM
FIELD.
WITH THAT I WOULD LIKE TO FINISH
MY TALK, HERE IS THE MEMBER OF
THE LAB AND I JUST LISTED
COLLABORATOR AND PEOPLE IN THE
LAB ON THE DIRECTORY INVOLVED
WITH THE PROJECT I SHOWED YOU.
YOU CAN SEE I HAVE SOME GRANT IN
GERMANY, BECAUSE MY PROGRAM IS A
CONTINUATION I WOULD LIKE TO
ACKNOWLEDGE THE FUNDING RESOURCE
AND ALSO NIH AND NHLBI.
THANK YOU FOR YOUR ATTENTION.
HAPPY TO TAKE QUESTIONS.
>> ANY COMMENTS OR QUESTIONS?
>> GREAT.
THANK YOU FOR THE TALK, VERY
COOL STUFF.
MY QUESTION, YOU TALKED ABOUT
INTEGRINS AND ADHESION
COMPLEXES, ARE YOU ABLE TO USE
THE SAME TECHNOLOGY TO VISUALIZE
MATRIX DEPOSITION AND MATRIX
MATURATION AND MATRIX
REMODELING?
>> I IMAGINE SO.
I HAVEN'T TOUCHED THE
EXTRACELLULAR PORTION YET BUT
THAT WILL BE INTERESTING.
BUT IN THIS CASE THEN I WOULD
LIKE TO ADD INFERENCE OF THE
FOLDS.
INFERENCE OF THE FOLDS, YEAH.
YEAH, YEAH, YEAH.
>> ANYONE ELSE?
OKAY.
THANK YOU VERY MUCH.
>> THANK YOU.
>> WE'RE NOW AT THE PORTION
WHERE WE'LL HAVE A REFRESHER OF
DECISION LENS TOOLS, BEFORE
CONCEPTS, A REVIEW AND THEN
WE'LL START WITH CONCEPTS.
I'LL TURN THIS OVER TO THE TEAM
>> LOOKING TO SHARE ON THE TEAMS
REAL QUICK.
>> COUNCIL MEMBERS CAN SEE ON
THEIR SCREENS BUT WE'RE HAVING
DIFFICULTY SHARING ON THE BIG
SCREEN.
WE'LL TALK YOU THROUGH IT AND
YOU'LL BE ABLE TO WATCH ON YOUR
MONITORS.
THANK YOU.
>> THANK YOU.
AGAIN, THANKS FOR HAVING US
BACK.
GOOD AFTERNOON.
I'LL BE GOING THROUGH THE
DECISION LENS REFRESHER
TRAINING.
WHAT I DROPPED IN THE CHAT OF
THE TEAMS IS THE LINK TO
DIRECTLY GET TO THE VOTING
SCREEN.
YOU SHOULD HAVE RECEIVED AN
E-MAIL LETTING YOU KNOW THE TASK
IS OPEN, USE THAT E-MAIL TO GET
TO THE SAME LOCATION.
ONCE YOU USE THE LINK YOU'LL BE
ABLE TO GET TO THE LOG-IN
SCREEN.
WE'LL USE E-MAIL AND PASSWORD,
IF YOU NEED HELP REMEMBERING
THAT OR RESETTING THAT LET ME
KNOW AND I CAN HELP.
AFTER YOU LOG IN, YOU SHOULD GET
TO A SCREEN THAT I'M SHARING IN
THE TEAMS CURRENTLY, YOU'LL SEE
A RATE ALTERNATIVE TASK AT THE
TOP.
CLICK ON THAT, THAT BRINGS YOU
TO ANOTHER PAGE OF THE DECISION
LENS RATING SCREEN.
WHAT WE'LL HAVE YOU DO IS CLICK
ON THE FIRST CONCEPT THAT WE'LL
BE RATING, STRENGTHENING HEALTH
SYSTEMS HERE AT THE TOP OF THE
LIST.
THIS WILL BRING UP YOUR FIRST
CONCEPT WE'LL BE VOTING ON AND
REVIEWING.
YOU'LL SEE THE CONCEPT NAME
LISTED AT THE TOP IN THE BLUE
TEXT, CLICK AND YOU'LL SEE THE
SIDE CAR CLICK UP ON, I.D. AND
PRESENTER.
ONCE YOU READ THE INFORMATION
ABOUT THE CONCEPTS, YOU'LL MOVE
DOWN THE PAGE AND MAKE YOUR
ASSESSMENT AGAINST EACH OF THE
CRITERIA.
THE CRITERIA ARE LISTED IN
PURPLE.
IF YOU WANT TO SEE THE FULL
CRITERIA DEFINITION, CLICK ON
THE PURPLE TEXT.
PURPLE TEXT WILL PROVIDE YOU THE
FULL DESCRIPTION ON THE SIDE.
ONCE YOU'RE READY TO MAKE YOUR
SELECTION, YOU'LL CLICK INTO THE
BOX THAT YOU WISH TO MAKE YOUR
JUDGMENT.
YOU'LL NOTICE THAT IT SAVES.
ONE MOMENT AS WE GET PLUGGED IN.
GREAT.
YOU'LL NOTICE YOUR RATING HAS
SAVED WHEN IT'S HIGHLIGHTED IN
GREEN.
EVERYTHING WILL AUTO SAVE IF YOU
GET DISCONNECTED OR LOGGED OUT,
YOU'LL BE ABLE TO JUMP BACK IN
AND PICK PICK UP WHERE YOU LEF.
THERE'S A. COMMENTING FEATURE.
IF YOU LEAVE A COMMENT,
QUESTION, FEEDBACK, YOU CAN
LEAVE THAT BY CLICKING THE
COMMENT BUBBLE HERE.
TYPING IN YOUR COMMENT.
AND THEN POSTING THE ADD COMMENT
BUTTON.
YOU'LL PROCEED TO GO DOWN THE
ENTIRE PAGE, MAKING YOUR
JUDGMENTS, AGAIN THEY WILL BE
HIGHLIGHTING IN GREEN KNOWING
THEY ARE SAVING IN THE SCREEN.
ONCE YOU REACH THE BOTTOM YOU'LL
SEE THE NEXT BUTTON AT THE
BUTTON, HIGHLIGHTED IN ORANGE.
IF YOU CLICK ON THAT IT WILL
BRING UP THE NEXT CONCEPT.
YOU'LL BE ABLE TO CHECK YOUR
OVERALL PROGRESS IN THE TOP
RIGHT-HAND CORNER, AS WE WORK
OUR WAY THROUGH WE'LL BE ABLE TO
SEE IF EVERYONE IS ON TRACK.
IF YOU MISS A JUDGMENT I MIGHT
TAP ON YOU THE SHOULDER AND LET
YOU KNOW SO YOU CAN ENTER THAT
VOTE.
IF YOU HAVE QUESTIONS I'LL BE
RIGHT HERE.
RAISE YOUR HAND AND COME FIND
ME.
THANK YOU.
>> WE'RE GOING TO MAKE SURE DR.
MENSAH, IN TERMS OF ORDER,
PRESENTING CONCEPTS, SO THEN
WE'LL COME BACK --
MAURA IS GOING TO LET US KNOW
WHERE COUNCIL MEMBERS ARE IN
TERMS OF COMPLETING THEIR VOTING
AFTER EACH CONCEPT.
WE'LL LOOK TO HER AND GO TO THE
NEXT CONCEPT.
>> OKAY.
>> THANKS.
I THOUGHT I WOULD SHARE THAT WE
REALLY APPRECIATE COMMENTS AND
SUGGESTIONS YOU'RE PUTTING IN
THE FIELD.
SO I STRONGLY ENCOURAGE YOU TO
TAKE ADVANTAGE OF IT AND ADD
YOUR COMMENTS.
THE CENTER FOR TRANSLATIONAL
RESEARCH AND IMPLEMENTATION
SCIENCE FIRST THREE, 5147, 48
AND 50, ALL THREE CONCEPTS ARE
PART OF THE GLOBAL ALLIANCE FOR
CHRONIC DISEASE INITIATIVE,
WHICH FOR THIS PRESENTATION I
WOULD ABBREVIATE GACD, THEY HAVE
NIH-WIDE SUPPORT, ALIGN WITH THE
GOAL TO REDUCE MORBIDITY AND
MORTALITY OF CHRONIC DISEASE
ACROSS THE LIFESPAN.
WE ARE ASKING YOU TO EVALUATE
EACH CONCEPT SEPARATELY, EVEN
THOUGH THEY SHARE A COMMON
BACKGROUND.
SO 5147 SUPPORTS IMPLEMENT
RESEARCH STRENGTHENING HEALTH
SYSTEMS, 5148 ADDRESSES
STRATEGIES BEYOND TRADITIONAL
HEALTH CARE SETTINGS, AND 5150
TARGETS EARLY INTERVENTION FOR
CHILDREN AND YOUTH.
OVERARCHING MISSION TO USE
IMPLEMENT RESEARCH IN LOW- AND
MIDDLE-INCOME COUNTRIES TO FIRST
OVERCOME BARRIERS TO SCALEUP AND
SPREAD OF PROVEN STRATEGIES, AND
SECOND TO BUILD RESILIENT HEALTH
SYSTEMS FOR CHRONIC DISEASE
PREVENTION AND CONTROL.
I'LL PROVIDE A BRIEF BACKGROUND
FOR ALL THREE AND WILL TAKE THEM
ONE BY ONE AND ASK YOU TO
PROVIDE YOUR COMMENTS AND TO
EVALUATE.
BACKGROUND, GACD IS
INTERNATIONAL COLLABORATION OF
LEADING PUBLIC HEALTH RESEARCH
FUNDING AGENCIES, THAT WORK
TOGETHER TO ADDRESS THE GLOBAL
BURDEN OF NON-COMMUNICABLE
CHRONIC DISEASES.
NIH IS THE FOUNDING MEMBER OF
GACD AND HAS BEEN REPRESENTED IN
THE ALLIANCE BY THE NHLBI
DIRECTOR AND DIRECTOR OF THE
FOGARTY INTERNATIONAL CENTER.
OVER THE PAST 14 YEARS THE
ALLIANCE HAS INVESTED OVER $370
MILLION IN 37 RESEARCH PROJECTS,
YIELDED MORE THAN 400
PUBLICATIONS, AND MOST
IMPORTANTLY THE GACD RESEARCH
FINDINGS LED TO POLICY CHANGES
WITH REAL WORLD IMPLICATIONS IN
GHANA, NIGERIA, PERU.
WE CAN SHARE MORE EXAMPLES WITH
YOU.
THE PREVIOUS OR PAST NHLBI
SUPPORTED RESEARCH HAS ADDRESSED
HYPERTENSION, CHRONIC DISEASES
IN URBAN ENVIRONMENTS, AND
MULTI-MORBIDITY MANAGEMENT BUT
IN ALL OF THESE EFFORTS THE
CENTRAL COMMITMENT HAS BEEN THE
DEVELOPMENT OF COMPREHENSIVE
SCALABLE SOLUTIONS FOR EACH OF
THE THREE INITIATIVES, NHLBI NOW
PLANS TO SUPPORT UP TO ONE
HIGH-QUALITY APPLICATION FROM A
LOW AND MIDDLE INCOME COUNTRY.
I WILL NOW BRIEFLY DESCRIBE THE
THREE INDIVIDUAL CONCEPTS AND
THEN ASK FOR YOUR COMMENTS AND
YOUR VOTING.
5147 AS I MENTIONED IS TARGETED
FISCAL YEAR 2026 ON
STRENGTHENING HEALTH SYSTEMS.
THE PRIMARY OBJECTIVE IN THIS
CONCEPT IS TO DEVELOP
CONTEXT-SPECIFIC STRATEGIES
USING IMPLEMENTATION SCIENCE TO
TRANSFORM HEALTH SYSTEMS AND
REDUCE BURDEN OF CHRONIC
DISEASES, EXAMPLES OF INTEREST
IMPORTANT AREAS THAT FOCUS ON
RESEARCH TO SUPPORT BUILDING
RESILIENT HEALTH SYSTEMS
ENHANCING WORKFORCE CAPACITY,
EFFECTIV TECHNOLOGY INTEGRATION,
INCORPORATING INNOVATIONS SUCH
AS PRACTICE FACILITATION, TEST
SHARING, ALL OF THESE STRATEGIES
SO THAT WE CAN IMPLEMENT
CULTURALLY TAILORED
COMMUNITY-INFORMED SOLUTIONS TO
ACCESS TO CARE AND TO CONTINUE
THE CARE, THAT'S THE FIRST ONE.
THE SECOND NUMBER 5148 IS
TARGETED FOR FISCAL YEAR 2027
GOES BEYOND TRADITIONAL HEALTH
SYSTEM.
IT SUPPORTS IMPLEMENTATION
RESEARCH THAT WOULD EXTEND
CHRONIC DISEASE PREVENTION
STRATEGIES BEYOND TRADITIONAL
SETTINGS WITH THE FOCUS ON
LEVERAGING CROSS-SECTOR
ENGAGEMENT IN LOW- AND
MIDDLE-INCOME COUNTRIES.
EXAMPLES OF KEY SEARCH AREAS
INCLUDE BUILDING STRATEGIC
PARTNERSHIPS WITH SECTORS LIKE
SCHOOLS WITHIN THE EDUCATION
SECTOR, HOUSING AND COMMUNITY
DEVELOPMENT THAT WOULD HELP
ADDRESS SOCIAL DETERMINANTS OF
HEART, LUNG, BLOOD, SLEEP
DISORDERS.
IT WOULD ALSO SUPPORT RESEARCH
TO PROMOTE WELLNESS THROUGH
EVIDENCE-INFORMED COMMUNITY
ENGAGEMENT IN ORDER TO ADVANCE
COMMUNITY HEALTH INTERVENTIONS.
THE FINAL CONCEPT 5150 TARGETED
FOR FISCAL YEAR 2028, ADDRESSES
HOW WE SCALE UP AND SPREAD EARLY
INTERVENTIONS.
IT WOULD SUPPORT RESEARCH TO
DEVELOP AND TEST THE SCALING UP
OF THESE INTERVENTIONS
SPECIFICALLY TARGETING CHILDREN
AND YOUTH IN LOW- AND
MIDDLE-INCOME COUNTRIES AND
WOULD BUILD ON INSIGHTS FROM
PREVIOUSLY FUNDED GACD WORK IN
THIS POPULATION.
SOME EXAMPLES ARE INTEGRATION OF
HEART LUNG BLOOD AND SLEEP
PREVENTION INTO SCHOOLS,
PEDIATRIC HEALTH SERVICES,
ACTIVE INVOLVEMENT ENGAGEMENT OF
FAMILIES AND PEERS, IN SHAPING
HEALTHY BEHAVIORS, AND USE OF
INTERACTIVE AND DIGITAL TOOLS TO
BOOST YOUTH ENGAGEMENT IN
PREVENTION.
THESE CONCEPTS ARE VITAL FOR
ACCELERATING PREVENTION AND
CONTROL OF CHRONIC DISEASES IN
THESE COUNTRIES, THEY HELP BRING
TOGETHER MULTI-DISCIPLINE
RESEARCH TEAMS, STRATEGIC
PARTNERS FOR MULTIPLE SECTORS TO
USE IMPLEMENTATION SCIENCE TO
HELP TRANSLATE RESEARCH INTO
PRACTICE.
THEY ALSO HELP REDUCE LONG-TERM
BURDEN AND RISK BY ADDRESSING
CRITICAL DEVELOPMENTAL STAGES BY
EMBEDDING PREVENTION STRATEGIES
EARLY IN LIFE AND BUILD -- THEY
ALIGN WITH NHLBI STRATEGIC
OBJECTIVES, AS YOU HEARD THIS
MORNING FROM DR. GIBBONS'
DIRECTOR'S REPORT AND ALSO
DIRECTLY SUPPORT THE NIH AND HHS
PRIORITIES FOR CHRONIC DISEASES,
ESPECIALLY IN CHILDREN AND
YOUTH.
I'LL STOP HERE TO SEE IF YOU
HAVE ANY CLARIFYING QUESTIONS OR
COMMENTS OR SUGGESTIONS.
AND THEN WE CAN ENCOURAGE YOU TO
PUT IN YOUR VOTES AND YOUR
COMMENTS.
THANK YOU.
AND I CANNOT SEE THE SCREEN SO
IF YOU COULD HELP ME WITH THE
COMMENTS ON THE SCREEN.
>> I HAVE ONE QUESTION.
MAY I PROCEED?
>> IF THERE ARE QUESTIONS GO
AHEAD AND VOTE.
PLEASE REMEMBER --
>> I HAVE A QUESTION.
YOU GUYS CAN'T HEAR ME?
HELLO?
>> DR. MENSAH, CAN YOU HEAR THE
DOCTOR, IN THE ROOM?
>> CHECK ONE, TWO, TEST.
LET ME CHECK ON THE CONNECTION.
>> OKAY.
>> WHO HAS A QUESTION?
>> I HAVE A QUESTION.
CAN YOU HEAR ME NOW?
>> YES.
>> THANK YOU.
DR. MENSAH, THAT WAS ELOQUENTLY
DESCRIBED BUT I CAN'T HELP
MYSELF AND ASK THIS QUESTION.
THREE OF THESE CONCEPTS ARE ON
GLOBAL HEALTH.
AND LOW- AND MIDDLE-INCOME
COUNTRIES, TRIBAL POPULATIONS,
SO MY QUESTION IS ONE THAT I'M
SURE MY COLLEAGUES ARE ALSO
THINKING ABOUT.
GIVEN THE CURRENT POSTURE THAT
WE'RE GETTING FROM THE
GOVERNMENT ABOUT PROGRAMS LIKE
THIS, AND I KNOW COLLEAGUES OF
MINE WHO HAD GLOBAL HEALTH
PROGRAMS REDEFINED, SOME BEING
CANCELED, SO CAN THE INSTITUTE
GIVE US AN ASSURANCE THAT THESE
CONCEPTS WILL PROGRESS AND
BECOME AVAILABLE FOR FOLKS TO
ACTUALLY COMPETE FOR FUNDING?
>> THANK YOU VERY MUCH, VERY
THOUGHTFUL QUESTION.
WAS DR. GIBBONS GETTING READY TO
BEYOND?
I CERTAINLY YIELD TO DR.
GIBBONS.
>> THROW ME THE SOFTBALL,
GEORGE.
>> SOLOMON, I APPRECIATE YOU
BRINGING UP YOUR QUESTIONS.
QUITE APPROACH IT,
UNDERSTANDABLE.
AND WE RECOGNIZE THAT THERE HAVE
BEEN A NUMBER OF TERMINATIONS IN
THE SPACE.
I THINK CLEARLY, I WOULD
CERTAINLY, BASED ON PRIOR
GUIDANCE FROM THIS
ADMINISTRATION, IT'S CLEARLY AN
ISSUE WITH WHAT THEY CALL
COUNTRIES OF CONCERN, GIVEN THE
ADMINISTRATION'S CONCERN ABOUT
THE NATIONAL SECURITY, STEALING
OF INTELLECTUAL PROPERTY, AND
OTHER ELEMENTS OF THAT.
SO THERE IS A -- I'LL SAY A
CIRCUMSPECTION ABOUT GLOBAL
COLLABORATIONS, WHERE THEY ARE,
WHO WE'RE COLLABORATING WITH
WITH TAXPAYER MONEY, FAIR TO
SAY, AND THERE'S THERE'S
SCRUTINY.
THE SECOND LAYER IS RELATED TO
THE SUBAWARD ISSUE, IS THAT MANY
OF THE STRUCTURES THAT WE DEAL
WITH IN THESE INTERNATIONAL
COLLABORATIONS, THE SUBAWARD MAY
BE IN A FOREIGN COUNTRY AND TO
THE DEGREE TO WHICH WE -- THE
ADMINISTRATION BELIEVES WE HAVE
PROBABLY LESS THAN OPTIMAL
OVERSIGHT OF THOSE SUBAWARDS,
THAT'S WHERE THERE'S BEEN A
SENSE OF MAYBE TAKING A STEP
BACK TO SEE HOW WE CAN REFINE
THAT CAPABILITY, AND SO WHAT'S
STILL UNCERTAIN WHETHER THERE'S
A PAUSE AS THAT'S GOING ON, BOTH
THE VETTING AS WELL AS DEFINING
THE OPERATIONAL PATH FORWARD,
VERSUS A COMPLETE ELIMINATION.
THOUGH I DO HEAR YOUR CONCERN,
AND CERTAINLY I THINK WE CAN BE
TRANSPARENT WITH THE PRESIDENT'S
BUDGET.
I DON'T THINK THERE WAS FUNDING
FOR FOGARTY IN THAT BUDGET.
AND SO THAT MAY REFLECT THIS
ADMINISTRATION'S POSITION BUT I
WOULD ALSO SAY THAT IN THE
REORGANIZATION STRATEGY THERE
COULD BE A SENSE OF MAINTAINING
CERTAIN FUNCTIONALITIES, EVEN IF
IT DIDN'T STILL CONTINUE TO
RESIDE IN A PARTICULAR CENTER,
LIKE FOGARTY.
AND JAY I THINK HAS BEEN ON THE
RECORD AS GENERALLY SUPPORTING
INTERNATIONAL COLLABORATIONS.
I THINK IT IS MORE THE HOW THAN
NEVER.
AT LEAST THAT'S OUR INITIAL
IMPRESSIONS.
BUT IT'S STILL EARLY.
IT'S FLUID.
AND TO THE DEGREE TO WHICH IT IS
EARLY AND FLUID, I THINK IT'S
PRUDENT FOR US TO CONTINUE TO
MAKE THE CASE FOR THIS RESEARCH
AND AS DR. MENSAH, AS YOU SAID,
ELOQUENTLY OUTLINED I THINK THE
GOOD CASE CAN BE MADE THAT THIS
IS IN LINE WITH ADDRESSING THE
BURDEN OF CHRONIC DISEASE,
RECOGNIZING ITS INTERNATIONAL
CHARACTER THAT INDEED THE
SECRETARY'S POINTED OUT,
COMPARING OURSELVES WITH WEALTHY
COUNTRIES.
IT IS ALSO I THINK
SCIENTIFICALLY SOUND TO ALSO
INCLUDE LOW- AND MIDDLE-INCOME
COUNTRIES TO ELUCIDATE THE
STRATEGIES TO ADDRESS CHRONIC
DISEASE.
SO WE'RE FOCUSED ON MAINTAINING
THE SCIENTIFIC ARGUMENT, AND
QUITE FRANKLY THIS WILL BE A
TEST CASE.
WE'RE GOING TO SEE WHERE THE
PRIORITIES FALL OUT, AND BUT
WE'RE HOPEFUL.
I HOPE THAT ADDRESSES A VERY
LEGITIMATE QUESTION, SOLOMON.
>> IT DOES.
THANK YOU SO MUCH.
>> THANKS, DR. GIBBONS.
LET ME ENCOURAGE YOU TO PLEASE
REMEMBER TO PUT YOUR COMMENTS
FOR ALL THREE INDIVIDUALLY AND
THEN WE'LL TRY AND GET YOU OUT
OF HERE ON TIME.
THANKS.
>> I THINK YOU CAN MOVE ALONG.
I'M OVER HERE NOW.
>> EXCELLENT.
I WILL TAG YOU.
>> NOW WE'RE MOVING TO THE
CONCEPT OF MY DIVISION,
CARDIOVASCULAR SCIENCES.
THE FIRST ONE, IDS NUMBER 5139,
STRONG HEART STUDY RENEWAL.
SO THE OBJECTIVE AIMS TO
CONTINUE THE STRONG HEART STUDY
WHICH IS THE LONGEST-RUNNING AND
LARGEST MULTI-CENTER PER OF
STUDY OF AMERICAN INDIANS.
WE WANT TO ENSURE IT REMAINS A
VITAL RESOURCE FOR ONGOING
EPIDEMIOLOGIC RESEARCH ON HEART,
LUNG, BLOOD, SLEEP DISORDERS AND
BEYOND AS WELL AS RELATED RISK
FACTORS AND DISEASES IN THIS
POPULATION.
THE STRONG HEART STUDY IS
CONDUCTED IN PARTNERSHIP WITH
TRIBAL GOVERNMENTS, AND
COMMUNITY PARTICIPANTS, FROM 12
TRIBAL COMMUNITIES IN THREE
GEOGRAPHIC AREAS OF THE U.S.,
INCLUDES DAKOTAS, OKLAHOMA, AND
ARIZONA.
AND WITH OVER 540 PUBLICATIONS
MANY IN HIGH IMPACT JOURNALS,
THE STUDY WAS INSTRUMENTAL OF
IDENTIFYING DIABETES AS THE
STRONGEST RISK FACTOR FOR
CARDIOVASCULAR DISEASE IN
AMERICAN INDIAN POPULATIONS AND
FOR IMPLEMENTING PROGRAMS BY
INDIAN HEALTH SERVICE TO REDUCE
THE BUFFERED OF DIABETES AND
CARDIOVASCULAR DISEASE IN THIS
POPULATION.
WE'RE PROPOSING THE NEXT PHASE
WILL CONTINUE TO BUILD UPON
REALLY SIGNIFICANT ACHEEVMENTS
OF THE STUDY OVER THE PAST 35
YEARS, BY SUPPORTING THE
CONTINUED COLLECTION OF ROBUST
DATA THAT IDENTIFIES HEALTH
NEEDS AND CHALLENGES FACED BY
AGING AMERICAN INDIAN
POPULATIONS AND ALSO ADDING DATA
COLLECTION FROM A YOUNGER
GENERATION TO SHAPE CULTURALLY
SPECIFIC PREVENTION AND
TREATMENT STRATEGIES ACROSS THE
LIFESPAN.
THE STRONG HEART STUDY HAS A
SUCCESSFUL TRACK RECORD IN
PUBLICATIONS BUT HAS COMMUNITY
ENGAGEMENTS THAT ARE STRONG WITH
PARTICIPATING TRIBAL COMMUNITIES
AND RENEWAL WILL ENSURE THESE
EFFORTS CONTINUE MOVING FORWARD.
AND THIS WILL CONTINUE THROUGH
DISSEMINATION OF RESULTS,
RELEVANT HEALTH INFORMATION VIA
ONLINE AND PRINTED MATERIALS,
COMMUNITY EVENTS, COMMUNITY
ENGAGED PROJECTS BY IMPLEMENTING
BEST PRACTICES AND AND
CONNECTIONS, WE'LL WORK AND
LEVERAGE ONGOING RESOURCES
PROVIDED BY NIH-WIDE INITIATIVES
SUCH AS COMMUNITY ENGAGEMENT
ALLIANCE, OR CEAL.
THE STUDY WILL CONTINUE TO TRAIN
AND MENTOR EARLY CAREER
RESEARCHERS AND HEALTHCARE
PROFESSIONALS INTERESTED IN
ADDRESSING THE NEEDS AND
CONDITIONS IN TRIBAL
COMMUNITIES.
IN SUMMARY THIS PROPOSED RENEWAL
OF THE STRONG HEART STUDY SEEKS
TO WORK IN PARTNERSHIP TO BEST
SERVE HEALTH NEEDS OF THE NATIVE
AMERICAN COMMUNITIES BY
CONTINUING THE COHORT OF
PARTICIPANTS WHILE EXPANDING TO
INCLUDE YOUNGER PARTICIPANTS.
WE WILL STRENGTHEN
COLLABORATIONS WITH INTERESTED
EXTERNAL RESEARCHERS IN THE
CONDUCT OF ANCILLARY PROJECTS AS
WELL, MAINTAINING COMMUNITY
ENGAGEMENT EFFORTS AND INVEST
TRAINING IN THE NEXT GENERATION
OF HEALTH PROFESSIONALS TO
ADDRESS TRIBAL HEALTH NEEDS.
THANK YOU.
HAPPY TO ANSWER QUESTIONS OR
HEAR ANY COMMENTS.
AND IF NOT, PLEASE FEEL FREE TO
CAST YOUR VOTE.
THANKS.
>> A LOT OF QUESTIONS, IS THE
PERCEIVED BENEFIT WORTH THE
COST.
I SHOULD HAVE ASKED FOR THE
OTHER ONE.
DO WE KNOW THE COST?
JUST ANSWER THE QUESTION?
>> I PERSONALLY THINK YOU SHOULD
BUT YOU SHOULD CERTAINLY KNOW
WHAT IT COST IN THE PREVIOUS
CYCLE.
>> AND IDS WRITE-UP, COST
ESTIMATES ARE IN THE WRITE-UPS,
YOU SHOULD HAVE ACCESS TO BUT WE
CAN PULL THAT UP AND BRING THAT
ON THE TABLE HERE.
>> YEAH, OR, GINA, IF YOU WANT
TO TELL THEM WHAT IT IS.
>> SURE, I CAN PULL THAT UP.
>> THE RANGE.
>> THIS IS A PROCEDURAL
QUESTION.
>> YEAH, IN GENERAL, NOT THIS
ONE SPECIFIC, BUT IS PERCEIVED
BENEFIT WORTH THE COST.
>> YES, WHEN I WAS READING THE
RUBRIC IT LOOKED LIKE IS THIS
WORTH FUND OF THIS IN LIEU OF
FUNDING A SEPARATE R01 OR OTHER
FUNDING MECHANISMS, SO IF IT'S
ABOUT EQUIVALENT, IT'S
EQUIVALENT, IF IT'S WORTH UNION
REDUCING ONE R01 TO FUND THIS,
ET CETERA, IS THAT THE RIGHT
UNDERSTANDING?
>> YEAH, YOU GOT IT.
>> TO A CERTAIN EXTENT WE ALL
HAVE BEEN ON BOTH SIDES.
AND SO WHEN YOU HAVE
INSTITUTE-SOLICITED ACTIVITIES
SOMETIMES AT THE EXPENSE OF
R01S, AND THAT'S OFTEN A USEFUL
BAROMETER AS TO HOW YOU ALL
WOULD FEEL ABOUT SOMETHING IN
TERMS OF OUR INVESTMENT
STRATEGY.
IS THIS WORTH MOVING IN THIS
AREA, WITH INSTITUTE
SOLICITATION RATHER THAN
INVESTIGATOR.
>> IT'S NOT FINANCIAL COST
IT'S OPPORTUNITY COST.
>> AND BOTH ARE ELEMENTS OF YOUR
JUDGMENT, EXACTLY.
>> ANOTHER SECOND OR TWO.
>> SURE.
>> YOU CAN MOVE FORWARD.
>> ALL RIGHT.
MOVE TO THE SECOND ONE.
THAT IS IDS 5149, CARDIOTHORACIC
SURGICAL TRIALS NETWORK RENEWAL.
RENEWAL OF IMPACTFUL
CARDIOTHORACIC NETWORK, CTSN,
LARGEST CARDIAC SURGICAL
RESEARCH NETWORK IN THE WORLD.
TRIAL RESULTS INFLUENCED
NATIONAL AND INTERNATIONAL
GUIDELINES AND CLINICAL
PRACTICE.
SO THE AIM OF THE CURRENT
INITIATIVE TO EXPAND THE SCOPE
OF THE NETWORK WHICH FOCUSES ON
HEART SURGERY, INTERVENTIONAL
CARDIOLOGY, RELATED
PERIOPERATIVE CARE TO INCLUDE
GREATER EMPHASIS ON
IMPLEMENTATION SCIENCE,
CIRCADIAN MEDICINE, MECHANISTIC
SCIENCE EFFORTS.
AT THE SAME TIME YOU WANT TO
STREAMLINE THE PROCESSES IN
CENTRALIZED TRAINING THAT WOULD
LEAD TO REDUCTION IN COST FROM
THE PREVIOUS RENEWAL.
JUST BRIEFLY CONDUCTS TIMELY
EFFECTIVENESS TRIALS WITH
PATIENT CENTERED OUTCOMES THAT
INDUSTRY WILL NOT TYPICALLY DO,
SO THEIR FOCUS IS ON OBTAINING
REGULATORY APPROVAL, AND JUST TO
BRAG ABOUT HOW SUCCESSFUL THIS
NETWORK HAS BEEN, IT HAS BEEN
TREMENDOUSLY SUCCESSFUL.
FOR EXAMPLE, TRAINED
APPROXIMATELY 100 CLINICAL
IMPLEMENTATION SCIENCE
INVESTIGATORS ACROSS
SPECIALTIES, INCLUDING ADULT,
PEDIATRIC CARDIAC SURGERY,
CARDIOLOGY, ICU, BIOSTATS, 538
PAPERS BY THESE TRAINEES,
PUBLISHED 24 PRIMARY OUTCOME
PAPERS IN HIGH-IMPACT JOURNALS
AS WELL AS 76 SECONDARY
ANALYSES.
RAPIDLY PIVOTED IN 2020 TO
BECOME A LEAD ENROLLER IN
MULTIPLE COVID-19 TRIALS,
PROVING IMENSURE VALUE OF HAVING
AN ALREADY EXISTING NETWORK TO
BENEFIT PUBLIC HEALTH
EMERGENCIES.
IN THIS CURRENT OR THIRD CYCLE,
DOUBLED FUNDING BY COLLABORATING
WITH INTERNATIONAL FUNDERS,
SMALL BUSINESS INVESTIGATORS,
OBTAINING ADDITIONAL GRANTS
THROUGH OUR NORMATIVE PROCESSES.
AND COLLECTIVELY THIS NETWORK
HAS WORKED WITH OVER 800
INVESTIGATORS, WHO ENROLLED OVER
5,000 PARTICIPANTS IN RANDOMIZD
CONTROLLED TRIALS, 14,000
PARTICIPANTS, 550 IN REGISTRIES
WORLDWIDE.
I WANT TO MENTION THAT NHLBI
RECONVENED AN EXPERT PANEL IN
2024 THAT UNANIMOUSLY
RECOMMENDED WE CONTINUE TO
INVEST PUBLIC MONEY INTO THIS
CTSN TO BUILD UPON THE
CONTRIBUTION THIS WORK HAS MADE
IN TERMS OF CARE FOR THE
PARTICIPANTS WITH CARDIOVASCULAR
DISEASE.
THEY HAVE PROPOSED 19 CHILD
CONCEPTS TO ADDRESS IN
GUIDELINES, WE WON'T BE PUTTING
ALL THAT IN OUR RENEWAL.
WE'RE GOING TO BE ASKING
INVESTIGATORS TO COME UP WITH
THOSE IDEAS AND FUND SEPARATELY
THAT WAY.
SPECIFICALLY, I WANT TO MENTION
FOR THIS PARTICULAR CYCLE
THERE'S GOING TO BE A
STREAMLINED PROCESS TO INCREASE
EFFICIENCY, DONE BY REORGANIZING
CTSN INFRASTRUCTURE TO BE A
SINGLE AWARD FOR DATA AND
COORDINATING CENTER AND THAT
WILL CONTRACT WITH CLINICAL
SITES.
YOU ALL HAVE THE CURRENT
PROPOSAL, DOES HAVE SEED FUNDING
PROPOSED TO CONDUCT TWO TO THREE
INVESTIGATOR-INITIATED TRIALS
AND COORDINATE THE TRAINING.
AND AS FAR AS -- AS WELL I
MENTION THIS WILL BROADEN
RESEARCH AND INTERVENTION
CARDIOLOGY AND CONTINUE TO
ATTRACT ADDITIONAL FUNDING FROM
BROAD STAKEHOLDERS INCLUDING
ACADEMIA, PROFESSIONAL
SOCIETIES, ET CETERA, AND
INTERNATIONAL RESEARCH ENTITIES.
FINALLY WE'LL EXPAND
IMPLEMENTATION SCIENCE EFFORTS
AS WELL AS MECHANISTIC AND
CIRCADIAN MEDICINE RESEARCH
THROUGH COLLECTION OF
BIOSPECIMENS, IMAGING DATA,
WEARABLES.
SO IN SUMMARY WE'RE PROPOSING TO
RENEW, WHICH GENERATED NUMEROUS
TRIALS RESULTS, THAT CHANGED
NATIONAL AND INTERNATIONAL
GUIDELINES IN INFLUENCING
CLINICAL PROGRAM WITHOUT THIS
RENEWAL WE WORK CLINICIANS COULD
GO BACKWARDS TO EARLIER DAYS
CONDUCTING PROCEDURES WITHOUT
EFFICACY AND SAFETY.
THANK YOU FOR YOUR ATTENTION.
>> ONE QUESTION, IN LOOKING AT
SOME OF THESE TRIALS, THEY LOOK
LIKE THEY WERE INVESTIGATING
KIND OF NOVEL THINGS THAT WOULD
HAVE BEEN -- THERE WOULD BE SOME
ADVANTAGE FOR THE COMPANIES THAT
MAKE THOSE VALVES, FOR EXAMPLE,
IS THERE A SEPARATE FUNDING
MECHANISM FOR THAT, YOU KNOW, IN
ORDER TO BE PART OF CTSN BUT THE
TRIAL PARTLY FUNDED BY THOSE
ORGANIZATIONS?
>> YEAH, THANK YOU FOR THAT.
I'LL DO MY BEST TO ANSWER.
SO, WE HAVE SEVERAL OTHER
MECHANISMS FOR -- LIKE SMALL
BUSINESS, FOR EXAMPLE, THAT CAN
TEST THOSE AND DEVELOP THOSE
PROCEDURES OR WHATEVER IT IS
THAT'S DEVELOPED.
SO, YEAH, I THINK BEFORE THEY
ACTUALLY COME TO CTSN THEY NEED
TO BE TESTED IN SOME WAY, SO WE
WOULDN'T BE USING, AT LEAST I
DON'T THINK SO, WOULDN'T BE
USING FOR FIRST IN HUMAN TRIALS
BUT MORE OF A BROADER --
>> WHAT I CAN ADD, IS THAT THERE
ARE PROTOCOLS DONE IN CTSNs
THAT ARE INDUSTRY FUNDED SO
THE -- WE FUND SOME TRIALS IN
CTSN BUT NOT ALL THE TRIALS IN
CTSA.
THAT'S SOMETHING WE WANT THE
INVESTIGATORS TO BE
ENTREPRENEURIAL AND IF WE INVEST
IN THE NETWORK AND THEY HAVE
THEM, THE INFRASTRUCTURE AND
CAPACITY, WE THINK THEY SHOULD
BECOME A GO-TO PLACE FOR
INDUSTRY TO COME AND SAY WE WANT
TO TEST OUR APPROACHES HERE.
NOW, WHAT WE SEE OFTEN IS THAT
THE INVESTIGATORS ARE INTERESTED
IN COMPARATIVE EFFECTIVENESS,
COMPANIES ARE NOT INTERESTED IN
COMPARATIVE EFFECTIVENESS
RESEARCH.
IF THEY HAVE A NEW VALVE THEY
DON'T WANT TO TEST AGAINST
ANOTHER VALVE, THEY JUST WANT TO
SEE DOES THEIR VALVE WORK.
THAT'S NOT THE QUESTION MOST OF
THESE INVESTIGATORS WITH
INTERESTED IN.
THEY WANT TO KNOW DOES IT WORK
BETTER THAN OR AS WELL AS
SOMETHING THAT'S ALREADY
AVAILABLE.
SO THEY ARE MORE INTERESTED IN
COMPARATIVE EFFECTIVENESS, SO
SOMETIMES THE DIVISIONS AND
MISSIONS DON'T ALIGN BUT WHEN
THEY DO THERE'S PARTNERSHIP.
>> WE JUST HAVE SOME PEOPLE
FINISHING UP THEIR VOTING.
>> WE HAVE THE PROGRAM OFFICIAL
HERE FROM CTSN, DR. KATHLEEN
FENTON, TO GIVE A LITTLE BIT
MORE ANSWER.
>> I WANTED TO ADD -- THANK YOU
FOR THE QUESTION, APPRECIATE IT.
ON THIS FUNDING CYCLE FOR
EXAMPLE THE CURRENT FUNDING
CYCLE WE HAVE HAD TWO TRIALS
THAT WERE BROUGHT IN BY SMALL
BUSINESSES, AND THE TRIAL
RESULTS HELPED THE BUSINESSES,
SORRY ABOUT THAT, I DON'T KNOW
HOW TO FIX IT, CONTRIBUTE TO THE
REGULATORY PAPERWORK FOR FDA.
ONE OF THEM WAS A TRIAL LOOKING
AT SOMATIC STEM CELLS, AND
ANOTHER ONE WAS LOOKING AT A
DEVICE.
SO AS DAVID MENTIONED, THE
BIG -- MOST OF THE BIG COMPANIES
LIKE MEDTRONIC AND ABBOTT HAVE
THEIR OWN TRIAL NETWORKS ALREADY
AND THEY HAVE THEIR WHOLE
SYSTEM.
SOME OF OUR INVESTIGATORS
ACTUALLY WORK WITH THEM AND WORK
WITH THE CTSN.
BUT THE SMALL COMPANIES REALLY
BENEFIT FROM BEING ABLE TO BRING
THINGS IN AND DO SORT OF SMALLER
TRIALS WITH US, IT'S NOT A
3,000-PATIENT TRIAL.
IT'S A SMALL TRIAL.
>> THIRD ONE, 5128, THE NEW
HEART HEALTH STUDY RENEWAL.
YOU HEARD ABOUT THIS FROM DR.
GIBBONS EARLIER TODAY AS WELL.
OBJECTIVE OF THE NEW MOM 2 BE IS
FOLLOW THIS RICHLY PHENOTYPED
COHORT OF WOMEN WHO HAVE BEEN
PART SINCE THE FIRST PREGNANCY,
FURTHER UNDERSTAND RELATIONSHIP
BETWEEN ADVERSE PREGNANCY
OUTCOMES AND CARDIOVASCULAR
DISEASE, BY ADVERSE WE MEAN
STILLBIRTH, SMALL FOR
GESTATIONAL AGE, PRE-TERM,
DISEASES PREGNANCY, GESTATIONAL
DIABETES.
WOMEN DONATED BIOSPECIMENS AND
DATA SINCE THIS STUDY INCEPTION
15 YEARS AGO.
AS A RESULT IMPORTANT
DISCOVERIES HAVE BEEN GLEANED
INCLUDING WHAT YOU HEARD EARLIER
SEMINAL FINDING WOMEN WITH
ADVERSE OUTCOMES 45% MORE RISK
THAN THOSE WITHOUT WITHOUT
ADVERSE PREGNANCY OUTCOMES TO
DEVELOP NEW ONSET HYPERTENSION
IN AS LITTLE AS 2 TO 7 YEARS
AFTER FIRST PREGNANCY, WOMEN
WITH AVERAGE OUTCOME MORE LIKELY
TO HAVE ATHEROGENIC
CHARACTERISTICS, HIGHER BLOOD
PRESSURES, GLUCOSE, LOWER
HDLs, IN PARTICULAR FOUND
HIGHER GLUCOSE AND HIGH
SENSITIVITY CRP WITH HIGHER RISK
OF HYPERTENSION 2 TO 7 YEARS
AFTER PREGNANCY.
THE PURPOSE OF THIS RENEWAL
SEVERAL FOLD.
NUMBER ONE, FURTHER ENHANCE AND
UNDERSTAND RISK FACTOR
PROGRESSION FROM ADVERSE
PREGNANCY OUTCOMES TO CARDIO AND
CEREBROVASCULAR DISEASE IN
PARTICIPANTS.
SECOND TO PROMOTE ADOPTION OF
HEALTHY LIFESTYLE BEHAVIORS
THROUGH HEALTH EDUCATION, VIA
VARIETY OF MODALITIES.
THIRD PROVIDE STATISTICAL POWER
TO PERFORM ANALYSES OF
PREDICTORS OF CLINICAL EVENTS.
FOURTH, STUDY PROGRESSION OF
SUBCLINICAL TO CLINICAL
CARDIOVASCULAR DISEASE, FIFTH TO
IDENTIFY NEW RISK FACTORS FOR
INTERACTIONS SUCH AS
PERIMENOPAUSE AMONG FACTORS THAT
INFORM DISEASE PATHOPHYSIOLOGY.
SO IN SUMMARY THIS RENEWAL WILL
CONTINUE THE FOLLOW-UP AND
REPEAT CLINICAL EXAMINATIONS
THAT WILL ADD TO RICH DATA AND
SAMPLES ALREADY AMASSED AND
ENABLE CAPTURE OF ADDITIONAL
DATA AS WOMEN ENTER
PERIMENOPAUSE AND MENOPAUSE, AN
IMPORTANT STAGE IN THEIR
LIFESPAN FOR STUDY TO UNCOVER
IMPACT OF BOTH PRIOR PREGNANCY
OUTCOMES AND NEW HORMONAL
CHANGES ON CARDIOVASCULAR HEALTH
AND OUTCOMES.
SO THAT WE WANT TO CAPTURE
CHANGES TO ADDRESS QUESTIONS
ABOUT THE DEVELOPMENT AND
PROGRESSION OF CLINICAL
CARDIOVASCULAR DISEASE AND
RELATED CONDITIONS.
SO THANK YOU FOR YOUR ATTENTION.
THIS CONCEPT IS OPEN FOR
COMMENTS, DISCUSSIONS, VOTING.
>> I HAVE A QUESTION.
CAN YOU COMMENT ON THE BUDGETARY
PLAN, LIKE THE CONTRACTING OUT
AND WHAT THE THOUGHT PROCESS FOR
THAT IS?
>> YES.
THIS IS MEANT TO BE -- THANK
YOU.
THIS IS OPEN SESSION, RIGHT?
I WANT TO MAKE SURE.
OKAY.
SORRY, WHY ARE WE BEING -- YES,
SO THIS IS GOING TO BE CHANGED,
CURRENTLY COOPERATIVE AGREEMENT,
WE'RE CHANGING -- PROPOSING TO
HAVE IT CHANGED TO A CONTRACT.
AND ALSO PROPOSED TO BE A SINGLE
CONTRACT AND THEN WILL HAVE
SUBCONTRACTS TO THE DIFFERENT
CENTERS THAT COLLECT THE DATA.
DOES THAT ANSWER YOUR QUESTION?
>> YES.
>> [OFF MICROPHONE].
>> YES, WE WANT TO KEEP THE --
FOR NOW WE WANT TO KEEP THE
STRUCTURE SIMILAR TO THE
COOPERATIVE AGREEMENT.
THE CURRENT IS THE SAME THING,
WHERE THE CENTERS --
COORDINATING CENTERS ARE THE
PRIMARY FUNDERS AND THEN THEY
PAY OUT THE FIELD CENTERS.
SO, YEAH.
THANKS.
>> SO I THINK THE QUESTION MIGHT
BE WHY CHANGE FROM COOPERATIVE
AGREEMENT TO CONTRACT, AND THIS
IS KIND OF NORMATIVE WITH OUR
OTHER LARGE COHORTS.
SO IF YOU THINK ABOUT OUR COHORT
PORTFOLIO, FRAMINGHAM, JACKSON,
MESA, ERICK, CARDIA, SOUL, THEY
ARE CONTRACTS.
THE REASON WE TAKE THIS
APPROACH, BEFORE I GOT HERE, SO
IT'S HISTORICAL IN NATURE, IT
PROVIDES A COUPLE -- MANY
ADVANTAGES TO THE INSTITUTE.
ONE IS WE HAVE GREATER ABILITY
TO PARTICIPATE ACTIVELY IN THE
SCIENCE OF THE CONTRACT IN TERMS
OF GUIDING WHAT HAPPENS WITHIN
THE COHORT.
WE ALSO -- DATA AND BIOSPECIMENS
WE MAIN UNDER MORE GOVERNMENTAL
CONTROL, IF YOU WILL, IN TERMS
OF LONG-TERM MANAGEMENT OF THE
RESEWERS. -- RESOURCE.
AT THE END OF SUN SETTING THE
COHORT THE BIOSPECIMENS AND THE
DATA ARE ACTUALLY GOVERNMENT
PROPERTY AS DELIVERABLES FROM
THE CONTRACT.
IT ALSO MAKES IT POSSIBLE FOR US
TO REALLY KIND OF GUARD AGAINST
VAGARIES OF ASSIGNMENT OF
APPLICATIONS FOR CORE SUPPORT
FOR THE COHORTS TO PEER REVIEW.
NOW, THE SCIENTIFIC COMPONENTS
GET ADDED ON BY ANCILLARY
STUDIES.
AND THAT GETS INFORMED BY PEER
REVIEW, BUT THE CORE
INFRASTRUCTURE OF THE COHORT,
ONGOING FOLLOW-UP, RETENTION,
MANAGEMENT OF THE DATA
REPOSITORY AND BIOREPOSITORY,
THOSE ARE IN THE BEST INTEREST
ST INSTITUTE AND WE BELIEVE THE
TAXPAYERS TO MAINTAIN UNDER
CONTRACT MECHANISM WHILE
ALLOWING THE SCIENCE TO EVOLVE
AND BE THE BEST SCIENCE
INVESTIGATORS CAN PROPOSE
THROUGH THE
INVESTIGATOR-INITIATED PEER
REVIEW SYSTEM.
SO I HOPE THAT HELPS IN
DESCRIBING WHY WE HAVE CORE
CONTRACTS FOR INFRASTRUCTURE
LAYERED ON TOP OF THAT ANCILLARY
STUDIES TO R01s TO STRENGTHEN
THE SCIENCE.
>> THANK YOU.
AND THANK YOU, I THINK IN TERMS
OF THE CONFLICT WE FOUND OUT
THAT IT WAS OKAY FOR -- SHE JUST
CAN'T VOTE, I THINK THAT'S
SQUARED AWAY.
READY TO MOVE ON.
THOSE THREE ARE PRETTY MUCH THE
HUGE INITIATIVES, AS YOU
NOTICED.
I'M GOING TO GO ON WITH
SECONDARY PARTICIPATION.
SO THIS IS IDS 51378 SECONDARY
PARTICIPATION IN RENEWAL,
LIMITED COMPETITION FOR NATIONAL
SWINE CENTER, SECONDARY
PARTICIPATION OF AN INITIATIVE
LED BY THE NIH OFFICE OF
RESEARCH INFRASTRUCTURE PROGRAM,
NIH OFFICE OF DIRECTOR.
THE PURPOSE OF THIS INITIATIVE
IS TO PROVIDE CONTINUOUS SUPPORT
FOR NATIONAL SWINE RESOURCE AND
RESEARCH CENTER.
TO INCREASE UNDERSTANDING OF
HUMAN HEALTH AND DISEASE YOU
BOUGH SWINE MODELS FOR
BIOMEDICAL RESEARCH, CREATES
GENETICALLY MODIFIED MODELS AS
REQUESTED BY SCIENTIFIC
COMMUNITY, REPOSITORY AND
DISTRIBUTION CENTER, AS WELL AS
OTHER RESOURCES SUCH AS REAGENTS
AND CULTURES INCLUDING CELLS,
TISSUES, ORGANS, THAT SERVE THE
BIOMEDICAL COMMUNITY AT LARGE.
THE CENTER IS THE ONLY PUBLICLY
FUNDED SWINE FACILITY TO SERVE
AS A REPOSITORY FOR NEW SWINE
MODELS GENERATED BY ACADEMIC
RESEARCHERS AND RESOURCE FOR
INBRED OR GENETICALLY ALTERED
MODELS.
THERE'S A GROWING AWARENESS OF
LARGE ANIMAL MODELS FOR USE IN
EXPEDITING BASIC RESEARCH TO
FIND CURES AND THERAPIES FOR
HOME.
THEY ARE CLOSELY RELATED TO
HUMANS IN TERMS OF ANATOMY,
GENETICS, PHYSIOLOGY, WITH
ORGANS SHARING COMMON FUNCTIONAL
FEATURES, IDEAL MODEL, A
CLINICAL RESOURCE FOR
UNDERSTANDING HUMAN BIOLOGY TO
REDUCE CORONARY ARTERY DISEASE,
DIABETES, OBESITY, HYPERTENSION,
HEART AND LUNG TRANSPLANTATION,
XENOTRANSPLANTATION, HEMOPHILIA
AND OTHER DISEASES, RESOURCE OF
INFLAMMATION AND TRAINING
RELATED TO USE OF THESE ANIMALS
IN BIOMEDICAL RESEARCH AS MODELS
OF HUMAN HEALTH AND DISEASE FOR
THE BROADER RESEARCH COMMUNITY.
AND HAVE FORMED CUTTING EMBEDDED
RESEARCH TO ADVANCE TECHNOLOGY
IN THIS AREA.
IN SUMMARY WE'RE PROPOSING TO
CO-FUND RENEWAL OF THE CENTER,
SO IT CAN CONTINUE TO SERVE AS
CENTRAL RESOURCE FOR THE
CREATION OF GENETICALLY MODIFIED
SWINE REAGENTS AND PROCUREMENT,
PRESERVATION, DISTRIBUTION OF
SWINE AND BIOLOGICAL MATERIALS
TO INVESTIGATORS THROUGHOUT THE
COUNTRY.
THANK YOU FOR YOUR ATTENTION.
THIS IS OPEN FOR COMMENTS,
QUESTIONS, VOTING.
YES.
>> [OFF MICROPHONE].
>> THE QUESTION, WHAT
PROPORTION, IT LOOKED LIKE A LOT
OF INSTITUTES ARE BENEFITING
FROM THE SWINE MODEL.
DO YOU KNOW WHAT PORTION IS
COVERED BY NHLBI VERSUS OTHER
INSTITUTES?
>> I WAS GOING TO LOOK IT UP.
THANK YOU.
19% IS THE ANSWER.
>> A QUICK QUESTION REGARDING
THE COMPETITION.
>> YES PLEASE, GO AHEAD.
>> I KNOW YOU SAY LIMITED
COMPETITION, I'VE SEEN LIMITED
COMPETITION APPLICATIONS ONLY
ONE ENTITY OR INSTITUTION WAS
ALLOWED TO APPLY.
HOW MANY INSTITUT NATIONAL
TUITIONS OR ENTITIES ARE ALLOWED
IN THIS?
>> LIMITED COMPETITION IS FOR
THE CENTER, TO RENEW CENTER TO
PROVIDE RESOURCE.
SO ONCE IT'S RENEWED THEN PRETTY
MUCH OPENED UP THE APPLICATIONS,
RESOURCES OPEN UP TO THE ENTIRE
U.S., THE RESEARCH COMMUNITY,
HOPE THAT HELPS.
>> IT DOES.
THANK YOU.
>> MOVING TO CONCEPT FIVE.
THIS IS IDS 5127, STIMULATING
ACCESS TO RESEARCH AND RESIDENCY
TRANSFER SCHOLAR, START FOR
SHORT.
MOVING, OBJECTIVE GOAL OF THE K
88 STIMULATING ACCESS TO
RESEARCH AND RESIDENCY
TRANSITION SCHOLAR, START,
CAREER DEVELOPMENT PROGRAM TO
HELP ENSURE MULTIPLE POOLS OF
HIGHLY TRAINED SCIENTISTS
AVAILABLE IN APPROPRIATE
SCIENTIFIC DISCIPLINES TO
ADDRESS THE NATION'S BIOMEDICAL,
BEHAVIORAL, CLINICAL RESEARCH
NEEDS.
AS YOU KNOW, NIH INSTITUTES AND
CENTERS SUPPORT A VARIETY OF
MENTORED AND NON-MENTORED CAREER
DEVELOPMENT AWARD PROGRAMS,
DESIGNED TO FOSTER TRANSITION OF
NEW INVESTIGATORS TO RESEARCH
INDEPENDENCE AND ALSO SUPPORT IN
ACHIVING OBJECTIVES.
SO THE PURPOSE FOR THIS
PARTICULAR --
[ NO AUDIO ]
HERE WE GO.
THIS PROGRAM PROVIDES INDIVIDUAL
MENTORED AWARDS TO RETAIN AND
SUPPORT CLINICIAN INVESTIGATORS
WHO HAVE SUCCESSFULLY COMPLETED
AND R 38 STAR PROGRAM, FOCUSED
ON RESIDENCY PREFERRED.
SO TO PROVIDE OPPORTUNITIES FOR
ADDITIONAL RESEARCH AND CAREER
DEVELOPMENT DURING SUBSEQUENT
CLINICAL FELLOWSHIPS OR EARLY
CAREER FACULTY, ANTICIPATED THAT
THE K 38 STAR PROGRAM WILL
PROVIDE PATHWAY TO RETAIN NEWLY
CREATED POOL OF INVESTIGATORS
GENERATED IN THE R 36 STAR
PROGRAM.
GRANTEES WOULD RECEIVE SUPPORT
FOR CONTINUED RESEARCH AND
CAREER DEVELOPMENT OPPORTUNITIES
AND BASIC CLINICAL AND/OR
TRANSLATIONAL RESEARCH,
PROVIDING POTENTIAL TO
ACCELERATE TRANSITION TO
INDEPENDENT RESEARCH CAREERS.
THIS AWARD SUPPORTS UP TO 28
MONTHS OF RESEARCH IN CAREER
DEVELOPMENT WITH SAME OR NEW
PRIMARY MENTOR DEPARTMENT AND/OR
INSTITUTION, AS THAT OF THE R
38.
PROVIDING A 75% OF SUPPORTED
TIME WHILE FACULTY ARE PROVIDED
50% AT THE SUPPORTED TIME FROM
THE AWARD.
THE AWARD INCLUDES RESEARCH
DEVELOPMENT FUNDS TO UNCOVER
COST OF RESEARCH SUPPLIES,
PROFESSIONAL DEVELOPMENT
ACTIVITIES, APPLICANTS ARE
STRONGLY ENCOURAGED TO PREPARE
AND SUBMIT APPLICATION FOR
ANOTHER MENTOR RESEARCH CAREER
DEVELOPMENT AWARD SUCH AS K01,
K23, ET CETERA, BEFORE THE END
OF THE PROGRAM.
TO DATE 15 OF THE R 38 PROGRAM
GRADUATES APPLIED TO THIS K 38
PROGRAM WITH 12 SUCCESSFULLY
OBTAINING FUNDING, ADDITIONAL
FIVE HAVE APPLIED IN FY 25, SO
THIS NUMBER OF APPLICATIONS WITH
THE K 38 REFLECTS APPROXIMATELY
30% OF THE ELIGIBLE R 38
GRADUATES, AND SO A LARGE
PROPORTION REMAIN IN FELLOWSHIP
TRAINING AND HAVE YET TO PURSUE
ANY GRANT FUNDING YET WHILE MANY
OTHERS OBTAINED T32, K12s, ET
CETERA.
WE'RE LOOKING FORWARD TO
RENEWING TO OPEN UP THIS
OPPORTUNITY.
THANK YOU.
>> I LOVE THIS.
I REALLY THINK SUPPORTING OUR
PIPELINE IS CRITICAL.
YOU'VE ALREADY PRE-SELECTED BY
THE FACT THESE ARE TRAINEES WHO
ALREADY SUCCESSFULLY HAVE GONE
THROUGH THE R 38 PROGRAM, SO I
THINK DEVELOPING A MECHANISM TO
CONTINUE THEIR SUPPORT IS SO
IMPORTANT, AND EVEN MORE
IMPORTANT IN THESE CURRENT
TIMES.
THANK YOU.
>> THANK YOU, DR. SCHNAPP.
>> WE'RE HAVING A PROBLEM WITH
THE MICS.
SOMETHING'S HAPPENING OVERALL.
WE'LL BE SHARING UNTIL THEY CAN
FIGURE OUT SOMETHING.
>> I'M GOING TO DO CONCEPT 8.
THIS IS ALSO ONE WHERE NHLBI IS
PRIMARY, SECONDARY ANALYSIS OF
EXISTING DATASETS, HEART, LUNG
AND BLOOD DISEASES AND SLEEP
DISORDERS.
SO THIS IS AN NHLBI-LED R21,
RENEWAL OF INITIATIVE AIMS TO
CONTINUE ENCOURAGING INNOVATIVE
SECONDARY DATA ANALYSIS TO
ADDRESS GAPS IN KNOWLEDGE AND
IMPORTANT SCIENTIFIC QUESTIONS
WITHIN OUR MISSION.
IT SEEKS TO PROVIDE
INVESTIGATORS ESPECIALLY EARLY
STAGE INVESTIGATORS WITH ABILITY
TO OBTAIN PRELIMINARY DATA
FOSTERING DEVELOPMENT OF
PROJECTS AND FURTHERING RESEARCH
CAREERS.
THIS PROGRAM WHICH INITIALLY
STARTED IN 2012 SUPPORTS R21
AWARDS FOR TWO YEARS WITH NO
MORE THAN $75,000 IN DIRECT COST
ALLOWED IN ANY SINGLE YEAR.
IT'S BEEN IMMENSELY POPULAR WITH
THE INVESTIGATOR COMMUNITY.
OVER THE PAST DECADE OR SO THE
PROGRAM HAS RECEIVED ALMOST 1500
APPLICATIONS WITH 25% COMING
FROM ESIs, EARLY STAGE
INVESTIGATORS, 181 GRANTS, 20%
TO EARLY STAGE INVESTIGATORS.
THE NUMBER OF APPLICATIONS
SUBMITTED YEARLY CONTINUES TO BE
AROUND 100 OR MORE.
THE PROGRAM HAS SUCCESSFULLY
INCREASED DATA USAGE WITH OVER
250 DATASETS AND HAS SUPPORTED
R01 PROJECTS WITH SECONDARY
ANALYSIS CONTENT.
ADDITIONALLY THE INITIATIVE HAS
GENERATED OVER 750 SCIENTIFIC
PUBLICATIONS, VARIOUS RESOURCES
INCLUDING STATISTICAL AND IMAGE
AND METHODOLOGIES, SOFTWARE,
DATASETS.
NEW DATA AVAILABILITY SUCH AS
FROM NHLBI BIODATA CATALYST OR
"ALL OF US" WILL ENHANCE
OPPORTUNITIES MAKING PROGRAMS
LIKE THIS QUITE VALUABLE TO HAVE
INVESTIGATORS LEVERAGE RESOURCES
FOR HEART, LUNG, AND BLOOD
DISORDERS.
GIVEN COST EFFECTIVENESS AND
PRODUCTIVITY WE'RE PROPOSING TO
RENEW THIS INITIATIVE FOR
ANOTHER THREE YEARS.
THANK YOU FOR YOUR ATTENTION.
THIS CONCEPT IS OPEN FOR
QUESTIONS, COMMENTS, VOTING.
I THINK WE'RE DONE.
BUT NOT QUITE YET.
ALL RIGHT.
THE FINAL TWO CONCEPTS, ONE
FOCUSES ON CAREER DEVELOPMENT, K
AWARDEES, THE OTHER ON
FIRST-TIME RPG AWARDEES.
FIRST IS CONCEPT 5144,
ADMINISTRATIVE SUPPLEMENT TO
PROMOTE RESEARCH CONTINUITY AND
RETENTION OF NIH MENTORED CAREER
DEVELOPMENT AWARD RECIPIENTS AND
SCHOLARS.
I WILL GO AHEAD.
SO THIS ONE, THE OBJECTIVE OF
THE SECONDARY SIGN-ON TO PROVIDE
ADDITIONAL RESOURCES TO OUR
CAREER DEVELOPMENT OR K AWARDEES
FOR FACING CRITICAL LIFE EVENT
THAT TAKES THEM IN RESEARCH FOR
EXTENDED PERIODS OF TIME DURING
THIS VULNERABLE CAREER STAGE,
THIS SUPPLEMENT PROGRAM ENHANCES
RETENTION OF INVESTIGATORS
FACING CRITICAL LIFE EVENTS
INCLUDING CHILD BIRTH, ADOPTION,
CARE OF IMMEDIATE FAMILY MEMBERS
WHO ARE ILL OR SEVERE PERSONAL
HEALTH ISSUE.
THESE CAN LEAD TO SIGNIFICANT
DISRUPTIONS DURING MENTORED
CAREER DEVELOPMENT AWARDS, AND
HINDER TRANSITION TO RESEARCH
INDEPENDENCE.
THROUGH THE SUPPLEMENTS NHLBI
CAREER DEVELOPMENT AWARDEES CAN
REQUEST ADDITIONAL FUNDS TO
SUPPORT THEIR RESEARCH WHILE
THEY ARE AWAY FROM THE LAB.
THESE FUNDS CAN BE USED TO
HIGHER PERSONNEL TO HELP WITH
PATIENT RECRUITMENT, LAB WORK,
DATA ANALYSIS, OR PURCHASE
EQUIPMENT OR SUPPLIES TO
ACCELERATE PROJECT COMPLETION.
THE PROGRAM IS INTENDED TO
SUPPORT CONTINUITY AMONG
RECIPIENTS BY PROVIDING
SUPPLEMENTAL RESEARCH SUPPORT TO
HELP SUSTAIN INVESTIGATORS'
FUTURE'S MOMENTUM DURING A
VULNERABLE STAGE OF THEIR
CAREER, SO BY -- WE ARE HOPING
THAT BY MITIGATING IMPACT OF
CRITICAL LIFE EVENTS THE
AWARDEES WILL HAVE RESOURCES TO
REMAIN COMPETITIVE FOR FUTURE
FUNDING SO WE CAN HELP ENCOURAGE
RETENTION OF THE NEXT GENERATION
OF HLBS RESEARCHERS.
I CAN PAUSE AND SEE IF PEOPLE
HAVE COMMENTS FOR THIS ONE.
OR I CAN GO TO THE NEXT.
DID YOU WANT TO SAY SOMETHING?
>> MINOR.
GIVEN THE COMMENTS ON THE
FEDERAL LEVEL SHOULD WE CHANGE
TO MALE-FEMALE, INSTEAD OF
MEN-WOMEN OR DO YOU THINK IT
WON'T MAKE A DIFFERENCE WITH IT
BEING SCOPED OUT USING A.I.?
I THINK IT'S VERY IMPORTANT, I'M
SORRY, I'M WONDERING IF IT'S
WORTH MAKING IT MALE-FEMALE.
>> I WOULD DEFER TO PROGRAM ON
THAT.
I HEAR YOUR SENSIBILITY.
AND QUITE FRANKLY, THERE HAVE
BEEN SOME INITIATIVES MAYBE
RELATED TO THE OTHER ONE,
MATERNAL HEALTH, WHERE THERE WAS
LANGUAGE ABOUT PREGNANT PEOPLE.
I THINK IT'S FAIR TO SAY THAT
HAS BEEN ALTERED IN THAT CONTEXT
AND YOU'RE ALLUDING TO OTHER
DEFINITIONS OF GENDER AND
IDENTITY WHICH AGAIN GIVEN THE
TRANSITION IS BEING CONSIDERED
IN LIGHT OF THE EXECUTIVE
ORDERS.
IN THIS CONTEXT THOUGH I DO
THINK IT RELATES TO BOTH SEXES.
I THINK WE'RE ACTUALLY TRYING TO
BE A LITTLE BIT MORE 21ST
CENTURY THAT WHETHER YOU'RE THE
DAD OR YOU'RE THE MOM HAVING A
CHILD IS A LIFE EVENT, AND IT
MAY AFFECT YOUR WORK.
SO IT IS SOMETHING THAT WE'VE
AWARDED BOTH MEN AND WOMEN.
SO, I THINK WE'RE OKAY, AS LONG
AS -- I APPRECIATE YOUR QUESTIN
AND THIS IS THE TIMES WE'RE IN.
>> AGAIN, SUPPORTING OUR
PIPELINE AT THE RELATIVELY
MODEST COST WITH TREMENDOUS
IMPACT ON THE INVESTIGATORS
IMPACTED BY IT SO I THINK IT'S A
GREAT INVESTMENT OF OUR
RESOURCES.
>> I APPRECIATE YOU SPREADING
THE WORD.
WE GET A GOOD RESPONSE.
I SOMETIMES WONDER WHETHER
EVERYBODY'S AWARE OF IT.
>> LAST ONE, 5145, THIS IS ALSO
THE ADMINISTRATIVE SUPPLEMENT
FOR CONTINUITY OF THE LIFE
EVENTS, THIS ONE IN PARTICULAR
IS FOR FIRST-TIME RECIPIENTS OF
NIH RESEARCH PROJECT GRANT
AWARDS.
AND SO I'LL BRIEFLY TALK ABOUT
THIS BECAUSE YOU HEARD MOST OF
THE RATIONALE FROM THE OTHER
ONE.
SO OBJECTIVE ALSO SECONDARY
SIGN-ON TO PROVIDE ADDITIONAL
RESOURCES TO NHLBI FIRST-TIME
RPG AWARDEES, AGAIN THESE ARE
THOSE FACING CRITICAL LIFE
EVENTS THAT CAN TAKE THEM AWAY
FROM RESEARCH FOR EXTENDED
PERIOD OF TIME.
THIS AIDS IN RETENTION OF
TALENTED YOUNG INVESTIGATORS
WITHIN OUR MISSION AND CRITICAL
COMPONENT IN THE DEVELOPMENT OF
FUTURE RESEARCHERS.
AND THE OVERARCHING GOAL TO HELP
MAINTAIN PRODUCTIVITY OF THESE
CURRENT FIRST-TIME RECIPIENTS OF
RPGs, DEALING WITH CRITICAL
LIFE EVENTS SUCH AS CHILD BIRTH,
ADOPTION, CARE OF IMMEDIATE
FAMILY MEMBERS WHO ARE ILL OR
WHO THEMSELVES HAVE HEALTH
ISSUES, TO HELP NEWLY
INDEPENDENT INVESTIGATORS WE
MAIN COMPETITIVE FOR FIRST
RENEWAL OR SECOND RESEARCH
PROJECT GRANT AWARD BY PROVIDING
FLEXIBLE FUNDING THAT CAN BE
USED FOR PERSONNEL, RESEARCH,
EQUIPMENT, SUPPLIES, AND
EQUIPMENT AND SUPPLIES.
RETAINING INVESTIGATORS IN THIS
CRITICAL PERIOD WILL PROTECT THE
RESEARCH INVESTMENT ALREADY MADE
VIA THE PARENT NIH AWARD.
AND SO I THINK I'LL END BY
SAYING THIS SUPPLEMENT PROGRAM
REPRESENTS STRATEGIC INVESTMENT
IN OUR WORKFORCE BY SUSTAINING
RESEARCH AND CAREER PRODUCTIVITY
DURING A CRITICAL LIFE EVENT.
THIS IS OPEN FOR DISCUSSION
AND/OR VOTING.
>> ARE WE READY TO GO?
>> THANK YOU.
100%.
>> CONCEPTS FOR DIVISION OF LUNG
DISEASES WE HAVE THREE, THE
FIRST ONE IS IDS 5124, SECONDARY
PARTICIPATION FOR HUMAN ORGANS
AND TISSUES.
COMPETITION RENEWALS U 42.
HUMAN TISSUE AND ORGAN RESEARCH
RESOURCE WILL SERVE AS
BIOREPOSITORY FOR RECEIPT,
STORAGE, DISTRIBUTION ACROSS
CLINICAL SITES.
DATA AND BIOSPECIMENS WILL BE
SHARED BY A PUBLIC ACCESS
PLATFORM THROUGH NATIONAL
DISEASE RESEARCH INTERCHANGE AND
RESOURCES DURING AND AFTER THE
END OF THE STUDY.
HTOR WILL FOCUS ON SICKLE CELL
DISEASE, HEMOPHILIA,
SARCOIDOSIS, HEART DISEASE,
INCLUDING HEART FAILURE, IN
CONSULTATION WITH BLOOD
DIVISION, TISSUES THAT WILL BE
FOCUSING ON SICKLE CELL DISEASE
INCLUDE FROM THE LUNGS, LIVER,
KIDNEYS, HEART, EYES, BONES,
JOINTS, BRAIN, SPLEEN,
HEMOPHILIA TO STUDY LIVER
ISSUES, INCLUDES HEART FAILURE
TISSUE SAMPLES, WILL COMPLEMENT
BIODATACATALYST, BioLINCC
WHILE HIGHLIGHTING A GAP, LIVING
TISSUES, WITH FOCUS ON RARE
DISEASES.
FIVE-YEAR BUDGET IS
1.250 MILLION, AIMS TO FUND A
U42 AWARD AT $250,000 PER YEAR,
HTOR IS CO-FUNDED AT $100,000
TOTAL COST PER YEAR AND RECEIVED
87 HEART TISSUES, 16 BRAIN
TISSUES, 43 BLOOD SAMPLES, OTHER
ORGAN TISSUES IN TWO YEARS, SO
REQUEST FOR CONTINUED FUNDING.
ANY QUESTIONS?
I GUESS WE MAY PROCEED FOR
DECISION LENS.
ALL RIGHT.
GREAT.
NEXT CONCEPT IS IDS 5146 RENEWAL
FOR LIMITED COMPETITION SMALL
GRANT PROGRAM FOR NHLBI, AND THE
PURPOSE OF THIS NOFO TO SOLICIT
K01s, SOME K25s FOR SMALL
GRANT SUPPORT TO EXPAND CURRENT
RESEARCH OBJECTIVES OR BRANCH
OUT RESULTING FROM THE RESEARCH
CONDUCTED UNDER K AWARDS.
THE OVERALL OBJECTIVES IS
PROVIDE A STEP-STONE FOR
AWARDEES WITH HIGH POTENTIAL BUT
FACE CHALLENGES AND NEED SUPPORT
TO HELP GENERATE CRITICAL DATA
AND/OR PUBLICATIONS TO
FACILITATE K TO R 2 TRANSITION,
MAJORITY ARE
PHYSICIAN-SCIENTISTS.
THIS PROGRAM HAS BEEN AROUND FOR
10 YEARS AND CURRENT NOFO WILL
EXPIRE ON JANUARY 8, 2026.
BETWEEN FISCAL YEAR 16 AND 24,
TOTAL OF 160 AWARDS MADE WITH
SUCCESS RATE OF 47%, 20 NEW
AWARDS PER YEAR, AWARDEES ARE
MORE LIKELY TO APPLY FOR AND
OBTAIN SUBSEQUENT R01 OR
EQUIVALENT INDEPENDENT GRANTS
AND LESS LIKELY TO DROP OUT FROM
RESEARCH.
WE BELIEVE THIS PROGRAM IS
ACHIEVING STATED GOAL PROMOTING
RESEARCH INDEPENDENCE FOR NHLBI
AWARDEES.
OBJECTIVE IS TO CONTINUE THE
PROGRAM TO K TO R TRANSITION
WITH MINOR REVISIONS.
FOR EXAMPLE IN RESPONSE TO
INFLATION, DIRECT COST FROM
$75,000 TO $85,000 A YEAR,
THERE'S BEEN A DECREASE IN R03
SUCCESS RATE, THERE'S A NEED FOR
INCREASING APPLICATIONS FROM
SOME OF THE OTHER DIVISIONS.
AS A RESULT SIGNIFICANT INCREASE
IN FUTURE APPLICATIONS IS
ANTICIPATED.
TO PREVENT FURTHER REDUCTION IN
SUCCESS RATE AND MEET K AWARDEE
COMMUNITY NEED WE PROPOSE TO
INCREASE TOTAL NUMBERS OF NEW
AWARDS FROM 20 TO 29 PER YEAR,
ADDING THREE MORE FOR EACH
COUNCIL ROUND.
CURRENT NOFO ALLOWS K AWARDEES
TO APPLY FROM SECOND YEAR OF K
AWARD PROJECT PERIOD BECAUSE
IT'S TOO EARLY TO EVALUATE IF AN
R03 IS NEEDED TO SUPPORT K TO R,
THIS HAS BEEN ONGOING FOR ONE
YEAR, WE PROPOSE TO DELAY THE
ELIGIBILITY FROM SECOND TO THIRD
YEAR OF THE PROJECT PERIOD, TO
GIVE ENOUGH TIME TO PREPARE FOR
R01 OR EQUIVALENT GRANT
APPLICATIONS, IN THE FOURTH TO
FIFTH YEAR USUALLY OF THE K
AWARD PERIOD.
AGAIN, WHAT WE'RE PROPOSING OR
REQUESTING IS RENEWAL FOR THIS
R03 LIMITED COMPETITION PROGRAM.
ANY QUESTIONS?
WE MAY PROCEED TO DECISION LENS
THEN.
>> THANK YOU.
THIRD AND LAST IS 5142,
SECONDARY PARTICIPATION IN HIV
AND AGING BASIC SCIENCE
INITIATIVE, R21 CLINICAL TRIAL
NOT ALLOWED.
AND THIS IS A NEW SECONDARY
SIGN-ON.
50 AND OLDER, THIS NUMBER IS
EXPECTED TO BE GREATER THAN 50%
BY 2030 ACCORDING TO CDC DATA.
THE LAST PATIENTS LIVING WITH
HIV IS SIMILAR TO THOSE WITHOUT
HIV, HEALTH SPAN HAS NOT
SIGNIFICANTLY CHANGED, AGING
WITH HIV PRESENTS PERSISTENT
CHALLENGES FOR MANY OLDER ADULTS
AS WELL AS PEOPLE WHO ARE
LIFETIME AND LONG-TERM SURVIVORS
AND MANAGING BOTH HIV AND HEALTH
CONCERNS.
THIS IS VERY COMPLEX.
THIS INITIATIVE USES R21
MECHANISM TO CULTIVATE A GROUP
OF INTERDISCIPLINARY
INVESTIGATORS ALREADY
ESTABLISHED IN EITHER HIV OR
AGING RESEARCH TO ADDRESS
MECHANISMS FOR THE INCREASED
INCIDENCE OF CO-MORBIDITIES IN
PEOPLE LIVING WITH HIV.
THE PROGRAM IS UNIQUE IN THAT
APPLICATIONS WILL REQUIRE
IDENTIFICATION OF SUITABLE
EXPERTS IN AREAS WHERE THE
PRINCIPAL INVESTIGATOR HAS LESS
EXPERIENCE WITH HIV OR AGING.
AND THIS NEW COLLABORATORS WILL
DEVELOP AND EXECUTE
COLLABORATIVE AND COMPLEMENTARY
RESEARCH PLAN THAT COMPLEMENTS
AND COMPLETES THE DESIGN STUDY
AIMS.
PROPOSED STUDIES WILL IMPROVE
UNDERSTANDING OF AGING IN
CARDIOVASCULAR, PULMONARY
SYSTEMS, WITH EMPHASIS --
[ NO AUDIO ]
AND WITH EMPHASIS ON -- WHERE I
WAS?
HERE IT IS.
EMPHASIS ON HOW HIV INFECTIONS
INFECT ASSOCIATED COMORBIDITIES.
PROPOSED STUDIES ARE EXPECTED TO
IDENTIFY PATHWAYS TO IMPROVE
RESILIENCE OF HIV-RELATED HEART,
LUNG, BLOOD AND SLEEP DISEASES
BY APPLYING CURRENT AGE AND
SCIENCE PARADIGMS.
SIMILAR TO OTHER KNOW NOFOS,
USING DATASETS FOR HIV AND
AGING.
OFFICE OF AIDS RESEARCH FUNDS
WILL BE USED IN TWO WAYS, FIRST
TO CROSS-CULTIVATE I.C. I.C. SUT
ACROSS INSTITUTES THAT SIGN TO
THE INITIATIVE, UP TO $2 MILLION
PER YEAR IN DIRECT COST FOR 2027
TO 2031 FISCAL YEARS.
SECOND IF COMPETITIVE
APPLICATIONS ARE RECEIVED THAT
ARE RELATED BUT NOT SUPPORTED BY
OAR UP TO THREE ADDITIONAL
APPLICATIONS PER RECEIPT DATE,
SO ONE PER YEAR, WILL BE
SUPPORTED BY NHLBI HIV OAR
ALLOCATED FUNDS, COMBINED BUDGET
MAY NOT EXCEED $275,000, NO MORE
THAN 200,000 REQUESTED IN A
SINGLE YEAR, BEGINNING IN 2027,
RUNNING FOR FIVE YEARS, THIS
WILL BE SUPPORTED FOR THREE
YEARS, WITH RENEWAL FOR FINAL
TWO YEARS.
SO ANY QUESTIONS?
>> I WILL SAY NOT HAVING NHLBI
SUPPORT THIS INITIATIVE IN MY
VIEW IS A MAJOR GAP GIVEN THE
FACT THAT HEART AND LUNG
COMORBIDITIES ARE THE MAJOR
COMORBIDITIES IN PERSONS LIVING
WITH HIV AND THE TOP CAUSES OF
MORBIDITY AND MORTALITY IN THIS
POPULATION.
SO I THINK IT MAKES A TON OF
SENSE.
I CAN'T IMAGINE HAVING THIS
WITHOUT NHLBI, SO GLAD WE'RE
DOING IT NOW.
>> THANK YOU, LYNN.
>> MY OWN KNOWLEDGE GAP
QUESTION, WHY IS THIS LUNG
DISEASE AND NOT HEART DISEASE?
>> NO, IT'S COVERING ACROSS
SPECTRUM OF HEART LUNG BLOOD AND
SLEEP DISORDERS.
IT'S ABOUT ALL OF IT.
APPLICANTS FROM ALL THOSE FIELDS
CAN APPLY.
>> ANY OTHER QUESTIONS?
WE LED LUNG LEAD SOME OF THE
TIME.
AND WE DO REALLY GOOD.
>> I GUESS WE CAN PROCEED TO
DECISION LENS THEN.
>> ALL RIGHT.
NOW, WE'LL CONTINUE PRESENTING
CONCEPTS.
>> THE FIRST OF THREE
INITIATIVES, BLOOD DIVISION WILL
PRESENT, IDS 5073, RENEWAL OF
THE MAXIMIZING SCIENTIFIC VALUE
OF THE NHLBI BIOLOGIC,
BIOSPECIMEN, BIOREPOSITORY.
SCIENTIFIC OPPORTUNITIES FOR
EXPLORATORY RESEARCH R21
MECHANISM, TO RENEW THIS
TRANSNHLBI R21, LAST RENEWED IN
FISCAL YEAR 2023, BIOSPECIMENS
FROM 62 CLINICAL STUDIES
CURRENTLY STORED IN THE NHLBI
BIOREPOSITORY, OPEN TO THE
COMMUNITY FOR NHLBI BioLINCC
WEB PORTAL AVAILABLE SAMPLES ARE
DISTRIBUTED TO RESEARCHERS AT
THE COST OF SHIPPING SOLELY.
THIS RFA HAS THREE OBJECTIVES,
TO PROVIDE SHORT-TERM FUNDING
FOR RESEARCHERS TO YOU THE --
UTILIZES SPECIMENS, FOR
REGENERATION OF DATA FOR
RESEARCH WHICH WILL DEVELOP THE
SCIENTIFIC WORKFORCE AT ALL
LEVELS AND TO CONTINUE TO
MAXIMIZE SCIENTIFIC VALUE OF THE
UNIQUE BIOSPECIMEN COLLECTIONS
STOREDDED IN BIOSPECIMEN
REPOSITORY.
DURATION OF EACH AWARD IS TWO
YEARS, WITH AWARD BUDGET UP TO
$100,000 IN DIRECT COST PER YEAR
PER GRANT.
PAST EXPERIENCE DEMONSTRATED
UTILITY TO PROMOTE SCIENTIFIC
UTILITY OF THE ARCHIVES
COLLECTIONS FROM COMPLETED NHLBI
FUNDED CLINICAL TRIALS AND
OBSERVATIONAL STUDIES,
IMPORTANTLY TO BRING AWARENESS
OF THE BIOREPOSITORY TO THE
PUBLIC AND PROVIDES A RESOURCE
FOR EARLY STAGE INVESTIGATORS TO
OBTAIN PRELIMINARY DATA TO HELP
LAUNCH SCIENTIFIC CAREERS,
ROUGHLY 21% OF PRIOR AWARDEES
WERE EARLY STAGE INVESTIGATORS.
REVIEW SHOWS A GOOD DISTRIBUTION
OF RESEARCH AREAS REPRESENTATIVE
OF HEART, LUNG, BLOOD, SLEEP
RESEARCH AREAS, AWARDEES FUNDED
FROM THE LAST ITERATION
DEMONSTRATED CAREER DEVELOPMENT.
RECIPIENTS REMAINED IN THE
RESEARCH WORKFORCE.
THE RFA HAS SUCCESSFULLY BROUGHT
AWARENESS OF THE RESOURCE AS
REQUESTS INCREASED DURING AND
FOR THE PERIOD AFTER THAT ACTIVE
PERIOD OF THE RFA.
CONTINUED SUPPORT OF THIS WILL
BOLSTER UTILIZATION AND IDENTIFY
NEW DIRECTIONS FOR HEART, LUNG,
SLEEP, AND BLOOD AREAS.
ANY QUESTIONS ON THIS INITIATIVE
FROM MEMBERS?
THE SECOND INITIATIVE FROM THE
DIVISION IS 5112, RENEWAL OF
BioLINCC RESOURCE CONTRACTS,
ESTABLISHED IN 2008, FACILITATE
ACCESS AND PROMOTE USE OF TWO
RESOURCES, REPOSITORY WHICH I
JUST SPOKE OF AND DATA
REPOSITORY MANAGED BY
EPIDEMIOLOGY BRANCH DIVISION OF
DCBS.
BioLINCC FITS WITHIN THE NHLBI
MISSION IN SEVERAL AREAS,
FACILITATING ACCESS TO RESOURCES
WHICH IN TURN INCREASES RETURN
ON INVESTMENT FOR NHLBI FUNDED
CLINICAL RESEARCH AND CONTINUING
TO MEET INSTITUTE PRIORITIES TO
ADDRESS CHANGING DATA SHARING
LANDSCAPE BY VIRTUE OF OUR
ONGOING INTEGRATION EFFORTS WITH
NHLBI BIODATA CATALYST CLOUD
RESOURCE.
CURRENT CONTRACT RENEWAL REQUEST
IS FOR ADDITIONAL FIVE YEARS,
OVERARCHING OBJECTIVES TO
MAINTAIN AND STRENGTHEN EXISTING
BIOLOGIC SPECIMEN AND DATA
REPOSITORY INFORMATION
COORDINATING CENTER PLATFORM,
MAXIMIZING THE SCIENTIFIC VALUE
AND UTILIZATION OF THESE
RESOURCES BY GREATER RESEARCH
COMMUNITY.
DATA AND BIOSPECIMENS USED FOR
GENERATING PILOT DATA,
FULFILLING AIMS, PERFORMING
META-ANALYSES, STATISTICAL
METHODS RESEARCH, QUANTITATIVE
APPROACHES TO CLINICAL TRIALS,
PREDICTION EQUATIONS, COHORT
CONTROLS.
CURRENTLY BioLINCC HOUSES
CLINICAL DATA FROM 233 CLINICAL
STUDIES FROM 61 STUDY
COLLECTIONS ROUGHLY 4 MILLION
VIALS FROM NHLBI-FUNDED STUDIES,
PROVEN INVALUABLE IN ALLOWING
RESEARCHERS TO PROBE MECHANISM,
GREATER THAN 2,000 PUBLICATIONS
SINCE 2008, THREE-FOLD INCREASE
IN ACTIVE USERS SINCE LAST
RENEWAL IN 2018.
OF THESE USERS APPROXIMATELY 48%
ARE EARLY STAGE INVESTIGATORS.
DO ANY MEMBERS HAVE ANY
QUESTIONS OR WISH TO DISCUSS
MORE ON THIS INITIATIVE?
WE'RE READY FOR THE THIRD AND
FINAL INITIATIVE, IDS NUMBER
5212, THIS NEW RFA TARGETS
IMPACT OF CLONAL HEMATOPOIESIS
ON HEART, LUNG, BLOOD AND SLEEP
DISEASES IN PEOPLE WITH LIVE.
CHIP REFERS TO SOMATIC MUTATIONS
GREATER THAN OR EQUAL TO 2% IN
BLOOD AND MARROW IN ABSENCE OF
MYELOID NEOPLASMS.
A TRIAL AIMED TO PREVENT
VASCULAR EVENTS IDENTIFIED CHIP
AMONGST THOSE LIVING WITH HIV.
THIS RFA SEEKS TO INVESTIGATE
THE DEVELOPMENT AND PROGRESSION
OF CHIP IN INDIVIDUALS LIVING
WITH HIV, AIMING TO UNDERSTAND
HOW CHRONIC INFLAMMATION AND
HIV-RELATED FACTORS CONTRIBUTE
TO CHIP.
ITS IMPACT ON DISEASES AND
BROADER BIOLOGICAL IMPLICATIONS
OF CHRONIC VIRAL INFECTIONS ON
HEMATOPOIETIC STEM CELL BIOLOGY
AND CLONAL EVOLUTION.
KEY SCIENTIFIC QUESTIONS INCLUDE
EXAMINING AGING AND DEMOGRAPHIC
FACTORS, BIOLOGICAL MECHANISMS
DRIVING CHIP, AND EFFECTS OF HIV
INFECTION AND LONG TEAM
ANTIRETROVIRAL THERAPY.
AIMS TO COMPARE WITH
COMORBIDITIES TO CHIP IN NON-HIV
INDIVIDUALS WITH AGE-RELATED
HEART, LUNG, BLOOD, SLEEP
CONDITIONS TO IDENTIFY
DIFFERENCES AND PREFERENCE AND
PROGRESSION.
THE RFA WILL INVESTIGATE HOW
FACTORS UNIQUE TO PEOPLE LIVING
WITH HIV AND OVERALL
INFLAMMATORY STATE ASSOCIATED
WITH HIV CONTRIBUTE TO HIGHER
INCIDENCE OF CHIP.
LASTLY THE RFA SEEKS TO
DETERMINE WHETHER CHIP PRODUCES
CLONES THAT DRIVE INFLAMMATION
IN PEOPLE WITH HIV, TO CLARIFY
RELATIONSHIP BETWEEN CHIP AND
INFLAMMATION IN THIS CONTEXT.
IN ADDITION TO RESEARCHING CHIP
IN CONTEXT OF HIV THIS WILL
PROVIDE BROADER BIOLOGICAL
INSIGHTS INTO HOW CHRONIC VIRAL
INFECTIONS INFLUENCE
HEMATOPOIETIC STEM CELL BIOLOGY
AND CLONAL EVOLUTION.
MOREOVER THERE ARE OTHER
RELEVANT HARD, LUNG, BLOOD,
SLEEP DISORDERS INFLAMMATORY IN
NATURE AND ASSOCIATED WITH
CLONAL HEMATOPOIESIS.
CHIP IS ASSOCIATED WITH
CONDITIONS SUCH AS
CARDIOVASCULAR DISEASE,
EMBOLISM, PULMONARY DISEASE,
THIS IS NOW OPEN TO MEMBERS FOR
DISCUSSION ON THIS CONCEPT IN
HIV, IN ADDITION I'M
PARTICULARLY INTERESTED IN
DISCUSSION ON THIS AREA OF
RESEARCH CLONAL HEMATOPOIESIS
AND INFLAMMATION AND IMPACT ON
OTHER HEART, LUNG, BLOOD, SLEEP
DISORDERS GIVEN KNOWN
ASSOCIATION WITH CARDIOVASCULAR
DISEASE, THROMBOSIS, LUNG
DISEASE.
>> SO, I WAS REALLY HAPPY TO
READ ABOUT THIS BECAUSE FOR
ANYONE WHO HAS FOLLOWED SICKLE
CELL IN THE PAST FEW YEARS KNOWS
THIS ISSUE OF CLONAL
HEMATOPOIESIS HAS COME UP QUITE
A BIT, AND THE DISCUSSION OF
OTHER INFLAMMATORY CONDITIONS
WOULD INCLUDE THINGS LIKE PNH,
APLASTIC ANEMIA,
UNDERAPPRECIATED AND WOULD BE
INTERESTING TO BE ABLE TO
COMPARE THOSE.
>> AGREED.
YEAH, WONDERFUL.
GOOD FURTHER EXAMPLES OF
POTENTIAL RELEVANT DISEASES.
ANY OTHER DISCUSSION FROM OTHER
MEMBERS ON THIS INITIATIVE?
>> I'LL RIF OFF ALLISON'S
COMMENT.
SORT OF BROADENING OUT FROM HIV,
NOW TO SEE AS WAS MENTIONED,
IT'S IN THE REPRIEVE TRIAL IN
HIV, BUT AS MANY ARE AWARE, CHIP
IS PROBABLY INVOLVED IN
ATHEROSCLEROSIS AS WELL,
GENERALLY WITHOUT THE HIV, AND
PERHAPS IT'S THAT THAT SYNERGY
IN REPRIEVE BETWEEN BASIC RISKS
OF ATHERO, PLUS HIV, AND SO I
THINK ONE QUESTION THAT MAYBE
COUNCIL CAN HELP US WITH IS
WHETHER THIS SHOULD BE BROADENED
TO NON-SORT OF HIV CONTEXT SORT
OF ALONG THE WAY, YOU WERE
SAYING, WOULD THAT BE SOMETHING
OF VALUE?
AND THIS IS OF SOME BROAD
INSTITUTE PERSPECTIVE BECAUSE
RESEARCH COMES FROM ALLOCATION
FROM THE AIDS PROGRAM, OAR,
WHERE AS IF WE BROADENED WOULDN
THE OPTION OF BASE FUNDING, IN
DISORDERS NON-HIV.
WHAT IS THE SENSE OF THE COUNCIL
ABOUT THE OPPORTUNITIES?
>> I'LL KEEP GOING SINCE MY MIC
IS WORKING.
I LIKE THE IDEA OF BROADENING
IT.
I WAS ONE OF THE PEOPLE THAT GOT
BROUGHT IN TO DISCUSS THE CLONAL
HEMATOPOIESIS WITH SICKLE CELL
WHEN IT FIRST EMERGED, AFTER THE
CURATIVE THERAPIES.
AND WE DIDN'T HAVE A TON OF DATA
TO GO OFF OF.
BUT I THINK THAT THERE'S GOOD
RATIONALE TO LOOK AT THIS, AND
MULTIPLE INFLAMMATORY STATES,
THEN WE WOULD HAVE BETTER
COMPARISONS ACROSS CONDITIONS.
AND GET A BETTER IDEA HOW MUCH
INFLAMMATION DRIVES VERSUS SOME
OF THE OTHER ISSUES.
>> A QUESTION ABOUT THAT.
I LIKE THE IDEA OF BROADENING.
MY QUESTION IS WHEN YOU PUT IN A
GRANT, IT HAS HIV IN IT, IT
USUALLY AUTOMATICALLY GETS
SHUNTED TO A PARTICULAR STUDY
SECTION.
AND I'M WONDERING IF THERE'S A
WAY, IF YOU BROADEN IT TO ENSURE
THAT HIV -- THOSE HIV GRANTS ARE
FOCUSED ON PEOPLE LIVING WITH
HIV, GOES TO THE PARENT STUDY
SECTION REVIEWING THESE GRANTS.
>> YEAH, AGAIN, THAT'S SOMETHING
THE PROGRAM CAN THINK THROUGH,
BUT THAT'S ONE OF THE OTHER
THINGS WE MIGHT THINK OF IN A
NOFO OR TYPICALLY IN THE DAYS
WE'RE CURRENTLY IN, THAT WE
WOULD NEED TO HAVE THAT KIND OF
STRATEGY WORKED OUT, BECAUSE
THERE ARE A LOT OF OTHER
MECHANISMS TO DRIVE IT TO
INVESTIGATOR-INITIATED ARE ALSO
EVAPORATING, SO THIS IS WHY THIS
IS A GOOD DIALOGUE FOR PROGRAM
TO REALLY WEIGH THOSE DIFFERENT
CONSIDERATIONS BOTH SCIENTIFIC
OPPORTUNITIES OF BROADENING IT
AND REVIEW CONSIDERATIONS THAT
MAY COME FROM HOW WE STRUCTURE
THIS SO I APPRECIATE THAT.
>> THANK YOU FOR THE RICH
DISCUSSION.
THAT'S VERY HELPFUL.
I WILL HAND THIS OVER TO DR.
LAMAR.
OR GUS?
>> ALL RIGHT.
HERE WE GO.
THE LAST ONE, I'M PRESENTING A
CONCEPT FROM DIVISION OF
EXTRAMURAL RESEARCH ACTIVITIES,
DERA, 5129, SECONDARY SIGN-ON
SBIR/STTR READINESS PILOT,
TECHNICAL ASSISTANCE, LATE
DEVELOPMENT.
SB 1 CLINICAL TRIAL NOT ALLOWED.
SO THE COMMERCIALIZATION
READINESS PILOT PROGRAM CRP IS
TRANS-NIH PROGRAM MOST RECENTLY
AUTHORIZED BY 2022 SBIR AND STTR
EXTENSION ACT.
CRP FACILITATES TRANSITION OF
PREVIOUSLY FUNDED PHASE 2, 2B
PROJECTS BY PROVIDING SUPPORT
FOR LATHE LATER STAGE TECHNICAL
ASSISTANCE.
DUE TO UNIQUE MECHANISMS, AWARDS
UNDER THE CRP ARE NOT SUBJECT TO
THE SAME SUBCONTRACT RESTRICTION
AS 42 OR 44 AWARDS, ALLOWS
AWARDS TO COVER COST OF
ACTIVITIES THAT SHALL NOT
TYPICALLY SUPPORTED THROUGH
PHASE 2 OR PHASE 2B GRANTS OR
CONTRACTS BUT ARE NECESSARY
INCLUDING BUT NOT LIMITED TO
CHEMISTRY, MANUFACTURING,
CONTROL ACTIVITIES, VERIFICATION
AND VALIDATION STUDIES FOR
DEVICES, SOFTWARE, STUDIES,
CLINICAL TRIAL DESIGN AND
PLANNING, ANIMAL STUDIES TO
DEVELOP SURGICAL TECHNIQUES
RELEVANT TO NEW DEVICE AND
DEVELOPMENT AND VALIDATION OF
ASSAYS FOR CLINICAL TRIALS.
FURTHERMORE, THIS MECHANISM
ALLOWS 2 AND 2B GRANTEES TO
RECEIVE SUPPORT CONCURRENTLY.
BETWEEN 2016 AND FIST FISCAL
YEAR 2025, NHLBI HAS RECEIVED
105 APPLICATIONS FOR CRP LEADING
TO 22 FUNDED SB 1 PROJECTS,
SINCE THE LAST SIGN ON, MAY 22
COUNCIL MEETING, RECEIVED 35
APPLICATIONS, MADE 8 AWARDS TO
DATE.
NHLBI INNOVATION AND
COMMERCIALIZATION OFFICE
OBSERVED POSITIVE FINANCIAL AND
CLINICAL OUTCOMES ASSOCIATED
WITH CRP AWARDEES OVER MORE THAN
8 YEARS OF PARTICIPATION.
SOME EXAMPLES OF SUCCESSES ARE
AS FOLLOWS.
JANUARY 2024, IDE APPROVAL FOR
RCT TO DETERMINE EFFICACY OF THE
DEVICES IN ALLOWING CLINICIAN TO
ASSESS MATURATION, IN PATIENTS
UNDERGOING HEMODIALYSIS.
APPROVAL FOR THIS WAS RECEIVED
FOLLOWING POSITIVE RESULTS IN
INITIAL CLINICAL STUDY, ENDING
IN SEPTEMBER 2023.
CONSORTIUM AWARDED DARPA
CONTRACTS.
THIS PROGRAM ALLOWED THEM TO
CONTINUE DEVELOPMENT OF THEIR
RED BLOOD CELL PRODUCTS.
AND IN 2024, CLINICAL TRIALS,
EARLY CANDIDATE IN HEALTHY
VOLUNTEERS, RENEWED SECONDARY
PARTICIPATION IS CRUCIAL FOR
COMPLETING PRODUCT DEVELOPMENT
ACTIVITIES, ADVANCING NHLBI
STRATEGIC VISION THROUGH
DEVELOPING AND OPTIMIZING NOVEL
DIAGNOSTICS AND STRATEGIES TO
PREVENT, TREAT, CURE, HEART,
LUNG, BLOOD, SLEEP DISEASES.
WE PROPOSE COUNCIL APPROVE NHLBI
SECONDARY PARTICIPATION OR
REQUEST AND THIS WILL BE FOR
CONTINUED SECONDARY
PARTICIPATION AND ALLOWS $2
MILLION PER YEAR FISCAL YEAR 26
AND 2.2 MILLION FROM 2027 TO
2029 FROM NHLBI SBIR AND STTR
BUDGET.
DO ANY COUNCIL MEMBERS HAVE
QUESTIONS?
WE MAY PROCEED TO VOTING.
AFTERWARDS, DR. LAMAR, I'LL
RETURN IT TO YOU.
>> SO, WE'RE ALMOST DONE WITH
THE VOTING ON THIS.
WE REACHED THE END OF THE DAY.
I'LL TURN IT OVER TO DR. GIBBONS
FOR FINAL COMMENTS OR IF COUNCIL
HAS FINAL COMMENTS OR QUESTIONS.
>> LIKE THE MICROPHONES, I THINK
WE'RE ALL ABOUT WORN OUT AFTER A
LONG DAY OF DOING THIS.
REALLY APPRECIATE YOU GUYS
HANGING IN THERE AND PROVIDING
SUCH VALUABLE INPUT.
AND I KNOW YOU'RE READY TO
TRAVEL.
SO SAFE TRAVELS.
AGAIN, MUCH GRATITUDE.
I GUESS WE'RE ADJOURNED.
HERE IS MY GAVEL.
[END OF PROGRAM]