Search Institute

IMMUNE TOLERANCE NETWORK

TECHNOLOGY TO EMPOWER CHANGES IN HEALTH (TECH) NETWORK PARTICIPANT TECHNOLOGIES CENTER

CONSORTIUM FOR HIV/AIDS VACCINE DEVELOPMENT

MICROBICIDE TRIALS NETWORK

THE BAY AREA ENVIRONMENTAL RESEARCH INSTITUTE (BAER INSTITUTE OR BAER), IN COOPERATION WITH THE UNIVERSITY CORPORATION AT MONTEREY BAY ON BEHALF OF C

CENTER FOR HIV/AIDS VACCINE IMMUNOLOGY AND IMMUNOGEN DISCOVERY

THE SOUTHWEST NATIONAL PRIMATE RESEARCH CENTER

THE COMPREHENSIVE CENTER FOR CHEMICAL PROBE DISCOVERY AND OPTIMIZATION AT SCRIPPS

BURNHAM CENTER FOR CHEMICAL GENOMICS

THE RECIPIENT WILL DESIGN, DEVELOP AND MANAGE A NETWORK OF OFFICES, PHYSICAL AND DIGITAL HUBS, AND OTHER COLLABORATIVE PARTNERSHIPS AND PROJECTS DESIGNED TO LOWER THE BARRIERS FOR ENTRY FOR COMMERCIAL AND DUAL-USE TECHNOLOGY INTO THE DEPARTMENT OF DEFENSE.

CONSORTIUM TO STUDY THE GENETICS OF LONGEVITY

NATIONAL FUNCTIONAL GENOMICS CENTER

CENTER FOR ANTIVIRAL MEDICINES & PANDEMIC PREPAREDNESS (CAMPP) - SUMMARY THE ONGOING COVID-19 PANDEMIC HAS BROUGHT TO LIGHT AN URGENT NEED TO ENHANCE THE THERAPEUTIC PREPAREDNESS FOR FUTURE VIRAL OUTBREAKS AND PANDEMICS. THE OVERARCHING GOAL OF THE “CENTER FOR ANTIVIRAL MEDICINES & PANDEMIC PREPAREDNESS” (CAMPP) IS THUS TO DEVELOP NOVEL STRATEGIES AND ENHANCE THE DRUG DISCOVERY PIPELINES FOR DIRECT-ACTING ANTIVIRALS AGAINST RNA VIRUSES OF PANDEMIC CONCERN. THE SPECIFIC FOCUS OF CAMPP WILL BE TO DEVELOP ANTIVIRALS AGAINST CORONAVIRUSES SARS-COV-2 (SCV2), SARS AND MERS; FLAVIVIRUSES INCLUDING ZIKA, WEST NILE AND DENGUE VIRUS; AND HEMORRHAGIC FEVER VIRUSES INCLUDING THE FILOVIRUS EBOLA, AND BUNYAVIRUSES SEVERE FEVER WITH THROMBOCYTOPENIA SYNDROME VIRUS AND LASSA VIRUS. INFECTION BY ANY OF THESE AGENTS HAS THE POTENTIAL TO CAUSE SEVERE HUMAN DISEASE WITH SIGNIFICANT MORTALITY RATES AND CURRENT OPTIONS FOR ANTIVIRAL TREATMENTS ARE LIMITED. THE ANTIVIRAL DRUG REMDESIVIR AND SEVERAL MONOCLONAL ANTIBODY TREATMENTS HAVE RECEIVED EMERGENCY USE AUTHORIZATION (EUA) FOR TREATMENT OF COVID-19, AND THE POLYMERASE INHIBITOR MOLNUPIRAVIR BY MERCK IS EXPECTED TO BE GRANTED EUA IN THE NEAR FUTURE. MONOCLONAL ANTIBODIES ARE ALSO AVAILABLE TO TREAT EBOLA VIRUS INFECTION, HOWEVER, NONE OF THESE DRUGS CAN BE ADMINISTERED ORALLY, POSING ADDITIONAL CHALLENGES IN TREATING EARLY INFECTION. THERE ARE NO APPROVED TREATMENTS FOR THE CAMPP FLAVIVIRUSES AND HEMORRHAGIC FEVER VIRUSES. TOWARD THIS END, WE HAVE ASSEMBLED A WORLD CLASS MULTIDISCIPLINARY TEAM OF INVESTIGATORS WITH EXPERTISE IN VIROLOGY OF RELEVANT VIRUSES, STRUCTURAL AND COMPUTATIONAL BIOLOGY, CHEMOPROTEOMICS, PHARMACOLOGY AND ORGANOID/ANIMAL MODELS, WHO WILL WORK CLOSELY WITH THE DRUG DEVELOPMENT EXPERTS AT THE DRUG DISCOVERY DIVISION OF THE SCRIPPS RESEARCH INSTITUTE, CALIBR, TO FURTHER THE DEVELOPMENT OF FOUR MAJOR CLASSES OF PROMISING ASSETS IN OUR DRUG DISCOVERY PIPELINE. FIRST, WE PROPOSE TO DEVELOP A POTENTIALLY BEST-IN-CLASS, ORALLY BIOAVAILABLE CORONAVIRUS PROTEASE (CLPRO) INHIBITOR FOR CORONAVIRUSES INCLUDING SCV2, FROM A LATE-STAGE DRUG ASSET UNDERGOING ADME OPTIMIZATION THAT IS EXPECTED TO ENTER IND-ENABLING STUDIES WITHIN THE NEXT THREE YEARS. SECOND, WE WILL IDENTIFY AND OPTIMIZE RNA POLYMERASE INHIBITORS FOR SCV2 AND OTHER CAMPP VIRUSES, WITH THE GOAL OF REACHING IND-ENABLING STUDIES WITHIN THE NEXT FOUR YEARS. THE THIRD FOCUS OF OUR PROPOSAL IS TO DEVELOP ANTIVIRALS AGAINST OTHER ‘DRUGGABLE’ PROTEINS ENCODED BY SCV2 AND ADDITIONAL VIRUSES POSING A PANDEMIC THREAT; THESE ASSETS INCLUDE INHIBITORS OF SCV2 HELICASE, E-PROTEIN ENCODED ION CHANNEL ACTIVITY, ENTRY AND FUSION ACTIVITIES, AND NUCLEOCAPSID, WITH THE GOAL OF OBTAINING IN VIVO PROOF-OF-CONCEPT FOR A SUBSET OF THESE MID-STAGE ASSETS. FINALLY, WE PROPOSE TO TARGET TRADITIONALLY CONSIDERED ‘UNDRUGGABLE’ NON-ENZYMATIC PROTEINS INCLUDING SCV2 AND FLAVIVIRAL STRUCTURAL PROTEINS AS WELL AS RNA STRUCTURE, TO DEVELOP NOVEL STRATEGIES FOR ANTIVIRAL DRUG DEVELOPMENT. CAMPP PROVIDES A HIGHLY INTEGRATED INFRASTRUCTURE OF INVESTIGATORS, EXPERTISE AND EXTERNAL PHARMACEUTICAL AND FOUNDING PARTNERS THAT WILL ENSURE THE CENTER’S SUCCESS IN ACHIEVING OUR GOALS AND NAVIGATING CHALLENGES OF THE DRUG DISCOVERY PROCESS.

MOFFITT CANCER CENTER SUPPORT GRANT

INFECTIOUS DISEASE, VACCINE, CLINICAL TRIALS AND ENTOMOLOGY AWARD (IDVCTEA)

MATRIX - MICROBICIDE 2021 R&D PROJECT: ADVANCING THE RESEARCH AND DEVELOPMENT OF INNOVATIVE HIV PREVENTION PRODUCTS FOR WOMEN

CANCER CENTER SUPPORT GRANT

APPLICATION FOR A RENEWAL OF THE ARC-CREST COOPERATIVE AGREEMENT.#NNX12AD05A

ASPIRIN IN REDUCING EVENTS IN THE ELDERLY

THE UNITED STATES AGENCY FOR INTERNATIONAL DEVELOPMENT (USAID), THROUGH THE CENTER FOR DEVELOPMENT RESEARCH (CDR) IN THE U.S. GLOBAL DEVELOPMENT LAB (LAB) PLANS TO INVEST IN A FIVE-YEAR COOPERATIVE AGREEMENT WITH A HIGHER EDUCATION INSTITUTION (HEI) TO SUPPORT A PROJECT ENTITLED LONG-TERM ASSISTANCE AND SERVICES FOR RESEARCH (LASER). THIS COOPERATIVE AGREEMENT AIMS TO SUPPORT THE DISCOVERY AND UPTAKE OF UNIVERSITY-SOURCED, EVIDENCE-BASED SOLUTIONS TO DEVELOPMENT CHALLENGES.

KANSAS IDEA NETWORK OF BIOMEDICAL RESEARCH EXCELLENCE

COG BIOSPECIMEN BANK

MID-SCALE RI-2 CONSORTIUM: BIOGEOCHEMICAL-ARGO: A GLOBAL ROBOTIC NETWORK TO OBSERVE CHANGING OCEAN CHEMISTRY AND BIOLOGY

SYSTEMS APPROACH TO IMMUNITY AND INFLAMMATION

KEMRI/CDC PROGRAM

DIMPLE: DATING AN IRREGULAR MARE PATCH WITH A LUNAR EXPLORER

PEDIATRIC HEART NETWORK DCC

ASPIRIN IN REDUCING EVENTS IN THE ELDERLY - EXTENSION

NORTHSTAR NODE OF THE CLINICAL TRIALS NETWORK

MICROBICIDE TRIALS NETWORK

NHLBI PEDIATRIC TRANSLATIONAL CONSORTIUM ADMINISTRATIVE COORDINATING CENTER

FRONTIERS: THE HEARTLAND INSTITUTE FOR CLINICAL AND TRANSLATIONAL RESEARCH

REIMBURSEMENT OF TRAVEL AND SUBSISTENCE EXPENSES FOR LIVING ORGAN DONATION

JOINT CENTER FOR STRUCTURAL GENOMICS

DATA COORDINATING CENTER FOR THE PEDIATRIC HEART NETWORK

HUMAN DENDRITIC CELLS AND IN VIVO IMMUNITY TO BIOTHREAT

SWOG BIOSPECIMEN BANK

SOUTHWEST NATIONAL PRIMATE RESEARCH CENTER

COORDINATING AND BIOINFORMATICS UNIT FOR THE AMDCC/MMPC

CNS EFFECTS OF ALCOHOL: CELLULAR NEUROBIOLOGY

CANCER CENTER SUPPORT GRANT

ESTABLISHMENT OF A SPF RHESUS MACAQUE COLONY

ASPHALT RESEARCH CONSORTIUM

PHASE II RANDOMIZED CONTROLLED TRIAL OF BENFOTIAMINE IN EARLY ALZHEIMER'S DISEASE - WE PROPOSE A SEAMLESS PHASE 2A-2B TRIAL INVESTIGATING BENFOTIAMINE, A PRODRUG OF THIAMINE, AS A FIRST-IN- CLASS SMALL MOLECULE TREATMENT FOR EARLY ALZHEIMER'S DISEASE (AD). WE CALL THIS PROPOSED TRIAL `BENFOTIAMINE IN EARLY ALZHEIMER'S DISEASE (BEAD)”. BRAIN TISSUE THIAMINE DEFICIENCY CAUSES MEMORY DEFICITS THAT ARE REVERSIBLE WITH THIAMINE TREATMENT IN PRECLINICAL AD MODELS AND IN HUMAN CONDITIONS INCLUDING WERNICKE KORSAKOFF SYNDROME. IN ANIMAL MODELS OF MILD IMPAIRMENT OF OXIDATIVE METABOLISM (I.E., THIAMINE DEFICIENCY), NEURONAL LOSS IS ACCOMPANIED BY CHANGES IN NEUROFILAMENT LIGHT (NFL), BY INCREASED NEUROINFLAMMATION (GLIAL FIBRILLARY ACID PROTEIN GFAP), BY ELEVATION OF ADVANCED GLYCATION END PRODUCTS (AGE) AND BY INCREASED PLAQUE AND BY TANGLE PATHOLOGY, ALL OF WHICH OCCUR IN AD. BENFOTIAMINE DRAMATICALLY RAISES BLOOD AND BRAIN TISSUE THIAMINE IN THESE MODELS, CONFERRING BEHAVIORAL BENEFIT AND REDUCED PLAQUE AND TANGLE FORMATION. WE PREVIOUSLY CONDUCTED AN EARLY PHASE 2 PILOT SINGLE-SITE 12-MONTH DOUBLE BLIND PLACEBO CONTROLLED RCT OF 600 MG OF BENFOTIAMINE IN 71 PERSONS WITH EARLY AD. BENFOTIAMINE WAS WELL TOLERATED, HAD ENCOURAGING PHARMACOKINETIC (PK) AND PHARMACODYNAMIC (PD) RESPONSES AND SHOWED BENEFITS ON THE CLINICAL DEMENTIA RATING (CDR), THE ADAS-COG, AND MARKERS OF BRAIN METABOLISM. THERE IS NEW EVIDENCE IN MICE THAT A 1200 MG OF BENFOTIAMINE FURTHER INCREASES THIAMINE LEVELS WITH GREATER COGNITIVE BENEFITS. THUS, WE ARE PROPOSING AN 18-MONTH PHASE 2A/2B RANDOMIZED PLACEBO CONTROLLED RCT OF BENFOTIAMINE TESTING 600 MG/DAY AND 1200 MG/DAY IN 400 PARTICIPANTS EARLY AD, INCLUDING MILD COGNITIVE IMPAIRMENT (MCI) AND MILD DEMENTIA WITH PLASMA EVIDENCE OF AMYLOID POSITIVITY. OUR OVERARCHING HYPOTHESIS IS THAT SIGNIFICANT BENEFITS IN COGNITION AND GLOBAL FUNCTION WILL OCCUR WITH DOSES OF BENFOTIAMINE THAT ARE SAFE, WELL TOLERATED, AND ACHIEVE SUFFICIENT TARGET ENGAGEMENT. IF THIS PHASE 2 TRIAL IS SUCCESSFUL WE HAVE A CONSOLIDATED SEAMLESS PHASE 3 DEVELOPMENT PLAN TO EXPEDITE BENFOTIAMINE REACHING PATIENTS. WE WILL TEST OUR OVERARCHING HYPOTHESIS THROUGH THE FOLLOWING AIMS:(1) TO EFFICIENTLY DETERMINE THE HIGHEST SAFE AND WELL-TOLERATED DOSE OF BENFOTIAMINE IN PHASE 2A (600 MG OR 1200 MG) THAT CAN BE ADVANCED TO LONG TERM CLINICAL ENDPOINTS AT 72 WEEKS; (2) TO EVALUATE THE EFFICACY OF BENFOTIAMINE IN PHASE 2B, TO BENEFIT (A) GLOBAL FUNCTION MEASURED WITH THE CDR SUM OF BOXES (CDR-SB) AND (B) COGNITION MEASURED WITH ADAS-COG13 DURING A TREATMENT PERIOD OF 72 WEEKS IN EARLY AD; (3) TO EVALUATE THE PK (SERUM THIAMINE AND IT'S ESTERS) AND PD EFFECTS (THIAMINE PYROPHOSPHATE ACTIVATION OF TRANSKETOLASE AND ADVANCED GLYCATION END-PRODUCTS (AGES)) OF BENFOTIAMINE, AND THEIR RELATION TO THE PRIMARY OUTCOMES; (4) TO EVALUATE THE DOWNSTREAM BIOLOGICAL EFFECTS OF TREATMENT WITH BENFOTIAMINE IN EARLY AD ON MEASURES OF NEURODEGENERATION (CORTICAL THICKNESS ON MRI, PLASMA NEUROFILAMENT LIGHT AND TOTAL TAU), NEUROINFLAMMATION (GLIAL FIBRILLARY ACID PROTEIN) AND AD PATHOPHYSIOLOGY INCLUDING P-TAU 231, AND ASS 42/40 RATIO.

CONSORTIUM FOR IMMUNOTHERAPEUTICS AGAINST VIRAL HEMORRHAGIC FEVERS

CONSORTIUM FOR VIRAL SYSTEMS BIOLOGY (CVISB)

SCRIPPS TRANSLATIONAL SCIENCE INSTITUTE

PURPOSE/SCOPE: THE UNIVERSITY OF KANSAS CANCER CENTER RECEIVED COMPREHENSIVE CANCER CENTER DESIGNATION BY THE NATIONAL CANCER INSTITUTE IN 2022. THIS IS THE HIGHEST LEVEL OF RECOGNITION AWARDED BY THE NCI. THE UNIVERSITY OF KANSAS CANCER CENTER WILL BEGIN NEW CONSTRUCTION ON A COMBINATION OF 200,000GSF OF CLINICAL SPACE AND 250,000GSF OF RESEARCH SPACE FOR A TOTAL OF 450,000GSF. THE PROPOSED NIST FUNDED PROJECT WILL PROVIDE CONSTRUCTION OF THE 7TH FLOOR RESEARCH WING AND WILL BE A TOTAL OF 33,000GSF OF RESEARCH AND RESEARCH OFFICE SPACE.ACTIVITIES TO BE PERFORMED: ACHIEVING NCI COMPREHENSIVE CANCER CENTER DESIGNATION WAS NOT THE END OF OUR JOURNEY. FOR LEADERSHIP OF THE UNIVERSITY OF KANSAS AND THE UNIVERSITY OF KANSAS HEALTH SYSTEM, THE WORK IS ONGOING TO SUSTAIN OUR STATUS AS THE PREMIER ACADEMIC MEDICAL CENTER IN OUR COMMUNITY, STATE, AND REGION WHOSE REPUTATION IS RESPECTED NATIONWIDE. THE FUNDING FROM THIS GRANT WILL BE TARGETED TOWARD THE CONSTRUCTION OF ONE OF OUR PRIMARY BASIC RESEARCH FLOORS IN OUR NEW KU CANCER CENTER BUILDING.EXPECTED OUTCOMES: THIS NEW HOME WILL PUT PATIENTS AT THE CENTER OF SCIENCE AND CLINICAL CARE, MAKING THE KU CANCER CENTER A GLOBAL DESTINATION FOR THE BEST IN CANCER TREATMENT. CANCER PROJECTIONS UNDERSCORE OUR URGENCY TO BUILD A NEW CENTRALIZED RESEARCH FACILITY. BY 2040, THE NUMBER OF NEW CANCER CASES PER YEAR IS EXPECTED TO RISE TO 29.5 MILLION AND THE NUMBER OF CANCER-RELATED DEATHS TO 16.4 MILLION. IN ORDER TO CONTINUE TO GROW OUR CANCER CENTER AND EXPAND OUR FOCUS ON IMMUNOTHERAPY AND OTHER PROMISING NEW CANCER THERAPEUTICS, WE WILL NEED TO EXPAND OUR RESEARCH AND CLINICAL TEAMS. FOR EXAMPLE, WITH THE CONSTRUCTION OF THIS BUILDING WE PLAN TO ADD 26 NEW INVESTIGATORS OVER THE NEXT TEN YEARS. THIS WILL BE CRITICAL TO OUR EFFORTS TO EFFECTIVELY SERVE OUR CATCHMENT AREA. IT IS ALSO IMPORTANT TO NOTE THAT A PRIMARY PURPOSE OF OUR NEW BUILDING IS TO CO-LOCATE OUR BASIC SCIENTISTS, OUR CLINICIANS, AND OUR POPULATION HEALTH INVESTIGATORS IN A SINGLE BUILDING WHICH WILL ALLOW INCREASED INTERACTIONS AND COLLABORATIONS.INTENDED BENEFICIARIES:FOR THE PEOPLE IN OUR REGION, COMPREHENSIVE DESIGNATION MEANS GREATER ACCESS TO LEADING-EDGE TREATMENTS, INCLUDING CLINICAL TRIALS, AS WELL AS THE BEST AND BRIGHTEST MINDS IN CANCER. A FACILITY CONTAINING NEARLY ALL BASIC, TRANSLATIONAL AND POPULATION SCIENCE FACULTY ADJACENT TO OUR NEWLY CONSTRUCTED ONCOLOGY IN-PATIENT TOWER WILL BE A SIGNIFICANT CATALYST FOR FURTHER GROWTH AND STRENGTHENING OF OUR CENTER. THIS WILL BE PARTICULARLY IMPORTANT FOR OUR DIVERSITY, EQUITY, INCLUSION AND ACCESSIBILITY EFFORTS AS MANY OF OUR POPULATION HEALTH RESEARCHERS FOCUS THEIR WORK ON UNDERSERVED AND MARGINALIZED POPULATION GROUPS.SUBRECIPIENT ACTIVITIES: WITH A PROJECT AS AMBITIOUS AND COMPLEX AS THIS NEW KU CANCER CENTER BUILDING, COMMUNITY PARTNERS, ENGINEERING AND CONSTRUCTION SUBRECIPIENTS ARE ABSOLUTELY NECESSARY FOR THE OVERALL VISION AND EXECUTION.USEFUL LIFE: 20 YEARS

AGE-INDUCED IMPAIRMENT OF NUTRIENT SIGNALING RESULTS IN BONE LOSS

LABORATORY CENTER (LC): MICROBICIDE TRIALS NETWORK

CITY OF HOPE LYMPHOMA SPORE

CHILD NEUROLOGIST CAREER DEVELOPMENT PROGRAM (CNCDP)

THE HUMAN ISLET DISTRIBUTION COORDINATING CENTER (UC4)

REVERSING IMMUNE DYSFUNCTION FOR HIV-1 ERADICATION - PROJECT SUMMARY ALTHOUGH THE RATE OF NEW HIV INFECTIONS HAS DECREASED, CONTAINMENT AND EVENTUAL ERADICATION OF THE HIV PANDEMIC REMAINS A TOP PRIORITY IN CONTEMPORARY BIOMEDICAL RESEARCH. ONE OF THE MAJOR CHALLENGES TO HIV CURE IS THE NEED TO RESTORE NORMAL IMMUNE FUNCTION IN ORDER TO EFFECTIVELY ELIMINATE THE ESTABLISHED VIRAL RESERVOIR. WE HAVE ASSEMBLED IN RID-HIV: “REVERSING IMMUNE DYSFUNCTION FOR HIV-1 ERADICATION”, BASIC AND CLINICAL SCIENTISTS WITH EXPERTISE IN VIROLOGY, IMMUNOLOGY, MICROBIOME BIOLOGY, EPIGENETICS, AND SYSTEMS BIOLOGY. IN ADDITION, MERCK RESEARCH LABORATORIES WILL INVEST SIGNIFICANT INTELLECTUAL, HUMAN AND MATERIAL RESOURCES TO COMPLEMENT THE EFFORTS OF THE ACADEMIC SCIENTISTS. THE RID-HIV COLLABORATORY WILL COLLECTIVELY FUNCTION TO EXPLORE THE UNDERLYING BASIS OF THE IMMUNE DYSREGULATION IN HIV-INFECTED INDIVIDUALS AND THE IMPACT IT HAS ON RESERVOIR PERSISTENCE AND VIRAL REBOUND CONTROL. WE WILL TEST FOR THE FIRST TIME SEVERAL INNOVATIVE CONCEPTS, INCLUDING IDENTIFYING EPIGENETIC MECHANISMS IMPRINTED BY THE MICROBIOME AND HOST AND BACTERIAL METABOLOMES THAT PREVENTS THE DEVELOPMENT OF EFFECTIVE INNATE AND ADAPTIVE IMMUNE RESPONSES THAT CAN CONTROL THE SIZE, QUALITY AND ANATOMICAL LOCALIZATION OF THE HIV RESERVOIR. THE OVERARCHING GOAL OF THE RID-HIV COLLABORATORY IS TO PROVIDE PRECLINICAL IN VIVO PROOF-OF- CONCEPT FOR A THERAPEUTIC PARADIGM THAT ENCOMPASSES IMMUNE RESTORATIVE TREATMENTS, USED IN CONCERT WITH ENHANCED VIRAL REACTIVATION AND ELIMINATION STRATEGIES, IN ORDER TO DELIVER A HIV-1 CURE. WE PROPOSE THREE HIGHLY INTEGRATED AND COMPLEMENTARY SCIENTIFIC RESEARCH FOCI (RFS), TO BE SUPPORTED BY RIGOROUS AND ITERATIVE MODELING OF OUTCOMES AND SHAPED BY OUR OUTREACH TO THE HIV COMMUNITY. IN RF1 WE WILL INVESTIGATE THE MECHANISMS WHEREBY HOST- AND MICROBIOME-DERIVED METABOLITES IMPACT INNATE IMMUNE RESPONSES AND INFLUENCE THE MAINTENANCE OF THE LATENT VIRAL RESERVOIR. IN RF2 WE WILL PURSUE THE HYPOTHESIS THAT IN ART/ATI CLINICAL COHORTS, METABOLITES THAT GOVERN INNATE IMMUNITY SHAPE THE ADAPTIVE IMMUNE RESPONSES THAT COULD PREVENT VIRAL REBOUND UPON TREATMENT INTERRUPTION. IN ADDITION, WE WILL EVALUATE THE CAPACITY OF ENGINEERED ALLOGENIC STEM MEMORY T CELLS TO PROVIDE SUPERIOR COGNATE HELP TO PROMOTE THE EFFECTOR FUNCTIONS OF ANTIVIRAL CD8 T CELLS, AND WILL ASSESS THE ABILITY OF FDA-APPROVED AND NOVEL IMMUNE MODULATORS TO RESET THIS BASELINE IMMUNE DYSFUNCTION AND ENHANCE THE FUNCTION OF THIS NOVEL CELL THERAPY PRODUCT. IN RF 3 WE WILL OPTIMIZE A BEST-IN-CLASS LATENCY REVERSAL AGENT (LRA) AND IDENTIFY CLINICAL-STAGE MOLECULES WITH SYNERGISTIC LRA ACTIVITY. CLEARANCE OF REACTIVATED CELLS WILL BE ENHANCED USING A NOVEL STRATEGY FOR NK CELL RECRUITMENT AND BY GENETICALLY MODIFYING B CELLS TO PRODUCE BROADLY NEUTRALIZING HIV-1 ANTIBODIES THAT ENHANCE RESERVOIR CLEARANCE. FINALLY, GENE EDITING WILL BE DEPLOYED FOR IN VIVO TARGETING AND ELIMINATION OF LATENT PROVIRUS NOT AMENABLE TO LRAS. THE OUTCOMES OF STUDIES IN RF1, RF2 AND RF3 WILL ENABLE THE SYNTHESIS OF A PREDICTIVE MATHEMATICAL MODEL TO ESTABLISH THE MOST LIKELY COMBINATIONS OF THERAPIES TO ACHIEVE AN HIV-1 CURE, AND WHICH WILL BE TESTED IN A CAPSTONE AIM TO ESTABLISH PROOF-OF-CONCEPT FOR THESE STRATEGIES IN NHP MODELS AND TO ENABLE TRANSLATION TO THE CLINIC.

CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE AT CHILDRENS NATIONAL

CHIANG MAI UNIVERSITY HIV/AIDS CLINICAL TRIALS UNIT

SCRIPPS CLINICAL AND TRANSLATIONAL SCIENCE HUB - PROJECT SUMMARY / ABSTRACT THE SCRIPPS RESEARCH TRANSLATIONAL INSTITUTE (SRTI) IS THE FOUNDATION FOR THE SCRIPPS HUB AND IS DEDICATED TO ACCELERATING SCIENCE THAT WILL IMPROVE HUMAN HEALTH. SRTI’S EMPHASIS ON GENOMICS, DIGITAL MEDICINE, AND INFORMATICS/ANALYTICS FOSTERS A MULTI-DIMENSIONAL UNDERSTANDING OF INDIVIDUALIZED HUMAN HEALTH. THE SCRIPPS HUB HAS PREVIOUSLY INCLUDED THE SCRIPPS RESEARCH INSTITUTE (SR) AND SCRIPPS HEALTH (SH) AS PRINCIPAL PARTNERS, INCLUDING RADY CHILDREN’S INSTITUTE OF GENOMIC MEDICINE (RCIGM) FOR GENOMIC MEDICINE INITIATIVES AND CALIFORNIA INSTITUTE FOR MEDICAL RESEARCH (CALIBR) FOR DRUG REPURPOSING / DISCOVERY. IN THE NEW CTSA CYCLE, OUR PARTNERS HAVE EXPANDED TO INCLUDE SAN DIEGO STATE UNIVERSITY (SDSU), ENABLING US TO COMBINE FORCES IN COMPUTER SCIENCE, ARTIFICIAL INTELLIGENCE, BIOSENSORS, AND DIVERSITY INCLUSION AND EQUITY INITATIVES. SRTI’S EXPERTISE IN GENOMICS WAS HIGHLIGHTED DURING THE PANDEMIC. WE BECAME ONE OF THE COUNTRY’S MOST PRODUCTIVE SEQUENCING CENTERS FOR SARS-COV-2 BY RAPIDLY FORMING THE “SEARCH” ALLIANCE TO PROCESS SAMPLES WITH THE SAN DIEGO COUNTY DEPARTMENT OF HEALTH, UCSD, SHARP HEALTH, CALIFORNIA DEPARTMENT OF PUBLIC HEALTH, HELIX, AND OUR PARTNERS RCIGM AND SH. DIGITAL MEDICINE HAS BEEN ONE OF SRTI’S CORE STRENGTHS, HAVING PIONEERED THE FIRST REMOTE, SITE-LESS DIGITAL CLINICAL TRIAL AND NOW EXPANDING THIS METHODOLOGY TO ADDRESS MANY OTHER MEDICAL CONDITIONS SUCH AS HEALTH DURING PREGNANCY AND SLEEP DISORDERS. OUR DIGITAL TRIALS CENTER LAUNCHED THE DIGITAL ENGAGEMENT & TRACKING FOR EARLY CONTROL AND TREATMENT SCRIPPS (DETECT) STUDY, AND IN A MATTER OF WEEKS OUR TEAM WAS ABLE TO ACCURATELY PREDICT THE LIKELIHOOD OF COVID WITH SARS-COV-2 USING PASSIVELY COLLECTED RESTING HEART RATE DATA FROM WRISTBAND SENSORS AND LATER TO IDENTIFY A PHYSIOLOGIC SIGNATURE THAT CORRELATES WITH LONG COVID (POST-ACUTE SEQUELAE OR SARS-COV-2 INFECTION). THE SCRIPPS HUB WILL INNOVATE CLINICAL AND TRANSLATIONAL SCIENCE TO IMPROVE HUMAN HEALTH ACROSS THE LIFESPAN AND DIVERSE RACIAL, ETHNIC, GEOGRAPHIC AND SOCIOECONOMIC COMMUNITIES. THE HUB WILL PROVIDE A NURTURING ENVIRONMENT FOR EDUCATION, TRAINING, AND CAREER DEVELOPMENT WITH A FOCUS ON INDIVIDUALIZED HEALTH DOMAINS OF GENOMICS, DIGITAL MEDICINE, AND BIOMEDICAL INFORMATICS, TO EMPOWER TOMORROW’S DIVERSE WORKFORCE.

CENTER FOR TRANSLATIONAL PEDIATRIC RESEARCH (CTPR)

PROTEIN CARBOHYDRATE INTERACTIONS IN CELL COMMUNICATION

IMMUNE CELL INTERACTIONS IN ATHEROSCLEROSIS

MITOCHONDRIAL DYSFUNCTION IN NEUROGEGENERATION OF AGING

RESEARCH AND DEVELOPMENT OF BETTER DIAGNOSIC TOOLS FOR MENTAL ILLNESS, NEUROLOGICAL DISORDERS, TRAUMATIC BRAIN INJURY AND POST TRAUMATIC STRESS DISOR

SCRIPPS TRANSLATIONAL SCIENCE INSTITUTE

POLICY, SCIENCE AND INNOVATION PROGRAM: COMPONENT 1 PAKISTAN STRATEGY SUPPO

GLOBAL EMERGING INFECTION SURVEILLANCE AND RESPONSE )GEIS) AVIAN INFLLIENAZ PANDEMIC INFLUIENZA

TRANSFUSION MEDICINE/HEMOSTASIS CLINICAL TRIALS NETWORK-DATA COORDINATING CENTER

ENDOTHELIAL INJURY AND REPAIR: CARDIOPULMONARY VASCULAR BIOLOGY COBRE

STRESS RELATED MECHANISMS OF HYPERTENSION RISK IN YOUTH

JOINT CENTER FOR STRUCTURAL GENOMICS (JCSG-2)

NEW GRANT - IFPRI

RARE DISEASES CLINICAL RESEARCH CONSORTIA (RDCRC) FOR THE RDCR NETWORK

CENTER FOR CHILDHOOD OBESITY PREVENTION

PEDIATRIC HEART NETWORK: DATA COORDINATING CENTER

INNOVATIVE INFRASTRUCTURE TO ENHANCE THE CALIFORNIA TEACHERS STUDY

PONCE SCHOOL OF MEDICINE-MOFFITT CANCER CENTER PARTNERSHIP (2/2)

HIV MACROMOLECULAR INTERACTIONS AND IMPACT ON VIRAL EVOLUTION OF DRUG RESISTANCE

BEST-CLI TRIAL-DCC

EARLY HEAD START

THE OBJECTIVE IS A HEALTHY AND PROSPEROUS CALIFORNIA COASTAL OCEAN POWERED BY INFORMATION SOLUTIONS. THE MISSION IS TO TRANSLATE DATA INTO ACTION THROUGH THE PRODUCTION, CURATION, AND DELIVERY OF HIGH-QUALITY OCEAN INFORMATION. THE CENCOOS REGION, EXTENDING 600 MILES FROM POINT CONCEPTION NORTH TO THE CALIFORNIA-OREGON BORDER, COVERS SOME OF THE WORLD'S MOST SPECTACULAR YET IMPERILED COASTLINE. SINCE ITS ESTABLISHMENT IN 2004, CENCOOS HAS BUILT A FOUNDATION BASED ON THE BEST AVAILABLE SCIENCE AND COLLABORATIVE PARTNERSHIPS. WE PROVIDE NEAR CONTINUOUS COVERAGE OF SURFACE CURRENTS ALONG THE COAST FROM 31 HIGH-FREQUENCY RADAR (HFR) STATIONS, OCEANOGRAPHIC SECTION DATA FROM THREE CONTINUOUS GLIDER LINE TRANSECTS, MORE THAN 15 SHORE STATIONS AND MOORINGS, AND INTEGRATION WITH >250 OTHER DATA PRODUCTS (I.E. DATA LAYERS) IN THE CENCOOS DATA PORTAL. MODEL ASSIMILATED CENCOOS OBSERVATIONS UNDERPIN HIGH-QUALITY OCEAN AND ATMOSPHERE FORECASTS, NOWCASTS AND HINDCASTS, ALL OF WHICH SERVE AS

DIET AND GENOTOYPE IN PRIMATE ATHEROSCLEROSIS

RECIPIENT SHALL ESTABLISH A SUSTAINABLE SEED ALLIANCE IN SELECTED WEST AFRICAN COUNTRIES LEADING TO A GROWTH IN A VIABLEAGRICULTURAL INPUT SYSTEMS

OMICS FOR TB DISEASE PROGRESSION (OTB)

USING COMBINATORIAL THERAPIES WITH DENDRITIC CELL THERAPIES TO IMPROVE SURVIVAL AND PREVENT RECURRENCE OF BREAST CANCER LEPTOMENINGEAL DISEASE (LMD)

EARLY HEAD START

PURPOSE: DESIGN AND DELIVER A FACILITY THAT MEETS THE INTENDED NEEDS OF THE CONSORTIUM AND ENABLES THE OTHER BIOWORKS COMPONENT PROJECTS TO ACHIEVE THEIR GOALS. ACTIVITIES TO BE PERFORMED: - ESTABLISH OCCUPANCY, SPACE, AND EQUIPMENT NEEDS TO CONDUCT OVERARCHING BIOWORKS BUSINESS AND PROMOTE GROWTH OF THE REGIONAL BIOMANUFACTURING ECOSYSTEM. - ESTABLISH OCCUPANCY, SPACE, AND EQUIPMENT NEEDS TO DELIVER CLASSROOM AND HANDS-ON LABORATORY/PILOT-SCALE TRAINING TO PREPARE STUDENTS FOR EMPLOYMENT IN BIOMANUFACTURING. - ESTABLISH OCCUPANCY, SPACE, AND EQUIPMENT NEEDS TO ENABLE SMALL BIOTECHS TO CONDUCT PROCESS DEVELOPMENT ACTIVITY AND MANUFACTURE DEMONSTRATION BATCHES. - DESIGN FACILITY, ESTABLISH EQUIPMENT SPECIFICATIONS, CREATE CONSTRUCTION DOCUMENTS, AND ESTABLISH A DETAILED SCHEDULE AND BUDGET. - IDENTIFY GENERAL CONTRACTOR. - PHYSICALLY CONSTRUCT THE FACILITY AND PROCURE EQUIPMENT. EXPECTED OUTCOMES: WRITTEN SUMMARY OF REQUIREMENTS DELIVERED TO THE ENGINEERING DESIGN TEAM FOR REGIONAL BIOMANUFACTURING ECOSYSTEM, BIOTRAIN TRAINING FACILITY, AND BIOLAUNCH PROCESS DEVELOPMENT AND DEMONSTRATION FACILITY. COMPLETED CONSTRUCTION DOCUMENTS, PROJECT SCHEDULE, AND CAPITAL BUDGET, WITH GENERAL CONTRACTOR HIRED AND MOBILE. COMPLETED AND OPENED FACILITY. INTENDED BENEFICIARIES: TECH HUB HQ TEAM GAINS ACCESS TO CUSTOMIZED FACILITY TO EXECUTE GOVERNANCE FUNCTIONS. STUDENTS AND LEARNERS BENEFIT FROM ACCESS TO NEWLY-DEVELOPED BIOTRAIN FACILITY, AND SMALL BIOTECHS BENEFIT FROM DEDICATED SPACE TO CONDUCT PROCESS DEVELOPMENT ACTIVITY AND MANUFACTURE DEMONSTRATION BATCHES. SUBRECIPIENT ACTIVITIES: THE RECIPIENT DOES NOT INTEND TO SUBAWARD FUNDS.

BIPARTISAN INFRASTRUCTURE LAW (BIL): OPTIMIZING INTERREGIONAL TRANSFER CAPACITY USING ADVANCED POWER FLOW CONTROL. THIS PROJECT IS A PARTNERSHIP BETWEEN THE RECIPIENT AND A HOST TRANSMISSION UTILITY, TO INSTALL AN AUTOMATIC POWER FACTOR CONTROLLER (APFC) DEVICE, THE SMARTVALVE, AT AN INTERREGIONAL TIE TO REDUCE TAP CHANGES AND INCREASE THE CONTROL RANGE OF A PHASE SHIFTING TRANSFORMER (PST) ACROSS A REGIONAL BORDER.

PHASE I MOLECULAR AND CLINICAL PHARMACODYNAMIC TRIALS ET-CTN

HUMANS EXPERIENCE WEATHER DIRECTLY, WHILE CLIMATE AND CLIMATE CHANGE CAN ONLY BE UNDERSTOOD THROUGH THE LENS OF DATA. THE NASA EARTH SYSTEMS SCIENCE

MILITARY SUICIDE RESEARCH CONSORTIUM: EXTENSION TO NEW OPPORTUNITIES AND CHALLENGES

PROVIDE SUBSTANTIAL GUIDANCE AND INPUT TPROBABILISTIC DESIGN FOR ROTOR INTEGRITY

ELICITING NEUTRALIZING ANTIBODIES AND B CELL RESPONSES USING NOVEL HIV ENV IMMUNOGENS IN NON-HUMAN PRIMATES - NEUTRALIZING ANTIBODIES ARE LIKELY TO BE REQUIRED FOR AN EFFECTIVE HIV-1 VACCINE. HOWEVER, FEW CANDIDATE VACCINES EFFICIENTLY ELICIT BROADLY NEUTRALIZING ANTIBODIES (BNABS) FOLLOWING VACCINATION. RECENTLY, THE VRC WORKING GROUP HAS ELICITED FUSION PEPTIDE-DIRECTED BNABS IN GUINEA PIGS AND NON-HUMAN PRIMATES (NHPS). SIMILARLY, WE RECENTLY ELICITED BNABS IN RABBITS FOLLOWING HETEROLOGOUS NFL (UNCLEAVED) TRIMER-LIPOSOME PRIME:BOOSTING AT SCRIPPS WHERE WE ACTIVATED B CELL RESPONSES WITH TARGETED N-GLYCAN DELETIONS IN THE PRIMING IMMUNIZATIONS (DUBROVSKAYA ET AL, IMMUNITY 2019). WE ISOLATED TWO RABBIT BNABS THAT RECAPITULATE THE SERUM ACTIVITY. THESE BNABS ARE DIRECTED AGAINST TWO DISTINCT SITES OF ENV VULNERABILITY. THE ELICITATION OF NEUTRALIZING RESPONSES WAS ENHANCED BY TARGETED N-GLYCAN DELETION, HIGH-DENSITY LIPOSOMAL ARRAY AND HETEROLOGOUS TRIMER RESTORATIVE BOOSTING ENV. IN INDEPENDENT EXPERIMENTS IN GUINEA PIGS, WE HAVE ELICITED BNABS IN MULTIPLE ANIMALS ALSO USING A N-GLYCAN DELETION, HETEROLOGOUS ENV NFL PRIME:BOOST APPROACH. THESE RECENT OUTCOMES ARE ENCOURAGING INROADS TOWARD THE SUCCESSFUL SOLUTION OF A 3-DECADE-LONG PROBLEM. THE NEW ERA OF NEAR-NATIVE TRIMERIC SPIKE MIMICS, COUPLED WITH PARTICULATE ARRAY, STRUCTURE-INFORMED DESIGN AND HIGH-RESOLUTION ANALYSIS OF ENV-SPECIFIC B CELL AND LYMPH NODE RESPONSES, AFFORD NEW OPPORTUNITIES TO MORE EFFICIENTLY ELICIT BNABS. WE PROPOSE AN INTEGRATED, MULTI-FACETED APPROACH BLENDING THE EXPERTISE OF WORLD LEADERS IN HIV ENV TRIMER DESIGN, ANALYSIS OF B CELL RESPONSES AND ABS FOLLOWING VACCINATION, NHP IMMUNE TISSUE ANALYSIS AND EM-BASED ANALYSIS OF ONGOING IMMUNE RESPONSES AND HIGH-RESOLUTION AB:TRIMER INTERACTIONS. WE WILL USE WELL-ORDERED TRIMER PRIME:BOOSTING THAT ELICITED BNABS IN RABBITS AND GUINEA PIGS TO ELICIT SUCH RESPONSES IN NHPS, TRANSLATING SUCCESS IN SMALL ANIMALS TO NHPS USING NOVEL IMMUNOGEN DESIGN AND PRESENTATION IN PROJECT 1 (WYATT) AND IMMUNIZATION OF NFL TRIMERS INTO NHPS VIA CORE B (SILVESTRI). WE WILL USE “REAL-TIME” SERUM FAB-TO-TRIMER BINDING EVALUATED BY EM POLYCLONAL IGG EPITOPE MAPPING (EMPEM) IN CORE C (WARD) IN COMPLEMENT WITH RAPID MAB NGS-BASED MAB CLONING, SEQUENCING AND FUNCTIONAL EXPRESSION IN PROJECT 2 (KARLSSON HEDESTAM). IN COLLABORATION WITH THE VRC (MASCOLA) WE WILL DEFINE EITHER NON-NEUTRALIZING MABS TO MASK UNWANTED NON-NEUTRALIZING EPITOPES OR TO BETTER DISPLAY THE EPITOPES OF CROSS-NEUTRALIZING MABS. WE WILL COMPARE NFL TRIMER-LIPOSOMES TO CELL SURFACE NFL TRIMER ARRAY EXPRESSED FROM THE EXCITING MRNA LIPID ENCAPSULATION TECHNOLOGY. WE WILL ASSESS IF IMMUNIZATION IN THE JUVENILE NHP B CELL REPERTOIRE COMPARED TO ADULT MACAQUES WILL BETTER GENERATE BNABS AS IS OBSERVED DURING HUMAN INFECTION. TO FOLLOW OUR DISCOVERY OF A TIER 2 CD4BS-DIRECTED BNAB FOLLOWING TRIMER-LIPOSOME VACCINATION, TERMED E70, WE WILL TARGET THE CD4BS BY DIRECTED NFL TRIMER DEGLYCOSYLATION IN THE NHPS. BASED ON OUR RECENT DISCOVERY OF THE VERY BROADLY NEUTRALIZING VACCINE-INDUCED MAB, 1C2, WE WILL ALSO FOCUS ON THE GP41:120 TRIMER INTERFACE. LEVERAGING THESE INITIAL LEADS, WE WILL UNDERTAKE A MULTIFACETED, CROSS-COMPONENT INTEGRATED APPROACH TO GUIDE THE ELICITATION OF BNABS IN NHPS FOLLOWING VACCINATION WITH NEAR-NATIVE, UNCLEAVED NFL ENV TRIMERS.

FILM ANTIRETROVIRAL MICROBICIDE EVALUATION

THE KANSAS INSTITUTE FOR PRECISION MEDICINE

SYSTEMS ANALYSIS VACCINE RESPONSES IN HEALTHY AND HYPORESPONSIVE HUMANS

PURPOSE: TRAIN NEW ENTRANTS TO THE BIOMANUFACTURING WORKFORCE AND PLACE THEM IN HIGH-QUALITY JOBS. DEVELOP AND DELIVER UPSKILLING TRAINING FOR COMPANY-SPONSORED EMPLOYEES. ESTABLISH A PLAN FOR EXPANDING THE BIOTRAIN TRAINING BEYOND THE ENTRY LEVEL ROLES AND BEYOND THE BIOWORKS HQ LOCATION. ACTIVITIES TO BE PERFORMED: 1) DEVELOP TRAINING AND DEFINE PATHWAYS FOR ENTRY LEVEL ROLES (OPERATOR AND LAB TECHNICIAN). 2) TRAIN INDIVIDUALS TO DEVELOP THE KNOWLEDGE, SKILLS AND ABILITIES REQUIRED FOR THE ENTRY LEVEL ROLES. 3) SUPPORT ~15% OF TRAINEES WITH WRAPAROUND SUPPORTING SERVICES. PROVIDING WRAPAROUND SERVICES SUCH AS TRANSPORTATION, CHILDCARE, CAREER COUNSELING, ETC. WILL HELP PROVIDE ACCESS TO THE TRAINING PROGRAM AND ENCOURAGE A HIGHER TRAINING COMPLETION RATE. 4) PROVIDE UPSKILLING TRAINING FOR INCUMBENT EMPLOYEES BASED ON EMPLOYER NEEDS TO ENSURE THE WORKFORCE HAS THE UP-TO-DATE SKILLS NEEDED. 5) SERVE EMPLOYERS AND COMMUNITIES OUTSIDE THE BIOWORKS HQ AREA WITH TRAINING AND UPSKILLING PROGRAMS FOR ENTRY LEVEL ROLES AND INCUMBENT WORKERS. EXPECTED OUTCOMES: TRAINING CURRICULUM BASED ON EMPLOYER/INDUSTRY INPUT TO DEVELOP THE KNOWLEDGE, SKILLS, AND ABILITIES REQUIRED FOR OPERATOR AND LAB TECH ROLES. DEVELOP 6 ENTRY LEVEL PATHWAYS TO FACILITATE ENGAGEMENT IN WORKFORCE. 340 PEOPLE TRAINED IN ENTRY-LEVEL CURRICULUM PATHWAYS EACH OF YEARS 3 THROUGH 5. IN YEARS 4 AND 5, PROVIDE HANDS-ON TRAINING TO 300 4-YEAR STUDENTS. INTEGRATE HANDS-ON TRAINING FOR 14 DEGREE PROGRAMS AT PURDUE UNIVERSITY BY YEAR 4. WRAPAROUND SUPPORT SERVICES MADE AVAILABLE TO ~48 TRAINEES IN EACH OF YEARS 3 AND 4. 450 OR MORE COMPANY-SPONSORED EMPLOYEES TRAINED IN EACH OF YEARS 3 THROUGH 5. TRAINING PROGRAMS EXPANDED BEYOND THE BIOWORKS HQ COMMUNITY IN WHICH THE PROGRAMS WILL LAUNCH. INTENDED BENEFICIARIES: STUDENTS, LEARNERS, AND PROSPECTIVE NEW ENTRANTS INTO THE TECH HUB?S INDUSTRY GAIN ACCESS TO TAILORED TRAINING. CURRENT INDUSTRY EMPLOYEES BENEFIT FROM RESOURCES AND INSTRUCTION THAT ENABLE UPSKILLING. EMPLOYERS BENEFIT FROM A LARGER AND BETTER-TRAINED WORKFORCE. SUBRECIPIENT ACTIVITIES: BIOCROSSROADS AND IVY TECH WILL DEVELOP A TRAINING CURRICULUM FOR NEW ENTRANTS TO THE BIOMANUFACTURING WORKFORCE. IVY TECH WILL DELIVER THE TRAINING ONLINE AND/OR IN PERSON. EMPLOYINDY WILL PROVIDE WRAPAROUND SUPPORT SERVICES. PURDUE UNIVERSITY WILL DEVELOP AND DELIVER UPSKILLING TRAINING. BIOCROSSROADS WILL DEVELOP A PLAN TO EXPAND TRAINING OUTSIDE OF THE AREA IN WHICH IT LAUNCHES.

UNIVERSITY OF KANSAS ALZHEIMER'S DISEASE CORE CENTER

GENOMICS FOR KIDNEY TRANSPLANTATION

UNIVERSITY OF KANSAS ALZHEIMER'S DISEASE RESEARCH CENTER (KU ADRC) - ABSTRACT: OVERALL THE UNIVERSITY OF KANSAS ALZHEIMER'S DISEASE RESEARCH CENTER (KU ADRC) PROMOTES ALZHEIMER'S DISEASE AND RELATED DISORDERS (ADRD) RESEARCH AT LOCAL, NATIONAL, AND INTERNATIONAL LEVELS. OUR STRENGTHS IN BASIC AND TRANSLATIONAL MITOCHONDRIA, LIFESTYLE MODIFICATION, AND PREVENTION RESEARCH DEFINE A METABOLISM THEME WE PURSUED AND REFINED OVER THE PAST DECADE. WE BOAST A SOPHISTICATED AND MATURE INFRASTRUCTURE THAT ADVANCES A BETTER UNDERSTANDING OF AD, BETTER CARE OF AFFECTED PERSONS, AND NEW TREATMENT INTERVENTIONS. THE KU ADRC WILL USE ITS INTELLECTUAL AND INFRASTRUCTURE ASSETS THIS NEXT CYCLE TO DRIVE AD RESEARCH AT A UNIVERSITY VESTED AND INVESTING IN OUR SUCCESS, AND IN DOING SO MOVE THE FIELD CLOSER TO A CURE. OUR CENTER MOVES SEAMLESSLY BETWEEN BENCH AND BEDSIDE, BOTH IN TERMS OF THE RESEARCH PROJECTS WE SUPPORT, AND IN THE INFRASTRUCTURE REQUIRED TO BACK INVESTIGATOR PROJECTS. LIFESTYLE INTERVENTION RESEARCH GENERATES FUNDAMENTAL MECHANISTIC QUESTIONS WE CALL ON WET LAB INVESTIGATORS TO ADDRESS, AND QUESTIONS OF CLINICAL IMPLEMENTATION AND PRACTICE ARE NOW THE FOCUS OF DRY LAB, CLINICAL, AND HEALTH CARE DELIVERY INVESTIGATORS. RESEARCH ADDRESSING AD'S MITOCHONDRIAL COMPONENT DEMONSTRATE A ROLE FOR MITOCHONDRIAL GENES IN AD RISK, THAT MITOCHONDRIA PLAY A CRITICAL ROLE IN CELL PROTEOSTASIS AND PROTEIN AGGREGATION, SPECIFIC LINKS BETWEEN MITOCHONDRIA AND AD HALLMARK PROTEINS, AND HOW TO MANIPULATE BRAIN ENERGY METABOLISM THROUGH LIFESTYLE AND PHARMACOLOGIC APPROACHES. TO DATE THESE EFFORTS LED US TO CREATE NOVEL COMPOUNDS THAT CONSTITUTE A UNIQUE THERAPEUTIC PIPELINE, AND CLINICAL TRIAL INFRASTRUCTURE THAT SUPPORTS ACTUAL STUDIES OF METABOLISM INTERVENTIONS IN ACTUAL AD PATIENTS. FOR THE 2021-26 CYCLE WE WILL USE OUR INTELLECTUAL AND INFRASTRUCTURE ASSETS TO ADDRESS CRITICAL GAPS IN THE AD FIELD, INCLUDING GAPS IN FUNDAMENTAL KNOWLEDGE AND CARE IMPLEMENTATION. DURING THIS CYCLE THE KU ADRC WILL WORK TO (1) EMPOWER INNOVATIVE AD AND BRAIN AGING RESEARCH, EDUCATION, AND CLINICAL PROGRAMS; (2) DRIVE FIELD-DEFINING METABOLISM RESEARCH, AND (3) BRING PRACTICAL AND NOVEL METABOLISM-DIRECTED THERAPIES TO THE BEDSIDE AND CLINIC.

SCRIPPS TRANSLATIONAL SCIENCE INSTITUTE (UL1)

JCSG CENTER FOR INNOVATIVE MEMBRANE PROTEIN TECHNOLOGIES

CORE GRANT FOR VISION RESEARCH

KANSAS IDEA NETWORK OF BIOMEDICAL RESEARCH EXCELLENCE

TO STRENGTHEN CAPACITY THROUGH IMPROVED MANAGEMENT AND COORDINATION OF LABORATORY, SURVEILLANCE, EPIDEMIOLOGY, VALIDATION AND TRAINING IN UGANDA UNDER PRESIDENT'S EMERGENCY PLAN FOR AIDS RELIEF (PEPFA

CENCOOS PARTNERSHIP: OCEAN INFORMATION FOR DECISION MAKERS

MULTIPLE MEDICAL THERAPIES FOR PEDIATRIC TBI; COMPARATIVE EFFECTIVENESS APPROACH

IDENTIFICATION, SURVEILLANCE, AND CONTROL OF VECTOR-BORNE AND ZOONOTIC INFECTIOUS DISEASES IN UGANDA

MILITARY SUICIDE RESEARCH CONSORTIUM

COMMUNITY PROJECT FUNDING/CONGRESSIONALLY DIRECTED SPENDING - CONSTRUCTION

INTEGRATED ISLET DISTRIBUTION PROGRAM (U24) - 2021 - PROJECT SUMMARY / ABSTRACT HUMAN PANCREATIC ISLETS ARE AN ESSENTIAL RESEARCH RESOURCE FOR RESEARCH ON THE PREVENTION, TREATMENT, AND PATHOPHYSIOLOGY OF DIABETES MELLITUS. RECENT DATA HAVE HIGHLIGHTED IMPORTANT DIFFERENCES BETWEEN MURINE AND HUMAN ISLETS, SUBSTANTIATING THE CONTINUED NEED FOR ACCESS TO HUMAN ISLETS, AS THE GOLD STANDARD IN DIABETES RESEARCH. CITY OF HOPE (COH) IS APPLYING FOR THIS U24 RENEWAL TO REMAIN AS THE INTEGRATED ISLET DISTRIBUTION PROGRAM COORDINATING CENTER (IIDP CC) FOR THE NEXT 5 YEARS, TO CONTINUE TO PROVIDE DISTRIBUTION OF HUMAN CADAVERIC ISLETS AND ANCILLARY TISSUE FOR BIOMEDICAL RESEARCH TO RESEARCHERS WORLDWIDE. OUR PROPOSAL LEVERAGES THE SIGNIFICANT INVESTMENT MADE BY NIH OVER THE LAST 19 YEARS THAT HAS ESTABLISHED AND SUCCESSFULLY MAINTAINED THE IIDP AT COH. FROM QUALIFICATION AND AUDITING OF HIGH-QUALITY ISLET ISOLATION CENTERS (IICS), TO FORECASTING, TRACKING, AND MEETING THE NEEDS OF INVESTIGATORS, SINCE 2002 OUR EXPERIENCED TEAM HAS WORKED WITH 20 DIFFERENT ISLET ISOLATION LABORATORIES TO COORDINATE THE DISTRIBUTION OF OVER 330 MILLION ISLET EQUIVALENTS TO MORE THAN 400 INVESTIGATORS ACROSS 16 COUNTRIES SINCE 2002, SUPPORTING 767 PEER REVIEWED PUBLICATIONS. THROUGH THIS RENEWAL WE WILL CONTINUE TO SUBCONTRACT WITH OUR 5 HIGHLY QUALIFIED IICS TO ISOLATE AND DISTRIBUTE HUMAN ISLETS AND ANCILLARY TISSUE VIA OUR ADVANCED ELECTRONIC ISLET ALLOCATION SYSTEM (IAS). WE WILL CONTINUE TO MANAGE THE REVIEW PROCESS FOR ISLET RECEIPT, PILOT STUDIES, AND OPPORTUNITY POOL FUNDING. WE WILL FURTHER ENHANCE OUR IAS TO BROADCAST OFFERS ONLINE AND NOTIFY APPROVED WAITING RESEARCHERS OF ISLET AVAILABILITY, IN A FAIR, EQUITABLE AND TIME SENSITIVE MANNER. IIDP WILL CONTINUE TO MAINTAIN THE EXISTING COST RECOVERY SYSTEM THROUGH SUBSCRIPTION FEES COLLECTED FROM ISLET RESEARCHERS, WHICH HAS GARNERED A TOTAL OF $9,303,950 SINCE THE IMPLEMENTATION OF SUBSCRIPTION FEES TO OFFSET THE EXPENSES OF PANCREATIC PROCESSING FOR THE IICS. WE WILL CONTINUE TO CLOSELY MONITOR AND HELP TO IMPROVE THE QUALITY OF ISLETS DISTRIBUTED, THROUGH THE CONTINUATION OF THE HUMAN ISLET PHENOTYPING PROGRAM (HIPP) THAT CONDUCTS ASSAYS ON A SAMPLE FROM EACH ISLET ISOLATION. IIDP HAS JUST ADDED A HUMAN ISLET GENOTYPING INITIATIVE (HIGI) TO GENOTYPE EACH ISOLATION AS WELL. PHENOTYPING AND GENOTYPING DATA, AS WELL AS UNOS DATA, EXTENSIVE DONOR AND ISLET ISOLATION DATA, WILL BE MADE AVAILABLE TO APPROVED INVESTIGATORS THROUGH ONLINE ACCESS TO THE IIDP RESEARCH DATA REPOSITORY, WITH IIDP AND NIDDK APPROVAL OF APPLYING SCIENTISTS. INVESTIGATORS CAN EASILY SEARCH THE REQUIRED DATA, SELECT FILTER CRITERIA, SAVE THEIR SEARCHES, AND DOWNLOAD THE INTEGRATED IIDP DATA FOR EXPLORATORY ANALYSES. THROUGH OUR PROVEN STATE-OF-THE-ART ADMINISTRATIVE, BUSINESS, TECHNICAL, STATISTICAL, QUALITY ASSURANCE, AND INFORMATICS PROCESSES AND TOOLS, THE ACCESSIBILITY OF HUMAN ISLETS FOR INVESTIGATORS CONDUCTING ESSENTIAL DIABETES MELLITUS RESEARCH WILL BE SECURED. WE WILL CONTINUE TO PROVIDE AN INDISPENSABLE RESEARCH RESOURCE FOR THE DIABETES RESEARCH COMMUNITY BY ENSURING THAT THE IIDP REMAINS STABLE, TECHNOLOGICALLY ADVANCED, CONTINUALLY ENHANCED, AND FULLY RESPONSIVE TO THE ISLET NEEDS OF THE RESEARCH COMMUNITY, PROMOTING THE NEXT GENERATION OF SCIENTIFIC EXPERIMENTATION TOWARD THE PREVENTION AND TREATMENT OF DIABETES.

HIGH RESOLUTION ANALYSIS OF ENV-DIRECTED B CELLS TO ACCELERATE VACCINE DESIGN

NATIONAL FUNCTIONAL GENOMICS CENTER

(EET BIOBANK) NCI EARLY-PHASE AND EXPERIMENTAL CLINICAL TRIALS BIOSPECIMEN BANK

HEALTH CARE INNOVATION CHALLENGE

INTEGRATED CARE FOR KIDS (INCK)

ADULT STEM CELLS FOR THERAPY OF VISUAL DISORDERS

CALIFORNIA TEACHERS STUDY

STUDIES OF JOINT AGING AND OSTEOARTHRITIS

EARLY HEAD START

ANTIBODY TARGETED RADIATION AND IMMUNOTHERAPY FOR THE TREATMENT OF SOLID TUMORS

NOVEL TARGETED THERAPIES FOR PULMONARY FIBROSIS

REGULATION OF PULMONARY INFLAMMATION BY LEUKOCYTES AND EXTRACELLULAR MATRIX

INCREMENTAL FUNDING IN THE AMOUNT OF $100,000.

CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE AT CHILDREN'S NATIONAL

ASSESSMENT OF OPPORTUNITIES FOR OPTIMAL RESERVOIR PRESSURE CONTROL, PLUME MANAGEMENT AND PRODUCED WATER STRATEGIES

WEST AFRICAN EMERGING INFECTIOUS DISEASE RESEARCH CENTER (WA-EIDRC)

PRECISION DELIVERY AND IMAGING TO ENHANCE SOLID TUMOR THERAPY

PERSONALITY AND HEALTH--A LONGTITUDINAL STUDY

HEALTH CARE INNOVATION CHALLENGE

TYPE 1 DIABETES TRIALNET CLINICAL NETWORK HUB

ALTERNATIVE FORMULATIONS OF TENOFOVIR AND UC781

RESOURCE FOR QUANTITATIVE FUNCTIONAL MRI

WISCONSIN CENTER OF EXCELLENCE IN GENOMICS SCIENCE

HEARTLAND INSTITUTE FOR CLINICAL AND TRANSLATIONAL RESEARCH

CENTER FOR ADAPTIVE NEUROTECHNOLOGIES

THE TUBERCULOSIS (TB) LOCAL ORGANIZATIONS NETWORK (LON) IS A KEY COMPONENT OF THE USAID GLOBAL ACCELERATOR TO END TUBERCULOSIS. USAID’S INVESTMENTS ARE MOST SUCCESSFUL WHEN THEY ARE COUPLED AND ALIGNED WITH STRONG COMMITMENTS FROM THE GOVERNMENT OF INDIA (GOI) AND LOCAL PARTNERS.  THE PURPOSE OF THIS ACTIVITY IS TO STRENGTHEN THE ABILITY OF THE GOVERNMENT OF INDIA (GOI) AND STATE GOVERNMENTS TO PROVIDE TB SERVICES TO TRIBAL POPULATIONS ACROSS THE COUNTRY AS ARTICULATED THROUGH THE NATIONAL STRATEGIC PLAN OF INDIA’S NATIONAL TB ELIMINATION PROGRAM (NTEP).

GENETICS OF ATHEROSCLEROSIS IN MEXICAN AMERICANS

THE EMERGENCY ID NET STUDY GROUP

NEUTROPHIL LINEAGE IN INFLAMMATION - ABSTRACT NEUTROPHILS CONSTITUTE THE FIRST LINE OF CELLULAR DEFENSE AGAINST PATHOGENIC MICROORGANISMS. IN RESPONSE TO PRO- INFLAMMATORY CUES, UNRESTRICTED NEUTROPHIL ACTIVATION INDUCES TISSUE DAMAGE. TO AVOID DELETERIOUS EFFECTS TO THE HOST, NEUTROPHIL NUMBERS, ACTIVATION, AND LIFESPAN MUST BE TIGHTLY REGULATED, BUT THE MOLECULAR MECHANISMS THAT CONTROL NEUTROPHILS IN THE CONTEXT OF INFLAMMATORY DISEASE REMAIN ELUSIVE. CARDIOVASCULAR DISEASE IS THE LEADING GLOBAL CAUSE OF DEATH. RECENT EVIDENCE SUPPORTS AN IMPORTANT ROLE FOR NEUTROPHILS IN THE DEVELOPMENT OF CORONARY ARTERY DISEASE (CAD). NEUTROPHILS ARE PRESENT IN EARLY AORTIC LESIONS AND IN RUPTURE-PRONE ATHEROSCLEROTIC PLAQUES, AND A POSITIVE CORRELATION BETWEEN PLASMA LEVELS OF NEUTROPHIL SECRETORY PROTEINS AND CAD HAS BEEN ESTABLISHED, SUGGESTING THAT NEUTROPHIL EXOCYTOSIS MEDIATES DETRIMENTAL EFFECTS IN CAD. FURTHERMORE, NEUTROPHIL PRODUCTION IS INCREASED IN THE BONE MARROW IN ATHEROSCLEROTIC MODELS AND NEWLY IDENTIFIED NEUTROPHIL PRECURSORS ARE NOW KNOWN TO MEDIATE INFLAMMATION. HOW NEUTROPHIL SUBSETS CONTRIBUTE TO DISEASE PROGRESSION IN CAD HAS NOT BEEN STUDIED AND THE REGULATION OF NEUTROPHIL DIVERSITY IN DISEASE IS UNKNOWN. THE INFLAMMASOME IS AN EMERGING DRIVER IN ATHEROSCLEROSIS; HOWEVER, THE ROLE OF THE NLRP3 INFLAMMASOME ACTIVATION SELECTIVELY IN NEUTROPHILS ON ATHEROGENESIS HAS NOT BEEN STUDIED AND THE MECHANISMS REGULATING THE FUNCTIONS OF NEUTROPHIL LINEAGE CELLS IN THE CONTEXT OF INFLAMMASOME ACTIVATION AND ATHEROGENESIS REMAIN UNKNOWN. IN THIS SYNERGISTIC PROGRAM, PROJECT 1 NEUTROPHIL DEVELOPMENT DURING INFLAMMATION AND ATHEROSCLEROSIS WILL STUDY HOW NEUTROPHIL HETEROGENEITY IS MODULATED IN HUMAN SUBJECTS WITH CAD, AND HOW THE NLRP3 INFLAMMASOME IN NEUTROPHIL PROGENITORS INFLUENCES GRANULOPOIESIS AND NEUTROPHIL HETEROGENEITY IN ATHEROSCLEROSIS. PROJECT 2 NEUTROPHIL MECHANISMS DURING INFLAMMATION AND ATHEROSCLEROSIS WILL TEST THE HYPOTHESIS THAT HYPERLIPIDEMIA DIFFERENTIALLY REGULATES VESICULAR TRAFFICKING AND ASSOCIATED FUNCTIONS OF NEUTROPHIL PRECURSORS IN CAD, ESTABLISH MECHANISMS OF NLRP3-INDUCED NEUTROPHIL EXOCYTOSIS DYSREGULATION AND IMPLEMENT TRANSLATIONAL APPROACHES TO DECREASE NEUTROPHIL INFLAMMATION IN CAD. PROJECT 3 NEUTROPHIL SURVIVAL AND DEMISE DURING INFLAMMATORY STATES WILL CHARACTERIZE THE EXPRESSION AND FUNCTION OF COMPONENTS OF THE NLRP3 INFLAMMASOME IN CELLS OF THE NEUTROPHIL LINEAGE, AND WILL DEFINE THE EFFECTS OF HYPERLIPIDEMIA-INDUCED INFLAMMATION AND THE ROLES OF DEATH RECEPTOR SIGNALING IN IL-1SS PRODUCTION, MITOCHONDRIAL APOPTOSIS IN VIABILITY OF NEUTROPHIL LINEAGE CELLS, AND NECROPTOSIS SIGNALING IN ATHEROGENESIS. OUR SYNERGISTIC AND UNIQUE PROGRAM USES THE COMPLEMENTARY EXPERTISE OF THREE RENOWN RESEARCHERS, EXPERTS IN THE AREAS OF NEUTROPHIL DEVELOPMENT, NEUTROPHIL INTRACELLULAR FUNCTION REGULATION AND INFLAMMATION, TO STUDY THE CENTRAL HYPOTHESIS THAT UNRESTRICTED ACTIVATION OF NEUTROPHIL PROGENITORS AND MATURE NEUTROPHILS IS A FUNDAMENTAL PROCESS IN CARDIOVASCULAR DISEASE. THESE STUDIES WILL LEAD TO NOVEL APPROACHES TO TREAT NEUTROPHIL-MEDIATED INFLAMMATION IN CAD.

THROMBUS FORMATION AND ANTITHROMBOTIC INTERVENTION

OPERATIONAL SUPPORT FOR THE GLOBAL OCEAN BIOGEOCHEMISTRY ARRAY (GO-BGC)

INFECTION DISEASE ENDEMIC TO KENYA, VACCINE AND DRUG TRIALS AND ENTOMOLOGY

CANCER AS A COMPLEX ADAPTIVE SYSTEM

PEDIATRIC OHIO-NEW YORK CANCER (PEDS-ONC) IMMUNOTHERAPY CENTER

DYNAMICS OF COLONIZATION AND INFECTION BY MULTIDRUG-RESISTANT PATHOGENS IN IMMUNOCOMPROMISED AND CRITICALLY ILL PATIENTS (DYNAMITE)

DEFINING THE ROLE OF ALTERED CYTOKINE SIGNALING PATHWAYS ON AUTOIMMUNITY

GEORGIA CARES

PURPOSE: LAUNCH THE START-UP ACADEMY, WHICH WILL FORMALIZE A NETWORK OF NAVIGATION RESOURCES, MENTORSHIP OPPORTUNITIES, AND FUNDING TO HELP INNOVATORS SUCCESSFULLY SCALE AND LAUNCH THEIR BIOPRODUCTS IN THE REGION. DEVELOP, IMPLEMENT, AND GROW THE BIORESOURCE COORDINATION AND ACCESS NETWORK (BIOCAN). ACTIVITIES TO BE PERFORMED: 1) HIRE BIOLAUNCH STAFF TO INVENTORY AND BUILD CONNECTIONS TO REGIONAL BIOTECHNOLOGY AND ENTREPRENEURSHIP RESOURCES. 2) LAUNCH AND GROW THE START-UP ACADEMY TO ASSIST AND ATTRACT BIOTECH INNOVATORS TO THE REGION. START-UP ACADEMY WILL HELP BIOTECH INNOVATORS NAVIGATE AND CONNECT TO THE RESOURCES AND MENTORSHIP NECESSARY TO GROW THEIR COMPANIES. 3) COORDINATE THE REGION?S STRONG CONTRACT DEVELOPMENT AND MANUFACTURING ORGANIZATION (CDMO) CAPACITIES AND CAPABILITIES AND ROBUST PILOT-SCALE LAB NETWORK, FUNNELING US INNOVATORS TO THESE RESOURCES. ENABLE SMALL BIOTECH INNOVATORS TO SURMOUNT KEY BARRIERS FROM LAB TO MARKET BY ACCELERATING AND SUPPORTING ACCESS TO REGIONAL SCALE-UP AND MANUFACTURING RESOURCES. EXPECTED OUTCOMES: A ROBUST NETWORK OF RESOURCES AVAILABLE TO BIOTECH INNOVATORS TO HELP THEM LAUNCH THEIR PRODUCTS IN THE REGION. NEW FOUNDER COMMUNITY FORMED, INNOVATORS ENGAGED IN CONFERENCES AND EVENTS, AND MENTORSHIP MADE AVAILABLE TO ENTREPRENEURS. 280 BIOTECH FIRMS RECEIVE CONCIERGE SERVICES, 140 BIOTECH FIRMS RECEIVE MENTORING SERVICES, AND 700 OR MORE HOURS OF MENTORING PROVIDED BY YEAR 5. DEVELOP THE BIOCAN GRANTS PROCESS, EVALUATION, AND SELECTION CRITERIA AND THE GRANTS PORTAL. 36 INNOVATORS WILL RECEIVE GRANTS, 28 NEW PRODUCTS ARE MANUFACTURED BY REGIONAL CDMOS, AND 34 INNOVATORS MATCHED WITH LAB SPACE BY YEAR 5. INTENDED BENEFICIARIES: INNOVATORS AND ENTREPRENEURS BENEFIT FROM CURATED BIOTECH RESOURCES, SUPPORT SERVICES, COMMUNITY, FUNDING, AND MENTORSHIP. CONTRACT DEVELOPMENT AND MANUFACTURING ORGANIZATION GAIN OPPORTUNITY TO PRODUCE NEW PRODUCTS. SUBRECIPIENT ACTIVITIES: BIOCROSSROADS WILL SUPPORT REVIEW AND CURATION OF REGIONAL BIOTECHNOLOGY AND ENTREPRENEURSHIP RESOURCES, AS WELL AS THE LAUNCH AND GROWTH OF THE START-UP ACADEMY.

A GENE THERAPEUTIC APPROACH TO STABLE SUPPRESSION OF HIV-1 REPLICATION

THE OBJECTIVE OF THIS PROJECT IS TO ADVANCE THE DEVELOPMENT OF A DIRECT AIR CAPTURE (DAC) HUB IN THE SOUTHERN SAN JOAQUIN VALLEY OF CALIFORNIA BY DESIGNING, ENGINEERING, AND PLANNING AN INTEGRATED DAC SYSTEM.

GENETICS OF MALE INFERTILITY: A MARKER OF OVERALL HEALTH

SYSTEMS IMMUNOLOGY PROFILING OF RESPIRATORY VIRAL INFECTIONS IN VULNERABLE POPULATIONS - SUMMARY/ABSTRACT – OVERALL ACUTE RESPIRATORY VIRAL INFECTIONS (ARVI) ARE THE MOST FREQUENTLY OCCURRING GLOBAL ILLNESS PRODUCING SIGNIFICANT MORBIDITY AND MORTALITY, PARTICULARLY IN VULNERABLE POPULATIONS. CHILDREN SUFFER HIGHER FREQUENCIES OF ARVI AND OFTEN EXPERIENCE RE-INFECTIONS. COMMON CHRONIC DISEASES OF CHILDHOOD, MOST NOTABLY ASTHMA BUT ALSO ALLERGIES (ATOPY) AND OBESITY, CAN PREDISPOSE TO INCREASED SEVERITY OF ARVI. SIMILARLY, ADULTS WITH CHRONIC INFLAMMATORY DISEASES OR ON IMMUNOSUPPRESSION SUFFER SIGNIFICANT CONSEQUENCES FROM ARVI. ADULTS WITH RHEUMATOID ARTHRITIS (RA) HAVE AN INCREASED RISK FOR INFECTION AND RESPIRATORY MUCOSAL INFLAMMATION MAY CONTRIBUTE TO AUTOIMMUNE DISEASE SEVERITY. THE GOAL OF THIS RESEARCH PROGRAM IS TO UNDERSTAND THE MOLECULAR AND CELLULAR IMMUNE SIGNATURES OF THE VULNERABLE HOST RESPONSE TO ARVI TO IDENTIFY NOVEL THERAPIES AND INDIVIDUALS AT RISK FOR CLINICAL COMPLICATIONS. THE PROGRAM INCLUDES A DETAILED SYSTEMS IMMUNOLOGY ASSESSMENT OF ACUTE AND LONG-TERM AIRWAY AND ADAPTIVE SYSTEMIC IMMUNE RESPONSES TO NATURALLY OCCURRING ARVI. THE FIRST PROJECT WILL IDENTIFY HOW ASTHMA, ATOPY, AND OBESITY LEAD TO MALADAPTIVE IMMUNE RESPONSES TO ARVI IN PEDIATRIC SUBJECTS. THE SECOND PROJECT WILL EXAMINE HOST RESPONSE TO ARVI IN ADULTS WITH RA. RA IS A DISEASE PROVOKED BY ENVIRONMENTAL STIMULI LIKE RESPIRATORY INFECTIONS AND RA PATIENTS HAVE BASELINE IMMUNE DIFFERENCES. THESE PROJECTS ARE COMPLEMENTARY AND SYNERGISTIC BY UTILIZING SIMILAR SAMPLE TYPES AND TIMING OF SAMPLE COLLECTION, AND COMMON CLINICAL ENDPOINTS. THE INDIVIDUAL PROJECTS BENEFIT FROM SHARED MULTI-OMICS APPROACHES THROUGH A GENOMICS CORE FOR THE SAMPLE PROCESSING AND GENERATION OF AIRWAY HOST TRANSCRIPTOME, PROTEOME, EPITHELIAL METHYLATION, AND VIRAL QUANTITY AND EXPRESSION DATA, ALONG WITH HOST GENETICS. THERE IS ALSO A SHARED ADAPTIVE PHENOTYPING CORE FOR THE GENERATION OF HIGH DIMENSIONAL CYTOMETRY DATA TO BROADLY CHARACTERIZE IMMUNE CELL PHENOTYPES AND FOR DETAILED IDENTIFICATION OF ANTIGEN-SPECIFIC CELLS. THIS WILL ALLOW FOR DIRECT COMPARISONS TO BE MADE BETWEEN THE ADULT AND PEDIATRIC COHORTS TO IDENTIFY COMMON AND DIVERGENT RESPONSES TO ARVI. IN THE OVERALL, THE FIRST SPECIFIC AIM IS TO DETERMINE SIMILAR AND DIVERGENT HOST RESPONSES TO ARVI CONSIDERING THE PEDIATRIC ALLERGY/ASTHMA (PROJECT 1) AND ADULT RA (PROJECT 2) COHORTS. THE SECOND SPECIFIC AIM IS TO CONSIDER THESE HOST RESPONSES IN THE CONTEXT OF OTHER LARGE PUBLICLY-FUNDED STUDIES OF VIRAL INFECTION THROUGH META-ANALYSES. THE FINAL SPECIFIC AIM WILL BE TO DEVELOP PREDICTIVE SPATIOTEMPORAL MODELS OF HOW MUCOSAL AND SYSTEMIC IMMUNE RESPONSES TO ARVI INFLUENCE CLINICAL OUTCOMES. OUR RESEARCH PROGRAM WILL PRODUCE NOVEL MECHANISTIC INSIGHTS INTO THE DIVERSITY AND COMMONALITY OF HUMAN IMMUNE RESPONSES TO ACUTE RESPIRATORY VIRUSES AND USE CUTTING- EDGE METHODS TO IDENTIFY POTENTIAL THERAPIES.

HUMAN ISLET RESEARCH ENHANCEMENT CENTER FOR THE HUMAN ISLET RESEARCH NETWORK

PURE AND AUTHENTIC HIV-1 ENV IMMUNOGENS

ONCOLOGY RESEARCH CAREER DEVELOPMENT PROGRAM

NATURAL HISTORY OF HPV INFECTION IN MEN: THE HIM STUDY

COORDINATING UNIT FOR DIACOMP

CYTOCHROME P-450 POLYMORPHISM

SCALABLE SYNTHESIS AND NEW BOND DISCONNECTIONS

REMOTE MONITORING AND VIRTUAL COLLABORATIVE CARE FOR HYPERTENSION CONTROL TO PREVENT COGNITIVE DECLINE - AGGRESSIVE MANAGEMENT OF HYPERTENSION (HTN) MAY REDUCE THE INCIDENCE OF COGNITIVE IMPAIRMENT, DEMENTIA, AND ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (ADRD). DESPITE THIS, 3 OUT OF 4 OLDER ADULTS WITH HTN FAIL TO REACH BLOOD PRESSURE (BP) GOALS. MULTIPLE BARRIERS CONSPIRE AGAINST THE EFFORTS OF PATIENTS AND THEIR CLINICIANS TO OPTIMIZE BP IN OLDER PATIENTS. WE BELIEVE THESE BARRIERS ARE LARGELY SURMOUNTABLE BY REORGANIZATION OF THE CURRENT MODEL OF HTN MANAGEMENT AND LEVERAGING NEW TECHNOLOGY, IMPLEMENTATION SCIENCE, AND TEAM-BASED SYSTEM-WIDE PROCESSES. GIVEN THE HIGH PREVALENCE OF HTN, THESE HEALTH SYSTEM-WIDE EFFORTS MAY HAVE A LARGE IMPACT ON THE PREVALENCE OF ADRD. AS A POTENTIAL PUBLIC HEALTH APPROACH TO ADRD PREVENTION, WE PROPOSE A PRAGMATIC-IMPLEMENTATION STUDY TESTING A HEALTH-SYSTEM WIDE STRATEGY LEVERAGING HOME BP MONITORING AND A “VIRTUAL” COLLABORATIVE CARE CLINIC (VCCC) DEPLOYED IN TWO HEALTH SYSTEMS. WE HYPOTHESIZE THIS APPROACH WILL SAFELY AND EFFECTIVELY LOWER BP AND SLOW AGE-RELATED DECLINE IN COGNITION WHILE REDUCING CARDIOVASCULAR RISK, MORTALITY, AND HEALTH CARE UTILIZATION. THE STUDY WILL BE STRUCTURED IN TWO PHASES. THE PRIMARY OBJECTIVE OF PHASE I (R61) IS TO DEMONSTRATE FEASIBILITY, ASSESS PATIENT ACCEPTABILITY AND SATISFACTION, AND REFINE PROCESSES AND PROCEDURES TO ENABLE HIGH SCALE DELIVERY OF THE VCCC AT THE HEALTH SYSTEM LEVEL. WE WILL OBTAIN IRB APPROVAL, ENGAGE KEY STAKEHOLDERS (HEALTH SYSTEM, PCP’S AND PATIENTS), OPTIMIZE ELECTRONIC HEALTH RECORD (EHR) PROCESSES (ALERTS AND REFERRALS), REFINE CARE ALGORITHMS AND PROCESSES, AND LAUNCH THE INTERVENTION IN 3 PRIMARY CARE CLINICS. WE WILL ENROLL N= 60 PATIENTS TO VCCC FOR 3 MONTHS TO ASSESS IMPORTANT IMPLEMENTATION OUTCOMES AND INFORM GO / NO-GO DECISIONS. UPON ACHIEVING THE MILESTONES OF PHASE I, WE WILL SCALE THE PROGRAM TO MEET THE PHASE II (R31) OBJECTIVE OF IMPLEMENTING THE INTERVENTION ACROSS TWO DIFFERENT HEALTH SYSTEMS (UNIVERSITIES OF KANSAS AND UTAH HEALTH SYSTEMS) TO RANDOMIZE N=1000 PATIENTS TO VCCC VS. CONTROLS (USUAL CARE WITH EDUCATION) FOR 2 YEARS. WE WILL ASSESS EFFECTIVENESS OF VCCC IN ACHIEVING BP GOALS (1º) AND REDUCING 2º MEASURES OF COGNITIVE DECLINE, MAJOR ADVERSE CARDIOVASCULAR EVENTS, ATHEROSCLEROTIC CARDIOVASCULAR DISEASE RISK, HEALTH CARE RESOURCE UTILIZATION, AND MORTALITY. WE WILL ALSO ASSESS CRITICAL IMPLEMENTATION OUTCOMES RELEVANT TO WIDE-SCALE ADOPTION INCLUDING FEASIBILITY, ACCEPTABILITY, APPROPRIATENESS, AND INTENTION TO ADOPT. OUR MULTIDISCIPLINARY COLLABORATIVE TEAM AND HISTORY OF COLLABORATION WITH OUR HEALTH SYSTEM PROVIDES AN EXCELLENT FOUNDATION FOR THIS STUDY. WE HAVE THE NECESSARY EXPERTISE IN CLINICAL TRIALS FOR ADRD PREVENTION, HTN MANAGEMENT, AND EHR FOCUSED PRAGMATIC TRIALS AT BOTH INSTITUTIONS. WITH THE SUCCESSFUL IMPLEMENTATION OF OUR BP LOWERING PROGRAM ACROSS THE TWO HEALTH SYSTEMS, WE WILL BE WELL-POSITIONED TO SCALE THE MODEL TO MULTIPLE HEALTH SYSTEMS FOR DEFINITIVE TESTING ON REDUCING THE INCIDENCE OF ADRD IN A MUCH LARGER COHORT.

THE CENTER FOR ACCELERATING SUICIDE PREVENTION IN REAL-WORLD SETTINGS (ASPIRES) - SUICIDE IS A MAJOR AND GROWING PUBLIC HEALTH PROBLEM AMONG YOUTH IN THE UNITED STATES. INTEGRATING SUICIDE PREVENTION STRATEGIES AS A CORE COMPONENT OF HEALTH CARE DELIVERY AND PROVIDING ACCESS TO HEALTH SERVICES FOR INDIVIDUALS AT RISK FOR SUICIDE IS A PRIMARY GOAL OF THE NATIONAL ACTION ALLIANCE FOR SUICIDE PREVENTION (NAASP). LACK OF PREVENTION STRATEGIES UNIVERSALLY ASSIMILATED INTO ROUTINE HEALTH CARE IS AN OBSTACLE TO ACHIEVING MEANINGFUL REDUCTIONS IN YOUTH SUICIDE. TO ADDRESS THIS PROBLEM, WE PROPOSE TO DEVELOP THE CENTER FOR ACCELERATING SUICIDE PREVENTION IN REAL-WORLD SETTINGS (ASPIRES) TO HASTEN THE IMPLEMENTATION OF EFFECTIVE AND SCALABLE EVIDENCE-BASED INTERVENTIONS TO REDUCE YOUTH SUICIDE. ASPIRES WILL FOCUS ON INTEGRATED PROGRAMS OF RESEARCH THAT SPAN THE CONTINUUM OF CARE FROM EARLY IDENTIFICATION IN PRIMARY AND SPECIALTY HEALTH CARE SETTINGS, TO ACUTE AND TRANSITIONAL CARE, AND BACK INTO THE COMMUNITY AS PART OF ROUTINE HEALTH CARE PRACTICE. THE TARGET POPULATION IS YOUTH AT ELEVATED RISK FOR SUICIDE, THE MAJORITY OF WHICH ARE FROM LOWER SOCIOECONOMIC HOUSEHOLDS EXPERIENCING SIGNIFICANT HEALTH DISPARITIES. THE SPECIFIC AIMS OF ASPIRES INCLUDE: (1) CREATE AN INFRASTRUCTURE TO FOSTER INNOVATIVE, TRANSDISCIPLINARY APPROACHES TO ACCELERATE THE IMPLEMENTATION AND UTILITY OF YOUTH SUICIDE PREVENTION INTERVENTIONS IN REAL-WORLD SETTINGS; (2) CONDUCT INTEGRATED PROGRAMS OF HIGH-IMPACT RESEARCH TO IMPROVE RISK DETECTION AND DEPLOY INNOVATIVE INTERVENTIONS THAT HAVE STRONG POTENTIAL FOR SCALABILITY AND SUSTAINABILITY IN REAL-WORLD SETTINGS; (3) CHARACTERIZE THE IMPLEMENTATION CONTEXT TO GENERATE RECOMMENDATIONS FOR CONTEXTUALLY SENSITIVE IMPLEMENTATION STRATEGIES FOR VARIED HEALTHCARE SETTINGS; (4) CULTIVATE THE NEXT GENERATION OF EMERGING AND ADVANCED SCHOLARS FROM DIVERSE BACKGROUNDS TO CONDUCT STATE- OF-THE-ART SUICIDE PREVENTION RESEARCH; (5) COORDINATE A PROGRAM OF PILOT STUDIES THAT TEST THE MOST PROMISING IDEAS TO ACCELERATE INNOVATIONS IN PRACTICE-BASED YOUTH SUICIDE PREVENTION; AND (6) COMMUNICATE AND DISSEMINATE CENTER-RELATED FINDINGS TO KEY STAKEHOLDERS AND PROMOTE DATA SHARING. THE CENTER’S PLANNED PORTFOLIO OF SCIENCE INCLUDES INTEGRATED EFFORTS PROMOTING ACCELERATED RESEARCH ACROSS A CONTINUUM OF HEALTH CARE SETTINGS THAT COULD NOT BE ACCOMPLISHED USING INDIVIDUAL PROJECT MECHANISMS. THE SIGNATURE (R01-LEVEL) HYBRID EFFECTIVENESS-IMPLEMENTATION PROJECT FOCUSES ON UNIVERSAL SUICIDE RISK SCREENING AND ENHANCING QUALITY IMPROVEMENT IN PEDIATRIC PRIMARY CARE SETTINGS. THREE EXPLORATORY PROJECTS INCLUDE: 1) TESTING AN ESTABLISHED INTERVENTION IN A SPECIALTY CARE SETTING TO ADDRESS YOUNG CHILDREN AT HIGH FAMILIAL RISK FOR SUICIDAL BEHAVIOR; 2) TESTING AN EVIDENCE-BASED TREATMENT ALTERNATIVE TO INPATIENT HOSPITALIZATION THAT TARGETS FAMILY FUNCTIONING TO REDUCE YOUTH SUICIDAL BEHAVIOR IN AN ACUTE CARE SETTING; AND 3) DEVELOPING A TECHNOLOGY-BASED INTERVENTION TO PROMOTE LETHAL MEANS RESTRICTION DURING THE “HIGH-RISK” TRANSITIONAL CARE PERIOD FOLLOWING DISCHARGE FROM A PSYCHIATRIC HOSPITAL. THE PROJECT TEAM IS WELL-SUITED TO RUN THE PROPOSED CENTER WITH EXPERTISE FROM MULTIPLE DISCIPLINES AND AN EXTENSIVE COMMUNITY-BASED STAKEHOLDER AND PATIENT NETWORK.

MECHANISMS OF SENSITIZATION IN HIGH RISK CORNEAL GRAFTS

STRENGTHENING CAPACITY THROUGH IMPROVED MANAGEMENT AND COORDINATION OF LABORATORY

THE UNIVERSITY OF KANSAS CANCER CENTER'S- MCA RURAL NCORP

A COMPARATIVE EFFECTIVENESS TRIAL OF EXTENDED RELEASE NALTREXONE VERSUS EXTENDED-RELEASE BUPRENORPHINE WITH INDIVIDUALS LEAVING JAIL

HUMAN SPECIMEN BANKING IN NCI-SUPPORTED CANCER CLINICAL

ENDOTHELIAL BARRIER PROTECTION AND REPAIR IN ACUTE LUNG INJURY

HIV INTERACTIONS IN VIRAL EVOLUTION

CIRI ONCOLOGY RESEARCH ALLIANCE (CORA)

MRN: MISSION OF DISCOVERY AND ADVANCEMENT OF CLINICAL SOLUTIONS FOR THE PREVENTION, DIAGNOSIS, AND TREATMENT OF MENTAL ILLNESS AND OTHER BRAIN DISOR

COMBINATION HIV ANTIRETROVIRAL RECTAL MICROBICIDE PROGRAM

SPORE IN LUNG CANCER

IDENTIFICATION OF THERAPEUTICS FOR THE TREATMENT OF SULFUR MUSTARD INJURY (U54)

CORRECTING THE ANTI-HER-2 CD4 TH1 RESPONSE IN BREAST CANCER THERAPY TO PREVENT RECURRENCE

MOLECULAR REGULATION OF CELL DEVELOPMENT AND DIFFERENTIATION

TARGETING DNA METHYLATION AND THE CANCER EPIGENOME

SINGLE-MOLECULE DNA SEQUENCING WITH ENGINEERED NANOPORES

HYPERBARIC OXYGEN BRAIN INJURY TREATMENT (HOBIT) TRIAL - CCC

PARENTS' TRANSLATIONAL RESEARCH CENTER

CENTER FOR TRANSPORT ONCOPHYSICS

ELECTROPHYSIOLOGY OF ALCOHOL IN EXTENDED AMYGDELA

OPTIMIZING HIV IMMUNOGEN-BCR INTERACTIONS FOR VACCINE DEVELOPMENT

PALLIATIVE CARE FOR QUALITY OF LIFE AND SYMPTOM CONCERNS IN LUNG CANCER

CENTER FOR SYSTEMATIC MODELING OF CANCER DEVELOPMENT

COMBATING SUBCLONAL EVOLUTION OF RESISTANT CANCER PHENOTYPES

BROADLY EFFECTIVE HCV VACCINE - PROGRAM SUMMARY THE OVERARCHING GOAL OF THIS P01 PROPOSAL IS TO DEVELOP NOVEL HEPATITIS C VIRUS (HCV) VACCINE CANDIDATES THAT CAN ELICIT POTENT BROADLY NEUTRALIZING ANTIBODY RESPONSES IN IMMUNIZATION. DESPITE HIGHLY EFFECTIVE ANTIVIRAL DRUGS AGAINST HCV NOW BEING AVAILABLE, THE CONTINUOUS INCREASE IN NEW INFECTIONS UNDERSCORES THE REAL-WORLD CHALLENGES IN COMBATING THIS HUMAN INFECTION WITHOUT A VACCINE. THIS P01 PROPOSAL “BROADLY EFFECTIVE HEPATITIS C VACCINE” IS BUILT ON THE HYPOTHESIS THAT AN HCV VACCINE EFFECTIVE AGAINST DIVERSE CIRCULATING HCV STRAINS CAN BE DEVELOPED THROUGH RATIONAL ENGINEERING OF VACCINES TO ENHANCE ANTIGEN IMMUNOGENICITY AND PRESENTATION OF CONSERVED NEUTRALIZING EPITOPES, AND TO TARGET WELL-DEFINED MULTIDONOR CLASS BROADLY NEUTRALIZING ANTIBODY (BNAB) RESPONSES TO HCV. MULTIDONOR CLASS ANTIBODY RESPONSES ARE ANTIBODIES SHARING COMMON GENETIC AND FUNCTIONAL FEATURES PRODUCED IN INFECTION OR VACCINATION AT THE POPULATION LEVEL. THIS P01 PROGRAM CONSISTS OF 2 RESEARCH PROJECTS, SUPPORTED BY AN ADMIN CORE AND 2 SCIENTIFIC CORES. THE OVERALL AIMS OF THE PROGRAM ARE: (1) TO DETERMINE THE STRUCTURES OF HCV ENVELOPE GLYCOPROTEINS IMPORTANT FOR RATIONAL VACCINE DESIGN; (2) TO RATIONALLY DESIGN HCV VACCINE ANTIGENS FOR ELICITATION OF BROADLY NEUTRALIZING ANTIBODIES THAT WILL BE EFFECTIVE AGAINST DIVERSE CIRCULATING VIRAL STRAINS; (3) TO DETERMINE THE ANTIBODY RESPONSES ELICITED BY HCV VACCINE ANTIGENS IN PRECLINICAL ANIMAL MODELS. SUCCESS IN THIS RESEARCH PROGRAM WILL RESULT IN BOTH BASIC SCIENTIFIC KNOWLEDGE AND A STRONG HCV VACCINE CANDIDATE FOR FUTURE PILOT PRODUCTION AND CLINICAL TESTING.

SOUTHERN RESEARCH SPECIALIZED BIOCONTAINMENT SCREENING CENTER (SRSBSC)

CHANGES IN FUNCTIONING AMONG MENTALLY RETARDED ADULTS

CENCOOS: INTEGRATING MARINE OBSERVATIONS FOR DECISION MAKERS AND THE GENERAL PUBLIC

KANSAS CENTER FOR METABOLISM AND OBESITY RESEARCH (KC-MORE) - CENTER OVERALL: PROJECT SUMMARY THIS COBRE PROPOSAL SEEKS TO ESTABLISH THE KANSAS CENTER FOR METABOLISM AND OBESITY RESEARCH (KC-MORE) WHICH WILL UNIFY INVESTIGATORS FROM MULTIPLE DEPARTMENTS AND RESEARCH CENTERS AT THE UNIVERSITY OF KANSAS MEDICAL CENTER TO FOCUS RESEARCH ON THE PATHOLOGY OF OBESITY, METABOLIC DYSFUNCTION, AND OBESITY-RELATED DISEASE. OBESITY IS A CRITICAL PROBLEM THAT IS HARMING THE HEALTH OF PEOPLE IN KANSAS AS WELL AS THE ENTIRE U.S. NEW RESEARCH-DRIVEN SOLUTIONS AND THERAPIES ARE NEEDED TO PREVENT AND TREAT OBESITY, INVESTIGATE METABOLIC SIGNATURES THAT UNDERLY OBESITY, AND EXAMINE MECHANISMS BY WHICH OBESITY INITIATES CHRONIC DISEASE. THE KC- MORE WILL SERVE TO MERGE THESE AREAS OF FOCUS BY (1) CREATING A SHARED INTELLECTUAL HOME FOR OBESITY-RELATED RESEARCHERS THROUGH A COMMON EDUCATIONAL AND SEMINAR PROGRAM, (2) PROVIDING FUNDING AND MENTORSHIP FOR EARLY STAGE OBESITY-RELATED INVESTIGATORS TO ESTABLISH INDEPENDENT RESEARCH CAREERS, (3) ESTABLISHING SCIENTIFIC CORES TO FACILITATE TRANSLATIONAL RESEARCH OF BOTH EARLY STAGE AND ESTABLISHED INVESTIGATORS, AND (4) PARTNERING WITH DEPARTMENTS TO JOINTLY RECRUIT NEW INVESTIGATORS TO KUMC FOCUSED ON THEMES OF THE KC-MORE. THIS CENTRAL ROLE IN LEADING AND COORDINATING OBESITY RESEARCH AND INCENTIVIZING FUTURE RESOURCES AND RECRUITMENT WILL ALLOW KUMC TO SYNERGIZE EFFORTS AND FORM MULTI-DISCIPLINARY COLLABORATIONS ON OBESITY, METABOLISM, AND OBESITY-INDUCED DISEASE RESEARCH IN WAYS THAT WOULD NOT OCCUR WITHOUT COBRE FUNDING. THE KC-MORE WILL BE LED BY TWO MULTI- PIS, DRS. STEVEN WEINMAN AND JOHN THYFAULT, AND A RENOWNED SENIOR INVESTIGATOR, DR. JOSEPH DONNELLY WHO WILL SERVE AS CHAIR OF THE STEERING COMMITTEE AND LEAD HUMAN ENERGY BALANCE RESEARCH. THESE LEADERS HAVE MULTI- DISCIPLINARY BUT COMPLIMENTARY EXPERTISE IN BASIC, CLINICAL, AND TRANSLATIONAL RESEARCH. PHASE 1 OF THE CENTER WILL SUPPORT THE DEVELOPMENT OF FOUR RESEARCH PROJECT LEADERS (RPLS) WITH STUDIES ON NEURAL CONTROL OF ENERGY BALANCE, CLINICAL-BASED APPROACHES TO WEIGHT LOSS IN RURAL COMMUNITIES, AND BASIC MECHANISMS OF OBESITY-RELATED FATTY LIVER DISEASE AND HYPERTENSION. KC-MORE WILL ALSO ADMINISTER A PILOT AWARDS PROGRAM TO DEVELOP ADDITIONAL KC-MORE RESEARCHERS. THE KC-MORE WILL LEAD 3 NEW SCIENTIFIC CORES THAT PROVIDE A FOUNDATION FOR TRANSLATIONAL RESEARCH CAPABILITIES (THE METABOLISM (MET) CORE, THE CELLS, TISSUES, BIOANALYSIS AND BIOINFORMATICS (CTBB) CORE, AND THE HUMAN ENERGY BALANCE (HEB) CORE). THE CORES WILL SUPPORT INFRASTRUCTURE AND METHODOLOGIES FOR THE RESEARCH PROJECT LEADERS, THE PILOT AWARD RECIPIENTS, AND A LARGE POOL OF ESTABLISHED OBESITY-RELATED RESEARCHERS ON CAMPUS. A CRITICAL GOAL OF PHASE 1 OF THE KC-MORE COBRE WILL BE TO HELP RPLS DEVELOP INDEPENDENT, R01-FUNDED RESEARCH PROGRAMS. OVERALL, THE ESTABLISHMENT OF THE KC-MORE WILL SERVE TO DEVELOP A TRANSLATIONAL AND MULTI-DISCIPLINARY OBESITY RESEARCH PROGRAM THAT WILL HAVE A SIGNIFICANT FUTURE IMPACT BY REDUCING THE BURDEN OF OBESITY-RELATED DISEASE CONDITIONS.

FOUR-DIMENSIONAL HETEROGENEITY OF FLUID PHASE BIOPSIES IN CANCER (4DB-CENTER)

MOLECULAR MECHANISMS LINKING AGING, ABETA PROTEOTOXICITY AND NEURODEGENERATION

DEVELOPMENT AND ADVANCEMENT OF BROAD-SPECTRUM RESPIRATORY ANTIVIRALS

FOLLOW-UP OF OVARIAN CANCER GENETIC ASSOCIATION AND INTERACTION STUDIES (FOCI)

MICRORNAS FOR THERAPY OF VISUAL DISORDERS

MANIPULATING NATURAL HOST IMMUNOREGULATION VIA IDO DURING VIRAL INFECTION

IDENTIFYING METABOLIC VULNERABILITIES IN LUNG CANCER - OVERALL PROJECT SUMMARY IDENTIFYING METABOLIC VULNERABILITIES IN LUNG CANCER LUNG CANCER IS THE MOST COMMON CAUSE OF CANCER DEATHS WORLD-WIDE. TYROSINE KINASE INHIBITORS AND IMMUNOTHERAPY HAVE BEEN SHOWN TO BE EFFECTIVE IN A SUBSET OF PATIENTS; HOWEVER, THE OVERALL SURVIVAL RATE FOR THIS DISEASE REMAINS LOW ESPECIALLY FOR METASTATIC DISEASE. MOREOVER, SMALL CELL LUNG CANCER (SCLC) PATIENTS HAVE A POOR PROGNOSIS, AND THERE ESPECIALLY EXISTS A GAP IN KNOWLEDGE IN UNDERSTANDING SCLC AND IDENTIFYING EFFECTIVE THERAPEUTIC STRATEGIES. OUR GOAL IN THIS PROPOSAL IS TO UNDERSTAND THE UNDERLYING BIOLOGY OF KEY DRIVERS IN LUNG CANCER BY IDENTIFYING METABOLIC VULNERABILITIES THAT CAN ULTIMATELY BE USED AS SINGLE AGENTS OR COMBINED WITH IMMUNOTHERAPY TO TARGET LUNG CANCER THERAPEUTICALLY. WE WILL ACHIEVE THIS GOAL BY ENGAGING EXPERTS THAT HAVE DEVELOPED PRECLINICAL MODELS WITH COMMON MOLECULAR SIGNATURES IN NON-SMALL CELL (NSCLC) AND SMALL CELL LUNG CANCER (SCLC) AND CUTTING-EDGE METABOLOMICS. WE HAVE AN ACTIVE AND COLLABORATIVE GROUP THAT MEETS TWICE MONTHLY WITH PROJECTS AND MANUSCRIPTS THAT ARE CO-AUTHORED BY THE LEADERS OF EACH PROJECT AND CORE. ADDITIONALLY, OUR PROGRAM PROJECT GRANT (PPG) TEAM IS LOCATED AT MOFFITT CANCER CENTER, WHICH IS AN IDEAL PLACE TO STUDY THE PATHOGENESIS OF LUNG CANCER. FLORIDA IS NUMBER 2 IN THE COUNTRY IN TERMS OF NEWLY DIAGNOSED LUNG CANCER PATIENTS. MOFFITT TREATS 10% OF THESE CASES. THE PPG CONSISTS OF FOUR PROJECTS AND FOUR CORES. THESE PROJECTS AND CORES COLLABORATE AND SYNERGIZE TO MEET FOUR OBJECTIVES: I. TO IDENTIFY METABOLIC VULNERABILITIES IN LUNG CANCERS THROUGH INTEGRATIVE ANALYSIS OF IN VIVO AND EX VIVO MODELS WITH COMMON MOLECULAR SIGNATURES, INCLUDING P53, NRF2/KEAP1, AND MYC (PROJECT #1, LED BY DR. FLORES, PROJECT #2, LED BY DR. DENICOLA, PROJECT #3, LED BY DRS. CLEVELAND AND HAURA, AND PROJECT #4, LED BY DR. RODRIGUEZ WITH SUPPORT FROM THE ADMINISTRATIVE CORE #1, LED BY DRS. FLORES AND HAURA, PRECLINICAL MODELS AND PATHOLOGY CORE #2, LED BY DRS. CRESS AND KARRETH, METABOLISM CORE #3, LED BY DR. KOOMEN, AND DATA SCIENCE CORE #4, LED BY DR. FRIDLEY), II. TO IDENTIFY METABOLIC VULNERABILITIES THAT SYNERGIZE WITH IMMUNOTHERAPY THROUGH EXAMINING THE TUMOR MICROENVIRONMENT AND GAINING A DEEP MOLECULAR UNDERSTANDING OF MYELOID DERIVED SUPPRESSOR CELLS (MDSCS). (PROJECT #4 IN COLLABORATION WITH PROJECTS #1 AND #2 AND CORE #2), III. TO BUILD MOUSE MODELS AS A PLATFORM TO UNDERSTAND THE METABOLIC PATHWAYS UTILIZED BY LUNG CANCERS WITH DIFFERENT GENETIC SIGNATURES AND TO ASSESS THERAPEUTIC STRATEGIES FOR LUNG CANCER. (CORE #2 SUPPORTING PROJECTS #1-4), AND IV. TO SHARE RESOURCES AND DATA LOCALLY AND GLOBALLY TO OBTAIN AN INTEGRATED MOLECULAR UNDERSTANDING OF METABOLIC VULNERABILITIES IN LUNG CANCER. (CORE #4 LEADING EFFORTS FROM ALL PROJECTS AND CORES).

COMMUNITY PROJECT FUNDING/CONGRESSIONALLY DIRECTED SPENDING - CONSTRUCTION - THE UNIVERSITY OF KANSAS CANCER CENTER RECEIVED COMPREHENSIVE CANCER CENTER DESIGNATION BY THE NATIONAL CANCER INSTITUTE IN 2022. THIS IS THE HIGHEST LEVEL OF RECOGNITION AWARDED BY THE NCI. COMPREHENSIVE DESIGNATION AFFIRMS THAT OUR PROGRAM DEMONSTRATES AN EXCEPTIONAL DEPTH AND BREADTH OF RESEARCH, SIGNIFICANT TRANSDISCIPLINARY RESEARCH THAT BRIDGES SCIENTIFIC AREAS, AND AN EFFECTIVE COMMUNITY OUTREACH PROGRAM. WE ARE THE ONLY NATIONAL CANCER INSTITUTE (NCI)-DESIGNATED COMPREHENSIVE CANCER CENTER IN THE REGION, AND 1 OF ONLY 53 IN THE NATION, TO RECEIVE THIS ELITE DISTINCTION. WITH 350 CANCER RESEARCHERS AND CLINICIANS, AND 150-PLUS DISEASE-SPECIFIC ONCOLOGISTS, WE ARE ELEVATING THE STANDARDS IN CANCER CARE. AT THE RECOMMENDATION OF OUR EXTERNAL ADVISORY BOARD, AND TO MOVE FORWARD WITH OUR STATED VISION OF UNIFYING THE PHYSICAL SPACES OF OUR CANCER CENTER UNDER ONE ROOF, WE ARE EMBARKING UPON THE CONSTRUCTION OF THE UNIVERSITY OF KANSAS CANCER CENTER BUILDING, WITH CONSTRUCTION SLATED TO BEGIN IN SEPTEMBER 2024. THIS 205,000 SQUARE FOOT BUILDING COLLECTIVELY BRING TOGETHER AND SUPPORT THE WORK OF OUR CANCER CENTER SCIENTISTS, CLINICIANS AND RESEARCHERS IN A CENTRALIZED BUILDING. THIS NEW HOME WILL ALLOW FOR THE EXPANSION OF OUR RESEARCH TEAMS IN BASIC SCIENCE, CLINICAL, AND POPULATION HEALTH, AND WILL ENCOURAGE INCREASED INTERACTIONS AND COLLABORATIONS. FOR THE PEOPLE IN OUR REGION, THIS MEANS GREATER ACCESS TO LEADING-EDGE TREATMENTS, INCLUDING CLINICAL TRIALS, AS WELL AS THE BEST AND BRIGHTEST MINDS IN CANCER. A FACILITY CONTAINING BASIC, TRANSLATIONAL AND POPULATION SCIENCE FACULTY ADJACENT TO OUR NEWLY CONSTRUCTED ONCOLOGY IN-PATIENT TOWER WILL BE A SIGNIFICANT CATALYST FOR FURTHER GROWTH AND STRENGTHENING OF OUR CENTER. THIS WILL BE PARTICULARLY IMPORTANT FOR OUR DIVERSITY, EQUITY, INCLUSION AND ACCESSIBILITY EFFORTS AS MANY OF OUR POPULATION HEALTH RESEARCHERS FOCUS THEIR WORK ON UNDERSERVED AND MARGINALIZED POPULATION GROUPS WITHIN OUR C ATCHMENT AREA. COMPLETION OF THIS PREMIER NCI COMPREHENSIVE CANCER CENTER BUILDING WILL POSITION THE UNIVERSITY OF KANSAS CANCER CENTER TO LEAD THE REGION IN NEW CANCER THERAPEUTICS, IMMUNOTHERAPY, AND CUTTING EDGE TECHNOLOGY TO GIVE OUR CANCER CENTER COMMUNITY THE CARE THAT IT DESERVES. OVER $105 MILLION HAS ALREADY BEEN SECURED FOR THE CONSTRUCTION OF THIS BUILDING, AND AN ADDITIONAL $100 MILLION IS FORTHCOMING UPON THE APPROVAL OF A $75 MILLION STATE OF KANSAS BUDGET LINE ITEM THIS SUMMER AND MATCHING PRIVATE PHILANTHROPIC GIFTS. THESE HRSA FUNDS WILL SUPPLEMENT THE CONSTRUCTION OF THIS FACILITY FOR THE BREAST CANCER RESEARCH GROUP.

COMMUNITY PROJECT FUNDING/CONGRESSIONALLY DIRECTED SPENDING - CONSTRUCTION - UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC., MSN 1039, 3901 RAINBOW BLVD, KANSAS CITY, KS 66103-2937 KUCC DIRECTOR: ROY JENSEN, MD, 913-588-2568, RJENSEN@KUMC.EDU $10,000,000 THE UNIVERSITY OF KANSAS CANCER CENTER (KUCC) IS A MATRIX CONSORTIUM CANCER CENTER WITH THREE RESEARCH PROGRAMS: 1) CANCER BIOLOGY, 2) CANCER PREVENTION AND CONTROL, AND 3) DRUG DISCOVERY, DELIVERY AND EXPERIMENTAL THERAPEUTICS. IN 2020, 171 MEMBERS OF KUCC ACCOUNTED FOR $9.7M OF NCI FUNDING AND A TOTAL OF $57M IN OVERALL CANCER-RELATED FUNDING, AN INCREASE OF $8M SINCE THE LAST CCSG SUBMISSION. SUPPORTED BY AN EXPERIENCED, NATIONALLY RECOGNIZED LEADERSHIP TEAM, ROY A. JENSEN, MD, HAS LED KUCC ON A STRONG UPWARD TRAJECTORY THAT HAS BEEN CATALYZED BY OVER $467M PHILANTHROPIC SUPPORT SINCE 2004. THE RESEARCH OF THE KUCC FACULTY MEMBERS IS SUPPORTED IN PART BY SEVERAL CORE FACILITIES AND SHARED RESOURCES ON THE KUMC CAMPUS. THESE SHARED FACILITIES ARE THE BACKBONE FOR EXPANDING INNOVATIONS IN CANCER RESEARCH OVER THE NEXT DECADE, AND CRITICAL FOR THE ADVANCEMENT OF CANCER RESEARCH AS A WHOLE. THIS PROPOSAL REQUESTS CANCER RESEARCH EQUIPMENT FOR THE FOLLOWING AREAS: PROTEOMICS, BIOSPECIMEN REPOSITORY, IMAGING, FLOW CYTOMETRY, BIOINFORMATICS, MICROSCOPIC IMAGING, AND ESSENTIAL BASIC SCIENCE EQUIPMENT. THESE NEW INSTRUMENTS WILL HELP PROVIDE CUTTING EDGE TECHNOLOGY AND THE OPTIMAL ENVIRONMENT TO FOCUS THE POWER OF PRECISION MEDICINE, BASIC SCIENCE INQUIRY, DRUG DISCOVERY AND DEVELOPMENT, AND BEHAVIORAL INTERVENTIONS TO DECREASE CANCER INCIDENCE, MORBIDITY, AND MORTALITY. THESE ENHANCEMENTS WILL INCREASE OUR COMPETITIVE CAPABILITIES AND ALSO ADVANCE TEAM SCIENCE BY FOSTERING INNOVATIVE PARTNERSHIPS AND COLLABORATIONS.

NEW; TITLE: MULTI-SCALE SYSTEMS BIOLOGY OF LOW-DOSE CARCINOGENESIS RISK; PI: LYNN HLATKY

NEW BIOSPECIMENS TO ENHANCE RESEARCH IN THE CALIFORNIA TEACHERS STUDY COHORT