WELCOME TO THE 148th MEETING OF THE NATIONAL ADVISORY COUNCIL ON AGING. MY NAME IS KEN SANTORA, THE DIRECTOR OF THE DIVISION OF EXTRAMURAL ACTIVITIES HERE AT NIA AND THE EXECUTIVE COUNCIL. FIRST OFF, BEFORE I TURN THE MEETING OVER TO OUR DIRECTOR, DR. RICHARD HODES, I'M GOING TO DO A ROLL CALL OF OUR COUNCIL MEMBERS. WHEN I CALL YOUR NAME, IF YOU COULD PLEASE INTRODUCE YOURSELF, GIVE YOUR NAME AND AFFILIATIONS AND WE'LL GO FROM THERE. SO STARTING OFF, DR. BAKER. >>OKAY, DARIN BAKER, MAYO CLINICMENT ASSOCIATE PROFESSOR OF BIOCHEMISTRY AND MOLECULAR BEAMINGY AND PEDIATRIC MEDICINE, VERY FUNNY AS BEING PART OF THE NATIONAL ADVISORY COUNCIL ON AGING. I HAVE BEEN HERE ROUGHLY A LITTLE OVER A YEAR AT THIS POINT. >>THANK YOU, DARIN. SHELLY? >>SHELLY, PROFESSOR OF MEDICINE AT HARVARD MEDICAL SCHOOL. I'M AN ENDOCRINOLOGIST BY TRAINING BUT MUCH OF MY RECENT WORK HAS BEEN IN AGING BIOLOGY. >>THANK YOU. DR. CASE. >>I'M ANN CASE, AN ECONOMIST AT PRINCETON UNIVERSITY AND MOST OF MY RECENT WORK HAS BEEN ON MID LIFE MORBIDITY AND MORTALITY AND ITS MOVEMENT INTO OLD AGE. >>THANK YOU. DR. CRUISE. >>GOOD MORNING. I AM THE PRESIDENT AND CEO FOR THE NATIONAL HISPANIC COUNCIL ON AGING. I HAVE A DOCTORATE IN PUBLIC HEALTH AND MOST OF MY WORK IS FOCUSED ON HISPANIC ISSUES AND OLDER ADULTS. >>THANK YOU. DR. DRISCOL. >>HI, GOOD MORNING. MONICA DRISCOL. DISTINGUISHED PROFESSOR IN THE DEPARTMENT OF MOLECULAR BIOLOGY AND BIOCHEMISTRY AT RUTGERS. MY RESEARCH INTERESTS ARE IN THE VERY FUNDAMENTAL BIOLOGY OF AGING AND NEURODEGENERATION. >>THANK YOU. DR. GREENSPAN. >>HI, I'M SUSAN GREENSPAN, PROFESSOR OF MEDICINE AT UNIVERSITY OF PITTSBURGH. I'M TRAINED ENDOCRINOLOGIST AND GERIATRICIAN AND MY FOCUS HAS BEEN ON FRAILTY, FALLS AND FRACTURES. >>THANK YOU. DR. WONG? I'M NOT SURE IF YOU CAN INTRODUCE -- >>I HOPE -- I GET BETTER TODAY. SENIOR INVESTIGATOR AT -- AND PROFESSOR AT UROLOGY UCSF. >>THANK YOU. >>I'M CYNTHIA HUMBLE, RETIRED PRESBYTERIAN PASTOR. ALZHEIMER'S AND DEMENTIA ADVOCATE AND I HAVE BEEN A RESEARCH PARTICIPANT FOR MORE THAN 13 YEARS. THANK YOU DR. WONGO? FRANK? ARE YOU ON? WE'LL COME BACK TO HIM. DR. MANLY. >>JENNIFER MANLY. I AM A NEUROPSYCHOLOGIST AND A PROFESSOR IN THE DEPARTMENT OF NEUROLOGY AT COLUMBIA UNIVERSITY. AND MY RESEARCH IS ON LIFE COURSE STRUCTURAL AND SOCIAL INFLUENCES ON COGNITIVE AGING AND ALZHEIMER'S DISEASE. >>THANK YOU. DR. PETERSEN? >>GOOD MORNING. I'M CHARLOTTE PETERSON, PROFESSOR AT THE UNIVERSITY OF KENTUCKY AND MY RESEARCH -- I'M A MOLECULAR AND CELLULAR BIOLOGIST WITH FOCUS ON MUSCLE WASTING, SARK PENIA AND LOSS OF FUNCTIONAL INDEPENDENCE WITH AGE. >>THANK YOU. DR. RUBIN. >>I'M DAVE RUBIN, GERIATRICIAN BASED AT UCLA AND MOST OF MY WORK HAS BEEN ON HEALTH SERVICES RESEARCH, INCLUDING IMPLEMENTATION AND SOME LARGE CLINICAL TRIALS, INCLUDING WITH SHALLY. AND THEN MY CURRENT WORK FOCUSES ALMOST EXCLUSIVELY ON DEMENTIA AND IMPROVING THE CARE OF PEOPLE WHO HAVE DEMENTIA. I HAVE A VERY CLINICAL TRIAL WITH PCORI AT NIA WE ARE IN THE MIDST OF. >>THANK YOU. DR. SNYDER? >>GOOD MORNING, EVERYBODY. I'M JULIE SNYDER. -- DEPARTMENT OF PATHOLOGY. IN OR ABOUTO PATHOLOGIST AND ENDOCRINOLOGIST -- DISEASE CENTER WHERE STUDY MOSTLY THE NEUROPATHOLOGY BASIS OF DECLINE AND MOTOR DECLINE WITH AGING. ESPECIALLY INTERESTED IN TRANSLATIONAL EFFORTS AND BIOMARKERS AND MECHANISMS, ESPECIALLY [ INAUDIBLE ] >>DR. BEN? >>I'M LINDA VANELEDDIC, DIRECTOR OF THE BROWN CENTER ON AGING AND THE UNIVERSITY OF KENTUCKY ALZHEIMER'S DISEASE CENTER AND PROFESSOR OF NEUROSCIENCE. MY OWN RESEARCH IS ON TRANSLATIONAL NEUROSCIENCE IN TERMS OF DYSREGULATED BRAIN INFLAMMATION AND USING THAT AS THERAPEUTIC TARGETS SO I BROUGHT COMPOUNDS INTO HUMAN TRIALS. >>THANK YOU. AND DR. WE'RE. >>I'M DAVID WE'RE. A PROFESSOR IN THE INSTITUTE FOR SOCIAL RESEARCH AT THE UNIVERSITY OF MICHIGAN AND DIRECTOR OF THE HEALTH AND RETIREMENT STUDY. I'M INTERESTED IN JUST ABOUT ANYTHING WE CAN LEARN ABOUT THE LIVES OF OLDER PEOPLE. >>THANK YOU. AND DR. WET FIELD. >>MORNING, EVERYONE. I'M KEITH WHITFIELD. I'M PROFESSOR OF PSYCHOLOGY, PROFESSOR OF BRAIN HEALTH AS WELL AS THE PRESIDENT OF THE UNIVERSITY OF LAS VEGAS. MY RESEARCH IS ON COGNITIVE AGING IN AFRICAN-AMERICANS AS WELL AS LONGEVITY IN AFRICAN-AMERICANS. THANK YOU. >>THANK YOU. AND BACK TO DR. LONGO. >>MORNING, EVERYONE. I'M FRANK LONG OH, NEUROLOGIST. I CHAIR THE DEPARTMENT OF NEUROLOGY AT STAMFORD. MY RESEARCH IS FOCUSED ON MECHANISM ELUCIDATION RELEVANT TO SYNAPSE DEGENERATION, ESPECIALLY IN CREATING SMALL MOLECULE APPROACHES TO TARGET THOSE MECHANISMS AND WE HAVE BROUGHT COMPOUNDS FROM IN VITRO THROUGH MICE AND INTO HUMAN TRIALS. >>THANK YOU. WE ALSO HAVE OUR EX-OFFICIO MEMBERS, DR. VAHALLA. >>HI, GOOD MORNING. I'M HOLLY FROM THE NATIONAL INSTITUTE ON DISABILITY AND INDEPENDENT LIVING AND REHABILITATION RESEARCH. THANK YOU. >>THANK YOU. DR. . >>ANN ORD WAY, PROGRAM SPECIALIST AT THE NATIONAL INSTITUTE ON DISABILITY INDEPENDENT LIVING AND REHABILITATION RESEARCH AND I LEAD THE RESEARCH PORTFOLIO AT THE INTERSECTION OF DISABILITY AND AGING. >>THANK YOU. AND FINALLY WE HAVE A FEW AD-HOC MEMBERS. THESE MEMBERS WILL BE OUR -- SOON ON-BOARDED AND BE OUR COUNCIL MEMBERS COME MAY. SO WE'LL INTRODUCE THEM. DR. SPANNA? >>GOOD MORNING. SANJAY, UNIVERSITY WISCONSIN-MADISON. I'M -- PROFESSOR OF MEDICINE IN. [ BACKGROUND NOISE ] AT THE MEDICAL SCHOOL. ALSO DIRECTSOR OF THE WIG CONSIN -- AND HEAD AT THE MEDICAL SCHOOL. MY RESEARCH INTERESTS ARE IN PRE-CLINICAL BIOMARKERS OF ALZHEIMER'S DISEASE AND I HAVE DONE A NUMBER OF CLINICAL TRIALS INVOLVING HORMONES, COGNITION AND DEMENTIA. >>THANK YOU. DR.-- >>GOOD MORNING. I AM -- LA BETTERO. I'M NOT A DOCTOR YET, STILL WORKING ON MY DISSERTATION. I AM PROFOUNDLY GRATEFUL TO BE HERE. AND STRENGTH END BY ALL YOUR EXPERTISE AND INTERESTS. I AM A LONG -- LIFELONG, I WOULD SAY, CAREGIVER AND CARE PARTNER FOR MY FAMILY AND MY MOTHER. CURRENTLY WHO IS IN A NURSING HOME. AND I AM A PATIENT ADVOCATE, SUPPORTER AND MY INTERESTS IN RESEARCH ARE CONTRIBUTING ALL I CAN TO MOVE FORWARD RESEARCH THAT WILL GIVE US A BETTER TREATMENT AND HOPEFULLY SOME DAY A CURE. THANK YOU. FOR ALZHEIMER'S DISEASE. THANK YOU. >>THANK YOU. DR. ANONI? >>YES, HI. I'M SHARON AND I AM REALLY HONORED TO BE HERE. I'M A PROFESSOR OF MEDICINE AT HARVARD MEDICAL SCHOOL. I'M TRAINED AS A GERIATRICIAN AND CLINICAL EPIDEMIOLOGIST. I'M BASED AT THE MARCUS INSTITUTE FOR AGING RESEARCH. AND MY RESEARCH FOCUSES ON REVERSIBLE CONTRIBUTORS TO COGNITIVE IMPAIRMENT, MOST SPECIFICALLY THE INTERFACE OF DELIRIUM AND DEMENTIA. AND I DO STUDIES RANGING FROM CLINICAL TO TRANSLATIONAL AND IMPLEMENTATION RESEARCH. THANK YOU. >>THANK YOU. DR. COLIN? >>HI, GOOD MORNING. I'M DR. KAHN. AND THIS IS A EXTREMELY IMPRESSIVE PANEL. FOR THE LAST TWO DAYS I'M THINKING WHAT AM I DOING HERE? BUT A LITTLE BIT ABOUT ME. I AM A TRAINED EPIDEMIOLOGIST. WENT TO MED SCHOOL AND HAVE BEEN WORKING WITH CHEROKEES FOR 29 YEARS. SO THE REASON FOR ME BEING HERE IS TO REPRESENT THE ISSUES FACING THE CHEROKEES AND AI IN COMMUNITIES. AND EVERY NOW AND THEN YOU WILL SEE MY COMMENTS THERE ARE UNIQUE ABOUT THEIR POINT OF VIEW AND PERSPECTIVE AND NEEDS IN TERMS OF RESEARCH. ALZHEIMER'S IS AN ISSUE AND AGING AND LIMITED RESOURCES AND I HAVE BEEN WORKING THERE FOR QUITE A LONG TIME. LIVED THERE IN RURAL OKLAHOMA. SO I BRING THAT PERSPECTIVE AND THE UNIQUE THING ABOUT ME YOU'LL FIND OUT PRETTY SOON, I'M NOT SHY ABOUT SHARING MY THOUGHTS. >>VERY GOOD, THANK YOU. AND FINALLY NANCY LYNDEN BERG. >>HI, I'M NANCY. CEO OF THE AMERICAN GERIATRIC SOCIETY AND A RECOVERING CAREGIVER. AND A NOD TO MARISA. I THINK A LOT OF US SHARE THAT DUTY AND SOMETIMES BURDEN. I AM A LAYPERSON SO I FEEL LIKE THIS -- YESTERDAY WAS SORT OF FUNNELING INTO THE INNER WORKINGS OF THE NIA BUT ALSO I WOULD SAY THAT I'M A FIERCE CHAMPION FOR ADVANCING THE WORK THAT IS DONE WITH FUNDING FOR NIA INTO CLINICAL PRACTICE AND REALLY LOOK FORWARD TO LEARNING AND COLLABORATING WITH ALL OF YOU. >>GREAT. THANK YOU VERY MUCH. AND WELCOME TO OUR NEW MEMBERS. ALL RIGHT, LET'S SEE. NEXT UP, I'LL INTRODUCE DR. RICHARD HODES, OUR DIRECTOR OF THE NATIONAL INSTITUTE AGING. SO I'LL TURN IT OVER TO RICHARD. >>DR. HODES: THANK YOU. I WILL ADD MY APPRECIATION TO OUR CURRENT AND IN-COMING COUNCIL MEMBERS. IT IS AN INVESTED GROUP. AND IMPRESSIVE EVERY TIME I SEE THE GALLERY COME BY. I'D LIKE TO OPEN THIS SESSION HERE NOW BY A BRIEF STATUS REPORT OF SOME OF THE EVENTS THAT HAPPENED SINCE OUR LAST MEETING. NEXT SLIDE, PLEASE. FIRST, WE WANT TO INTRODUCE TO YOU, AND SHE CAN PLEASE GO ON CAMERA AMY. I THINK BY NOW A LOT OF YOU GOT TO KNOW HER. AMY KELLY IS OUR DEPUTY DIRECTOR SINCE SEPTEMBER AND HAS BEEN FANTASTIC IN THESE FIRST MONTHS. SHE CAME TO US FROM MOUNT SINAI WITH HER BACKGROUND IN HEALTH POLICY, IN PARTICULAR GERIATRICS AND PALLIATIVE CARE. AMY, SAY HELLO. >>AMY: GOOD MORNING, EVERYBODY. IT'S WONDERFUL TO SEE YOU ALL AND JUST FANTASTIC OPPORTUNITY TO GET TO KNOW OUR NEW MEMBERS. SOME ARE FAMILIAR WITH ME ALREADY AND JUST THANK YOU ALL FOR SUPPORTING NIA. >>DR. HODES: THANK YOU, AMY. NEXT SLIDE. SO THIS IS THE FIRST COUNCIL MEETING WE'VE HAD SINCE WE HAD THE PASSAGE OF OUR LAST APPROPRIATION THE FY2023 BUDGET. IT SAW IN KEYS IN TOTAL NIH, 47.7 BILLION DOLLARS FOR NIA WITH INCREASE TO 4.4 BILLION DOLLARS. THERE WERE SEVERAL TARGET INCREASES IN THE NIH BUDGET, ONE OF THE LARGEST WAS AGAIN FOR AD AND ADRD RESEARCH, TOTAL OF 226 MILLION DOLLARS, 151 MILLION DOLLARS TO NIA, 75 MILLION DOLLARS OF WHICH TO OUR GREAT PARTNER IN THESE EFFORTS, NINDS; PLEASE. WE WERE ALSO ABLE TO ANNOUNCE THAT THE POINT IN THE YEAR, OUR PAY LINE. SO FAR BESIDES PROJECTIONS NOW THAT WE KNOW OUR FUNDING AND BUDGET. AND BREAKING IT DOWN AS YOU SEE HERE FIRST FOR THE CSR REVIEWED APPLICATIONS WHICH RECEIVED PERCENTILES, THERE IS A GENERAL PAY LINE WHICH MEANS THAT UNTARGETED RESEARCH NOT SPECIFIED FOR ADADRD, FOR THE MOST COMMON APPLICATIONS FALLS UNDER $500,000. WE HAVE THAT THE POINT A PAY LINE OF UPON 15 PERCENTILE. FOR NEW INVESTIGATORS AND EARLY-STAGE INVESTIGATORS, RESPECTIVELY, THE PAY LINES WILL 18-20 PERCENTILE WHICH REFLECT OUR CONTINUING PRIORITY TO NEW PEOPLE ENTERING THE FIELD. THE GENERAL PAY LINE FOR THE MORE EXPENSIVE APPLICATIONS GREATER THAN $500,000 SET A HIGHER BAR IN EACH CATEGORY. IF WE LOOK AT AD/ADRD PAY LINES, WE HAVE AGAIN FOR APPLICATIONS EITHER BEFORE OR UNDER OR OVER 500K THEY ARE REALLY THE SAME, THE 25th PER CERTAINLY TILE, 28 AND 30 PERCENTILE IS FOR NEW INVESTIGATORS AND ESIs. THAT THE POINT OF THE YEAR, IT'S POSSIBLE AS WE LEARN MORE, WE WILL BE ABLE TO MODIFY, HOPEFULLY IN THE DIRECTION OF INCREASING FURTHER OUR PAY LINES. BUT THESE ARE OUR ALLOCATIONS AT THIS POINT. AND THE NEXT SLIDE DEALS WITH THOSE PAY LINES WHICH ARE FOR NON CSR. THEY ARE NIA REVIEWED APPLICATION AND RECEIVED IMPACT SCORE RATHER THAN PRIORITY SCORE AND YOU CAN SEE HERE AGAIN THE GENERAL AND ADA PAY LINES FOR PROGRAM PROJECTS OTHER THAN NIA RESEARCH. FUNDED RESEARCH, CAREER DEVELOPMENT OF A HIGHER AND FELLOWSHIP AWARDS AT HIGHER STILL PAY LINE IN BOTH CATEGORIES. NEXT, PLEASE. THIS IS JUST TO REMIND US ALL OF THE INCREASE WE HAVE BEEN SEEING IN THE NIA APPROPRIATION FROM 2014 TO THE PRESENT. AND 2015 WE WERE AT ONE BILLION DOLLAR LEVELED AND NOW 4.4 BILLION DOLLARS. GOOD BIT OF THIS DUE TO THE TARGET INCREASE IN ADADRD RESEARCH BUT NOT ENTIRELY -- SUBSTANTIAL INCREASE ACROSS OUR GENERAL COMPONENT OF OUR APPROPRIATION AS WELL. NEXT, PLEASE. SOME UPDATES. WE WANTED TO SUMMARIZE FOR YOU THE ACTIVITY IN NIA FUNDED A. AND ADRD CLINICAL TRIALS. THIS IS UPDATE OF THE ACTIVE SUPPORTIVE TRIALS RIGHT NOW. A TOTAL OF 459, A STRIKING NUMBER. THEY ARE DIVIDED AS YOU WILL SEE HERE, FOR PHARMACOLOGIC AND NON PHARMACOLOGIC TREATMENTS AIMED AT PREVENTING TREATING, SLOWING PROGRESSION OF ALZHEIMER'S. 66 PHARMACOLOGIC, ONE HUNG 52 NON PHARMACOLOGIC AND 210 THAT ARE TARGETED AT DEMENTIA CARE AND CARE GIVING AS WELL AS STUDIES AIMED AT NEUROPSYCHIATRIC SYMPTOMS AND DIAGNOSTIC AND ASSESSMENT AND IMAGING TOOLS. NEXT SLIDE. JUST TO GIVE YOU REVEALING COMPONENTS OF WHERE THESE FALL. FOR 66 PHARMACOLOGIC TRIALS, YOU LOOK FIRST AT THE 7 TRIALS THAT ARE PHASE II OR PHASE III. THESE ARE ADVANCED TRIALS POTENTIALLY DEFINITIVE IN IDENTIFYING EFFECTIVE INTERVENTIONS. OF THE 7, 4 ARE AMYLOID TARGETED. 3 ARE NOT AS YOU CAN SEE. THESE REFLECT THE PREDOMINANCE OF AMYLOID AS A TARGET STUDY OVER PAST YEARS AND THE NUMBER OF YEARS IT TAKES TO PROGRESS FROM STAGE TO STAGE IN THESE STUDIES. IF YOU LOOK AT THE EARLIER PHASE TRIALS, PHASE I AND PHASE II, SOME 59 OF THEM, YOU WILL SEE 340s OF THEM ARE TO TARGETS OTHER THAN AMYLOID. AMYLOID REMAINS IMPORTANT BUT THIS REFLECTS THE DIVERSITY OF WHAT WE HAVE LEARNED THAT THE UNDERLYING PATHOPHYSIOLOGY OF ALZHEIMER'S AND OUR ABILITY TO TARGET THOSE COMPONENTS, THESE WILL BE IN THE NEXT GENERATIONS AS THEY MOVE TO PHASE II AND PHASE III STUDIES SHOULD THEY PROVE PROMISING AND PHASE I AND PHASE II. NON PHARMACOLOGIC TRIALS, 152 BROKEN DOWN HERE BY CATEGORIES INCLUDING EXERCISE AND IN OR ABOUTO STIMULATION, COGNITIVE TRAINING, SLEEP-RELATED TRIALS AND SO ON. SO A DIVERSITY WHICH EFFECTS A CONVICTION OF THE FACT THAT THE ADADRD PROCESS ITSELF IS A COMPLEX ONE. AND THAT BEING ABLE TO ADDRESS MULTIPLE TARGETS ARE GOING TO GIVE US THE BEST OPPORTUNITY TO FIND THE BEST INDIVIDUAL OR COMBINATION THERAPIES FOR GIVEN INDIVIDUALS AS WE LEARN MORE AND MORE ABOUT THE HETEROGENEITY IN THE DISEASE PROCESSES. NEXT, PLEASE. AMONG THE DEMENTIA CARE AND CARE GIVING TRIALS. AGAIN, YOU'LL SEE THE SUBCATEGORIES SHOWN HERE RANGING FROM FORMAL CARE TO IMPROVING CAREGIVER HEALTH AND WELL-BEING. AND AGAIN THE DIVERSITY MUCH EXPANDED. EVERY BIT AS IMPORTANT AND RIGOROUS AS WE TRY TO DEAL WITH THE BEST APPROACHES AND INDIVIDUALS CURRENT LEAD LIVING WITH DEMENTIA, EVEN AS WE TRY TO REDUCE THE NUMBER THROUGH PREVENTION IN OUR STUDIES TO UNDERSTAND BETTER THE UNDERLYING PATHOGENESIS. AND IMPORTANT AREAS OF DIAGNOSTIC TOOL DEVELOPMENT AND ASSESSMENT AND TREATMENT FOR NEUROPSYCHIATRIC SYMPTOMS. NEXT, PLEASE. WOULD I WANT TO POINT YOU TO THE ADADRD PROGRESS REPORT MOST RECENTLY RELEASED IN NOVEMBER. THIS IS A SUMMARY EACH YEAR OF SCIENCE ADVANCES ACROSS MULTIPLE RESEARCH TOPICS. LINKS SHOWN HERE AND WE INVITE YOU TO LOOK AT WHAT WE THINK ARE VERY IMPRESSIVE ASPECTS OF CARE SERVICES, UNDERLYING PATHOPHYSIOLOGY, ADVANCES IN ALL THESE AREAS. NEXT, PLEASE. AN UPDATE ON ONE OF THE NEWER ACTIVITIES HERE AT NIA AND NIH. THE NIH CENTER FOR ALZHEIMER'S RELATED DEMENTIAS ARE HARD. THIS IS ESTABLISHED THE COLLABORATION BETWEEN. THIS IA AND NINDS AS PART OF OUR INTRAMURAL PROGRAM N SEPTEMBER WE HAD A REALLY WONDERFUL DEDICATION CEREMONY ON CAMPUS AS IT WAS NAMED THE ROY BLUNT CENTER FOR ALZHEIMER'S DISEASE RELATED DEMENTIAS RESEARCH. ROY BLUNT WHO HAS BEEN A LONGSTANDING CHAMPION FOR RESEARCH AT NIH VERY MUCH INCLUDING NIA AND RESEARCH. PRIMARY ASPECTS OF THIS CENTER ARE A STRONG COMMITMENT TO RESOURCE SHARING WITH NEW ONLINE PORTAL TO DEVELOP A INITIATIVES AS THEY COME FORWARD. INFRASTRUCTURE AND IDENTIFICATION OF RESEARCH TOOLS SUCH AS THE INTRODUCTION OF A PANEL OF INDUCED POTENTIAL STEM CELLS. LIBRARY BECOMES AVAILABLE TO THE RESEARCH COMMUNITY AND SOME UNIQUE PREMIER DEVELOPMENT EXPERIENCE AS WELL. AS WE ATTEMPT TO BRING IN NOT JUST A FACULTY BUT AN ONGOING PASSTHROUGH OF INDEPENDENT SCIENTISTS WHO MAY SPEND PARTS OF THEIR TIME AT CARD AND THEN ARE PROVIDED WITH TRANSITION TO OTHER ASPECTS OF NIH RESEARCH AND EVEN THE CAREERS BEYOND NIH. NEXT, PLEASE. IN TERMS OF OUR COMMUNITY, PROGRESS AND POTENTIAL IN ALZHEIMER'S, ONE OF OUR COMMUNICATION STRATEGIES HAS BEEN TOW PUT TOGETHER A SERIES OF VERY EFFECTIVE VIDEOS. AND SINCE ONE OF THE AUTHORS, ONE OF THE SPOKESPERSONS SHEAR WITH US AS A COUNCIL MEMBER, WE CAN SEE IF WE TAKE A MINUTE TO SHOW YOU A PART OF JENNIFER MANLY'S PRESENTATION. [ MUSIC PLAYING ] >>FOR ABOUT 25 YEARS, I HAVE BEEN WORKING WITH COMMUNITY-BASED COHORTS OF OLDER ADULTS THAT LIVE AROUND COLUMBIA UNIVERSITY IRVINE MEDICAL CENTER. THIS IS A REALLY DIVERSE NEIGHBORHOOD, REALLY INTERESTING NEIGHBORHOOD AND AN EPIC ENCLAVE FOR CARIBBEAN HISPANICS OR LATINX PEOPLE. THERE IS ALSO A LONG HISTORY OF PEOPLE WHO ARE AFRICAN-AMERICAN, AND THEN THERE IS A GROUP OF PEOPLE WHO DESCRIBE THEMSELVES AS NON-HISPANIC AND WHITE. AFRICAN-AMERICANS AND HISPANICS ARE 1.5-TWO TIMES MORE LIKELY TO DEVELOP ALZHEIMER'S DISEASE AND DEMENTIA. AND YET, THEY REPRESENT NO MORE THAN 2% OF PARTICIPANTS IN ALZHEIMER'S DISEASE CLINICAL TRIALS. PROGRESS IN ALZHEIMER'S DISEASE RESEARCH, IT WON'T BE AS RELEVANT AND IT WON'T BE USEFUL UNLESS IT IS ABLE TO INCLUDE PEOPLE WHO ARE REPRESENTATIVE OF OLDER ADULTS IN THE UNITED STATES. AND IT ALSO WON'T BE AS USEFUL IF THEIR -- >>THANK YOU. SO SORRY TO KEEP CUT YOU OFF. WE WANTED TO PROVIDE AN EXAMPLE OF SOME VERY EFFECTIVE COMMUNICATIONS TO OUR PUBLIC BY IN ALL RESPECT ARES, A DIVERSE GROUP OF INVESTIGATORS. I URGE YOU TO ENJOY CLICKING ON THESE LINKS AS WE GO FORWARD. NEXT. ALSO NOTEWORTHY -- SO FORMS ARE RELEASED LIST OF WORLD'S TOP FEMALEANIST 2022. -- FEMALE SCIENTISTS. AMONG IN THE LIST, INCLUDED AMONG THE TOP 10 ARE THREE WHO ARE SUPPORTED BY OR MEMBERS OF PRIOR NAI. SO VIRGINIA LEE, NEUROSCIENTIST AT UPENN AND FORMER COUNCIL MEMBER. TERRY MOFFITT, SIMILARLY AND TAMARA HARRIS, A LONG TIME LEADER IN THE INTRAMURAL PROGRAM. THERE ARE MANY MORE AS WE GO DOWN THE LIST BUT IT'S REALLY GRATIFYING AND TESTIMONY TO OUR ABILITY TO RECRUIT THESE OUTSTANDING PEOPLE TO OUR PROGRAMS. SO CONGRATULATIONS TO YOU AND TO ALL IN THIS. NEXT, PLEASE. IN TERMS OF OUR COMMUNICATING WITH THE PUBLIC, THIS IS JUST A LISTING BY THE NUMBERS OF THE NUMBER OF RELEASES WE HAVE HAD AND RESEARCH HIGHLIGHTS AND BLOGS, ANNOUNCEMENTS. IN TERMS OF THE ACTIVITIES FROM MYSELF AND I GUESS NOW IT'S DOCTOR KELLY AND AMY AND MELANED OVER THIS PAST MONTH. THESE ARE OUR CONVERSATIONS WITH STAKEHOLDER ADVOCACY GROUPS AS WELL AS OUR SIX CONGRESSIONAL BRIEFINGS WITH MORE TO COME. MANY OF YOU INVOLVED WITH RESEARCH ARE VERY, PERHAPS ALL TOO AWARE OF THE IMPACT THAT WE ARE GOING TO HAVE POSITIVELY AND WITH THE COST IN TERMS OF EFFORT, OF ENACTING THE NIH POLICY FOR DATA MANAGEMENT AND SHARING. PRINCIPLES ARE, WITHOUT DEBATE, CRITICAL AND IMPORTANT. THAT IS TO MAKE MOST BROADLY AVAILABLE THE OUTCOMES OF OUR RESEARCH TO THE BIOMEDICAL COMMUNITY. IT APPLIES TO ALL RESEARCH FUNDED BY NIH. TWO KEY REQUIREMENTS ARE SUBMISSION OF THE DATA MANAGEMENT AND SHARING PLAN. THAT'S A PART OF APPLICATIONS COMING FROM EXTRAMURAL SCIENTISTS. AND THIS IS ALSO NOW WORK, OUR INTRAMURAL SCIENTISTS ARE ENGAGED IN AS WELL. AND THEN COMPLIANCE ULTIMATELY WITH A PLAN THAT IS APPROVED. IT WILL BE A LOT OF WORK TO BRING IT TOGETHER AND WE'LL DO OUR VERY BEST TO GUIDE THE RESEARCH COMMUNITY IN AN EXTRAORDINARILY VALUABLE ENHANCEMENT OF COMMUNICATION OF OUR DATA GENERATED THROUGH RESEARCH. NEXT, PLEASE. NIH WIDE STRATEGIC PLAN FOR DEIA. THAT'S A DIVERSITY EQUITY AND INCLUSION AND ACCESSIBILITY. IT'S BEEN DEVELOPED OVER THESE PAST MONTHS AND IT IS -- WE ARE HERE AT PHASE V, DUE TO BE RELEASED. THIS IS NOT THE BEGINNING. IT'S THE CULMINATION OF A PLANNING PROCESS AND A FURTHER SERBALLIZATION AND COMMITMENT ACROSS ALL OF NIH, THE PRIORITIES OF DEIMENTED A. VERBALIZATION. IN TERMS OF TURNOVER AT NIH. WITHOUT EXAGGERATION THE EVENT WAS THE RETIREMENT OF TONY FAUCI AS NIAID DIRECTOR N THAT POSITION FOR 38 YEARS. ADVISED AND SERVED SEVEN PRESIDENTS ACROSS BOTH PARTIES. EXTRAORDINARY. THE DEPUTY DIRECTOR AT NIAID IS CURRENTLY ACTING CAPACITY AND WE ARE IN THE PROCESS NOW RAFT SEARCH FOR A NEW DIRECTOR OF NIAID. IT'S BEEN IMPORTANT TO THE NATION AND A DEPARTMENT PARTNER WITH NI. IN AGE-RELATED RESEARCH. NEXT, PLEASE. ANOTHER NEW APPOINTMENT NAMED THE INAUGURAL DIRECTOR OF ARMA H. AND AS YOU WILL SEE IN THE PROGRAM, AND HAVE A CHANCE TO SPEAK WITH THE FIRST FOUNDING DEPUTY DIRECTOR TO LEARN MORE ABOUT THE PROGRAM. JUST A WAY IN WHICH OUR TWO AGENCIES ARE GOING TO INTERACT AND DEVELOP OVER TIME BUT A CRITICAL OPPORTUNITY TO EXPAND OUR OVERALL RESEARCH EFFORTS. UP COMING EVENTS. POINT YOU TO COMING UP QUICKLY, MARCH, THE CARE AND SERVICES FOR PERSONS LIVING WITH DEMENTIA AND THEIR PARTNERS. THIS WILL BE A VIRTUAL MEETING AND I ENCOURAGE THOSE OF YOU TO REGISTER AND PARTICIPATE. IT'S A MEANS FOR HUNDREDS OF HAVINGS FROM PROFESSIONAL TO LAY AND THOSE INTERESTED. MAKE THEIR CONTRIBUTIONS THROUGH THE AIRPORT GREATED PLANNING EFFORTS FOR RESEARCH IN THIS FIELD. AND THE YEARS TO COME, WE'LL HAVE THE OTHER SUMMITS, THE ALZHEIMER'S RESEARCH SUMMIT AND THE ALZHEIMER'S RELATED DEMENTIA RESEARCH SUMMIT. NEXT, PLEASE. THE FOURTH SUM LIT OCCUR THIS YEAR. IT IS SCHEDULED TO BE IN PERSON AND HYBRID ON THE NIH BETHESDA CAMPUS IN APRIL. YOU SHOULD SOON BE SEEING THE AGENDA AND ENCOURAGE PARTICIPATION HERE. THIS INVOLVES NOT JUST NIA BUT A CONSORTIUM OF MOST OF THE INSTITUTES ACROSS NIH WITH NIA DOING AN IMPORTANT ROLE IN LEADERSHIP. I TRIED TO TIE THE BIOLOGY, BEHAVIOR OF AGING IN A WAY WHICH IT TIES TO THE RISKS AND PREVENTION OF DISEASE AND DISORDERS. NEXT, PLEASE. WILLIAM SCHOLARS PROGRAM WILL BE OCCURRING AGAIN THIS YEAR. FOR THE PAST TWO YEARS IT OCCURRED REMOTELY AND IT HAS BEEN SUCCESSFUL IN THAT CAPACITY. IT'S SCHEDULED FOR AUGUST 23-25. APPLICATIONS ARE DUE APRIL 21. WE ARE ENCOURAGING JUNIOR FACULTY AND RESEARCHERS IN THE FIELD OF AGING TO PARTICIPATE IN WHAT HAS BEEN AN OUTSTANDING, PRODUCTIVE COUNTRY-DEFINING EVENT AND PATRICIA JONES IS TAKING A LEAD IN THIS. AND WE WILL BE DELIGHTED TO HEAR IF YOU HAVE QUESTIONS. THE LINK IS HERE. AND THE APPLICATIONS ARE BEING RECEIVED. NEXT, PLEASE. AND NOW, WE TURN TO SOMETHING IN PERSON AND HAVE A CHANCE TO LET THE NEW RECRUITS, STAND UP AND INTRODUCE THEMSELVES BUT WE'LL DO IT ALL REMOTELY. SO WE'LL DO THIS DIVISION BY DIVISION. WE'LL START WITH THE AB. >>SHOULD I DO THAT, RICHARD? >>YES, PLEASE. >>THANK YOU. SO WE WELCOME TWO NEW PROGRAM OFFICERS TO THE DIVISION OF AGING BIOLOGY. DR. FU JOIN US IN SEPTEMBER OF 2022 TO MANAGE RESEARCH PORTFOLIO FOCUSED ON MOLECULAR EPIDEMIOLOGY IN AGING WHICH TIMES BROADEN THE UNDERSTANDING OF AGING AS A RISK FACTOR FOR FUNCTIONAL DECLINE. AND THAT WAS FUNCTIONAL DECLINES PERMISSIVE OR CONTRIBUTE TO DYSFUNCTION DEFICIT, ACCUMULATION AND MORBIDITIES. PREVIOUSLY, SHE HELD POSITIONS AT THE OFFICE OF BIOSTATISTICS RESEARCH AT THE NATIONAL HEART AND LUNG BLOOD INSTITUTE AND ALSO WORKED EXTENSIVELIED IN ANALYSIS OF THE FRAMINGHAM HEART STUDY. SHE RECEIVED HER DOCTORATE IN EPIDEMIOLOGY FROM UNIVERSITY OF OF TEXAS AT HOUSTON AND POSTDOCTORAL RESEARCH AT THE NATIONAL CANCER INSTITUTE. DR. AMANDA BOYS IS A NEW BRANCH CHIEF FOR THE AGING PHYSIOLOGY BRANCH IN THE DIVISION OF AGING BIOLOGY. SHE RECEIVED HER BACHELOR'S DEGREE FROM THE UNIVERSITY OF TEXAS AT AUSTIN AND COMPLETED HER PH.D. IN CELL BIOLOGY AND RESEARCH AT THE UNIVERSITY OF ALABAMA AT BIRMINGHAM. AND THEN POSTDOCTORAL RESEARCH AT THE NATIONAL INSTITUTED OF ARTHRITIS AND MUFFIN LOW SKELETAL AND SKIN DECEASES WHERE SHE WAS INTRAMURAL RESEARCHER FOR A NUMBER OF YEARS AND THEN CAME TO THE PROGRAM SIDE N2006 SHE CAME TO US IN 2022. SHE HAS A PORTFOLIO OF NEUROMUSCULAR AND CONNECTIVE TISSUE WHICH HAS EMPHASIS ON MUSCLE FUNCTIONING AND THE DECLINE IN MUSCLE FUNCTIONING IN AGING. THANK YOU. >>HELLO, EVERYONE I OF I'M LIZ NIELSEN FROM THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH. IT'S MY PLEASURE TO INTRODUCE OUR NEW STAFF. THE FIRST IS -- WHO JOINED VSR AS A PROGRAM OFFICER IN THE PROCESSES BRANCH TO MANAGE A PORTFOLIO IN OUR GROWING COGNITIVE AGING PROGRAM SPREAD ACROSS SEVERAL PROGRAM DIRECTORS IN THE DIVISION. SHE COMES TO US FROM NCCIH WHERE SHE SUPPORTED TRAINING AND CAREER DEVELOPMENT INITIATIVES. SHE COMPLETED A POSTDOCTORAL FELLOWSHIP AT THE NATIONAL CANCER INSTITUTE AND RECEIVED HER PH.D. IN COGNITIVE PSYCHOLOGY FROM THE UNIVERSITY OF HOUSTON. HER WORK HAS FOCUSED ON BRIDGING THE GAP BETWEEN BASIC COGNITIVE SCIENCE AND CLINICAL NEUROPSYCHOLOGY TO ADVANCE COGNITIVE MEASUREMENT, PARTICULARLY FOCUSED ON CANCER SURVIVORS. AND SHE SERVES AS A REPRESENTATIVE TO THE COGNITIVE SCIENCE AND CANCER-RELATED COGNITIVE IMPAIRMENT NETWORK. SECOND PROGRAM OFFICER ALSO IN THE INDIVIDUAL BEHAVIORAL PROCESS BRANCH IS ELISE RICE WHO JOINS FROM THE BEHAVIORAL AND SOCIAL RESEARCH BRANCH AT THE NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH. SHE HAS BEEN HIRED TO HELP US DEVELOP OUR PORTFOLIO IN COMMUNICATEDY AND BEHAVIORAL ENTER VENTIONS ALIGNED WITH THE NIH STAGE MODEL. SHE SERVES ALSO AS CO-LEAD ON THE NIH HEALTH BEHAVIOR THEORIES WORKING GROUP OUT OF OBSSR. SHE EARNED HER PH.D. IN PSYCHOLOGY FROM THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL AND WILL A POSTDOCTORAL FELLOWSHIP AT THE NATIONAL CANNER INSTITUTE, A THEME WE ARE HEARING IN OUR NEW STAFF. WE THANK NCI FOR SENDING US THEIR GREAT POSTDOCS. HER RESEARCH GREW OUT OF SOCIAL PSYCHOLOGY AND FOCUSED ON HOW POSITIVE SPONTANEOUS THOUGHTS UNDERLIE APPROACH MOTIVATION FOR HEALTH BEHAVIORS AND OTHER ASPECTS OF EVERYDAY LIFE. NEXT SLIDE, PLEASE. ALSO LIKE TO INTRODUCE DR. JOHN WHO IS AN ASSISTANT PROFESSOR IN THE HEALTH SCIENCES AT NORTHEASTERN UNIVERSITY AND WHO HAS JOINED US IN NOVEMBER AS ANG IPA IN THE INDIVIDUAL BEHAVIORAL PROCESS BRANCH TO HELP US DEVELOP OUR DIGITAL HEALTH PORTFOLIO. DR. JOHN IS A TRAINED EXERCISE PHYSIOLOGIST AND EXPERT IN THE APPLICATION OF WEARABLE SENSORS TO MEASURE AND MODIFY PHYSICAL DAVE AND HOW TO ACCURATELY QUANTIFY PHYSICAL ACTIVITY AND SEDENTARY BEHAVIOR. HE WILL BE REPRESENTING US ON MULTIPLE DIGITAL HEALTH WORKING GROUPS, INCLUDING COLLABORATIONS WITH NSF ON SMART AND CONNECTED HEALTH AND HELPING TO SUPPORT OUR GROWING SBIR PROGRAM OF TECHNOLOGICAL SOLUTIONS TO SUPPORT ADAPTIVE AGING. AND THEN LAST BUT NOT LEAST, DORI SULLIVAN JOINED US IN NOVEMBER AS A PATHWAYS INTERN WORKING WITH OUR ADMINISTRATIVE TEAM. SHE IS CURRENTLY PURSUING HER MPH AT THE GEORGE WASHINGTON UNIVERSITY SCHOOL OF PUBLIC HEALTH AND PRIOR TO JOINING, SHE RECEIVED HER BS IN BEHAVIORAL COMMUNITY HEALTH AT THE UNIVERSITY OF MARYLAND AND WAS PREVIOUSLY AN INTERN WITH NIA'S OFFICE OF PLANNING,INALIS AND EVALUATION. THANK YOU. >>GOOD MORNING. I'M FROM THE DIVISION OF NEUROSCIENCE IT'S ALSO MY PLEASURE TO WELCOME THE NEW TEAM MEMBERS TO THE DIVISION OF NEUROSCIENCE. FIRST, RICHARD KWOK WHO JOINED THE POPULATION STUBBEDDIES ON GENETICS BRANCH. RICHARD COMES NIHS AND HAS TREMENDOUS EXPERIENCE ON ENVIRONMENTAL EXPOSURE RESEARCH EXPOSOME RESEARCH. HE IS WORKING ON MANAGING A PORTFOLIO THAT IS RELATED TO EPIDEMIOLOGY OF ENVIRONMENTAL EXPOSURE, GLOBAL HEALTH, POPULATION STUDIES AND SO FORTH. AND ALSO JOINING THE DIVISION OR THE POPULATION STUDIES AND GENETICS BRANCH IS DR. GHALEH. SHE COMES FROM NINDS ALSO WITH A VERY STRONG BACKGROUND IN RESEARCH AND NEUROSCIENCES. AND SHE WILL BE MANAGING PORTFOLIOS ON EPIDEMIOLOGY OF ALZHEIMER'S DISEASE AS WELL AS GLOBAL HEALTH. BOTH OF THEM COME TO TREMENDOUSLY REINFORCE OUR EFFORTS TOWARD EXPANDING POPULATION STUDIES IN ADADRD. AND NEXT, ALSO JOINING THE DIVISION, SASHA. SHE COMES FROM NIMH AND SASHA JOINED AS PART OF THE TEAM MANAGING THE ALZHEIMER'S DISEASE RESEARCH CENTER, THE CENTERS HAVE CONTINUED TO GROW TREMENDOUSLY, NOW UP TO 35 CENTERS. AND SHE ALSO WILL BE HELPING IN THE IMPLEMENTATION OF THE DATA MANAGEMENT AND SHARING PLANS AND ALL CLINICAL RESEARCH RELATED TO NEUROSCIENCE IN THE CONTEXT OF THE ALZHEIMER'S STANDARDS. AND IN TERMS OF THE NEUROBIOLOGY OF AGING AND NEURODEGENERATION BRANCH, JOE POTTACKAL RECENTLY JOINED US. HE CAME FROM A UNIVERSITY OF MARYLAND, ALSO WITH A BACKGROUND IN NEUROSCIENCE, VERY STRONG BACKGROUND NEUROSCIENCES. AND HE IS GOING TO BE WORKING ON THE BRANCH PROVIDING SUPPORT ON PROGMALTIC RESEARCH ON VARIOUS AREAS OF NEUROBIOLOGY OF AGING, ALZHEIMER'S DISEASE AND ADRD IN SUPPORT OF THE OVERALL EFFORTS OF THE BRANCH. AND FINALLY, JERRY BOWER IS OUR NEW PATHWAY INTERN. HE ALSO COMES FROM A UNIVERSITY OF MARYLAND BALTIMORE COUNTY. AND HE WILL BE WORKING ON OUR ADMINISTRATIVE PROGRAMS AND SUPPORT AS A PATHWAY FELLOW. THANK YOU. >>ALL RIGHT, SO IT'S MY PLEASURE TO INTRODUCE THE NEW MEMBERS TO THE DIVISION OF EXTRAMURAL ACTIVITY. FIRST, IN OUR OFFICE OF CLINICAL RESEARCH, WE HAVE TWO NEW FEDERAL EMPLOYEES. FIRST IS DR. SHAH. SHE IS GOING TO BE A SUPERVISORY PROGRAM OFFICER. SHE IS JOINING US FROM NIAID, ALLERGY AND INFECTIOUS DISEASE. IN THEIR DIVISION OF AIDS RESEARCH AND SHE IS GOING TO BE PROVIDING A LOT OF SUPPORT FOR OUR CLINICAL RESEARCH OFFICE, ESPECIALLY IN REGULATORY AFFA AFFAIRS. WE ALSO HAVE GENE JAHVARIS GIBSON. SHE IS GOING TO BE A HEALTH COMMUNICATION SPECIALIST AND SHE HAS BEEN PREVIOUSLY A CONTRACTOR WITH US IN THE OFFICE OF CLINICAL RESEARCH BUT CONVERTED TO FEDERAL EMPLOYEE, FINALLY. AND SHE IS GOING TO HELP DEVELOP MATERIALS FOR ONE OF OUR MAJOR TOOLS FOR RECRUITMENT OUTREACH PRO. AND HELP OTHER CLINICAL TRIAL WORKGROUP STRATEGIES WITHIN THE OFFICE. NEXT SLIDE. WE HAVE TWO NEW SROs, SCIENTIFIC REVIEW OFFICERS IN THE SCIENTIFIC REVIEW BRANCH. FIRST WE HAVE -- JOINING US FROM BAILOR SCOTT AND LIGHT HEALTH. SHE IS GOING TO BE ONE OF THE TWO NEW SCIENTIFIC REVIEW OFFICERS. ALSO WE HAVE IVAN REBUSTINI. HE IS JOIN US US FROM THE EYE INSTITUTE AS A SCIENTIFIC REVIEW OFFICER. NEXT. AND ALSO WE HAVE TWO NEW MEMBERS OF OUR OFFICE OF STRATEGIC EXTRAMURAL PROGRAMS. THIS IS THE OFFICE THAT HANDLES OUR SMALL BUSINESS AND OUR TRAINING PROGRAMS. FIRST WE HAVE DR. JOSHUA HOOKS. HE IS A AAAS SCIENCE AND TECHNOLOGY POLICY FELLOW AND HE IS JOINING US FROM JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE. SO SHE GOING TO BE WORKING WITH US ON OUR VARIOUS TRAINING PROGRAMS FOR SMALL BUSINESS AND START UPS FOR NEW ENTREPRENEURS AND HE WILL DO A LOT OF OUR EVALUATION FOR OUR PROGRAMS, ESPECIALLY TO DIVERSIFY OUR AGING TECHNOLOGY AND RESEARCH WORKFORCE. WE ALSO, JUST THIS WEEK, STARTS DR. KUMAR. HE IS JOINING US FROM LAYOLA UNIVERSITY MARYLAND. HE IS GOING TO BE COORDINATING OUR SMALL BUSINESS FUNDING OPPORTUNITIES AND HE IS GOING TO HELP WITH IDENTIFYING BIOMEDICAL INNOVATIONS AND DEVELOP NEW INITIATIVES FOR SMALL BUSINESS. NEXT SLIDE. WE HAVE ONE NEW MEMBER IN OUR CONTRACTS MANAGEMENT BRANCH. WE WELCOME LAURA PEOPLE WHO WILL BE A SUPERVISOR, GRANTS MANAGEMENT SPECIALIST. SHE IS ALSO JOINING US FROM NI AIA AND SHE IS GOING TO BE SUPERVISING SEVERAL OF OUR GRANT SPECIALISTS BUT ALSO COORDINATE A LOT OF OUR COMPLEX GRANT PORTFOLIO THAT WE MANAGE IN OUR GRANTS PROGRAM. THANK YOU. >>GOOD MORNING, PATRICK IN THE EXECUTIVE OFFICE. TWO NEW MEMBERS TO OUR FINANCIAL MANAGEMENT BRANCH. LAURA LAIN AND CUDDY COBARNETT. THESE ARE THE FOLKS THAT MAKE SURE THAT THE DATA THAT WE PROVIDES IN ANALYSIS IS ACCURATE, TIMELY AND AVAILABLE FOR RICHARD AND AMY. WE ARE EXCITED TO HAVE THEM. LAUREN JOINS US FROM THE CLINICAL CENTER AT NIHED AND HE JOINS US FROM THE NAVAL RESEARCH LABORATORY OPERATIONS. THE NEXT BRANCH, WORKFORCE ADMINISTRATOR MANAGEMENT BRANCH, AS YOU'RE SEEING THIS, A LOT OF HIRING AND STAFFING GOING ON ACROSS THE NIA IN SUPPORT OF THE IMPORTANT MISSION WE HAVE AND ANDREA AND BETH ARE IN THAT TEAM AND OPPORTUNITY WORK TO MAKE SURE WE CAN ON BOARD AND BRING THE STAFF NECESSARY TO SUPPORT THE ACTIVITIES BOTH INTERN TO SUPPORT STAFF AND GET NEW FOLKS ONBOARD. SO THANK YOU. EXCITED TO HAVE THEM. THIS IS A NEW OPERATION THAT WE STOOD UP WITH CONTRACTS ACCUSATION AND PROCUREMENT BRANCH. THESE ARE FOLKS THAT ARE PREPARING TO SEE INCREASES IN OUR WORKLOAD REACTED TO R&D CONTRACTS, SO OUTWARD FACING, AS WELL AS CONTRACTS WE NEED INTERNALLY TO SUPPORT THE GROWTH. AND TONY AND DIANA COME FROM OTHER PARTS OF THE NIH. AND MICHELLE IS A BRAND NEW FAN AND LOOKING FORWARD TO HER CREATIVITY AND INNOVATION IN THIS SPACE. AND OUR INFORMATION TECHNOLOGY BRANCH HAS A COUPLE OF NEW FOLKS. THESE ARE THE TEAMS THAT SUPPORT MEETINGS LIKE THIS ACROSS THE ORGANIZATION AND SUPPORT OUR WORKPLACE FLEXIBILITY DURING THE PANDEMIC. WE HAVE A NEW INFORMATION SECURITY SYSTEMS OVERS, DAVE. HE COMES FROM US FROM THE OUTSIDE AS A CONTRACTOR. WE ARE EXCITED TO HAVE HIM JOIN US WITH HIS EXPERIENCE AND SELENA COMES TO US AGAIN FROM AN OUTSIDE COMPANY WITH HER CREATIVITY AND VISION TO SUPPORT FUTURE AUTOMATION AND DIGITIZATION ACROSS THE NIH OPERATIONS. THANK YOU. >>THANK YOU. MY NAME IS OLIVIA KENT. I LEAD THE DIGITAL MEDIA BRANCH IN THE OFFICE OF COMMUNICATIONS AND PUBLIC LIASON AT NIA. I'M EXCITED TO INTRODUCE DERRICK WHO JOINED THE TEAM THE WEEK OF THANKSGIVING AND HAS ALREADY BEEN MAKING AN IMPACT IN MANY AREAS. HE HAS A BACKGROUND IN GRAPHIC AND WEB DESIGN SO SHE OUR FIRST-EVER IN HOUSE GRAPHIC DESIGNER. AND YOU WILL LIKELY SEE THE OUTPUT OF HIS WORK AT THE NEXT MEETING. HE IS ALREADY WORKING ON AN UPDATED SLIDE PRESENTATION DECK AS WELL AS A COUPLE OF OTHER WEB PROJECTS AROUND DOING CONTENT AUDITING FOR US. SO VERY HAPPY TO HAVE DERRICK ONBOARD. >>-- [ INAUDIBLE ] I'M GOING TO PRESENT THE FIVE PEOPLE THAT WILL JOIN TODAY -- LET ME GET THIS OPPORTUNITY TO WISH YOU HAPPY NEW YEAR. SO NATALIE LANDECK FORMERLY WAS A FELLOW IN THE LABORATORY OF NEUROGENETICS FOCUSING ON INNOVATION HOW PARKINSON'S DISEASE AFFECT NEURONAL FUNCTION AND IS BECOMING A RESEARCH FELLOW. AND THEN CHELSEA WALTER AND MONICA SULLIVAN, THE FIRST COMING FROM THE ADMINISTRATION WHERE SHE WAS A SUPPORT ASSISTANT AND FREQUENTLY MEDICAL INSTITUTE WHERE SHE WAS PROVIDING ADMINISTRATIVE HELP. AND THEY ARE BOTH SUPPORTIVE OFFICERS THAT WILL BE MOSTLY FOCUSING ON HANDLING TRAVEL, AND SOME TRAINING FOR EMPLOYEES. NEXT SLIDE. ALSO A POSTDOCTORAL FELLOW. HE IS AN EXPERT IN HEMATOPOIETIC STEM CELL IN GENERAL. ALSO IN HUMAN AND FOCUSING ON EP GENOMICS. AND HE WILL BE REALLY HELPING THE ENTIRE TEAM AND TRAINING POSTDOC AND WITH MANUSCRIPT WRITING AND REVIEWING. AND HE IS NOW RESEARCH FELLOW. THE LAST BUT NOT LEAST, DAHLIA MARZOUK, THE NEW ADMINISTRATIVE MANAGER OF THE LABORATORY OF CARDIOVASCULAR SCIENCE AND SHE BASICALLY HANDLES THE ENTIRE INFRASTRUCTURE OF THE LABORATORY BY LOOKING AT TRAVEL PLANS AND SUPERVISING ALL THE ADMINISTRATION PERSONNEL THAT IS IN THE LABORATORY. AND SHE JOINS US IN SAINT LUKE'S HEALTH SYSTEM. >>LET ME JUST PAUSE AT THIS POINT TO EXPRESS OUR EXCITEMENT AND ENTHUSIASM FOR THE FACT WE HAVE BEEN ABLE TO RECRUIT TALENTED AND COMMITTED PEOPLE TO THE INSTITUTE. THEY WILL JUST ADD TO THE RICHNESS OF OUR CREATIVITY AND PRODUCTIVITY AND WELCOME ALL AGAIN. WISH THEY WERE HERE IN THE ROOM FOR A ROUND OF PLAYS AND SOME FURTHER RECOGNITION, BUT WE LOOK FORWARD TO YOUR CHANCE TO INTERACT WITH THEM IN THE TIMES COMING. FINALLY WE HAVE HERE SOME OF THE LINKS TO WAYS IN WHICH YOU CAN STAY INFORMED WITH WHAT NIA IS DOING. FIRST OF THOSE IS FOR ALL ACTIVE FUNDING OPPORTUNITIES. HERE THEY ARE FOR YOU TO PERUSE AND CONFORM YOUR OWN RESEARCH DECISIONS AND PLANS. AND THEN LATEST APPROVED CONCEPTS, MANY OF COME WILL BE FINALIZING IN TERMS OF CONCEPT APPROVAL THAT THE COUNCIL. THESE ARE CONCEPTS APPROVED TO GO FORWARD. MANY OF THEM WILL TURN INTO FUNDING OPPORTUNITIES. AND THEN AS THE MOST PROACTIVE WAY TO KEEP IN TOUCH WITH WHAT IS HAPPENING AT THE INSTITUTE, I ENCOURAGE YOU TO SUBSCRIBE TO THE BLOG SO IT COMES TO YOU GENERALLY WEEKLY BASIS. DESCRIBING A LOT OF THE LATEST INFORMATION OF RELEVANCE TO THE RESEARCH COMMUNITY AND THE BROADER PUBLIC. THANK YOU. I'M HAPPY TO ADDRESS ANY QUESTIONS YOU MAY HAVE. OTHERWISE IT'S BACK TO A TALK ABOUT FUTURE MEETINGS AND WHAT COMES NEXT. >>THANK YOU. ANY QUESTIONS FOR DR. HOSED? HE WILL BE ON HAND THROUGHOUT THE MEETING. IF YOU HAVE ANY QUESTIONS LET US KNOW AND WE'LL CONTINUE ON. FOR EVERYONE'S KNOWLEDGE, OUR FUTURE MEETINGS FOR 2023 AND 2024 ARE POSTED HERE. WE WILL BE HAVING AN IN-PERSON MEETING. OUR ATTEMPT IS FOR MAY AND SEPTEMBER COUNCILS. THIS WILL BE ON OUR MAIN CAMPUS BUILDING 45 HERE AT THE NIH CAMPUS. WE LOOK FORWARD TO MEETING PEOPLE IN PERSON IN THE NEAR FUTURE. NEXT UP -- >>CAN I ASK A QUESTION BEFORE YOU MOVE ON FROM THAT? >>SURE, GO AHEAD. >>SO, SOME OF US NEVER HAD AN IN-PERSON AS PART OF THE COUNCIL BEFORE. AND SO RELATED TO ALL OF THE TRAVEL THAT WOULD BE ASSOCIATED WITH THAT, THAT WOULD ALL BE FIRST ORIGINATING FROM PEOPLE AT NIA COMING TO US OR SHOULD WE DO THINGS ON OUR OWN SIDE? >>ABSOLUTELY. YES, SO YOU WILL BE RECEIVING A DETAILED E-MAIL FROM LINDA ADDISON HARVEY FROM OUR TEAM AND JASMINE. AND IT WILL OUTLINE EXACTLY WHAT YOU NEED TO DO FOR TRAVEL. AND THEY WILL BE HANDLING THE TRAVEL. >>BUT WAIT FOR IT TO ORIGINATE FROM YOUR SIDE BEFORE DOING ANYTHING? >>YES, CORRECT. >>GOT IT. THANK YOU. >>KEN ALSO IN THE CHAT, MARISA IS ASKING ABOUT AVAILABILITY OF THESE SLIDES AND LINKS. ABSOLUTELY WE WILL SEE THAT THESE ARE MADE AVAILABLE. >>YES. ABSOLUTELY. NEXT UP, IT'S OUR CONSIDERATION OF THE MINUTES FROM OUR LAST SEPTEMBER 2022 COUNCIL. THESE ARE AVAILABLE IN THE ELECTRONIC COUNCIL BOOK. I JUST LIKE TO THEN GET A MOTION TO APPROVE THE MINUTES FROM THE LAST MEETING. >>SO MOVED. >>SECOND? >>SECOND. >>ALL IN FAVOR. >>AYE. >>ANY OPPOSED? NOT HEARING ANY. WE HAVE APPROVAL OF THE MINUTES. R. FROM THE 2022 SEPTEMBER COUNCIL. THANK YOU VERY MUCH. NEXT UP IS OUR REPORT FROM OUR TASK FORCE ON MINORITY AGING. I'M TURN THIS OVER TO DR. MANLY. >>DR. MANLY: I'M GOING TO SHARE SOME SLIDES, IF THAT'S OKAY. HOPEFULLY IF YOU CAN SEE MY SCREEN RIGHT NOW -- >>YES. >>DR. MANLY: AND JUST WANT TO ORIENT LISTENERS THAT JUST LIKE THE NACA COUNCIL ADVISES THE SECRETARY OF HHS, THE DIRECTOR OF NIH AND DR. HOSED ON NIA'S MISSION, THE TASK FORCE FOR MINORITYEDS AGING RESEARCH COMMITTEE IS A SUBCOMMITTEE OF NACA. ALL COUNCIL MEMBERS ARE ACTIVE MEMBERS OF OUR TASK FORCE SUBCOMMITTEE AND THE TASK FORCE HAS A SPECIAL ROLE TO ADVISE NIH AND DR. HOEDS ABOUT OUR UNDERSTANDING OF HOW AGING RESEARCH CAN ADDRESS HEALTH INEQUALITIES FOR MINORITY WOMEN, MINORITY GROUPS AND PEOPLE WITH DISABILITIES. WE HAVE DR. PATRICIA JONES, THE DIRECTOR OF THE NIA OFFICE OF SPECIAL POPULATIONS WHO WORKS WITH THE TASK FORCE TO ACHIEVE ITS GOALS, AND DR. YANIRA CRUZ ARE THE CO-CHAIRS. DR. HEALTH WHITFIELD THIS IS HIS LAST MEETING AT COUNCIL, WHICH IS A VERY SAD THING. BUT DR. CRUZ IS STEPPING UP TO TAKE PART IN AS A CO-CHAIR. AND WHAT WE DO IN THE TASK FORCE, IS WE TRY TO HIGHLIGHT INNOVATIVE AND IMPACTFUL HEALTH RESEARCH FUNDED BY NIA THROUGHOUT EACH OF THE DIVISIONS, ESPECIALLY THE RESEARCH THAT USES THE NIA HEALTH DISPARITIES FRAMEWORK. AND WE ALSO TRY TO ENGAGE IN A DISCUSSION ABOUT SUPPORT FOR TRAINING AND OTHER NIA RESOURCES THAT CAN HELP TO ACCELERATE AND ADVANCE HEALTH AND AGING RESEARCH. AND SO, PRIOR TO EVERY NACA MEETING, THE CO-CHAIRS AND DR. JONES MEET TO TRY TO COME UP WITH WHAT WE ARE GOING TO DO AT THIS MEETING. AND THIS TIME WE CHOSE TWO SPEAKERS TO PRESENT TO COUNCIL TO HIGHLIGHT THE CONTRIBUTION OF BIOLOGICAL RESEARCH OR BASIC BIOLOGY RESEARCH AND BIOLOGICAL MECHANISMS TO UNDERSTANDING HEALTH AND AGING DISPARITIES RESEARCH. SO LET ME TELL YOU ABOUT THOSE TALKS RIGHT NOW AND I'M GOING SHOW YOU SLIDES FROM THE PRESENTERS. THESE ARE NOT MY SLIDES. THESE ARE SLIDES FROM THE PRESENTERS. OUR FIRST TALK WAS FROM DR. CHANTAL MARTIN WHO IS AN ASSISTANT PROFESSOR OF EPIDEMIOLOGY AT THE GILLINGS SCHOOL OF GLOBAL AND PUBLIC HEALTH. SHE IS A SOCIAL EPIDEMIOLOGIST WHO FOCUSES ON SOCIAL AND STRUCTURAL DRIVERS OF HEALTH AND EQUALITIES IN COGNITIVE DISEASE RISK ACROSS THE LIFE COURSE. AND THE POTENTIAL UNDERLYING BIOLOGICAL MECHANISMS. AND SHE BEGAN HER TALK BY PROVIDING AN OVERVIEW FOR US OF STRUCTURAL RACISM AS A FUNDAMENTAL CAUSE OF HEALTH DISPARITIES. SHE PROVIDED A QUOTE TO US FROM ZIN WE HAVE BAILEY, AN EXPERT ON STRUCTURAL RACISM AND HEALTH AND THAT BASICALLY SAYS THAT STRUCTURAL RACISM IS INTERCONNECTED INSTITUTIONS WHOSE LINKAGES ARE HISTORICALLY ROOTED AND CULTURALLY ENFORCED. IT'S THE TOTALITY OF WAYS IN WHICH THE SOCIETIES FOSTER RACIAL DISCRIMINATION THROUGH MUTUALLY REINFORCING I BELIEVE EQUITABLE SYSTEMS AND -- INEQUITABLE SYSTEMS AND REINFORCE DISCRIMINATORY BELIEFS, VALUES AND DISTRIBUTION OF RESOURCES WHICH TOGETHER AFFECT THE RISK OF ADVERSE HEALTH OUTCOMES. SO DR. MARTIN DESCRIBED HER WORK TO US TO UNDERSTAND HOW STRUCTURAL RACISM THAT I JUST GAVE YOU A DEFINITION FOR, IN PARTICULAR RESIDENTIAL SEGREGATION INFLUENCES CHANGES IN BIOLOGICAL, PHYSIOLOGICAL, PSYCHOLOGICAL, BEHAVIORAL AND SOCIAL FUNCTIONING. ONE OF THE INNOVATIVE WAYS THAT RESEARCHERS HAVE BEEN TRYING TO UNDERSTAND THESE INFLUENCES IS BY MEASURING BIOLOGICAL AGING AND ESSENTIALLY THIS IS BIOMARKERS THAT PREDICT THE FUNCTIONAL CAPABILITY OF A PERSON OR THEIR ORGANS AND HOW IT CHANGES WITH AGE. SO, COMMON MEASURES OF BIOLOGICAL AGING INCLUDE ALOE STATIC LOAD, TELOMERE LENGTH AND IMMEW MUNE FUNCTION BUT DR. MARTIN TOLD US ABOUT DNA METHYLATION WHICH IS BIOMARKER OF BIOLOGICAL AGING THAT IS RESPONSIVE TO ENVIRONMENTAL STRESSORS. IT OFFERS INSIGHT INTO POTENTIAL MOLECULAR PATHWAYS THAT LINK STRESS AND THE ENVIRONMENT TO HEALTH IN THE BODY. AND LET PLEASE JUST QUICKLY SHOW YOU SOME OF HER RESULTS. SHE LOOKED AT THE ASSOCIATION -- ASKED THE QUESTION HOW IS THIS TO STRUCTURAL RACISM AND ADVERSE NEIGHBORHOOD CONDITIONS CONTRIBUTE TO EP GENELNETIC CHANGES AND ACCELERATED AGING THROUGHOUT THE LIFE COURSE. SHE FOUND USING THE DETROIT NEIGHBORHOOD HEALTH AND AGING STUDY THAT NEIGHBORHOOD QUALITY WAS ASSOCIATED WITH ACCELERATED DNA METHYLATION AGING. IN MODELS THAT WERE STRATIFIED ON SOCIAL COHESION, THE ASSOCIATION OF NEIGHBORHOOD DISORDER WITH DNA METHYLATION REMAINED ELEVATED FOR PEOPLE LIVING IN NEIGHBORHOODS WITH LOWER SOCIAL COHESION BUT WERE NULL FOR PEOPLE WHO LIVED IN NEIGHBORHOODS WITH HIGHER SOCIAL COHESION. SO, DR. MARTIN'S RESEARCH SUGGESTED THAT LIVING IN AN ADVERSE NEIGHBORHOOD ENVIRONMENT CAN SPEED UP THIS EPIGENETIC AGING WHILE POSITIVE NEIGHBORHOOD ATTRIBUTES MAY BUFFER THOSE EFFECTS. LET ME MOVE ON QUICKLY TO THE NEXT TALK THAT WE HEARD YESTERDAY. DR. GERMANE DAVIS IS AN ASSISTANT PROFESSOR IN THE DEPARTMENT OF BIOCHEMISTRY, CANCER BIOLOGY AND NEUROSCIENCE AT THE HARRY MEDICAL COLLEGE AND IS A MEMBER OF THE CENTER FOR STRUCTURAL BIOLOGY AT VANDERBILT. HE IS A PH.D. IN BIOCHEMISTRY AND MOLECULAR BIOPHYSICS AND IS AN ALUMNUS AT THE BUTLER WILLIAM SCHOLAR PROGRAM, ONE OF THE KEY ACTIVITIES OF THE OFFICE OF SPECIAL PROGRAMS AT NIA. AND ONE IMPORTANT PART OF WHAT DR. DAVIS DOES IS TRIES TO UNDERSTAND THE CONTRIBUTION OF GENETICS TO THE DISPARITY IN ALZHEIMER'S DISEASE RISK BETWEEN AFRICAN-AMERICANS AND NON-HISPANIC WHITES, WHICH VIDEO ME JUST SAID ABOUT 20 MINUTES AGO, 20 OR 30 MINUTES AGO, IN THE VIDEO. AND DR. DAVIS IS TRYING TO UNDERSTAND GENETIC VARIANTS THAT ARE ASSOCIATED WITH ALZHEIMER'S DISEASE THAT ARE MORE PREVALENT IN EUROPEANS OF AFRICAN DECENT THAN THEY ARE IN PEOPLE OF EUROPEAN ANCESTRY. SO HE IS TRYING TO UNDERSTAND THIS A7 GENE, WHICH HAS BEEN SHOWN TO HAVE STRONGER ASSOCIATIONS WITH AD RISK IN PEOPLE WITH AFRICAN ANCESTRY THAN IN PEOPLE WITH EUROPEAN ANCESTRY. IN FACT, IT HAS A STRONGER EFFECT ON AD RISK THANG THE APOE4 GENE OR ALLELE IN AFRICAN-AMERICANS. SO HE IS TRYING TO UNDERSTAND THIS TRANSMEMBRANE PROTEIN THAT'S INVOLVED IN LIPID HOMEOSTAYSIS AND PHAGOCYTOSIS, AND THE DYSFUNCTION OF THE ABC A7 JEAN IS ASSOCIATED WITH INCREASED AMYLOID BETA PRODUCTION, REDUCED AMYLOID BETA CLEARS, IMPAIRED MICROGLIAL RESPONSE TO INFLAMMATION AND ENDOPLASMIC RETICULUM STRESS. SO, LET ME SHOW YOU MY LAST SLIDE, WHICH IS ALSO FROM DR. DAVIS'S TALKS. SO THIS IS DR. DAVIS'S SLIDE AND DATA. SOME OF IT WAS PRESENTED IN AAIC. AND THE QUESTION THAT HE HAS WAS, HOW A7 CONTRIBUTES A DO. A MOLECULAR LEVEL. HE SHOWED US HOW HE ISUDING A COMBINATION OF STRUCTURAL AND CELL BIOLOGY TECHNIQUES TO DO THIS. HE IS LOOKING AT HOW THE ABC A7 VARIANT MAY CONTRIBUTE ALZHEIMER'S DISEASE BY REDUCING THE LEVEL OF THIS SUBSTANCE CALLED, PIP 2 IT'S A PHOSPHOLIPID REPORTED TO BE DECREASED IN THE AD BRAIN. SO THAT VERY INTERESTING WORK WAS PRESENTED BY HIM YESTERDAY. IN ADDITION TO THE CAREFUL AND INNOVATIVE WORK HE IS DOING TO UNDERSTAND THESE GENETIC CONTRIBUTIONS, THE KNACK COUNCIL WAS VERY IMPRESSED WITH HIS EMPHASIS ON COMMUNITY ENGAGEMENT. -- NACA -- THIS IS A RESEARCHER WHO ALWAYS KEEPS IT REAL WITH THE COMMUNITY. HE ENGAGES THEM ABOUT HIS RESEARCH AND RESEARCH PARTICIPATION, AND THROUGH THE MEMBERS OF HIS LAB AND HIS WORK, HE EMPHASIZES THE IMPORTANCE OF EMBEDDING HIS SCIENCE IN THE CONCERNS OF THE COMMUNITIES WE ARE TRYING TO SERVE. SO THAT IS MY REPORT. LET ME JUST ASK DR. CRUZ IF YOU HAVE ANYTHING TO ADD? >>THANK YOU DR. MANLY. I THINK YOU HAVE DONE A VERY NICE JOB JUST COVERING WHAT WE HEARD YESTERDAY. IT WAS FASCINATING PRESENTATION AND I THINK A GREAT OPPORTUNITY TO CONTINUE TO DO GOOD WORK TO ADDRESS HEALTH EQUITIES IN OUR SOCIETY. >>DR. MANLY: THANK YOU. >>THANK YOU DR. MANLY AND DR. CRUZ. ANY OTHER COMMENTS OR QUESTIONS FROM OUR PANEL? >>THIS IS SANJAY. THAT WAS A BEAUTIFUL SUMMARY, JENNIFER. JUST A COMMENT AND I THINK MANY OF YOU ARE AWARE THAT SOME WORK BY DR. AMY KLEIN HAS SHOWN THAT PEOPLE WHO RESIDE IN POOR NEIGHBORHOODS ACTUALLY HAVE WORSE COGNITIVE PERFORMANCE, CARDIOATROPHY ON MRI SCANS AND ALSO INCREASED AMYLOID BURDEN AS A MEASURE TO BIOMARKER. THERE SEEMS TO BE DIRECT RELATIONSHIP BETWEEN NEIGHBORHOOD DISADVANTAGE AND SOME BIOLOGY AS WELL. IT NEEDS TO BE CONFIRMED IN ADDITIONAL STUDIES. I WONDER IF YOU MIGHT HAVE SOME INSIGHT INTO THE -- DR. MARTIN'S PRESENTATION. I WONDER IF AS PEOPLE MOVE FROM ONE NEIGHBORHOOD TO ANOTHER DURING THEIR LIFE COURSE, AND IF THEIR LIVING CONDITIONS IMPROVE, WOULD THAT AFFECT THE BIOLOGICAL AGING MARKERS THAT DR. MARTIN TALKED ABOUT? WILL YOU HAVE ANY SENSE ABOUT THAT? >>DR. MANLY: I MEAN, I THINK WHAT I WOULD SAY IS THAT I DON'T THINK WE KNOW THE ANSWER TO YOUR QUESTION YET. AND PART OF WHAT OUR DISCUSSION IS MOVING FORWARD IS, WHAT CAN -- WHAT OPPORTUNITIES, WHAT STUDIES CAN BE LEVERAGED? SO YOU SAW DR. MARTIN LEVERAGE THE DETROIT STUDY. SHE IS ALSO A FREQUENT USER OF THE ADD HEALTH STUDY, WHICH IS A LONGITUDINAL STUDY OF ADOLESCENTS. THESE FOLKS ARE GETTING UP THERE NOW. I THINK THAT IT ARE ABOUT MY AGE. SO THESE ARE THE KINDS OF DATA RESOURCES THAT WE NEED TO UNDERSTAND THE ANSWER TO YOUR QUESTION. OBVIOUSLY IF WE HAVE A GROUP OF PEOPLE WHO ARE IDENTIFIED WHO LIVE IN A PARTICULAR NEIGHBORHOOD LIKE THE ONE THAT I WORK IN IN WASHINGTON HEIGHTS, THERE ARE PEOPLE WHO ARE THERE WHO LIVED THERE THEIR WHOLE LIVES AND THERE ARE PEOPLE WHO MOVED THERE FROM THE SOUTH OR IMMIGRATED FROM OTHER COUNTRIES. AND SOY, THIS IS THE RICH KIND OF LIFE COURSE TRAJECTORY WE NEED TO UNDERSTAND. AND ONE KEY PART OF THAT IS TO GET A RESIDENTIAL HISTORY FROM PEOPLE. AND THAT TAKES A WHILE. SO THAT TAKES RESOURCES. AND THE FLIP SIDE IS TO BE ABLE TO LINK PEOPLE TO ADMINISTRATIVE RECORDS OF WHERE THEY HAVE LIVED AND THEN ONE OTHER -- LIKE ADD HEALTH, WHICH IS ESSENTIALLY FOLLOW PEOPLE FROM A VERY YOUNG AGE, VISIT THEM EVERY 2-3 YEARS AND FIND OUT -- MEASURE DIRECTLY FROM THEM. THAT'S HOW I WOULD ANSWER YOUR QUESTION. AND I SEE THAT THERE IS ANOTHER HAND UP. >>HI, JENNIFER. WONDERFUL FEATURING OF THIS EXCITING WORK. I WAS WONDERING, AD-HOC RIGHT NOW, I DIDN'T HAVE ACCESS TO THE BRIEFING BOOK, BUT WILL WE GET, AS COUNCIL MEMBERS, FILLED IN ON HOW NIA IS DOING ON DEIA INITIATIVES AND JUST IN GRANTS THAT ARE FUNDED ACROSS THE ORGANIZATION ABOUT INVESTIGATORS AT DIFFERENT STAGES OF THEIR CAREERS? IS THAT SOMETHING WE WILL BE GETTING BRIEFED ON? >>DR. MANLY: YES, BUT I THINK IT'S ALSO SOMETHING THAT COUNCIL MEMBERS NEED TO ASK FOR. AND SINCE WE ARE ALL MEMBERS OF THIS TASK FORCE, WE NEED TO SORT OF ASK SPECIFICALLY FOR INFORMATION ABOUT THESE PROGRAMS. AND ASK FOR THE LEVEL OF DETAIL THAT WE NEED TO UNDERSTAND WHETHER THERE HAS BEEN PROGRESS AND WHAT HAS BEEN EFFECTIVE. SO LET'S TALK SOME MORE. ANY FEEDBACK THAT COUNCIL MEMBERS HAVE FOR US ABOUT WHAT FUTURE AGENDA SHOULD BE FOR THE TASK FORCE, WE WOULD LOVE THAT. DR. KAHN? >>DR. KAHN: DR. MANLY, I WAS CURIOUS IF ANY COMPARABLE RESEARCH HAS BEEN DONE IN RURAL COMMUNITIES, ESPECIALLY UNDERSERVED COMMUNITIES. JUST THIS MORNING I GOT THE WORD THAT ONE OF MY CHEROKEE FRIENDS, HER MOM, PASSED AWAY AND SHE WAS SUFFERING FROM ALZHEIMER'S FOR YEARS. AND I KNOW THE STRUGGLE OF HER AND HER FAMILY GETTING CARE FOR HER. ANY SUPPORT WAS JUST QUITE AN EXPERIENCE FOR THEM. SO JUST CURIOUS TO KNOW. >>DR. MANLY: ABSOLUTELY. AND I'M VERY SORRY ABOUT YOUR FRIEND'S LOSS. I THINK THAT THERE ARE A NUMBER OF INITIATIVES. I'M A PART OF ONE AND I'LL JUST TALK ABOUT THAT VERY QUICKLY. THE -- AND I THINK SOMEBODY PUT SOMETHING IN THE CHAT. LET ME READ THAT IN A MINUTE. BUT THE REGARD STUDY, IS AN NINDS-FUNDED STUDY. IT HAS NIA SUPPORT AS WELL TO LOOK AT BRAIN HEALTH IN PEOPLE WHO LIVE ACROSS THE UNITED STATES. AND THEY OVERSAMPLE PEOPLE IN THE STROKE BELT, MUCH OF WHICH IS RURAL. AND ONE OF THE SPIN OFF STUDIES FROM THAT IS CALLED, RURAL, THE RURAL STUDY, TO UNDERSTAND HEALTH IN RURAL ENVIRONMENTS. LET ME READ THIS CHAT JUST IN CASE. OKAY, LIZ, THANK YOU. COMES TO THE RESCUE. INTERDISCIPLINARY NETWORK ON RURAL POPULATION HEALTH AND AGING. SHE PROVIDES A LINK FOR THAT. BUT, RURAL RESIDENTS IS ONE OF THOSE KEY SORT OF FUNDAMENTAL GEOGRAPHIC PLACE AND SPACE DRIVERS OF HEALTH. AND SO IT'S SOMETHING THAT I THINK THERE IS A NUMBER OF PEOPLE OUT THERE TRYING TO UNDERSTAND THOSE MECHANISMS. >>ALL RIGHT. THANK YOU VERY MUCH, JEN. APPRECIATE THE RESPONSES TO THE COMMENTS. I THINK WE WILL MOVE ON. NEXT UP WE HAVE A REPORT ON WORKING GROUP ON PROGRAM. SO I'LL TURN THIS OVER TO MONICA DRISCOLL. MONICA? >>DR. DRISCOLL: THANK YOU VERY MUCH. SO, YESTERDAY WE STARTED OFF OUR WORK WITH A PRESENTATION FROM STEVE WHO IS KIND OF OVERSEEING THE EFFORT TO REVIEW THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY. SO I THINK WE WERE ALL IMPRESSED WITH THE PANEL CREDENTIALS AND THEIR EXPERIENCE, THE ORGANIZATION AND THE PROGRESS THAT THIS GROUP HAS MADE AND WITH THE FINAL ANTICIPATED REPORT FOR MAY. SO YOU CAN ALL HAVE THAT TO LOOK FORWARD TO AT THE NEXT MEETING. WE THEN TURNED TO CONCEPT CLEARANCES. AND AGAIN I'LL JUST START BY THINKING THE NIA FOR PUTTING TOGETHER A REALLY TERRIFIC SET OF EXCITING AND IMPORTANT INITIATIVES AND THANKING THE COUNCIL MEMBERS FOR THEIR HARD WORK AND THOUGHTFUL COMMENTS. WHAT WE'LL DO TODAY IS JUST, I'LL CALL ON THE PRIMARY REVIEWER TO REVIEW THE -- SUMMARIZE THE DISCUSSION. AND THEN WE WILL VOTE AT THE END ON BLOCK FOR THE ACCEPTANCE OF THESE. SO, LET'S BEGIN WITH THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH ON THE INITIAL CONCEPT CLEARANCE CALLED BEHAVIORAL AND SOCIAL RESEARCH ON THE ROLE OF IMMIGRATION ON LIFE COURSE HEALTH AND AGING INCLUDING AD/ADRD. THE PRIMARY VIEWER OF DR. MANLY, SECONDED WAS DR. WE'RE. DR. MANLY IF YOU COULD SUMMARIZE FOR US. >>DR. MANLY: SURE, SO THIS WAS AN EXCELLENT CONCEPT CLEARANCE, VERY CLEARLY WRITTEN AND JUSTIFIED. IT WOULD BE A NEW INITIATIVE FOR OUR PHASE FOR RESEARCH ON LIFE COURSE SOCIAL AND STRUCTURAL FACTORS THAT SHAPE AGING, HEALTH AND ALZHEIMER'S DISEASE AND RELATED DISORDERS AMONG BLACK, LATINO AND ASIAN IMMIGRANT GROUPS IN THE UNITED STATES. THERE WAS A RECENT NATIONAL ACADEMY OF SCIENCES WORKSHOP THAT RECOMMENDED THAT IN ORDER TO UNDERSTAND INEQUALITIES AND HEALTH AND AGING, NOT ONLY DO WE NEED A TRANSDISCIPLINARY LENSE AND LIFE COURSE MODELS BUD ALSO RESEARCH THAT DISAGGREGATES MY NORMAL TIESED GROUPINGS BEYOND SOCIOECONOMIC STATUS. SO THE DIVISION OF SOCIAL AND BEHAVIORAL RESEARCH HAS DECIDED THAT ONE WAY TO DO THAT IN ORDER TO RESPOND TO THAT REPORT, IS TO FOCUS ON THE ROLE OF IMMIGRA IMMIGRATION. AS ONE ASPECT OF THAT DISAGGREGATION. MANY PEOPLE WHO ARE LISTENING MAY KNOW THAT THERE ARE SOMETHING CALLED THE IMMIGRANT HEALTH PARADOX, WHICH IS THAT MORE RECENT IMMIGRANTS HAVE BETTER HEALTH THAN PEOPLE WHO ARE U.S. BORN OR IMMIGRATED LATER IN LIFE. BUT AS OUR RESEARCH IN THIS AREA GROWS, THERE IS SOME STUDIES THAT SHOW THE OPPOSITE, WHICH IS THAT RECENT IMMIGRANTS, HEALTH IS WORSE AND IT DEPENDS ON WHAT THE HEALTH OUTCOME IS, HOW YOU STUDY IT, WHEN YOU STUDY IT. SO THIS NEEDS TO BE LOOKED INTO FURTHER. AND THAT IS WHAT IS CALLED FOR IN THE CONCEPT CLEARANCE. THE CONCEPT CLEARANCE IS FOR BOTH RO1 AND R21 MECHANISMS WITH A STRONG RATIONAL FOR EACH MECHANISM BEING USEFUL IN CONDUCTING THIS WORK. R21s MAY BE USEFUL IN DOING SOME OF THE COMMUNITY-BASED AND MIXED METHODS APPROACHES THAT MAYBE MOST IDEALLY SUITED TO UNDERSTAND SOME OF THE MEASUREMENT ISSUES IN THE POPULATION AND THE CONCEPT ALSO ENCOURAGED LEVERAGING OF EXISTING NIA STUDIES LIKE THE HEALTH AND RETIREMENT STUDY AND THE HARMONIZED COGNITIVE ASSESSMENT PROTOCOL, HAD. RS SISTER STUDIES AROUND THE WORLD AND ADD HEALTH. BUT PRIMARY DATA COLLECTION IS ALSO POSSIBLE. THIS CONCEPT INDIVIDUAL A SET ASIDE FUNDS AND ALSO A SPECIALIZED REVIEW. AND THIS IS IMPORTANT BECAUSE THE CONCEPT CLEARANCE SHOWED DATA AT THE LAST TIME NIA SIGNED ON TO A ANNOUNCEMENT, FUNDING ANNOUNCEMENT TO ADDRESS HEALTH DISPARITIES AMONG IMMIGRANT POPULATIONS. VERY FEW APPLICATIONS WERE SENT IN FOR THAT THAT WERE NIA, FOCUSED. ALL THE STUDIES WENT TO EXISTING STUDY SECTIONS AND ALL OF THEM WERE SCORED ABOVE THE CURRENT PAY LINE. SO THIS IS AN OPPORTUNITY FOR PEOPLE WHO ARE DOING RESEARCH OR WHO WANT TO DO RESEARCH IN IMMIGRANT GROUPS TO HAVE THIS OPPORTUNITY TO SUBMIT TO SPECIAL REVIEW GROUP. AND THE COUNCIL WAS ENTHUSIASTIC ABOUT THIS CONCEPT CLEARANCE. >>GREAT, THANK YOU VERY MUCH. THE SECOND CONCEPT THAT WE CONSIDERED WAS ENHANCING USE OF HCAP DATA. THE PRIMARY REVIEWER OF DR. WE'RE AND THE SECONDARY WAS DR. MANLY. DR. WE'RE IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>DR. WE'RE: HCAP IS THE HARMONIZED COGNITIVE ASSESSMENT PROTOCOL THAT JEN JUST MENTIONED. THAT IS AN ASSESSMENT AIMED AT RESEARCH DIAGNOSIS OF DEMENTIA AND MILD COGNITIVE IMPAIRMENT DEVELOPED WITHIN THE HEALTH RETIREMENT STUDY TO ADDRESS THE NEED FOR MORE COST EFFECTIVE APPROACHES IN LARGE POPULATIONS STUDIES. IT WAS DONE IN CONSULTATION WITH SEVERAL OF THE INTERNATIONAL PARTNER STUDIES. THE NIA HAS SUPPORTED NOW TWO WAVES OF HCAP IN THE HRS WE'LL IN MULTIPLE OTHER COUNTRIES AROUND THE WORLD SO THERE IS A ESTABLISHED AND GROWING BODY OF DATA. AND THIS CONCEPT AIMS TO LEVERAGE THAT INTO REAL RESEARCH. THOSE STUDIES WERE FUNDED TO CREATE THE RESOURCE NOT TO REALLY EXPLOIT IT. SO THIS IS A TARGETED SET OF RO1s THAT WILL USE THE HCAP, RESOLVE SOME OF THE CHALLENGES TO INTERNATIONAL CULPABILITY AND MOVE THE FIELD FORWARD TAKING ADVANTAGE OF THE INFORMATION ABOUT LIFE EXPERIENCES AND ENVIRONMENTAL CONTEXT THAT YOU CAN GET FROM INTERNATIONAL COMPARISONS FROM ANY ONE COUNTRY. SO STRONG SUPPORT. >>THANK YOU SO MUCH. THE NEXT CONCEPT THAT WE CONSIDERED IS GRAND CHALLENGE; PREDICTING EARLY ALZHEIMER'S DEAND RELATED DEMENTIAS. DR. MANLY WAS THE PRIMARY REVIEWER AND DR. WHITFIELD WAS THE SECONDARY. DR. MANLY IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>DR. MANLY: SORRY FOLKS, TRYING TO SHUFFLE MY DIGITAL PAPERS HERE. THIS WAS A CONCEPT CLEARANCE WE SEEN A YEAR AGO AND THE GOAL OF THIS CONCEPT IS TO SUPPORT A CONTRACT THAT WOULD PROVIDE THE INFRASTRUCTURE FOR DEVELOPMENT, COORDINATION AND ADVERTISEMENT OF COMPETITIONS THAT ADDRESS THE GRAND CHALLENGE OF PREDICTING EARLY ALZHEIMER'S DISEASE AND RELATED DEMENTIAS. SO ESSENTIALLY THIS CONTRACTOR WOULD ENGAGE EXPERT ADVISORS AND PROVIDE SCIENTIFIC DIRECTION, IDENTIFY HIGH-PRIORITY DATA SOURCES FOR POTENTIALLY USE FOR THIS. AI CHALLENGE, WHICH IS TO TAKE A BUNCH OF DATA AND PREDICT WHO WILL GET ALZHEIMER'S DISEASE, TO ESTABLISH CLOUD SPACE FOR COMPETITIONS AND TO EVALUATE THOSE COMPETITIONS. THIS IS ESSENTIALLY A COMMUNITY, RESEARCH COMMUNITY BUILDING GRANT. IT DOESN'T DESCRIBE HOW EXACTLY THE CHALLENGE WILL BE MET BUT IT IS A CRITICAL INFRASTRUCTURE AND HUMAN CAPITAL BUILDING STEP. AND THE GOAL IS TO ENGAGE A DIVERSE SCIENTIFIC COMMUNITY TO BEGIN TO COLLABORATE SO THE CHALLENGE CAN BE MET IN THE BEST WAY POSSIBLE. AND BY DIVERSE, I MEAN AI RESEARCHERS AND ENGINEERS, DATE SCIENTIFIC, NEUROSCIENTISTS, PSYCHOLOGISTS, SOCIOLOGISTS, AND CITIZEN SCIENTISTS AND COMMUNITY PARTNERS INCLUDING SMALL BUSINESS. AND THEY WANT TO ENGAGE PEOPLE IN THEIR CAREERS ALL THE WAY FROM STUDENTS, TRAINEES, EARLY INVESTIGATORS, ALL THE WAY TO MORE SEASONED INVESTIGATORS. THE COUNCIL THOUGHT THIS WAS EXTREMELY TIMELY. THEY WERE ENTHUSIASTIC ABOUT THIS RESOURCE BUILDING CONCEPT CLEARANCE AND RECOMMENDED IT. S. >>THANK YOU VERY MUCH. OKAY, THE NEXT ONE THAT WE CONSIDERED IS THE CONSORTIUM FOR PAYMENT UTILIZATION AND ACCESS FOR DEMENTIA CARE. THE PRIMARY REVIEWER WAS DR. CASE AND THE SECONDARY WAS DR. WE'RE. DR. CASE IF YOU COULD SUMMARIZE FOR US. >>DR. CASE: SURE. THE CONCEPT MADE A STRONG CASE FOR THE NEED FOR RESEARCH IN ADDRESSING THE EXTRAORDINARY ARRAY OF DECISIONS AND DIFFICULTIES FACED IN PROVIDING CARE FOR PEOPLE LIVING WITH DEMENTIA. THE PROPOSAL IS FOR A CONSORTIUM WITH A COORDINATING CENTER THROUGH A U54 AND SIXER R1s TO ADDRESS SPECIFIC AD/ADRD MILESTONES SUCH AS HOW FEDERAL POLICIES AND PAYMENT MODELS EFFECT CARE FOR PEOPLE LIVING WITH DEMENTIA, HOW CARE VARIES ACROSS INSTITUTIONAL SETTINGS, HOW PAYMENT MECHANISMS AFFECT UTILIZATIONAL SERVICES, AND ACCESS TO CARE. SO THE CONCEPT IS TIMELY. THE MOTIVATION IS CLEAR. THE U54 WILL PLAY A POWERING UP COORDINATING ROLE ACROSS THE RO1s COORDINATING MEETINGS AND STAKEHOLDER ENGAGEMENT, IDENTIFYING COMMON DATA ELEMENTS, IDENTIFY TRAINING PROGRAMS, TRANSLATION AND AVAILABILITY OF RESOURCES. AND THE COORDINATING CENTER CAN ALSO SOLICIT STUDIES TO DIRECTLY ADDRESS MILESTONES THAT AREN'T ALREADY BEING ADDRESSED BY THE FUNDED RL1s. SO THERE WAS A GREAT DEAL OF ENTHUSIASM FOR THIS CONCEPT CLEARANCE. >>THANK YOU VERY MUCH. THE NEXT CONCEPT DISCUSSED IS TITLED DEMENTIA CARE COORDINATION RESEARCH CENTER. DR. RUBIN WAS THE PRIMARY REVIEWER AND DR. WHITFIELD WAS THE SECONDARY. DR. RUBIN IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>DR. RUBIN: THIS IS A CONCEPT THAT STEMMED FROM THE 2020 DEMENTIA CARE SUMMIT. AND THE RATIONAL FOR IT IS THAT THERE IS AN URGENT NEED TO BETTER UNDERSTAND WHAT WORKS IN TERMS OF THE BENEFIT CARE COORDINATION AND CARE TRANSITION COMMUNITY SETTINGS. THIS IS GOING TO BE A U54 MECHANISM AND IT'S TO SUPPORT DEMENTIA CARE INTEGRATION RESEARCH NETWORK. IT WILL BE A CENTER FOR ORGANIZING PARTNERSHIPS WITH REGIONAL DATA PROVIDERS AND RESEARCHERS. AND A DATA HUB FOR DATA SHARING THAT WILL INCLUDE PILOTS. IT WILL ALSO RECOGNIZE THE MULTIPLE STAKEHOLDERS THAT ARE INVOLVED, INCLUDING STATES, INCLUDING HEALTH CARE ORGANIZATIONS, INCLUDING COMMUNITY-BASED ORGANIZATIONS, INCLUDING INSURERS. SO IT IS VERY BROAD, ESPECIALLY SET ASIDE IS REQUESTEDS AS WELL AS SPECIAL EMPHASIS PANEL. AND WITH SOME WORD SMITHING AND SOME REVISION, THE CONCEPT WAS APPROVED UNAN HUESLY BUT A FINAL VERSION WILL BE DISTRIBUTED TO COUNCIL FOR FINAL APPROVAL. >>GREAT. THANK YOU VERY MUCH FOR THE SUMMARY. THE NEXT CONCEPT THAT WE CONSIDERED IS ENTITLEDDED LEVERAGING SOCIAL NETWORK TO PROMOTE WIDESPREAD INDIVIDUAL BEHAVIOR CHANGE. DR. RUBIN WAS THE PRIMARY REVIEWER AND DR. WHITFIELD WAS THE SECONDARY. DR. RUBIN IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>DR. RUBIN: THIS WAS A VERY INTERESTING AND WELL-RECEIVED CONCEPT. IT RECOGNIZES THE POTENTIAL OF SOCIAL NETWORKS TO PROMOTE BEHAVIORAL CHANGE INCLUDING TARGETING INITIAL DOCTORS AND AS WELL AS MODIFICATION OF NETWORK STRUCTURE COMPOSITION. AND THIS IS PARTICULARLY TIMELY BECAUSE OF THE EXPLOSION OF SOCIAL NETWORKING THROUGH THE WIDESPREAD ADOPTION OF SOCIAL MEDIA, WHICH PRESENTS BOTH OPPORTUNITIES AND CHALLENGES IN THE MANAGEMENT OF OLDER PERSONS WITH RESPECT TO THE BEHAVIORAL CHANGES. THIS WAS ENTHUSIASTICALLY EMBRACED BY COUNCIL AND WE ARE EXCITED ABOUT IT. IT WILL BE RO1 MECHANISM. >>GREAT. THANK YOU VERY MUCH FOR THAT CONCISE SUMMARY. THE NEXT CONCEPT WE CONSIDERED IS NETWORKS TO DEVELOP BEHAVIORAL AND SOCIAL SCIENCE RESEARCH IN AGING AND AD/ADRD. PRIMARY REVIEWER WAS DR. WHITFIELD AND THE SECONDARY WAS DR. CASE. DR. WHITFIELD, IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>DR. WHITFIELD: CERTAINLY, THIS CONCEPT PROPOSAL WAS INTENDED TO OFFER A NIMBLE MEANS TO SUPPORT HIGH PRIORITY AREAS OF RESEARCH FOR BSR. THE CONCEPT WOULD ADDRESS SEVEN DIFFERENT OPPORTUNITIES THAT WERE RECOMMENDATIONS FROM THE 2019BSR REVIEW AS WELL AS THE NAI,AD/ADRD MILESTONES. THIS CONCEPT CLEARANCE WOULD USE R24 MECHANISM. SO AWARD RESEARCH THROUGH SUPPORT NETWORKS THAT WOULD BE THE BASIS FOR THE CREATION OF THE INNOVATIVE RESEARCH GROUPS THAT WOULD LEAD FROM DISCOVERING, SUPPORTING, IDENTIFYING EMERGING RESEARCH AND THINKING ABOUT CONSIDERING AND ELUCIDATING OTHER RESEARCH RESOURCES. THE AREAS OUTLINED FROM THE 2019BSR REVIEW WILL PROVIDE IMPORTANT PLATFORMS FOR INTERESTING RESEARCH NETWORKS TO BE CREATED. THE R24 MECHANISMS EXCELLENT MECHANISM FOR FOSTERING INTER DISCIPLINARY GROUPS OF GROUPS SENATOR SCIENTISTS AND TO THINK ABOUT IMPORTANT AREAS IN SUPPORT OF ADVANCING NEUROSCIENCE. THIS CONCEPT AS WE DISCUSSED IT IS CLEARLY PROVIDE AN ENTREE AND FACILITATE THE ABILITY TO HAVE COLLABORATIONS BOTH WITHIN BS R AND ACROSS DIVISIONS. AND WITH THAT, THE DISCUSSION WAS VERY SUPPORTIVE AND WE APPROVE THIS CONCEPT. >>THANK YOU SO MUCH. THE NEXT ONE THAT WE CONSIDERED IS MEASURE SYSTEM FINANCIAL HARDSHIP AMONG PEOPLE AND FAMILIES LIVING WITH AD/ADRD. DR. CASE WAS THE PRIMARY REVIEWER AND DR. WE'RE WAS SECONDARY. DR. CASE, IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>DR. CASE: SURE. THIS CONCEPT STARTS WITH THE OBSERVATION THAT PEOPLE WITH AD/ADRD ARE NOT OR EVENTUALLY WILL NOT BE IN A POSITION TO REPORT THE FULL RANGE OF FINANCIAL STRESS AND STRAIN AND ASSET COMPLETION AND COSTS THAT AD/ADRD BRING WITH IT. AND THAT THEY DO NOTE BEAR THE ENTIRE COST FOR THE SUPPORT THEY RECEIVE. AND THAT AS A RESULT, THE EXISTING FINANCIAL WELLNESS SCREENERS ARE NOT REALLY ABLE TO CAPTURE THE COSTS ASSOCIATED FULLY CAPTURE THE COSTS ASSOCIATED WITH THE DEGREE. THE DISCUSSION, THERE WAS SOME CONFUSION, PRIMARILY MY OWN, ON EXACTLY WHAT THE CONCEPT WAS CALLING FOR. BUT THE CONCEPT IS FOR A CALL FOR RO1 PROPOSALS TO FIND WAYS TO CHARACTERIZE THE NETWORK OF SUPPORT RECEIVED AND TO FIND WAYS TO CAPTURE THE FINANCIAL STRESS AND STRAIN AND COSTS BORN BY THE NETWORK OF PEOPLE, FAMILY, FRIENDS, OTHER SOCIAL CONTACTS, THAT SUPPORT A PERSON DIAGNOSED AND LIVING WITH DEMENTIA. SO, THERE WAS ENTHUSIASM ON SE SEEING THIS TAKEN FORWARD. WITH SOME SUGGESTION ON MAKING IT CLEARER, PRECISELY WHAT THE -- WHAT IS BEING CALLED FOR IN TERMS OF DEVELOPING METHODS FOR UNDERSTANDING THE ELICITATION OF THE COSTS ASSOCIATED WITH PROVIDING CARE FOR PEOPLE WITH AD/ADRD. >>THANK YOU VERY MUCH. THE NEXT ONE THAT WE CONSIDERED IS NATIONAL HEALTH AND AGING TRENDS, AND NATIONAL STUDY OF CARE GIVING. THIS CONCEPT WAS REVIEWED BY DR. WE'RE AND DR. CASE. DR. WE'RE, IF YOU COULD SUMMARIZE FOR US. >>DR. WE'RE: SURE. THIS CONCEPT WAS FOR RENEWAL OF THE STUDY AND ITS COMPANION STUDY OF CAREGIVERS. THE NHATS IS A SUCCESSOR TO THE NATIONAL LONG-TERM CARE SURVEY WHICH WENT FOR 20-SOMETHING YEARS PRIOR TO THAT. SO IT CONTINUES A VERY LONG TRADITION OF ASSESSMENT OF DISABILITY IN THE OLDER POPULATION AND THE DEMANDS FOR CARE. WHAT'S EXCITING ABOUT NEAR FUTURE IS THAT NIA HAS RESTRUCTURED GOVERNANCE FOR THIS STUDY WITH EFFECTIVE DATA MONITORING COMMUNITY WHICH HAS BROUGHT NEW FOCUS TO ADADRD CONCERNS GIVEN TRADITIONAL STRENGTHS AND UNDERSTANDING DISABILITY AND ADAPTATION TO DISABILITY, EXTENDING THIS TO THE NEEDS FOR ALZHEIMER'S PATIENTS. SO LIKE A REAL WINNER FOR NIA. SO, WE WERE STRONGLY SUPPORTIVE OF CONTINUING. >>THANK YOU VERY MUCH FOR THAT CONCISE SUMMARY. WE'LL CONTINUE WITH THE DCG CONCEPT CLEARANCES. NEXT IS DEVELOPMENT AND VALIDATION OF HARMONIZED METHODOLOGIES TO MEASURE NAD PLUS AND RELATED LEVELS IN CLINICAL TRIALS. THE PRIMARY REVIEWER WAS DR. VASEEN AND THE SECONDARY WAS DR. GREENSPAN. DR. BHASIN IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. THANK YOU. >>THANK YOU. SO THIS CONCEPT PROPOSAL DEVELOPING VALIDATION OF HARMONIZED METHODOLOGIES TO MEASURE NAD, SEEKS TO SUPPORT STUDIES TO DEVELOP AND VALIDATE METHODS FOR ACCURATE MEASUREMENT OF NAD+ AND RELATED METABOLITES IN HUMAN BLOOD AND TISSUES. THERE HAS BEEN A LOT OF EXCITEMENT ABOUT NAD EVEN THOUGH NAD HAS BEEN KNOWN FOR THE ROLE IN SYNTHESIS FOR 60-70 YEARS. MORE RECENT INVESTIGATIONS OVER THE LAST 15 YEARS HAVE REVEALED MUCH MORE EXPANSIVE ROLE OF NAD IN EMERGING BIOLOGY. AND THE NUMBER OF STRATEGIES ARE BEING DEVELOPED THROUGH AUGMENT NAD AS A -- AS A THERAPEUTIC INTERVENTION TO PREVENT AND TREAT A NUMBER OF AGE-RELATED DISEASES. NAD PRECURSORS HAVE BEEN INVESTIGATED IN PRE-CLINICAL AS WELL AS AT SOME EARLY PHASE HUMAN STUDIES AND THE DATA FROM THESE EARLY STUDIES ARE TANTALIZING AND HAVE SHOWN THE PROMISE OF THIS STRATEGY. BUT THERE IS ALSO BEEN DIFFICULTIES IN THIS DATA BECAUSE OF MET LOGIC PROBLEMS IN MEASURING NAD AND ITS METABOLITES IN THE SERUM AND IN OTHER TISSUES, PARTICULARLY IN TISSUES. THERE ARE THREE TYPES OF DIFFICULTIES, HOW TO STABILIZE NA. AND METABOLITES, PARTICULARLY NADA, NADPH AND DOWNSTREAM METABOLITES IN THE HUMAN SERUM AS WELL AS IN TISSUES PRIOR TO MEASUREMENT. AND SECOND, HOW TO HARMONIZE THE VARIOUS ASSAYS TO MINIMIZE IN THE LABORATORY HETEROGENEITY AND FINALLY, CAN WE MEASURE NAD AND METABOLITES IN SIT YOU USING MAGNETIC RESONANCE SPECTROSCOPY? AND THEN THERE IS A NEED TO HARMONIZE THESE METHODS SO THE EVALUATION BEING REPORTED BY DIFFERENT LABORATORIES ARE COMPARABLE AND ARE BEING BENCHMARKED WITH HIGHER ORDER OF CALIBRATOR. SO THIS PARTICULAR INITIATOR THAT HAS BEEN PROPOSED IN THIS CONCEPT CLEARANCE AS A UL1 MECHANISMS IS VERY URGENTLY NEEDED TO PROMOTE RESEARCH IN THIS SPACE. IT WAS A LOT OF ENTHUSIASM FOR SUPPORTING THIS CONCEPT. >>GREAT. >>AND THE NEED FOR SPECIAL EMPHASIS ALSO IS WELL JUSTIFIED. >>THANK YOU VERY MUCH. THE NEXT CONCEPT THAT WE CONSIDERED IS CALLED ELUCIDATING VARIABILITY OF PHYSIOLOGIC AND FUNCTIONAL RESPONSES TO EXERCISE TRAINING IN OLDER ADULTS. THE PRIMARY REVIEWER IS DR. GREENSPAN AND THE SECONDARY IS DR. BHASIN. DR. GREENSPAN, IF YOU COULD RECOUNT THE DECISION FROM YESTERDAY, PLEASE. >>DR. GREENSPAN: THANK YOU, MONICA. ALTHOUGH THERE ARE SIGNIFICANT EVIDENCE THAT THERE IS BOST EXERCISE AND PHYSICAL ACTIVITY FOR PREVENTION OF DISEASE IN OLDER ADULTS, THERE IS ALSO SIGNIFICANT VARIABILITY IN INDIVIDUALS RESPONSE TO EXERCISE. AND THERE HAVE BEEN SEVERAL KEY STUDIES THAT HAVE DEMONSTRATED THIS VARIABILITY INCLUDING ONE VERY LARGE NIA-SUPPORTED STUDY, THE LIFE TRIAL, THAT SHOWED A REDUCTION IN THE TRANSITION TO MOBILITY DISABILITY, BUT 1/3 OF THE PARTICIPANTS HAD A DECLINE IN GAIT SPEED AND DECLINE IN OTHER FUNCTIONAL TESTS. THERE WAS AN NIH WORKED SHOP IN APRIL OF 2022 THAT HIGHLIGHTED THE HETEROGENEITY OF RESPONSE TO EXERCISE TRAINING AND FOUND THAT THERE WERE KEY GAPS IN ELUCIDATING THE RELATIONSHIPS BETWEEN EXOGENOUS AND INTRINSIC VERSUS EXOGENOUS, EXTRINSIC FACTORS UNDERLYING THE VARIATIONS IN THIS RESPONSE TO EXERCISE. FURTHERMORE, THEY NOTED THAT A POSITIVE OUTCOME IN ONE DOMAIN DID NOT ALWAYS PROVIDE A POSITIVE RESPONSE IN ANOTHER IMPORTANT OUTCOME OR DOMAIN. SO THIS CONCEPT WILL BE AN RFA FOR RL1s, SET ASIDE FUNDS TO DESIGN CONTROL STUDIES WITH MULTIDISCIPLINARY TEAMS UTILIZING INNOVATIVE APPROACHES. THE CONCEPT WILL SUPPORT NEW STUDIES TO UNDERSTAND THE MECHANISM UNDERLYING THE RESPONSE AND VARIABILITY TO EXERCISE TRAINING IN OLDER ADULTS. IT WAS SUGGESTED THAT INVESTIGATORS DESIGN TRIALS THAT CONTROL FOR EXERCISE EXPOSURE, THE ENVIRONMENT, EXAMINE TEMP ASPECTS, EXAMINE THE INTERACTIONS OF DRUG AND EXERCISE INTERACTIONS, LOOK AT THOSE WITH MULTIPLE CHRONIC CONDITIONS, HOW THEY RESOLVE THE RESULTS AND MECHANISMS OF SEX AND AGE DIFFERENCES ALONG WITH OTHER CONFOUNDERS AND FACTORS. WE FELT THAT THIS WAS A TIMELY AND IMPORTANT RFA THAT WILL DIRECT INVESTIGATORS TO EXAMINE A HOST OF THESE FACTORS THAT LEADS TO THIS VARIABILITY IN THE EXERCISE RESPONSE. THERE WAS A GOOD DISCUSSION AND A LOT OF ENTHUSIASM FOR THIS CONCEPT. >>THANK YOU, SO MUCH. THE LAST ONE FROM THE DGCG IS CLONAL HEMATOPOIESIS IN AGING HUMANS, DETECTION, RISK FACTORS AND RELATIONSHIPS TO AGING-RELATED PATHOPHYSIOLOGY AND CONDITIONS, AND CLINICAL UTILITY IN SCREENING AND PROGNOSIS. DR. BAKER WAS THE PRIMARY REVIEWER AND DR. HUANG WAS THE SECONDARY. DR. BAKER IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>DR. BAKER: ABSOLUTELY. SO THIS CONCEPT IS FOR A NEW RFA FUNDING MECHANISM THAT IS LOOKING TO GET RO1s WITH THE 3-5 YEAR PERIOD TO INVESTIGATE CLONAL HEMATOPOIESIS IN AGING HUMANS. WITH THE INTENTION TO DETECT, IDENTIFY RISK FACTORS, ESTABLISH RELATIONSHIPS TO AGE-RELATED PATHOPHYSIOLOGY AND CONDITIONS AND DAUGHTER-IN-LAW THE CLINICAL UTILITY AND SCREENING AND PROGRESSINOSIS FOR PATIENTS -- DETERMINE -- IT WAS A JOINT PROPOSAL. FOR A LONG PERIOD, MOST OF THE STUDIES HAVE FOCUSED PRIMARILY ON PRE CANCEROUS ALTERATION THAT IS SUPPORT NEOPLASTIC TRANSFORMATION TO BLOOD-TYPE CANCERS. ABOUT 15-20% OF PEOPLE OVER THE AGE OF 70 HAVE BLOOD CELLS WITH CANCER ASSOCIATED CHANGES BUT THEY DO NOT THEMSELVES DEVELOP TUMORS. SO WITH ADVANCES IN SEQUENCING TECHNOLOGIES AND REDUCTIONS IN THE INVESTMENT NEEDED TO ENTER INTO THE SPACE, THERE IS AMPLE OPPORTUNITY TO FURTHER UNDERSTAND HOW THESE VARIATIONS THAT OCCUR WITH AGE AND HOW THEY ALSO MAYBE ARE OCCURRING IN DIVERSE POPULATIONS AND TO THIS END, MORE THAN 60,000 PARTICIPANTS HAVE BEEN INVESTIGATED FOR CLONAL HEMATOPOIETIC ALTERATIONS OF INDETERMINATE POTENTIAL AND GENERALLY LONG-LIVED PATIENTS TEND TO HAVE FEWER CLONAL CHANGES. THERE WAS A WORKSHOP TO EXPLORE THIS RELATIONSHIP IN 2021. A LOT OF EXCITEMENT AROUND THIS. LARGELY THIS RFA IS COMING FROM THE OUTCOMES FROM THAT PARTICULAR WORKSHOP. IT SEEMS TO FITTED WELL WITHIN THE BEING HIGH PRIORITY WITH THE NIA AND THERE WAS NO HESITATION WITHIN THE COUNCIL FOR SUPPORTING THIS PARTICULAR INITIATIVE. >>GREAT. THANK YOU VERY MUCH. WE WILL MOVE ON TO NOW THE DIVISION OF NEUROSCIENCE CONCEPT CLEARANCES. THE FIRST ONE IN THAT GROUP WE CONSIDERED WERE NEURONAL AND NON NEURONAL MECHANISMS, UNDERLYING GAIT AS A PRE-CLINICAL MARKER FOR ALZHEIMER'S DISEASE AND ALZHEIMER'S DISEASE RELATED DEMENTIAS. DR. BHASIN WAS PRIMARY REVIEWER AND DR. RUBIN WAS SECONDARY. DR. BHASIN IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>DR. BHASIN: THANK YOU VERY MUCH. THIS CONCEPT PROPOSAL SEEKS SET ASIDE FUNDS TO ENCOURAGE RESEARCH IN ELUCIDATING THE NEURAL AS WELL AS NON-NEURAL MECHANISMS THAT UNDERLIE THE ASSOCIATION BETWEEN MOBILITY AND COGNITION IN AGING AND ADRD. THERE IS WIDE AGREEMENT THAT IMPAIRED MOBILITY PRECEDES AND PREDICTS IMPAIRED COGNITION AND ALSO PREDICTS AN INCREASE RISK OF DEVELOPING ALZHEIMER'S DISEASE. THE PREDICTIVE ABILITY OF GAIT SPEED IS MARKER OF HEALTH AND PHYSICAL DISABILITY, COGNITIVE DECLINE AND ALZHEIMER'S AND MORTALITY IS WIDELY RECOGNIZED. EVEN THOUGH THE NEURAL AS WELL AS NON-NEURAL MECHANISMS THAT LINK WALKING AND OTHER MOTOR FUNCTIONS WITH COGNITION AND SUBSEQUENT DECLINE IN COGNITION AND DEVELOPMENT OF ALZHEIMER'S DISEASE ARE INCOMPLETELY UNDERSTOOD. THAT IS WHAT IS BEING ENCOURAGED IN THIS PARTICULAR CONCEPT PROPOSAL. SO THE PROPOSAL SEEKS TO SET ASIDE FUNDS AND SPECIAL EMPHASIS PANEL TO REVIEW THE RESULTING GRANT APPLICATIONS. THERE WAS GENERAL ENTHUSIASM THAT THIS IS A VERY IMPORTANT AREA FOR INVESTIGATION THAT NEEDS TO BE SUPPORTED AND THIS MECHANISM SEEMS APPROPRIATE. THERE WAS LIVELY DISCUSSION AROUND THIS AND SOME SUGGESTION WERE MADE TO NEURODOWN THE FOCUS OF THE INITIATIVE AND FOCUS ON THE NEURAL MECHANISMS. BUT THERE WAS WIDE SUPPORT AND ENTHUSIASM FOR THIS CONCEPT PROPOSAL. >>THANK YOU SO MUCH. THE NEXT ONE THAT WE CONSIDERED IS ANALYTICAL AND CLINICAL VALIDATION OF BIOMARKERS FOR ALZHEIMER'S DISEASE AND RELATED DIMENS YALS. PRIMARY REVIEWER WAS DR. SNYDER AND THE SECONDARY WAS DR. VANELEDIC. DR. SNYDER, IF YOU COULD REVIEW THE DISCUSSION FOR US. ED. >>DR. SNYDER: SO THIS IS CONCEPT CLEARANCE -- [ LOW AUDIO ] [ INAUDIBLE ] FOCUSES ON HIGH QUALITY, COST EFFECTIVENESS AND UNDER REPRESENTED COMMUNITIES AND WHILE IT'S NOT RESTRICTED TO LOW BIOMARKERS, THERE IS SPECIFIC -- OF PROMISE OF BIOMARKERS -- NEED FOR CLINICAL UTILITY STUDY. ALSO BIOMARKERS -- FRAMEWORK INCLUDES THE FRAMEWORK AND BIOMARKERS FOR TOOLS FROM MEDICAL DEVICE DEVELOPMENT -- SO PRETTY WIDE OPEN INCLUDING FLUID, PLASMA, IMAGING AND REALLY FOCUS ON THE ANALYTICAL AND CLINICAL VALIDITY. UL1 MECHANISM WHICH WE THOUGHT WAS APPROPRIATE MECHANISM THAT ALLOWS COOPERATIVE AGREEMENT AND WITH NIA MILESTONES AND INPUT, THE TYPE -- REALLY IMPORTANT BECAUSE REALLY THE ULTIMATE BUT NOT REQUIRED GOAL IS TO APPLY FOR FDA BIOMARKER -- PROGRAM. SO VERY -- RESPONSIVE TO THE STRATEGIC PLAN. OVERALL WE THOUGHT IT WAS TIMELY AND MUCH-NEEDED INITIATIVE STANDARDS REQUIRED VIA FDA. WE LIKED IT BECAUSE BIOMARKERS AND REALLY ACROSS -- WE WERE SUPPORTIVE. THERE WERE A FEW QUESTIONS EASILY ANSWERED BY PROGRAM AND WE ARE EXCITED. >>THANK YOU. THE NEXT APPLICATION IS ENTIT ENTITLED -- CHIMERIC ANTIGEN RECEPTOR APPROACHES. THE PRIMARY REVIEWER WAS DR. HUANG AND THE SECONDARY WAS DR. BAKER. DR. HUAN GOVERNMENT IS STRUGGLING WITH LOSING HIS VOICE SO DR. BAKER TOOK ON THE VERGEAL PRESENTATION. AND I THINK THAT -- NOT SURE WHO WILL TELL US ABOUT TODAY -- >>I CAN TAKE IT. SO YES, BASICALLY WE WERE VERY MUCH IN AGREEMENT ON THIS WORN. >>[ INDISCERNIBLE ] >>CAN YOU HEAR ME? THIS CONCEPT CLEARANCE IS FOR A NEW R61R33 MECHANISMS FOR CHIMERIC ANTIGEN RECEPTOR APPROACHES. WE ARE AVAILABLE WITH CAR AND MA SLUG CEASE SO IN THIS CASE WHAT THEY ARE TRYING TO DO IS GO AFTER MORE PROOF OF PRINCIPLE THAT IS SIMILAR APPROACH COUPLING CHIMERIC ANTIGEN RECEPTORS AGAINST THINGS THAT ARE RELEVANT FOR ALZHEIMER'S DISEASE AND ALZHEIMER'S DISEASE-RELATED PATHOLOGIES TO BE POTENTIALLY USEFUL. SO IN ESSENCE, THAT WAS THE MAIN THING IT'S GOING TO BE EXISTING IN TWO STAGES. R61 IS DURING THE FIRST TWO YEARS OF THE FUNDING CYCLE WHERE THERE ARE MILESTONES PEOPLE WILL NEED TO MEET AND THEN SUBSEQUENTLY LEADING INTO R33 MECHANISMS FOR THE REMAINING THREE YEARS OF FUNDING FOR THIS. OVERALL, THERE WAS THIS FEELS LIKE IT FIDDLE A VERY IMPORTANT PRIORITY AND TO DEVELOP NEW ANIMAL MODELS THAT MAY HAVE HIGH PREDICTIVE VALUE FOR THINGS THAT COULD BE USEFUL FOR DRUG DEVELOPMENT FOR TRANSLATIONALLY RELEVANT TREATMENT OPPORTUNITIES FOR PEOPLE. NO HESITATIONS WITH SUPPORT OF THIS. AGAIN A VERY WELL WRITTEN RFA REQUEST. >>GREAT. THANK YOU VERY MUCH. THE NEXT CONCEPT WAS BUILDING NEUROSCIENCE RESEARCH INFRASTRUCTURE FOR ALZHEIMER'S DISEASE AND RELATED DEMENTIAS IN AFRICA. DR. WE'RE, IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>SURE. WE FELT THIS WAS A DYNAMIC AND TIMELY INITIATIVE T REPRESENTS A COOPERATION BETWEEN DN AND THE SPONSOR AND DBSR. THE FOCUS IS ON SUB-SAHARAN AFRICA WHICH IS A REGION THAT IS GREATLY UNDERSTUDIED AND IS A POTENTIALLY GREAT VALUE TO GENETIC RELEVANCE AND DIVERSITY, DUE TO THE UNIQUE DISEASE AND ENVIRONMENTAL EXPOSURES IN THAT PART OF THE WORLD. SO WE FELT THAT FOCUS WAS WELL JUSTIFIED IT'S TIMELY IN THAT THERE HAS BEEN NOW STUDIES IN SOUTH AFRICA AND IN KENYA COLLABORATING WITH THE NETWORKS TO BUILD COMPARABLE DIAGNOSTIC TOOLS. THERE WAS MEETING SPONSORED IN NAIROBI WELL ATTENDED BY SCIENTISTS FROM THE U.S. AND AFRICA. SO THE POTENTIAL REALLY DOES SEEM TO BE THERE NOW FOR THINGS TO START HAPPENING. THE MECHANISM IS STAGE UG3UH3 IN WHICH THERE WILL BE MILESTONES IN THE START UP PHASE AND ONLY SUCCESSFUL PROJECTS WILL GO FORWARD. AND THE MAIN CRITERION WHICH SUCCESS WILL BE EVALUATED IS THE BUILDING OF CAPACITY IN AFRICA. SO THIS IS NOT TO FINANCE DRIVE BY STUDIES FROM U.S. INVESTIGATORS. IT'S REALLY TO PARTNER AND DEVELOP CAPACITY ON A MORE PERMANENT BASIS IN AFRICA. SO WE HAVE GREAT ENTHUSIASM FOR THIS PROJECT. >>THANK YOU SO MUCH. GREAT. THE NEXT CONCEPT THAT WE CONSIDERED IS ARTIFICIAL INTELLIGENCE IN PRE-CLINICAL DRUG DEVELOPMENT FOR AD/ADRD. DR. LONGO WAS THE PRIMARY REVIEWER AND DR. H. ANG WAS SECONDARY. DR. LONG OH, IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>DR. LONGO: SURE. THIS IS A UH2/UH3 MODEL TO DEVELOP AI APPROACHES FOR PRE-CLINICAL DRUG DEVELOPMENT. SO WHAT THIS TECHNOLOGY ALLOWS ONE TO DO IS DESIGN SMALL MOLECULES OR OTHER ENTITIES IN A MORE EFFICIENT WAY LIKELY EFFECTIVE WAY, TO DESIGN THEM TO INTERACT WITH GIVEN TARGET THAT MIGHT BENEFIT ALZHEIMER'S AND RELATED AREAS. SO, THIS IS A VERY TIMELY PROPOSAL FOR TWO REASONS, ONE IS THE CAPABILITIES IN AI FOR DRUG AND THERAPEUTIC DESIGN CONTINUING TO ACCELERATE AND BECOME MORE AND MORE EFFECTIVE AND CRITICAL TOOLS IN THE FIELD AT THIS POINT. NUMBER 2, OTHER NIA PROGRAMS, INCLUDINGASM AD, TREAT AD, ARE BEING SUCCESSFUL IN FINDING NOVEL TARGETS, NOVEL NON AMYLOID TARGETS THAT MIGHT BE OF BENEFIT. AND SO THIS APPROACH WILL ALLOW THESE TARGETS TO BE MORE QUICKLY EFFICIENTLY EFFECTIVELY ADDRESSED. IT'S APPROPRIATELY STAGE PROGRAMS WHERE THE APPROACHES ARE DEVELOPED IN THE UH2 AND THEN APPLIED EITHER CONCEPTUALLY OR WITH EXPERIMENTS IN THE UH3. SO I THINK WE THOUGHT THAT THIS WOULD DEVELOP INTO ENHANCING THE DEVELOPMENT OF THERAPEUTICS. >>GREAT. THANK YOU VERY MUCH. THE NEXT CONCEPT THAT WE CONSIDERED WAS SMALL RESEARCH GRANT PROGRAM FOR THE NEXT GENERATION OF RESEARCHERS IN AD/ADRD RESEARCH. DR. SNYDER WAS THE PRIMARY REVIEWER AND DR. MANLY WAS THE SECONDARY. DR. SNYDER IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>DR. SNYDER: THANK YOU MONICA AND LET ME KNOW IF YOU CAN'T HEAR ME. >>YOU SOUND PERFECT NOW. THANK YOU. >>GOOD. I CHANGED MY MICROPHONE. SO THE CONCEPT PROPOSED HERE IS A RE-ISSUANCE OF THE NEXT GENERATION PROGRAM. THE OVERALL GOAL OF THIS FOA IS RESEARCH IN VARIOUS MEETING FOR SCIENTIFIC INVESTIGATIONS FOCUSING ON PREVENTION, DIAGNOSIS AND TREATMENT. SO BROAD RANGE OF TOPICS. THE MAIN THEME IS TO ENCOURAGE THE NEXT GENERATION AS IN THE TITLE,FUL RESEARCHERS THEIR RESEARCH ACADEMIC CAREERS IN ADADRD. ANOTHER AIM IS LIKE NOVEL RESEARCH IDEAS IN OTHER FIELDS. SO THIS IS A RE-ISSUANCE BUT IT'S CHANGED. INSTEAD OF BEING MULTIPLE DIFFERENT MECHANISMS, SMALL GRANTER OPPORTUNITIES, IT'S ALL WITHIN NOW RFA AND THE GOAL IS TO GET -- ALSO CHANGED THAT IT IS REALLY TO GET NEW INVESTIGATORS. OR INVESTIGATORS WHO HAVE NOT HAD RO1 FUNDING. SO THAT'S A TAKE FROM THE ORIGINAL. THE ORIGINAL WAS VERY PRODUCTIVE AND DID QUITE WELL, HOWEVER, THEY DID WANT TO KIND OF REFOCUS ON THIS NEW NEXT GENERATION BECAUSE SOME OF THESE PEOPLE WERE MORE SENIOR. SO THEY ARE EXPECTING NOW THAT ABOUT HALF WILL BE EARLY-STAGE INVESTIGATORS TO ACHIEVE THE GOAL OF FOSTERING NEW DEVELOPMENT. AGAIN SUCH THAT THEY CAN'T HAVE A SEPARATE STUDY SECTION BUT THEY WILL HAVE SET ASIDE FUNDS FOR THESE RESEARCH GRANTS. SO WE'RE REALLY ENTHUSIASTIC ABOUT THIS. ENTRY OF PROMISING NEW INVESTIGATORS IN THE AGING RESEARCH, ENCOURAGE THE ESTABLISHED INVESTIGATORS TO ENTER NEW AREAS OF AGING RESEARCH AND GOING TO BE USED AS PILOTS THAT HOPEFULLY WILL LEAD TO RO1s FOCUSED ON AGING AND SIGNIFICANT AGING RESEARCH. SO WE WERE HIGHLY SUPPORTIVE OF THIS. >>THANK YOU VERY MUCH. SO THE NEXT ONE THAT WE CONSIDERED IS SEAMLESS EARLY STAGE CLINICAL DRUG DEVELOPMENT FOR NOVEL THERAPEUTIC AGENTS FOR THE SPECTRUM OF ALZHEIMER'S AND ALZHEIMER'S-RELATED DEMENTIAS. THE PRIMARY REVIEWER WAS DR. VANELEDIC AND THE SECONDARY WAS DR. LONGO. IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>YES, THANK YOU. SO THIS CONCEPT PROPOSES A NEW UG3/UH3 PHASED AWARD INITIATIVE AIMED AT STREAMLINING EARLY STAGE EVALUATION OF PROMISING NOVEL PHARMACOLOGICAL INTERVENTIONS. AND THE WAY THEY ARE GOING TO DO THIS IS TO FUND PHASE I CLINICAL TRIALS FIRST AND THEN SEAMLESSLY MOVE TO PHASE I B2A TRIALS BASED ON PRE-SPECIFIED GO-NO-GO SAFETY AND TOLERABILITY CRITERIA IN PHASE I. THE THERAPEUTIC CANDIDATES MUST TARGET NON AMYLOID AND CAN BE TESTED IN INDIVIDUALS ACROSS ANY STAGE OF DISEASE PROGRESSION. AND THERE ARE ALSO REQUIREMENTS FOR DIVERSITY WITHIN THE TRIAL COHORTS AND DATA AND BIOSAMPLE SHARING. WE THOUGHT THIS WAS A VERY IMPORTANT INITIATIVE BECAUSE IT WILL ALLOW TIMELY TESTING AND PRIORITIZATION OF PROMISING INTERVENTIONS WITHOUT THE USUAL SIGNIFICANT FUNDING DELAY BETWEEN CONCLUSION OF PHASE I A TRIALS AND THE START OF PHASE 1B2A STUDIES. THE REQUIREMENT FOR NON AMYLOID NON TAU INTERVENTIONS WAS GOOD BECAUSE THERE IS ALREADY SIGNIFICANT EFFORT BY PHARMA AND BIOTECH TO TARGET AMYLOID AND TAU AND THERE ARE SO MANY OTHER POTENTIAL DISEASE MECHANISMS THAT NEED TO BE EXAMINED AND PRIORITIZED EITHER MOVED FORWARD OR MOVED OFF. ALSO, FINALLY THE REQUIREMENTS FOR COHORT DIVERSITY AND DATA SAMPLE SHARING ARE CRITICAL TO ENSURE BROAD APPLICABILITY AT THE RESULTS. SO WE WERE VERY HIGHLY SUPPORTIVE OF THIS CONCEPT. >>THANK YOU VERY MUCH FOR THAT SUMMARY. WE WILL MOVE ON TO THE DIVISION OF EXTRAMURAL ACTIVITY AND OFFICE OF COMMUNICATIONS AND PUBLIC LIASON. WHO PRESENTED TWO CONCEPTS, NATIONAL IN INSTITUTE ON THE AGING CLINICAL SUPPORT SERVICES. PRIMARY REVIEWER WAS DR. GREENSPAN. IF YOU COULD SUMMARIZE FOR US. >>THANK YOU, MONICA. SO THE NIA HAS A RESPONSIBILITY TO MANAGE CLINICAL RESEARCH GRANTS AND THE RESPONSIBILITY HAS BEEN INCREASING EXPONENTIALLY. AND A REPORT IN 2021 FOUND THERE WAS BROAD SUPPORT FOR SOME KIND OF CENTRALIZED CLINICAL RESEARCH MANAGEMENT ACROSS THE INSTITUTE. THE PROPOSAL WILL PROVIDE CONTRACT TO EXPAND, CENTRALIZE AND INTEGRATE ADMINISTRATIVE REGULATORY, STATISTICAL SUPPORT TO MANAGE NIA CLINICAL RESEARCH STUDIES. THIS WILL STREAMLINE THE SERVICE AND ENSURE CONSISTENCY ACROSS THE INSTITUTE AND MOREOVER, IT WILL REDUCE THE BURDEN ON BOTH THE STAFF AND ON INVESTIGATORS. SO THE SPECIFIC TASKS WILL INCLUDE REGULATORY OVERSIGHT AND SUPPORT, FOR EXAMPLE HELP WITH IDENTIFYING A DATEY SAFETY MONITORING BOARD, RISK ASSESSMENT, TRACKING COMPLIANCE, TRACKING TRAINING FOR GOOD CLINICAL PRACTICE, MAKING SURE THAT THEY ARE MAINTAINING A DATABASE, HELPING WITH RECRUITMENT AND RETENTION, REALLY TO HELP IDENTIFY BEST PRACTICES AND PARTICULARLY MAKING SURE THAT THEY ARE ENROLLING UNDER REPRESENTED POPULATIONS. ASSURING A QUALITY ASSURANCE FOR CLINICAL RESEARCH OPERATIONS. PROVIDING STATISTICAL AND METHODOLOGICAL CONSULTATIONS, MAINLY FOR PROGRAM AND TRAINING THE STAFF IN CLINICAL REACH PROCEDURES. THERE WAS A LOT OF ENTHUSIASM FOR THIS. THERE WAS A NEED FOR NIA TO OVERSEE A WIDE RANGE OF CLINICAL TRIALS THAT INCLUDE MANY COMPLICATION AND -- COMPLICATED AND DIVERSE POPULATIONS. AND THIS IS EXPANDED WITH THE INCREASE IN AD AND ADRD RESEARCH CLINICAL TRIALS. WE FELT THAT THIS WOULD BE A GREAT BENEFIT FOR BOTH NIA AND INVESTIGATORS TO SUPPORT THE OVERALL PROGRAM. SO THERE WAS A LOT OF ENTHUSIASM FOR THIS. >>GREAT. THANK YOU VERY MUCH. AND OUR FINAL IS NIA INFORMATION RESOURCE CENTERS. DR. SNYDER WAS THE PRIMARY REVIEWER AND DR. HUMBLE WAS THE SECONDARY REVIEWER. D. SNYDER IF YOU COULD SUMMARIZE THE DISCUSSION FOR US. >>DR. SNYDER: THIS IS FOR THE RENEWAL OF A CONTRACT WHICH IS ONGOING SINCE 1990. BROADLY TO THE PUBLIC, HEALTH CARE PROFESSIONALS AND SCIENTIFIC COMMUNITY. IT PROVIDES COMMUNICATION SUPPORT TO ADVANCE NIA'S DISSEMINATION OF INFORMATION. IT'S A SMALL ACCIDENT SET ASIDE -- SMALL BUSINESS SET ASIDE AND TWO INFORMATION RESOURCE CENTERS. THERE IS THE CONGRESSIONALLY MANDATED -- WHICH IS RELATED TO EDUCATIONAL REFERRALS AND THE NIA INFORMATION RESOURCE CENTER. SO THE CONTRACT PROVIDES PUBLIC INQUIRY RESPONSE, WEBSITE DESIGN, PUBLIC DEVELOPMENT -- PUBLICATION DEVELOPMENT OF PRINTING, WAREHOUSING EDITORIAL SCIENCE WRITING, DATABASE DEVELOPMENT, COMMUNICATION RESEARCH. SO ALSO CONFERENCE SUPPORT AND OTHER COMMUNICATION SUPPORT SERVICES. SO IT DOES QUITE A BIT. WE WERE VERY ENTHUSIASTIC ABOUT RENEWING THIS CONTRACT BOTH DR. HUMBLE AND MYSELF HAD A FEW QUESTIONS. I THINK DR. HUMBLE POSED GREAT QUOS REGARDING UTILIZATION AND THEY WERE ABLE TO COME BACK WITH REALLY THE GREAT JOB THAT THEY ARE DOING WITH REACHING OUT TO PEOPLE AND MAKING THEM AWARE OF WHAT IS HAPPENING IN THE ALZHEIMER'S FIELD. AND JUST GREAT PROGRESS WITH REACHING OUT NOT ONLY TO THE PUBLIC BUT ALSO TO PHYSICIANS. SO, IT APPEARS THAT THAT THERE REALLY ARE ON TRACK TO CONTINUE GREAT WORK AND REALLY HIGHLY SUPPORTIVE OF CONTINUING THE SUPPORT INITIATIVE. >>GREAT. THANK YOU VERY MUCH VERY, VERY MUCH. SO, THAT CONCLUDES THE SUMMARY OF THE CONCEPTS THAT WE CONSIDERED YESTERDAY. AT THIS POINT, I'LL ASK FOR MOTION TO VOTE UNBLOCK FOR APPROVAL OF THE RECOMMENDED CONCEPTS WITH A VERY TINY ASTERISK TO REMIND YOU THAT WE ASK FOR A TRANSIENT DEFERRAL FOR THE DEMENTIA CARE COORDINATION PROPOSAL PENDING ADDITION OF A LITTLE BIT MORE INFORMATION AND REFINEMENT. BUT THAT WAS THE SUMMARY OF THE RECOMMENDATION THAT I WOULD LIKE SOMEONE TO GO FOR THAT MOTION. >>SO MOVED. >>AND SO SECOND? >>SECOND. >>OKAY. ANY -- ALL THOSE IN FAVOR? >>AYE. >>ANY OPPOSED? NOT SEEING ANY. THE COUNCIL ENTHUSIASTICALLY VOTES TO MOVE THESE CONCEPTS FORWARD AND THANKS PROGRAM FOR ALL THEIR HARD WORK. AND I THANK ALL THE MEMBERS OF COUNCIL FOR THEIR VERY NICE CONCISE SUMMARIES YESTERDAY AND TODAY AND GREAT DISCUSSION. SO THANK YOU. >>THANK YOU VERY MUCH, MONICA. JUST ALSO WANT TO REITERATE AND SEND MY THANKS TO ALL OUR COUNCIL MEMBERS FOR THEIR CONCEPTS AND THE PROGRAM PEOPLE FOR ALL THEIR HARD WORK PUTTING INTO THESE CONCEPTS. JUST TO REMIND THE PUBLIC, THESE CONCEPTS WILL BE POSTED ON OUR WEB PAGE AS OUTLINED AND BY DR. HOEDINGS SLIDE. THERE IS A LINK FOR THESE CONCEPTS AND PROBABLY WITHIN THE WEEK, THESE WILL BE ALL LISTED ON OUR WEBSITE. SO TAKE ADVANTAGE OF THE AFFECT THAT THESE ARE POTENTIAL FUNDING OPPORTUNITIES IN THE NEAR FUTURE AND START THINKING ABOUT APPLICATIONS. I WANT TO THANK DR. MONICA DRISCOL FOR BEING THE CHAIR OVER THE PAST YEARS OF OUR WORKING GROUP. MONICA WAS REALLY A PLEASURE WORKING WITH YOU ALL THESE YEARS, ESPECIALLY THROUGH OUR COVID YEARS AND BEING ON LINE INSTEAD OF IN PERSON ALL THIS TIME. SO WE THANK YOU VERY MUCH. AND WE ALSO WELCOME DR. GREENSPAN AS OUR NEW CHAIR OF THE WORKING GROUP. >>AND THANK YOU ALL SO MUCH. A COMPLETE HONOR AND PRIVILEGE TO BE ABLE TO MEET ALL OF YOU AND HEAR ALL OF THIS EXCITING -- ALL THESE EXCITING THINGS COMING UP FOR NIA. IT'S FANTASTIC. SO THANK YOU. >>KEN, SORRY, CAN I JUST ASK -- I KNOW THAT THE -- THIS ATTENDANCE OF THIS MEETING WAS PUT ON AN AGENDA FOR THE DIRECTORS YESTERDAY. AND HOPEFULLY THEY PASSED IT ON TO SOME OF THEIR GRANTEES. AND WHAT I GET ASKED A LOT IS, SO YOU DID THESE CONCEPT CLEARANCES, NOW WHAT? WONDERING IF -- I KNOW YOU JUST SAID THAT THESE ARE GOING TO BE PUT ON THE WEBSITE AND YOU GAVE THE DIRECTIONS HOW TO DO THAT. AND YOU SAID, THIS IS SORT OF A NOTICE TO THE RESEARCH COMMUNITY ABOUT WHAT MIGHT BE OUT THERE. AND SO PEOPLE MIGHT WANT TO START THINKING ABOUT IT. BUT, I'M WONDERING IF YOU COULD GIVE A LITTLE MORE DETAIL. SHOULD RESEARCHERS POTENTIALLY TALK WITH PROGRAM OFFICERS ABOUT IT? LIKE MAYBE YOU CAN EXPAND A LITTLE BIT ON WHAT IT MEANS FOR CONCEPT CLEARANCE TO BE OUT THERE AND WHAT RESEARCHERS MIGHT DO TO PREPARE. >>OKAY. GREAT QUESTION, JEN. HAPPY TO ADDRESS THAT. SO NOW THAT THESE CONCEPTS HAVE BEEN APPROVED, THEY ARE IN THE PUBLIC DOMAIN TOO, AND WE ENCOURAGE EVERYONE TO START DISSEMINATING THIS INFORMATION TO EVERYONE AND START THINKING ABOUT POTENTIAL PROJECTS AND BUILDING TEAMS, ET CETERA. BUT YES, PLEASE ON THE WEBSITE, EACH OF THESE CONCEPTS WILL HAVE THE PROGRAM OFFICER WHO IS IN CHARGE OF EACH OF THESE CONCEPTS LINKED TO EACH OF THE CONCEPTS. SO YOU ABSOLUTELY CAN GET IN TOUCH WITH THEM, START DISCUSSING YOUR IDEAS, ET CET ET CETERA. HOWEVER, ONE OF THE CAVEATS IS, THERE IS REALLY NO GUARANTEE THAT A FUNDING OPPORTUNITY WILL BE GENERATED FROM THESE CONCEPTS. IT REALLY DOES DEPEND ON OUR FISCAL SITUATION THROUGHOUT THE YEAR. WE NEVER KNOW. DIFFERENT PRIORITIES MAYBE COME IN. WE MIGHT HAVE TO SHIFT FOCUSES, ET CETERA. SO THERE ARE POTENTIALS. BUT, YOU KNOW, THERE IS A VERY HIGH LIKELIHOOD THAT THESE WILL BE TURNED INTO FUNDING OPPORTUNITIES AS WITH HISTORICAL KNOWLEDGE OF OUR PAST PRACTICES, ALL THE CONCEPTS HAVE BEEN IN THE PAST TURNED INTO FUNDING OPPORTUNITY ANNOUNCEMENTS. UNLESS THERE HAVE BEEN ISSUES WITH COUNCIL AND WE DECIDED NOT TO MOVE THEM FORWARD. SO, YES, PLEASE GET IN CONTACT WITH THE PROGRAM OFFICERS. YES, DEFINITELY START THINKING ABOUT THE POTENTIAL IDEAS FOR APPLICATIONS IN THE FUTURE AND KEEP THAT CONVERSATION GOING. ALL RIGHT. WE HAD TWO SPEAKERS COMING UP NEXT. BUT I WOULD LIKE TO GIVE OUR COUNCIL, EVERYONE A 5-MINUTE BREAK AT THIS POINT, TO JUST TO HAVE A SHORT BREAK BEFORE WE START OUR TWO SPEAKERS. SO IF EVERYONE COULD JUST MUTE AND STOP THEIR VIDEO, WE'LL TAKE A 5-MINUTE BREAK AND BE BACK TO HEAR OUR FIRST SPEAKER WHO IS DR. ERIC ORWOLL. >>GOOD AFTERNOON, EVERYONE. IT'S MY GREAT PLEASURE TO INTRODUCE DR. ERIC ORWOLL, HE IS PROFESSOR OF MEDICINE IN THE DIVISION OF ENDOCRINOLOGY DIABETES AND CLINICAL NUTRITION AT OREGON HEALTH AND SCIENCE UNIVERSITY. HE IS AN INTERNATIONALLY RECOGNIZED EXPERT IN THE AREA OF AGE-RELATED CHANGES AND MUSCULOSKELETAL HEALTH INCLUDING SARKO PENIA. DR. ERIC ORWOLL HAS BEEN THE PI OF MANY NIH-SUPPORTED STUDIES AND SO TODAY, WE ARE GOING TO HEAR ABOUT THE WIDE RANGING IMPACT OF THE STUDY OF OSTEOPRIORITYIC FRACTURES IN MEN STUDY OR Mr. OS ON AGING RESEARCH. INITIATED IN 1999 AND LED BY DR. ERIC ORWOLL, Mr. OS WAS ONE OF THE FIRST PROSPECTIVE STUDY OF RISK FACTORS IN OLDER MEN AND AS THE COHORT TRANSITIONED TO OLDER AGES, ITS AIMS EXPANDED TO ADDRESS IMPORTANT GERIATRIC OUTCOMES SUCH AS SLEEP, FALLS, PHYSICAL PERFORMANCE AND FUNCTIONAL DECLINE. MORE RECENTLY, THE WEALTH OF EXISTING LONGITUDINAL TYPIC DATA FROM THE COHORT, THE GWAS DATA AND BIOSPECIMEN COLLECTION HAVE BEEN LEVERAGED FOR STUDIES OF EXCEPTIONAL LONGEVITY AND HEALTH SPAN. I'D LIKE TO THANK DR. ERIC ORWOLL FOR JOINING US TODAY AND THE TITLE OF HIS TALK IS Mr. OS, A 20+ YEAR STUDY OF AGING IN OLDER MEN. ERIC? >>ERIC ORWOLL: THANK YOU VERY MUCH. LET ME SEE IF I CAN SHARE MY SCREEN. SO PROGRAM ASKED THAT I REVIEW SOME OF THE PROGRESS MADE WITH Mr. OS, WHICH IS A LONGITUDINAL STUDY OF AGING IN OLDER MEN. I'D START WITH THE BASIC STUDY DESIGN, HIGHLIGHT SOME OF THE PROGRESS MADE OVER THE COURSE OF THE STUDY AND FINISH WITH SOME RECENT FINDINGS IN SEVERAL AREAS, INCLUDING SARK PENIA AND PROTEOMICS AND BIKE ROW BIOME. Mr. OS WAS DESIGNED PRIMARILY TO UNDERSTAND MUSCULOSKELETAL AGING, OSTEOPOROSIS AND FRACTURE BUT COVERED BROAD AREAS OF AGING AS WELL. IT STARTED WITH THE RECRUITMENT OF ABOUT 6000 MEN OVER THE AGE OF 65 AT SIX CLINICAL SITES ACROSS THE U.S. THE MEAN AGE AT BASELINE WAS 74 YEARS WITH A WIDE RANGE. THERE WERE FEW EXCLUSION CRITERIA SO THE COHORT IS FAIRLY REPRESENTATIVE OF MEN AT THAT AGE, ALTHOUGH SOMEWHAT MORE HEALTHY THAN RANDOMLY SELECTED COHORTS LIKE NHANES. AT BASELINE, MEN WERE PHENOTYPED WITH EMPHASIS ON MUSCULOSKELETAL TRAITS AND SERUM, URINE, DNA AND IMAGE LIBRARY. PARTICIPANTS HAVE BEEN FOLLOWED REGULARLY WITH QUESTIONNAIRES EVERY FOUR MONTHS AND REGULAR IN-CLINIC EVALUATIONS WHERE ADDITIONAL PHENOTYPING AND SPECIMEN COLLECTION. RETENTION HAS BEEN OUTSTANDING WITH CONTENT MAINTAINED WITH GREATER THAN 95% OF SURVIVORS AND Mr. OS WAS EXPANDED EARLY ON TO INCLUDE 3000 MEN IN SWEDEN AND 2000 MEN IN HONG KONG. OVER THE YEARS, Mr. OS HAS BEEN VERY PRODUCTIVE. MANY, MANY INVESTIGATORS HAVE BEEN INVOLVED. MORE THAN 1000 ANALYSIS PLANS HAVE BEEN ENACTED. 500 PEER-REVIEWED PUP INDICATIONS HAVE RESULTED AND AT PRESENT, THERE HAVE BEEN 89 INDEPENDENTLY-FUNDED ANCILLARY STUDIES IN ADDITION TO THE NIH SUPPORT FOR THE PARENT STUDY. OF COURSE THE COHORT HAS AGED OVER THE 20 YEARS OF FOLLOW-UP SO THE MEAN AGE OF SURVIVORS ON THE LEFT IS NOW MORE THAN 90 AND ON THE RIGHT, MORE THAN 80% OF THE PARTICIPANTS HAVE DIED THUS Mr. OS NOW IS A COHORT OF A BIT LESS THAN 1000 VERY ELDERLY MEN, WHICH CONTINUES TO OFFER UNIQUE ONGOING RESEARCH OPPORTUNITIES. WE ARE JUST IN THE MIDDLE OF THE LATEST CYCLE OF NIA FUNDING. Mr. OS CONTRIBUTED TO A VARIETY OF ISSUES RELATED TO AGING. IT'S BEEN A MAJOR SOURCE OF KNOWLEDGE ABOUT MUSCULOSKELETAL AGING LIKE OST YORE PROSIS AND SARCOPENIA. BUT ALSO ACTIVE IN A NUMBER OF OTHER AREAS AS ARE LISTED. ON THE RIGHT ARE SHOWING SOME OF THE PARADIGM CHANGING WORK WHICH Mr. OS HAS BEEN A MAJOR FACTOR. A UNIQUE CONTRIBUTION OF Mr. OS IS THE COLLABORATION WITH THE STUDY OF OSTEOFRACTURES WHICH IS A SIMILAR NIA-FUNDED STUDY OF ABOUT 9000 WOMEN OF THE SAME AGE RANGE AS Mr. OS. INTENTION ALLEY, Mr. OS WAS DESIGNED TO INCLUDE PHENOTYPIC MEASURES THAT WERE IN MOST CASES IDENTICAL TO THOSE IN THE SOF, ENABLING A VARIETY OF SEX COMPARISONS. FOR INSTANCE HERE ON THE LEFT, COMBINED ANALYSIS OF Mr. OS AND SOF REVEALED THAT BOTH LOW TRAUMA AND HIGH TRAUMA FRACTURES HAVE THE SAME RELATIONSHIP TO LOW BONE MINERAL DENSITY. FINDING THAT SOME FUNDAMENTALLY CHANGED HOW WE CONSIDER FRACTURES IN OLDER PEOPLE BOTH CLINICALLY AND IN RESEARCH SETTINGS. ON THE RIGHT, A SIMILAR ANALYSIS IN SO. AND Mr. OS SHOWS THAT FRACTURES IN OLDER MEN ARE MUCH MORE LIKELY TO BE RELATED TO HIGH ACTIVITY AND TRAUMA COMPARED TO WOMEN, FINDING WHICH INFLUENCES IMPORTANT PUBLIC HEALTH PREVENTIVE STRATEGIES. Mr. OS HAS BEEN THE PLATFORM FOR THE DEVELOPMENT OF IMPORTANT NEW METHODS FOR EVALUATING MUSCULOSKELETAL HEALTH. ONE EXAMPLE IS THE USE OF CENTRAL QCT IN FINITE ELEMENT ANALYSIS OF BIOMECHANICAL BONE STRENGTH AS AN ASSESSMENT OF FRACTURE RISK. ANOTHER MORE RECENT DEVELOPMENT IS NOVEL WAY TO MEASURE MUSCLE MASS. THE SUMMARY OF THOSE RESULTS ARE SHOWN HERE. BASICALLY, MUSCLE MASS MOST OFTEN HAVE BEEN ESTIMATED BY USING DEXABASED MEASURES OF LIEN MASS, AN APPROACH THAT IS FUNDAMENTALLY FLAWED BECAUSE LIEN MASS IS MADE UP OF A VARIETY OF TISSUES OTHER THAN MUSCLE. TO REMEDY THIS, BILL EVANS AND MARK HELLERSTEIN AT BERKLEY TOOK ADVANTAGE OF THE FACT THAT CREATINE IS VIRTUALLY ENTIRELY LOCALIZED IN CONTRACT ON MUSCLE AND DEVELOPED AN APPROACH THAT USES D3 CREATINE TO MEASURE THE CREATINE POOL AND ENHANCE ACCURATE LEMUSEL MASS IN-VIVO. AND THIS TECHNIQUE WAS APPLIED INITIALLY ON A LARGE-SCALE IN Mr. OS AND WE USED IT TO INVESTIGATE A VARIETY OF QUESTIONS. AND THE UPPER MIDDLE PANEL, I HAVE ILLUSTRATED HOW D3 CREATINE MUSCLE MASS AND DEXAMEASURES COMPARE AS A PERCENT OF BODY WEIGHT IN ABOUT 1400 Mr. OS MEN. MUSCLE MASS BY D3 CREATINE IS IN DARK BLUE WITH MEN ARRAYED ACROSS THE AXIS HERE, HIGH MUSCLE MASS ON THE LEFT, LOWER MUSCLE MASS ON THE RIGHT. DEXAMESS BASED MEASURES ARE SHOWN, INCLUDING BONE MASS IN BLACK AT THE TOP, FAT MASS AND TOTAL LEAN MASS. OBVIOUSLY D3 CREATINE MUSCLE MASS IS VERY DIFFERENT THAN TOTAL LEAN MASS AND POORLY CORRELATED WITH IT. AND SHOWN IN THE YELLOW DOTS AND IN THE SCATTER PLOT IN THE UPPER RIGHT, IS SHOWN THAT D3 CREATINE MUSCLE MASS IN LEAN MASS ARE NOT CORRELATED. BASICALLY THEY ARE QUITE DIFFERENT MEASURES. IN THE BOTTOM GRAPHS, ARE THE RELATIONSHIP OF WALKING SPEED AND LOWER EXTREMITY POWER TO QUARTILES OF D3 CREATINE MUSCLE MASS IN THE OPEN BARS. AND QUARTILES OF LEAN MASS IN THE GRAY BARS. CLEARLY A MEASURE -- THESE MEASURES OF PHYSICAL FUNCTION ARE MUCH MORE RELATED TO D3 CREATINE MUSCLE MASS THANG TO LEAN MASS. WE HAVE SHOWN THERE IS SIMILAR RELATIONSHIPS THAT D3 CREATINE MUSCLE MASS WITH FRACTURES, DISABILITY, FRAILTY AND MORTALITY ED. BASICALLY THESE MEASURES OF MUSCLE MASS HAVE VERY MUCH CHANGED THE FIELD OF SARCOPENIA RESEARCH. D3 CREATINE MEASURES HAVE ALSO ALLOWED US TO RECONSIDER THE CONCEPT OF MUSCLE QUALITY. IT'S LONG BEEN KNOWN THAT MUSCLE PERFORMANCE DECLINES WITH AGE. IN THE ABSENCE OF MAJOR CHANGES IN LEAN MASS, A FINDING THAT HAS BEEN INTERPRETED AS EVIDENCE THAT MUSCLE QUALITY DECLINES INDEPENDENT OF MUSCLE MASS. HOWEVER, WHEREAS MEASURES OF LEAN MASS CHANGE LITTLE OVER TIME IN Mr. OS, AS IS SHOWN BY THE LEFT HAND BARS ON THE GRAPH, D3 CREATINE MUSCLE MASS IN THE MIDDLE BARS DECLINES QUICKLY AND IN PROPORTION TO THE DECLINES IN PERFORMANCE MEASURES, WALKING SPEED IN THE RIGHT BARS. THUS CONTRARY TO PREVIOUS BELIEF, THIS FINDING SUGGESTS THE PRIMARY IMPORTANCE OF CHANGE IN MUSCLE MASS IN DETERMINING THE DECLINE IN PHYSICAL PERFORMANCE WITH AGE. THIS DOESN'T MEAN THAT MUSCLE QUALITY ISN'T IMPORTANT. AND THE AVAILABILITY OF ACCURATE MUSCLE MASS MEASUREMENTS WITH D3 CREATINE ALLOWS US TO MORE EFFECTIVELY CALIBRATE THE CONTRIBUTIONS OF MUSCLE MASS VERSUS QUALITY. FOR INSTANCE, ON THE RIGHT, IS SHOWN THE PERCENT OF Mr. OS MEN WITH ABNORMAL WALKING SPEED ON THE Y AXIS. AS A FUNCTION OF QUARTILES OF BOTH D3, CREATINE MUSSEL MASS ON THE RIGHT. AND TO THE MUSCLE DENSITY BY CT ON THE BOTTOM. LOW MUSCLE DENSITY BY QCT IS A REFLECTION OF MUSCLE FAT ACCUMULATION WHICH IS IT LINKED TO MUSCLE QUALITY AND PERFORMANCE. HERE, ITS CLEAR THAT THE MEN WITH THE LOWEST MUSCLE MASS AND THE LOWEST US MUSCLE DENSITY HAVE THE WORST WALKING SPEED. AND THAT BOTH MEASURES CONTRIBUTE INDEPENDENTLY TO WALKING SPEED. WALKING SPEED IS SHOWN HERE BUT WE FOUND SIMILAR RELATIONSHIPS WITH OTHER MEASURES OF PERFORMANCE AS WELL AS DISABILITY AND MORTALITY. THIS IS ANOTHER EXAMPLE OF HOW Mr. OS RECONFIGURING SARCOPENIA RESEARCH. THE ABILITY OF THE Mr. OS BIOBANK WITH LONGITUDINAL PHENOTYPING MAKES POSSIBLE UNIQUE OPPORTUNITIES TO EXAMINE THE BIOLOGICAL UNDERPINNINGS OF AGING. ONE DIRECTION WE HAVE TAKEN IS TO USE LARGE-SCALE PROTEOMICS. IN ABOUT 2015, WE UNDERTOOK WHAT WAS AT THAT POINT THE LARGEST POPULATION BASED PROTEOMICS EXPERIMENT. WE USED A NOVEL HIGH-THROUGHPUT MASS SPEC BASED PROTEOMICS APPROACH DEVELOPED AT SPECIFIC NORTHWEST NATIONAL LABS TO MEASURE THE ABUNDANCE OF SERUM PROTEINS IN ABOUT 2500 MEN AT BASELINE AND EXAMINED THEIR ASSOCIATIONS WITH INCIDENT LONGEVITY, DEFINED THOSE REACHING AT LEAST THE 90th PERCENTILE OF SURVIVAL DURING 15 YEARS OF FOLLOW-UP FOLLOWING BASELINE. WE IDENTIFIED A GROUP OF PROTEINS ASSOCIATED WITH LONGEVITY SHOWN IN THE VOLCANO PLOT. MOST OF THESE PROTEINS WERE LOWER ABUNDANCE IN THE LONG-LIVED MEN, COMPARED TO MEN WHO DIED EARLIER. WE MAPPED THESE PROTEINS TO BIOLOGICAL PATHWAYS AND MANY WERE RELATED TO INFLAMMATION. AS SHOWN IN THE TABLE ON THE RIGHT, THESE PROTEINS WERE ALSO ASSOCIATED WITH BETTER STATUS IN ADDITION TO LONGEVITY. IN A DIFFERENT TO LONGEVITY, WE EXAMINED ASSOCIATIONS OF SERUM PROTEINS WHERE OTHER PHENOTYPES, INCLUDING MORTALITY WITHIN FIVE YEARS OF BASELINE AND BONE LOSS FOLLOWING BASELINE. INTERESTINGLY, THERE WERE CONSIDERABLE OVERLAP IN THE PROTEINS ASSOCIATED WITH THE THREE PHENOTYPES AS IS SHOWN. AND PERHAPS NOT UNEXPECTEDLY, AS SHOWN IN THE HEAT MAP, THE ASSOCIATIONS WITH MORTALITY AND BONE LOSS WERE IN THE OPPOSITE DIRECTION FROM THOSE WITH LONGEVITY. ADDITIONAL FINDINGS WAS THAT AS DEATH APPROACHED, THE ABUNDANCE OF THOSE PROTEINS ASSOCIATED WITH LONGEVITY, TENDED TO INCREASE ON THE LEFT AND TO REVERT TO LEVELS SEEN IN CONTROL MEN. THE PROTEINS NOT SOCIALED WITH LONGEVITY DID NOT CHANGE. THIS FINDING IF REPLICATED HAS OBVIOUS IMPLICATIONS FOR THE UNDERSTANDING OF THE BIOLOGY OF LONGEVITY AND MORTALITY. BUT ALSO THE UNDERSTANDING OF HOW PROTEOME CHANGES WILL IMPLEMENTS WE IDENTIFY BIOMARKERS OF IMPORTANT AGE-RELATED OUTCOMES. THESE PROTEOMICS CHANGES IN Mr. OS WERE AN IMPORTANT PART OF THE DESIGN OF THE CURRENT CYCLE OF THE LONGEVITY CONSORTIUM. THE LONGEVITY CONSORTIUM IS A LARGE NIA-FUNDED UNDERTAKING THAT HAS ANIMAL COHORT BASE AND COMPUTATIONAL PROJECTS. THERE ARE ALL UNDERSTANDING THE BIOLOGY OF LONGEVITY AND IDENTIFYING POSSIBLE INTERVENTION TO INCREASE HEALTH PROTEOMICS IS A IMPORTANT PART OF THE WORK AND MASS SPEC PROTEOMICS IS BEING DONE ON SERUM OBTAINED FROM FOUR COHORTS, Mr. O16789, SOF, HEALTH AB R AND CHS -- Mr. OS. TO COMPARE LONG-LIVED INDIVIDUALS TO CONTROLS. METABOLOMICS IS ALSO BEING DONE AND SYSTEMS APPROACHES ARE BEING USED TO ANALYZE THE COMBINED DATA PRELIMINARY ANALYSIS OF THE PROTEOMICS FINDINGS LOOKS LIKE TWO-THIRDS OF THE PROTEINS THAT WE PREVIOUSLY FOUND TO BE ASSOCIATED WITH LONGEVITY IN Mr. OS ARE ALSO ASSOCIATED IN COMBINED COHORTS AND WE ARE ONCE AGAIN SEEING THE PREVIOUSLY-NOTED CHANGES ASSOCIATED WITH IMPENDING DEATH. WE HOPE THESE STUDIES WILL CONSIDERABLY INCREASE OUR UNDERSTANDING OF THE BIOLOGY OF LONGEVITY INCREASE BIOMARKER DISCOVERY AND DESIGN INTERVENTIONS. FINALLY, THE IMPORTANCE OF A MICROBIOME TO HUMAN HEALTH HAS BECOME OBVIOUS BUT THERE IS LIMITED UNDERSTANDING OF HOW THE GUT MICROBIOME CHANGES THROUGHOUT ADULTHOOD. AND HOW THOSE CHANGES INFLUENCE HOST PHYSIOLOGY. ALMOST 10 YEARS AGO WE COLLECTED STOOL SAMPLES FROM ABOUT 1000 MEN IN Mr. OS AND UNDERTOOK 16 GENOTYPING. A NUMBER OF ANALYSIS HAVE BEEN PUBLISHED, INCLUDING THE ASSOCIATIONS OF THE MICROBIOME WITH THE MEASURES ON THE RIGHT. I'LL SPECIFICALLY MENTION ONE COLLABORATION WITH THE GROUP AT THE INSTITUTE FOR SYSTEMS BIOLOGY IN SEATTLE IN WHICH WE EXAMINED THE MICROBIOME AND AG AGING. THE CURRENT CONCEPT OF HOW THE GUT MICROBIOME REALITIES TO AGING AND HEALTH IS SHOWN THE LEFT. ESSENTIALLY AS AGING INCREASES, THOSE WHO AGE WELL PRESUMABLY HAS A LESSER ACCUMULATION OF DETRIMENTAL BACTERIAL SPECIES OR PATHOBIOMES. ACQUIRE MORE PROTECTEDDIVE SPECIES AND AS A RESULT, HAVE LESS INFLAMMATION AS ONE MAJOR RESULT. WE EXAMINED THIS ISSUE IN CONCERT WITH THE COHORT FROM SEATTLE, ABOUT 3600 ADULTS HEAVILY PHENOTYPED AND OF A BROAD AGE RANGE AND DATA FROM THE AMERICAN GUT PROJECT, ABOUT 1600 ADULTS WITH A BROAD AGE RANGE AS WELL. THE MAJOR FINDINGS OF OUR ANALYSIS WERE FIRST THAT INDIVIDUAL GUT MICROBIOMES BECAME INCREASING MORE UNIQUE TO EACH INDIVIDUAL WITH AGE STARTING IN MID TO LATE ADULTHOOD AS SHOWN ON THE LEFT. THE GRAY CURVE IS UNIQUENESS SCORE INCREASED WITH AGE AT THE BOTTOM AND IN THE HUMAN GUT PROJECT, ABOVE. THIS UNIQUENESS WAS POSITIVELY ASSOCIATED WITH MICROBIAL METABOLIC MARKERS PREVIOUSLY IMPLICATED IN IMMUNE REGULATION, INFLAMMATION, AGING AND LONGEVITY. INCLUDING A NUMBER OF END GOALS. SECOND UNIQUENESS WAS ASSOCIATED WITH MORE HEALTHY AGING. IN THE UPPER RIGHT GRAPH, THE RELATIVE ABUNDANCE OF ONE OF THE CORE TAX DECREASE WITH AGE IS PLOTTED WITH AGE IN Mr. OS. HEALTHY INDIVIDUALS ON THE LEFT SHOW A DECLINE IN THIS WHEREAS THIS PATTERN WAS ABSENT IN THOSE WHERE WORSE HEALTH. FINALLY IN THE OLDEST Mr. OS MEN RETENTIONFUL HIGH RELATIVE ABUNDANCES AND LOW GUT MICROBIOME UNIQUENESS. BOTH ASSOCIATED WITH SIGNIFICANTLY DECREASED SURVIVAL IN THE COURSE OF A FOUR-YEAR FOLLOW-UP. THE ASSOCIATION WITH UNIQUENESS TO MORTALITY IS SHOWN IN THE LOWER RIGHT. THE HYPOTHESES WE FORMED FROM THIS WORK ARE SHOWN HERE WITH HEALTHY AGING BEING ASSOCIATED WITH REDUCTIONS AND CORPS TAXA AND THE ACCUMULATION OF UNIQUE TAXA WITH ASSOCIATED METABOLIC CHANGES WHILE LESS HEALTHY AGING IS NOT. THIS IS OBVIOUSLY STILL A VERY INVESTIGATION SO THE STORY CONTINUES TO UNFOLD. THE MICROBIOME WORK IN Mr. OS HAD A MULTIPLIER EFFECT. Mr. OS ANALYSIS OF THE GUT MICROBIOME ASSOCIATIONS WITH BONE MASS AND STRUCTURE LED TO A FOLLOW ON RO1 IN A COLLABORATION BETWEEN Mr. OS AND FRAMINGHAM WHERE THERE ARE SHARED BONE PHENOTYPES AND AVAILABLE STOOL SPECIMENS. AS PART OF THAT COLLABORATION WE ARE LEVERAGING MORE IN-DEPTH MEHTA GENOME SEQUENCING AT THE BRODE TO DIG DEEPER INTO THE MICROBIOME BONE RELATIONSHIPS. AS WELL WITH THAT SHARED MEHTA GENOME DATA, RESEARCHING A NUMBER OF AREAS RELEVANT TO AGING SHOWN HERE ON THE RIGHT HAVE BEEN CATALYZED. FOR INSTANCE, THE AVAILABILITY OF THE ACCURATE D3 CREATINE MUSCLE MASS MEASURES MAKE MICROBIOME MUSCLE MASS ASSOCIATIONS A PARTICULARLY INTERESTING TARGET. ON THE LAST SLIDE I WANT TO ACKNOWLEDGE THE AMAZING CONTRIBUTIONS OF OUR PARTICIPANTS. MANY INVESTIGATORS HAVE CONTRIBUTED, PARTICULARLY THE CURRENT CO-PIs AND THE PIs OF THE CONTRIBUTING CENTERS AS WELL AS THE FUNDING FROM THE NIH THAT HAVE MADE ALL OF THIS POSSIBLE. THANK YOU VERY MUCH. >>TERRIFIC! THANK YOU DR. ERIC ORWOLL. GREAT PRESENTATION AND OVERVIEW IN EXPLAINING HOW THE VAST AMOUNT OF RESEARCH THAT WAS DONE IN THE Mr. OS COHORT. I'LL OPEN IT UP FOR QUESTIONS FROM OUR PANEL. SHELLY? >>HARRY, CONTHE GRATES. WHAT A TOUR DE FORCE AND WHAT A PRODUCTIVE COHORT THAT HAS MADE SUCH IMPORTANT DISCOVERIES. THE QUESTION I HAD RELATES TO THE APPLICATION OF D3 CREATINE IN AGING STUDIES. THE CREATINE CLEARANCE WOULD BE EXPECTED TO DECREASE WITH ADVANCING AGE AND DUE TO OTHER INCREASING PREVALENCE OF KIDNEY DISEASE WITH ADVANCING AGE. HOW MIGHT THAT EFFECT CREATINE CLEARANCE AND THE ESTIMATES OF SKELETAL MUSCLE MASS BASED ON D3 CREATINE DIPOLLUTION? >>GREAT QUESTION. OBVIOUSLY THERE ARE A NUMBER OF ELEMENTS OF CREATINE BIOLOGY THAT HAVE TO BE TAKEN INTO ACCOUNT HERE. ONE BEING RENAL FUNCTION. AND WE HAVE LOOKED THAT PRETTY CAREFULLY AND IT TURNS OUT THAT CHANGES IN RENAL FUNCTION DON'T MAKE MUCH DIFFERENCE PRIMARILY BECAUSE WHAT YOU'RE LOOKING AT HERE, THE ENDPOINT IS CREATINE RATIO TO UNLABELED CREATINE. SO THE CREATININE FUNCTION REALLY DOESN'T PLAY A PART SINCE YOU'RE LOOKING AT THE RATIO. AND THE LABELED CREATINE AND THE UNLABELED CREATINE ARE HANDLED BASICALLY THE SAME BY THE KIDNEY. AT ANY RATE, RENAL FUNCTION DOESN'T SEEM TO PLAY MUCH OF A PART. >>THANK YOU FOR THAT: I ALSO WAS GOING TO ASK -- [ INAUDIBLE ] >>ALSO IMPORTANT QUESTIONS. SO HAVEN'T BEEN COMPLETELY EXPLORED, OUR EXPERIENCE WITH Mr. OS IS OF COURSE WITH AMBULATORY COMMUNITY DWELLING MEN, RATHER THAN THE KIND OF ILL CONDITIONS THAT YOU ALLUDED TO. THOSE STUDIES ARE ONGOING. AND I THINK THOSE ANSWERS WILL COME IN THE FUTURE. >>FOLLOW-UP -- [ INAUDIBLE ] WE END UP WITH A LOT OF WOMEN -- IT WOULD BE WONDERFUL TO BE ABLE TO DO COGNITIVE FUNCTIONS -- [ INAUDIBLE ] >>SO COGNITION WITH SOME BROAD MEASURES AT LEAST, LIKE TRAILS BEE AND GENERAL STUFF, HAVE BEEN PART OF THE Mr. OS PHENOTYPING FROM THE BEGINNING. SO, WE HAVE SOME ESTIMATES OF COGNITION OVER THE 20-YEAR SPAN. AND THAT'S BEEN THE SOURCE OF A NUMBER OF PUBLICATIONS. I THINK GOING FORWARD COGNITION MIGHT BE A REALLY INTERESTING THING TO INCLUDE. WE THOUGHT ABOUT BRAIN DONATIONS. HAVEN'T DONE ANYTHING ABOUT IT. I GUESS THIS IS A GOOD TIME TO ENCOURAGE PEOPLE WHO WANT TO JUMP IN TO TAKE ADVANTAGE OF THE Mr. OS COHORT TO DO SO WITH ANCILLARY STUDIES. SO, COME AT US. >>THANK YOU. >>THANK YOU. REALLY GREAT TALK. AND I GUESS IN THESE KINDS OF LONGITUDINAL STUDIES IN THE CONTEXT OF AGING ON AN INDIVIDUAL BASIS, YOU CAN GET ENTRAPPANCY OF CHRONOLOGICAL AGE VERSUS THE PATTERNS THAT YOU'RE SEEING IN YOUR DATA OR SOME -- INDIVIDUALS ARE CHRONOLOGICALLY OLDER OR THE OTHER WAY AROUND? IS THAT IN THIS CONTEXT, DID Mr. OS GIVE YOU INSIGHTS INTO AGING MECHANISMS? IS THAT ONE OF YOUR APPROACHES? >>YOU MEAN SORT OF BIOLOGICAL CLOCKS? THAT KIND OF THING? >>WE HAVE THOUGHT ABOUT TRANSFORMING PROTEOMICS DATA AND WE ARE ADDITIONALLY GAINING SOME EXPERIENCE WITH METABOLOMICS AND OTHER OMICS INTO AN AGING CLOCK OR BIOLOGICAL CLOCK. VIOLENT DONE THAT SO FAR. I THINK THERE ARE SOME OPPORTUNITIES TO DO SO BUT RIGHT NOW, WE DON'T HAVE PROTEOMICS MEASURES OTHER THAN AT BASELINE. OBVIOUSLY WHAT WOULD BE IDEAL IS TO HAVE LONGITUDINAL MEASURES OF PROTEOMICS, METABOLOMICS AND OTHER THINGS TO INCORPORATE. THAT'S ONE OF THE THINGS THAT I THINK WOULD REALLY BENEFIT THE BIOLOGICAL CLOCK DEVELOPMENT AND HYPOTHESIS. SO, IT'S A GREAT DIRECTION. HAVEN'T PROCEEDED WITH IT YET. >>THE LONGITUDINAL WOULD BE GREAT. SOUNDS LIKE IT WOULD BE GREAT TO HAVE EXTRA FUNDING TO DO THAT. >>YES, IT WOULD, INDEED. [ LAUGHS ] >>AND RELATED TO THAT, I GUESS IT WOULD BE MORE OF A LONGITUDINAL QUESTION. WHEN YOU SEE THESE CHANGES, YOU ALWAYS ASK ARE THEY CAUSAL OR COMPENSATORY? I THINKFUL INFLAMMATORY STUFF AS BAD BUT I GUESS YOUR DATA ANALYSIS WILL GET INTO THAT AS WELL? >>YES, EXACTLY. THESE ARE OBSERVATIONAL STUDIES. ALTHOUGH WE CAN INFER COGNITION, WE CAN'T DEMONSTRATE IT. SO, FOR INSTANCE, THE LONGEVITY CONSORTIUM IS LOOKING NOT ONLY AT THESE SORTS OF OBSERVATIONAL STUDIES BUT ALSO HOPING TO DEVELOP INTERVENTIONS THAT CAN BE TESTED. BOTH IN ANIMAL MODELS AND IN HUMAN MODELS TO GET MORE CAUSATION. >>THANK YOU. >>MONICA? >>YES, SO, THAT WAS A FANTASTIC TALK. I REALLY ENJOYED IT AND SORRY TO BRING THE WOMAN PERSPECTIVE IN HERE BUT A LOT OF WOMEN ARE TAKING DRUGS, ANTI-PROSIS DRUGS, FOUR EXTENDED PERIODS OF TIME. AND I'M CURIOUS IF ANY -- IF THESE INTERVENTIONS ARE GIVEN TO MEN AND IF THERE IS ANYTHING UNDERSTOOD ABOUT THEIR IMPACT -- OBVIOUSLY IN BONE -- BUT MUSCLE HEALTH, ESPECIALLY USING SOME OF THE NEW TECHNOLOGIES? >>YES, IT'S A GREAT QUESTION. IT TURNS OUT THAT -- OBVIOUSLY OSTEOPOROSIS HAPPENS IN MEN AS WELL. NOT INFREQUENTLY. AND THAT OSTEOPOROSIS THERAPY IN MEN IS UNDERTAKEN PROPORTIONATELY MUCH LESS THAN IN WOMEN. THERE ARE SOME MEN IN Mr. OS, A SMALL PROPORTION, THAT USE OSTEOPOROSIS THERAPIES. AND WE THOUGHT ABOUT HOW WE COULD LEVERAGE THE TREATMENTS TO TRY AND UNDERSTAND THEIR INFLUENCE. WE HAVEN'T UNDERTAKEN THOSE STUDIES. THERE ARE STUDS OUTSIDE Mr. OS THAT DO SUGGEST THAT WHAT YOU PAUSE IT MAY BE TRUE. THAT INTERVENTIONS DIRECTED AT BONE MAY HAVE INFLUENCERS ON MUSCLE. AGAIN, NOTHING VERY DEFINITIVE AS OF YET BUT THE RELATIONSHIP BETWEEN MUSCLE AND BONE IS INTIMATE AND YOU WOULD EXPECT THAT SOME INTERVENTION THREAT WOULD INFLUENCE MUSCLE. CAN'T CONCLUDE VERY MUCH FROM THOSE STUDIES YET. SORRY ABOUT THE NOISE. I'M IN CALIFORNIA AND THEY ARE CUTTING DOWN A TREE OUTSIDE OF MY WINDOW. >>ALMOST AS BAD AS JEN'S JACKHAMMERS YESTERDAY. >>YES. >>THANK YOU FOR A GREAT PRESENTATION. JUST A FOLLOW-UP TO DR. SNYDER'S COMMENT. I WONDER IF IN ADDITION TO COGNITION YOU MIGHT THINK OF COLLECTING SOME ULTIMATE BIOMARKERS AND IMAGING DATA. THE REASON I SAY THIS IS BECAUSE SO MUCH IMPRESSED IN ASSESSING THE RELATIONSHIP BETWEEN PRE-CLINICAL ALZHEIMER'S AND GAIT CHANGES AND EVENTUALLY MOBILITY CHANGES. YOUR COHORT IS VERY WELL PLACED GIVEN YOU HAVE BEEN FOLLOWING UP FOR SUCH A LONG TIME. TO START COLLECTING SOME BIOMARKERS DATA ON THE ALZHEIMER'S SIDE AND THAT COULD BE DONE AS AN INDEPENDENT RO1 OR ANCILLARY STUDY. BUT I WONDER IF YOU THOUGHT ABOUT THAT AS WELL. >>WE HAVE THOUGHT ABOUT IT. AGAIN, WE ARE A BUNCH OF PRIMARILY A BUNCH OF MUSCULOSKELETAL TYPES RATHER THAN COGNITION AND ALZHEIMER'S TYPES. BUT I AGREE THE STUDY IS VERY WELL POSITIONED TO LOOK AT BIOMARKERS FOR COGNITION. OVER 20 YEARS. SO AGAIN, THIS IS A PERFECT KIND OF ANCILLARY STUDY THAT I THINK SHOULD BE ENTERTAINED BY PEOPLE IN COGNITION. SO AGAIN, BRING IT ON. >>THANK YOU. >>ALL RIGHT, I THINK WE HAVE TIME FOR THE LAST TWO QUESTIONS. >>WHAT PROPORTION OF THE COHORT WAS MINORITIES AND NATIVE-AMERICANS? I'M CONCERNED ABOUT -- THE REASON I SAY THAT IS, WORKING WITH CHEROKEES FOR SO LONG, A LONG TIME AGO I WAS TOLD THAT THEY ARE LACTOSE INTOLERANT AND I THINK IT'S A COMMON TRAIT AMONG A LOT OF NATIVE-AMERICANS. AND THAT MAY ACCOUNT FOR LODI TERRY CALCIUM INTAKE -- ACCOUNT FOR LOW DIAGNOSIS OF CALCIUM IN TAKE. LODI TERRY. >>LESS THAN WE HOPED DESPITE ACTIVE ATTEMPTS TO ENCOURAGE IT. ABOUT 10% WAS OVERALL COHORT. WE CONSIDERED TO BE MINORITY. A VAR SMALL PERCENTAGE WERE NATIVE. WE THOUGHT ON NUMEROUS OCCASIONS HOW TO LEVERAGE EVEN THAT SMALL PROPORTION OF MINORITIES AND JUST HAVEN'T THOUGHT WE HAD THE POWER TO DO ANYTHING VERY EFFECTIVE IN THAT REGARD. OBVIOUSLY WE WOULD BE OPEN TO ANY NOVEL APPROACH THAT IS MIGHT ALLOW US TO TAKE ADVANTAGE OF THE SMALL PROPORTION OF MINORITIES THAT WE HAVE. >>AND SUSAN? >>ERIC, THAT WAS REALLY, REALLY TERRIFIC. AMAZING WORK THAT YOU HAVE DONE. >>THANK YOU. >>REALLY IMPRESSIVE. A QUESTION FOR YOU. SO, AS YOU KNOW, THERE IS SORT OFOG GOING DEBATE IN THE BONE WORLD WHETHER OR NOT WE SHOULD REALLY USE FRAC OR NOT BECAUSE IT'S MISSING IMPORTANT THINGS SUCH AS FALLS AND I KNOW YOU SEE THESE PEOPLE EVERY FOUR MONTHS. SO THE QUESTION IS, HAVE YOU THOUGHT ABOUT, OR DO YOU HAVE FALLS DATA AND HAVE YOU THOUGHT ABOUT RE-THINKING FRACS OR SOME TYPE OF RISK PREDICTION WHICH WOULD INCLUDE FALLS IN THIS MALE POPULATION? BECAUSE THAT WOULD JUST BE SO VALUABLE TO BE ABLE TO GET A BETTER RISK PREDICTION. AND ALSO RATHER THAN 10 YEARS OUT TO DO SOMETHING SHORTER THAT WOULD BE CLINICALLY RELEVANT LIKE FIVE YEARS OUT. >>BOTH OF THOSE THINGS ARE REALLY INTERESTING TO ME. WE HAVE LOOKED AT FRAC. AND Mr. OS IN COMPARISON AND TOGETHER IN NUMEROUS PUBLICATIONS. MOST RECENTLY, NICK HARTLEY FROM THE GROUP, HAS LOOKED AT THE Mr. OS DATA TO EXAMINE EXACTLY THOSE ISSUES. THE INFLUENCE OF FALLS AND MOST RECENTLY, THE INFLUENCE OF MUSCLE AND MUSCLE DENSITY. SO YOU MIGHT LOOK AT A COUPLE OF HIS RECENTLY PUBLICATIONS. IT LOOKS FROM THE Mr. OS ANALYSIS THAT YOU MIGHT EXPECT A CHANGE IN FRACS IN THE NEAR FUTURE AND INCORPORATE QUESTIONS ABOUT FALLS AND INCORPORATE QUESTIONS ABOUT MUSCLE. SO, IT'S BEEN VERY ACTIVE AS A Mr. OSFRACS COLLABORATION. LOOK FOR NICK HARVEY AND HIS PUBLICATIONS. >>THANKS. OF. >>THANK YOU AGAIN, ERIC FOR A REALLY TERRIFIC TALK. WE APPRECIATE YOU TAKING THE TIME OUT SPEAKING WITH US AND ANSWERING MANY QUESTIONS AND PERHAPS YOU MAY BE CONTACTED IN THE FUTURE WITH SOME NEW COLLABORATIONS T SOUNDS LIKE. >>I THINK THAT WOULD BE FABULOUS. THANK YOU VERY MUCH. >>THANK YOU VERY MUCH. ALL RIGHT, NEXT WE HAVE OUR NEXT SPEAKER. SO DR. RICHARD HODES WOULD YOU LIKE TO INTRODUCE OUR NEXT SPEAKER? >>IT'S MY PRIVILEGE TO INTRODUCE DR. SUSAN WHO WAS APOINTED AS THE FOUNDING DEPUTY DIRECTOR OF ARPH, AN AGENCY WHICH NIH LOOKS AT WITH GREAT INTEREST AS A PARTNER AND COLLABORATIONS. SUSAN HAS HAD A DISTINGUISHED CAREER WHICH PROVIDES HER WITH A STRONG BACKGROUND FOR APPOINTMENT AS AN OUTSTANDING FOUNDING DIRECTOR. SHE PREVIOUSLY LED STRATEGY ANALYSIS AND RISK MANAGEMENT FOR ARPAH AND ACTING DEPUTY DIRECTOR FOR A BIT OF TIME PRIOR TO THAT. SHE WAS AT HRSA PRIOR TO THAT WHERE SHE WAS THE FOUNDING DIRECTOR FOR THE CENTER FOR INNOVATION AND HEALTH RESOURCES AND SERVED IN THE WHITE HOUSE AND ASSISTANT DIRECTOR FOR NATIONAL HEALTH SECURITY, INTERNATIONAL AFFAIRS IN THE OFFICE OF SCIENCE AND TECHNOLOGY, OSDP. OUR ACADEMIC BACKGROUND INCLUDED FASFA DEGREE AND DOCTORATES FROM YY OF WISCONSIN MAD SONG AND MICROBIOLOGY AND IMMUNOLOGY AND FELLOWSHIP IN AAAS AT STANFORD. SO CAREER IN PUBLIC SERVICE AND ACADEMICS THAT MAKE HER A STRONG AND OPTIMAL CANDIDATE AND NOW SELECTEE FOR THE POSITION OF DEPUTY DIRECTOR OF ARPAH. I THINK MANY OF US AT NIH AND NIA AND IN THE COUNCIL LOOK FORWARD TO HEARING FROM YOU. SO ONE OF THE EARLIEST OPPORTUNITIES WE INTERACT. SO WELCOME, PLEASE TAKE IT AWAY. >>THANK YOU! I WAS ABLE TO JOIN FOR A LITTLE BIT OF THE SCALE OF THAT PRESENTATION AND I KEPT THINKING TO MYSELF, A YEAR FROM NOW, I WANT TO BE ABLE TO TELL A GREAT STORY ABOUT THE RESEARCH WE HAVE FUNDED AND THE POTENTIAL FOR IT TO TRANSFORM SOME PART OF THE ECOSYSTEM. SO THANK YOU FOR LETTING ME JOIN YOUR GROUP TODAY. I'M HAPPY TO WALK YOU THROUGH WHERE WE ARE, WHERE WE ARE GOING AND THEN WELCOME QUESTIONS. I KNOW WE ARE RUNNING A LITTLE BIT OVER ON TIME BUT I BLOCKED MY AFTERNOON OFF FOR THIS. SO I CAN TAKE QUESTIONS IF YOU ALL HAVE THE TIME TO DO THAT. SO WHY DON'T I JUST JUMP IN. AR APPROXIMATE. AH, ADVANCED HEALTH RESEARCH AGENCY ADVANCED PROJECTS RESEARCH AGENCY FOR HEALTH MODELS ADD DARPA. OUR GOAL IS REALLY TO MAKE SURE THAT WE ARE ACCELERATING BETTER OUTCOMES FOR EVERYONE. SIMILAR TO HOW DARPA REALLY WORKED TO DISRUPT AND INNOVATE WITHIN THE DEFENSE ARENA. SO THEIR MISSION WAS VERY MUCH STREAMLINED. OF COURSE TO THE DEFENSE ECOSYSTEMS. OUR IS EVERYONE, THE AMERICAN PUBLIC AND REALLY TRYING TO OPEN UP EVERYTHING WE DO TO REALLY FUND THOSE TRANSFORMATIONAL ACTIVITIES WHERE 3-5 YEARS FROM NOW OR 10 YEARS FROM NOW, WE SAY TO OURSELVES, OH, MY GOSH, WE NEVER THOUGHT WE WOULD GET HERE. NEVER THOUGHT WE WOULD DO SOMETHING TO SUPPORT SLOWING DOWN OR REDUCING AGING. WE WERE JUST HEARING ABOUT. SOMETHING JUST SLIGHTLY TRANSFORMATIONAL. THAT'S OUR MISSION AND WHAT DRIVES US EVERY DAY. NEXT SLIDE. WE ARE VERY FORTUNATE TO HAVE SUCH GREAT SUPPORT FOR THIS ADMINISTRATION. SO PRESIDENT BIDEN WHO IS A STRONG SUPPORTER FOR HEALTH AND SCIENCE BOTH AT THIS TIME AND AS VICE PRESIDENT, WAS REALLY TRANSNORIMATIONAL IN SAYING WE NEED AN AGENCY LIKE ARPAH, AN ORGANIZATION THAT IS CONNECTED TO WORLD CLASS RESEARCH SCIENTISTS LIKE THOSE AT NIH BUT WHO CAN TAKE ON THESE HIGH RISK, HIGHER REWARD TASTES NO ONE ELSE CAN TAKE. WE UNDERSTAND THAT FAILURE IS PART OF WHAT WE GOING TO BE WORKING TOWARDS. BUT WE TELL OURSELVES IT'S NOT FAILURE IF YOU LEARN SOMETHING. IF WE SHARED THAT LEARNING WITH OTHERS. THAT'S WHERE WE ARE PLACED AND WE WANT TO MAKE SURE THAT WE ARE JUST BREAKING THE MOLD ON HOW WE SUPPORT FUNDAMENTAL RESEARCH AND THE DEVELOPMENT OF COMMERCIAL PRODUCTS THAT ARE AVAILABLE TO EVERYONE IN THE HEALTH ECOSYSTEM. NEXT SLIDE. WE TALK A LOT RIGHT NOW AS WE ARE BUILDING THE AGENCY ABOUT WHAT IS IT THAT IS DRIVING US? AND WE ANCHOR OURSELVES IN THE CONCEPT OF THE SLOW SPUTNIK MOMENTS. WE THINK ABOUT WHEAT ARE IN AN ERA OF COMPLEX TECHNOLOGY WITH MASSIVE ECONOMIC AND SOCIAL DISRUPTIONS. POWERFUL BIOLOGICAL FACTORS INCLUDING WHAT WE LIVED THROUGH, THE PANDEMIC, BUT ALSO KNOWING EMERGING BIOTECHNOLOGIES ARE CHANGING ALMOST DAILY, WEEKLY, MONTHLY AND THERE IS SO MUCH POTENTIAL TO LEVERAGE THESE TECHNOLOGIES TO BE TRANSFORMATIONAL. OUR PROMISE IS OUR PROGRAM MANAGERS WHICH WE WILL TALK ABOUT, THEY ARE THE ENGINE THAT DRIVES US, THEY WILL DESIGN, BUILD AND LAUNCH THESE SOLUTIONS TO CREATE THE BEST VERSIONS OF OUR HEALTH FUTURE. NEXT SLIDE. SO MUCH LIKE KNOWING WHAT ANCHORS US IS THERE IS A SPUTNIK MOMENT, A NEED FOR TRANSFORMATIONAL APPROACHES TO DISRUPTION AND INNOVATION IN THE HEALTH ECOSYSTEM. WE ALWAYS ARE CHALLENGING OURSELVES WITH THESE MANAGE IF STATEMENT. IMAGINE IF YOU COULD TRANSFORM THE ECOSYSTEM. A FEW EXAMPLES HERE. WHAT IF WE HAD CELL THERAPY THAT COULD BE BUILT AND ASSEMBLED ON DEMAND? AND READILY PROGRAMMED FOR EACH NOW DISEASE TARGET? WHAT IF MRIs COULD BE DELIVERED IN YOUR HOME? WHAT ABOUT A PERSONALIZED CANCER VACCINE COST THE SAME AS A CUP OF COFFEE? IF WE ARE ABLE TO ACHIEVE THIS WITHIN THE HEALTH ECOSYSTEM, WE COULD ALL REALIZE A BETTER HEALTH FUTURE. NEXT SLIDE. SO, WHERE WE ARE PLACED, WE SORT OF LOOK AT IT AS HAVING THE BEST OF BOTH WORDS WORLDS. ON THE ONE HAND, WE HAVE DIRECT AUTHORITY AND DIRECT RELATIONSHIP WITH HHS SECRETARY. SO WE HAVE THE ABILITY TO GO AND DIRECTLY SORT OF SEEK GUIDANCE AND OFFER SOLUTIONS AND HAVE THAT RELATIONSHIP BUT WE ARE ALSO DIRECTLY CONNECTED TO OUR COLLEAGUES AT NIH. SO WE ARE A DOTTED LINE TO THE NIH DIRECTOR AND WHAT WE ARE HOPING TO DO IS BUILD OUT THE NIH AND ICs AS PARTNERS. KEY PARTNERS, INDIVIDUALS WHO HAVE SUCH DEPTH AND BREATH OF EXPERIENCE IT WILL ONLY ALLOW US TO BECOME BETTER AS WE DEVELOP OUR PROGRAMS AND HIRE OUR PROGRAM MANAGER BY BEING THIS CONNECTION TO OUR NIH COLLEAGUES. WE GENERALLY HAVE TWO BIG SIDES OF THE ORGANIZATION. WE HAVE OUR PROGRAM MANAGERS AND WE'LL TALK ABOUT THOSE. THOSE ARE THE ONES THAT ARE REALLY GOING TO DRIVE WHAT WE DO AS AN AGENCY. AND THEN WE HAVE BUSINESS TEAM MEMBERS. SO THOSE ARE THE ONES THAT KEEP THE LIGHTS ON AND MAKE SURE THAT FOLKS GET PAID AND WE HAVE SEATS TO SIT IN AND CONTRACTS TO BE LET AND SO IT'S THOSE TWO LARGE DIVISIONS. AND AT A GLANCE, WE RECEIVE 1-- ONE BILLION DOLLARS IN. IF YOU Y22 AND ANOTHER WORN.5 IN FY23 -- 1.5 -- WE HAVE 2 1/2 BILLION DOLLARS WE ARE LOOKING TO EXPEND OVER THE NEXT COW OF YEARS. EVERYTHING WE DO IS EXTRAMURAL. IT'S GOING TO BE DISEASE AGNOSTIC AND THE MONEY GOES OUT. WE DON'T HAVE BRICKS AND MORTAR OR LABS. THE PROGRAM MANAGERS ARE THE ENGINE. THEY DRIVE THE IDEAS AND THEY DRIVE THE DECISION-MAKING. OUR GOAL IS TOW REMAIN LEAN AND NIMBLE. WHEN YOU LOOK AT HOW BIG OF AN ORGANIZATION WE WILL BE, WE HOPE TO HAVE A VERY BALANCED APPROACH BETWEEN THE PROGRAM MANAGERS AND THE BUSINESS TEAM MANAGERS BUT THE TOTAL FOOTPRINT OF POTENTIALLY 100 OR SO PROGRAM MANAGERS DEPENDING ON THE BUDGET AND THEN THE BUSINESS SIDE WE'LL HAVE 100 OR SO BUSINESS MEMBERS. AND THE GOAL IS TO FUND THIS HIGH UNCERTAINTY, HIGH CONSEQUENCE RESEARCH. SO THINGS THAT ARE ON THE CUSP OF RISK THAT NO ONE ELSE CAN TAKE ON. AND WE ARE WILL BE TO ACCEPT THAT RISK TO TRANSFORM THE HEALTH ECOSYSTEM. NEXT SLIDE. SO, THIS IS THE GENERAL WAY WE THINK ABOUT PROGRAM FOUNDATION. SO THE FIRST IS, IT'S PROGRAM MANAGERCENTRIC. SO MUCH LIKE DARPA, WE WILL NOT FUND PROGRAMS UNLESS WE HAVE A PROGRAM MANAGER WHO COMES IN WITH AN IDEA OF SOMETHING RELATED TO THAT PROGRAM THAT IS NEW AND NOVEL AND BASED ON THE QUESTIONS THAT IS SOMETHING THAT REALLY ARE THIS FRAMEWORK THAT ALLOWS US TO CONSIDER THE UNIQUENESS OF THE PROGRAM AND THE WAY THE PROGRAM MANAGER SEEKS TO ACTUALLY FIELD THAT PROGRAM. SO LOOKING AT THE PROGRAM MANAGER IDENTIFYING DIFFICULT HEALTH RELATED CHALLENGES THAT IS RIGHT FOR SOLVING. SO, THE CHALLENGES THAT WE WANT TO TAKE - ARE THOSE THAT SHOULD NOT BE EASILY SOLVABLE THROUGH TRADITIONAL ACTIVITY. SO IT'S SOMETHING THAT OUR COLLEAGUES AT NIH THROUGH THEIR PROCESSES, THEIR INNOVATING AND PUSHING AT THE CUTTING-EDGE OF RESEARCH AND TECHNOLOGY AND THIS WOULD BE ONE STEP FURTHER DOWN THE PIKE WHERE JUST WOULDN'T BE APPROPRIATE FOR THE WAY THAT THEIR FUNDING ACTIVITIES NOW. BUT WE ALSO LOOK FOR PARTNERSHIPS. WHEN WE ARE GOING TO TAKE ON THIS RESPONSIBILITY OF FUNDING IT, WE HAVE OUR COLLEAGUES AT NIH TO HELP WITH THE GUIDING THE PROGRAMS. ONCE WE HAVE IDENTIFIED THE CHALLENGE, WE HAVE OUR PROGRAM MANAGERS ONBOARD, WE GO TO THE NEXT STEP WHICH IS THE LAUNCH. SO THE PROGRAM MANAGER WILL OVERSEE SEVERAL GROUPS OF PERFORMERS AIMED AT SOLVING PROBLEMS. SO THIS IS ALL CONTRACTOR OR COOPERATIVE AGREEMENT FUNDING. NOT GRANTEES. WE MAKE SURE THAT THE PROGRAM OR PERFORMERS ARE ABLE TO COMPETE TO CARRY OUT THE POTENTIAL INNOVATIVE SOLUTIONS TO THE CHALLENGE. SO IT'S A LITTLE BIT DIFFERENT THAN THE GRANT-BASED MODEL WHERE THERE IS ACTUALLY CONTRACT OR COOPERATIVE AGREEMENT BASED. NEXT SLIDE. BECAUSE WE HAVE THE ABILITY TO SUPPORT CONTRACTS, WE WANT TO REALLY MAKE SURE WE HAVE A ROBUST EVALUATION PROCESS IN PLACE. SO WE WILL FUND MULTIPLE PERFORMERS FOR ANY PARTICULAR PROGRAM AND REALLY HELPING THAT THE BEST PERFORMER WAS ABLE TOL CONTRIBUTE THE SOLUTIONS THAT WE NEED. AND SO FOR EXAMPLE WE HAVE PEOPLE WORKING ON A PARTICULAR PROGRAM AREA. WE'LL DESIGN A SERIES OF PHASE GATES AND MILESTONES FOR US TO BE ABLE TO EVALUATE, ARE THESE PERFORMERS MEETING THOSE STRUCTURED CRITERIA? AND IF THEY ARE NOT, OUR GOAL IS TO BE ABLE TO TAKE THOSE RESOURCES THAT HAVE BEEN APPLIED TO THE PERFORMERS THAT ARE WORKING IN THIS SPACE THAT ARE FAILING AND THEN REAPPLY THEM EITHER TO THE PERFORMER THAT IS WORKING OR TO OTHER AREAS WITHIN THE ORGANIZATION. AND BY DOING THIS APPROACH, WHAT WE ARE HOPING IS THAT OF THE PERFORMERS, ONE OR MORE THAT REACHES THROUGH ALL THE VARIOUS MILESTONES ANDISTS TO REACH THE FINAL STATE OF THE PROGRAM OR ACTIVITY THAT WE WERE HOPING TO SEE FROM WITHIN THAT PERFORMER COHORT. NEXT SLIDE. WE ARE NOT DONE THERE. SO OUR BIG GOAL WITH OR PROGRAMS IS TRANSITION. SO, GIVING THE PROGRAM MANAGERS AND THE PERFORMERS ALL THE RESOURCES NECESSARY TO REACH SUCCESS AND THEN TAKING WHATEVER SUCCESS LOOKS LIKE, WHATEVER THAT PRODUCT IS AND WORKING WITH OUR TRANSITION PARTNERS SO THAT WHEN THE CHALLENGE, PER SE IS SOLVED, THE PROJECT CAN THEN TRANSFER TO OTHER PARTNERS WHO HAVE BEEN INVOLVED IN THE START AND CAN SCALE THE SOLUTION TO THE COMMUNITY THAT WOULD BE -- THAT WOULD BENEFIT FROM HAVING THAT SOLUTION IN THEIR ECOSYSTEM. SO, THE GOAL IS TO TAKE EVERYTHING THAT WE DO, STOP AT SOME POINT AND TRANSITION IT TO OTHERS WHO CAN TAKE IT ON TO WHATEVER THE NEXT STEPS ARE IN THAT PRODUCT DEVELOPMENT PATHWAY. >>NEXT SLIDE. THE PROGRAM MANAGERS ARE THE CENTER OF THEUBE VERSE. WE BRING THEM ON FOR 3-6 YEARS SO THERE IS AN URGENCY THEY ALL HAVE TO BE ABLE TO MAKE SURE THEY ARE COMING IN WITH WELL DEFINED CHALLENGES. WE SUPPORT THEM WITH ESSENTIALLY WRAP AROUND SERVICES FROM EVERYTHING HOW TO WORK IN THE FEDERAL GOVERNMENT, HOW TO DO CONTRACTING, HOW TO LEAD TEAMS, HOW TO MAKE SURE THAT YOU'RE WORKING WELL WITH TRANSITION PARTNERS FROM THE BEGINNING OF YOUR TENURE. AND THEN MOVE THEIR PROGRAMS TOWARDS SOLUTIONS. SO THEY HAVE THROUGH-6 YEARS WITH US AND -- 3-6 YEARS AND AND THEN THE PROGRAMS WILL LAST 2-4 YEARS. AND THEY WILL BE HANDOFFS ON OCCASION BETWEEN PROGRAM MANAGERS THAT ARE OUTGOING AS THEIR 6 YEARS COMES TO AN END AND IN COMING WHEN THEY ARE JUST STARTING AND THEY WILL HAND OVER OR TAKE ON SOME PROGRAMS THAT WERE ALREADY IN THE PIPELINE. NEXT SLIDE. WE FULLY RECOGNIZE THAT A HEALTHY ECOSYSTEM IS VERY COMPLEX. MUCH MORE COMPLEX THAN YOU WOULD SEE WITH DARPA OR ANYWHERE ELSE. SOME OF THE OTHER ARPAs IN THE FEDERAL GOVERNMENT. AND WE WANT TO MAKE SURE WE ARE EMBRACING THIS COMPLEXITY BY PARTNERING WITH OUR COLLEAGUES WITHIN HHS, FEDERAL GOVERNMENT, INDUSTRY, ACADEMIA, PATIENT GROUPS, HEALTH CARE PROVIDERS AND THE AMERICAN PUBLIC BOTH ON THE WHAT IS THE MOST URGENT AND PRESSING NEEDS WITHIN THE HEALTHY ECOSYSTEM AND ALSO AS WE ARE DEVELOPING THESE CAPABILITIES, WHAT DOES SUCCESS LOOK LIKE FOR TRANSITION MAKING SURE THEY ARE SUPPORTING THE BROADEST SET OF CONSTITUENCIES WITHIN THE HEALTHY ECOSYSTEM. NEXT SLIDE. SEE JUST TO TALK ABOUT WHAT WE HAVE DONE AT NIH. I CAN'T EMPHASIZE ENOUGH HOW MUCH WE WANT TO MAKE SURE THAT WE ARE PARTNERING WITH OUR AMAZING COLLEAGUES AT NIH. SO WE HAVE ALREADY HAD SEVERAL OPPORTUNITIES TO WORK TOGETHER MOSTLY NOW IT'S JUST TALKING AND WE ARE HOPING THAT AT SOME POINT IT'S ACTUALLY DOING MORE OF THE TALKING, EXCHANGING TECHNICAL INFORMATION, POTENTIALLY COFUNDING VARIOUS ACTIVITIES. REALLY MAKING SURE THAT WE ARE OPTIMALLY LEVERAGING OUR RELATIONSHIP WITHIN NIH. SO WE HAVE DONE SEVERAL. WE DID THE KICKOFF EVENT AT HOWARD, A NUMBER OF DIFFERENT SPEAKING ENGAGEMENTS THAT THE DIRECTOR OF ARPAH ENGAGED IN FROM -- YOU CAN READ THOSE. SO JUST REALLY MAKING SURE THAT WE ARE OPEN AND TRANSPARENT AND REALLY MAKING SURE THAT WE ARE REACHING ACROSS THE CAMPUS IT OUR NIH COLLEAGUES SO WE CAN BUILD THOSE PARTNERSHIPS. AND WE HAVE SEVERAL THINGS WE ARE GOING AT OR ABOUT DOING IN THE FUTURE. AND ALL OF WHICH WE ARE VERY, VERY EXCITED ABOUT. NEXT SLIDE. I TALK A LITTLE BIT ABOUT THE PROGRAM MANAGER, PROGRAM LIFE CYCLE. THIS GIVES A LITTLE BIT MORE OF THE -- A LITTLE MORE OF THE DETAILS. I'M NOT GOING TO GO INTO ALL OF THE SPECIFIC ELEMENTS. YOU HAVE THE SLIDES. REALLY THE GOAL IS TO MAKE SURE THAT WE HAVE A CONSISTENT SUCCESSFUL APPROACH FOR ALL THE PROGRAM MANAGERS THAT COME ON THAT WE HAVE WELL DEFINED PROBLEMS. THE PROGRAMS ARE DESIGNED TO ADDRESS THOSE PROBLEMS AND THAT AT THE END OF THE TENURE OF THE PROGRAM MANAGER OR THE PROGRAM, THAT WE CAN SUCCESSFULLY COMMERCIALIZE OR TRANSITION AS APPROPRIATE THE VARIOUS PRODU PRODUCTS. NEXT SLIDE. SO THIS IS WHERE WE ARE STARTING FROM OUR TECHNICAL STRATEGY. SO WITHIN THE FIRST MONTH OR SO OF COMING ONBOARD WAS THINKING ABOUT HOW TO STRUCTURE OUR PORTFOLIOS. SO WE COVER THE BREATH OF THE HEALTHY ECOSYSTEM BUT PUSHING PUSHING TOWARDS THOSE AREAS THAT ARE PARTICULARLY IN NEED OF INNOVATION. SO, WE SETTLED ON THESE FOUR DIFFERENT LARGE DOMAINS THAT WE'LL BE SUPPORTING PROGRAMS IN. THE FIRST IS HEALTH SCIENCE FUTURES. AND THAT IS REALLY THINKING ABOUT PLATFORMS THAT CAN APPLY TO A BROAD RANGE OF DISEASES. SO RATHER THAN GO ON THE DISEASE BY DISEASE SPECIFIC PURSUIT OF VARIOUS THERAPEUTICS AND INTERVENTIONS, THIS IS SAYING WHAT CAN WE DO FROM A PLATFORM PERSPECTIVE THAT WOULD ALLOW US TO ADDRESS AS MANY OF THESE CHALLENGES AS POSSIBLE WITH A SINGLE TOOL OR A SINGLE PLATFORM. SCALABLE SOLUTIONS IS REALLY THINKING ABOUT HOW TO WE MAKE SURE THAT THE SOLUTIONS THAT ARE BEING DEVELOPED, AND THERE ARE SOME SOLUTIONS THAT WORK AT A SMALL SCALE FOR A SMALL POPULATION, BUT REALLY NEED SOME INNOVATION TO REACH EVERYONE AND REACH EVERYONE WHO NEEDS THE INTERVENTION AND THE THERAPY VACCINE, WHATEVER IT HAPPENS TO BE. AND TO DO SO QUICKLY. SO LOOKING AT BOTH GEOGRAPHY, MANUFACTURING, DATA INFORMATION, ECONOMIES OF SCALE. SO TAKING EXISTING PRODUCTS AND EXISTING 50s SAYING, HOW CAN WE HELP SCALE THESE SOY THAT EVERYONE CAN BENEFIT? PROACTIVE HEALTH IS THINKING ABOUT KEEPING PEOPLE FROM BEING PATIENTS IN THE FIRST PLACE. SO LOOKING AT PREVENTIVE PROGRAMS IN DIFFERENT WAYS THAT THINKING ABOUT CHARACTERIZING DISEASE RISK AND PROMOTING TREATMENTS AND BEHAVIORS THAT AMOUNT THOSE THREATS SO WE CAN MITIGATE THE POTENTIAL TO HEALTH IMPACTS BY UP STREAMING BY BEING PROACTIVE ABOUT THE INTERVENTIONS THAT WILL BE PURSUING AND THEN RESILIENT SYSTEM SYSTEM. THIS IS ABOUT HOW DO WE CREATE A BETTER HEALTH CARE SYSTEM? SO LOOKING AT CAPABILITIES, BUSINESS MODELS, INTEGRATION THAT ALLOWS US TO WEATHER CRISIS SUCH AS PANDEMICS, SOCIAL DISRUPTIONS, CLIMATE CHANGE, ECONOMIC INSTABILITY. SYSTEMS THAT ARE SUSTAINED BETWEEN CRISIS FROM THE MOLECULAR TO THE SOCIETAL. AND I THINK WE HAVE SEEN THIS. I HAVE BEEN IN GOVERNMENT FOR QUITE SOMETIME AND IN LEADERSHIP POSITIONS IN THE HEALTH INNOVATION FOR QUITE SOMETIME AND THERE IS NOTHING MORE FRUSTRATING WHEN YOU HAVE ANG EMERGENT CRISIS AND EVERYTHING RUSHES TO FIND A SOLUTION AND THERE IS NEVER TIME TO ACTUALLY GET FROM SOLUTION IDEATION TO DEPLOYMENT OF SOMETHING THAT IS SUSTAINABLE BEFORE THAT CRISIS ENDS UP PASSING AND ATTENTION GETS DILUTED IN OTHER CRISIS COME ON. AND THEN YOU FIND YOURSELF IN THAT SAME SITUATION TWO, 5, 10 YEARS LATER AND IT'S ALMOST LIKE, GROUNDHOG DAY WHERE YOU'RE SAYING, WE WERE JUST HERE AND WE DIDN'T ACTUALLY DEVELOP SOMETHING THAT WAS READY TO BE PUT IN PLACE RAPIDLY TO MITIGATE THE CIRCUMSTANCES OF THE EMERGING ISSUE. SO THINKING ABOUT WHAT RESILIENT SYSTEMS AND HEALTH CARE LOOKS LIKE. NEXT SLIDE. OY TALKED A LOT ABOUT THE PROGRAM MOTHER-IN-LAW. THIS IS WHERE WE CAN USE YOUR HELP. -- MANAGER. WE ARE LOOKING FOR INDIVIDUALS WHO WILL COME ON TO CHAMPION THE VARIOUS PORTFOLIO AREAS WITH PROGRAMS THAT WE ALL KNOW ARE SO CRUCIAL AND IMPORTANT. AGING IS ONE OF THOSE HOW DO WE AGE MORE HEALTHY? HOW DO WE ACTUALLY THINK ABOUT THE -- WHETHER OR NOT THERE ARE BEHAVIORAL HEALTH OR CLINICAL CARE, INTERVENTIONS THAT WOULD ALLOW US TO AGE BETTER TO REDUCE THE POTENTIAL DISEASES THAT COME ON WITH AGING. SO REALLY THINKING ABOUT THAT AS AN OPPORTUNITY TO IDENTIFY PROGRAM MANAGERS WHO ARE PASSIONATED ABOUT THIS SECTOR AND THEY ARE WILLING TO COME ON FOR 3-6 YEARS, TAKE ON REALLY HARD PROBLEMS AND BE GIVEN ALL THE RESOURCES NECESSARY TO BE SUCCESSFUL. AND IT IS FULLY SUPPORTIVE. WE HAVE BUSINESS AND TECHNICAL TEAMS THAT WILL ALLOW SOMEONE WHO MAYBE NEVER WORKED IN GOVERNMENT, NO THE TO HAVE TO WORRY ABOUT HOW DOES THAT WORK. BECAUSE WE'LL SUPPORT OR FILL IN THE GAPS ASSOCIATED WITH THAT WITH OUR TEAM. AND THEN THE RESPONSIBILITY ONCE THEY ARE IN THE DOOR, AND THEY HAVE IDENTIFIED THE PROBLEMS, IS TO ASSEMBLE A TEAM FROM INDUSTRY, ACADEMIA AND GOVERNMENT AND GO OUT AND SOLVE THE PROBLEMS. NEXT SLIDE. PEOPLE ASK US, WHAT ARE THE CRITERIA FOR OUR PROGRAM MANAGER? AND THE ANSWER IS, WE DON'T HAVE ANY SET CRITERIA THAT ONE NEEDS TO HAVE GONE THROUGH THE PHASE GATES ASSOCIATED WITH IT. WE ARE LOOKING FOR UNCOMMON PEOPLE WITH UNCOMMON TRAITS. SO PEOPLE WHO HAVE EXPERTISE THAT ARE JUST INIZATIONABLY CURIOUS. HOW COME THIS? HOW DOES THIS WORK THIS WAY? IT'S HELPFUL TO HAVE AN INTERDISCIPLINARY TRACK RECORD. SO THEY WORKED IN ACADEMIA, GOVERNMENT, PRIVATE SECTOR AND MORE THAN ONE PORTFOLIO AREA. IT'S NOT A -- IF YOU DON'T HAVE THAT, YOU CAN'T BE HIRED. IT'S JUST THAT IT WOULD BE HELPFUL TO YOU AND THEM AS THEY ARE WORKING WITHIN THE GOVERNMENT. SERIOUSLY SO YOU ONLY HAVE 3-6 YEARS. WE NEED PEOPLE WHO WAKE UP EVERY DAY WHO ARE READY TO JUST KEEP PUSHING ALONG AND IT IS INTENSE TRYING TO MAKE SURE THAT YOU CAN CONTRIBUTE SOMETHING OF SIGNIFICANCE COMING OUT OF HERE IN YOUR LIMITED TENURE HERE. AND NO FEAR OF FAILURE. SO FAILURE TO US IS NOT THAT THE PROGRAM DIDN'T WORK. THE FAILURE IS IF TWEE DIDN'T LEARN ANYTHING. AND IF WE DIDN'T TAKE THOSE FINDINGS OF IF SOMETHING FAILED AND SHARE IT SO NOT ONLY ARE WE LEARNING WITHIN THE ORGANIZATION WHY SOMETHING DIDN'T WORK BUT WE GIVE THAT KNOWLEDGE OUT TO EVERYONE ELSE WHO MAY BE THINKING ABOUT THE SAME TYPE OF ACTIVITY OR PORTFOLIO. IN WHICH CASE, THEN IT'S NOT A FAILURE, IT'S AN INCREDIBLE VALUE TO THE RESEARCH THAT IS GOING ON. AND THEN TECHNICAL HONESTY. OUR GOAL IS TO BE ABLE TO TRANSITION PRODUCTS THAT CAN GO OUT AND BE EFFECTIVE IN THE HEALTHY ECOSYSTEM. SO ALL ALONG THE WAY WE HAVE TO MAKE SURE THAT THEY HAVE THE HIGHEST LEVEL OF INTEGRITY TO MAKE SURE THAT WE ARE BUILDING SOMETHING THAT WILL WORK AND IS SUSTAINABLE. AND THEN THERE ARE DIFFERENT APPROACHES TO THE CAREER STAGE, I'M NOT GOING IN THERE. YOU CAN READ THOSE. BUT REALLY THAT IDEA IS THAT THERE IS NO ONE TYPE OF INDIVIDUAL THAT WE ARE LOOKING FOR IN THE PROGRAM MANAGER. WE ARE LOOKING FOR EVERYONE WHO SORT OF HAS SOME COMPOSITION OF IDEAS OF THESE CRITERIA AND IS REALLY EXCITED ABOUT COMING TO JOIN US. NEXT SLIDE. THESE ARE THE QUESTIONS. SO THIS IS HOW WE THINK ABOUT WHETHER OR NOT A PROGRAM MANAGER HAS CONCEPTUALIZED THE CHALLENGE AND THE SOLUTION IN A WAY THAT WE CAN UNDERSTAND AND ASSESS HOW UNIQUE IT IS AND WHETHER OR NOT IT IS GOING TO HAVE A TRANSFORMATIONAL IMPACT. SO THESE ARE DERIVED FROM THE DARPA QUESTIONS AND THEY ARE VERY SIMPLE TO WRITE. THEY ARE MISLEADINGLY HARD TO ADDRESS. ESPECIALLY WE HAVE A REALLY STRONG TECHNICAL TEAM THAT IS EVALUATING EVERY SUBMISSION AND REALLY TOO IING TO MAKE SURE THAT THE BEST ANSWERS ARE COMING THROUGH FROM THE POTENTIAL PROGRAM MANAGERS. WE DID ADD TWO CRITERIA. SO FIRST 8 COME FROM TARP A THE LAST TWO ARE ONES WE ADDED BECAUSE THEY ARE SO IMPORTANT FOR OUR HEALTH ASPECT OF BEING IN OUR BOAT. THE FIRST IS WE WANT TO MAKE SURE THAT THERE IS EQUITABLE ACCESS FOR ALL PEOPLE. SO, ENSURING THAT COST, ACCESSIBILITY AND USER EXPERIENCE WILL ALL BE ADDRESSED IN TERMS OF THE PROGRAM. AND THEN THE LAST ONE IS MISPERCEPTION OR MISUSE. WE KNOW THAT THERE ARE CHALLENGES IN SCIENCE COMMUNICATION AND ASSEMBLY FROM THE BROADER PUBLIC AND SO MAKING SURE THAT IF WE ARE DESIGNING A PROGRAM OR A PARTICULAR SOLUTION FROM WITHIN THE PROGRAM AREA, THINKING REALLY CRITICALLY, LIKE HOW COULD THIS POTENTIALLY BE MISPERCEIVED OR MISUSED? AND THEN HOW WOULD WE MITIGATE THAT AND MAKE SURE THAT IS BUILT IN FROM THE PROGRAM DESIGN IN THE FIRST PLACE? NEXT SLIDE. SO, HOW DO WE THINK ABOUT SUCCESS? WE TALKED ABOUT THE WELL DEFINED PROBLEMS. WE TALKED ABOUT THE PROGRAM LIFE CYCLE. THE GOAL IS, THESE PRODUCTS OR ACTIVITIES WE ENGAGE IN, THEY CAN MEANINGFULLY HELP REAL PEOPLE WHO WANT THEM AND WILL ADOPT THEM. WE TALK ABOUT SEPARATING THE IMPROBABLE FROM IMPOSSIBLE. OCCASIONALLY YOU SAY YOU WANT TO DO THIS THING AND YOU GET A CONSTITUENCY THAT SAYS, THAT IS IMPOSSIBLE. WE DON'T THINK ANYTHING IS IMPOSSIBLE. WE THINK WITH THE RIGHT THINKING WE CAN TAKE IT TO IMPROBABLE AND THAT IS REALLY WHERE WE WANT TO EXIST IS THOSE THINGS THAT SEEMINGLY ARE IMPOSSIBLE, WHAT CAN WE DO TO DESIGN A PROGRAM TO MAKE THEM MEASURE IN THE IMPROBABLE SIDE AND THEN WE'LL TAKE ON THAT RISK AND WITH THE RIGHT PROGRAM MANAGERS AND THE RIGHT FUNDING, WE'LL SEE IF WE CAN ADDRESS IT. AND THEN AGAIN, DELIVER A BETTER HEALTH RESULTS TO EVERYONE. SO, WE, IT'S WIDE OPEN THE WAY WE ARE THINKING ABOUT HOW WE PRIORITIZE WITHIN THE HEALTHY ECOSYSTEM AND SO LOOKING FOR THE PROGRAM MANAGERS TO HELP DRIVE THAT. AND OUR FUNDING WILL BE VERY FLEXIBLE, CONTRACTS AND COOPERATIVE AGREEMENTS, OTHER TRANSACTIONAL AUTHORITY IS IT'S NOT GRANTS BASED WHICH IS AGAIN A UNIQUE CAPABILITY WE HAVE WITHIN THE NIH ECOSYSTEM. NEXT SLIDE. THE LAST THING I WANT TO TALK ABOUT AND I'LL STOP AND OPEN UP FOR QUESTIONS, THE WAY WE ARE THINKERRING ABOUT ENSURING THAT WE CAN TAKE A PRODUCT AND REALLY TRANSITION IT TO THE CURRENT SECTOR OR CURRENT MARKET. WHICH IS CRITICALLY IMPORTANT FOR THE VAST MAJORITY OF WHAT WE DO. WE ARE BUILDING IN, DEVELOPED AN ENTIRELY NYE OFFICE DIFFERENT THAN DARPA AND THE OTHERS AND IT SPECIFICALLY IS DEDICATED TO TRANSITION OF PATIENTS. SO WE HAVE A SUPPORT PROGRAM. WHEN A PROGRAM MANAGER IS DESIGNING THAT PROGRAM, WE WILL DO A NUMBER OF DIFFERENT ACTIVITIES INCLUDING MARKET ACCESSMENT AND HUMAN SUBJECT DESIGN TO SUPPORT OMIZEDING THAT PROGRAM. MAKING SURE THAT DURING BAA DEVELOPMENT, THE WE THINK WHO ARE THE PERFORMERS AND HOW CAN WE LEVERAGE INNOVATION HUBS TO BE ABLE TO SUPPORT THE PROGRAM DEVELOPMENT. WE'LL DO VENTURE CAPITAL STYLE DUE DILIGENCE MAKING SURE THE PERFORMERS CAN BE TRUSTED WITH THE RESOURCES THAT WE ARE AFFORDING THEM, THE TIME WE ARE AFFORDING THEM. AND VALIDATE THE TRANSITION POTENTIAL. LOOK AT A LOT OF EARLY PROGRAM PERFORMS. I TALKED ABOUT THAT. BRINGING FROM INVESTORS, TRYING TO MAKE SHUSH THAT WE IDENTIFY MITIGATING RISK. THE REGULATORY PROCESS IS HUGELY COMPLEX MAKING SURE THAT ANY OF THE PERFORMERS AND THE PROGRAM MANAGERS UNDERSTAND THAT. AND MAKING SURE THAT WE PROTECT IT, HELP COMPANY FORMATION. SO IF A PRODUCT CAN GO OFF AND BECOME A COMPANY, MAKING SURE THAT IT IS DONE IN A SUSTAINABLE WAY, HELPING WITH LEGAL AND MARKETING SERVICES AND THEN ULTIMATELY TRANSITIONING THE OUTPUTS AS WE SAY TO SURVIVE IN THE WILD SO THEY CAN TRANSITION TO THE THIRD PARTY INVESTMENTS AND THEN CONTINUE WITH MENTORSHIP AND ACCESS TO KEY CUSTOMERS AND INVESTORS. I THINK -- NEXT SLIDE. SO THESIS ARULE JUST -- WHERE WE ARE NOW. SO WE ARE STANDING UP AND ACHIEVING A LOT OF EXTERNAL ENGAGEMENT, POTENTIAL COOPERATIVE PARTNERS TO REALLY MAKE SURE THAT WE ARE SETTING OUR AGENCY UP FOR SUCCESSFUL NEXT SLIDE. THAT'S IT. SO, OUR CALL TO ACTION IS, IF YOU KNOW OF ANY PROGRAM MANAGERS THAT REALLY EMBODY THAT INNOVATIVE SPIRIT AND THAT RISK TAKING, WE ARE ACTIVELY LOOKING FOR PROGRAM MANAGER APPLICANTS RIGHT NOW. OUR GOAL IS TO HIRE 10-20 THIS YEAR. WE HAVE NONE. AND OUR GOAL IS TO SCALE THAT TO POTENTIALLY UP TO 30 BY THE END OF NEXT FISCAL YEAR. SO WE ARE IN THE RAPID GROWTH PHASE WHICH MEANS THAT IF YOU HAVE A PROGRAM MANAGER WITH A GREAT IDEA IN AN AREA YOU'RE PARTICULARLY PASSIONATE ABOUT, THEY STAND A BETTER CHANCE RIGHT NOW OF MAKING IT THROUGH THE PIPELINE QUICKLY WHILE WE ARE STILL IN THIS PHASE. I WILL STOP THERE AND HAPPY TO TAKE ANY QUESTIONS THAT YOU MAY HAVE. >>THAT WAS GREAT. I HAVE SO MANY QUESTIONS. LET ME TAKE THE LIBERTY OF ASKING A COUPLE OF MANY AND I'LL TRY TO MAKE THEM GENERAL. FIRST UNDERSTANDING THE IMPORTANCE OF THE PROGRAM OFFICER. DO THE IDEAS AND PROPOSALS COME FROM THE PROGRAM MANAGER TO ARPAH OR DO YOU IN ANY WAY REACH OUT SOLICITING INTEREST IN CERTAIN AREAS CENTRALLY? SO IS IT DETERMINING OR DO YOU DEPEND ON THE PROGRAM OFFICER? AND THEN THE SECOND PART AND IT'S RELATED. MANY OF US, NIH PARTICULAR ARE SENSITIVE TO THE IMPORTANT BUT AT TIMES CONTROVERSIAL RELATIONSHIP BETWEEN NIH AND ARPAH. WHAT DO YOU SEE AS THE NON-CONTROVERSIAL, PURELY PRODUCTIVE WAYS THAT WE CAN INTERACT WITH ARPH WITHOUT RAISING CONCERNS ABOUT THE NEED FOR THESE TO BE THROUGH THESE DISTINCT AGENCY? >>IT'S BOTH. RIGHT NOW WE HAVE A OPEN SOLICITATION FOR PROGRAM MANAGERS COMING IN AND BRINGING WITH THEM THEIR PROBLEMS. SO IT'S VERY MUCH A PUSH FUNCTION. YOU NEED TO DO MORE IN WHATEVER PARTICULAR HEALTHY ECOSYSTEM DOMAIN OR BIOTECH DOMAIN. BUT WE ARE ALSO DOING THE EVENTS LIKE THIS WHERE WE KNOW WE WANT TO FUND RESEARCH. WE WANT TO FUND SOMETHING IN THIS SPACE. AND SO, PROACTIVELY REACHING OUT TO YOUR COMMUNITY OR OTHER COMMUNITIES WHERE WE ARE HOPING THAT BY OUR PARTICIPATION IN YOUR EVENTS, WE ACTUALLY CAN GET PROGRAM MANAGER. SOMEONE ON THIS CALL OR SOMEONE YOU KNOW WHO IS LIKE, I LOVE TO DO THAT. LIKED YOUR CONSTITUENCY AND YOUR COLLEAGUES. AND THEN THAT WAY, TRYING TO BALANCE THE PUSH AND PULL FUNCTION SO WE GET A REALLY ROBUST, BROAD SET OF ACTIVITIES THAT CROSS OUR PORTFOLIO AREAS. IN TERMS OF PRODUCTIVE ENGAGEMENT WITH OUR NIH COLLEAGUES, THAT FOR ME IS ONE OF MY PRIORITIES. I HAVE HAD THE OPPORTUNITY TO WORK NEAR NIH -- THIS IS MY FIRST OPPORTUNITY TO WORK AT NIH. I'M SUPER EXCITED ABOUT IT AND I HAVE SUCH TREMENDOUS RESPECT FOR THE COLLEAGUES AND EVERYTHING YOU DO WITHIN YOUR ICs. SO TRYING TO FIGURE OUT WHAT IS THE ROUTINE ENGAGEMENT THAT WE HAVE WITH YOU SUCH THAT YOU KNOW WHAT WE ARE DOING, WE CAN BENEFIT FROM KNOWING WHAT YOU'RE DOING. WE DON'T DUPLICATE ACTIVITIES. WE DON'T COMPETE FOR THE POTENTIAL PARTNERS TO DO THE WORK WE NEED TO DO. UNLESS WE ARE ACTUALLY IN A PLACE WHERE WE CAN DO SORT OF -- I DON'T KNOW WE CAN DO CO-FUNDING. I WOULD HAVE TO ASK OUR BUDGET FOLKS. BUT CAN WE WORK IN PARALLEL WITH ON THE SAME TYPE OF PROBLEM? WE'LL TAKE SOME OF THE RISKIER ASPECT, YOU TAKE SOME OF THE WORK THAT YOU KNOW YOU CAN DO WITHIN YOUR -- WHATEVER THE STRUCTURES ARE WITHIN YOUR IC, BUT WE COME TOGETHER TO HAVE THESE VERY PRODUCTIVE RELATIONSHIPS. AND I THINK ONE OF MY GOALS AS WE GET PROGRAM MANAGERS ON, AND THE PROGRAM MANAGERS ARE INTERESTED IN DOING SOMETHING THAT WE KNOW IS ALREADY THE TOPICALLY ONGOING AT NIH, NOT BEING SHY. LIKE NOT LIKE LET'S NOT HUDDLE AND JUST PRETEND NO ONE ELSE IS DOING IT. LET'S TALK ABOUT WHAT WE THINK WE ARE GOING TO DO AND GET FEEDBACK. THERE IS A LIKELIHOOD AND I SAY THIS ALL THE TIME. WITHIN THE ICs YOU'RE THE LEADING EDGE TECHNICAL EXPERTS WITHIN THOSE AREAS. AND SO FOR US, THE HUBRIS THINKING WE ARE THE FIRST PEOPLE TO THINK OF IT, PROBABLY WON'T WORK OUT SO WELL. SO WE THINK OF SOMETHING LIKE, WE HAVE TO DO THIS, GOING OVER TO THE IC AND HAVING A CONVERSATION AND HAVING THE IC SAY TO US, WELL, WE TRIED THAT THREE YEARS AGO AND HERE IS WHY IT DIDN'T WORK. OR WE ALREADY HAVE THREE PROGRAMS THAT ARE WORKING IN THAT SPACE AND ALLOWING US TO TAILOR OUR PROGRAM TO OCCUPY UNIQUE SPACES. SO I SEE GREAT POSITIVE POTENTIAL TO WORK WITH COLLEAGUES AT NIH AND I'M HOPEFUL IT'S A BIDIRECTIONAL RELATIONSHIP. IF WE CAN'T TAKE THAT RISK, PASS IT TO US SO WE MIGHT BE ABLE TO THINK ABOUT IT IF WE HAVE THE RIGHT PROGRAM MANAGER IN PLACE. I HOPE TO HAVE IT. >>GREAT EXCITING ANSWER. SHALL WE TAKE QUESTIONS FROM SOME OF OUR MEMBERS? SHELLY? >>THANK YOU VERY MUCH FOR YOUR VERY INSPIRATIONAL TALK. I WAS VERY ENERGIZED BY YOUR BOLD WISH AND EXPEDITING INNOVATION. THE QUESTION I HAD IS A CLARIFYING ONE. DO YOU ENVISION THAT THE PRODUCTS AND THE PROJECTS WILL BE INITIATED BY THE PROGRAM STAFF? OR DO YOU SEE A PROCESS FOR INVESTIGATOR INITIATIVE PROPOSAL TO BE REVIEWED AND THEN COULD THOSE LEAD TO FUNDING? >>IT'S A REALLY GOOD QUESTION. SO, THE VAST MAJORITY ARE GOING TO COME IN AS PROGRAM MANAGER DESIGNED PROGRAMS SO THEY COME IN WITH THE PROBLEMS THAT THEY COME UP WITH THE PROGRAM DESIGN AND THEN WE FUND PERFORMERS THAT ARE ALIGNED THE ASPECTS OF THEIR PROGRAM DESIGN. BUT WE ARE GOING TO HAVE AN OPEN VAA AND WHAT THAT MEANS IS THAT IT'S SORT OF GOING TO LAY OUT SOME FOUNDATIONAL PRINCIPLES ABOUT WHAT ARE WE LOOKING FOR IN INNOVATION ACROSS THE HEALTHY ECOSYSTEM? SO IT'S NOT DEFINED TO A SPECIFIC DISEASE OR A SPECIFIC SOLUTION SET BUT IT'S RATHER MORE OPEN AND IT SAYS, PARAPHRASING, WHAT IS IS IT WE ARE NOT DOING? WHAT IS IT NOT BEING FUNDED THAT IS PARTICULARLY INNOVATIVE THAT WE WOULD REALLY WANT TO -- THAT LIKE AN INVESTIGATOR SAYS, YOU KNOW, ARPAH YOU NEED TO FUND THIS TYPE OF RESEARCH PORTFOLIO. AND I DON'T WANT TO OVER PROMISE BUT REALLY GOOD IDEAS COME THROUGH THAT TYPE OF AN OPEN VAA. AND THAT WOULD ALLOW US TO SAY, OH, MY GOSH, WE HAVE NOT -- WE DON'T HAVE A PORTFOLIO OR A PROGRAM MANAGER AND THEN BEFORE WE FUND IT OF COURSE, WE WOULD HAVE TO FIND A PROGRAM MANAGER THAT COULD RUN THAT PARTICULAR ACTIVITY. IN AN IDEAL WORLD YOU'D HAVE AN INVESTIGATOR WHO PUTS IN SOMETHING IN THE OPEN VAA THAT SAYS YOU MUST FUND THIS. AND THEN RAISES THEIR HAND AND SAYS, I WILL BECOME YOUR PROGRAM MANAGER. AND IF IT WORKS OUT WE HAVE THE IDEA AND THE PROGRAM MANAGER AT THE SAME TIME. SO, THERE IS AN OPPORTUNITY OUTSIDE OF THE PROGRAM MANAGERS THROUGH THESE OPEN VAAs THAT WE'LL PUT OUT THERE. WE'RE HOPING TO BE ABLE TO GET OUR OPEN VAA OUT. WE ARE BRAND NEW AND VERY EXCITED. WITHIN THE NEXT SIX MONTHS HOPING TO GET A OPEN VAA OUT THERE TO START TO GENERATE THESE INVESTIGATOR OF-INITIATED IDEAS. >>ABC ANNOUNCEMENTS AND I THINK NIH HAS THE AUTHORITY AND HAS USED IT INFREQUENTLY, CORRECT? >>YES, ABSOLUTELY. I GUESS IT'S THE CLOSEST THING IN THE CONTRACT WORLD TO A UNSOLICITED GRANT MECHANISM, REALLY. >>THAT'S RIGHT. ANN: THANK YOU VERY MUCH. THIS WAS REALLY EXCITING. I HAVE A KIND OF -- I'M AN ECONOMIST BY TRAINING AND I HAVE A QUESTION ABOUT, SO WE PAY FOR THE HIGH-UNCERTAINTY HIGH CONSEQUENCE RESEARCH AND THEN WHAT STOPS THAT FROM IN 5 YEARS TIME BEING A DRUG THAT APPEARS ON THE MARKET WITH A PRICE TAG OF 36,000? I MEAN, I ASSUME THAT WAS UNDER PART 9 OF YOUR 10 QUESTIONS BUT IT IS ONE THAT I THINK CERTAINLY HAS BIG CONSEQUENCES FOR US ALL BEING ABLE TO BENEFIT FROM THIS. >>ABSOLUTELY. IT IS PART OF -- BUILT INTO PART 9 ENSURING EQUITABLE ACCESS. IT WILL BE A VERY PROACTIVE PART OF WHAT WE ARE THINKING ABOUT SO YOU HAVE YOUR PROBLEM. HERE IS HOW YOU'RE DESIGNING YOUR PROGRAM. HERE IS WHAT YOU ARE THINK THE SOLUTION S HOW IS THAT GOING TO BE EQUITABLE? AND REALLY MAKING SURE, WE'LL CALL IT PROWELL CONDUCT PROFILES. SO IF YOU'RE GOING TO CREATE A PRODUCT, PART OF YOUR TARGET PRODUCT PROFILE HAS TO BE COST EFFECTIVE. AND SO, WHAT DOES YOUR PRODUCT HAVE TO LOOK LIKE TO ACHIEVE COST EFFECTIVE NATURE? SO WE TALKED ABOUT THE CANCER VACCINE FOR THE PRICE OF A CUP OF COFFEE. SO IT'S ON OUR MIND AND IT WILL BE A CONSTRAINT FOR SOME OF OUR PROGRAMS WHERE WE SAY, IF IT'S GOING TO COST US 36,000 DOLLARS A TREATMENT DOSE AND THAT'S THE OUT OF REACH FOR SO MANY PEOPLE WHO MAY HAVE THAT CONDITION, THEN IT'S NOT FOR US. UNLESS THERE IS A WAY WE CAN TAKE IT FROM 36,000 DOLLARS AND WE CAN SCALE IT SO THAT IT BECOMES 3.60 OR SOMETHING LIKE THAT. WE ARE ALSO PUTTING IN PLACE, AND THIS -- MANY ARE FAMILIAR WITH IT, IT IS AN LC PROGRAM SO THE ETHICS LEGAL AND SOCIETAL IMPLICATIONS ABOUT MAKING SURE WE HAVE A MATURE WAY TO THINK ABOUT OUR PORTFOLIO AND PROGRAMS SPECIFICALLY. AND PART OF WHAT THEY ARE TASKED WITH IS THIS EVALUATION COST BENEFIT AND IMPACT TO SOCIETY. SO, WE ARE BAKING IT IN IN A NUMBER OF DIFFERENT WAYS BECAUSE YOU'RE RIGHT. THERE IS BOST DEVELOPING SOMETHING THAT MAYBE IS SO UNIQUE THAT ONE COULD SAY, WELL, WE SHOULD CHARGE 36,000 DOLLARS A YEAR. BUT IT'S NOT IN LINE WITH WHAT OUR GOALS ARE AS AN AGENCY. >>THANK YOU. >>SUSAN? >>SUSAN: THIS WAS REALLY, REALLY EXCITING. SO I HAVE A QUESTION SORT OF ABOUT TRYING TO GET MY HEAD AROUND THIS IN TERMS OF, CAN YOU GIVE US AN EXAMPLE OF -- I WAS NOT CLEAR ON HOW SPECIFIC THIS WOULD BE VERSUS HOW BROAD FINDINGS COULD BE OR PROGRAM MANAGER INDIVIDUAL AN IDEA TO DO SOMETHING REALLY BROAD, REALLY FOCUSED AND MAYBE AN EXAMPLE OF SOMETHING THAT WAS A SUCCESS VERSUS SOMETHING THAT WAS A FAILURE AND WHY. JUST TO GET A BETTER GRASP. >>THE GOOD NEWS IS WE HAVEN'T HAD ANY SUCCESS SYSTEM OR FAILURES YET BECAUSE WE HAVEN'T SPENT ANY MONEY. BUT GIVE US TIME. I CAN GIVE YOU A COUPLE OF IDEAS THAT HAVE COME THROUGH. SO AS WE INTERVIEWED THESE PROGRAM MANAGERS AND THEY ARE TELLING US OR GIVING US THEIR PITCH FOR WHAT THEY WOULD WANT TO WORK ON. SO SOMETHING AS SMALL AS LIVING CELLS THAT COULD IMPLANTED AND SECRETE SMALL BIOMOLECULES TO TARGET CERTAIN DISEASE STATES OR CERTAIN THERAPEUTIC INTERVENTION. AND IT WOULD NEED TO BE NECESSARILY TAILORED TO THE PHYSIOLOGY OF THE INDIVIDUAL TA IS RECEIVING THE LIVE REPLICATING CELLS THAT ARE PRODUCING THE SMALL MOLECULES. SO SOMETHING ON THAT SCALE. AND THEN ALL THE WAY ON THE SCALE WHERE WE ARE LOOKING AT USING AIML TO HELP FILL IN THE GAPS FOR BEHAVIORAL HEALTH CHALLENGES. SO INDIVIDUALS WHO ARE POTENTIAL RISK OF ABUSING OPIOIDS OR GOING THROUGH RECOVERY AND TRYING TO CREATE AT SCALE SORT OF COMPANION TO ALLOW US, AN AI COMPANION ALLOWING 24-7 INTIMATE CULTURALLY APPROPRIATE AND TAILORED CARE FOR THE INDIVIDUALS KNOWING THAT THAT IS GOING TO BE AN INCREDIBLY -- LIKE THAT ON RISK, WHEN YOU TALK ABOUT RISK, THAT ONE IS GOING TO BE SUPER HIGH RISK AND THERE IS SO MUCH CHALLENGES ASSOCIATED WITH IT. SO THINKING ABOUT THAT. WE HAD OTHER PEOPLE PROPOSE CHANGES TO CITY DESIGN TO CREATE A HEALTH AND WELLNESS ENVIRONMENT. WE HAD PEOPLE TALK ABOUT HEALTHY BUILDINGS. I MEAN JUST A NUMBER OF DIFFERENT ASPECTS OF THE HEALTHY ECOSYSTEM WHICH GETS US SUPER EXCITED AND THAT'S EXACTLY WHERE WE WANT TO BE IS NOT JUST A BIOTECH COMPANY. WE WANT TO BE AN ORGANIZATION THAT CAN SUPPORT INNOVATION ACROSS THE HEALTH ECOSYSTEM. ASK ME IN A YEAR AND I'LL GIVE YOU A MORE BIG ANSWER ABOUT WHAT WORKED AND WHAT HAS NOT WORKED. >>THANK YOU. >>I THINK WE JUST HAVE TIME FOR MAYBE ONE MORE QUESTION. SO SHARON DO YOU WANT TO ASK YOUR QUESTION? >>THANK YOU. IT WAS A WONDERFUL TALK. I REALLY AM VERY EXCITED. I REALLY APPRECIATED IT. HAVING BEEN INVOLVED IN ANOTHER KIND OF GRAND CHALLENGE LIKE THIS, AND KNOWING THAT COMMERCIALIZATION IS ONE OF THOSE THINGS ON YOUR LAST SLIDE IT SOUNDS LIKE IT'S NOT ONLY FINANCIAL. YOU'RE GOING TO LOOK AT THE GREATER GOOD AND SOCIETAL IMPACTS BECAUSE WE CAN ALL, I'M SURE, THINK OF SO MANY EXAMPLES OF MAJOR PUBLIC HEALTH INNOVATIONS OR CLIMATE CHANGE INNOVATIONS THAT MAY NOT BRING IN THE DOLLARS IMMEDIATELY BUT WOULD BE SO ESSENTIAL TO ADVANCE THE GREATER GOOD. SO, I JUST WANT TO MAKE SURE EXPLICITLY THAT WILL BE FACTORED IN? >>IT REALLY IS. OUR CHALLENGE IS, WE HAVE LIMIT DOLLARSS AND WE DON'T HAVE DOLLARS FOR SUSSTATEMENT. SO IF BEE DEVELOP SOMETHING THAT HAS THAT IMPACT FOR THE GREATER GOOD, WHICH I HOPE WE DO. ONE OF THE THINGS I DID IN MY PREVIOUS WORK AT THE HEALTH RESOURCES AND SERVICES ADMINISTRATION IS TO THINK MORE POPULATION LEVEL IMPROVEMENTS. THAT'S WHERE I SORT OF WORKED ON MY REN ORIVATION TO THINK ABOUT HOW DO WE CHANGE THE WHOLE SYSTEM? HOW DO WE BENEFIT WHOLE POPULATIONS? THE CHALLENGE IS, AND YOU CAN APPRECIATE THIS, YOU CAN COME UP WITH AN INCREDIBLY SMART DESIGN OR CAPABILITY OR WHATEVER IT HAPPENS TO BE, POLICY AND PROCEDURES AND TECHNOLOGY, BUT IF YOU DON'T HAVE A SUSTAINMENT PARTNER AND IF THERE IS JUST A RELIANCE ON THE GOVERNMENT FOR SUSTAINMENT, IT STARTS TO CONSTRAIN WHAT YOU CAN MEANINGFULLY DEVELOP AND THEN TRANSITION. SO WE HAVE TO KEEP THAT IN MIND THAT DOESN'T MEAN WE CAN'T DEVELOP NOVEL PARTNERSHIPS FOR SUSSTATEMENT AND THERE IS A LOT OF ORGANIZATIONS THAT WE CAN POTENTIALLY TRY TO PARTNER WITH FOR NON-BIOTECH INNOVATIONS. AND THAT IS SOMETHING WE'LL LOOK AT. BUT I DO HOPE WE CAN INNOVATE ON A LEVEL OF IMPACT. >>SUSAN, THANK YOU VERY MUCH FOR YOUR TALK WE REALLY APPRECIATE THIS OVERVIEW AND WISH YOU ALL THE BEST. WE ARE DRINKING FROM THE FIRE HYDRANT AND SETTING UP A NEW AGENCY LIKE THIS. WE DO LOOK FORWARD TO COLLABORATIONS AND PLEASE REACH OUT TO US AT ANY TIME. BECAUSE WE HAVE A LOT OF PRIORITIES WITH OUR AGING POPULATION AND OBVIOUSLY WE HOPE THAT ARPAH WILL BE AN INTEGRAL PART OF SOLVING SOME OF THESE ISSUES THAT WE HAVE. >>THANK YOU. AND LIKEWISE. PLEASE DO NOT HESITATE TO REACH OUT TO US. WE WOULD LOVE NOTHING MORE THAN TO DEVELOP A STRONG PARTNERSHIP SO WE CAN EXCHANGE IDEAS AND ACTIVITIES AND EVERYTHING. >>SURE THING. THANK YOU, AGAIN. >>THANK YOU. >>YES. >>ALL RIGHT, THANK YOU ALL. NEXT UP NOW WE'LL MOVE ON WITH OUR PROGRAM. NEXT WILL BE ASKING DR. LUIGI FERRUCCI, OUR HEAD OF OUR CLINICAL CENTER TO GIVE OUR INTRAMURAL PROGRAM REPORT. SO LUIGI? >>LUIGI FERRUCCI: THANK YOU. -- [ INAUDIBLE ] *6 WORLD EXPERT IN NON CODING -- I THINK NEW FRONTIER OF GENOMICS. AND SHE HAS BEEN REVIEWING VERY RECENTLY AND WE SUBMIT THAT ONE RESPONSE TO THE REPORT WAS ABSOLUTELY POSITIVE AND SHE WILL INCLUDE IN HER PRESENTATION SOME ANSWER TO THE COMMENT FROM THE BOARD OF SCIENTIFIC COUNCIL. THE SECOND TALK WILL BE GIVEN FROM DR. RANHAN SEN, CHIEF OF THE MOLECULAR BIOLOGY AND IMMUNOLOGY. DR. SEN IS A VERY WELL-KNOWN IMMUNOLOGIST. HIS WORK ON NF-kB AND CONTRIBUTED SUBSTANTIALLY IN THE FUNCTION OF THIS VERY IMPORTANT SYSTEM. IT IS SOMETIMES SLOWLY PROGRESSIVELY CONVINCING -- ABOUT AGING AND SO I THINK HE WILL TALK TO YOU ABOUT SOME REALLY GREAT WORK. AND AFTER THAT, I WILL GIVE YOU SOME DESCRIPTION ABOUT WHAT HAPPENED IN THE IP IN THE LAST YEAR. I WILL TRY TO SHORTEN MY PRESENTATION AND GIVEN THE FACT WE HAVE ACCUMULATED SOME DELAY. WITHOUT HESITATION, I ASK MYRIAM GOROSPE TO SHARE HER SLIDES. >>MYRIAM GOROSPE: SO THANK YOU ALSO SENIOR LEADERSHIP AND COUNCIL MEMBERS FOR GIVING ME AN OPPORTUNITY TO PRESENT AN UPDATE IN THE LABORATORY OF GENETICS AND GENOMICS IN OCTOBER 2021. AND I'LL START WITH THIS BIC PICTURE VIEW OF HOW WE CONTRIBUTE TO THE MISSION OF THE. THIS IA TO REDUCE DELAY AND PREVENT ASSOCIATED DISEASE AND DISABILITY IN THE LABORATORY OF GENETICS AND GENOMICS BY CONTRIBUTING TOOLS AAPPROACHS AND METHODS AND EXPERTISE OF CELL AND MOLEC LABILES WHICH IS WHAT WE ARE ALL IN IN LGG. SO THE LABORATORY IS COMPRISED OF THREE SECTIONS. HEADED BY THREE SENIOR INVESTIGATORS. AND VERY BRIEFLY, WE DON'T WANT -- [ INAUDIBLE ] AS YOU'LL SEE ALL OF US FOCUS VERY MUCH ON THE PROCESS OF GENE REGULATION, FLOW OF GENETIC INFORMATION IN ONE WAY OR ANOTHER. WE FOCUS ON POST TRANSCRIPTIONAL GENE REGULATORY PROCESSES IN AGING PARADIGMS AND FOCUSES ON TELOMERE MAINTENANCE AND TELOMERE FUNCTION. WE ALSO HAVE TWO INVESTIGATORS. LOOKING AT CHROMATIN REMODELING AND REGENERATION AND ANOTHER LOOKS AT ONLY DYNAMICS AS WELL BUT FOCUSING STRONGLY ON COMPUTATIONAL BASIS OF GENE REGULATION. WE ALSO HAVE ANOTHER JUNIOR INVESTIGATOR IN THE LAB, AN INDEPENDENT RESEARCH COLLABORATOR. AND THE HER RESEARCH FOCUSES ON OUTCOMES OF SENESCENCE IN THE CONTEXT OF AGING, IN PARTICULAR ARTHROSCLEROSIS. AND THE FINAL GROUP IS LED BY THE COMPUTATIONAL GENETICS AND COMPUTATIONAL CORE, AND SUPPORTS US AND COMPLIMENTS WHAT WE DO WITH SUPPORT AND THE CORE OF COURSE SUPPORTS MANY PROGRAMS ACROSS. SO WHAT I'D LIKE TO DO TODAY IS TOUCH ON TWO THINGS. SWONE GIVE YOU A BRIEF UPDATE OF WHAT EACH OF THESE SECTIONS AND UNITS HAVE DONE OVER THE PAST YEAR SINCE WE WERE REVIEWED. AND THEN I'LL CONCLUDE WITH SPECIFIC WAYS IN WHICH WE ARE ADDRESSING THE VERY HELPFUL AND VALUABLE RECOMMENDATIONS AND ADVICE. SO I'LL START WITH THE PROGRESS UPDATES. SO WE DON'T HAVE DEDICATED A BIT OF TIME OVER THE PAST FEW YEARS LOOKING AT DATA. OVER THE PAST YEAR, THESE EFFORTS HAVE LED TO A NUMBER OF PUBLICATIONS. ONE OF WHICH IDENTIFIES SUBSETS OF mRNAs WHO TRANSLATION AND STABILITY ARE CONTROLLED BY TOP 3. IN ANOTHER ARTICLE THEY HAVE ESTABLISHED THAT TOP 3 DATA IS DISPENSABLE FOR VIOLATES REPLICATION. THIS IS A POINT THAT HASH MADE EARLIER AND THEY BROUGHT SUPPLIES TO THIS QUESTION. AND IN ANOTHER ARTICLE THEY HAVE A CATALOG, TRANSCRIPTION FACTORS IMPORTANT FOR HUMAN EMBRYONIC STEM CELLS. MY OWN LAB CONTINUES TO LOOK AT GENE REGULATION, VERY MUCH FOCUSED ON REGULATION OF RNA FROM THE POINTED OF TRANSCRIPTION UNTIL THE RNA IS USED FOR SYNTHESIS AND MOST FOCUS IS ON THE FACTORS, RNA BINDING PROTEINS THAT DRIVE THIS POST TRANSCRIPTIONAL MESSENGER RNA. OVER THE PAST YEAR, WE HAVE MADE PROGRESS IN FOUR DIFFERENT AREAS OF EFFORT IN THE LABORATORY. WE HAVE IDENTIFIED SIGNALING PATHWAYS THAT ARE CRITICAL IN THE PROCESS OF CELL SENESCENCE AND LOOKED AT TISSUE AGING. WE ALSO HAVE IDENTIFIED SOME LONGER CODING RNAs ESSENTIAL FOR MUSCLE REGENERATION AS WELL AS MACROPHAGES THAT CHANGE ACROSS THE LIFESPAN IN THE MUSCLES. WE HAVE HAD THE OPPORTUNITY TO DO A HISTORICAL REVIEW OF RNAs FOR THE PAST 25 YEARS. AND RECENTLY WE WERE ABLE TO BEGIN TO LOOK AT CIRCULAR RN56789s. NOT REVIEWED IN 2021 BECAUSE SHE HAD JUST MOVED TO THE LGG, BUT OVER THE PAST YEAR, HER WORK HAS CONTINUED TO BE -- TO MAKE EXCITING PROGRESS. IN THREE OF THE ARTICLES, SHE HAS BEEN ABLE TO IDENTIFY THE PROTEIN RAT 1 AS BEING A KEY MOLECULAR FACTOR IN MAINTENANCE. SHE ALSO DEVELOPED A METHOD THAT IS QUITE USEFUL IN BEING ABLE TO MEASURE CONVENIENTLY TELOMERE DYSFUNCTION AND SHE HAS LOOKED AT INTERVENTIONS -- IN SHORT TELOMERE SYNDROMES IN HUMANS. MOVING ON TO THE TENURED TRACK INVESTIGATORS AND LOOKING AT EPIGENETIC MECHANISMS OF TISSUE AGING. THIS IS A PERIOD FOR HER OVER THE PAST YEAR. AND I'M EXCITED TO TELL YOU THAT ONE OF HER MAJOR PROJECTS IN THE LAB WHICH LOOKS AT TISSUE REGENERATION, LIVER REGENERATION,S AS A FUNCTION OF AGE IN MUSCLE WITH LOOKING AT CHROMATIN CHANGES IS NOW IN FINAL STAGE LESS OF REVISION. ALSO CONTINUING TO LOOK AT RNA DYNAMICS OVER THE PAST YEAR AND THIS WORK HAS LED TO ADDITIONAL ARTICLES, ONE OF WHICH ALSO I'M EXCITED TO SAY CAPTURES A LOT OF WORK THEY HAVE DONE OVER THE PAST COUPLE OF YEARS IN MOUSE MODELS OF AGING LOOKING AT RNA DYNAMICS, IN PARTICULAR LOOKING AT RNA LENGTH AND USING TECHNIQUES SUCH AS SEQUENCING WITH A VERY STRONG AND CUTTING-EDGE COMPUTATIONAL SUPPORT WHICH IS ACTUALLY LED TO THE DEVELOPMENT OF SOFTWARE AND OTHER APPROACHES IN-HOUSE BY THE TEAM. LEADING THE PROGRAM, THE NEWEST IN THE LGG. SHE HAS BEEN DEVELOPING CELL AND MOUSE MODELS OF VASCULAR SENESCENCE AND IDENTIFYING DRUGS THAT TARGET SINESENCE IN THIS NICHE. SHE ALSO HAD BEEN QUITE BUSY OVER THE PAST YEAR AND ONE OF THE RECENT STUDIES IN WHICH SHE HAS LOOKED AT SINGLE CELL POPULATIONS IN THE ARTHROSCLEROSIS NICHE IN MOUSE IS NOW AGAIN IN FINAL STAGES. SO REVISION AND PLANS TO SEND IT BACK IN THE FUTURE. AND FINALLY, WE HAVE BEEN QUITE BUSY SUPPORTING ALL OF THE GROUPS WHILE THE GROUPS IN. THIS IA BY PROVIDING DIVERSE OMICS DATA BY COORDINATING DATE TA SCIENCE EXPERTISE, BY ACQUIRING AND MAINTAINING INSTRUMENTS AND SOFTWARE THAT ALLOWS US TO BUILD MUCH OF THE WORK WE DO. AND IN SOME CASES, BY WORKING WITH US WITH INDIVIDUAL GROUPS TO SET UP SPECIFIC PROJECTS THAT REQUIRE EXPERTISE THAT WE DON'T HAVE IN OUR OWN GROUPS. AND THEY ARE ABLE TO VERY QUICKLY HELP US DEVELOP METHODS AND APPROACH THAT IS WE CAN USE. SO THIS IS THE UPDATE OVER THE PAST YEAR BY ALL OF THE TEAMS THAT COMPRISE THE LGG. AND SO WHAT I'D LIKE TO DO IN THE REMAINING FEW MINUTES IS TELL YOU HOW WE ADDRESSED THE RECOMMENDATIONS AND ADVICE FROM THE BSC. SO THE BSC PROPOSED OR SUGGESTED THAT MORE VERIFICATION OF FINDINGS AND MODELS IN PATIENT SAMPLES AND WE HAVE TAKEN THIS ADVICE VERY SERIOUSLY. WE HAVE ADDITIONAL SENESCENCE MODELS WE ARE BEGINNING TO PUBLISH, INCLUDING MODELS OF SENESCENCE SIGNALING AND TELOMERE ATTRITION. SO THESE ACTUALLY INCLUDING MOUSE MODELS OF SENESCENCE. AND WE ARE ALSO VERY KEEN ON FOLLOWING THE ADVICE OF BRANCHING OUT AND EXPANDING INTO PATIENT SAMPLES AND WE ARE TEAMING UP WITH THE LARGE ENTERPRISE AT NIA. WE HAVE BEEN LOOKING AT MUSCLE AND SKIN IN THIS SPACE AND IN OTHER EFFORTS, WE ARE LOOKING AT LIVER FROM PATIENTS AS A FUNCTION OF AGE AND WE HAVE BEEN, AS I MENTI MENTIONED EARL, LOOKING AT ALS SAMPLES FROM HUMAN BIOPSIES AND NECROPSY. TO ILLUSTRATE THIS POINT, THIS IS A PROJECT THAT SEEKS TO CATALOG CHANGES ACROSS THE HUMAN LIFESPAN USING A VERY HEALTHY COHORT OF INDIVIDUALS OF DIFFERENT AGES FROM 20S TO THEIR 80s. AND A NUMBER OF TISSUES HAVE BEEN COLLECTED IN THIS STUDY. IN THIS CASE WE LOOKED AT SKIN BIOPSIES COLLECTED FROM THE PARTICIPANTS FROM WHICH WE OBTAINED FIBROBLASTS AND THEN COLLECT RNA, WHICH WE ARE NOW STUDYING AND PROTEINS THAT WAS STUDIED IN THE ARTICLE THAT WE LISTED A FEW MONTHS AGO. AND HERE ANALYSIS OF PROTEINS LED US TO IDENTIFY SPECIFIC PATHWAYS THAT WERE CHANGING AS A FUNCTION OF AGING IN THIS COHORT. THE BSC ALSO INDICATED THAT WE SHOULD BEGIN TO DESCRIBE MORE TRANSLATIONAL STUDIES TO MAKE OUR EFFORTS IN THIS SPACE MORE IMPACTFUL. WE ARE ALSO TAKING THIS RECOMMENDATION TO HEART. WE HAVE WORKED WITH IN STUDIES LED BY OTHERS LOOKING AT NOVEL THINGS ELIMINATES SENESCENCEIS AND TRACK INHABITORS TO CREATE DRUGS THAT ONE CAN EXPLOIT AND ADDITIONAL EFFORTS ARE ONGOING. ONE OF THESE STUDIES TO ILLUSTRATE THIS POINTED SO AFTER CAUSING CELL DAMAGE IN FIBROBLASTS AND OTHER CELLS, IS THE CELL RESPONSE INCLUDES ACTIVATION OF THE KINASE SAR? THAT CELL IS MORE LIKELY TO UNDERGO SENESCENCE. BUT IF SARIS INHIBITED OR IS SILENCERRED OR OTHERWISE IMPAIRED, THAT CELL IS MORE LIKELY TO UNDERGO APOPTOSIS AND WE CAN TEST THESE DRUGS IN PRE-CLINICAL PROD ELSE SUCH AS THIS ONE. THIS IS A MOUSE IN WHICH SENESCENCE IS TRYING TO APPLY INJECTION. TREATMENT WITH THESE TWO INHIBITORS TP1 AND 2 CAUSE NUMBER OF SENESCENCE CELLS TO DECREASE AS YOU CAN SEE IN THIS SLIDE. THE BSC ALSO ENCOURAGED FOR OTHER SUPPORT PROGRAM AND IN PARTICULAR THE DEVELOPMENT OF ADDITIONAL MODELS. AND WE ARE VERY THANKFUL TO THE OFFICIAL SCIENTIFIC DIRECTOR WHICH HAS COMMITTED PEOPLER ADDITIONAL FUNDS TO STUDY SENESCENCE AND MODELS AS WELL AS BY CREATION OF AN ADDITIONAL POSTBAC POSITION FOR MOUSE WORK. MOUSE MODELS THAT WE ARE ADOPTING AND DEVELOPING INCLUDE A MODEL WHICH WE ARE TESTING THE GINGER NONE A DRUG AND OTHER INHIBITORS AND OF TEADB AND I'LL USE MY LAST SLIDE TO ILLUSTRATE THIS POINT. IN ANOTHER RECENT ARTICLE, WE DISCOVERED THAT SENESCENT CELLS EXPRESS BOTH TRKB AND BDNF. AND THIS PARADIGM IS ONE THAT WE THOUGHT WAS ON THE -- RESTRICTED. BUT SENESCENCE ACQUIRED THIS PHENOTYPE AS WELL. AND IN FACT, IF THIS AUDIO CRIN OR RESPONSE IS IMPAIRED IN ANY WAY, THOSE CELLS ARE MORE LIKELY TO DIE THROUGH APOPTOSIS. AND SO WE CAN USE INHIBITORS OF TRKB IN PARTICULAR TO TEST THE POSSIBILITY OF INTERFERING WITH THE SENESCENCE PROCESS IN THIS MANNER. AND SO HERE TWO INHIBITORS TO BLOCK TRKB ACTIVITY. THIS WILL INJECT -- IN THREE MONTHS AND AS I CAN SEE IN KEEPING IN LINE WITH LIVER, THE NUMBER OF SENESCENCE CELLS DECLINE AS A FUNCTION OF ADMINISTRATION OF THE DRUG. THE FINAL RECOMMENDATION FOR WHICH WE ARE SUPER GRATEFUL TO THE BSC IS THAT A STAFF SCIENTIST BIOINFOMATIC EXPERT BE ADDED TO THE LAB. SO WESTERN ABLE TO RECRUIT DR. CHRISTINA MASON -- SO WE WERE ABLE TO RECRUIT -- SHE JOINEDIS 2022 AND SHE ALREADY ENRICHED THE PROGRAMMING IN MANY, MANY DIFFERENT WAYS. SO WITH THIS, I WILL THANK THE GROUP THAT I'M SO EXCITED TO BE A PART OF AND SO PROUD OF WORKING WITH. AND I WILL THANK ALL OF YOU FOR YOUR ATTENTION AND END HERE. THANK YOU. >>THANK YOU. GIVEN THE FACT THAT WE ARE LATE, WHY DON'T WE GO ON AND SEE THE OTHER PRESENTATION AND THEN PEOPLE CAN ASK THEIR QUESTIONS. >>OKAY. >>RAB JAN YOU CAN START SHARING YOUR SCREEN. >>RANHAN SEN: OKAY, I WILL. IS THAT VISIBLE AND I CAN BE HEARD? >>YES. >>THANK YOU VERY MUCH FOR THE KIND INTRODUCTION. GOOD AFTERNOON COUNCIL MEMBERS AND NIA LEADERSHIP AND OF COURSE ALL OF OUR COLLEAGUES WITH THE NIA. IT'S MY PRIVILEGE TODAY TO INTRODUCE TO YOU THE LABORATORY OF MOLECULAR BIOLOGY AND IMMUNOLOGY WHICH IS A PART OF THE INTRAMURAL RESEARCH PROGRAM OF THE NATIONAL INSTITUTE ON AGING. AT THE MOMENT, WE ARE SIX INVESTIGATORS. SUNG IS A TENURE-TRACK INVESTIGATOR INTERESTED IN TRANSCRIPTIONAL REGULATION. AND THE OTHER FIVE OF US ARE TENURED SENIOR INVESTIGATORS THAT HEAD OUR INDEPENDENT SECTIONS OF WHICH I WILL TALK ABOUT IN THE NEXT FEW MINUTES. A DEPUTY LAB CHIEF AND ALL OF US ARE INTIMATELY INVOLVED IN EACH OTHER'S PROGRAMS WITHIN THE LAB. AND I WILL OFTEN REFER TO IT IN SHORT AS LMBI. THE RESEARCH PROGRAMS SHARE THE GOALS OF ELUCIDATING MOLECULAR AND CELLULAR MECHANISMS TO REGULATE IMMUNITY AND THEREBY UNDERSTAND THE DECLINE IN RESPONSES. AS YOU ALL KNOW, THE COVID PANDEMIC OVER THE LAST FEW YEARS HAS REALLY HIGHLIGHTED AGAIN THE NEED TO UNDERSTAND AND AMELIORATE THE AGE ASSOCIATE SAID IMMUNE DYSFUNCTION IN HUMANS. GIVEN THE NEW SYSTEM IS VERY BROAD-BASED, I HAVE A SLIDE TO SHARE WITH YOU TO GIVE YOU ASTHENIES OUR INVESTIGATORS THAT ARE INVOLVED IN MANY ASPECTS OF IMMUNITY I. SO IN THE BACKGROUND HERE, WE START WITH IMMUNE DEVELOPMENT AND THIS COULD BE IMMUNE CELLS OF THE INNATE IMMUNE SYSTEM OR ADAPTIVE IMMUNE SYSTEM. ONCE THESE CELLS EXIST IN THE ORGANISM THEY ARE THERE TO MOUNTAIN IMMUNE RESPONSE SHOULD THE ORDER OF THEM BE FACED WITH SUCH A NEED. THAT IMMUNE RESPONSE THEN LEADS TO SO-CALLED EFFECTOR FUNCTIONS. THOSE ARE FUNCTIONS MEDIATED BOTH BY SOLUBLE MEDIATORS OR BY THE CELLS THEMSELVES THAT TRY TO GET RID OF THE INVADING PATHOGEN OR THE DANGER THAT THE ORGANISM FACES. ADAPTIVE IMMUNITY IN PARTICULAR, HAS THE EXTREMELY IMPORTANT PROPERTY OF BEING ABLE TO DEVELOP MEMORY. AND MEMORY IS THE BASIS FOR ALL VACCINATION AND ALSO THE REASON WHY ONCE INFECTED WITH ONE PATHOGEN ONE IS LESS SUSCEPTIBLE TO THAT SAME PATHOGEN LATER ON. AND FINALLY, THE IMMUNE RESPONSE HAS TO BE REGULATED. TOO MUCH OF AN IMMUNE RESPONSE LEADS TO IMMUNITY AND TOO LITTLE OF IMMUNE RESPONSE LEADS TO IMMUNODEFICIENCY. THERE IS A SILTS BALANCE THAT THE IMHUGE SYSTEM HAS TO ACHIEVE -- SUBTLE BALANCE. OUR INVESTIGATORS ADDRESS MANY OF THE THESE ASPECTS OF IMMUNITY IN THEIR INDIVIDUAL RESEARCH PROGRAM. FOR THE PRESENTATION THIS AFTERNOON, I THOUGHT I WOULD FOCUS ON THE RECENT ADVANCES MADE BY THREE OF OUR INVESTIGATORS, MA -- AND ALSO GIVE OFF A SENSE OF WHAT THE THREE OF US DO AND HOPE TO GIVE YOU THEIR UPDATE IN THE NEXT TIME WE PRESENT TO THE COUNCIL. NOW AT THIS POINT, SUN'S LAB JUST PUBLISHED THE DEVELOPMENT AND USE OF AN EXTREMELY VALUABLE REAGENT. MA'S LAB WORKS ON THE TRANSCRIPTION FACTOR NF-kB T IS CENTRAL EVOLVED IN ESSENTIALLY ALL IN FLAM TORY RESPONSES. SO SHE HAS GENERATED IN MICE, THESE REPORTER ALLELES OF TWO OF THE DIFFERENT FAMILY MEMBERS OF THE NF-kB FAMILY. IN THIS CASE, RAD A PROTEIN IS TAGGED WITH THE GFB. THE REL IS TAGGED WITH A DIFFERENT COLORED MARKER. SHE HAS SHOWN THESE FUSION PROTEINS DO NOT EFFECT DEVELOPMENT IN THE MOUSE SO THEY ARE EXPRESSED IN ALL CELLS. AND YOU CAN THEN BREED A MOUSE THAT HAS AN ALLELE FUSED TO A GREEN TO ONE THAT HAS A WELL FUSED TO A RED FLUORESCENT PROTEIN TO GENERATE DOUBLE EXPRESSERS WHERE ONE ALLELE OF EACH OF THESE PROTEINS IS CHECKED. REALLY BRIEFLY A SENSE OF WHAT CAN BE ACHIEVED FROM THESE ANIMALS. SO THE FIRST TIME IN PRIMARY CELLS, YOU CAN FOLLOW THE ABUNDANCE OF SPECIFIC PROTEINS BECAUSE THEY HAVE BEEN EXPRESSED FROM THE ENDOGENOUS LOCUS. YOU CAN TAKE A TISSUE, PURIFY THE CELLS OF INTEREST AND MEASURE THE LEVELS OF THE PROTEIN BECAUSE THESE ARE FUSION PROTEINS THAT EXPRESS. WE CAN ALSO ASSAY IN THE CELLS THE PRESENCE OF HOMOHETERODIMERS. HOW MUCH VED COUPLED WITH GREEN OR HOW MUCH GREEN IS BY ITSELF, ET CETERA. AND FINALLY ONE CAN ISOLATE CELLS FROM THE MICE AND STIMULATE THEM IN CULTURE BECAUSE THE TRANSCRIPTION FACTOR IS INVOLVED IN RESPONSE TO EXOG FLUS OR ENDOGENOUS DANGER SIGNALS AND FOLLOW THE KINETICS AND ASK WHAT HAPPENS TO EACH OF THESE KINDS OF PROTEINS WHEN A CELL IS STIMULATED? SO THE DEVELOPMENT OF THIS EXTREMELY IMPORTANT REAGENT AND ITS APPLICATION TO ONE BIOLOGICAL PROBLEM, F NCAPA B ACTIVATION WAS PUBLISHED BY A GROUP IN CELL REPORTS, TO CONSIDERABLE INTEREST FROM THE EXTRAMURAL COMMUNITY AND HIGHLIGHTED IN OUR OWN LOCAL PUBLICATION, THE NIH CATALYST, AS A STUDY OF SOME IMPORTANCE. THE DOCTOR WHO HEADS THE IMMUNOREGULATION SECTION HAS BEEN INTERESTED IN THAT INTERFACE BETWEEN HOW THE NEW SYSTEM IS REGULATED SO AS NOT TO BECOME TOO MUCH OR NOT TO BE TOO LITTLE. BUT IN THE SET OF EXPERIMENTS I'M GOING EMPHASIZE THIS AFTERNOON, IS THIS ANALYSIS WHERE THIS SECTION BEGAN TO STUDY THE POTENTIAL ROLE OF ADAPTIVE IMMUNE CELLS IN THE CONTEXT OF ALZHEIMER'S DISEASE MOUSE MODELS. AND THE THRUST OF THE FIRST PAPER THAT WAS PUBLISHED LAST YEAR, OR NOW TWO YEARS AGO, IS THAT IN THIS PARTICULAR MODEL WHICH FOR THOSE OF YOU WHO STUDIED THESE AS A TRIPLE TRANSGENIC MODEL OF AD IN THE MOUSE, YOU CAN SEE IN THE NORMAL, CONTEXT OF THE TRIPLE TRANSGENIC, YOU HAVE PLATS SHOWN IN THE GREEN AS EXPECTED ACTIVATED MICROGLIA SHOWN IN THE RED OVER HERE, BUT WHEN THIS GENETIC MODEL IS MOVED INTO THE BACKGROUND OF A MOUSE THAT DOES NOT HAVE B CELLS. IT HAS EVERY OTHER KIND OF IMMUNE CELL PRESENT INCLUDING THE ADAPTIVES IMMUNE T-CELLS, THOSE MICE HAVE SUBSTANTIALLY REDUCED A DATA BLACKS AND ACTIVATED MICROGLIA. SO CONCLUDING FROM THESE OBSERVATIONS, B CELLS ARE INTIMATELY INVOLVED IN THE PROGRESSION AND MANIFESTATION OF THE PHENOTYPES OF AD IN THIS MOUSE MODEL. AND THEIR FUTURE WORK WILL TRY TO DISSECT WHAT IS ACTUALLY GOING ON. THE RESULTS SO FAR SHOW THAT A KIND OF IMMEAN CELL IS INTIMATELY INVOLVED. AND FINALLY THE THIRD RESULT THAT I WILL ELABORATE ON TO SOME EXTENT, IS DEVELOPED BY A LAB WHO HEADS UP THE LYMPHOCYTE SECONDS AND FOR MANY YEARS HAS BEEN THE DRIVER OF STUDYING HUMAN IMMUNITY AND HOW IT CHANGES WITH AGE IN OUR INSTITUTE, IN OUR INTRAMURAL PROGRAM. AND IN THIS CASE, HE HAS LOOKED AT THE SO-CALLED ALPHA BETA T-CELL RECEPTOR REPERTOIRE. LET ME JUST GIVE ONE SENTENCE OR TWO SENTENCE UPDATE OF WHAT THE IMPLICATION OF THIS IS. NOW IT HAS BEEN PROPOSED FOR MANY YEARS, MOSTLY BASED ON CROSS SECTIONAL STUDIES EVEN IN MICE, THAT ONE OF THE REASONS FOR THE IMMUNE DECLINE THAT OCCURS WITH AGE IS BECAUSE THERE AREN'T CELLS THERE THAT WOULD RECOGNIZE THE POTENTIAL ANTIGEN OR PATHOGEN WHEN IT COMES INTO THE ORGANISM. AND THIS IS BECAUSE THE LARGE RANDOMLY ASSORTED REPERTOIRE OF B-CELL RECEPTORS AND T-CELL RECEPTORS, THE ANTIBODIES OF THE T-CELL RECEPTORS IN THE CASE OF T-CELLS, HAVE REDUCED IN THEIR COMPLEXITY. AND SO, THIS IS A HYPOTHESIS THAT HAS BEEN AROUND FOR A WHILE. AND DIRECTLY TESTED THIS USING THE INVALUABLE RESOURCE OF THE LONGITUDINAL STUDY ON AGING TO LOOK WITHIN INDIVIDUALS OF DIFFERENT AGES SEPARATED BY NINE YEARS. SO 15 MALES SEPARATED BY NINE YEARS ACROSS THE AGING SPECTRUM. 15 FEMALES. PURIFIED CD4 AND CD8 MEMORY CELLS, BEING THE HALLMARK OF ADAPTIVE IMMUNITY. FIGURED OUT WHAT THEIR COMPLEXITY OF THE T-CELL RECEPTOR ALPHA AND BETA CHANGES USING RNA-SEQ. AND THE RESULTS ARE VERY BEAUTIFULLY SUMMARIZED ON THIS RIGHT PANEL SHOWING THE DIVERSITY OF THESE CELLS IS MUCH HIGHER IN YOUNGER INDIVIDUALS AND NOW GIVES YOU A NUMBER FOR THE RATE AT WHICH THIS DIVERSITY REDUCES WITH AGE. SO YOU WANT TO FIGURE OUT HOW MANY FEWER WIDELY DIVERSELY EXPRESSING T-CELL RECEPTORS AS A PRESENTS AS A FUNCTION OF AGE IN HUMANS. HE DOES THIS FOR CD4 AND CD8. SO WITH THOSE THREE EXAMPLES WANT I WANT TOED TO EMPHASIZE IS GIVE YOU ASCENSUS OF THE RANGE OF OUR ENTERPRISE FROM OUR MECHANISTIC STUDIES GOING THROUGH TO MOUSE MODELS AND PHYSIOLOGICAL SITUATIONS AS DIVIDED FROM THE KIND OF EXPERIMENT I SHOWED YOU FROM THE OTHER LAB, ALL THE WAY TO HUMAN IMMUNITY AND THE IMPLICATIONS OF T-CELL RECEPTOR REPERTOIRE DECLINE IN LEADING TO IMMUNE DYSFUNCTION WITH AGE. THE OTHER THREE INVESTIGATORS HAVE CORRESPONDINGLY INTERESTING RESEARCH PROGRAMS SO DR. GEAR HEART, HER LAB IS SPECIFICALLY LOOKING AT THE ANTIBODY IN A DIFFERENT CONTEXT. WHAT HAPPENS IN THE B CELLS IN AGING. HOW IS HIGH AFFINITY ANTIBODIES GENERATED DURING IMMUNE RESPONSES? IS THERE A ROLE FOR ANTIBODIES IN ARTHROSCLEROSIS? AND THE LATEST PROJECT IN THE LAB LOOKS AT CHANGES IN HEMATOPOIETIC STEM CELLS THAT MIGHT LEAD TO REDUCED ANTIBODY DIVERSITY WITH AGE. DR. MICHAEL'S SECTION IS STUDYING REP DECLARATION STRESS. AND WE TAKE REPLICATION STRESS. THIS IS REPLICATION AS IN DNA REP SITUATION DURING THE CELL CYCLE. WE THINK THIS IS AN EXTREMELY IMPORTANT AREA THAT SYNERGIZES WITH IMMUNITY BECAUSE ONE OF THE FUNDAMENTAL PRINCIPLES OF ADAPTIVE IMMUNITY IS A SO-CALLED PHENOMENON OF CLONAL SELECTION. IN A NAIVE INDIVIDUAL YOU HAVE A LARGE DIVERSITY CELLS THAT COULD POTENTIALLY RECOGNIZE MANY DIFFERENT KINDS OF ANTIGEN. THESE HAVE BEEN GENERATED AGNOSTIC OF WHAT ANTIGEN HUMAN LIFE OR HUMAN ORGANISM MIGHT FACE. BUT WHEN SUCH AN ORGANISM COMES ALONG, FULL OF ANTIGENS, ANTIGEN-SPECIFIC CELLS, SOME LIMITED, VERY LIMITED NUMBER OF SELECTED AND CLONALLY EXPANDED GO THROUGH 8, 10, 12 ROUNDS OF DIVISION TO CREATE A POOL OF CELLS THAT CAN MOUNT A GOOD IMMUNE RESPONSE. AND MICHAEL'S LAB LOOKS AT THE STRESS THAT IS INVOLVED DURING THIS CELL DIVISION AND DURING DNA REPLICATION. AND THEY HAVE IDENTIFIED THAT EARLY REPLICATING REGIONS OF THE CHROMOSOME USE A DIFFERENT SUBSET OF PROTEINS TO SENSE A STRESS TO THE NUCLEOSOME, A STRESS TO THE REPLISOME, EXCUSE ME, BLOCKED BECAUSE OF SOME DANA DAMAGE WHICH REVENTS REPLICATION TO TAKE PLACE. AND MY OWN PROGRAM HAS THREE MAJOR COMPONENTS TO UNDERSTAND MOLECULAR MECHANISM OF CELL SPECIFIC GENE EXPRESSION, WHICH WE DO IN ANALYSIS OF DEVELOPMENT AND THE EXPRESSION OF IMMUNOGLOBULIN. HEAVY CHAIN LOCUS. WE ARE INTERESTED IN STUDYING GENE REGULATION BY NF-kB, AN AREA WE SYNERGIZE AND COMPLIMENT MIA'S PROGRAM. AND FINALLY A PART, INTEGRAL PART OF THE HUMAN IMMUNE STUDIES THAT WAS MENTIONED JUST A FEW MINUTES AGO. I WOULD LIKE TO CONCLUDE, THOUGH, WITH A BIT OF SELF REALIZATION THAT OCCURRED TO US ABOUT 6-8 MONTHS AGO. AND THIS IS IT. EVEN THOUGH EACH OF OUR INVESTIGATORS HAD THEIR OWN RESEARCH PROGRAMS THAT THEY WERE -- HAD BEEN FOLLOWING UP, IT TURNS OUT THAT THERE WERE ASPECTS THAT WERE POTENTIALLY SHARED THAT WE WERE NOT USING TO OUR ADVANTAGE AS MUCH AS WE COULD. SO FOR EXAMPLE, MIA AND MYSELF, HAD BEGUN TO LOOK AT MICROGLIAL GENE EXPRESSION FROM THE PERSPECTIVE OF NF-kB ACTIVATION. WE -- BUT AT THE SAME TIME -- THEY DEVELOPED MODELS IN THE ROLE OF B CELLS. WE STUDIED B CELLS FOR A LONG TIME, AS HAS DR. GEAR HEART'S LAB. NOW MIA'S LAB IS LOOKING AT CD8 CELLS IN THIS CONTEXT IN THESE MODELS. SO WE THOUGHT THIS IS THE PRIME OPPORTUNITY FOR US NOT ONLY TO DRIVE OUR OWN PROGRAMS BUT TO COME TOGETHER IN A WAY TO UNDERSTAND, TO BRING OUR COMPLEMENTARY INTERESTS AND EXPERTISE IN IMMUNITY AND INFLAMMATORY GENE EXPRESSION TO UNDERSTAND INFLAMMATORY INTERACTIONS IN AD RELATED DEMENTIAS. WE HAVE NOW COME TOGETHER TO FOCUS ON A LIMITED NUMBER OF MODELS WHERE WE CAN BRING TO FOCUS OUR INTERESTS IN THE INTERMISSION, BE THAT INVESTIGATORS HERE, OUR INTEREST IN B-CELL OR T-CELLS TO COORDINATE AND COORDINATELY STUDY THE POTENTIAL ROLE OF IMMUNITY. INNATE OR ADAPTIVE. AND ITS ROLE IN AGE RELATED DEMENTIA. SO I CERTAINLY AM VERY EXCITED ABOUT THE POSSIBILITIES THAT ALL SIXER OF US CAN CONTRIBUTE TO THIS STORY AND BE ABLE TO HOPEFULLY CLEARLY DELINEATE THE POSSIBLE ROLLS OF INNATE AND AADAPTIVE IMMUNITY DURING THE NEURODEGENERATIVE DISEASES. FINALLY, THE LABORATORY ALSO OVER SEAS THE IRB, INTRAMURAL PROGRAM, OVERSEEN HERE BY HUANG. AND I GIVE YOU A SENSE OF OUR THREE WONDERFUL PERSONNEL THAT RUN THE CORE, SERVICE THE ENTIRE IRB -- AND THE IDEA OF THE VARIOUS INSTRUMENTATIONS WE HAVE AVAILABLE, NOT JUST FOR THE USE OF NIA BUT THE ENTIRE IRB. WITH THAT I'LL STOP AND SEE IF THERE IS ANY QUESTIONS. THANK YOU VERY MUCH FOR YOUR ATTENTION.