>> WE WOULD LIKE TO WELCOME THE MEMBERS OF BOTH THE BOARD OF SCIENTIFIC ADVISORS FROM THE NATIONAL CANCER ADVISORY BOARD, NACB EXO FISH YO MEMBERS OF CANCER PANELISTS STAFF MEMBERS AND PANELISTS AND MEMBERS OF THE PUBLIC WANTING TO EXPRESS VIEWS MAY DO SO BY WRITING TO PAULET GRAY THE EXECUTIVE SECRETARY OF THE BOARD WITHIN 10 DAYS AFTER THE MEETING AND WRITTEN STATEMENTS AND QUESTIONS SUBMITTED BY MEMBERS OF THE PUBLIC WILL RECEIVE CAREFUL CONSIDERATION. AS BOARD MEMBERS, I WANT TO REMIND YOU THAT YOU MUST ABSENCE YOURSELVES VIRTUALLY DURING SPECIFIC DISCUSSIONS DURING PARTICIPATION AND DLIBATIONS ON A PARTICULAR PRODUCT PROGRAM OR SPECIFIC MATTERS TO CONSTITUTE A CONFLICT OF INTEREST OR CREATING THE APPEARANCE OF ONE AND IS INCUMBENT UPON YOU TO ADVISE THE EXECUTIVE SECRETARY DR. GRAY AND ABSTAIN FROM ANY PARTICIPATION OR DISCUSSION OR ACTION REGARDING THAT MATTER CONCERNING CURRENT POLICIES REGARDING CONFLICT OF INTEREST BASED ON FINANCIAL HOLDINGS FOR SPECIAL GOVERNMENT EMPLOYEES WHICH INCLUDES ALL MEMBERS OF BOTH BOARDS WE MUST DEPEND ON YOU VOLUNTARILY AT [INAUDIBLE] YOURSELVES OF ANY DISCUSSIONS OF MATTER TO CONCEIVABLY IMPACT STATUS OF THOSE HOLDINGS AND WE HAVE TO TRUST YOUR JUDGMENT TO ABSTAIN APPROPRIATELY AND DURING CLOSED SESSION OR MATERIALS OR DISCUSSIONS OF A CONFIDENTIAL NATURE DELIBERATED ON TODAY ARE PRIVILEGED INFORMATION MADE AVAILABLE TO YOU ON NEED TO KNOW BASIS AND DELIBERATIONS ARE PRIVATE AND CONTENTS SHOULDN'T BE DIVULTHED AND ORDER OF BUSINESS WOULD BE FUTURE MEETING DATES THAT ARE LISTED ON THE AGENDA AND PDF THAT YOU HAVE AND ARE ALSO PROVIDED ON CANCER.GOV WEBSITE. HOWEVER, WE DO NEED TO CONFIRM THE BSA AND NCB2020 MEETING DATES AND KEITH AND I WILL WORK TOGETHER ON THIS. KEITH, ARE YOU HERE? IF SO, COULD YOU TURN ON YOUR MIC AND CAMERA? KEITH? DO WE HAVE KEITH? >> LOOKS LIKE HE HASN'T JOINED YET. I APOLOGIZE. JOY, SHOULD WE CONTINUE WITH THE MCBA PORTION OF THE MEETING? >> YES. WE CAN DO THAT AND CALL UNTIL ACTING CHAIR ARRIVES. >> I HAD PROBLEMS WITH MY COMPUTER. WHY DON'T WE GO TO GET STARTED. >> THANK YOU, PAULET. WE DON'T HAVE KEITH. PAUL ET, CAN YOU HEAR ME? >> I CAN NOW. I'M HAVING PROBLEMS WITH MY LAPTOP. SO -- >> OKAY. WE DON'T HAVE KEITH FLARE ETE YET. >> KEITH IS NOT ON YET? >> DO WE HAVE AN ACTING CHAIR FOR BSA IN HIS ABSENCE? >> YOU CAN DO BOTH FOR BSA AND NCAB. >> GREAT. I WILL MOVE FORWARD THEN. >> OKAY. YES. >> SO, WE NEED TO APPROVE NCAB2024 MEETING DATES. I WOULD LIKE TO CALL FOR A MOTION. >> YEAH. >> SO MOVED. >> SO MOVED. >> SECONDED? >> SECOND. >> OKAY. NCAB MEMBERS SHOULD VOTE. DO WE HAVE NAYS OR ANYONE NEEDING TO ABSTAIN? OKAY. SO, WE WILL MOVE ON TO THE BSA2024 MEETING DATES. KI GET A MOTION TO APPROVE THOSE DATES? >> SO MOVED. >> MOTION APPROVED. >> MOVED AND SECONDED? >> SECOND. >> SECOND. >> OKAY. FOR BSA MEMBERS ONLY, DO WE HAVE ANY NAY VOTES? ANYONE NEED TO ABSTAIN? RIGHT. IT HAS BEEN MOVED AND SECCED SO WE CAN MOVE FORWARD. WE NEED TO ALSO FOR NCAB MEMBERS WE NEED TO APPROVE THE FEBRUARY 2022 VIRTUAL MEETING MINUTES. WE NEED TO -- DO WE HAVE A MOTION TO APPROVE THE MINUTES? >> MOVE APPROVAL. >> SECOND. >> SECONDED. >> WE NEED TO VOTE ANY NAYS OR ABSTENTIONS? OKAY. LET'S MOVE ON TO THE BSA. THE -- MARCH 28-29BSA VIRTUAL MEETING MINUTES. DO WE HAVE A MOTION TO APPROVE THE MINUTES? >> SO MOVED SFWL SECOND? >> SECOND. >> SECOND. >> PROPERLY MOVED AND SECONDED. IN TERMS OF VOTING, DO WE HAVE ANY NAYS? ANYONE NEED TO ABSTAIN. >> JOHN HERE. >> OKAY. GREAT. SO, LET'S MOVE ON. SO, CONCERNING QUORUM. BY LAW QUORUM OF BOARD MEMBERS IS REQUIRED FOR EACH INSTANCE IN WHICH A VOTE MAY OCCUR WHETHER AN OPEN OR CLOSED SESSION DURING THIS MEETING WHEN BOTH BOARDS ARE VOTING MINIMUM OF 24 MEMBERS MUST BE PRESENT TO VOICE VOTES SINCE WE CAN'T PREDICT TIME OR OCCURRENCE OF ANY MOTION PRESENCE IN VIRTUAL ROOM FOR ALL SEGMENTS OF THE MEETING IS REQUIRED AND A MUST AND SHOULD BE NOTED THAT WHEN WE DO NOT AND WHEN WE DO ACTUAL CONCEPTS LATER TODAY WHILE BOTH BOARDS CAN PARTICIPATION IN THE DISCUSSIONS ONLY BSA MEMBERS CAN BE COUNTED IN THE VOTE FOR CONCEPTS LATER TODAY AND THUS QUORUM AT THAT TIME WILL BE 15 MEMBERS THAT IS BSA MEMBERS AND ADDITIONALLY FOLLOWING SUB-COMMITTEE REPORT TOMORROW ONLY MCAB MEMBERS WILL BE COUNTED IN THE VOTE AND ALL BOARD MEMBERS COULD PARTICIPATE IN THE DISCUSSION HOWEVER AND QUORUM WILL BE 9. DR. GRAY, DO WE HAVE A QUORUM? >> YES, WE DO. >> TO ENSURE THERE IS NO INTERRUPTIONS TODAY, PLEASE ENSURE YOU ARE MUTED AND REMAIN MUTED UNTIL RECOGNIZED BY EITHER ME OR KEITH OR THE EXECUTIVE SECRETARY WHO IS -- OR THE ACTING NCI DIRECTOR OR THE SPEAKER AND TO ADVANCE OUR AGENDA TODAY, WE WILL NOW HAVE OUR FIRST AGENDA ITEM THAT IS THE NCI ACTING DIRECTOR'S REPORT FROM DR. LOEY OR DOUG. >> JOHN, THANK YOU SO MUCH. I WANT TO WELCOME EVERYONE FROM THE BSA AND NCAB AND THANK YOU FOR TAKING TIME OUT OF YOUR BUSY SCHEDULES BOTH FOR TODAY AS WELL AS FOR TOMORROW. AND ALSO TO WELCOME THOSE PARTICIPANTS WHO ARE NOT ON THE BSA OR NCAB. THANK YOU FOR JOINING. I WILL COVER A NUMBER OF DIFFERENT AREAS IN MY PRESENTATION TO DISCUSS LEADERSHIP TRANSITION AND NCI BUDGET CANCER EQUITY AND RECENT CANCER RESEARCH ADVANCES AS WELL AS THE CANCER MOON SHOT AND I HAVE TWO SLIDES IT THAT IF I CAN HAVE THE NEXT SLIDE IS A SAD SLIDE AND ANOTHER SLIDE IS A HAPPIER ONE THIS SLIDES COMMEMORATES SLIDE ON JUNE THIRD FROM PORTER AND CONGRESSMAN FROM ILLINOIS IN 1980S TO 2001 AND WHO WAS REALLY INSTRUMENTAL AS A STRONG SUPPORTER OF NIH FOR DOUBLING THE NIH BUDGET IN THE LATE 1980S AND EARLY 2000S. AND EVEN AFTER HE LEFT CONGRESS, HE WAS THE CHAIRMAN OF THE BOARD OF DIRECTORS FOR RESEARCH AMERICA FROM 2005 UNTIL HIS DEATH SEVERAL DAYS AGO. AND LIKE YOU SEE ON THE BOTTOM LEFT ON THE JOHN EDWARD PORTER NEW SKRIENS RESEARCH CENTER THAT WAS DEDICATED IN 2014 AND NAMED AFTER MR. PORTER AND YOU HAVE QUOTES FROM TOM COLE AND RICHARD DUR BAN ON BOTH SIDES OF THE AISLE ABOUT HOW MR. PORTER, A REPUBLICAN, WAS REALLY A BIPARTISAN MEMBER OF CONGRESS. WE ARE ALL SADDENED BY HIS LOSS. HE WAS A TRUE CHAMPION FOR RESEARCH AS WELL AS FOR AREAS OF GUN CONTROL AND OTHER AREAS AS WELL. IF I COULD HAVE THE NEXT SLIDE. THIS SLIDE REALLY IS SOME OF THE RECENT NOTES FOR MEMBERS OF AN NCAB AND BSA AND ELECTROPASS GET 10 DAYS AGO RECEIVING AMERICAN CANCER SOCIETY CANCER PREVENTION AWARD AND KAREN WAIK FIELD WAS ELECTED FOLLOWING AMERICAN SOCIETY OF CLINICAL ONCOLOGY AND BOARD OF SCIENTIFIC ADVISORS JENNIFER BRANDIS WAS ELECTED AS A FELLOW OF AACR ACADEMY AND OTIS BROWLEY AS WELL AND ONLY PROBLEM IS THAT HE HAS SO MANY LETTERS AFTER HIS NAME HE NEEDS A SPECIAL BUSINESS CARD TO BE MAID FOR HIM. I AM SURE HE IS UP TO THE JOB. NEXT SLIDE. SO, THIS SLIDE DEPICTS FOR YOU WHAT HAS HAPPENED SENSE 2010 WITH LEADERSHIP AT NCI. HOWARD VARMIS WAS NCI DIRECTOR IN 2010 THROUGH 2015 AND I WAS INTERIM DIRECTOR FROM 2015 TO 17 AND NED SHARPLESS WAS DIRECTOR FROM 2017 UNTIL 2022 AND SOME OF YOU MIGHT REMEMBER THAT NED WENT OVER TO FDA AS ACTING COMMISSIONER IN 2019 AND I WAS ACTING DIRECTOR DURING THAT TIME. NOW, I'M ONCE MORE THE ACTING DIRECTOR. NEXT SLIDE. I WANT PEOPLE TO UNDERSTAND THAT THE NCI IS MUCH MORE THAN THE CURRENT DIRECTOR. IT ALSO IS MUCH MORE THAN WHAT IS LISTED HERE AS THE LEADERSHIP TEAM. JUST TO GIVE YOU AN EXAMPLE THAT MANY PEOPLE ON THE LEADERSHIP TEAM HAVE BEEN HERE FOR QUITE A WHILE. WE END UP, YOU KNOW, BASICALLY BEING ABLE TO SUPPORT WHOEVER IS THE DIRECTOR AT THAT TIME. I SHOULD POINT OUT THAT THERE ARE TWO IMPORTANT ATTRIBUTES OF THIS GROUP OF PEOPLE. ONE IS IT THAT WE FREQUENTLY DISAGREE WITH EACH OTHER. THE SECOND IS THAT WE ALMOST ALWAYS REACH CONSENSUS. NEXT SLIDE, THIS IS A LIST OF SOME OF THE DECISIONS THAT OCCURRED WHILE I HAVE BEEN ACTING DIRECTOR AND PRECISION P MEDICINE INITIATIVE ON ONCOLOGY AND CRYOUSER M FACILITY WERE IN 2015 AND 2016 THE CANCER MOON SHOT AND STARTING IN 2016 AND GOING THROUGH NOW A 40 MILLION DOLLAR INCREASE IN P30 SUPPORT GRANTS FOR NCI DESIGNATED CANCER CENTERS OFTEN REFERRED TO IN PHASE 1 AND PHASE 2 AND DURING 2019 ENABLED CONGRESS TO RECOGNIZE LOW NCI FUNDING RATES FOR INVESTIGATOR INITIATED RESEARCH AND NEXT SLIDE. THESE ARE SOME CURRENT AND NEAR FUTURE ACTIVITIES AT NCI. THIS WEEK, ACTUALLY ON THURSDAY MORNING, THE CANCER GRANT CHALLENGE THAT WE ARE DOING WITH CANCER RESEARCH UK, FIRST AWARDS WILL BE ANNOUNCED THIS WEEK. WE WILL PARTICIPATE IN THE DEVELOPMENT AND PROCESS FOR THE NEXT ROUND. CANCER MOON SHOT, WE NEED TO CONTINUE TO FUND THE MOST PROMISING INITIATIVES OF INITIAL CANCER MOON SHOT TO ESTABLISH A SOFT LANDING AND WE -- THIS COMING YEAR IS A YEAR OF PLANNING FOR THE NEXT PHASE. FOR THE CANCER CENTERS, WE WILL BE DEVELOPING PHASE 3 FOR THE P30 CANCER CENTER SUPPORT GRANTEDS AND FOR FRED ERIC NATIONAL LAB, WE WILL SELECT AT LEAST ONE NEW SIGNATURE PROJECT AT THE FED ERIC NATIONAL LAB DEANNA SINGER AND ED HARLOW AND OTHERS HAVE BEEN CONDUCTING MEETINGS WITH YOU AND OTHERS TO GET INPUT IN ADDITION TO HAVING AN ARE. FI IN THE RECENT PAST FOR THOSE SUGGESTIONS. THESE ARE SOME OF THE ACTIVITIES. NEXT SLIDE. THIS SLIDE SHOWS YOU SOME OF THE MEETINGS AND EVENTS WHERE I HAVE BEEN PARTICIPATING ALTHOUGH I BECAME ACTING DIRECTOR ON APRIL 30TH, THE ARC MEETING THAT OCCURRED AFTER EDANNOUNCED HIS RESIGNATION AND BEFORE IT ACTUALLY OCCURRED I PARTICIPATED IN REMARKS IN A FIRESIDE CHAT WITH DAVE WHO WAS HEAD OF AACR THIS PAST YEAR AND WITH A PRESS MEETING CALLED A GAGGLE. I MADE A PRESENTATION TO THE NATIONAL ASSOCIATION OF CANCER CENTER DEVELOPMENT OFFICERS AND PUBLIC AFFAIRS AND MARKETING NETWORK. THEN 10 DAYS AGO, PARTICIPATED IN THE ASK MEETING WITH BOARD OF DIRECTORS AND MADE A PLENARY SESSION PRESENTATION. HERE I AM WITH EVERETT VOEKS, THE CURRENT PRESIDENT OF ASCO AND CHIEF SCIENTIFIC OFFICER CLIFF AND IN OCTOBER I WILL MEET WITH AACI THIS IS TWO SLIDES ON BUDGET OF NCI AND TIM WILL TALK TO YOU MORE ABOUT THAT WHEN I PARTICIPATED IN HEARING ON HOUSE COMMITTEE ON APPROPRIATIONS FOR NIH. ONCE AGAIN, BIPARTISAN SUPPORT FOR NIH IN GENERAL AND NCI IN PARTICULAR AND IN THE BOTTOM LEFT AFTER THE HEARING WAS OVER, TOM COLE, THE RANKING MEMBER AND CHAIR DELORO FOR THE COMMITTEE CAME OVER TO TALK TO ME. WE HAVE BOTH KNOWN EACH OTHER FOR A WHILE. NEXT SLIDE. THIS SLIDE DEPICTS FOR YOU WHAT HAS HAPPENED OVER THE LAST FEW YEARS. IN ORANGE IS THE PRESIDENT'S BUDGET AND BLUE/GREEN IS ACTUAL ENACTED APROPRIATION AND NOTE THAT EACH YEAR THE PROPOSAL FOR THE PRESIDENT'S BUDGET WAS LOWER THAN WHAT WAS ACTUALLY APPROPRIATED. REASONS ARE AS I MENTIONED STRONG BIPARTISAN SUPPORT FOR CANCER RESEARCH ACROSS CONGRESS. CONGRESS HAS DECLINED TO CUT FUNDING TO CANCER RESEARCH IN CHALLENGE EVERING BUDGET CYCLES. I AM CAUTIOUSLY OPTIMISTIC THAT WE CAN LOOK FORWARD TO A SIMILAR OUTCOME. IT ONLY HAPPENS [AUDIO CUT OUT] [AUDIO BREAKING UP]. AND IMPORTANCE OF CANCER RESEARCH FOR HELPING PATIENTS BOTH FOR PREVENTING CANCER AND TREATING CANCER WHEN IT OCCURS. NEXT SLIDE. RECENTLY, WE HAD AN ONLINE CONVERSATION ABOUT HEALTH EQUITY AND PAULET AND I PARTICIPATED ALONG WITH JEFFREY HALL FROM THE CDC AND RANDY JONES FROM ONCOLOGY NURSING SOCIETY COMMEMORATE JUNETEENTH. DR. HALL HAD A REALLY NOTABLE QUOTE THAT YOU CAN READ. IF YOU WANT TO LISTEN AND WATCH IT AND URL IS SHOWN ON BOTTOM LEFT AND NEXT SLIDE SHOWS TWO POSITIVE RESULTS AND TWO NEGATIVE RESULTS ABOUT WHAT HAS HAPPENED TO CANCER MORTALITY BY RACE AND ETHNICITY OVER THE LAST 20 YEARS. GOOD NEWS NO. 1, IT IS GOING DOWN. CANCER MORTALITY RATES ARE GOING DOWN FOR VIRTUALLY ALL GROUPS. GOOD NEWS NO. 2, IN THE TOP LINE RED LINE RATES OF DECLINE ESPECIALLY FOR BLACK MEN HAVE BEEN FASTER THAN RATES OF DECLINE FOR OTHER GROUPS. PIECES OF BAD NEWS. FIRST, BLACK MEN AND WOMEN ARE STILL DYING AT A HIGHER RATE THAN THAT OF OTHER GROUPS AND SECOND PIECE OF BAD NEWS IS SQUIGGLY ORANGE LINE SHOWS YOU ESPECIALLY FOR AMERICAN INDIAN AND AMERICAN AND ALASKAN NATIVE MALES HAVE NOT BEEN FITTED TO THE SAME DEGREE AS OTHER ETHNIC GROUPS FROM ADVANCES IN CANCER RESEARCH AND IF YOU WANT TO SEE MORE ABOUT TRENDS IN CANCER MORTALITY AMONG BLACKS IN THE UNITED STATES DURING THIS TIME PERIOD, WAYNE LAWRENCE, ET AL PUBLISHED A PAPER LAST MONTH THAT LOOKS AT THE ISSUE IN LOTS OF DETAIL. NEXT SLIDE. ONE REASON THAT CANCER MORTALITY RATES ARE GOING DOWN IS BECAUSE OF LUNG CANCER. LUNG CANCER ACCOUNTS FOR ABOUT 1/3 OF MORTALITY FROM CANCER. AS WE ALL KNOW, TOBACCO CONSUMPTION IS THE MAJOR CAUSE OF LUNG CANCER. IT IS ALSO A CAUSE OF OTHER CANCERS. BUT, IT IS NOT JUST A DECREASE OF THE INCIDENCE OF TOBACCO CONSUMPTION THAT IS FUELING DECREASE IN LUNG CANCER INCIDENCE AND MORTALITY BUT ALSO ADVANCES IN LUNG CANCER TREATMENT. THIS SLIDE, TAKEN FROM THE LUNG CANCER RESEARCH FOUNDATION, IT DEPICTS FOR YOU, ESPECIALLY IN THE LAST 20 YEARS HOW MANY ADVANCES IN TARGETED THERAPY AS WELL AS IMMUNOTHERAPY THAT HAVE OCCURRED ESPECIALLY IN THE AREA OF NONSMALL CELL LUNG CANCER. FOR THOSE THAT ARE INTERESTED, WE PUBLISHED A PAPER IN 2020 TRYING TO DOCUMENT THAT ADVANCES IN LUNG CANCER TREATMENT ACTUALLY IS HAVING A SUBSTANTIAL EFFECT POPULATIONWIDE IN THE UNITED STATES IN ADDITION TO DECREASES IN INCIDENCE. NEXT SLIDE. THIS SLIDE, ALSO, IT TALKS ABOUT SOME ACTUAL ADVANCES AND HOPE FOR ADVANCES IN CANCER RESEARCH AND DEALS WITH KRASS MUTANTS. KRASS MUTATIONS WERE IDENTIFIED FIRST IN THE EARLY 1980S. MY LABORATORY WAS FORTUNATE ENOUGH TO COLLABORATE WITH SEVERAL OTHER LABORATORIES TO IDENTIFY THE FIRST CODON 12 MUTATION IN RASS. BUT, FOR THE NEXT 30 YEARS, RASS WAS CONSIDERED TO BE AN ENTRACTABLE MUTANT PROBLEM. WE DIDN'T HAVE GOOD TREATMENT. BUT, ADVANCES THAT WERE PIONEERED BY CUBAN SHOE CUT AND HIS COLLABORATORS PAVED THE WAY FOR G12C INHIBITORS TO BE FDA APPROVED IN MAY OF LAST YEAR. IF YOU LOOK AT THE SLIDE, AT THE TABLE ON THE LEFT THAT IS TAKEN FROM A RECENT REVIEW FROM FRANK MCKORMIC AND OTHERS AND IN THE RASS INITIATIVE ABOUT RASS MUTATIONS AND HOPE YOU CAN SEE THAT G12C ACCOUNTS FOR A LITTLE MORE THAN HALF OF THE ACTUAL RASS MUTANTS IN LUNG CANCER THAT IS UNCOMMON IN PANCREATIC CANCER AND ACCOUNTS FOR A PROPORTION OF CANCER OF COALO RECTAL CANCERS AND NOW THERE ARE PRECLEN CAL DATA FOR DEVELOPMENT OF G12D INHIBITORS AND THE EXPECTATION THAT EARLY PHASE CLINICAL TRIALS WILL SOON START FOR G12D INHIBITORS AND NOTE GOING BACK TO THE TABLE NOW IN THE RIGHT-MOST COLUMN THAT MORE THAN HALF OF PANCREATIC CANCERS HAVE G12DKRASS MUTATIONS AND MY HOPE IS THAT THE ADVANCES WITH G12D INHIBITORS THAT THEY WILL PROVE ALSO TO BE PROVEN TO BE CLINICAL BY USEFUL. BOTTOM LEFT I HAVE DEPICTED MASHIENT DERIVED MODEL REPOSITORY AT NCI HAS AVAILABLE A WIDE RANGE OF PATIENT DERIVED XENO GRAPHS AS WELL AS OTHER MODELS. FOR EXAMPLE, ALTHOUGH PANCREATIC CANCER WITH G12C MUTATIONS ARE DISTINCTLY UNCOMMON, THERE IS ACTUALLY TWO PATIENT DERIVED XENO GRAPHS OF PANCREATIC CANCER OF G12C MUTATIONS THAT ARE AVAILABLE FOR ANYONE WHO REQUESTS THEM FOR STUDY. NEXT SLIDE, PLEASE. SO, THERE ALSO HAS BEEN CONCERNING NEWS IN TERMS OF RECENT REPORTS. THIS IS ABOUT UTERINE CANCER DEATH RATES INCREASING BY MEGAN CLARK ET AL. THE CITATION IS SHOWN ON THE BOTTOM AND DEATH RATES ARE HIGHEST AMONG BLACK WOMEN IN THE UNITED STATES. BLACK WOMEN ARE TWICE AS LIKELY TO DIE OF UTERINE CANCER AND RACIAL/ETHNIC GROUPS AND MORTALITY INCREASE IS ATTRIBUTABLE TO NONUTERINE IMMUTABLE CANCER THAT EFFECTS BLACK AND HISPANIC WOMEN AND THAT PARTICULAR CANCER IT HAS INCREASED 3.5% PER YEAR FOR BLACK WOMEN AND MORE THAN 6% PER YEAR FOR HISPANIC WOMEN BETWEEN 2010 AND 2017 AND THEREFORE IS AN URGENT NEED FOR NEW RESEARCH OF THE EFFECTED POPULATIONS WE WILL SCHEDULE TWO INTERNAL DISCUSSIONS TO TRY TO CONSIDER WHAT RESEARCH GOING FORWARD SHOULD BE CONDUCTED TO BETTER UNDERSTAND THESE CONCERNING EVENTS. NEXT SLIDE. NOW, NEXT SLIDE, PLEASE. I WANT TO END THE SCIENCE PART, IF YOU WILL, BY ANOTHER PIECE OF GOOD NEWS AND IS IN THE AREA OF TREATMENT OF HIGH GRADE ANAL DYSPLASIA IN RANDOMIZED TRIAL RESULTS WAS RECENTLY SHOWN TO REDUCE RISK OF PROGRESSION OF HIGH RATE EPITHELIAL DISPLASIA WHEN TREATED TO REDUCE RISK OF PROGRESSION TO INVASIVE ANAL CANCER THAT WAS IN HIV POSITIVE MEN AND WOMEN. ON THE LEFT IS DEPICTED PROGRESSIVE INCREASE IN ANAL CANCER THAT HAS OCCURRED OVER THE LAST PERIOD. BUT, ON THE RIGHT IS SHOWN WHAT HAPPENED WITH ACTIVE MONITORING IN THE ANCHOR TRIAL VERSUS TREATMENT RESULT. THERE IS MANY FEWER INVASIVE ANAL CANCERS THAT ARE OCCURRING IN THE TREATMENT GROUP AND THE PAPER REPORTING THIS WILL BE PUBLISHED ON THURSDAY IN THE NEW ENGLAND JOURNAL OF MEDICINE JOEL POLESKY WAS PRINCIPLE AUTHOR AND INVESTIGATOR OF THE ANCHOR TRIAL. NEXT SLIDE. THIS IS THE LAST TOPIC TALKING ABOUT THE CANCER MOON SHOT. THIS FIRST SLIDE IS TALKING ABOUT THE FIRST PHASE, THE ONE THAT STARTED IN 2017. THE GOALS OVERARCHING WORK TO ACCELERATE DISCOVERY INCREASE COLLABORATION AND EXPAND DATA SHARING. IF YOU LOOKED ON THE LEFT, THERE IS MORE -- THERE HAVE BEEN IN THE FIRST FEW YEARS MORE THAN 2,000 PUBLICATIONS THAT RESULTED FROM THE CANCER MOON SHOT. ALMOST 50 CLINICAL TRIALS AND MORE THAN 30 PATIENT APPLICATION FILINGS. IF YOU LOOK ON THE RIGHT, AS I'M SURE ALMOST ALL OF YOU ARE AWARE, THE NEXT FISCAL YEAR, FY23, IT WILL BE THE LAST YEAR OF FUNDING FOR THIS FIRST PHASE OF THE CANCER MOON SHOT. AS NOTED ON THE BOTTOM, WE SHOULD STRIVE TO CONTINUE TO SUPPORT THE MOST PROMISING INITIATIVES FROM THE INITIAL CANCER MOON SHOT WHILE DEVELOPING ADDITIONAL ACTIVITIES TO MEET CHALLENGING NEW GOALS. THEY ARE SHOWN ON THE NEXT TWO SLIDES. THE NEXT SLIDE, THERE -- WHEN PRESIDENT BIDEN, NEXT ANNOUNCED ON FEBRUARY 2ND, WHAT I CONSIDERED THREE CRITICAL ASPIRATIONAL GOALS. FIRST, TO DECREASE CANCER DEATH RATE AT LEAST IN HALF WITHIN THE NEXT 25 YEARS. SECOND, TO TRANSFORM THE MEANING OF CANCER. THIRD, TO ADDRESS CANCER ASSOCIATED INEQUITIES. WHAT WE AT NCI ARE TRYING TO DO IS TO PLAY A CRITICAL ROLE IN HELPING TO TAKE THESE ASPIRATIONAL GOALS AND MAKE THEM FEASIBLE. NEXT SLIDE. THERE ARE FOUR OVERARCHING WAYS IN WHICH WE ARE THINKING ABOUT DOING THIS AT THE MOMENT. ONE IS TO INVEST IN THE PIPELINE OF NEW DRUGS FOR CANCER PREVENTION FOR INTERCEPTION AND FOR TREATMENT. 2, TO GREATLY EXPAND CLINICAL TRIALS AND SPEED EVALUATION OF CANDIDATE INTERVENTIONS IN DIVERSE POPULATIONS, RACIAL, ETHNIC, AND GEOGRAPHIC. IMPORTANTLY, TO ENSURE EQUITABLE HEALTH CARE DELIVERY OF CURRENT AND NEW STANDARDS OF CARE BY CONDUCTING CRITICAL IMPLEMENTATION SCIENTIFIC RESEARCH. 4TH, TO INCREASE DIVERSITY OF CANCER RESEARCH AND CANCER CARE WORKFORCE TO MAKE IT MORE CLOSELY RESEMBLE THE COMMUNITIES THAT WE SERVE. NEXT SLIDE. SO, THIS SLIDE IS SOME FY23 ACTIVITIES. THEY ARE THAT WHICH WE ARE PLANNING TO SUPPORT THE ONGOING MOON SHOT AND TO JUMPSTART THE NEXT PHASE. TOMORROW, YOU WILL BE HEARING ABOUT TWO PROPOSED FUNDING OPPORTUNITY ANNOUNCEMENTS THAT WE REALLY HOPE WILL BE PART OF THE FOUNDATION FOR THE NEXT PHASE OF THE CANCER MOON SHOT. ONE WILL BE CANCER MOON SHOT SCHOLARS DIVERSITY PROGRAM THAT IS FOR EARLY STAGE INVESTIGATORS. THE OTHER IS TO HEAR ABOUT A FEASIBILITY TRIAL FOR ASYMPTOMATIC MULTICANCER DETECTION SCREENING. IN ADDITION, WE ARE ALSO TRYING TO CONTINUE WITH THE CURRENT PHASE OF THE CANCER MOON SHOT THAT WILL BE SPECIAL INTEREST NOTICE AS WELL AS REQUEST FOR INFORMATION TO ADAPT VISUALIZATION METHODS TO ENHANCE CANCER MOON SHOT DATA AND FUSION ONCHOPROTEINS IN CHILDHOOD CANCERS AND HARMONIZE EXISTING DATA TO HUMAN TUMOR ATLAS NETWORK STANDARDS. FOR THE LAST PART, YOU WILL HEAR PRESENTATIONS ABOUT THE HUMAN TUMOR ATLAS NETWORK THAT IS LATER THIS AFTERNOON. SO, THE LAST SLIDE IS TO THANK EVERYONE FOR THEIR ATTENTION. I LOOK FORWARD TO HEARING YOUR COMMENTS AND YOUR QUESTIONS. >> THANK YOU, DOUG, FOR THAT COMPREHENSIVE PRESENTATION ON WHERE THINGS ARE IN THE AGENDA FOR THE NCI CURRENT AND FUTURE. WE WOULD LIKE TO NOW OPEN THE FLOOR FOR QUESTIONS. PLENTY OF TIME FOR QUESTIONS. WELL, I WILL START UNTIL WE SEE A FEW HANDS RAISED. PLEASE USE THE HAND RAISE TOOL IN WEBEX SO I CAN RECOGNIZE YOU IF YOU HAVE A QUESTION. DOUG, ONE THING THAT FLASHED BY IS -- WAS -- IS SORT OF NEXT INITIATIVES FOR FREDERICK NATIONAL LABS. CAN YOU GIVE US UPDATES ON WHAT IS GOING ON WITH FREDERICK NATIONAL LAB AND MAYBE EVEN PROVIDE A FEW COMMENTS ABOUT NCI'S RELATIONSHIP WITH FRED ERIC NATIONAL LAB AND WHERE THINGS ARE? >> SURE, JOHN. I WILL SAY THAT FIRST THERE HAVE BEEN A LOT OF COVID-RELATED ACTIVITIES THAT ARE BOTH AT NCI AS WELL AS NIAIV. WE HAVE DISCUSSED SOME OF THEM IN THE LAST -- IN THE LAST COUPLE OF YEARS. BUT, I AM ALSO VERY PLEASED THAT CANCER RESEARCH IS ALIVE AND WELL UP THERE AS WELL. RASS INITIATIVE IS IN ITS 9TH YEAR AND SEEMS TO BE GOING WELL AND LAST MEETING OF THE CANCER AND RASS INITIATIVE ATTRACTED MORE THAN 1500 PARTICIPANTS THAT WAS HELD VIRTUALLY AND NEXT MEETING WILL BE IN THE MIDDLE OF OCTOBER OF THIS YEAR. IT IS HOPED TO BE AN IN PERSON MEETING UP IN FREDERICK AND RASS INITIATIVE WILL BE UP FOR REVIEW IN FEBRUARY AND WE HAVE MODELS INITIATIVE THAT I MENTIONED. JEN DORSO HAS BEEN SPEARHEADING THAT AND MENTION THERE ARE MANY REAGENTS RELATED TO RASS PATHWAYS THAT ARE READILY AVAILABLE THROUGH FREDERICK IN TERMS OF NEW SIGNATURE INITIATIVE, DEANNA SINGER MIGHT WANT TO TALK ABOUT THIS. WE HAVE BEEN SAYING FOR A NUMBER OF YEARS WE SHOULD SERIOUSLY CONSIDER HAVING AT LEAST ONE ADDITIONAL SIGNATURE INITIATIVE WHETHER OR NOT RASS INITIATIVE IS, YOU KNOW, RENEWED. I SHOULD ALSO POINT OUT THAT CRYO-EM INITIATIVE HAS BEEN VERY SUCCESSFUL AND PRESENT ON THAT PREVIOUSLY AND DANA, WANT TO SAY A FEW WORDS ON THE PROCESS OF LOOKING FOR ONE OR MORE NEW INTIVITIATIVE INITIATIVES? >> SURE. HAPPY TO. DOUG ELUDED TO IN HIS STATEMENT IS WE HAD AN RFI OUT ABOUT A YEAR AGO LOOKING FOR IDEAS AND WE HAVE ALSO BEEN MUCH MORE PROACTIVE AND WE HAVE ALREADY HAD 9 BASICALLY THINK TANKS TO GET IDEAS FROM THE COMMUNI COMMUNITY. WE INVITED A BROAD RANGE OF CANCER RESEARCH COMMUNITY TO PARTICIPATE AND WE ARE STILL PLANNING FOUR MORE THAT WILL BE MORE FOCUSED. WE ARE GOING TO NOW PULL OUT FROM THAT COMMON THEMES AND TRY TO DEVELOP IDEAS THAT COULD THEN BE CONSIDERED BY THE BOARDS TO TAKE FORWARD AS NEW PROGRAMS FOR FREDERICK NATIONAL LAB. WE ARE HOPING THAT WILL ALL BE WITHIN THE NEXT YEAR THAT WILL BE ABLE TO BRING SOMETHING BACK YOU TO FOR CONSIDERATION. >> FANTASTIC. >> I THINK JOHN, IF YOU HAVE A QUESTION OR COMMENT? >> HEY, DOUG. GREAT PRESENTATION. I HAVE A QUESTION. YOU ARE PARTICIPATING IN THE PRESIDENT'S -- FROM THE PRESIDENT'S MOON SHOT ANNOUNCEMENT EARLIER AND FROM THE CANCER CABINET. GIVE US A LITTLE BIT OF AN OVERVIEW WHAT IS HAD HAPPENING THERE AND SORT OF A HOOIM LINE AND YOUR ROLE IN IT SO WE UNDERSTAND THAT IS AN INCREDIBLE OPPORTUNITY TO HAVE THE HEAD OF SO MANY DIFFERENT FEDERAL AGENCIES WORKING AND DISCUSSING CANCER. THANK YOU. >> SURE. THANK YOU, JOHN. SO, WHAT THE PRESIDENT HAS TALKED ABOUT IS REALLY AN ALL GOVERNMENTAL-APPROACH IN DEALING WITH CANCER AND ACHIEVING GOALS I MENTIONED IN THE PRESENTATION. SO, THERE IS A CANCER CABINET THAT INVOLVES QUITE A FEW DIFFERENT AGENCIES OF THE GOVERNMENT. IT HAS MET ONCE AND THEN PARTICIPATED AND THERE ALSO ARE DEPUTIES FOR THE CANCER CABINET. I MET IN THAT CAPACITY ONCE. DEANNA AND JIM HAVE ALSO MET IN THAT CAPACITY AND ALSO IN MEETING PERIODICALLY WITH DANIELLE KARNIVAL WHO PRESIDENT DESIGNATED AS COORDINATOR FOR THE NEW PHASE OF THE CANCER MOON SHOT. WE ALSO HAVE BEEN HAVING MEETINGS, PUBLIC MEETINGS, ET CETERA, AND WE HAD -- LAST MONTH WE HAD A MEETING ABOUT CLINICAL TRIALS. AND IT INCLUDED PATIENT ADVOCATES AND PEOPLE FROM CANCER CENTERS AND OTHERS THAT WERE TALKING ABOUT THE IMPORTANCE OF CLINICAL TRIALS TO TRY TO BE ABLE TO ACCRUE MORE PATIENTS AND DO IT EQUITABLY AND TO DO THIS SO THAT WE CAN MAKE FASTER ADVANCES IN CANCER BOTH FOR PREVENTION SCREENING AND FOR TREATMENT BECAUSE PATIENT ACCRUAL AND EQUITABLE ACCRUAL ARE ABSOLUTELY CRITICAL TO MAKING ADVANCES THAT ARE THEN GOING TO LEAD TO NEW STANDARD OF CARE AND FOR IMPLEMENTATION RESEARCH TO IMPROVE THE DISSEMINATION OF IT. THANK YOU, JOHN. >> YES. IT IS TEMPTING TO PASS UP THE OPPORTUNITY TO ASK YOU JOHN AND JOHN AND KEITH AND GIVEN ALL ACQUIRED POWERING ON THIS SCREEN. YOU TALKED ABOUT ALL OF GOVERNMENT IN THE FEDERAL APPROACH TO CANCER. ALSO, ONE, WE WANT TO THINK ABOUT EQUITY-ALL APPROACH AND HOW WE DEAL WITH CANCER RESEARCH OR RESEARCH IN GENERAL. AS POINTED OUT WITH THE CONTINUUM OF CARE AND RISK FACTORS TO DELIVERY OF CARE AND RISK SCIENCE STUFF AND ALL THIS IN-BETWEEN IS REALLY IMPORTANT AND WONDERED TO WHAT EXTENT IN THE CONVERSATIONS YOU ARE HAVING AND KNOW JOHN IS PRESENTING ABOUT PRESENT CANCER PANEL OR SHORTLY PRIOR TO THAT APPROACH OF EQUITY AND ALL COULD BE INTEGRATED TO PROVIDE A FRAMEWORK FOR HOW THAT SORT OF GETS INSINUATED IF YOU WANT INTO THE CORE OF EVERYTHING THAT IS DONE. AFTER ALL, TO MAKE ADVANCES IN CANCER AND IN ANY OTHER CONDITION, WE HAVE TO ADVANCE EQUITY AND EXTEND BENEFITS IN OUR SOCIETY. >> TROY, THANKS. AS YOU KNOW, THIS IS AN EASY QUESTION AND COMPLICATED ANSWER. WHEN IT COMES TO THE DELIVERY OF HEALTH CARE, OUR ROLE, NCI'S ROLE IS PRIMARILY TO TRY TO SUPPORT IMPLEMENTATION AND SCIENCE RESEARCH IN THAT AREA. CERTAINLY DANIEL CARNIVAL AND OFFICE OF SCIENCE AND TECHNOLOGY POLICY ARE DEEPLY INVOLVED IN TRYING TO PROMOTE EQUITY FOR HEALTH CARE DELIVERY BEYOND IMPLEMENTATION RESEARCH. AT THE LEVEL OF CLINICAL TRIALS AS I ELUDED, WE NEED TO ENSURE THAT CLINICAL TRIAL PARTICIPANTS ARE GOING TO BE REFLECTIVE OF THE COMMUNITIES THAT WE SERVE. THEN THE SECOND -- THE OTHER ASPECT WITH THE MOON SHOT SCHOLARS PROGRAM THAT YOU WILL DO TOMORROW AND OTHER PROGRAMS AT CENTER TO REDUCE HEALTH CARE DISPARITIES AND OTHER PROGRAMS, WE ARE, YOU KNOW, TRYING TO ESSENTIALLY HELP WITH THE WORKFORCE OF TOMORROW SO THAT IT MORE REFLECTS THAT OF THE GENERAL COMMUNITY. CHAD, DID YOU WANT TO ADD SOMETHING? >> YEAH. YOU HAVE MULTIPLE HANDS. ALL RIGHT. I GUESS THIS SECOND, THANKS SO MUCH FOR THAT RESPONSE. THE SECOND QUESTION IS THEREABOUTS ABOUT RESEARCH IN GENERAL NOT JUST CLINICAL TRIAL. I THINK THAT THE IMPORTANCE OF CLINICAL TRIAL IS [INAUDIBLE] AND INCLUSIVE ACROSS AREAS OF RESEARCH THAT IS JUST POPULATION-BASED RESEARCH OR CLINICAL RESEARCH. SO, WOULD THERE BE EMPHASIS THAT IS SIMILAR TO THE EMPHASIS AND WHAT DOES EMPHASIS OF CLINICAL TRIAL AND SHAKING HEAD AS WELL AND INCLUSIVE RESEARCH BROADLY ACROSS THE SPECTRUM AT NCI? >> CHAD, I'M NOT QUITE SURE WHAT YOU MEAN BY INCLUSIVE. ASKING ABOUT IMPLEMENTATION RESEARCH, WHETHER IT WILL INCLUDE A WIDE RANGE OF POPULATIONS AND UNDER-REPRESENTED GROUPS, WE CERTAINLY HOPE SO. OKAY? BUT, IF YOU ARE TALKING ABOUT, YOU KNOW, VERY BASIC RESEARCH, I THINK THAT WE WANT RESEARCHERS TO BE MORE EQUITABLY DISTRIBUTED AND NOT SURE ABOUT RESEARCH ITSELF. OKAY? WHEN IT COMES TO FUNDAMENTAL RESEARCH. IT IS NOT THAT WE WILL NEGLECT THOSE CANCERS WHERE THERE ARE IMPORTANT HEALTH DISPARITIES BUT THAT WILL BE ONE OF NUMEROUS CRITERIA. >> THANK YOU, DOUG. WE HAVE -- I THINK WE HAVE TIME FOR ADDITIONAL QUESTIONS. I THINK I SAW ANA'S HAND FIRST AND THEN MICHELLE. >> YOU ARE MUTED. >> YEAH. >> I CAN'T BELIEVE I DID THAT. THAT IS THE FIRST TIME IN THE HISTORY OF THE WORLD I DID THAT. SO, IN MOON SHOT 1.0, GOING BACK TO WHAT WAS THEN VICE PRESIDENT'S MAJOR CONCERN WITH DATA AND DATA QUALITY AND DATA SHARING AND DATA MODELS AND EVERYTHING DATA. THAT IS STILL THERE AND IS VERY MUCH BEHIND THE SCENES AND WONDER AND MAYBE DEANNA COULD ADDRESS THIS. WE HAVE DONE PROBABLY THE BEST JOB I HAVE SEEN ANYWHERE THAT IS STARTING TO ADDRESS THESE BIG DATA ISSUES IN TERMS OF HOW WE INCREASE QUALITY AND DEVELOP RIGHT DATA MODELS AND DEVELOP COMMENTS THAT WE REALLY NEED. IS THERE A PLAN TO FURTHER ENHANCE WHAT WE ARE DOING IN DATA SHARING AND BUILDING DATA COMMONS FOR MOON SHOT 2.0? >> GO AHEAD. SORRY, DOUG. >> ANA, LET ME SAY THAT FIRST AT THE LEVEL OF PEDIATRIC CANCER RESEARCH WE ARE -- THE GOAL IS TO BE ABLE TO BASICALLY HAVE ALL CHILDREN WITH CANCER AS LONG AS THEY AND THEIR FAMILIES ARE AGREEABLE FOR THEIR DATA TO BE IN A DATABASE AND BE AVAILABLE TO RESEARCH COMMUNITY. THAT IS THE -- THAT IS THE GOAL. WE ALSO WOULD LIKE FOR PEDIATRIC CANCER FOR AS MANY COUNTRIES AS POSSIBLE TO PARTICIPATE WITH US FOR DATA SHARING. WE ARE ALSO IN THE PROCESS OF PUTTING LARGE DATABASE IN THE CLOUD SO THERE WILL BE OPPORTUNITY FOR MULTIOMICS ANALYSIS BEYOND GDC SO THAT CANCER RESEARCHERS CAN LOOK AT THOSE ISSUES. DEANNA, WOULD YOU LIKE TO SEE MORE? >> YEAH. I WAS GOING TO REALLY ADDRESS MORE OF THE MOON SHOT 1.0 RESPONSE WHERE WE TRIED TO TACKLE IT FROM A COUPLE OF DIFFERENT ANGLES AND ONE IS BEING REQUIRING ALL MOON SHOT FUNDED STUDIES TO MAKE DATA OPEN AND ACCESSIBLE IMMEDIATELY UPON PUBLICATION WE SUPPORTED IMPROVEMENTS IN CANCER RESEARCH DATA COMMONS TO ALLOW COMMON DATA STANDARDS AND INTEROPERABILITY AND MORE RECENTLY WE HAVE TALKED TO SYLVIA P. AND OTHER PEOPLE AND SYLVIA BEING CONCERNED ABOUT THE ISSUE OF HAVING COMMON DATA STANDARDS AND SHARING ESPECIALLY FOR CLINICAL DATA AND DON'T KNOW IF YOU WANT TO COMMENT, SYLVIA. WE ARE TRYING TO ADDRESS THE PROBLEM AT MULTIPLE LEVELS AND IS NOT AN EASY PROBLEM BUT WE WILL CERTAINLY CONTINUE TO WORK ON IT. >> YEAH. IT IS NOT EASY BUT CRITICAL AND THINK NCI SHOULD HAVE MORE VISIBILITY IN THIS AREA THAT WE ARE LEADING IN. IT IS IS A VERY HARD AND THE PROBLEM TO SOLVE. >> YES. >> LET'S TRY TO GET ONE LAST QUESTION IN FROM MICHELLE BEFORE WE MOVE TO KAY'S PRESENTATION. MICHELLE? >> THANKS FOR YOUR PRESENTATION. I'M DELIGHTED AT WHAT NCI IS DOING WITH THE CLINICAL TRIAL OF M SENSE. ARE YOU ABLE TO SXAEXPAND ON THAT? SHOULD WE WAIT UNTIL TOMORROW? >> MICHELLE, TO EXPAND ON CLINICAL TRIALS ISSUE? >> NCI'S PLANS THAT WILL BE ANNOUNCED TOMORROW. >> PLANS FOR EXPANDING CLINICAL TRIALS. YOU TOUCHED ON T WANTED TO KNOW IF WE SHOULD WAIT UNTIL TOMORROW. >> SORRY, MICHELLE. ONLY ASPECT BEING PRESENTED TOMORROW IS FOR WHAT ARE OFTEN REFERRED TO AS MULTICANCER EARLY DETECTION TASKS AND PHIL TAS ELWILL TALK ABOUT THAT IT IS WHAT HE AND HIS COLLEAGUES ARE REFERRING TO AS A VANGUARD STUDY THAT IS AN AREA THAT MANY PEOPLE ARE INTERESTED IN AND EXCITED ABOUT. AT THE MOMENT THERE IS NO EVIDENCE EARLY DETECTION OF ASYMPTOMATIC CANCER WILL ACTUALLY SAVE LIVES. MY HOPE IS THAT THIS APPROACH OF NCI BEING INVOLVED WILL BE ANALOGOUS TO THE NATIONAL LUNG CANCER SCREENING TRIAL WHERE HELICALLE CT HAD POTENTIAL AND PROMISE BUT HAD NOT ACTUALLY BEEN SHOWN TO SAVE LIVES AND CANCER SCREENING TRIAL WAS ABLE TO DO THAT. HOWEVER, I DO HOPE THAT IN EVENT THAT THIS TRIAL DOES SHOW ONE OR ANOTHER OF THESE TASKS ACTUALLY WORKS AND SAVES LIVES OF BETTER FASTER UPTAKE THAN THERE HAS BEEN OF LUNG CANCER SCREENING. >> IF ANYONE HAS ADDITIONAL QUESTIONS, FEEL FREE TO REACH OUT TO DR. GRAY. I'M SURE SOME HAVE DIRECT LINE INTO DOUG AND SURE HE WOULD BE HAPPY TO ADDRESS THOSE QUESTIONS AND IN INTEREST OF TIME WE WILL MOVE FORWARD WITH THE NEXT AGENDA ITEM IT THAT IS A PRESENTATION BY MK HOLO HAN ON THE LEGISLATIVE REPORT. MK? >> THANK YOU FOR THE OPPORTUNITY TO SPEAK WITH YOU TODAY. IN LIMITED TIME WE HAVE I WILL PROVIDE A BRIEF UPDATE ON APPROPRIATIONS AND NOTE PENDING LEGISLATION TO WATCH AND TOUCH ON CONGRESSIONAL CALENDAR AND WHERE THINGS ARE WITH UPCOMING MIDTERMS AND DETAILED LEGISLATIVE SUMMARY IN MEETING MATERIALS THAT COVERS FAR MORE THAN WE CAN IN OUR TIME TODAY AND IF YOU HAVE QUESTIONS REACH OUT WE ARE HAPPY TO HEAR FROM YOU AND YOUR STAFF AT ANY TIME. E-MAIL ME. I'M HAPPY TO HEAR FROM YOU. NEXT SLIDE, PLEASE. >> A LITTLE BACKGROUND AND REMINDING EVERYONE OF MECHANICS IN HOW WE RECEIVE APROPRIATION AND FY22 OM ANYBODIUS WASN'T ENACTED UNTIL MARCH 15TH EARLY FISCAL YEAR CASCADE EFFECT WHEN THINGS HAPPEN LATE IN TIME AND TRADITIONALLY PRESIDENT'S BUDGET RELEASED IN FEBRUARY AND STEP 1 HAPPENED MARCH 2 EIGHTH. TWO WEEKS AFTER FY22 IS FINALIZED AND RED X HERE SHOWS WHERE WE ARE CURRENTLY FOR APPROPRIATIONS PROCESS FOR FY23 AND COMMITTEE HELD HEARINGS AND FOLLOW-UP QUESTIONS AND DRAFTING AND MARKING OF BILLS AND APPROPRIATIONS COMMITTEE RELEASED SCHEDULE TO MARKUP BILLS BY END OF JULY AND DR. LOWY MENTIONED APPROACH REATORS HELD HEARINGS ON BUDGET HOUSE AND SENATE MEETING WAS MAY 17TH AND TESTIFYING FOR HEARINGS IN SUPPORT OF BUDGET REQUEST CONGRESS WANTS TO HEAR FROM OTHERS WE HAVE SEEN CONSISTENT INTEREST FROM CONGRESS HEARING FROM CANCER RESEARCHERS AND CANCER PATIENTS. NEXT SLIDE, PLEASE A FEW EXAMPLES THIS YEAR HOUSE APPROACH REIATORS OF ACS TO TESTIFY AT PUBLIC HEARING A FEW WEEKS AGO FY23 AND LAST YEAR PARALLEL HEARING FY22 AND PRESIDENT DR. DAVID TUVISON WAS TESTIFYING AT SAME HEARING FOR FY22 AND HOUSING SIDE MARCH OF THIS YEAR COMMERCE COMMITTEE -- TO TESTIFY ABOUT DIVERSITY AND CLINICAL TRIALS AS PART OF A LARGER HEARING WITH SEVERAL HAD HEALTH BILLS BEING DISCUSSED AND ARE A FEW EXAMPLES. THERE HAVE BEEN MANY AND GRATIFIED CONGRESS CONTINUES ENGAGE WITH RESEARCHERS AND EXPERTS TO SHARE VIEWPOINTS ABOUT TREMENDOUS OPPORTUNITIES IN CANCER RESEARCH THAT IS MORE IMPORTANT AS WE HAVE TREMENDOUS VOLUME OF APPLICATIONS. CONGRESS IS INTERESTED IN HEARING FROM PEOPLE WHO ARE WRITING GRANT APPLICATIONS AND RUNNING CANCER CENTERS AND CAN PROVIDE MEANINGFUL CONTEXT. WE LOOK FORWARD TO DOG IT AND LOOK FORWARD TO OPPORTUNITIES IN THE FUTURE AND NEXT SLIDE, PLEASE. I WOULD LIKE TO TAKE A MOMENT HERE TO ADDRESS AN ISSUE LEADING TO SOME CONUNDERSTANDABLE CONSTERNATION ABOUT FY23 BUDGET REQUEST. WE WERE FUNDED BY CONTINUING RESOLUTION UNTIL MID-MARCH KEEPING US AT FY21 LEVEL BASELINE FOR FY23 BUDGET CALCULATION AND WHAT YOU CAN SEE HERE IS THE NCI -- NCI NUMBER IS FY22 AND THERE WAS A $353 MILLION INCREASE AND WHEN FY23 BUDGET CAME OUT WHAT IT LOOKS LIKE IS PROPOSING $199 MILLION CUT AND THERE HAS BRN CONFUSION ABOUT THIS THIS IS NOT UNIQUE TO NCI. 11 OTHER ICS HAVE SIMILAR DELTAS BETWEEN FY22 ENACTED LEVEL AND FY23 BUDGET REQUEST AND HAS BEEN ENOUGH QUESTIONS ABOUT IT ACTING NIH DIRECTOR LARRY TABEK POSTED A BLOG ABOUT THIS AND INSIGHTS INTO PROCESS AND CLARIFIED ADMINISTRATIONS INTENT WASN'T TO REDUCE FUNDING OF ICS BUT RELATED TO BASELINE COMPARITIOR USE AND IS HELPFUL TO HAVE CONTEXT AND DR. LOWY SHOWED IN SLIDE DEPICTING BUDGET REQUEST NUMBERS AND ENACTED APPROPRIATIONS FOR NCI AND COULD EXTRACT THAT OUT TO ENTIRE AGENCY OF NIH AND THEY TAKE THIS VERY SERIOUSLY AND DECIDE WHAT APROPRIATION NUMBERS WILL BE AND EXPRESSION SOMETIMES YOU WILL HEAR APPROACH REATORS REPEAT KORN GREYS HAD MULTIPLE BUDGET REQUESTS OVER TIME THAT INTENDED TO CUT FUNDING FOR NIH AND NCI AND THEY HAVE DECLINED TO DO THAT AND TO CUT FUNDING FOR CANCER RESEARCH CONSISTENTLY DURING VERY CHALLENGING BUDGET CYCLES AND DURING SCENARIOS WHERE STRICT BUDGET CUTS THEY HAD TO ADHERE TO THAT IS HELPFUL CONTEXT TO UNDERSTAND WHERE WE ARE WITH FY23. NEXT SLIDE, PLEASE. LAST WEEK, MOVING THIS PROCESS FURTHER, HOUSE ADOPTED A DEEMING RESOLUTION IN PLACE OF A BUDGET RESOLUTION. I WILL AVOID DETAILS WHY THEY PICKED THIS AND BUDGET RESOLUTION AND FOR PURPOSES WHAT IS IMPORTANT IS SETTING TOP LINE DISCRETIONARY SPENDING VALUES AND ENABLES APPROACH REATORS TO SET NUMBERS IN HOUSE AND SETS OVERALL NUMBER NOT RESOLVING BIGGEST CHALLENGE HOW MUCH WILL BE FOR DEFENSE AND HOW MUCH FOR NONDEFENSE BUDGET SPENDING AND BIGGEST STICKING POINT FOR FY22 AND CREATED A REAL DELAY IN MOVING FORWARD AND NUMBER DOESN'T GIVE SUB COMMITTEES EACH OF 12 SUB COMMITTEES THERE INDIVIDUAL ALLOCATION THAT SOMETIMES IS REFERRED TO AS 302BS CHAIR OF LABOR HHS SUB-COMMITTEE KNOWS WHAT THEIR NUMBER IS AND TOP REPUBLICAN SENATOR IN THE SENATE SHELBY PREDICTED LAST WEEK THERE IS 50/50 CHANCE THEY GET TO BIPARTISAN AGREEMENT BETWEEN SPENDING DEFENSE AND MUCH MORE SO IN ELECTION YEAR AND DON'T EXPECT ACTION UNTIL APROPRIATION OF MIDTERMS THAT TIMEFRAME IS CONSISTENT WITH WHAT WE EXPERIENCE AS FAIRLY ROUTINE AND THERE IS CONJECTURE THAT IF THE GOP IS CONFIDENT AND IF THEY END UP RETAKING MAJORITIES IN HOUSE AND PERHAPS SENATE AS WELL THEY MIGHT WANT TO PUNT COMPLETING FY23 APPROPRIATIONS INTO NEXT CONGRESS WHEN THEY HAVE MORE CONTROL OVER FINAL PRODUCT AND IS A FEW DISINCENTIVES FOR THAT AND ONE IS NEXT PROP OF LEADERSHIP IN COMMITTEES TO EXTENT THERE ARE CHANGES WANTS TO START FRESH AND VIEWPOINT RETIRING APPROACH REATORS WANT TO HOLD PEN ONE MORE TIME AND THEY HAVE MANY OF THEM AND NOT ALL MEMBERS HAVE DECIDED TO REQUEST EARMARKS AND THOSE THAT HAVE WANT TO DELIVER FOR CONSTITUENTS AND IS NOT A SMALL ISSUE AND MEMBERS IN FY22 AND EARMARKS INCLUDED IN THAT BILL AFTER OVER A DECADE OF BEING BLOCKED AND THEY AMOUNTED TO ABOUT HALF A BILLION DOLLARS AND THERE IS REAL MONEY AT ISSUE HERE THAT MIGHT MILLTATE TOWARDS GETTING THESE DONE. NEXT SLIDE, PLEASE. TOUCHING ON ARPAH MANY QUESTIONS REMAIN FROM AUTHORIZERS AND APPROACH REATORS AND IS A DEVELOPING ISSUE IN FY22 PROVIDED A BILLION DOLLARS FOR ARPAH AND COULD SPEND OVER THREE YEARS AND APPROPRIATIONS BILL ALLOWED SECRETARY TO DIRECT MONEY IN NIHHS AND AS MANY ARE AWARE THERE IS RODID BUST DEBATE IN PUBLIC AND IN HEARINGS ABOUT WHAT ARPAH AND RELATIONSHIP WITH NIH SHOULD BE AND HOW DISTINCT IT SHOULD BE OR HOW SEPARATE AND IS A VIEWPOINT MAYBE IT SHOULD TAKE ADVANTAGE OF EXISTING INFRASTRUCTURE AND MIGHT BE REAL EFFICIENCY AND BY APPROPRIATE REATORS ALLOWING SECRETARY TO DIRECT MONEY TOWARDS NIH PAVED WAY TO MAKE CHOICE AND TRANSFERRED MONEY IN APRIL OF THIS YEAR THERE WERE A FEW QUESTIONS ABOUT THIS FY23 REQUEST ADDITIONAL $4 BILLION AND THERE HAVE BEEN AUTHORIZING BILLS NONE COMPLETED TO FY22 AND APROPRIATION IS LAW THAT WE HAVE ON ARPAH AT THIS POINT AND BILLS HAVE TAKEN DIFFERENT APPROACHES WITHIN NIH OR OUTSIDE OF NIH ISSUE AND HOUSE MEMBERS ARE WORKING TOGETHER TO COORDINATE THEIR APPROACH AND LAST WE HEARD ABOUT THIS. SENATE HAS A DIFFERENT APPROACH BILL INTRODUCED IN SENATE RICHARD FROM NORTH CAROLINA AND PATTY FROM WASHINGTON STATE SPECIFY NEW LOCATION OF AGENCY CAN'T BE IN CAPITAL AREA OR ANYWHERE NEAR NIH CAMPUS AND MANY STATE DELEGATIONS HAVE BEEN HAPPY TO HAVE NEW AGENCY COME TO THEIR STATES AND SENATE BILL HAS LANGUAGE PROHIBITING -- WITHIN THREE PREVIOUS YEARS AND WE WILL WATCH CLOSELY AND POSSIBLE THAT A COMPROMISED VERSION AUTHORIZING LEGISLATION WILL EMERGE AND MOVE LATER THIS SUMMER AND MIGHT NOT GIVEN THERE IS APROPRIATION THAT AGENCY EXISTS AND CAN CONTINUE IN THAT FORM AND WILL SEE WHAT HAPPENS THERE. NEXT SLIDE, PLEASE. THERE IS A LONG LIST OF LEGISLATIVE PRIORITIES AND MUST PASS LEGISLATION IN A SHORT TIMEFRAME AND ARE EXPIRING AUTHORIZATIONS THAT ARE MUST PASS AND FDA USER FEE REAUTHORIZATION EXPIRES END OF SEPTEMBER AND SBARTT PROGRAM EXPIRES AT END OF SEPTEMBER AND EACH YEAR IS REQUIREMENT FOR CONGRESS TO DO NDAA NATIONAL DEFENSE AUTHORIZATION ACT THAT SETS POLICY AND TOP-LINE FUNDING GOAL FOR DEFENSE PROGRAM THAT IS NOT APROPRIATION ITSELF, HOWEVER. WE WILL SEE AS PART OF THAT DISCUSSION THAT WILL BRING TO A HEAD SPLIT OF DEFENSE VERSUS NONDEFENSE SPENDING AND IS OTHER PRIORITIES FOR ADMINISTRATION INCLUDING AMERICAN COMPETITIVENESS LEGISLATION THAT IS A BILL KNOWN BY MANY DIFFERENT NAMES ENDLESS FRONTIERS ACT AMERICAN INNOVATION ACT AND MAKE IT AMERICA ACT AND IN CONGRESS RIGHT NOW AND THAT IS PROCESS TO RESOLVE DIFFERENCE BETWEEN HOUSE AND SENATE VERSIONS AND WE WILL SEE WHAT HAPPENS WITH THAT AND MAY ALSO SEE ANOTHER ATTEMPT TO MOVE THE BUILD BACK BETTER RECONCILIATION PACKAGE OR A SCALED DOWN VERSION OF THAT ASSOCIATION IS WORKING WITH SENATOR MANCHIN AND DOMESTIC PRIORITIES OF THE ADMINISTRATION AND HAVE TO DO BY END OF SEPTEMBER ALSO. THAT PACKAGE IS BASED ON RECONCILIATION INSTRUCTION THAT ALLOWS THEM TO PASS IT ONLY ON SIMPLE MAJORITY IN THE SENATE. IF THEY CAN ACHIEVE THAT THEY CAN GET IT DONE WITHOUT GETTING 60 VOTES THAT IS TO BE DETERMINED IF THEY CAN DO THAT AND MIGHT SEE IN COVID FUNDING THERE HAVE BEEN THREE ATTEMPTS AND NUMBERS HAVE BEEN SCALED DOWN FROM HIGH OF 22 BILLION TO ABOUT 10 BILLION THERE WERE ISSUES AND THEY PRESENT OPPORTUNITY FOR BILLS TO BE ATTACHED AND THEY ARE CALLED WRITERS AND MIGHT BE THESE PRIORITIES AND LEGISLATIONS IN -- MUST-PASS LEGISLATIVE ISSUES AND NEXT SLIDE, PLEASE. SHOWING YOU CONGRESSIONAL CALENDAR FOR A VISUAL OF REALLY I THINK HOW LITTLE TIME REMAINS YELLOW SHOWS WHEN HOUSE AND SENATE ARE IN SESSION. 148 DAYS UNTIL MIDTERMS AND 109 DAYS UNTIL GOVERNMENT FUNDING RUNS OUT THAT MIGHT NOT SOUND LIKE SUPER SHORT AMOUNT OF TIME. ONLY 30 LEGISLATIVE DAYS WAREHOUSE AND SENATE ARE IN SESSION AND IS NOT A LOT OF TIME HERE. OVERLAYING INTO THIS FACT MIDTERMS ARE NOVEMBER EIGHTH AND CAMPAIGNING GOING ON WITH MEMBERS OF HOUSE AND 1/3 OF SENATE UP FOR RE-ELECTION AND ARE KEY NOMINATIONS THAT REQUIRE TIME ON SENATE CALENDAR AND RELEVANT TO US WE DON'T YET HAVE NOMINEES ANNOUNCED FOR NIH DIRECTOR SLOT OR OXTP DIRECTOR SLOT AND SENATE CONFIRMATION THAT WOULD NEED TIME ON CALENDAR. NEXT SLIDE, PLEASE. THIS HAS BEEN PRETTY WIDELY REPORTED. HISTORY TELLS US PRESIDENT'S PARTY USUALLY LOSES SEATS IN MIDTERM ELECTIONS. IN HOUSE HAS BEEN TWO EXCEPTIONS TO PATTERN SINCE 1946 ONE WAS AFTER 9/11 AND THIS EXPECTATION WILL EFFECT ALL OF LEGISLATIVE ACTIVITIES AND CONGRESS'S SORT OF WORK PACE OVER THE NEXT COUPLE MONTHS. NEXT SLIDE, PLEASE. SO, WE ARE HEADING INTO MIDTERMS IN A SCENARIO WHERE THE HOUSE AND SENATE MAJORITIES ARE VERY, VERY CLOSE AND 50/50 SENATE AND 12 SEATS IN THE HOUSE AND RETIREMENTS HAVE BEEN ANNOUNCED DEMOCRATIC RETIREMENTS REACHED A 30 YEAR HIGH AND NOT SIGNIFICANT AMOUNT OF REPUBLICAN RETIREMENTS AS WELL. THIS FLUX SORT OF ADDS TO VOLATILITY UNPREDICTABILITY OF MIDTERMS WE KNOW ABOUT CONGRESS IT WILL HAVE LOTS OF NEW FACES THAT WE WILL LOSE IN SENATE SENIOR APPROACH REATORS AND LONG-TIME NIH CHAMPIONS AND -- ROY BLUNT AND SEEING DEPARTURE OF STRONG CANCER RESEARCH ADVOCATES IN HOUSE INCLUDING REPRESENTATIVES JACKIE SPEAR AND REPRESENTATIVE GK BUTTER FIELD AND FRED UPTON AND GRATEFUL FOR EFFORTSES AND REMAINING CHAMPIONS IN BIOMEDICAL RESEARCH REMAINING IN CONGRESS AND RENEWED ACTION BY CAUCUSES TO PUT A LOT OF ENERGY TO REMAIN ENGAGE DURING THIS TIME OF COVID PANDEMIC AND WORKING VIRTUALLY AND HAVE BEEN PLEASED TO HAVE INVITATIONS FOR LEADERSHIP TO ENGAGE WITH THOSE MEMBERS AND NEXT SLIDE, PLEASE. GLAD TO TAKE QUESTIONS YOU HAVE NOW OR IN FOLLOW UP AFTER THE MEETING. THANK YOU. >> THANK YOU, KAY. ALWAYS FIND IT FASCINATING ALL IDIOSINCRACIES GOING INTO THE BUDGETARY PROCESS. DO WE HAVE QUESTIONS? I HAVE A QUESTION THAT IS BASED A LITTLE ON ASSUMPTION. THERE IS ONE BILLION FOR ARPAH IF IN 2022; CORRECT? >> UH-HUH. >> THAT IS ONLY FOR THIS BUDGET YEAR. WHAT HAPPENS? WHEN WILL FUNDS EXPIRE? >> FUNDS ARE GOOD THREE YEARS AND DON'T HAVE TO BE. >> THREE YEARS. OKAY. DIDN'T KNOW THAT. >> ASSUMPTION IS CONGRESS CAN HAVE MULTIBUDGET AUTHORITY DON'T HAVE TO SPEND IN ONE YEAR AND SOMETIMES NO MONEY AND NO EXPIRATION DATE ON DOLLARS BUT GIVES FLEXIBILITY PARTICULARLY BRAND NEW ENTITY DIDN'T GET THAT FUNDING UNTIL VERY LATE INTO THE FISCAL YEAR. >> YES, ANA? ANNE. >> SORRY. MK GETTING BACK TO QUESTION THAT JOHN ASKED. THAT BILLION, IS THAT A PROJECT MANAGEMENT FOCUSED ACTIVITY AND WHAT DARNA IS AND ARPAH IS SUPPOSED TO BE AND HOW DO WE GET INVOLVED IN TERMS OF ACCESSING THOSE FUNDS? CAN WE? >> I REALLY DON'T KNOW DR. BARKER. I MEAN IT WOULD BE OR I CAN TELL YOU CONGRESS MADE IT CLEAR THAT IN APPROPRIATIONS LANGUAGE IN FY22 THEY MADE IT CLEAR APPROACH REATORS EXPECT ARPAH TO FOCUS ON DISEASE AREAS THAT SPECIFICALLY ARTICULATED CANCER, ALS, DIABETES AND ALZHEIMER'S DISEASE AND WE EXPECT THEY WILL DO THAT AS COMMITTEES MADE CLEAR AS EXPECTATION AND THERE IS SO MUCH UNKNOWN ABOUT WHAT IT WILL -- HOW THIS ORGANIZATION WILL WORK AND HOW IT WILL INTERFACE WITH OTHER RESEARCH EVERIES AND HOW IT MIGHT INTERFACE WITH NIH THAT IS A SENSE TICH POINT AND POINT OF A LOT OF ATTENTION. I DON'T HAVE ANSWER TO THAT QUESTION AND I JUST SAW LAST WEEK THAT THERE WAS NIH ADVISORY COMMITTEE FOR THE DIRECTOR MEETING AND DR. TERRA S. IN NIH DID PRESENTATION ABOUT ARPAH AND PROVIDED AS MUCH DETAIL AS EXISTED NOW AND WOULD ENCOURAGE ANYONE WHO IS INTERESTED TO GO AND TAKE A LOOK AT PRESENTATION AND THERE IS A POWERPOINT YOU CAN DOWNLOAD OR PDF YOU CAN DOWNLOAD AND QUESTION POPPED UP IN CHAT WHO IS IN CHARGE OF ARPAH. TERRIFIC QUESTION ALSO. APPOINTMENT OF DEPUTY DIRECTOR OF NIH AND DR. RUSSELL IS HIS NAME AND I DON'T HAVE INFORMATION ABOUT THAT. REALLY, WHO IS -- WHO IS ON THE SHORT LIST FOR BEING CONSIDERED. I DON'T KNOW. >> WORKING WITH ARPAH AND MANY PEOPLE ON CALL TODAY MIGHT IN FACT BE CONTACTED FOR BOTH IDEAS AND TO CONTRIBUTE PROJECT MANAGERS EVENTUALLY FOR THIS. USUALLY A 2 OR 3 SENT AND IF THEY CAN FOLLOW SAME MODEL. >> DR. SHA WIETS'S PRESENTATION PART OF CONVERSATION THEY TALKED ABOUT THREE YEAR CAP FOFR PROJECT MANAGERS TO HAVE I ACHURN. >> IT IS REALLY TO BE DETERMINED AND THAT PRESENTATION IS MOST RECENT AND MOST COMPREHENSIVE INFORMATION THAT I HAVE SEEN ABOUT WHAT THE VISION IS. OBVIOUSLY, YOU KNOW, WHO IS THE DIRECTOR GOING TO BE AND WHAT WILL THEIR VISION BE AND HOW WILL THEY NAVIGATE THIS? IT WILL BE INTERESTING TO SEE HOW DISEASE-SPECIFIC FOCUS PLAYS OUT AND WILL BE SOMETHING THAT WILL PROVIDE OPPORTUNITIES FOR PROGRESS IN CANCER RESEARCH. >> THANK YOU. >> MIGHT HAVE TIME FOR -- IS IT -- CHRIS, IS IT A QUICK SUCCINCT QUESTION? >> IT WILL CERTAINLY BE SO. THANK YOU. YEAH. THIS IS A TOUCH ISSUE AND WE ARE SINGING FROM SAME HIM BOOK AND RESEARCH COMMUNITY WANTS TO ENGAGE IN THIS AND HAVE ADVANCES AND WE ARE PARALYZED HERE. I WOULD SAY SOME ARE MORE INVOLVED THAN OTHERS IN THIS CONVERSATION AND FOR THOSE WITH SEAT AT TABLE RESEARCH COMMUNITY IS LOOKING FOR CLARITY AND LOOKING FOR REAL CLARITY AND WHAT DECISION MAKING PRINCIPLES WILL BE AND CLEAR TIMELINE AND UNDERSTAND POLITICS INVOLVED AND IT WILL BE VERY, VERY DIFFICULT FOR RESEARCH COMMUNITY TO ENGAGE MEANINGFULLY AND GET GOOD SCIENCE OUT OF THIS UNLESS WE HAVE MESSAGING AND CLAIRIT AS TO WHAT ADMINISTRATION AND CONGRESS IS LOOKING TO DO NOT ASKING MK TO DO THAT BUT SOME ARE IN VERY IMPORTANT POSITIONS THAT CAN HAVE INFLUENCE. I WOULD ASK FOR THOSE BEING ASKED TO WEIGH IN TO PLEASE REALLY RESONATE AT THAT POINT. IT IS A MISSED OPPORTUNITY UNLESS WE GET CLARITY HERE. THANK YOU. >> ABSOLUTELY. I COULDN'T AGREE WITH YOU MORE. SO, AGAIN, MK PROVIDED REALLY AMAZING INFORMATION. I THINK IT WILL BEHOOF SOME OF US TO DO SOME OF OUR OWN DUE DILIGENCE BASED ON COMMENTS AND TRYING TO PULL OUT AS MUCH INFORMATION AS WE CAN AND DURING NEXT MEETING WE CAN GET ADDITIONAL UPDATES. THANK YOU. >> THANK YOU. >> SO, NEXT AGENDA ITEM IS A PRESENTATION FROM DR. JOHN WILLIAMS WHO WILL PROVIDE A REPORT FROM THE PRESIDENT'S CANCER PANEL AS CHAIR. JOHN? >> THANK YOU AND EVERYONE FOR BEING HERE AND LOOK FORWARD TO WHEN WE CAN ACTUALLY MEET IN PERSON. I THINK THERE IS A LOT THAT VIDEO CONFERENCING OFFERS AND LOTS OF EFFICIENCY BUT IS SOMETHING ABOUT THE HUMAN TOUCH AND BEING AT THE SAME TABLE THAT WILL HELP US DO OUR JOBS AND RESPONSIBILITIES TOGETHER AND WANT TO TELL YOU ABOUT OUR REPORT THAT WE ISSUED IF EBB WITH THE PRESIDENT'S CANCER MOON SHOT AND CLOSING GAPS IN CAPTIONER SCREENING, CONNECTING PEOPLE, COMMUNITY, AND SYSTEMS TO IMPROVE EQUITY AND ACCESS. NEXT SLIDE. AS YOU ALL ARE AWARE AND I PRESENTED JUST OVER A YEAR AGO BACKGROUND ABOUT THE PRESIDENT'S CANCER PANEL 3-PERSON GROUP ESTABLISHED NATIONAL CANCER ACT AND OUR ROLE IS TO MONITOR DEVELOPMENT EXECUTION OF ACTIVITIES OF NATIONAL CANCER PROGRAM AND REPORT TO THE PRESIDENT. IN PURPOSE AND IN REALITY, WE WORKED FOR A YEAR TO TAKE ONE CRITICAL TOPIC AND HAVE PUBLIC MEETINGS AND FORMULATE A REPORT AND ISSUE A REPORT TO THE PRESIDENT, WHITE HOUSE AND ALL STAKEHOLDERS AND CANCER AND HAVE A WONDERFUL PANEL DR. OOEJIC MITCHELL AND BOB ENGRAM AND WORK SEAMLESSLY TOGETHER WITH THAT ONE GROEL AND WOULD LIKE TO SAY OUR PANEL REALLY HAS NO POWER. WE DON'T DISTRIBUTE FUNDS AND DON'T DO ANYTHING BUT GATHER A REPORT AND TRY TO GIVE EVERYONE A PUSH AND ALL STAKEHOLDERS OF WHICH YOU ARE AN IMPORTANT ONE. NEXT SLIDE. IN EARLY 2020 COVID PANDEMIC HIT AND CRITICAL THING IN CANCER THAT BECAME AMAZINGLY APPARENT WAS LACK OR DROP OFF OF CANCER SCREENING BY 90% FOR MAMMOGRAPHY AND COLONOSCOPIES FOR COALO RECTAL CANCER AND SCREENINGS AND KNEW THIS WAS A PROSH LEM AND OTHER PROBLEMS IN CANCER TREATMENT AND DR. [INAUDIBLE] ISSUED REPORT WITH DATA ANTICIPATING IN NEXT 10 YEARS 10,000 DEATHS EXCESSIVELY OCCURRED AS RESULT OF PANDEMIC BREAST AND COALO RECTAL CANCER BREAST CANCER CAUSES 1/6TH OF CANCER DEATHS IN OUR COUNTRY AND THIS IS A TOPIC WE TOOK AND HAVE SPENT LAST YEAR AND A HALF COMING UP. NEXT SLIDE. PUTTING TOGETHER WORKING GROUPS AND PUTTING TOGETHER FOUR WORKING GROUPS TOGETHER FOUR SCREEN REMAINING BASED TYPES AND CANCERS HAVE SCREENING INVOLVED WITH THEM AND THIS IS AN OVERVIEW OF LUNG CANCER AND CO-CHAIRS AND AMONGST WE HAD WORKING GROUP MEMBERS INCLUDING CHAI KOO PARTICIPATING IN THE GROUP CERVICAL AND BREAST CANCER SCREENING AND IF NEXT SLIDE. WE HAD GROUPS THAT WORKED EFFECTIVELY IDENTIFYING CRITICAL ITEMS AND BARRIERS AND OPPORTUNITIES FOR EACH TUMOR TYPES AND CROSS-CUTTING THEMES AND GATHERED OVER THE FALL OF 2020 PUBLIC MEETINGS FOR FOUR DIFFERENT TUMOR TYPES. WE GATHERED 160 OR MORE STAKEHOLDERS TO PARTICIPATE IN THE PUBLIC MEETINGS AND MANY OTHER ON SIDE CONVERSATIONS AND REQUEST FOR INFORMATION. WE TOOK THAT INFORMATION IN FACILITATED PUBLIC MEETINGS AND SCREENINGS AROUND THOUGHT LEADERS THINKING OUTSIDE OF THE BOX AND IN HEALTH CARE WE STRUGGLE WITH THAT AGGRESSIVELY. WE TOOK GOOD INFORMATION FROM PEOPLE WHO ARE THINKING DIFFERENTLY AND PUT IT TOGETHER AND BEGAN TO WRITE OUR REPORT. NEXT SLIDE. WHAT WE CONCLUDED ALTHOUGH COVID CAME AND SHUT DOWN CANCER SCREENING DRAMATICALLY, WE REALIZED THAT WASN'T THE MAIN TOPIC THAT IT WOULD HURT PEOPLE BUT CANCER SCREENING IS GETTING BACK TO PRE-COVID BASELINE AND IDENTIFIED CANCER SCREENING UPTAKE AND PERCENTAGE OF PEOPLE GETTING CANCER SCREENING THAT BENEFIT BASED ON EVIDENCE-BASED GUIDELINES ISSUED IT AND THIS GRAPH OUTLINES IT. UPTAKE FOR BASELINE THAT IS ALL PRE-COVID IS INCOMPLETE AND UNEVEN. WE HAVE LOTS OF WORK TO DO. WE HAVE NOT SPENT AS MUCH VISIBLE AND POLITICAL FOCUS ON THIS AND FELT IT WAS A GREAT TIME TO DO THIS CANCER SCREENING IN GENERAL FROM PRESIDENT'S CANCER PANEL. SIGNIFICANT GAPS EXIST OBVIOUSLY IN UPTAKE FOR MANY COMMUNITIES OF COLOR AND SOCIO ECONOMICALLY ADVANTAGED POPULATIONS LOW EDUCATIONAL ACHIEVEMENT. RURAL URBAN DIFFERENT GEOGRAPHICAL AREAS IN COUNTRY AND BARRIERS AND LACK OF AWARENESS AND UNDERSTANDING AND LOTS OF BARRIERS FROM PROVIDER SIDE WE ARE NOT OFFERING CANCER SCREENING TO SO MANY PEOPLE. FROM A PHYSICIAN AND PROVIDER PERSPECTIVE. THERE IS LOGISTICAL AND STIGMA AND FEAR CHALLENGES TO DIFFERENT CANCER TYPES AND COST. ALL OF THESE -- NEXT SLIDE. SOME ARE CROSS-CUTTING ISSUES WE IDENTIFIED AND SOME ARE TUMOR SPECIFIC. SO, WITH THAT, EFFECTIVE AND EQUITABLE IMPLEMENTATION OF EXISTING EVIDENCE GUIDELINES OF SCREENING MODALITIES, WE HAVE TO IMPLEMENT THEM. WE CAN IMPROVE CANCER OUTCOMES AND DETECTING THEM EARLIER AND ACHIEVING PRESIDENT'S ULTIMATE GOAL LESSENING DEATH RATE OF CANCER OVERALL DONE FOUR MAJOR GOALS FACILITATING EQUITABLE ACCESS STRENGTH IF IN WORKFORCE COLLABORATIONS CREATING BETTER EFFECTIVE SYSTEM FOR SCREENING AND NEXT SLIDE RECOMMENDATIONS FOR ALL 4. LY BRIEFLY GO THROUGH THIS GOOGLING PRESENCE CANCER PANEL IT IS ON OUR WEBSITE YOU CAN DOWNLOAD OUR ENTIRE REPORT. FIRST AND FOREMOST WHAT CAME ACROSS FOR ALL TUMOR TYPES AND ACROSS ALL TUMORS IS THAT WE NEED TO DO A BETTER JOB COMMUNICATING THE OPPORTUNITY AND BENEFITS OF CANCER SCREENING AND HARMS ALSO. WE NEED TO MAKE IT EASY FOR PEOPLE TO GET INFORMATION. WE ALSO NEED TO GIVE PEOPLE SO THAT THEY UNDERSTAND INFORMATION AND IN AN EASY TO UNDERSTAND FORMAT IN THEIR OWN LANGUAGE. WE HAVE TO GIVE PEOPLE INFORMATION TO APPRAISE AND MAKE THEIR OWN DECISION TO ENTER INTO SCREENING FOR BREAST CANCER, FOR EXAMPLE. YOU ARE STARTING A LIFE -- A HEALTH AND LIFESTYLE SYSTEM FOR YOURSELF AND WE HAVE TO MAKE IT EASY TO ACCESS AND APPLY. A TASK AND ASK ALL OF YOU TO ALWAYS BRING THE COMMUNICATION ASPECT OF WHATEVER ROLE AND ESPECIALLY LEADERSHIP ROLE THAT YOU PLAY IN TRYING TO COMMUNICATE BENEFITS OF CANCER SCREENING AND ONE CRITICAL OPPORTUNITY AND IF NOT FAMILIAR WITH AMERICAN CANCER SOCIETY'S NATIONAL CANCER ROUNDTABLE MODEL BUT TWO ROUNDTABLES BOTH LUNG CANCER SCREENING AND COALO RECTAL SCREENING OR COALO RECTAL ROUNDTABLE AND PREDOMINANT ROLE IS PROMOTING SCREENING IT THAT BOTH CAME UP WHEN COLONOSCOPIES NEED A BOOST TO IMPLEMENT THEM AND LUNG CANCER IS INNIN FANCY WE SCREEN LESS THAN 10% AND MORE LIKE 5% OF THOSE THAT BENEFIT AND WE NEED TO STRENGTHEN THOSE IS ROUNDTABLES THAT LOTS OF TIMES REQUIRES FUNDING AND WE PROPOSE TO CREATE A NATIONAL BREAST CANCER ROUNDTABLE AND NATIONAL CERVICAL CANCER ROUNDTABLE WITH EMPHASIS AMONGST OTHER THINGS SCREENING. NEXT SLIDE. FACILITATE EQUITABLE ACCESS. WE HAVE TO NOT ONLY IDENTIFY THOSE THAT WE LEAVE BEHIND. WE HAVE TO ALSO HAVE A HIGH TOUCH, SO-TO-SPEAK. DO HARD WORK TO TOUCH COMMUNITIES THAT DO NOT GET CANCER SCREENING WHETHER GEOGRAPHIC OR WHETHER IT IS LANGUAGES AND CULTURES AND PEOPLE OF COLOR AND COMMUNITIES OF COLOR. WE HAVE TO BUILD RELATIONSHIPS WITH COMMUNITIES. WE HAVE TO PROVIDE INFORMATION AND PROMOTE FOLLOW UP CARE IN SCREENING AND HAVE TO ALSO FACILITATE ACCESS TO RESOURCES AND SERVICES ALL THINGS WE TALK ABOUT. ONE CRITICAL OPPORTUNITY IS PROVIDING FUNDING. NOT ONLY FOR COMMUNITY ORIENTED ORGANIZATIONS THAT DO THIS ON THE GROUND AND MOST ARE LAY PEOPLE BUT ARE MOTIVATED TO HELP AND KNOW THEIR COMMUNITY AND WE HAVE TO FIND SUSTAINABLE FUNDING MECHANISMS FOR COMMUNITY HEALTH WORKERS IN A VERY SIMILAR MODEL. WE SUPPORT THAT AND ALSO WITH ACCESS WE NEED TO INCREASE ACCESS TO SELF-SAMPLING AND WE DO THAT WITH STOOL BASED TESTING COALO RECTAL CANCER IN FIT TEST THAT ARE UNDERUTILIZED AND BRINGING IN PEOPLE WITH A FEAR OR STIGMA ASSOCIATED WITH COLONOSCOPIES AND OPPORTUNITIES FOR CANCER SCREENING AT HOME NOT ENTERING HEALTH CARE SYSTEM AND LEARNED ABOUT THAT DURING COVID COULDN'T GO IN OR PEOPLE WERE VERY FEARFUL WE SENT MESSAGE TO SCREENING COMMUNITY AND IF WE THINK THERE SAY GREAT OPPORTUNITY FOR SELF-SAMPLING FOR HPV CERVICAL SELF SAMPLE WILLING TO SPAN CANCER SCREENING AND IT IS NOT FDA APPROVED BUT THINK THERE IS INCREDIBLE OPPORTUNITIES AND STRENGTHENING WORKFORCE COLLABORATIONS RECOGNIZE CANCER PANEL MADE PREMISE PRIMARY CARE PHYSICIANS AND OTHERS THAT ACT AS PRIMARY CARE PROVIDERS GYNS FOR EXAMPLE OVERWORK HAVE TOO MANY REGULATORY AND TOO MANY MEDICAL RESPONSIBILITIES TO ADD MORE SUCH AS TELLING THEM TO DO MORE FOR CANCER SCREENING AND OPPORTUNITY COMING UP ACROSS THE BOARD IN TUMOR DISCUSSION WE HAVE TO UTILIZE WORKFORCE IN OFFICE AND FRONT DESK PEOPLE RESOURCE AND TECHNOLOGY IN WAITING AREA AND CAN TALK TO PATIENTS ABOUT CANCER SCREENING WITH THREE OR FOUR PEOPLE WITH CONVERSATIONS WITH THEIR PROVIDERS AND PROVIDER TEAM AND WE NEED TO ALSO EDUCATE OUR TEAM ABOUT IDENTIFYING SOMEONE WHO IS NOT GETTING MAMMOGRAPHIC OR COALO RECT CAL OR CERVICAL CANCER SCREENING AND SHARED DECISION MAKING REQUIREMENT FOR LUNG CANCER SCREENING IS BIGGEST OPPORTUNITY FOR IDENTIFYING PEOPLE WHEN IN A CURABLE STAGE OF CANCER AND CMS HAS REQUIREMENTS REGARDING SHARED DECISION MAKING AND WE WOULD LIKE TO SEE A WAY WHERE SHARED DECISION MAKING CAN BE A TEAM-ORIENTED PROCESS NOT REQUIRING A PHYSICIAN THAT PHYSICIAN ONE ON ONE REQUIREMENT THAT IS DESIGNED TO PREVENT THE HARMS OF OVERSCREENING AND WE FEEL IT IS A MAJOR BARRIER. NEXT SLIDE. >> GENETIC TESTING CAME UP AMONGST MANY DIFFERENT TUMOR TYPES AND THERE IS SO MANY THAT ARE NOT OFFERED OR IDENTIFIED TO BE AT RISK FOR HARBORING CANCER CAUSING GENETIC MUTATION AND NEED TO EXPAND GENETIC DRUM LINE TESTING TO THOSE THAT BENEFIT FOR IT AND ONE OPPORTUNITY TO TEAR DOWN MAJOR BARRIER AND ENSURES REQUIRING GENETIC COUNSELORS UP FRONT AND PROVIDERS SHOULD BE ABLE TO OFFER GENETIC TESTING WITH CONFORMED CONSENT AND HAVE AVAILABILITY FOR GENETIC COUNSELING WHEN ONE IS NEEDED AND IS WHAT WE FEEL HARMS ARE OF SO MANY THAT ARE NOT IDENTIFIED OR TESTED THAT OUTWEIGH HARMS OF NOT HAVING CGC ENGAGING EVERY PATIENT. WE WANT TO ALSO SUPPORT CERTIFIED GENETIC COUNSELORS AND HAVE OR SUGGEST TO CMS AND CONGRESS TO MAKE THEM HEALTH CARE PROVIDERS FROM CMS PERSPECTIVE AND NEXT SLIDE. OUR HEALTH IT SYSTEM IS AN INCREDIBLE OPPORTUNITY FOR SCREENING PERSPECTIVE. WHEN WE MAKE CANCER SCREENING DECISIONS WHETHER SOMEONE BENEFITS FROM CERVICAL CANCER SCREENING OR GENETIC SCREENING OR GENETIC TESTING, WE HAVE TO COLLECT DATA AND ASSIMILATE FAM PLY HISTORY AND MOM HAD BREAST CANCER AT 35 OR EARLY ONSET COALO RECTAL CANCER OR UTERINE CANCER FOR LYNCH SYNDROME TAKING INFORMATION CREATING A SYSTEM TO BE APPLIED TO OTHER MANY DIFFERENT EMRS, WE CAN CREATE COMPUTABLE GUIDELINES. GUIDELINES NCC AND PREVENTIVE TASK FORCE AND SCREENING GUIDELINES THAT WE RECOMMEND ARE ALL OR ARE MADE TO BE COMPUTABLE OR MACHINE READABLE AND IS ACTUALLY NOT THAT DIFFICULT AND SOUNDS A LITTLE OVERWHELMING AND CREATES AN ALGORITHM FOR WHAT THEY ARE ALREADY DOING AND INPUTTING BETTER DATA AND COMPUTER FORMAT GOES TO WHAT ALGORITHM AND SCREENING GUIDELINES TA ARE COMPUTABLE AND HELPS US IDENTIFY THOSE THAT WE ARE NOT SCREENING AND ALSO NOT OVERSCREENING. THERE IS LOTS OF OPPORTUNITY WITH HEALTH IT. WE ARE HERE TO HELP. IF YOU HAVE IDEAS, PLEASE SHARE THEM WITH US. NEXT SLIDE. SO, ULTIMATELY, WITH VERY TO WORK TOGETHER TO CLOSE THE GAP AND SCREENING AND OUR LARGER WORK TOOK A LOOK AT REALLY THE WHOLE OCEAN OF CANCER SCREENING AND CLEARLY IT INVOLVES PEOPLE AND COMMUNITIES AND ACCESS AND IMPLEMENTATION RESEARCH. WE CAN MAKE A DIFFERENCE NOW. MOST IMPORTANT THING IS IMPLEMENTING EXISTING CANCER SCREENING THAT WE KNOW THAT WORK. NEXT SLIDE. OUR REPORT WAS ISSUED WITH THE PRESIDENT REIGNITING CANCER MOON SHOT IN FEBRUARY. NEXT SLIDE. OSTP AND MOON SHOT NOT ONLY INCLUDED ON WEBSITE BUT FOUNDATION FOR CANCER SCREENING AMONGST OTHER PILLARS OF CANCER MOON SHOT THAT WE WERE THRILLED TO SEE. NEXT SLIDE. PRESIDENT AND FIRST LADY AND VICE PRESIDENT WHEN THEY SPOKE IN OSTP PRIORITIZED ONE THING WE CAN DO NOW AND UP FRONT TO HELP CANCER SCREENING TO ACHIEVE REDUCTION IN OVERALL DEATHS IN CANCER IS TO IMPLEMENT AND IMPROVE CANCER SCREENING. NEXT SLIDE SOMETHING COMING OUT OF REPORT RELEASED IN FEBRUARY IS AMERICAN CANCER SOCIETY 10 DAYS IN MOON SHOT AND LAUNCH OF REPORT KAREN KENNUTESON WHO YOU KNOW TOOK AN INNOVATIVE AND FAST MOVING AND SOMEWHAT RISKY STEP TO ANNOUNCE AMERICAN CANCER SOCIETY HOUSING ROUNDTABLES CREATES ADMINISTRATIVE REPORT LAUNCHING NATIONAL BREAST CANCER TABLE AND CERVICAL ROUNDTABLE AND ARE BEING DEVELOPED THIS YEAR AND EXCITING DEVELOPMENT TO HELP PEOPLE FOR YEARS TO COME IN SCREENING AND IN TREATMENT. NEXT SLIDE. WHITE HOUSE IN MAY IDENTIFIED MANY DIFFERENT PRIVATE SECTOR INITIATIVES AND NON-PROFIT INITIATIVES. CORPORATE INITIATIVES TO TOUCH AND IMPROVE CANCER SCREENING IN SO MANY DIFFERENT COMMUNITIES AND THIS IS ON THEIR WEBSITE THAT IS A NEAT LIST OF HOW OUR SYSTEM WORKS. IT IS VERY COMPLICATED AND THERE IS LOTS OF GREAT WORK DODGE ON THE GROUND ACROSS OUR COUNTRY. NEXT SLIDE. WHAT CAME OUT AS RESULT OF REPORTS NATIONAL LUNG CANCER ROUNDTABLE HAS, AGAIN, THEIR MAIN FOCUS IS TO IMPROVE AND EXPAND LUNG CANCER SCREENING AND THEY HAVE AFTER OUR REPORT INITIATED A SUMMIT TO TRY TO ACCELERATE LUNG CANCER SCREENING THAT WILL BE IN WASHINGTON, DC NEXT MONTH. NEXT SLIDE. ALL OF YOU ARE STAKEHOLDERS. WE MAKE RECOMMENDATIONS. NOTHING HAPPENS UNLESS STAKEHOLDERS GET INVOLVED AND PATIENTS GET INVOLVED. WE HAVE A CANCER CABINET AS DOUG OUTLINED EARLIER ALL OF US INCLUDING PRIVATE ORGANIZATIONS CITIZENS HEALTH CARE PROVIDERS AND INSTITUTIONS WE HAVE TO TAKE HEALTH CARE SCREENING AND MOVE IT FORWARD AND CALL AS PRESENCE CANCER PANEL AND CALL TO ACTION FOR YOU TO DO HARD WORK NOT ONLY INDIVIDUALLY WITH PEOPLE WE CARE FOR ONE ON ONE BUT COLLECTIVELY. NEXT SLIDE. REPORT AND E-MAILS ON WEBSITE DIRECTLY E-MAILED TO US BOTTOM OF WEBSITE NEXT SLIDE AND THANKING TEAM OR PANEL AND NEXT SLIDE AND MORE IMPORTANTLY OUR NCI TEAM THOSE THAT ARE HEART AND SOUL OF PANEL AND KEEP US MOVING IN RIGHT DIRECTION AND WORK IS REFLECTED IN EVERY ASPECT OF 70-PAGE REPORT. NEXT SLIDE. THANKING ALL OF YOU FOR WHAT YOU DO AND ASKING YOU TO HELP US CLOSE GAPS IN CANCER SCREENING AND YOU ARE A CRITICAL STAKEHOLDER AND THANKS FOR YOUR TIME AND LOOKING FORWARD TO SOME QUESTIONS AND SEE OETIS RAISED HAND FIRST AND EARLY. >> A COUPLE HANDS WERE RAISED. THANK YOU, JOHN. STARTING WITH OETIS AND GOING TO ANDREA. >> DR. WILLIAMS, THANK YOU VERY MUCH FOR YOUR REPORT AND YOUR WORK. IT IS VERY IMPORTANT WORK THAT I WANT TO KNOW IS ALL ABOUT HOW TO GET PEOPLE TO GET SCREENED AND NATIONAL LUNG CANCER SCREENING TRIAL USING AS AN EXAMPLE ONE OF BEST SCREENING STUDIES EVER DONE AND DOCUMENTED HARMS AND BENEFITS FOR EVERY 5.4 LIVE SAVE TWO PECHL WENT TO INTENSIVE CARE UNIT AND ONE PERSON DIED AS A RESULT OF INVASETIVE PROCEDURE LEADING AND CAUSING BY SCREENING AND 1/3 OF PEOPLE WHO DIED DIDN'T HAVE CANCER ON AUTOPSY AND IS REASON WHY MEDICARE WILL NOT PAY FOR SPIRAL CT SCREENING UNLESS THERE IS INFORMED DECISION MAKING ALLOWING PATIENT TO DECIDE IF THEY WANT TO GET SCREENED OR NOT GET SCREENED AND NUMBERS I GAVE YOU 5.4 LIFE SAVED FOR ONE LIFE LOST IS WHEN SCREENING IS DONE AND ONE IS 33 OF BEST HOSPITALS IN THE UNITED STATES. WHAT ARE WE DOING TO KEEP THE RATIO THAT HIGH WHEN WE IMPLEMENT SPIRAL CT SCREENING IN PLACES THAT ARE NOT MAJOR UNIVERSITY HOSPITALS? >> I PRACTICE IN ONE OF THEM. I'M IN PRIVATE PRACTICE. I'M CONFIDENT THAT THE OUTCOMES OF IT THAT STUDY AND STILL RELATIVELY HIGH, THERE IS A DEFINITIVE MORTALITY THAT IS GOING TO GO UP. THERE IS ABSOLUTELY NO QUESTION ABOUT THAT. WHEN WE DO APPLY SOMETHING, IT GET AS PLIED BROADLY AND SOMETIMES BASED ON HIGH LEVEL RESEARCH AND CLINICAL SKILL THAT IS NOT APPLICABLE OUT IN THE COMMUNITY ACROSS THE COUNTRY. YOU KNOW, ONE OPPORTUNITY, OTIS, I HAD TALKED TO LUNG CANCER ROUNDTABLE SEVERAL TIMES. WHAT WE WANT TO RAISE IS WHAT IS THE -- NOR ARE WE AS A PANEL EXPERTS ON HARMS OF IT. THERE ARE CLEARLY HARMS. ONE THING THAT I THINK THE ROUNDTABLE MODEL AND USE THIS WHY IT IS HELPFUL TO CREATE OTHER ROUNDTABLES WE CAN -- IS THAT YOU HAVE PEOPLE WHO ARE THORACIC SURGEONS AND PEOPLE THAT PARTICIPATE IN STUDIES AND PEOPLE THAT ARE OUT IN THE COMMUNITY. WHEN I BELIEVE THEY ARE INTERESTED IF IN FINDING A SHARED DECISION MODEL THAT WILL WORK AND MINIMIZE HARMS OF CANCER SCREENING AND HOPEFULLY IMPROVE AND ON SHARED DECISION MAKING PROCESS WE ALREADY HAVE. IN SOME WAYS HOW CAN WE MAKE THAT SHARED DECISION MAKING BETTER? OUR SUGGESTION IS I THINK IT IS KIND OF TIME TO CONTINUE TO REVISIT THAT. EXPERTS REALLY NEED TO REALLY PARTICIPATE AND HARMS ARE SIGNIFICANT. >> GREAT, GREAT QUESTION. THANK YOU FOR ADDRESSING THAT, JOHN. WE HAVE ABOUT 6 MINUTES. LET'S GO TO ANDREA AND TO ELECTRA. >> THANK YOU, DR. LIZ, FOR THE WONDERFUL PRESENTATION. QUESTION I HAD WAS IF YOU COULD EXPAND A LITTLE MORE ON EDUCATION EFFORTS THAT YOU WERE DISCUSSING IN SOME EARLIER SLIDES. I THINK THAT IS REALLY A CRITICAL ASPECT OF HOW WE INCREASED THE NUMBER OF FOLKS THAT GET CANCER PREVENTION WHEN THEY NEED IT. I WAS WONDERING IF IT IS BEING ENVISIONED AS A SOCIAL MEDIA ROLE. YOU KNOW, PAPER PAMPHLETS MAILED TO PHYSICIANS AND HOW YOU SEE THAT EDUCATION BEING ROLLED OUT. >> YOU TOUCH ON THE CRITICAL ASPECTS OF THAT. ULTIMATELY, OUR COMMUNITY AND CITIZENS, THEY ARE AT RISK AND NEED TO KNOW ABOUT THIS. HOW DO WE GET TO THEM? WE FALL BEHIND IN WAY THAT WE COMMUNICATE. THAT IS A SPECIALTY IS COMMUNICATION MAKING ONLINE CONTENT FOR EDUCATING PATIENTS IT THAT WE DON'T DO IT WELL. AND WE DID NOT COME UP WITH THE RECOMMENDATION OF A CANCER SCREENING PROGRAM AND THAT IS FUNDED BY X NUMBER OF DOLLARS. WHAT WE ALSO IDENTIFIED ARE TWO THINGS. NO. 1, IF WE ADDRESS EQUITABLE SCREENING IN DIFFERENT COMMUNITIES AND ALL OF THE DIFFERENT DIVERSE POPULATIONS, WE HAVE TO TAKE A GOOD MESSAGE AND TRANSLATE IT TO THOSE DIFFERENT SMALLER GROUPS THAT ARE NOT ONLY SMALLER GROUPS IN NUMBERS BUT ARE SMALLER GROUPS IN DIFFERENT GEOGRAPHIC LOCATIONS AND IS A REASON WHY I SAY THAT ROUNDTABLES ARE CRITICAL FOR COMMUNICATION. WHEN YOU HAVE LIKE-MINDED PEOPLE WITH A COMMON GOAL TO LET'S SAY IMPROVE CANCER SCREENING, EVERYONE COMES TO TABLE YOU HAVE ENOUGH RESOURCES TO HAVE A SOPHISTICATED MESSAGE SMALLER GROUPS AFRICAN-AMERICAN, INDIAN, ASIAN, RURAL CAN TAKE THAT MESSAGE, ONE MESSAGE, A GOOD MESSAGE, AND TRANSLATE AND TAKE TO THEIR COMMUNITIES. IF I REPRESENT THE AMERICAN INDIAN RESERVATIONS I CANNOT, NOT ONLY PRODUCE THAT CONTENT THAT DOESN'T MAKE SENSE BECAUSE I DON'T HAVE CRITICAL MASS BUT I THEREFORE TAKE WRONG MESSAGE TO MY PEOPLE OR GIVE UP ON IT BECAUSE IT IS TOO HARD AND IS A BEAUTY OF THE ROUNDTABLE THAT IS EVERYBODY FROM SMALL GROUPS TO LARGE GROUPS AND IS ORGANIZATION OF ORGANIZATIONS. WHERE IT WORKS AND WHERE IT ADDRESSES INEQUITIES IS WHERE WE BRING THOSE THAT DON'T HAVE A LARGE SMALL PEOPLE OR GROUPS THAT REPRESENT A SMALLER NUMBER OF PEOPLE TO THAT TABLE. I DON'T KNOW IF IT IS HELPFUL. >> THANK YOU. >> THAT IS GREAT. THE WHOLE CONCEPT OF TAILORED BEST PRACTICES. SO, I WOULD LIKE TO. >> FIRST OF ALL, JOHN, I WANT TO THANK YOU AND THE GROUP FOR A FABULOUS AND SCREENING IS NEAR AND DEAR TO MY HEART SINCE IT THAT IS WHAT I DO FOR LATE 1980S AND DEVOTE MY CAREER TOO AND WOULD LIKE TO THANK YOU FOR THIS REPORT AND MAKING TWO COMMENTS. FIRST OF ALL, I DIDN'T HEAR PATIENT NAVIGATION MENTIONED IN YOUR REPORT. YOU MENTIONED COMMUNITY HEALTH WORKERS THAT I WILL SAY IS NOT EQUIVALENT. TO THAT END, THE NATIONAL NAVIGATION ROUNDTABLE THAT YOU MENTIONED ROUNDTABLES. WE JUST PUBLISHED A SPECIAL SUPPLEMENT IN JOURNAL COUNCIL RELEASED TODAY THAT IS A COMMENTARY DELINEATING DIFFERENCE BETWEEN COMMUNITY HEALTH WORKERS AND PATIENT NAVIGATORS AND IMPORTANT DISTINCTION AND COMMUNITY HEALTH WORKERS CAN GET REIMBURSED AND PATIENT NAVIGATORS CAN'T WE WON'T INCREASE SCREENING OR ADDRESS DISPARITIES AND AREN'T GOING TO BE ABLE TO TAILOR MESSAGES TO POPULATIONS THAW ELOQUENTLY DESCRIBED UNLESS WE HAVE PATIENT NAVIGATORS AND HAVE TO HAVE FUNNING FOR PATIENT NAVIGATION AND LAST THING TO MENTION I WROTE IN THE CHAT IS LAST REPORT AMERICAN CANCER SOCIETY PUBLISHED IS FACTS AND FIGURES AND CERVICAL CANCER IS ONLY CANCER THAT CONSISTENTLY DECREASES IN SURVIVAL RATES OVER TIME THAT I WOULD ENCOURAGE PEOPLE TO LOOK AT THAT AND WE HAVE TO UNDERSTAND WHY AND STOP IT. CERVICAL CANCER IS PREVENTABLE. NOT DOG ENOUGH OF THAT. THANK YOU AGAIN ALL OF YOU WONDERFUL REPORT. WE NEED TO GET MOVING ON IT. >> ELECTRA, THANKS FOR YOUR COMMENTS. TWO QUICK THINGS IS PATIENT NAVIGATION THROUGHOUT ALL WORKPLACE PLAYS A HUGE ROLE AND ULTIMATELY WE HAD TO MAKE A DECISION TO HAD HIGHLIGHT PATIENT NAVIGATION THAT HAS BEEN HIGHLIGHTED AND HAS VISIBILITY AND WE UNDERSTAND POWER OF IT. TRACY BET AGOLIA AND WHOLE TEAM IS PART OF SO MANY DISCUSSIONS THAT I COMPLETELY AGREE WITH YOU AND FELT IT WAS TIME TO ELEVATE THOSE IN COMMUNITIES THAT CAN TOUCH DIVERSE COMMUNITIES. YOU HAVE TO PICK AND CHOOS WHAT YOU HIGHLIGHT. MAYBE NOT. NO. 2, WITH CERVICAL CANCER IS AN OPPORTUNITY WE LOOK AT AND HIGHLIGHT SELF-SAMPLING FOR HPV AND DECREASE IN SCREENING THAT IS MULTIFACT TORIAL AND MIGHT BE ABLE TO OFFSET IT IF FDA HAS ENOUGH INFORMATION TO APPROVE BENEFIT FOR OUR COUNTRY. >> IN INTEREST OF TIME, SUSAN, I SEE YOUR HAND. LET'S TAKE THIS ONE QUESTION AND TRY TO KEEP IT SUCCINCT SO WE CAN MOVE FORWARD. THERE IS ALSO OPPORTUNITIES TO TYPE QUESTIONS AND COMMENTS IN THE CHAT. THERE IS ACTIVE CONVERSATION IT THAT IS ONGOING RIGHT NOW. >> THANK YOU. MAYBE MORE OF A THOUGHT OR SUGGESTION IS JUST THAT ISSUE OF COMMUNICATION AND COMMUNICATION TO DIVERSE AUDIENCES IS NOT NEW. CAUTION US THROWING BABY AWAY WITH BADGE WATER AND LOOKING AT EVIDENCE-BASED INTERVENTIONS THAT NCI HAS A GREAT REPOSITORY OF INTERVENTIONS AND COMMUNICATIONS AND DIFFERENT AUDIENCES AND LOVE YOU PUT IT ALL TOGETHER AND HOW CAN WE MAKE SURE WE ARE BRINGING THAT WORK ALONG AS WE ARE ENCOURAGING PEOPLE TO MOVE FORWARD. >> THANK YOU, SUSAN. JOHN, THANK YOU VERY MUCH FOR PRESENTATION AND SUPPORT WORK THAT YOU AND CANCER PANEL ARE DOING. KUDOS. >> THANK YOU, EVERYBODY. YOU DO IMPORTANT WORK AND WE TRY TO PLAY OUR ROLE. >> FANTASTIC. WE WILL MOVE ON IN OUR AGENDA AND NEXT IS A PRESENTATION AND SOME SCIENCE. WE HAVE MYELOID MALIGNANCIES JOURNEY FROM BASIC BIOLOGY TO CLINICAL APPLICATIONS FROM DR. DAI LARSON AND CO-CHAIR FOR NIH MYELOID MALIGNANCIES PROGRAM CO-DIRECTOR NCI PARTNERSHIP FOR INTEGRATIVE CANCER RESEARCH AND LABORATORY RECEPTIVE BIOLOGY AND GENE EXPRESSION FOR CANCER RESEARCH AND NCI. DAN? WE HAVE DAN? CAN YOU UNMUTE? >> YES. >> THANK YOU. >> READY? >> YES. WE CAN HEAR YOU. >> THANK YOU VERY MUCH FOR THAT INTRODUCTION. IT IS A PRIVILEGE TO BE HERE SPEAKING IF IN FRONT OF THE BOARDS AND COME YOU TO TODAY IN MY CAPACITY PRIMARILY AS CODIRECTOR OF NEW TRANS NIH PROGRAM IN MYELOID MALIGNANCIES THAT ARE A HETEROGENOUS COLLECTION OF DISEASES AND SPECIFIC EMPHASIS IN THIS PROGRAM ON MILO DISPLASTIC SYNDROMES A PRIMARY EXAMPLE ABBREVIATED AS MDS THAT IS DISEASE OF BONE MARROW AND STEM CELL DISEASE AND IN DISEASE BONE MARROW CELLS HAVE ABNORMAL DISTRIBUTION OF CELL TYPES AND MORPHOLOGY. ON THE RIGHT I AM SHOWING YOU EXAMPLES OF MORPHOLOGICALLY DISPLASTIC BONE MARROW CELLS FOR EXAMPLE MILO BLASTS THAT IS PRIMARILY A FAILURE OF HEMATOPOEESIS AND PATIENTS PRESENTING WITH DISEASE WITH PROFOUND CRYTOPINAS AND THEY HAVE POTENTIAL TO TRANSFORM TO SECONDARY ACUTE MYELOID LEUKEMIA A PROLIFERATIVE DISEASE WITH A PROGNOSIS AS WELL AND THERE IS 30,000 CASES PER YEAR IN THE US AND 10 TO 20% OF THEM ARE THERAPY RELATED MEANING THEY ARISE BECAUSE OF TREATMENT FOR OTHER MALIGNANCIES AND 80 TO 90% OF MDS CASES ARE DE NOVO AND ESPECIALLY WHEN MDS APPEARS IN CHILDREN AND YOUNGER ADULTS. THE PROGNOSIS FOR MDS PASH YENTDS IS NOT GOOD. 1/3 WILL DIE OF CRYTOMEANIAS AND 1/3 TRANSFORM TO -- AND 1/3 WILL DIE OF UNRELATED CAUSES BECAUSE THIS IS DISEASE OF ELDERLY. THERE IS COMORBIDITIES AND CLEAR NOW GENETICS DRIVES DISEASE THAT I WILL TALK MORE ABOUT THIS LATER AND TREATMENT FOR PATIENTS IS REALLY SUPPORTIVE CARE TRYING TO ACHIEVE HEEM TOLLOGICAL IMPROVEMENT AND STIMULATING AGENTS AND RARE SUBSETS OF PATIENTS [INAUDIBLE] IS USED AND ONLY NEW DRUG APPROVED FOR MDS IN NEXT TWO DECADES IS [INAUDIBLE] SPECIFICALLY FOR PATIENTS THAT FAIL STIMULATING REGIMES AND CURE FOR MDS IS STEM CELL TRANSPLANT AND MENTIONED THIS IS DIFFICULT TO ACHIEVE IN PATIENTS WITH OTHER COMORBIDITIES AND MDS MIGHT NOT BE FAMILIAR TO YOU. I COMPARE HERE TO COMMON MALIGNANCY THAT IS LUNG CANCER AND MORTALITY IS SIMILAR WHEN MDS IS COMPARED TO LUNG CANCER ACROSS DIFFERENT STAGES. BECAUSE OF PREPONDERANCE OF SOMATIC MUTATIONS BECAUSE OF PROPENSITY TO TRANSFORM TO ACUTE -- AND BECAUSE OF THIS MORTALITY PROFILE WE FEEL NATURAL CLINICAL HOME FOR MDS IS IN NCI AND WORK I WILL PRESENT TODAY IS FROM INVESTIGATORS ACROSS INTRAMURAL INSTITUTES NLHBI AND NLHGI AND CLINICAL ACTIVITIES OF NEW PROGRAM OCCUR UNDER THE BANNER OF NCI. NUMBER OF BARRIERS MAKING PROGRESS ON THESE DISEASE. ONE, LIMITED UNDERSTANDING OF DISEASE BIOLOGY AND FEW MODELS NO CELL LINES OR ROBUST XENO GRAPHS AND NO DEVELOPED METHODS AND DEFINITION AND MEASURABLE DISEASE TO GUIDE THERAPIES AND MANY PATIENTS ARE ELDERLY WITH COMORBIDITIES AND GOOD TIME TO FOCUS ON RELATED DISEASES WITHIN INTRAMURAL PROGRAM AND VARIETY OF REASONS FOR DECISION. I INDICATED A RECALCTRANT [INAUDIBLE] AND RARE DISEASE AND BEEN LITTLE PROGRESS OVER LAST 15 YEARS SCIENTIFICALLY UNIQUE DISEASE MODEL STUDYING INTERPLAY BETWEEN EVOLUTION OF DISEASE AND CONNECTIONS TO INFLAMMATION AND GENETIC DEFECTS. IT FITS IN PLACE OF STRENGTH OF SCIENCE OF INTRAMURAL PROGRAM LONGSTANDING EXPERTISE IN NIH AND HUMAN IMMUNOLOGY AND INFLAMMATION AND MDS IS PARTICULARLY RELEVANT FOR NEW [INAUDIBLE] WITHIN INTRAMURAL NCI SUCH AS THE BIOLOGY PROGRAM SUBAUTO CUTE CLINICAL COURSE STABLE FOR OUTPATIENT MANAGEMENT AND SEE OPPORTUNITY TO STUDY MDS IN COORDINATED APPROACH ACROSS PROTOCOLS IN CHILDREN AND ADULTS AND EMPHASIS ON CHILDREN AND ADULTS IS IMPORTANT AND SPEAKS TO UNIQUENESS WHAT WE CAN DO HERE IN BETHESDA. WE THINK WE CAN NUKE LEEATE ACTIVITY IN INTRAMURAL AND EXTRAMURAL COMMUNITIES AND BROADER MDS SCIENTIFIC COMMUNITY WE SPONSORED TWO SYMPOSIA ON TOPIC MOBILIZED RESEARCH FOR TRIALS AND BIODEVELOPMENT MARKET AND NEW CLINICAL MODELS AND OPPORTUNITY TO STUDY NATURAL HISTORY OF DISEASE VIS-Ë-VIS INHERITED EXAMPLES THOSE THAT ARISE IN [INAUDIBLE] AND GADA 2 AND TRANSMISSION OF MALIGNANCY PROGRAM IS DEVELOPING COMPREHENSIVE PROGRAM AIMED AT UNDERSTANDING AND TREATING MALIGNANCIES IN CHILDREN AND ADULT AND TO SUCCESSFUL CURE AND PREVENT MDS IN [INAUDIBLE] AND BRIEF HISTORY HOW WE ARRIVED AT MISSION IS CONVERSATIONS BEGAN HERE INTRA MURAL INVESTIGATORS IN 2018 LEADING TO EXPLORATORY SEMINAR SERIES AND 2019 STARTED ORGANIZATIONAL PLANNING AND ESTABLISHMENT OF MILESTONES FOR SUCCESS AND 2020 MYELOID MALIGNANCY PROGRAM WAS FORMALLY ESTABLISHED AND 2021 BEGAN RECRUITMENT OF STAFF AND THEMES FOR PROGRAM REALLY PLAYED TO STRINGS OF INTRAMURAL SCIENCE AND FIRST THEME IS POST TRANSCRIPTION REGULATION AND MDS AND MAL AND CLOSE TO AREAS OF LABS AND INTEREST AND 3 IS PRECLINICAL MODELS STUDYING MDS BIOLOGY AND THERAPY AND THEME 4 ROLE OF IMMUNE SYSTEM IN PROGRESSION AND CONTROL OF MDAS AND MDL AND THIS IS THE PROGRAM. WE ARE LED BY CLINICAL DIRECTOR STEVE PCHLTD WHO HAS A LONG HISTORY AND INTERNATIONAL REPUTATION OF TRANSPLANT AND HOST DISEASE AND DR. P IS ADVISED BY STEERING COMMITTEE THAT I AM CO-CHAIR. YOU CAN SEE FROM THE AFFILIATIONS AND DEGREES FROM PEOPLE LISTED HERE THAT THIS IS AN EFFORT ACROSS NIH AND FOLKS FROM NCI AND LBI TO NAME A FEW AND MOST PEOPLE INVOLVED ARE MDS OR MDPHDS AND HOWEVER THERE IS NUMBER OF BASIC SCIENTISTS. THAT IS USED TO MORE BASIC SIDE OF MYELOMALIGNANCIES AND MUTATION DRIVING DISEASE MUTATIONS DNA METHYL MACHINERY AND PROTEIN COHESION IN CDCF AND IN CHROMATIN AND MACHINERY IS -- GADDA 2 THAT I MENTIONED AND DISCOVERIES IN RECENT YEARS INDICATE HIGH PREVALENCE OF MUTATIONS IN SPLICING MACHINERY THAT DREW US ORIGINALLY TO THIS DISEASE AND MUTATIONS IN SRF2 AND SRF1 AND [INAUDIBLE] AND THEY ARE NOT READILY IDENTIFIED SOMATIC MUTATIONS IN TRANSLATION MACHINERY AND DELETIONS IN RIBOSOME SUBUNITS YOU WILL SEE MOMENTARY WILL I THAT TRANSLATION MIGHT BE MISSING PIECE TO THE PUZZLE IN A SIMPLISTIC WAY YOU CAN THINK OF MDS AS DISEASE OF DIFFERENTIATION FAILURE OF HEMATOPOEESIS NOT POPULATING [INAUDIBLE] IN THE BLOOD AND AML IS A DISEASE OF ABNORMAL DIFFERENTIATION AND PROLIFERATION AND AS I INDICATED SPLICING MUTATIONS ACCOUNT FOR OVER 50% OF PATIENTS. SO, THEME 1 IS POST TRANSCRIPTION MDSMAL AND WHERE MY LABORATORIES WORK CLOSELY ALIGNED AND DISPLACING MACHINERY DISCOVERED IN LARGE SCALE CANCER SEQUENCES IN LAB IN 2012 AND SHORTLY THEREAFTER IN 2015, FIRST STRUCTURE OF SPLICING ZONE WAS SOLVED AND WORKED BY [INAUDIBLE] AN AMAZING ENZYME RIBONUCLEAR COMPLEX COMPOSED OF 200 PROTEINS IN NRA AND SHOWN ON RIGHT IS STRUCTURE ON COVER ARTICLE OF SCIENCE IN 2015 AND SPLICING ZONE IS RESPONSIBLE FOR GENERATING SPLICED MNRA TRANSLATED INTO PROTEIN AND SINGLE TURNOVER ENZYME FASCINATING FROM BIOCHEMICAL POINT OF VIEW AND SPLICES ON SYMBOLS SPLICES AND FALLS APART FOR EVERY INTRON AND NRA PRODUCED IN THE NUCLEUS THAT IS FREQUENTLY MUTATED IN MDAS AND MDL AND SINCE ORIGINAL STRUCTURE IN 2015 HAS BEEN A REVOLUTION IN STRUCTURAL UNDERSTANDING OF LYSOSOME AND BIOCHEMICAL PROCEDURE OF LYSOSOME PROCEEDING COUNTERCLOKWISE ALL THE WAY THROUGH TO FINAL SPLICED MNRA AND [INAUDIBLE] THAT IS EX-CRIES THE AND DEGRADED AND DATES ON PUBLICATIONS ARE DATES WHERE EACH OF THE STRUCTURAL INTERMEDIATES WAS SOLVED FOR HUMAN LYSOSOME AND OUTPOURING OF DATA WITHIN THE LAST FEW YEARS AND ADVANCES IN STUDY OF LYSOSOME MAKE THIS THE RIGHT TIME TO INVEST AND IN UNDERSTANDING HAD HOW MUTATIONS CAN CONTRIBUTE TO DISEASE AND RAPID GROWTH OF BIOCHEMISTRY MAKING FOR EXCITING TARGET IN MDS. I WILL SHOW YOU ONE BRIEF VIGNETTE FROM MY LAB AND STARTED TO WORK ON SPLICES IN MUTATIONS AND RESULTED EVENTUALLY IN THERAPY. MY LAB HAS A LONG HISTORY. YOU KNOW, ALMOST 20 YEARS NOW IN DEVELOPING CUTTING EDGE APPROACHES FOR UNDERSTANDING TRANSCRIPTION SPLICING AND GENE REGULATION IN SINGLE CELLS FOR RNA SEQUENCING AND SPLICING AND TRANSCRIPTION AND STARTED TO WORK ON MUTATIONS IN MIU 2AF1 WHICH HAS NONCANON CAL ROLE IN TRANSLATION AND SHOWING [INAUDIBLE] THAT INDICATES THAT EFFECT. ONE MAIN TARGET MISREGULATED BY MECHANISM TURNS OUT TO BE CRYTOCYANINTERLEUKIN 8 AND SEE IN PRESENCE OF SINGLE HETEROZYGOUS MUTANTS IN FY21 IS HIGHER IN LYSOGENIC CELL LINE AND CLINICAL COLLABORATIRE WHO IS A HEEM ATOLOGIST AND LGBI AND SPLICING MUTATIONS ENRICHED IN REFRACTORY ML PATIENTS ON RIGHT IS ACCESS YOU CAN SEE HEALTHY DONORS COMPARED TO MLA PATIENTS IN STUDY MUTATION SPLICEOSOME FACTORS THAT YOU CAN SEE IN THESE YOU HAVE POOR PROGNOSIS IL8 IS EXTREMELY HIGH AND YOU ARE SEEING BY TWO PLOTS IN HIERARCHICAL CLUSTERING AND IN MODEL -- THIS IS A LUNG MODEL WE CAN BLOCK TO PROGRESSION NEUTRALIZING ANTIBODY ANNIHILATE AND SAME TIME DEVELOPING FULLY HUMAN ANTIBODY TO IL8 HUME AXE IL8 APPROACH THEM PREAPPROVED IN CLINICAL STUDIES IN OCTOBER 2019 AND RECEIVED FDA INVESTIGATIONAL NEW DRUG APPROVAL IN SEPTEMBER OF 21 AND EXPECTING PATIENTS TO ARRIVE IN THE CLINICAL CENTER REALLY ANY DAY NOW. SO, MOVING ON TO THEME 2 OF PROGRAM WHICH IS PREDISPOSITIONS TO THIS YOU CAN SEE. WE HAVE NUMBER OF EFFORTS IN THIS AREA AND NIH HAS A LONGSTANDING TRACK RECORD OF SUCCESS AND DOG NATURAL HISTORY STUDIES. AND STUDYING PATIENTS WITH GERM LINE PREDISPOSITION AND WILL HIGHLIGHT ONE STUDY FROM COLLEAGUE DR. LANING CUNNING HAM TO INCREASE [INAUDIBLE] ACTIVITY AND PATIENTS WITH GERM LINE MUTATIONS AND [INAUDIBLE] THESE PATIENTS WHICH HAVE COMELE TO NIH AS PART OF NATURAL HISTORY STUDY WITH LEA DR. CUNNINGHAM AND PAUL LOU SHOW VARIETY OF CLINICAL CHARACTERISTICS REDUCING PLATELET COUNTS DUE TO VIETO PINA AND HAVE STRONG DISPOSITION FOR HEEM TOE LOGICAL MALIGNANCIES MOST OF THE PATIENTS WILL DEVELOP -- AND THERE IS STRONG INFLAMMATORY COMPONENT OF DISEASE THOUGHT TO BE IMPORTANT FOR SELECTION OF MUTATED CLONES. PRECLINICAL DATA HAS SHOWN TREATING PATIENTS WITH THIS CAN RESULT IN HEEM TOLLOGICAL IMPROVEMENT AND DR. CUNNINGHAM HYPOTHESIZED FURTHER THAT PATIENTS WILL HAVE A DECREASED ACQUISITION OF SECONDARY SOMATIC MUTATIONS AND WHAT ARE SECONDARY SOMATIC MUTATIONS? PATIENTS WITH DRUM LINE MUTATIONS HAVE PROPENSITORY VEPING THIS HERE DATA FROM PAPER BLOTTING BLOOD AND SOMATIC MUTATIONS ACQUIRE A DIFFERENT SPECTRUM OF SECONDARY MUTATIONS THAT YOU CAN SEE MY FRAF RIT GENE U2F1 AND -- HAVE A 20% CHANCE OF GETTING MUTATION AS SECONDARY MUTATION. AS I ELUDED TO BEFORE THERE IS A DEARTH OF PRECLINICAL MODELS AND VERY FEW PRECLINICAL MODEL IN FIELD IS DEVELOPED BY COLLEAGUE PETER A. THAT IS MDS MODEL AND THEY DEVELOP CRYTOPINAS AND TRANSFORMED AML AND THIS MODEL HAS BEEN WIDELY DISTRIBUTED TO OVER 2 DOZEN ACADEMIC LABS AND HAS BEEN NUMBER OF COMMERCIAL LICENSES. MOST IMPORTANTLY THIS MODEL WAS MODEL USED TO APPROVE THIS [INAUDIBLE] THAT I SAID BEFORE IS ONLY NEW FDA APPROVAL FOR MDS DRUG IN 15 YEARS. FINALLY LAST SCIENTIFIC THEME OF PROGRAM IS USING ROLE OF IMMUNE SYSTEM TO CONTROL MDS AND AML. ONE PRIME EXAMPLE OF EFFORT IS A FIRST IN HUMAN AND FIRST IN CHILD CD TLE 3T CELL THERAPY AND TRIAL LED BY ONCOLOGY BRANCH BY DR. SHAW AND EXCELLENT PRECLINICAL DATA SHOWING THAT THEY MIGHT BE TARGETS THAT COULD BE THERAPEUTIC TARGETS IN CONTROL OF AML AND CD123 AND CD33 ARE EXPRESSED ON MAJORITY OF MYELOBLASTS IN THESE PATIENTS AND VARIETY OF REASONS CD33 IN PARTICULAR IS SEEN AS A LOW OR LESSER RISK TARGET FOR FIRST PRIOR T CELL THERAPY FOR THIS DISEASE. THIS PARTICULAR STUDY INDICATES STRENGTHS OF INTRAMURAL AND EXTRA TRA MURAL PARTNERSHIPS HIGHLY INTERDISCIPLINARY COLLABORATIVE PROPOSAL BETWEEN NCI CHILDREN'S HOSPITAL OF PENNSYLVANIA AND UNIVERSITY OF COLORADO AND THIS WAS INVENTED BY TERRY FRY WHEN SHE WAS AN INVESTIGATOR HERE AT NCI AND VECTOR MANUFACTURING HAS OCCURRED AT CHOP. YOU CAN SEE OTHER FOLKS INVOLVED IN THIS INCLUDING CLINICAL TRIAL IMD AND MENTIONED CLINICAL SITES ARE AT BOTH NCI AND AT CHOP AND ONE IS BEING LED BY DR. SHAW WHO IS HERE IN PEDIATRIC ONCOLOGY BRANCH AND OTHER BY RICHARD CLINIC. I HAVE GIVEN YOU SENSE OF UNIFYING THEMES OF RESEARCH. WHERE IS PROGRAM NOW AND WHERE DO WE HOPE TO GO AND GOAL WAS TO FORM MDS CLINIC STUDYING DISEASE PRESENTATION AND BIOLOGY AND DEVELOP ASSESSMENT TOOLS AND TO INITIATE NEW PROTOCOLS IN AREA AND TO THAT END CLINICAL TEAM INCLUDING PHYSICIAN SCIENTISTS AND STAFF PHYSICIAN AND NURSING RESEARCHES MANY HAVE OCCURRED AND RESULT PAST 2 YEARS -- ONE IS PHASE 1 STUDY OF ANTI-CD330 CARD T I DISCUSSED OPENS NATURAL HISTORY AND BIOSPESIM ENPROTOCOL FOR MDS AND DISCUSSED PHASE 2 TRIAL FOR MDLS AND IMPORTANT ASPECT WHERE WE HOPE TO GO AND WHERE WE ARE LOOKING NOW IS INCREASING AND EVOLVING IN BASIC SCIENTIST AND IS PRIMARY PU VIEW AND RECRUITING INVESTIGATORS -- ALSO TO PUR SUEDE EXISTING INVESTIGATORS AT NIH DISEASE MODEL HIGHLY RELEVANT TO BASIC SCIENCE THAT IS GOING ON HERE. IN TERMS OF FUTURE I THOUGHT I WOULD HIGHLIGHT A PROTOCOL THAT IS CLOSE TO BEING APPROVED CD123CD3 BY SPECIFIC T CELL ENGAGER WORKED OUT BY COLLABORATOR AT CHARLES HOPKINS AND STAFF CLINICIAN AT NCI NOAH HOLTSMAN AND SHAW IS INVOLVED AS CLINICAL DIRECTOR STEVE P. AS WELL AND SOME MIGHT BE FAMILIAR WITH THIS STRATEGY AND BY SPECIFIC T CELL ENGAGERS AND IDEA IS MAKING CHIMERA OF CD3123 AND CD3 YOU CAN RECRUIT TOXIC T CELLS TO MYELOBLASTS AND IN PARTICULAR PROTOCOL IN THIS CASE INVOLVES ENGINEER T CELL ENGAGERS CALLEDBYTES THAT ARE PRODUCED BY T CELLS THAT ARE THERAPEUTIC AND GO INTO THE PATIENT AND PRODUCE BITE AND IDEA OF RECRUITING T CELLS TO MYELOBLASTS AND WE HAVE A VARIETY OF THERAPIES IN PIPELINE AND IN EXISTENCE NOW. A CRITICAL PART OF THIS PROGRAM IS MEASURING HOW THEY ARE WORKING AND WHAT I'M HIGHLIGHTING HERE IS PROGRAM INITIATED BY COLLEAGUE AND WITH INVESTIGATORS AND CHRIS IS HERE IN NHLBI AND EXPERT IN USING NEXT GENERATION SEQUENCING TO ASSESS MEASURABLE RESIDUAL DISEASE IN MAL AND YOU CAN SEE PHARMACEUTICAL PARTNERS INVOLVED IN THAT AND ASK EFFORT COORDINATED BY THREE INVESTIGATORS AND INVOLVING SITES AND CENTERS THROUGHOUT THE COUNTRY AND HERE YOU CAN SEE WHERE THEY ARE LOCATED AND WHAT INITIATIVE IS CALLED. IT IS CALLED MEASURE AND ANTICIPATED LAUNCH OF TRIAL IS IN AUGUST OF 22. I WILL STOP HERE AND OPEN FLOOR FOR QUESTIONS AND AGAIN WANT TO INDICATE SCOPE OF PROGRAM AND PEOPLE INVOLVED AND HIGHLIGHT WORK THAT I PRESENTED IN TALK FROM NOAH HOLTMAN STAFF CLINICIAN WORKING UNDER SUPERVISION OF DR. PAV LET ITCH AND ANITA KIM AND INVESTIGATOR AT NHGRI. WITH THAT I WILL STOP AND TAKE QUESTIONS. >> THANK YOU, DAN. TREMENDOUS PRESENTATION ON ADVANCEMENTS AND IN THIS SPECIFIC FIELD IN TUMOR TYPE. IF WE CAN REMOVE THE PRESENTATI PRESENTATION. THERE IS A FEW HANDS. WE WILL START WITH MICHELLE AND GO TO FRANCIS. WE HAVE AMY ALSO. >> THANK YOU, JOHN. THANKS FOR THE PRESENTATION. I'M PLEASED NCI IS DEVELOPING THIS INITIATIVE AND TWO QUESTIONS FOR YOU. THAT IS THAT THERE ARE ALREADY A NUMBER OF CONSORTIUMS AND FOUNDATIONS BOTH NATIONALLY AND INTERNATIONALLY WORKING ON MDIS AND IS THERE AN OPPORTUNITY TO INTERACT WITH EFFORTS THAT REALLY COVER BOTH BIOLOGY AND MOLECULAR AND CLINICAL STUDIES AS WELL AS CLASSIFICATIONS. >> >> ABSOLUTELY. I THINK THOSE FOUNDATIONS AND PATIENT ADVOCACIES ARE CRITICAL TO OUR EFFORT. WE HAVE CONNECTIONS WITH EVANS AND MDS AND I THINK THAT RUFRNGS 1 INITIATIVE BENEFITED TREMENDOUSLY BEING INVOLVED IN FOUNDATIONS AND ADVOCACIES THERE AND WILL BE CRITICAL TO OUTREACH AND REFERRALS TO ALL ASPECTS OF THE PROGRAM. >> ALSO, I'M REFERRING TO A NUMBER OF WORK PROFESSIONAL ORGANIZATIONS AND OF SCIENTISTS AND NOT ONLY FROM [INAUDIBLE] THAT ARE WORKING ON MDS. >> RIGHT. THERE IS LARGE -- THERE IS NATURAL HISTORY STUDY BEING ORCHESTRATED BY LBHI. I THINK WE SEE OUR INTENT IS TO WORK WITH THEM. THEY HAVE PARTICIPATED IN TWO OF THE MDS SYMPOSIA THAT WE SPONSORED. IN TERMS OF SCIENTIFIC FOCUS OF OUR PROGRAM WE THINK WE ARE ADDRESSING UNMET UNIQUE NEEDS IN MDS AND LOTS OF CLINICAL TRIALS WILL USE NEXT GENERATION CLINICAL CORRELATES AND FOCUS ON TRANCE REGULATION PROETEE AMIC STUDIES I THINK ARE NOT WIDELY USED BUT WE ARE AWARE OF OTHER EFFORTS AS WELL. >> THANKS, DAN. FRANCIS? >> IF I MAY. A GREAT RISK FACTOR NOW IS CHRONIC INFORMATION AND AGING FOR MDS AND THERE IS INTEREST IN HOW WE MIGHT BE ABLE TO PREVENT IT TO REDUCE [INAUDIBLE] IS THAT AN AREA THAT NCI IS ENTERTAINING? >> WE ARE. IN FACT, RESEARCH FROM MY OWN LAB HIGH LIGHTED INFLAMMATORY CHANGES OCCURRING IN RESPONSE TO SPLICING FACTOR MUTATIONS INITIATING MUTATIONS IN THE DISEASE THAT OCCUR LONG BEFORE A PRESENTATION AND WE WOULD LIKE TO THINK THESE ARE WORKING PRIMARILY THROUGH INFLAMMATION. SO, THERE IS A LOT OF EXPERTISE HERE IN PROGRAM IN MYELOINFLAMMATION AND NCLA WAS DISCOVERED AND IS AN AREA OF INTEREST. >> THANK YOU. >> FRANCIS? >> I WILL BE QUICK. THE -- SOUNDS LIKE A GREAT AND WONDERFUL PRESENTATION AND ABOUT A LITTLE OVER A DECADE AGO ANDY ANDERSON HOSTED CLINICAL TRIAL WITH GSDP1 INHIBITOR. GSDP1 YOU KNOW IS A PHASE 2 INHIBITIVE PROTEIN AND SIGNALING AND BIOLOGY BEHIND IT HAD TO DO WITH INFLAMMATORY PROCESSES ASSOCIATED WITH MDR. I'M NOT SURE. COULD YOU COMMENT ON THAT? AND IS THAT BEING LOOKED AT? >> SO, I DON'T KNOW SPECIFICS OF THAT PARTICULAR TRIAL OR THAT DRUG. I DO KNOW THAT ALMOST EVERY -- BOTH NATURAL HISTORY PROTOCOL AND ALL OF THEUM BRELA PROTOCOL FOR PATIENTS COMING TO MCI FOR TREATMENT HUGE AMOUNT OF CYTOKINE PROFILING AND ALSO PROTEOMICS ON INFLAMMATORY PATHWAYS IT THIS HAS FRONT AND CENTER IN OUR THINKING. >> MIGHT BE INTERESTING. THEY HAVE REALLY DRAMATIC RESPONSES IN SUBSET OF PATIENTS. >> GREAT SEGUE. I REVIEWED AMY'S QUESTION IN THE CHAT. AMY? >> ALSO ALIGNED WITH COMMENTS THAT FRANCIS HAS MADE AND POSTED ANOTHER ARTICLE THAT APPEARED IN JCI A COUPLE YEARS AGO AND NOTICED ON ONE OF LAST SLIDES YOU HAD CONTINUED AFFILIATION WITH ASTO ZENNICA AND CLINICAL WORK IN XENO GRAPH MODELS NOT AS SOPHISTICATED IN YOUR ANIMAL MODEL YOU SHOWED US THAT IS ANOTHER POTENTIAL THERAPEUTIC. OTHER THAN THAT COMMENT, I WANTED TO MORE OR LESS ASK YOU GIVEN YOUR SORT OF PROGRAM AND FACT YOU HAVE AISLEA AND CARD T CELLS AND BITES HOW ARE YOU PRIORITIZING AND SELECTING PIPELINE FOR PARTICULAR AGENTS YOU WILL COLLECTIVELY DECIDE TO MOVE FORWARD INTO CLINICAL TRIALS AND WHAT NEXT WILL YOU USE COMPANION BIOMARKERS? >> GREAT QUESTIONS. SO, SO THE -- THIS IS IN BACK OF PRIMARY FUNCTION OF STEERING COMMITTEE THAT IS -- I'M A PHD BIOLOGIST ON STEERING COMMITTEE AND MOST FOLKS ON THERE ARE MDS AND FUNCTION OF STEERING COMMITTEE MAIN FOCUS IS DOING PRIORITIZATION OF WHICH PROTOCOLS WE WILL PURSUE AND IN DR. PAVLETICH'S CLINIC AND LOTS OF CONSIDERATIONS AND WHICH ONES DO WE THINK WE CAN MAKE NEAT CONTRIBUTION TO THAT FITS SOME BIOLOGICAL QUESTIONS WE HOPE TO ANSWER AND ARE PRIME TO ANSWER AND, TWO, TRYING TO HAVE CLINICAL TRIALS PORTFOLIO WHERE ONE MIGHT FEED INTO OTHER FOR EXAMPLE PATIENT MIGHT STATE ONE THING THAT IS LISTED THERE AND ONE THING I MENTIONED THERE WAS TRIAL WITH LTNX WHICH IS A [INAUDIBLE] INHIBITOR AND IF PATIENTS PROGRESS ON THAT TRIAL WHAT COULD THEY DO NEXT? ANOTHER TRIAL THEY CAN PLACE OR GO ON TO AND HAVE SOME SORT OF OVERARCHING CONSIDERATION THERE AND RETREAT IS SCHEDULED THIS SUMMER TO DEAL WITH QUESTION MORE IN DEPTH AND CURRENTLY THE MAIN IMMUNOLOGY-BASED TRIALS ANDBYTE TRIAL AND THOSE THAT I WANT TO SHARE ARE OPENING SOON. >> SO, THANK YOU, DAN. IF YOU HAVE TIME, PLEASE REVIEW THE CHAT. THERE IS A FEW QUESTIONS AND COMMENTS THERE IN THE CHAT THAT WOULD BE OF INTEREST TO YOU AND YOU CAN PERHAPS ADDRESS A FEW QUESTIONS AND ANNE HAD A QUESTION AND CHRIS HAD AN IMPACTFUL COMMENT AS WELL AND IN INTEREST OF TIME LET'S MOVE FORWARD. FRANCIS, COW HIT THE HAND RAISED BUTTON. >> SORRY. >> THANK YOU, SIR. LET'S MOVE ON. NEXT PRESENTATION IS A REPORT ON HUMAN TUMOR ATLAS NETWORK AND UPDATE AND WILL PROVIDE BY DOCTORS ETHAN DIRECTOR KNOWLEDGE GROUP AND DANA FASHER AND DR. MARTHA WHO IS A RESEARCH PROFESSOR OF MEDICINE AT VANDERBILT AND PROFESSOR GRAYS BIOLOGIST IN BIOENGINEERING AT SCHOOL OF MEDICINE AND WE WILL HAVE A PRESENTATION AND REMINDING BOARDS THAT HTAN IS A MOON SHOT PROGRAM AND TODAY'S SPEAKERS WILL SHARE WITH US PROGRESS THAT HAS BEEN MADE TO DATE AS WELL AS PROVIDING IDEAS OF NEXT STEPS AND WE WILL HOLD QUESTIONS UNTIL THE END. WE HAVE THREE TAG TEAM SPEAKERS. I THINK WE WILL START WITH ETHAN AND GO TO MARTHA AND JOE. ETHAN? >> THANK YOU FOR OPPORTUNITY TO PRESENT TODAY. TODAY I'M REPRESENTING H10 DATA COORDINATING CENTER ALSO KNOWN AS DCC. MY TALK TODAY IS FOCUSED IN THREE PARTS. NO. 1, I WANT TO PROVIDE A GENERAL INTRODUCTION TO HTN NETWORK AND INTRODUCTION TO DATA COORDINATING CENTER AND SECOND TALK ABOUT DATA STANDARDS AND INTEGRATION WORK WE HAVE BEEN INVOLVED IN FOR MANY YEARS NOW. THIRD, TALK ABOUT GENERAL DATA AVAILABILITY AND VISUALIZATION OF HTM DATA WE ALREADY HAVE MADE PUBLIC. QUICK INTRODUCTION TO NETWORK FOR THOSE THAT MIGHT NOT BE QUITE AS FAMILIAR WITH OUR WORK. FIRST AND FOREMOST I THINK OF HTM NETWORK AS COLLABORATIVE NETWORK OF MANY INDIVIDUALS. ACTUALLY 150 INDIVIDUALS ACTIVELY INVOLVED IN NETWORK AND 10 RESEARCH CENTERS THAT HAVE BEEN FUNDED AND 5 HAVE BEEN FUNDED TO DEVELOP PRECANCER ATLASES. 5 HAVE BEEN FUNDED TO DEVELOP TUMOR ATLASES. WE HAVE ONE PILOT PRECANCER OBJECT CALLED P CAP AND ONE PILOT CANCER ATLAS PROJECT CALLED H TAP. IN THINKING ABOUT H10 IN COMPARISON TO OTHER NCI PROJECTS AND IN PARTICULAR IN COMPARISON TO [INAUDIBLE] PROJECT TWO DISTINGUISHING FACTORS TO H10 PROJECT IT IS FOCUSED ON UNDERSTANDING TRANSITIONS IN CANCER AND SPECIFICALLY UNDERSTANDING MOLECULAR BASIS OF TRANSITIONS SHOWN GRAPHICALLY ON RIGHT HERE AND THOSE UNDERSTANDING TRANSITION FROM PRECANCEROUS DISEASES TO CANCER OR TRANSITION FROM PRIMARY TUMORS TO METASTATIC TUMORS OR IN CASE OF BOTTOM PANEL WE HAVE ATLASES FOCUSED ON UNDERSTANDING INITIAL RESPONSE TO TREATMENT AND EVENTUAL DEVELOPMENT OF RESISTANCE TO THE SAME TREATMENT. THE SECOND DISTINGUISHING FACTOR OF H TAN REALLY IS DATA ITSELF AND GROUPS HAVE STRONG FOCUS ON SINGLE CELL ANALYSIS AND MULTIPLEX IMAGING MODALITIES AND SHOWING NUMBER OF EXAMPLES OF IT THAT THROUGHOUT MY TALK AND SECONDLY WE HAVE A FOCUS ON TRANSITIONS IN CANCER AND RESEARCH GROUPS ARE GENERATING RICH LONGITUDINAL SETS INFORMATION ABOUT PATIENTS OVER TIME OR SINGLE CELL DATA OVER TIME OR IMAGING DATA OVER TIME, ET CETERA. GETTING MORE INFORMATION ABOUT H TAN NETWORK AS A WHOLE AND INDIVIDUAL ATLASES CURRENTLY UNDER CONSTRUCTION WE HAVE PAPER OUT IN CELL YOU CAN CHECK OUT AND MAINTAIN WEBSITE HUMOR TUMOR A- THE LASS ORG THAT HAS DATA I WILL PRESENT IN A MOMENT AND HAS INFORMATION ABOUT DATA STANDARDS WE HAVE DEVELOPED. I REALLY AM HERE TO REPRESENT DATA COORDINATING CENTER QUICK NOTE DCC SPANS 4 DIFFERENT INSTITUTIONS ALL OF WHICH ARE LISTED HERE AND HAVE A STRONG IMAGING COLLABORATION WITH PETER'S GROUP AT HARVARD MEDICAL CENTER. AND WHAT IT COMES DOWN TO AT DCC IS A TWO FOLD MISSION IN LIFE IF YOU WILL. NO. 1, WE ARE IN BUSINESS OF DEVELOPING H TAN DATA STANDARDS ENABLING OVERALL DATA INTEGRATION IN H TAN NETWORK AND ENABLE DATA SHARING AND DATA VISUALIZATION TO DATA TO MAKE DATA AVAILABLE TO SCIENTIFIC COMMUNITY AND TO THE WIDER PUBLIC. A LOT OF WHAT WE SPEND TIME THINKING ABOUT AT DCC IS WHAT EXACTLY IS AN ATLAS AND WHAT GOES INTO MAKING AN ATLAS AND THERE IS A NUMBER OF WAYS THINKING ABOUT THIS AND I HAVE ALL OF THE RICH DATA BEING GENERATED BY RESEARCH CENTERS CLINICAL AND BIOSPECIMEN DATA AND TYPES OF PROFILING AND IMAGING DATA -- MAKING SURE DATA IS AVAILABLE TO EVERYONE AND YOU HAVE PROBABLY HEARD ABOUT FAIR DATA PRINCIPLES CAUSES CONFUSION IN COMMUNITY AND H TAN IT IS CLEAR WHAT WE HAVE TO DO. NO. 1, MAKE SURE DATA IS FINDABLE SO USERS CAN FIND DATA AND QUERY IT FOR SPECIFIC SUBSETS OF DATA THEY ARE MOST INTERESTED IN AND SECONDLY MAKING SURE DATA IS ACCESSIBLE IN AS MANY MODES AS POSSIBLE AND PROVIDE 5 DIFFERENT MODES OF ACCESS I WILL DESCRIBE IN A MOMENT AND MAKING SURE DATA IS INTEROBRABLE AND REUSABLE AND BIG ELEMENT TO THAT IS MAKING SURE WE HAVE DATA ANNOTATED WITH METADATA AND USERS CAN DOWNLOAD DATA PROCESSING IN CLOUD AND DO RESEARCH STUDIES GETTING OWN PUBLICATIONS OUT IN THE FUTURE. UNDERLYING ALL OF THIS THOUGH IS WE NEED A PLATFORM TO STORE ALL H TAN DATA. THERE IS THREE ELEMENTS OF THAT PLATFORM I WANTED TO HIGHLIGHT HERE. NO. 1, WE BUILT A ROBUST DATA MANAGEMENT PLATFORM ON TOP OF SYNAPSE A DATA MANAGEMENT PLATFORM DEVELOPED BY BIONETWORKS OVER MANY YEARS WITH CLOSE CONNECTION WITH CANCER GENOMICS CLOUD CANCER CLOUD RESOURCES AND WE HAVE PROCESS BY WHICH WE TRANSFER DATA FROM RESEARCH CENTERS TO CENTRAL DATA REPOSITORY AND WE HAVE VALIDATION PROGRAMS AND DASHBOARDS, ET CETERA. THIRD, IN ORDER TO GET DATA INTO OUR SYSTEM DATA FROM RESEARCH CENTERS HAS TO ADHERE TO SET OF WELL-DEFINED DATA STANDARDS. ONCE WE HAVE ALL THAT DATA WITHIN A CENTRAL SYSTEM WE CAN DISTRIBUTE IT TO WIDER SCIENTIFIC COMMUNITY AND DO THAT THROUGH SEVERAL MECHANISMS. NO. 1 WE HAVE DEDICATED H TAN DATA PORTAL AND NO. 2 WE PROVIDE DIFFERENT DATA VISUALIZATION OPTIONS AND OPEN SOURCE SOFTWARE TOOLS WE DO AND SLICES OF H TAN DATA TRANSFERRING TO DIFFERENT NODES IN CANCER RESEARCH DATA COMMONS THAT IS IMPORTANT WE WANT TO MAKE SURE H TAN IS PART OF LARGER MOON SHOT INITIATIVE WE ARE PART OF AND PART OF LARGER NCI CANCER DATA ECOSYSTEM WE ARE IN THE PROCESS OF BUILDING. A REALLY BIG PART OF WHAT WE FOCUS THOUGH ON AT DCC IS DATA STANDARDS AND DATA INTEGRATION AND AS PART OF THAT WE DEVELOPED OVERALL PROCESS BY WHICH WE HAVE DEVELOPED H TAN DATA MODEL. THERE IS THREE ELEMENTS OF THAT I WANTED TO MENTION BRIEFLY. NO. 1, CREATED PROCESS WE CALL REQUEST FOR COMMENTS AFFECTIONATELY CALL RFC PROCESS THAT IS COMMUNITY DRIVEN WAY WE ENGAGE WITH EXPERTS ACROSS H TAN NETWORK DEVELOPING DATA STANDARDS GONE WELL AND GOTTEN LOTS OF ENGAGEMENT AND LOTS OF BUY-IN THROUGHOUT THE NETWORK AND HAVE UNIFIED SCHEMA WE CAN USE TO DEVELOP DATA MODEL TO ENABLE US TO CREATE VALIDATION TOOLS AND ENABLES US TO LINK PIECES OF DATA TOGETHER FOR EXAMPLE LINKING PATIENTS TO BIOSPESIMMENS TO IMAGING DATA, ET CETERA. THIRD WE HAVE DATA LEVELS THAT WE SUPPORT LARGELY INSPIRED BY TCGA PROJECT WE GO FROM RAW DATA YOU TO PROCESSED HAM BURGER DATA AND DIFFERENT LEVELS OF PROCESSING DATA WE SUPPORT DEPENDING ON THE DATA TYPE. OUT OF THIS PROCESS WE HAVE FINALIZED NUMBER OF DATA STANDARDS FOR EXAMPLE WE HAVE A RICH CLINICAL DATA MODEL BUILT IN LARGE PART ON PIONEERING WORK DONE IN GENOMIC DATA COMMONS IN TERMS OF THEIR DATA MODEL AND SUPPORT METADATA BIOSPESIM ENMETADATA BULK SEQUENCING AND SUPPORT DIFFERENT MODALITIES OF MULTIPLEX IMAGING AND HAVE NUMBER OF RFCS THAT ARE STILL IN PROGRESS MASS SPECK TA PUBLICATIONS AND TOOLS BEING GENERATED BY NETWORK. JUST TO GIVE EXAMPLE OF TWO DATA TYPES I WILL SHOW YOU SINGLE CELL AND MULTIPLEX IMAGING. SINGLE CELL RNA SEEK FOR EXAMPLE WE HAVE AS POSSIBLE HARMONIZING DATA MODELS WITH THOSE IN SCIENTIFIC COMMUNITY THAT IS DONE BY HUMAN CELL ATLAS AND SUPPORT DIFFERENT LEVELS OF SINGLE CELL DATA GOING FROM LEVEL 1 UNALIGNED SEQUENCE REEDS TO LEVEL 4 WHERE WE HAVE CELL TYPE ASSIGNMENTS. I'M SURE YOU ARE AWARE THERE IS EXPLOSION OF IMAGING TECHNOLOGIES IN LAST SEVERAL YEARS AND ALL I THINK ARE IN USE WITH H TAN. SOME ARE SHOWN ON LEFT WE HAVE GROUPS USING NIMBY AND SIZE SEF AND MULTIPLEX FLOUR ESSENCE AND YOU CAN SEE CHALLENGES YOU HAVE WITH IMAGING MODALITIES. INSTEAD OF 4 OR 5 CHANNELS SOME TECHNOLOGIES HAVE 40 OR 50 OR 60 CHANNELS AND IT REPRESENTS VERY LARGE DATA FILES THAT REPRESENT SOME UNIQUE CHALLENGES IN TERMS OF DATA MANAGEMENT AND IN TERMS OF DATA SHARING OUTSIDE OF THE H TAN NETWORK AND WE HAVE BEEN INVOLVED IF IN LARGER EFFORT STARTED BY PETER'S GROUP AT HMS THAT IS A DATA STANDARD CALLED MIGHTY I WON'T GO THROUGH ALL DETAILS BUT SIMILAR TO SINGLE CELL MODEL WORKS AND RAW IMAGING TILES COMING OFF THE MACHINE AND LEVEL 2 WE CAN ASSEMBLE TILES TO LARGER MULTICHANNEL IMAGES AND ON THE RIGHT IS LEVEL 5 WHERE WE CAN ANNOTATE REGIONS OF INTEREST AND ANNOTATE DIFFERENT REGIONS WITH TEXT AND SHARE NARRATIVES AROUND MULTIPLEX TISSUE IMAGES WE CREATED IN H TAN THIRD TOPIC IS DATA AVAILABLE THE AND VISUALIZATION AND IMPORTANT THING TO STRESS IS WE HAVE 5 MODES OF DATA ACCESS FOR H TAN. NO. 1, H TAN DATA PORTAL AND NO. 2 WE SUPPORT DIFFERENT TYPES OF VISUALIZATION AND EXPLORATORY DATA ANALYSIS. THIRD, OUR SYSTEM IS BUILT ON TOP OF SYNAPSE WITH RICH PROGRAMATIC INTERFACE. USERS CAN DOWNLOAD DATA THROUGH APPLICATION INTERFACE AND DIFFERENT LANGUAGES LIKE PYTHON AND 4 SUPPORT DIFFERENT NODES IN CANCER RESEARCH COMMONS AND THESE ARE LIVE AND FIFTH IS COMING SOON WE WILL MAKE H TAN DATA AVAILABLE THROUGH GOOGLE SERVICE CALLED BIG KWOOERY. THIS MATRIX SHOWS YOU WHERE EVERYTHING IS NOW. I WON'T GO THROUGH DETAILS ON THIS. FAIR AMOUNT OF INFORMATION AND IF LOOKING FOR OPEN ACCESS DATA AND FOR EXAMPLE DEIDENTIFIED CLINICAL AND BIOSPESIM ENDATA OR LEVEL 4 SEQUENCING DATA IMAGES IS AVAILABLE IN THE PORTAL AND IN SYNAPSE AND IF LOOKING FOR ACCESS CONTROLLED DATA AVAILABLE IF IN CANCER DATA SERVICE CONNECTED TO 7 BRIDGES NCI CLOUD RESOURCE WE HAVE A STRONG COLLABORATION WITH IMAGE DATA COMMONS MAKING AVAILABLE IN IT IN THE NEXT FEW MONTHS AND WE CURRENT WILL I DO RELEASES EVERY 3 TO 4 MONTHS AND LAST RELEASE WAS IN MAY AND SEEING STATS ON CURRENT RELEASE WE HAVE DATA ON 10 ATLASES AROUND 1200 CASES AND 2700 BIOSPECIMENS. ALL OF THIS DATA IS AVAILABLE IN OUR H TAN DATA PORTAL. I HAVE A FEW MOMENTS LEFT AND WANT TO SHOW YOU QUICKLY HOW TO ACCESS DATA THROUGH DATA PORTAL. IT IS AT URL DATA HUMAN TUMOR ATLAS AT ORG AND INFORMATION IS ORGANIZED BY ATLAS AND YOU CAN SEE FOR EXAMPLE CLICKING ON THIS CENTER YOU CAN DRILL DOWN INTO WHAT THEY ARE DOING AND SEE FILES THEY GENERATED WE HAVE ADVANCED FILTERING OR INTERFACE THAT YOU CAN FILTER BY DIFFERENT CRITERIA AND FOR EXAMPLE SINGLE CELL RNA SEEK DATA LEVEL 4 PERFECT BU YOU CAN ENTER CRITERIA HERE. YOU WILL GET UPDATE ON ALL FILES MATCHING SPECIFIC CRITERIA THAT YOU ARE LOOKING FOR. THIRD, YOU CAN EASILY DOWNLOAD METADATA FROM ANY ATLASES. FOR EXAMPLE DOWNLOADING CLINICAL DATA OR BIOSPESIM ENDATA OR ANNOTATIONS ON IMAGING DATA FOR EXAMPLE YOU CAN DOWNLOAD FROM THIS COLUMN AND LAST COLUMN IS MY FAVORITE AND WAYS YOU CAN VISUALIZE DIFFERENT DATA TYPES THAT CAN BE GENERATED BY H TAN AND BRIEFLY I WILL SHOW YOU THREE EXAMPLES OF WAYS IN WHICH WE PROVIDE VISUALIZATION OF H TAN DATA AND FIRST AND HOPEFULLY YOU CAN SEE THIS VIDEO. IT IS INTEG GRAITION WITH A TOOL CALLED MINERVA THAT HAS BEEN DEVELOPED BY PETER'S GROUP AT HMS. YOU CAN SEE HERE ON THE LEFT THAT FOR MULTIPLEX TISSUE IMAGES WE HAVE A PIPELINE THAT AUTOMATICALLY GENERATES THUM LINE IMAGES FOR ALL TISSUES. IF YOU CLICK ON ANY OF THOSE YOU GET A FULL SCREEN MODE OF MINERVA WHERE YOU CAN TURN ON AND OFF CHANNELS AND VIEW ANNOTATIONS AND ZOOM AND PAN AND IF YOU HAVE NEVER TRIED TOOL OUT I HIGHLY RECOMMEND YOU TAKE A LOOK AT IT ON H TAN PORTAL AND SECONDLY PROVIDE VISUALIZATION OF SINGLE CELL DATA THROUGH WHAT IS LEADING TOOL IN TERMS OF SINGLE CELL VISUALIZATION AND EXPLORATORY ANALYSIS THAT IS A TOOL CELL BY GENE AND COLLABORATION WITH INSTITUTE NOW FOR SEVERAL YEARS AND IDEA YOU CAN LOAD UP H TAN DATA WITH CELL BY GENE AND COLOR CODE BY DIFFERENT CRITERIA AND ZOOM IN AND OUT AND FILTER LARGE-SCALE DATA SETS. LASTLY, WE PROVIDE VISUALIZATION THROUGH PORTAL THROUGH CANCER GENOMICS AND PORTAL TO VISUALIZE AREAS OF GENOMIC AND IMAGING DATA AND SHOWING EXAMPLE OF WAYS WE IMPROVED BIOPORTAL IN TERMS OF VISUALIZING LONGITUDINAL CLINICAL DATA THAT IS EXAMPLE THAT I CAN SHOW THAT GRAY WILL PRESENT ON IN A FEW MOMENTS AND THANK YOU FOR YOUR TIME AND ACKNOWLEDGING MANY PEOPLE IN DCC THAT MADE THIS HAPPEN. THANK YOU. >> THANK YOU, ETHAN. WE WILL GO THROUGH THREE PRESENTATIONS AND HAVE Q & A TOWARDS THE END. NEXT IS DR. [INAUDIBLE] AND HOPE I PRONOUNCED IT CORRECT. IF YOU CAN UNMUTE WOE HAVE SLIDES UP. >> YES. THANK YOU. IT IS CLOSE AND IT IS SHRUB SOLE. >> OKAY. >> THANK YOU FOR THE OPPORTUNITY TODAY TO SHARE WORK THAT WE HAVE BEEN DOING IN VANDERBILT PCA PRECANCER@LIST AND SPEAKING ON BEHALF OF FELLOWS. WE ARE FOCUSED ON COALO RECTAL CANCER AT VANDERBILT AND NEEDS WITH COALO RECTAL CANCER FOR IMPROVED MODALITIES FOR SCREENING AND MODALITIES FOR INTERVENTION AND RECEPTION AND KEY ADVANCEMENT IN AREAS IS FACILITATED BY BETTER UNDERSTANDING OF MOLECULAR PHENOTYPES OF PRECANCEROUS LESIONS AND UNDERSTANDING PROGRESSION AND PROGRESSION POTENTIAL AND IDEA AND CONCEPT OF DIFFERENT MOLECULAR PHENOTYPES BEING IMPORTANT IS CERTAINLY NOT FOREIGN TO THIS AUDIENCE AND UNDERSTANDING THAT ON THE CANCER LEVEL UNDERSTANDING MOLECULAR PHENOTYPES MAKES IMPORTANT ADVANCES IN PHENOTYPIC OBSERVATIONS AND UNDERSTANDING PRESENCE OF MICRO SATELLITE -- THERE ARE IMPORTANT DIFFERENCES IN PRECANCEROUS LESIONS FOR SOME SUBTYPES OF IMPORTANCE IN TODAY'S TALK CONVENTIONAL@O GNOMAS AND ASSOCIATED FELLOWS THAT WE WILL FOCUS ON AND DEVELOPED PROJECT OR COLON MAP WHERE WE ARE FOCUSED ON BEING ABLE TO MAP SPATIAL AND TEMPORAL RELATIONSHIP AS CROSS SPECTRUM OF NORMAL COLON EARLY POLYPS AND AGAIN A KEY FEATURE FOR US IS TO LOOK AT SIMILARITIES AND DIFFERENCES ACROSS CONVENTIONAL@O GNOMAS AND ASSOCIATED POLYPS AND IMPORTANT PART OF MAP STUDY IS PARTICIPANTS WHO ARE INDIVIDUALS SCHEDULED FOR COLONOSCOPIES AT VANDERBILT AND PULLING FROM A CLOSED RECRUITMENT POOL IN PATIENT POPULATION AT A SINGLE CENTER AND AS A RESULT WE KNEW BACK IN 2018 AS WE DESIGNED STUDY SHOULD WE RELY SIMPLY ON RANDOM SAMPLING THAT WE WOULDN'T BE ABLE TO OPTIMIZE RACIAL/ETHNIC DIVERSITY OF PARTICIPANTS AND WE HAVE INSTEAD IMPLEMENTED STRATIFIED SAMPLING ALLOWING US TO ENHANCE THAT UP TO ABOUT A QUARTER OF PARTICIPANTS. THEY ARE GENEROUS WITH TIME IN COMPLETING SURVEYS TO PROVIDE INDIVIDUAL LEVEL DATA THAT ETHAN MENTIONED AS WELL AS PROVIDING PERMISSION FOR BIOSPESIM ENPREVENTION AND POLYPS ARE REMOVED AND UNIQUELY WE BISECT POLYPS AND TAKE A PORTION FOR CLINICAL DIAGNOSIS AND OTHER PORTION IS RESERVED SOLELY FOR RESEARCH PURPOSES AND WILL GO BACK AND RETRIEVE AND USE FFPE POLYPS AS WELL TO FACILITATE WORK THAT YOU WILL SEE TODAY. IMPORTANT COMPONENT OF OUR DIAGNOSIS IS TO BE ABLE TO DO A STANDARDIZED RESEARCH PATHOLOGY REREVIEW OF POLYPS REMOVED FROM EVERY INDIVIDUAL AND NOW SWITCHING A LITTLE TO BIOLOGY AND WE ARE FAMILIAR WITH MODEL OF COALO RECTAL TUMOR GENERALO SIS WITH STEM CELLS CELL OF ORIGIN FOR COALO RECTAL CANCER THAT IS A BOTTOM UP MODEL BASE OF THE CRYPT THERE IS ATORATIONS WITHIN THE STEM CELL COMPARTMENT THAT LEAD TO POLYPS AND ON TO CANCER AND HAVE A QUESTION WHETHER OR NOT THERE MIGHT BE OTHER MODELS AND FOR EXAMPLE IN STOMACH THERE IS EXAMPLE OF H PILE ORRI AND METAPLASIA PRIMARY MODEL DIFFERENTIATION OF CELL INTO NONREGENERATIVE STATE TYPICAL OF OUR MODEL AND KEY QUESTIONS BECAME DO WE FIND EVIDENCE OF DIFFERENT ORIGIN OF TUMOR GENERALO SIS AND IMMUNOTONE AND MICRO ENVIRONMENT AND CUTTING TO CHASE HERE ANSWER TO BOTH QUESTIONS IS YES AND I WILL SHOW YOU EXAMPLES OF THAT AND STARTED BY DOG SINGLE CELL RNA SEEK AND DATA WAS PUBLISHED IN CELL BACK IN SEPTEMBER OF 2021 AND ANALYSIS CONDUCTED BY BOB CHAN AT KEN LOU'S LAB AT THE TIME AND THERE IS CELL POPULATIONS DEMONSTRATING AT LEAST 7 DIFFERENT TYPES OF EPITHELIAL CATEGORIES IN SAMPLES WE ANALYZED AND COMPARING TO HISTOLOGY YOU SEE WE SEE IN CIRCLED AREAS AND POLYPS AND CELLS WE CALL CERTIFY RATED SPECIFIC CELLS INCLUDING HYPERPLASTIC POLYPS AND LACERATED POLYPS IN AREA OF CONVENTIONAL ATTOGNOMIC OR SPECIFIC CELLS AND LOOKING TO SEE TO IDENTIFY GENE PROGRAMS AND PATHWAYS THAT MIGHT BE ACTIVATED COMPARED TO NORMAL AND AS EXPECTED PATHWAY ACTIVATION. WE DIDN'T SEE THESE IN -- WE SAW DIFFERENTIATED CELL CHARACTERISTICS IN PARTICULAR HIGHLY ENRICHED IN GENES IN MUK COSSA AND COORDINATED REGULATION OF GENES AND PATHWAYS AND LOOKING AT MAP FIGURE HERE YOU SEE IN CERTIFY RATED AREA YOU SEE EXPRESSION OF MUCK 5AC AND COMPARE SIGNATURES WE SEE IN@O GNOMAS AND CERTIFY RATED POLYPS YOU SAW SIGNATURE INDICATIVE TO EPITHELIAL RESPONSE TO MICROBIAL ASSAULT AND HYPOTHESIZING 2 DIFFERENT MODELS AND BOTTOM UP MODEL SOMETHING OCCURRED WITHIN STEM CELL XART M AND HOWEVER WITH CERTIFY RATED POLYPS DEALT WITH DIFFERENTIATED MODELS AND TOP DOWN MODEL PROVIDING HISTLOGICAL EVIDENCE OF THIS MAPPED -- MULTIPLEX FOR ESSENCE AND HISTLOGICAL IMAGING ALONG THIS SLIDE AND BOTTOM LINE HERE YOU CAN SEE FIGURE THAT HAS A LACK OF STEM EXPRESSION WITHIN POLYP AND WE SEE INCREASE OF MUCK 5AC THAT IS LARGELY ABSENT FROM THE BASE OF THE KRIP AND ADO GNOMAS WE SAW OPPOSITE PROVIDING FURTHER EVIDENCE. BACK TO SINGLE CELL RNA SEEK DATA WE SEE CLUTTERING OF ATTOGNOMA SPECIFIC CELLS ALONG WITH AB SDOFSHTIVE CELLS AND POSITIVE STEM CELLS WITH CERTIFY RATED CLUSTER AND WE SEE THESE ARE CLUSTERING WITH GOBLET CELLS AND PROVIDING EVIDENCE WITH DIFFERENT CELLS OF ORIGIN FOR TYPES OF POLYPS AND BECAUSE WE WANT TO LOOK ULTIMATELY AT HOW IT MIGHT IMPACT CANCER WE WANT TO SEE IF SIGNATURES CARRIED FORWARD INTO COALO RECTAL CANCERS AND IN HIGH MSI CANCERS WE SAW THEY RETAINED METAPLASTIC SIGNATURES OF CERTIFY RATED POLYPS AND SEE THEY BEGAN STEM CELL PROPERTIES WHILE RETAINING OWN UNIQUE FEATURES THAT IS DEMONSTRATED WELL HERE IN THIS SLIDE USING SAME MARKERS WE SHOWED BEFORE AND POINTING OUT WE HAVE AREA OF HIGH MUCK 5AC ALONG THIS EDGE OF THE TUMOR. CORRESPONDING TO IN ABSENCE OR DECREASE OF STEM CELL EXPRESSION AND WE ALSO SAW LOW MUCK 5AC REGION WHERE STEM POTENTIAL WAS PRESENT AND LOOKED AT IT IN BULK RNA SEEK DATA WE HAD AVAILABLE FROM TCGA AND SAW GASTRIC METROPLASIA IN C3 NOT CMS2. FOR THE NEXT ANALYSIS WE WANTED TO LOOK AT SECOND QUESTION IN IMMUNE TONE WE SAW MOST IMMUNE CELLS WERE INCREASED IN RELATIONSHIP TO NORMAL AND WEREN'T NECESSARILY DIFFERENT BETWEEN CELL POPULATION TYPES HOWEVER CYTOTOXIC IMMUNE CELLS WERE INCREASED IN CERTIFY RATED POLYPS IN COMPARISON TO ADO GNOMAS CHARACTERISTIC WE SAW CARRIED OVER TO MICRO SATELLITE IN STABLE CANCERS VERSUS INSTABLE CANCERS AND IMPORTANT THING CONVEYED TO US BY PEER REVIEW OF THE RESEARCH COMMUNITY IS AS IMPORTANT AS ATLAS WAS THEY WANTED SEE FUNCTIONAL VALIDATION OF WORK WE WERE REPORTING. SO, WE WERE ABLE TO PARTNER WITH VANDERBILT GI SPORE LED BY BOB COFFEE AND JORDAN BERLIN TO DO LIMITED MOUSE MODEL WORK AND ORGANOID WORK TO LOOK AT FUNCTIONAL VALIDATION. WE WERE ABLE TO IDENTIFY AND VALIDATE THAT PATTERNS AND SIGNATURES THAT WE WERE OBSERVING PARTICULARLY WITH CYTOTOXIC IMMUNITY CARRIED OVER INTO MODELS SO WE HAVE FURTHER FUNCTIONAL VALIDATION OF OBSERVATIONS THAT I HAVE JUST TOLD YOU. THERE IS A LOT OF OTHER DATA THAT WE HAVE GENERATED AND ANALYSIS FROM THESE DATA AND CELL PAPER THAT I MENTIONED. I DON'T HAVE TIME TO GO INTO ALL OF THAT TODAY. I WILL SUMMARIZE SOME BIOLOGY TO SAY THAT WHAT WE HAVE OBSERVED AND DIFFERENCES BETWEEN TWO POLYP TYPES AND ACTIVATION OF WHEN VERSUS METAPLASTIC RESPONSE AND DIFFERENCE OF STEM CELLS IN DIFFERENCE OF COMMITTED AB SORPTIVE CELLS AND CRYTOTOXIN ENVIRONMENT FINDINGS RELATED TO CYTOTOXIC POLYPS WILL BE IN WAY WE THINK OF CARCINOGEN ESIS IN THE COALON AND PURSUING DIFFERENT AVENUES TO UNDERSTANDING THESE DIFFERENT POLYPS IN PARTICULAR AND ANOTHER IMPORTANT COMPONENT OF H TAN IS TRANS-NETWORK PROJECTS FUNDING PROVIDED SPECIFICALLY TO ENCOURAGE COLLABORATION ACROSS H TAN CENTERS AND WE PARTICIPATED IN MULTIPLE AND I WILL HIGHLIGHT A FEW FOR YOU HERE SO YOU HAVE AN IDEA OF SOME WORK THAT IS BEING DONE ACROSS CENTERS AND VERY FIRST ONE IS CALLED SAR DONA AND THIS WAS A TNP TO LOOK AT IMAGING METHODS ACROSS CENTERS AND YOU SAW FROM ETHAN WE USE VARIETY OF DIFFERENT METHODOLOGIES AND USING COMMON SPECIMENS TO COMPARE THESE AND ENLIST HELP OF COOPERATIVE NETWORK BASED AT VANDERBILT TO PROVIDE SAMPLES AT THIS PROJECT AND BECAUSE OF CLOSE PHYSICAL PROXIMITY WE COULD DO SINGLE CELL RNA SEEK ON SAMPLES TO BE USED ACROSS CENTERS AND ANOTHER IS COALO RECTAL LIVER METASTASIS PROJECT THAT IS LED BY LEE DING AT WASH U. THIS IS AN OPPORTUNITY TO CROSS-TEST PLATFORMS AND METHODS TO EVALUATE DIFFERENT APPROACHES AND PROVIDE FURTHER BIOLOGICAL INSIGHTS AND ONE THAT WILL BE INCREASINGLY IMPORTANT AS THEY MAKE PROGRESS OVERCOMING YEAR IS TISSUE CELLULAR NEIGHBORHOODS INITIATIVE ATTEMPT TO DEVELOP GOLD STANDARD CELLULAR NEIGHBORHOOD ANNOTATION AS CROSS TISSUES TO BE USED BY BROADER RESEARCH COMMUNITY AND FURTHER DEVELOPING IT THIS WITH COLLABORATION OF OTHER CONSORT YA OUTSIDE OF [INAUDIBLE] AND FINALLY ONE ON THIS SLIDE TO HIGHLIGHT IS THE WORK OF OUR DIVERSITY INCLUSION WORKING GROUP. ONE KEY PROJECTS OF THIS WORKING GROUP HAS BEEN TO DEVELOP THE OPPORTUNITY TO INCLUDE RESEARCH ADVOCATES PART OF STEERING COMMITTEE FOR H TAN THAT IS IN PROCESS AND WILL BE COMPLETED THIS SUMMER AND IS A WORKING GROUP FOCUSED ON FINDING WAYS TO ADDRESS SCIENTIFIC QUESTIONS RELATED TO DIVERSITY ACROSS H TAN FOR EXAMPLE THERE IS A PROJECT THAT IS IN DEVELOPMENT TO LOOK AT GENETIC ANCESTRY AND THINGS SUCH AS IMMUNOPHENOTYPES AND LOOKING AT COMMUNITY ENGAGED PRACTICES ACROSS H TAN AND ENCOURAGE INDIVIDUAL CENTERS AND AT H TAN LEVEL TO ADOPT SOME PRACTICES AND AS WELL AS TO LOOK AT DIVERSITY OF RESEARCH TEAMS. I RECENTLY STEPPED DOWN FROM CO-LEADING THIS WORKING GROUP. I'M PLEASED TO REPORT THAT MY REPLACEMENT IS A JUNIOR INVESTIGATOR AND AN INDIVIDUAL FROM AN UNDER-REPRESENTED COMMUNITY. FINAL TMP I WANT TO MENTION IS ONE WE ARE LEADING AND S- CINDY IS A KEY INVESTIGATOR OF COLON MAP PROJECT CO-LEADING BIOSPESIM ENUNIT BASED AT HOPKINS AND IS A WORLD EXPERT ON MICROBES AND COALO RECT CAL CANCER AND MICROBIAL BIOFILMS COULD BE A WAY THAT ASSAULT COULD HAPPEN IN COALO RECT CAL GENESIS AND INTERESTED IN CONTINUING TO PURSUE THAT FURTHER TO PROVIDE MORE INFORMATION AND UNFORTUNATELY SAMPLES ARE NOT AVAILABLE WITHIN US THAT WOULD BE APPROPRIATE FOR THIS DUE TO PATIENTS RECEIVING HIGH DOSE OF ANTIBIOTICS PRIOR TO SURGERY WIPING OUT MICROBIAL BIOFILMS AND PARTNERING WITH WASH U AND STANFORD TO PROVIDE IMAGING OF SAMPLES TO IDENTIFY REGIONS OF INTEREST TO DO NANOSTRING AND MULTIPLE REGIONS OF INTEREST AND HOPEFUL IN NEXT YEAR WE CAN REPORT ADDITIONAL FINDINGS FROM THIS PROJECT. SO, A LITTLE OF A SUMMARY OF SOME CONTRIBUTIONS SPECIFICALLY TO DATE. WE HAVE CERTAINLY WORKED HARD TO CHASHTHIZE PARTICIPANTS AND BIOSPESIMMENS TO ENHANCE DIVERSITY AND GENERATED LARGEST SINGLE CELL RNAC DATA SET OF POLYPS WE CONTINUE TO ADD TO AND DEPOSITED DATA TO DCC AND OTHER DATA AND KNOW IN PARTICULAR SINGLE CELL RNA SEEK DATA IS GENERATING LOTS OF INTEREST FROM SCIENTIFIC COMMUNITY WITH MULTIPLE INVESTIGATORS ACROSS THE WORLD REQUESTING THOSE DATA AND WE PUBLISHED OVER 15 PUBLICATIONS TO DATE AND COMBINATION OF SCIENTIFIC FINDINGS AS WELL AS METHODS WE HAVE HAD TO DEVELOP PART OF MOON SHOT PROJECT AND CREATED THINGS LIKE DROP KICK A SOFTWARE TOOLLE FOR QUALITY FILTERING RNA SEQUENCING DATA AND MERE & THAT IS A PIPELINE FOR CELL SEGMENTATION AND QUANTITY FICTION INCORPORATING MACHINE LEARNING BASED PIXEL -- LEADERSHIP IN MULTIPLE WORKING GROUPS OF H TAN BIOSPESIM ENWORKING GROUP AND MOLECULAR CHARACTERIZATION WORKING GROUP AND DIVERSITY INCLUSION WORKING GROUP AND WE HAVE ALSO BEEN LOOKING FOR AND INCLUDING JUNIOR INVEST TRAINING AND RESEARCH OPPORTUNITIES AND I WILL MENTION A FEW MORE. YOU HAVE SEEN A FEW ON SLIDES TODAY IN ADDITION WITHIN H TAN WE HAVE EMPHASIS ON JUNIOR INVESTIGATORS INVOLVED ACROSS WORKING GROUPS THAT THEY ORGANIZE AND RUN AN ANNUAL MEET FORGE JUNIOR INVESTIGATORS AS WELL AND AT VANDERBILT WE HAVE BEEN INTENTIONAL IN TRYING TO LEVERAGE OTHER RESOURCES TO ENHANCE SCIENTIFIC GOALS AND IMPACT OF MOON SHOT FUNDING AND EXAMPLE PARTNERING WITH GI SUPPORT TO DO FUNCTIONAL VALIDATION OF ATLAS AND WE HAVE OTHER ONES I CAN MENTION HERE A RECENT PAPER IN THAT IT WAS RECENTLY ACCEPTED IN CANCER DISCOVERY THIS IS A PROJECT COMING OUT OF COLLABORATION THROUGH COLON MAP IN HOPKINS AND VANDERBILT AND JUNIOR INVESTIGATORS LISTED HERE ARE ANLE TO DEMONSTRATE -- AND SO WE ARE VERY PLEASE TODAY BE ABLE TO CONTRIBUTE TO THAT PUBLICATION. IN TERMS OF NEXT STEPS AND ONGOING ACTIVITY WE CONTINUE TO EXPAND SAMPLE SIZE AND CONTINUE TO ADD ADDITIONAL IMAGING TO CHARACTERIZE SPATIAL NEIGHBORHOODS AND THIS CONTINUES TO REQUIRE DEVELOPMENT OF METHODS TO ANALYZE DATA THAT OUR TEAM IS WORKING ON AND FOLLOWING UP PARTICIPANTS FOR OUTCOMES ON FUTURE COLONOSCOPIES AND PROCEDURES AND ESTABLISHED AND USE COLONOIDS AND COMING YEAR DEVELOPING NEWSLETTER AND SUMMARIES AND NEWSLETTER WILL GO TO STUDY PARTICIPANTS THROUGH COLLABORATION OF CANCER CENTERS AND COMMUNITY OUTREACH AND ENGAGEMENT TEAM. WE ARE TRYING TO LOOK BEYOND H TAN TO CONTINUE TO WORK AND MOVE WORK FORWARD THAT THIS HAS BEEN ABLE TO PROVIDE BY HAVING ADDITIONAL FUNDING AND HOPE TO HAVE NEWS FOR THAT EARLIER THIS YEAR AND TEASER OF WORK WE ARE CONTINUING TO DO AS WELL AND I HAVE NOT YET SHOWN TODAY. THAT IS SPATIAL TRANSCRIPTOMICS AND WE HAVE BEGUN WORK ON SPATIAL TRANSCRIPTOMICS AND WITH GOAL TO FURTHER CHARACTERIZE POLLIMS AND DOING THIS ON SOME SAMPLES WHERE WE HAVE MATCHING SINGLE CELL RNA SEEK DATA. IN SUMMARY I WANT TO MAKE SURE I ACKNOWLEDGE THIS TAKES A LOT OF DIFFERENT PEOPLE AND GROUPS TO MAKE HAPPEN. IN PARTICULAR, I WANT TO POINT OUT THAT WE HAVE HAD CONTRIBUTIONS OF MULTIPLE OF OUR CCSG SUPPORTED SHARED RESOURCES IT THAT CONTRIBUTED THEIR ACTIVITY TOWARDS STUDY AS WELL AS WORKING ACROSS. IT IS TRULY A MULTIDISCIPLINARY PROJECT THAT IS ACROSS P MANY DIFFERENT GROUPS AT VANDERBILT AND HOPKINS. THANK YOU. >> THANK YOU, SUSAN. FASCINATING. AND THERE IS, AGAIN, ACTIVE COMMENTARY IN THE CHAT IF YOU WANT TO SCROLL TO THE BOTTOM AND WORK YOUR WAY UP A BIT. WE WILL NOW HAVE I THINK THE FINAL PRESENTATION FROM DR. GREY, JOE. >> THANK YOU FOR THE OPPORTUNITY TO PRESENT ON OHSU ADVANCED CANCER ATLAS H TAN CENTER AND CENTER FOCUSED PRIMARILY ON DYNAMICS OF TUMOR EVOLUTION AND WE INTERESTED IN CLINICAL IMPLICATIONS OF EVOLUTIONARY PRINCIPLES AND I WILL TALK YOU TO TODAY A PRIMARY SUMMARY OF MULTIDIMENSIONAL SPATIAL ATLAS WE HAVE WITH PATIENT FOR 4 YEARS AND -- OVER ARCHING GOAL OF CENTER IS TO REALLY IDENTIFY THE TUMOR INTRINSIC AND EXTRINSIC MECHANISMS OF RESPONSE AND RESISTANCE TO THERAPY AS THEY EVOLVE ACROSS THE PATIENT AND OVER TIME AND OUR PARTICULAR EMPHASIS IS DEVELOPING ACTIONABLE GUIDANCE TO ADDRESS SOME THERAPEUTIC RESISTANCE THAT ARISES. NEXT SLIDE, PLEASE. WE HAVE SEVERAL CONCEPTS AROUND WHICH THE CENTER IS BUILT. FIRST, WE ARE DEPLOYING DIVERSOMIC AND MULTISCALE AND MULTIPLEX IMAGING TOOLS WITH IDEA THAT LE WILL GIVE ROBUST ABILITY TO IDENTIFY MECHANISMS THAT WILL OCCUR AND DO THIS IN A WAY THAT IS IN CLINICAL REAL TIME THAT IS TO SAY FAST ENOUGH THAT IF WE IDENTIFY ACTIONABLE INFORMATION THAT IT COULD POSSIBLE WILL I BE USE THE TO TREAT THE PATIENT UNDERSTUDY. WE CREATE AND COLLECT DETAILED CLINICAL DATA FOR REASONING ABOUT THERAPEUTIC RESPONSE AND COLLECT BLOOD BIOMARKERS AND ANO-TOMIC IMAGES TO PROVIDE QUANTITATIVE RESPONSE METRICS AND CREATE DETAILS TREATMENT INFORMATION ENABLING TREATMENTS TO BE TREATED AS INFORMATIVE PERTURBATIONS TO UNDERSTAND HOW AND WHY CANCERS ARE EVOLVING AS THEY ARE AND GENERATE CLEA ANALYTICS AND SPECIAL PROET EOMICS AND INFORMATION TO BE USE TODAY MANAGE TREATMENT OF THE PATIENT AND TO INFER MECHANISMS WE COMPARE PREAND ON TREATMENT BIOPEN SEIZE TO REVEAL MECHANISMS OF PERSISTENCE AND DIFFERENCES BEFORE AND AFTER TREATMENT AND WE HAVE DEVELOPED A SUBSTANTIAL INFRASTRUCTURE ALLOWING US TO COLLECT AND MANAGE SERIOUS BIOSPECIMENS AND RESEARCH INFORMATION THAT GOES ALONG WITH THEM ESSENTIAL TO INTERPRET MECHANISMS AS THEY ARISE AND CENTER IS DEEPLY COMMITTED TO DATA SHARING AND COLLABORATION IN THE CENTER AND ACROSS THE CONSORTIUM AND IN AREA OF ASSAY VALIDATION YOU HAVE HEARD FROM, FROM MIRTHA AND ALGORITHM TO HELP WITH INTERPRETATION AND INTEGRATION. NEXT SLIDE, PLEASE. APPROACH IS ILLUSTRATED SCHEMATICALLY HERE COMPLEX ENGINEERING DIAGRAM AND WHAT WORKFLOW ENABLES US TO DO IS ACQUIRE SOOERIAL BIOPSIES FOR THOSE ENROLLED IN SMART PROGRAM AND PATIENTS CONCEPTED CONTROLLED RELEASE AND CLINICAL DATA AND DEPLOYED VALIDATEDOMIC TOOLS TO IDENTIFY MECHANISMS OF RESISTANCE INTRINSIC AND EXTRINSIC AND FINALLY WORKFLOW ENABLES US TO ORGANIZE INTEGRATED RESULTS FOR DISCOVERY RESEARCH AND FOR CLINICAL ACTION. NEXT SLIDE. FROM A BIOPSY POINT OF VIEW, ESSENTIALLY WHAT WE ARE DOING IS ACQUIRING SERIAL BIOPSIES AND PREPARING IN VARIETY OF DIFFERENT WAYS AND FIXATION AND ALD AHIDE FIXATION FOR EM AND [INAUDIBLE] FOR PROTEOMIC ANALYSIS AND FROZEN SPECIMENS FOR SPATIAL ANALYSIS. ALL THIS IS DONE QUICKLY AND THE AVERAGE TIME FROM ACQUISITION TO BIOPSY TO STARTING PRESERVATION IS ABOUT TWO MINUTES AND WE DO THE BEST WE CAN IN TERMS OF PRESERVING SPATIAL FEATURES IN PROETEE OHM AND REPORT OUT ABOUT 11 DIFFERENT ANALYTICAL METRICS BASED ON WORKFLOW THAT WE CAN REALLY EXECUTE ON EACH PATIENT. NEXT SLIDE. ONE OF THE THINGS THAT IS IMPORTANT ABOUT ALL THIS IS TO CAPTURE AS MUCH CLINICAL INFORMATION AS WE CAN. THIS INITIALLY TURNED OUT TO BE QUITE COMPLICATED AND MORE OR LESS AUTOMATED PROCESS SO MOST CLINICAL INFORMATION WE CAPTURE AND REPORT OUT IS AUTOMATICALLY EXTRACTED FROM ELECTRONIC HEALTH RECORDS. THIS ALLOWS US TO COMBINE VARIOUS CLINICAL DATA ELEMENTS AND ASSAY RESULTS AND PULL IT OUT AND PULL INTO CLINICAL DATA MANAGEMENT SYSTEM WHERE WE CAN COMBINE CLINICAL INFORMATION WITH RESEARCH USE ONLY DATA AND COMBINATION OF DATA ARE PRESENTED TO RESEARCH BOARDS FOR MECHANISM DISCOVERY AND CLINICAL TUMOR BOARDS AND [INAUDIBLE] IS PRESENTED TO CLINICAL BOARDS FOR PATIENT MANAGEMENT. NEXT SLIDE FROM AN OMIC PERSPECTIVE WHAT WE ARE ATTEMPTING TO DO IS IDENTIFY MECHANISMS FROM COMPARATIVE ANALYSIS THROUGH RNA SEEK AND DNA SEEK PROTEIN COMPARATIVE DATA AND SAMPLES AND COMPARING PATIENTS AND SMART COHORT AND TCGA AND ATTEMPT TO IDENTIFY FEATURES ASSOCIATED FOR EXAMPLE WITH RESPONSE TO PRECLINICAL DATA SETS AND ALL CASES I SAID BEFORE EMPHASIS IS ON IDENTIFYING ACTIONABLE MECHANISMS AND QUANTIFYING MULTIPLE METRICS FOR EVERY ANALYSIS AND SINGLE GENE EXPRESSION AND PROTEIN ABUNDANCE AND GENE SET ENRICHMENT DATA MASTER REGULATOR ACTIVITY AND SEND TRANSCRIPTIONAL SIGNATURES AND FOCUS ON TUMOR ENTRIN SDIK AND EXTRINSIC MECHANISMS AND IN CASE WE DO DISCOVER POTENTIALLY ACTIONABLE MECHANISMS IN RESEARCH DATA WE HAVE OPPORTUNITY TO DO REFLEX TESTING USING CLEA APPROACHED ASSAYS SO THEY CAN BE WITH PATIENT MANAGEMENT AND FROM IMAGING POINT OF VIEW WE DEPLOY MULTISCALE AND MULTIPLEX IMAGING THAT IS AS MARJA DESCRIBED AS SOMETHING THAT IS BEING WORKED ON INTENSELY THROUGH THE H TAN COLLABORATIONS AND IN MULTIPLEX IMMUNOANALYSIS AND WE ARE WORKING ON DATA OR ASSAY DEVELOPMENT AND DEVELOPMENT OF METADATA STANDARDS TRYING TO UNDERSTAND HOW DATA AND MIHC DATA COMPARES TO MULTIPLEX IMAGING MODALITIES ARE DEPLOYED IN H TAN AND WORKING WITH GROUP ON CELL SEGMENTATION AND PROXIMITY ANALYSIS AND DEVELOPMENT OF DATA DICTIONARIES TELLING US WHAT VARIOUS PIPES AND FUNCTIONALITIES OF CELLS ARE THAT COMPRISE OUR TISSUES DEPLOYING 2D AND ELECTRON MIKE ROSS COPY AND FEATURES OF CANCERS AND EMPHASIS IS ON ACTION ABILITY. NEXT SLIDE, PLEASE. THIS GENERATES A LOT OF DATA AND MULTIPLE DATA TYPES BOTH CLINICAL AND RESEARCH AND WE HAVE DEVELOPED A ROBUST DATA MANAGEMENT SYSTEM PRIMARILY AROUND THE LAB KEY SYSTEM THAT ALLOWS US TO MANAGE MULTIPLE DATA TYPES ALLOWING US TO VISUALIZE THEM VIA WEB BROWSERS AND IMPORTANTLY WE HAVE THIS ORGANIZED AND IS VEENENTALLY ABLE TO EXPORT DATA VIA API TO DCC FOR DISTRIBUTION AS ETHAN DESCRIBED. NEXT SLIDE, PLEASE. WHAT I WILL DO NOW IS TO TAKE YOU THROUGH A FEW ELUS TRATTIVE RESULTS FROM THE PAPER I PUBLISHED ON A SINGLE PATIENT WITH POSITIVE METASTATIC BREAST CANCER AND NEXT SLIDE, PLEASE. CLINICAL PERSPECTIVE WURNGS THING THIS ALLOWS US TO DO IS CAPTURE DETAILED INFORMATION ABOUT THE TREATMENT INCLUDING ACCURATE RECORDING OF DRUG TREATMENT TIME AND DOSE. AGAIN, THIS ALLOWS US TO TREAT THESE OR TREATMENTS NOW AS INFORMATIVE PERTUBATIONS AND KEEP TRACK OF NOT ONLY ANTICANCER DRUGS BEING DEPLOYED BUT SUPPORTING DRUGS SINCE THEY MIGHT HAVE POTENTIAL TO INTERACT WITH ANTICANCER DRUGS AND STIMULATE BIOMARKERS TO FORMULATE RESPONSE AND CT AND PET IMAGING REPORTING ON INDIVIDUAL LESION RESPONSES AND WHAT WE SEE FROM ALL THIS IS FIRST STRONG AND TRANSIENT RESPONSES TO EACH TREATMENT PHASE TO INDUCTION OF RESPONSE TO SEE PROGRESSION. FROM IMAGING DATA WE GET REMARKABLE INFORMATION ABOUT HETEROGENOUS RESPONSES OCCURRING TEMPORALLY AND ALSO BETWEEN LESIONS AND SEE LESIONS AT ONE TIME RESPONDING AND OTHERS NOT AND GIVES GOOD INFORMATION ON HETEROGENEITY. NEXT SLIDE, PLEASE. GENOMIC PERSPECTIVE WE GET GOOD MEASURES HOW IT IS TUMORS EVOLVE UNDER TREATMENT AND TYPICALLY WE SEE IN THIS PARTICULAR CASE WE SEE A FEW UBIQUITOUS MUTATIONS AND PRIVATE ONES IT THAT OCCUR AS TUMOR EVOLVES AND IDENTIFIED CLINICALLY RELEVANT MUTATIONS AND DELETIONS IN D1 AMPLIFICATION THAT IS PRESENT IN ALL OF THE BIOPSIES AND PICKED UP PIC 3C MUTATION AND KINASE INHIBITOR AND PICKED UP AMPLIFICATION OF -- AFTER TREATMENT WITH CRYTOMEAN AND FOUND -- TARGET FOR CAPE CRYTOBEEN THAT IS AMPLIFIED AND NONRESPONSE SYSTEM AND THINK THAT IS WHY TUMOR EVOLVED ON CAPE SIDO BEAM AND INTERESTINGLY ENOUGH BIOPSY 3 IN PARTICULAR STUDY TURNED OUT TO BE EVOLUTIONARILY MUCH EARLIER WITH TEMPORAL TIME AND LEADING TO BELIEVE THIS IS A RESULT WITH EARLIER TUMOR BEING PERHAPS A SLOW GROWING AND SELECTED CADENCE IT THAT WE DEPLOYED. NEXT SLIDE COMPARING TRANSCRIPTOMICS AND PROTEOMIC ANALYSIS AND BIOPSY 2 AND OTHER BIOPSIES IN COHORT AND YOU CAN SEE STRONG INDUCTION OF INTERFERENCE AND QUITE A LARGE NUMBER OF INTERLEUKINS AS RESULT OF TREATMENT INCREASED KRAZ SIGNALING AND NONCANON CAL REACTION THAT SUGGESTED THAT PATIENT MIGHT BE SUSCEPTIBLE OR SENSITIVE TO THIS EVEN THOUGH SHE WAS PROGRESSING ON [INAUDIBLE] THAT WAS LATER CONFIRMED CLINICALLY AND NEXT SLIDE, PLEASE FROM IMMUNE PERSPECTIVE AND ASSAY DEVELOPED LABORATORY AND AGAIN FOCUSING ON BIOPSY 2 AND [INAUDIBLE] WAS PRESENT AND WE SAW INCREASED MACRO FILL OJ MONOCITES REDUCED T REGULATORY CELLS AND DECREASED EXHAUSTED LATE EFFECT POSITIVE T CELLS ALL THIS INDICATING POTENTIAL FOR ANTI-PD1 RESPONSE. NEXT SLIDE. TUMOR MICRO ENVIRONMENT INFORMATION THAT WE GET AND ESSENTIALLY THIS GIVES US INFORMATION ABOUT THE TUMOR AND STROEMO COMPOSITIONS STATES AND INTERACTIONS AND GIVES INFORMATION ABOUT THE INTERACTIONS AND ONE THING THAT WAS INTERESTING IN THIS ANALYSIS WAS THE APPEARANCE OF TUMOR NESTS THAT ARE ENCOMPASSED BY STROEMO CELLULAR ECM BOUNDARIES THAT IS FUNCTIONALLY IMPORTANT AND ONE THING NOTED IF IN SPATIAL ANALYSIS TUMOR EXPRESSION AND PROLIFERATION APPEARS TO INCREASED IN CELLS THAT ARE IN CLOSE PROXIMITY TO COLOGIN BOUNDARIES. NEXT SLIDE. WE HAVE INTERESTING INFORMATION FROM OUR 3D ELECTRON MICROSCOPY THAT WE THINK IS ACTIONABLE. WE SAW A REMARKABLE MANNEST STATION OF FILLO POED YA PROTRUSIONS IN THIS PARTICULAR TUMOR THAT CHANGED OVER TIME THAT MIGHT IN FACT PLAY A ROLE IN FLD MEDIATED MOTILITY AND INHIBITION OF RECEPTOR RECYCLING AND SAW INTERESTING EVIDENCE FOR FORCED MITOCHONDRIAL NUCLEAR INTERACTIONS PERHAPS AS RESULT OF CELL MOVEMENT THROUGH THE TISSUE AND SAW MITOCHONDRIA FORCED INTO FOLDS OF THE NUCLEI IN WAYS WE SPECULATE IN NUCLEAR -- AND REPAIR DAMAGED MECHANISMS AND SAW INCREASES IN ACIDIC LYSOSOMES THAT IS IMPORTANT AND KNOWN MECHANISM BY WHICH CELLS COULD SEQUESTER BASIC DRUGS AND RENDER THEM INOPERATIVE THAT IS THERAPIUTICALLY REVERSIBLE POTENTIAL EVENT AND STRONG NUTRIENT SKAFAGEING AND POINT OF VIEW THAT IS INTERESTING BECAUSE GIVES OPPORTUNITY TO TREAT WITH PROTEIN CONJUGATED TOXINS THAT MIGHT CONVERT MACRO PENCEATOSIS SURVIVAL MECHANISM IN [INAUDIBLE] AND NEXT SLIDE, PLEASE. THAT IS WHERE WE ARE AND THAT IS ONE PATIENT AND WE HAVE TO NOW MOVE FROM THE SINGLE PATIENT TO COHORT STUDIES AND JEREMY HAS THIS UNDERWAY. WE ANALYZED 5 PATIENTS LOOKING MORE OR LESS LIKE THE ONE I JUST TALKED ABOUT. EARLY INFORMATION THAT COMES OUT OF THAT ANALYSIS IS THAT TUMOR INTRINSIC MECHANISMS OF RESISTANCE ARE QUITE DIVERSE AND ARE MANY WAYS TO INCREASE PROLIFERATION AND THEY VARY FROM TUMOR TO TUMOR AND FOCUS ON TUMOR EXTRINSIC MECHANISMS OF RESISTANCE THEY ARE SIMILAR ON IMMUNE MODULATION AND MANAGING EXTRA CELLULAR MECHANISMS MIGHT BE EASIER THAN INTRINSIC MECHANISMS AND LOOKING TO INCREASE SIZE OF COHORTS AND DO WORK TO DEFINE MINIMUM ASSAY REQUIREMENTS ARE AND RUNNING BIG WORKFLOW AND WOULD LIKE TO DECREASE IT AS MUCH AS POSSIBLE AND WE THINK THAT HAVING INFORMATION FROM THREE DIMENSIONS IS REALLY REMARKABLY MORE POWERFUL IN ELUS DATING MECHANISMS IN TWO DIMENSIONS AND WANT TO MOVE IN THAT DIRECTION AND ARE VERY MUCH INTERESTED IN GENERATING INTEGRATED MULTIMODAL AND SPATIAL BIOMARKERS IN RESPONSE IN RESISTANCE THAT COULD BE TESTED IN LARGER CLINICAL TRIALS AND THINK IT IS REALLY IMPORTANT TO CONNECT ATLASES WE ARE GENERATING TO SYSTEMS BIOLOGY COMMUNITY TO HELP ELUS DATE FUNCTIONS THAT ARE INFLUENCED BY INTERACTIONS WE ARE SEEING AND TO HELP IDENTIFY SYNERGISTIC TREATMENTS TO HELP COUNTER SOME TEMPORAL EVOLUTION AND SPATIAL HETEROGENEITY WE ARE OBSERVING AND WE ARE INTERESTED IN COMING UP WITH ALTERNATIVES TO INVASIVE BIOPSIES THAT ARE DIFFICULT TO GET AND ARE SUBJECT TO HETEROGENEITY THAT EXISTS SPATIALLY WITHIN THE PATIENT. WE ARE TURNING TO LIQUID BIOPSIES THAT ARE ASSISTED BY FOCAL IRRADIATION OF SELECTED LESIONS AND TWO MOLECULARLY ATOMIC LESION IMAGING AND NEXT SLIDE AND BRINGS ME TO SUMMARY AND WE ARE TO POINT NOW WE DEMONSTRATED WE CAN RELY BRI AND ROUTINELY EXECUTE SERIAL MULTIMODAL ANALYSIS OF EVOLVING TUMORS AND DO THESE WORK FLOWS IN CLINICAL REAL TIME AND HAVE SHOWN IN EACH ANALYSIS MODALITY PROVIDES NOVEL INSIGHTS TO RESISTANCE RESPONSE MECHANISMS AND INTEGRATED VIEW IS A MUCH MORE POWERFUL VIEW OF RESISTANCE AND RESPONSE THAN YOU GET WITH EVERY SINGLE MODALITY AND THINK CAREFUL MONITORING AND TREATMENTS OF TIMING WILL ALLOW DISINFORMATIVE PERTURBATIONS AND ANALYSIS OF SERIAL BIOPSIES REVEAL ACTUAL DIFFERENCES [AUDIO STOPPED] OTHERS HAVE POINTED OUT THIS IS A LARGE MULTIDISCIPLINARY TEAM CARRYING OUT STUDIES I TALKED ABOUT CENTER IS LED CURRENTLY BY JEREMY GEX AT HSU AND IMPORTANT COLLABORATIONS WITH LABORATORY AT HARVARD AND LABORATORY AT MD ANDERSON AND SUPPORT FROM QUANTITATIVE IMAGING SYSTEMS FROM [INAUDIBLE] AND MICHELLE L.. THANK YOU. >> THANK YOU. I'M SURE THAT ALL OF THE ATTENDEES AGREE WITH SORT OF EXCITING, YOU KNOW, FANTASTIC SERIES OF TALKS THAT WERE PRESENTED THANKS TO YOU AND MARTHA AND ETHAN FOR PROVIDING REAL SORT OF BIRD'S EYE VIEW OF WHAT IS GOING ON WITH H TAN. WE ARE SLATED TO END AT 3:20. I HAVE BEEN GIVEN GO AHEAD TO EXPAND IN 5 MINUTES OR SO AND CAN END AROUND 3:25 TO GET IN MORE QUESTIONS AND THERE IS ACTIVE COMMENTARY AND DISCUSSION IN THE CHATS THAT COULD BE ADDRESSED. SO, I WILL START WITH I SEE ANNE'S HAND AND TREY'S HAND. WE WILL START THERE. >> FIRST, THANK YOU, EVERYBODY. ALL THREE PRESENTATIONS WERE JUST UNBELIEVABLE AND VERY, VERY NICE WORK. JOE, THINKING ABOUT YOUR COMMENT ON CONNECTING THIS TO ASSISTIVE BIOLOGY AND LISTENING TO ALL THREE PRESENTATIONS ACROSS ALMOST ALL BUY LOGIC SCALES THAT ARE HERE IN THEES TRACE ANALYSIS AND WONDERING COMING BACK TO YOUR FOCUS ON EVOLUTION IT IS A COMPLEX ADAPTIVE SYSTEM AND WE SHOULD START TO THINK THAT WAY AND IS IT POSSIBLE TO START TO THINK ABOUT COMBINING DATA THROUGH, YOU KNOW, SOME REALLY GOOD MODELS AND THEORETICAL CONSTRUCTS TO START TO PREDICT CHANGES IN FITNESS LANDSCAPES THAT ARE OCCURRING? WITH THIS DATA YOU CAN START WITH ESPECIALLY SPATIAL DATA YOU CAN START TO PREDICT WHEN FITNESS LABDSCAPES ARE CHANGING IN CELLS AND DON'T KNOW HOW QUICKLY WE CAN DO THIS BUT IT IS DOABLE WITH DATA YOU ARE GENERATING, JOE. >> SO DO WE. I THINK SYSTEMS BIOLOGY COMMUNITY IS BEGINNING TO APPRECIATE FACT THAT DATA IS AVAILABLE AND YOU MADE POINT WE ARE REPORTING OUT SNAPSHOTS OVER TIME OF THE CHANGES IN THE SYSTEMS IT THAT ARE RESPONDING TO PERTURBATIONS AND NEAT THING ABOUT KEEPING TRACK OF DRUG TREATMENTS AND INDIVIDUAL DOSE TIME IS IT ALLOWS YOU TO THINK ABOUT YOUR DATA AS A PERTURBED SYSTEM IT THAT YOU NEED IN SYSTEMS BIOLOGY STUDIES AND TAKING THAT INFORMATION DEVELOPING MODEL SYSTEMS IN LABORATORY TO TAKE SAME KIND OF PERTUBATION DATA AND BRING IT THERE I BELIEVE IN FACT WE ARE POISED TO UNDERSTAND HOW IT IS ALL OF THE INTERACTIONS BETWEEN TUMOR AND STROMAL CELLS THAT INFLUENCE THERAPEUTIC RESPONSES. >> THIS IS WHAT WE DREAMED OF STARTING TCGA. CONGRATULATIONS. >> AMAZING. TREY? YOU ARE MUTED. >> HOW ABOUT NOW? >> THERE YOU GO. >> THANKS, JOHN. THIS COMMENT HOPEFULLY FOLLOWS ABOUT DIFFERENT LEVELS IT THAT ONE CAN BUILD ATLASES AND HAVE SEEN THREE BEAUTIFUL TALKS WITH DIFFERENT WAYS OF SYSTEMATICALLY BUILDING DIFFERENT KINDS OF CANCER ATLASES AND THINK A GOOD BSA-LEVEL DISCUSSION WOULD BE WHAT IS THE SCOPE OR INTENDED SCOPE OF H TAN? WHAT IS IT NOT MEANT TO COVER IN TERMS OF LEVELS AND ATLASES AND IMPRESSION MARK OR ETHAN AND ARE VERY NICELY FOCUSED ON SINGLE CELL AND ABOVE THAT IS ATLAS OF CELLS AND DIFFERENT CELL TYPES AND TUMOR TISSUES AND AT TCGA LEVEL WE HAVE ATLAS OF GENES AND MUTATED GENES AND PROTEINS YOU FIND CURRENTLY IN DIFFERENT COHORTS. I THINK AS JOE'S TALK GETS INTO WHAT IS THE GAP IN BETWEEN THERE IS CANCER MECHANISMS AND PATHWAYS AND EVERYTHING HAD HAPPENING INSIDE OF THE CELL OPPOSED TO SINGLE CELL SUBCELLULAR HALLMARK PATHWAYS CATEGORIZING THOSE SYSTEMATICALLY IS A WORTHWHILE THING TO DO AND OTHER A- THE LASSES THAT PEOPLE HAVE IN MIND AND MY CONCERN WOULD BE WITH BEAUTIFUL DATA WE HAVE ONE LEVEL OF A- THE LASS AND WE MIGHT ASSUME THAT H TAN -- SHOULD WE ASSUME THAT H TAN WILL EXPAND IN FUTURE YEARS TO SYSTEMATICALLY MAP A CANCER MECHANISM AND DAN'S BEAUTIFUL TALK ABOUT SPLICEOSOME IS A COMPONENT OF AN ATLAS THAT NEEDS TO BE BUILT AND PROTEIN COMPLEXES UNDER MUTATIONAL COMPLEXES AND IN CANCER AND IS THAT SOMETHING H TAN WOULD DO OR ANOTHER LATER ON FOLLOW ON PROJECT TO DO? I WILL STAND DOWN. BEAUTIFUL TALKS THAT MAKES P ME THINK ABOUT WHAT IS IN AN A- THE LASS? WHAT IS THE SCOPE OF THIS ONE? >> SURE. I MEAN WE HAVE JOE, MARTHA, AND ETHAN. DON'T KNOW IF EITHER OF YOU WANT TO TAKE A STAB AT THAT. >> I WILL TAKE A STAB AT IT. YOU HIT ON SOMETHING I HAVE BEEN THINKING A LOT ABOUT. AS YOU APPRECIATE FROM THESE TALKS AND, YOU KNOW, 10 OTHERS YOU COULD HAVE HAD TODAY, THERE IS A LOT OF DIFFERENT VIEWS OF CANCER YOU CAN GENERATE THAT ALL INTEGRATE TOGETHER. YOU KNOW, THE MOLECULAR NETWORKS RELATE TO ULTRA STRUCTURE FEATURES RELATING TO CELL INTERACTIONS AND SO ON. AS WE THINK ABOUT WHERE WE ARE GOING IN THE FUTURE AND ONE THING THAT IS MY OWN PERSONAL PERSPECTIVE NOW IT IS HARD TO INTEGRATE BETWEEN DIFFERENT CENTERS AS THEY LOOK AT DIFFERENT CANCERS AND THINK IF WE WILL GENERATE A COMPREHENSIVE A- THE LASS YOU HAVE TO FOCUS ON ONE CANCER TYPE TO SEE WHAT YOU CAN LEARN FROM FROM DIFFERENT TYPES OF PEOPLE. >> YOU ARE SPOT ON WITH THATTLAS YOU HAVE TO FOCUS ON ONE CANCER TYPE TO SEE WHAT YOU CAN LEARN FROM FROM DIFFERENT TYPES OF PEOPLE. >> YOU ARE SPOT ON WITH THAT. GREAT POINT. TREY, YOUR QUESTION IS A GOOD ONE. I WILL TAKE ANOTHER LEVEL TALKING ABOUT SALE AND PATHWAYS AND WHAT ABOUT TISSUE PHYSIOLOGY; RIGHT? HYPE OXY AND HYPOXY REGIONS AND SPECIES AND DIFFERENT THINGS PLAY AN IMPORTANT ROLE IN THE MICRO ENVIRONMENT AND WE HAVE SHANDRA AND MICHAEL'S HANDS AND I WILL DO THE LAST TWO QUESTIONS BEFORE WE ADJOURN. CHANDRA AND MICHAEL. >> CAN YOU HEAR ME. >> YES. >> THANK YOU FOR THE WONDERFUL PRESENTATION. >> WE CAN BARELY HEAR YOU. >> HOW ABOUT NOW? >> THAT IS A LITTLE BETTER. >> OKAY. I THOUGHT THOSE WERE EXCELLENT PRESENTATIONS AND EXCITING TIMES AND HAD SOME. >> WE STILL CAN'T HEAR YOU. >> I HAVE SOME GENERAL QUESTIONS. >> YOU NEED TO GET REALLY CLOSE TO YOUR MIC. >> WHY DON'T YOU HAVE THE OTHER PERSON GO. >> OKAY, MICHAEL. YUP. FEEL FREE TO TYPE YOUR QUESTION OR COMMENT IN THE CHAT, KHUNDRA. MICHAEL. >> CAN YOU HAD HEAR ME CLEARLY? >> YEAH. >> OKAY. SPATIAL BIOLOGY AREA WE ARE ENTERING IN WITH CELL INTERACTIONS AND ROLE AGAINST BIG CANCERS ARE CLEARLY AT CENTER OF THE GOAL HDM PROGRAM AND KUDOS ON THIS BUT THIS PARTICULAR PROGRAM WAS HELD AS GREAT PROMISE FOR FUELING MOON SHOT AND BEYOND LEVELS OF ACTIVITIES AND WHAT IS LEVEL OF INTERACTION WITH SYSTEMS BIOLOGY CONSORTIUM AND ANY DISEASE-FOCUSED SPORES OR ANY OTHER MANY PIECES OF DIFFERENT ARCHITECTURE WITHIN NCI AND HOW ARE WE GOING TO MAKE THE BRIDGE BETWEEN THESE MAPS AND ACTUALLY APPLICATIONS IN TRANSLATION? >> I'M NOT SURE IF THAT IS A QUESTION TO ANY OF US BUT I HAVE A COMMENT ON IT. IT THAT IS THAT I THINK IF YOU LOOK AT ALL OR MANY H TAN CENTERS THAT ARE ALREADY INDIVIDUALLY CONNECTING WITH SPORES AND IN OUR CASE WE ARE CONNECTING WITH CLINICAL PROGRAMS AND WITH THE SYSTEMS BIOLOGY COMMUNITY. IT IS ALREADY BEGINNING TO HAPPEN, I THINK. PERHAPS NOT IN AS FORMAL OF A WAY AS YOU WOULD LIKE. I THINK IT WOULD TAKE ONLY A SMALL NUDGE TO GET IT TO HAPPEN PRETTY ROBUST WILL I. >> ADDING TO THAT TOO BUT WITH CAVEAT I'M EPIDEMIOLOGISTS OF THE GROUP AND NOT SYSTEMS BIOLOGIST. WE HAVE SEEN A NATURAL INVOLVEMENT ACROSS CENTERS INDIVIDUALS THAT ARE INVOLVED IN OTHER ACTIVITIES ARE ALSO PART OF H TAN CENTERS AND THERE HAVE BEEN JOINT SESSIONS FOR EXAMPLE TO LOOK AT METHODS FOR ANALYSIS. I MENTIONED TMPS THAT WE ARE LOOKING TO CROSS CONSORTIA TO WORK TOGETHER TO DEVELOP METHODS AND I AGREE WITH JOE THAT SOME IS HAPPENING AND HAPPENING WITH INTENTION WITHIN H TAN AND SOME IS HAPPENING BECAUSE THERE IS -- INVESTIGATORS ARE RECOGNIZING THAT NEED. THEY ARE INVOLVED ALSO IN SOME OF THOSE AND CERTAINLY IF THERE IS WAYS TO IMPROVE THAT AS WELL. >> THIS IS A FOLLOW-ON QUESTION. YOU KNOW, DATA SHARING WAS CENTRAL TO MOON SHINE AND HTN AND ITS PLANS AND FI GO TO GDC TODAY I CAN'T SEE ANY OF THIS MUCH LESS THE MAJORITY OF MOON SHOT INITIATIVE DATA. HOW WILL WE CATCH UP AND FULFILL A PROMISE WE STARTED WITH AND MAKE IT REAL? DATA SHARING TO ME REMAINS A MAJOR CONCERN. WE ARE SPENDING HUNDREDS OF MILLIONS OF DOLLARS IN PUTTING REALLY IMPORTANT DATA OUT THERE BUT ARE NOT GETTING TO THE GOAL OF GDC OR YET TO BE DEFINED ENTITY AND USING A MECHANISM THAT IS NOT IN MY MIND GDC COMPLIANT AND HAVE GREAT CONCERN CONCERN. >> WE SPEND A LOT OF TIME AT THE DCC THINKING ABOUT DATA SHARING MECHANISMS IN MY TALK AND THINK LONG TERM VISION OF H TAN IS WE WON'T HOST DATA ON INFRASTRUCTURE WE HAVE AND ALL DATA WILL GO TO LARGER NODES WITHIN CANCER RESEARCH DATA COMMONS AND THERE ARE OTHER NODES WE INTERACT WITH AND -- AROUND DATA DISTRIBUTION DATA STANDARDS AND IF YOU THINK ABOUT WHERE DO WE GO WITH DATA IN THE LONG TERM AND DATA WE FOCUS ON NOW IS HAVING FLEXIBILITY TO HAVE -- FOR EXAMPLES I SHOWED HERE AND LONG TERM VISION IS TO MAKE SURE THAT ALL DATING AH GOES INTO LARGER DATA ECOSYSTEM AND SPEND A LOT OF TIMES WITH MEMBERS IN LARGER VISION THAT NCI SENDS OUT. >> FUNDING AS WELL AND [INAUDIBLE] NETWORK THAT OBVIOUSLY HAS BROAD IMPLICATIONS TO MANY CANCERS AS WELL AS AGING AND TROUBLES ME TO SEE ARCHITECTURE AND GDC ON ANOTHER ARCHITECTURE AND SEND THAT PROPOSING CENTRAL TO COMMON FUND ARCHITECTURE AND NONE OF THESE THINGS WILL MEET IN THE MIDDLE UNLESS WE GET BUSY TAKING INVESTMENT WITH NCI MAKING THEM REAL TO ESSENTIALLY A WINNING NIHWIDE DATA SHARING INFRASTRUCTURE. IT IS A CHALLENGE. >> HUGE CHALLENGE, MICHAEL. AS WE CONTINUE TO INTEGRATE MULTIDIMENSIONAL DATA I'M TRYING TO UNDERSTAND HOW DATA SORT OF INTEGRATE AND INTERACT WITH EACH OTHER AND FANTASTIC SET OF TALKS AND THANKS SO MUCH FOR THOSE UPDATES AND NOW THE BOARDS WILL TAKE A BREAK. THE OPEN SESSION IS NOW ADJOURNED. SO, THIS CONCLUDES TODAY'S MEETING. WE LOOK FORWARD TO SEEING YOU TOMORROW VIRTUALLY.