Yale University

INSULIN RESISTANCE INTERVENTION AFTER STROKE TRIAL

CLINICAL AND TRANSLATIONAL SCIENCE AWARD

DATA COORDINATION CENTER FOR THE RMN

YALE UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE AWARD PROGRAM

GRADUATE RESEARCH FELLOWSHIP PROGRAM

EXPERMENTAL STUDIES

MEDICAL SCIENTIST TRAINING PROGRAM

PSYCHOTHERAPY DEVELOPMENT RESEARCH CENTER

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

YALE TOBACCO CENTER OF REGULATORY SCIENCE

PERUVIAN/BRAZILIAN AMAZON CENTER OF EXCELLENCE IN MALARIA

TAS::89 0222::TAS; NEW; RELATIVISTIC HEAVY ION PHYSICS; PI - JOHN HARRIS

REGULATION OF LIVER BY NUCLEAR CA2+ SIGNALING

MOLECULAR MECHANISMS OF ARTERIGENESIS

CONSUMER ASSESSMENT OF HEALTHCARE PROVIDERS AND SYSTEMS

RESEARCH IN ELEMENTARY PARTICLES AND INTERACTIONS

PREDOCTORAL PROGRAM IN CELLULAR AND MOLECULAR BIOLOGY

GEORGE M O'BRIEN KIDNEY CENTER AT YALE

TOWARDS FAULT-TOLERANCE IN A HARDWARE-EFFICIENT MODULAR ARCHITECTURE

GRANT

PROGRAM IN MACROMOLECULAR STRUCTURE, MOTION, CONTROL

MATERIALS LIMITS ON COHERENCE IN CHARGE QUBITS

YALE CENTER FOR MENDELIAN GENOMICS

MOLECULAR BASIS OF VIRAL AND CELLULAR TRANSFORMATION

ERROR-CORRECTED QUANTUM REGISTERS FOR A MODULAR SUPERCONDUCTING QUANTUM COMPUTER

CELLULAR AND MOLECULAR STUDIES OF RENAL TRANSPORT

YALE TRANSDISCIPLINARY COLLABORATIVE CENTER FOR HEALTH DISPARITIES RESEARCH (YALE-TCC)

CENTER FOR INNOVATIVE STRUCTURES AND PHENOMENA

BRINGING RESEARCH TO IMPACT FOR DEVELOPMENT, GLOBAL ENGAGEMENT, AND UTILIZATION (BRIDGE-U) UNDER EXISTING SCIENCE, TECHNOLOGY, INNOVATION, AND PARTNERSHIP ANNUAL PROGRAM STATEMENT APS NO.: 7200AA18APS00003

TAS::89 0227::TAS RECOVERY ACT HIGH ENERGY PHYSICS RESEARCH, TASKS A, B, C, D, F, G, K AND J

STUDIES ON TRANSFER RNA

ADDRESSING RISK THROUGH COMMUNITY TREATMENT FOR INFECTIOUS DISEASE AND OPIOID USE DISORDER NOW (ACTION) AMONG JUSTICE-INVOLVED POPULATIONS

THIS PROJECT IS AIMED AT DEVELOPING A LOW COST NOVEL DEVICE FOR BREAST MRI. MRI IS A PROVEN MODALITY FOR IMAGING CANCERS OF THE BREAST AND THE PRIMARY FACTOR LIMITING ITS WIDESPREAD USE IS ACCESS WHICH IS LIMITED DUE TO THE HIGH COST OF MRI MACHINES AND DIFFICULT SITING DUE TO THEIR LARGE SIZE. IMPROVED ACCESS TO BREAST MRI COULD MAKE ANNUAL SCREENING AVAILABLE FOR THE MAJORITY OF WOMEN AND IN TURN THIS WOULD SAVE MANY LIVES. EARLY DETECTION OF CANCER IS A KEY TO IMPROVED OUTCOMES. INCLUDING BREAST MRIS AS PART OF AN ANNUAL EXAM FOR ALL WOMEN WOULD HAVE A MAJOR POSITIVE OUTCOME ON WOMENS HEALTH. THERE ARE NO SUBRECIPIENTS.

MECHANISMS OF SOCIAL ENGAGEMENT IN AUTISM SPECTRUM DISORDERS

1/8-PREDICTORS AND MECHANISMS OF CONVERSION TO PSYCHOSIS

YALE HEAD AND NECK CANCER SPORE: OVERCOMING TREATMENT RESISTANCE IN HEAD AND NECK CANCER

POLYCYSTIC KIDNEY DISEASE: A DISORDER OF GLOMERULOTUBULAR SYNCHRONIZATION

TARGETING BREAST CANCER BRAIN METASTASES WITH AN ANTI-DNA AUTOANTIBODY

RISK STRATIFICATION IN OLDER PERSONS WITH ACUTE MYOCARDIAL INFARCTION: SILVER-AMI

CELLULAR, MOLECULAR, AND FUNCTIONAL IMAGING APPROACHES TO UNDERSTANDING EARLY NEURODEVELOPMENT IN AUTISM

YALE CENTER FOR MENDELIAN DISORDERS

SYSTEMS ANALYSIS OF PHENOTYPIC SWITCH IN CONTROL OF CANCER INVASION

THIS PROPOSED PROJECT FOCUSES ON ESTIMATING HOW KEY FACTORS CONTRIBUTING TO EMISSIONS, AIR QUALITY AND HEALTH AFFECT REGIONAL AND LOCAL DIFFERENCES I

NEUROEXPLORER: ULTRA-HIGH PERFORMANCE HUMAN BRAIN PET IMAGER FOR HIGHLY-RESOLVED IN VIVO IMAGING OF NEUROCHEMISTRY

TRANSCRIPTIONAL ATLAS OF HUMAN BRAIN DEVELOPMENT

MECHANISMS OF BILE SECRETION AND CHOLESTASIS

WEST CAMPUS B3(WB3)VIVARIUM

STRUCTURE AND FUNCTION OF ARP 2/3 COMPLEX

MOLECULAR AND CELLULAR BASIS OF COGNITIVE AGING IN PREFRONTAL CORTICAL NETWORKS

LINKS BETWEEN PRODUCTION AND PERCEPTION IN SPEECH

FATTY ACID AMIDE HYDROLASE (FAAH) INHIBITOR TREATMENT OF CANNABIS USE DISORDER (CUD)

A SYSTEMS APPROACH TO THE DEVELOPMENT AND FUNCTION OF C4 PHOTOSYNTHESIS

SILENT ALLOSTERIC MODULATION OF MGLUR5 FOR SAFE AND EFFECTIVE THERAPY OF ALZHEIMER'S DISEASE

STRATEGIES TO OVERCOME IMMUNE RESISTANCE IN HEAD AND NECK CANCERS

OXOMANGANESE CATALYSTS FOR SOLAR FUEL PRODUCTION

YALE ALZHEIMER DISEASE RESEARCH CENTER

PREDOCTORAL TRAINING PROGRAM IN GENETICS

YOUNG WOMEN WITH ACUTE MYOCARDIAL INFARCTION

FYN INHIBITION BY AZD0530 FOR ALZHEIMERS DISEASE

NEURONEX: THE FABRIC OF THE PRIMATE NEOCORTEX AND THE ORIGIN OF MENTAL REPRESENTATIONS. FROM TRANSCRIPTOMICS TO SINGLE NEURONS AND NEURONAL NETWORKS.

PREDICTIVE PERSONALIZED PUBLIC HEALTH (P3H): A NOVEL PARADIGM TO TREAT INFECTIOUS DISEASE

ORIGIN OF CORTICAL SPECIES-SPECIFIC DISTINCTIONS

FUNCTIONAL GENOMICS OF HUMAN BRAIN DEVELOPMENT

ALCOHOL AND MULTISUBSTANCE USE IN THE VETERANS AGING COHORT STUDY

MODERNIZATION OF THE YALE PET CORE - POSITRON EMISSION TOMOGRAPHY (PET) IS A POWERFUL IMAGING MODALITY THAT ENABLES VISUALIZATION AND QUANTIFICATION OF BIOLOGICAL FUNCTIONS USING RADIOPHARMACEUTICALS. HOWEVER, DUE TO THE SHORT HALF-LIVES OF PET ISOTOPES (E.G., 20 MINUTES FOR C-11, 2 HOURS FOR F-18), THE ENTIRE PROCESS FROM CYCLOTRON TO RADIOPHARMACEUTICAL SYNTHESIS TO QUALITY CONTROL TO INJECTION, AND IMAGING MUST BE STREAMLINED TO ENSURE EFFICIENCY AND RADIOCHEMICAL YIELD. THE RADIOPHARMACY FACILITIES AT THE YALE SCHOOL OF MEDICINE (YSM) ARE HOUSED WITHIN THE YALE PET CORE WHICH OPERATES AS A REVENUE-NEUTRAL INTER-SERVICE PROVIDER OFFERING FULL PET STUDY SERVICES EXCLUSIVELY FOR RESEARCH. THE PET CORE SERVES INVESTIGATORS IN PSYCHIATRY, NEUROLOGY, CARDIOLOGY, ENDOCRINOLOGY, AND BASIC NEUROSCIENCE. INVESTIGATORS ARE PART OF A LARGE NIH-FUNDED COMMUNITY AT YALE AND THROUGHOUT NEW ENGLAND, AS WELL AS SEVERAL INSTITUTIONS NATIONALLY THROUGH CLINICAL TRIALS RECRUITING SUBJECTS IN THE YALE PET CORE. SINCE ITS INCEPTION IN 2006, THE PET CORE HAS GROWN RAPIDLY, PERFORMING PET IMAGING RESEARCH STUDIES IN HUMANS AND A VARIETY OF ANIMAL SPECIES. OVER 1,100 SCANS ARE PROJECTED FOR 2025. DESPITE A SIGNIFICANT INCREASE IN THE NUMBER OF SCANNERS AND EFFICIENCY IN THE PET CORE, RADIOCHEMISTRY PRODUCTION CAPABILITIES HAVE NOT GROWN ACCORDINGLY. CURRENTLY, THERE ARE 7 PET SCANNERS AVAILABLE FOR ROUTINE USE, WITH MORE EXPECTED TO BE INSTALLED SHORTLY, WHILE THE RADIOPHARMACY FACILITIES WERE ORIGINALLY DESIGNED TO SUPPORT RADIOTRACER PRODUCTION FOR 3 PET SCANNERS. TO OPERATE AVAILABLE PET SCANNERS AT FULL CAPACITY, THE PET CORE WILL REQUIRE A SUBSTANTIAL INCREASE TO THE EXISTING RADIOCHEMISTRY INFRASTRUCTURE. THIS WOULD SIGNIFICANTLY REDUCE THE WAITING TIME (4-6 WEEKS) TO PERFORM A PET SCAN. FURTHERMORE, A UNIQUE OPPORTUNITY EXISTS TO EXPAND AND UPDATE THE PET CORE FACILITIES TO BRING THE RADIOPHARMACY MANUFACTURING TO 21 CFR PART 212 CURRENT GOOD MANUFACTURING PRACTICE (CGMP) FOR PET DRUG PRODUCTION. SINCE THE RADIOCHEMISTRY AND RADIOPHARMACY FACILITIES HAVE NOT UNDERGONE A MAJOR REDESIGN SINCE 2006, A SIGNIFICANT UPGRADE IS NECESSARY. THIS WILL ENABLE THE PRODUCTION OF APPROVED COMPOUNDS IN THE AREAS OF ONCOLOGY, NEURODEGENERATION AND CARDIAC IMAGING, WHILE ENABLING SHIPPING RADIOPHARMACEUTICALS FOR HUMAN USE OUTSIDE THE YALE CAMPUS. MOST IMPORTANTLY, THE EXPANSION AND UPGRADES TO THE RADIOCHEMISTRY FACILITIES WILL ENHANCE THE INVESTIGATORS’ ABILITY TO EFFICIENTLY WORK ON THE DISCOVERY AND DEVELOPMENT OF NOVEL RADIOCHEMISTRY COMPOUNDS FOCUSED ON THE DETECTION, UNDERSTANDING, AND TREATMENT OF DISEASE AND STREAMLINE TRANSLATION TO RADIOPHARMACEUTICAL PRODUCTION. THE PET CORE MULTI-PHASE RENOVATION AND EXPANSION PROJECT WILL OCCUR WITHIN THE MAGNETIC RESONANCE RESEARCH CENTER BUILDING (MRC). THE REQUESTED C06 FUNDS WILL BE USED IN THREE PHASES TO: I) BUILD A NEW RADIOCHEMISTRY/RADIOPHARMACY/QC LAB CGMP SUITE, II) UPGRADE THE EXISTING RADIOCHEMISTRY LAB TO CGMP, AND III) CONVERT THE QC LAB TO A RESEARCH HOT CHEMISTRY LAB. THIS SCOPE WILL ACCELERATE DISCOVERY AND DEVELOPMENT OF NOVEL RADIOCHEMISTRY COMPOUNDS, ENABLE SHIPPING OF PET RADIOTRACERS TO OUTSIDE ENTITIES, REDUCE WAITING TIME FOR PET IMAGING AND MAXIMIZE YALE’S UNIQUE PET RESOURCES’ REACH AND ACCESSIBILITY.

TM INTERACTIONS IN MEMBRANE PROTEIN FOLDING AND FUNCTION

TRANSFORM-HF CCC

OOCYTE DEVELOPMENT IN DROSOPHILA

ALCOHOL ASSOCIATED OUTCOMES AMONG HIV+/- AGING VETERANS

TAS::89 0222::TAS - NUCLEAR PHYSICS-EXPERIMENTAL RESEARCH

THIS AWARD IS ISSUED FOR A PROGRAM TO SUPPORT BUILDING EFFECTIVE, RESILIENT, AND TRUSTED POLICE ORGANIZATIONS IN MEXICO.

SYNDECAN FUNCTION IN ENDOTHELIAL CELLS

GENETICS OF OPIOID DEPENDENCE

GAINING EARLY AWARENESS AND READINESS FOR UNDERGRADUATE PROGRAMS (GEAR UP PARTNERSHIP)

MENTAL HEALTH NEW ENGLAND TECHNOLOGY TRANSFER CENTER (MH-NETT)

THE IDENTIFICATION AND CHARACTERIZATION OF GENETIC VARIANTS UNDERLYING CARDIOVASCULAR DISEASES

PATHOGENESIS OF YOUTH ONSET PRE DIABETES AND TYPE 2 DIABETES.

EVOLUTIONARY GENETICS OF TSETSE AND ITS SYMBIONTS

THIS COOPERATIVE AGREEMENT SHALL BE PERFORMED IN ACCORDANCE WITH STATEMENT OF WORK, ENTITLED 'IDEAL: AN INTELLIGENT DESIGN ENVIRONMENT FOR ASYNCHRONO

EMBED: PRAGMATIC TRIAL OF USER-CENTERED CLINICAL DECISION SUPPORT TO IMPLEMENT EMERGENCY DEPARTMENT-INITIATED BUPRENORPHINE FOR OPIOID USE DISORDER

RF CONTROL AND MEASUREMENT OF SUPERCONDUCTING QUBITS

GEAR-UP

BII: PREDICTING THE GLOBAL HOST-VIRUS NETWORK FROM MOLECULAR FOUNDATIONS -THE VIRAL EMERGENCE RESEARCH INITIATIVE BIOLOGY INTEGRATION INSTITUTE (VERENA BII) WILL INTEGRATE DATA AND BIOLOGICAL THEORY ACROSS THE FIELDS OF MICROBIOLOGY, IMMUNOLOGY, ECOLOGY, EVOLUTION, AND GLOBAL CHANGE BIOLOGY, WORKING TOWARDS A UNIFIED UNDERSTANDING THAT IMPROVES OUR ABILITY TO PREDICT VIRAL EMERGENCE. THE COVID-19 PANDEMIC HIGHLIGHTS A PRESSING NEED TO UNDERSTAND THE ECOLOGY AND EVOLUTION OF EMERGING VIRUSES. THESE GLOBAL DYNAMICS ARE DETERMINED FIRST AND FOREMOST BY THE GENETIC CODE OF BOTH VIRUSES AND THEIR HOSTS, AND BY MICROSCOPIC INTERACTIONS BETWEEN THE TWO AT THE LEVEL OF PROTEINS AND CELLS. HOWEVER, BIOLOGISTS FREQUENTLY STRUGGLE TO CONNECT THEORY ACROSS THESE SCALES. AT THE HEART OF THIS RESEARCH EFFORT IS AN OPEN CLEARINGHOUSE OF BIG DATA, CREATING NEW OPPORTUNITIES TO APPLY ARTIFICIAL INTELLIGENCE TO REAL-WORLD PROBLEMS. TO FOSTER A CORE SET OF DATA FLUENCY AND INTERDISCIPLINARY RESEARCH SKILLS, THE LIGHTHOUSE LEARNING COMMUNITY WILL TRAIN PARTICIPANTS AT EVERY CAREER STAGE IN THE BOUNDARY-SPANNING SCIENCE OF THE HOST-VIRUS NETWORK, INCLUDING MORE THAN 100 EARLY CAREER SCIENTISTS. UNDERGRADUATES WILL BE INTRODUCED TO BOTH BIOLOGY AND DATA SCIENCE THROUGH A COURSE-BASED UNDERGRADUATE RESEARCH EXPERIENCE IN ?THE FUNDAMENTALS OF DISEASE SURVEILLANCE,? WHILE GRADUATE STUDENTS AND POSTDOCTORAL FELLOWS WILL EXPLORE THESE METHODS DEEPER THROUGH A BIOLOGY INTEGRATION WORKSHOP SERIES, INCLUDING A NEW SUMMER IN THE CAPITOL PROGRAM IN WASHINGTON, D.C. THIS COHORT OF EMERGING SCHOLARS WILL USE OPEN SOURCE MATERIALS, K-12 OUTREACH, AND DIGITAL MEDIA TO HARNESS PUBLIC INTEREST IN EMERGING DISEASES LIKE COVID-19, RAISING AWARENESS ABOUT KEY ISSUES WHILE SHARING THE IMPORTANCE OF BASIC BIOLOGICAL RESEARCH TO SAVE LIVES AND PROTECT ECOSYSTEMS. TO IDENTIFY THE MECHANISTIC AND MOLECULAR RULES OF LIFE THAT GOVERN HOST-VIRUS DYNAMICS AT PLANETARY SCALES, THE VERENA BII WILL LEVERAGE A UNIQUE MIX OF DATA SYNTHESIS, COMPUTATIONAL INNOVATION, FIELD SAMPLING, AND LABORATORY EXPERIMENTS TO IDENTIFY THE MOLECULAR UNDERPINNINGS OF HOST-VIRUS INTERACTIONS. AN UNPRECEDENTED COMPARATIVE STUDY OF THE CHIROPTERAN WITHIN-HOST ENVIRONMENT WILL GENERATE AND TEST HYPOTHESES ABOUT THE IMMUNOLOGICAL ADAPTATIONS THAT ALLOW BATS TO TOLERATE DEADLY VIRUSES. IN PARALLEL, MODEL-GUIDED EXPERIMENTS WILL MEASURE THE FEATURES OF THE INVERTEBRATE IMMUNE SYSTEM THAT PLAY THE GREATEST ROLE IN MOSQUITOES? COMPETENCE AS ARBOVIRAL VECTORS. TOGETHER, THESE MODEL SYSTEMS WILL ILLUMINATE THE HARD-CODED BASIS OF HOST-VIRUS COMPATIBILITY, SUPPORTING NEW MACHINE LEARNING METHODS TO PREDICT ECOLOGICAL AND EVOLUTIONARY NETWORKS AND ANTICIPATE GLOBAL RISKS OF VIRAL EMERGENCE IN A CHANGING CLIMATE. MORE BROADLY, THE VERENA BII WILL EXPAND AN EXISTING ROLE AS A HUB OF OPEN DATA, SOFTWARE, AND CYBERINFRASTRUCTURE FOR HOST-VIRUS INTERACTIONS, EXPERIMENTAL VIROLOGY, AND WILDLIFE DISEASE SURVEILLANCE. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

MOLECULAR GENETIC ANALYSIS OF SALMONELLA CELL INVASION

PARAMEDIC REFERRALS FOR INCREASED INDEPENDENCE AND DECREASED DISABILITY IN THE ELDERLY (PRIDE)

DNA REPAIR IN CANCER BIOLOGY AND THERAPY

INVESTIGATION OF NEUTRINO PROPERTIES AND FUNDAMENTAL SYMMETRIES AT YALE

CHRONIC DTH AND IFN-GAMMA IN HUMAN GRAFT ARTERIOSCLEROSIS

NEURAL MECHANISMS OF ITCH

FOOD CUES, STRESS, MOTIVATION FOR HIGHLY PALATABLE FOODS AND WEIGHT GAIN

HIGH-RESOLUTION QUANTUM CONTROL OF CHEMICAL REACTIONS

SENSELAB: INTEGRATION OF MULTIDISCIPLINARY SENSORY DATA

INJURY AND RECOVERY IN DEVELOPING BRAIN

INJURY AND RECOVERY IN DEVELOPING BRAIN

MOBILE HEALTH FOR IMPLEMENTATION OF HOME-BASED TB CONTACT INVESTIGATION IN UGANDA

MOBILE HEALTH FOR IMPLEMENTATION OF HOME-BASED TB CONTACT INVESTIGATION IN UGANDA

STRUCTURE-FUNCTION RELATIONSHIPS IN THE SPIROCHETAL FLAGELLAR MOTOR

ENDOTHELIAL-TO-MESENCHYMA TRANSITION AND ATHEROSCLEROSIS

ENDOTHELIAL-TO-MESENCHYMA TRANSITION AND ATHEROSCLEROSIS

IN VIVO PATHWAY DISCOVERY IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

IN VIVO PATHWAY DISCOVERY IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

YALE MURINE-TMC ON IMMUNE CELL SENESCENCE DERIVED INFLAMMATION - SUMMARY YALE-MURINE TMC (MTMC), THROUGH APPLICATION OF HIGH-CONTENT AND HIGH THROUGHPUT SINGLE-CELL AND SPATIAL OMICS TECHNOLOGIES, WE AIM TO ACCELERATE THE DISCOVERY OF SENESCENT BIOMARKERS, APPLY THEM TO MOUSE MODELS, AND GENERATE HYPOTHESES TO TEST MECHANISMS OF ORGANISMAL AGING. OUR PROPOSED UNBIASED ANALYSES WILL ALSO ANSWER THE QUESTION WHETHER SENESCENT CELLS (STROMAL OR HEMATOPOIETIC LINEAGE) EXIST IN SUFFICIENT QUANTITIES TO ALTER THE INFLAMMATORY LANDSCAPE AND BIOLOGY. YALE-MTMC WILL USE LINEAGE-MARKED MOUSE TO CLASSIFY TYPES OR SUBTYPES OF SENESCENT CELLS, THEIR SPATIAL HETEROGENEITY AND HOW THESE CELLS IMPACT THE TISSUE ENVIRONMENTS. YALE-MTMC WILL ASSEMBLE 1) A MULTIDISCIPLINARY TEAM TO GENERATE THE MOLECULAR AND CELLULAR MAPS OF CELLULAR SENESCENCE IN THYMUS, BONE MARROW, SPLEEN, PBMCS, MESENTERIC AND INGUINAL ADIPOSE TISSUE. 2) DEVELOP AND DEPLOY A SUITE OF HIGH-RESOLUTION, HIGH-CONTENT AND HIGH THROUGHPUT SINGLE-CELL AND SPATIAL OMICS TECHNOLOGIES TO CHARACTERIZE THESE SPECIMENS AND 3) PERFORM INTEGRATED INFORMATICS TO IDENTIFY BIOMARKERS OF SENESCENT CELL HETEROGENEITY AND TO CONSTRUCT COMPREHENSIVE MOLECULAR AND CELLULAR MAPS OF CELLULAR SENESCENCE AND INCLUDING AN I.V CD45 ANTIBODY LABELING/SORTING APPROACH TO STUDY TISSUE RESIDENT IMMUNE CELLS IN NON-LYMPHOID TISSUES. WE WILL UTILIZE THE ANALYSIS PLATFORMS ESTABLISHED THROUGH THE YALE HUMAN TMC TO ENABLE CROSS-SPECIES VERIFICATION OF BIOMARKERS. THREE MAJOR BIOLOGICAL ANALYSIS PIPELINES ARE: (A) MULTIPLEX IMAGING (MI) INCLUDING CODEX, IMC, AND SMI, COMPLEMENTED BY 3D LIGHT SHEET MICROSCOPY OF CLEARED TISSUES, (B) SINGLE CELL ANALYSIS (SCA) INCLUDING SCCITE-SEQ FOR PROTEIN AND MRNA PROFILING, CYTOF FOR HIGH-PLEX IMMUNOPHENOTYPING, AND SINGLE-CELL PROTEIN SECRETOME PROFILING TO MEASURE SASP HETEROGENEITY, AND (C) SPATIAL MULTI-OMICS SEQUENCING (SMOS) USING DBIT-BASED SPATIAL-CITE-SEQ FOR SPATIALLY RESOLVED PROTEO-TRANSCRIPTOMIC MAPPING AT GENOME SCALE. THE COMBINATION OF THESE PIPELINES ALLOWS FOR HIGHLY SENSITIVE AND SINGLE-CELL RESOLUTION MAPPING OF SENESCENT CELLS AND ASSOCIATED TISSUE ENVIRONMENTS. YALE-MTMC AIMS TO ASSEMBLE A MULTIDISCIPLINARY TEAM LED BY PI: DIXIT (DIRECTOR, YALE CENTER FOR RESEARCH ON AGING), AND MPI: MONTGOMERY (IMMUNOLOGIST, ASSOCIATE DEAN FOR SCIENTIFIC AFFAIRS) WITH CORE LEADS DR. FAN (BIOENGINEER), DR. KLUGER (INFORMATICS AND DATA ANALYTICS) AND KEY PERSONNEL DR. BOOTH (MOUSE PATHOLOGIST), DR. LUCAS, HABERMAN (IMMUNOLOGISTS, EXPERT IN PET STORE MOUSE MODEL, IMAGING) WITH IAB COMPOSED OF SCIENTIFIC LEADERS DRS. MEDZHITOV, IWASAKI AND RUDDLE. WE HAVE EXPERIENCE IN MANAGEMENT OF LARGE, MULTI-COMPONENT PROGRAMS AND PRIOR EXPERIENCE WITH GENERATING SIGNIFICANT HIGH-QUALITY IMAGING AND OMICS DATA AS PART OF A CONSORTIUM. A DEDICATED PROGRAM MANAGER WILL MANAGE AND COORDINATE ALL ACTIVITIES ACROSS THE CENTER AND WITH THE SENNET CONSORTIUM. COMPLEMENTARY AND MULTIDISCIPLINARY SCIENTIFIC EXPERTISE OF THE TEAM WILL TRANSLATE INTO THE COLLECTIVE CAPABILITY OF THE TMC TO FOSTER INTEGRATION OF MULTI- DIMENSIONAL, MULTIPARAMETER DATA GENERATION AND COORDINATION WITH SENNET AND OTHER TMCS FOR GREATER IMPACT

BIPOLAR & SCHIZOPHRENIA CONSORTIUM FOR PARSING INTERMEDIATE PHENOTYPES

BIPOLAR & SCHIZOPHRENIA CONSORTIUM FOR PARSING INTERMEDIATE PHENOTYPES

MOLECULAR BASIS FOR MEMBRANE LIPID HOMEOSTASIS

TRANSCRIPTIONAL AND EPIGENETIC SIGNATURES OF HUMAN BRAIN DEVELOPMENT AND AUTISM

TRANSCRIPTIONAL AND EPIGENETIC SIGNATURES OF HUMAN BRAIN DEVELOPMENT AND AUTISM

FLUCTUATIONS IN IONIC CURRENT THROUGH MEMBRANE CHANNELS

FLUCTUATIONS IN IONIC CURRENT THROUGH MEMBRANE CHANNELS

PREDOCTORAL PROGRAM IN BIOPHYSICS

PREDOCTORAL PROGRAM IN BIOPHYSICS

MECHANISMS OF CELL REGULATION AND MANIPULATION BY THE UBIQUITIN SYSTEM

GLUCOREGULATORY HORMONE INTERACTIONS IN DIABETES

YALE CORE GRANT FOR VISION RESEARCH

1/2 CELL TYPE AND REGION-SPECIFIC REGULATORY NETWORKS IN HUMAN BRAIN DEVELOPMENT AND DISORDERS

1/2 CELL TYPE AND REGION-SPECIFIC REGULATORY NETWORKS IN HUMAN BRAIN DEVELOPMENT AND DISORDERS

YALE SCOR ON GENDER-SENSITIVE TREATMENT FOR TOBACCO DEPENDENCE

YALE SCOR ON GENDER-SENSITIVE TREATMENT FOR TOBACCO DEPENDENCE

TREATMENT OF OBESITY AND BINGE EATING: BEHAVIORAL WEIGHT LOSS VERSUS STEPPED CARE

TREATMENT OF OBESITY AND BINGE EATING: BEHAVIORAL WEIGHT LOSS VERSUS STEPPED CARE

NATURALLY-ACQUIRED AND VACCINE-MEDIATED IMMUNITY TO LEPTOSPIROSIS

NATURALLY-ACQUIRED AND VACCINE-MEDIATED IMMUNITY TO LEPTOSPIROSIS

CHINESE HERBAL MEDICINE AS A NOVEL PARADIGM FOR CANCER CHEMOTHERAPY

CHINESE HERBAL MEDICINE AS A NOVEL PARADIGM FOR CANCER CHEMOTHERAPY

SIGNALING MECHANISMS AND FUNCTIONS RELATED TO PATHO-PHYSIOLOGY OF VASCULAR, LUNG AND BLOOD SYSTEMS

SIGNALING MECHANISMS AND FUNCTIONS RELATED TO PATHO-PHYSIOLOGY OF VASCULAR, LUNG AND BLOOD SYSTEMS

WORMGUIDES: A RESOURCE FOR GLOBAL UNDERSTANDING IN DYNAMIC EMBRYONIC SYSTEMS

WORMGUIDES: A RESOURCE FOR GLOBAL UNDERSTANDING IN DYNAMIC EMBRYONIC SYSTEMS

ALLOIMMUNITY TO PROGENITOR CELL-DERIVED HUMAN VASCULAR CELLS

ALLOIMMUNITY TO PROGENITOR CELL-DERIVED HUMAN VASCULAR CELLS

INTEGRATED RF AND B-MODE DEFORMATION ANALYSIS FOR 4D STRESS ECHOCARDIOGRAPHY

INTEGRATED RF AND B-MODE DEFORMATION ANALYSIS FOR 4D STRESS ECHOCARDIOGRAPHY

ANTIDEPRESSANT EFFECT OF NICOTINIC RECEPTOR BLOCKADE

EXPANDING MEDICATION ASSISTED THERAPIES IN UKRAINE

EXPANDING MEDICATION ASSISTED THERAPIES IN UKRAINE

SITE-SELECTIVE CATALYSIS FOR BIOACTIVE SCAFFOLD DIVERSIFICATION

A RANDOMIZED CONTROLLED TRIAL TO REDUCE PNEUMONIA IN NURSING HOME RESIDENTS

A RANDOMIZED CONTROLLED TRIAL TO REDUCE PNEUMONIA IN NURSING HOME RESIDENTS

GENETIC AND CELLULAR MECHANISMS OF NAFLD AND HEPATIC INSULIN RESISTANCE

GENETIC AND CELLULAR MECHANISMS OF NAFLD AND HEPATIC INSULIN RESISTANCE

IMPACTS OF INDIVIDUAL AND SOCIAL BEHAVIOR ON INFLUENZA DYNAMICS AND CONTROL

IMPACTS OF INDIVIDUAL AND SOCIAL BEHAVIOR ON INFLUENZA DYNAMICS AND CONTROL

ACME: ADVANCED COLD MOLECULE ELECTRON ELECTRIC DIPOLE MOMENT SEARCH

ACME: ADVANCED COLD MOLECULE ELECTRON ELECTRIC DIPOLE MOMENT SEARCH

UNDERSTANDING SKIN TISSUE REPAIR IN LIVE MAMMALS

YALE RHEUMATIC DISEASE RESEARCH CORE CENTER

YALE RHEUMATIC DISEASE RESEARCH CORE CENTER

THE YALE WRHR CAREER DEVELOPMENT CENTER

ARTERIOGENESIS AND ARTERIAL BRANCHING

ARTERIOGENESIS AND ARTERIAL BRANCHING

MOLECULAR MECHANISMS OF CELLULAR MOTILITY

MOLECULAR MECHANISMS OF CELLULAR MOTILITY

GENE TARGETS FOR IVH

GENE TARGETS FOR IVH

QUANTITATIVE MULTIMODAL IMAGE GUIDANCE FOR IMPROVED LIVER CANCER TREATMENT

CORTICAL DYNAMICS AND NEURAL/BEHAVIORAL PERFORMANCE

CORTICAL DYNAMICS AND NEURAL/BEHAVIORAL PERFORMANCE

CORE CENTER FOR QUANTITATIVE NEUROSCIENCE WITH MAGNETIC RESONANCE (QNMR)

CORE CENTER FOR QUANTITATIVE NEUROSCIENCE WITH MAGNETIC RESONANCE (QNMR)

CELL TRANSFORMATION BY BOVINE PAPILLOMAVIRUS

CELL TRANSFORMATION BY BOVINE PAPILLOMAVIRUS

ENDING HIV: BRINGING INTEGRATED PREVENTION AND TREATMENT SERVICES TO PEOPLE WHO USE DRUGS WHERE THEY LIVE - PROJECT ABSTRACT: THE UNITED STATES (U.S.) ENDING THE HIV EPIDEMIC (EHE) PLAN’S PRIMARY GOAL IS TO REDUCE THE NUMBER OF NEW HIV INFECTIONS BY 90% BY 2030, BUT THIS WILL NOT HAPPEN UNLESS WE DEVELOP WAYS TO BRING THE EVIDENCED- BASED SERVICES TO PERSONS WHO USE DRUGS (PWUD). OVERDOSE DEATHS ARE DRAMATICALLY INCREASING IN THE US, AND FENTANYL AND STIMULANTS ARE FUELING NEW HIV EPIDEMICS. MY CAREER AND MY PASSION REVOLVE AROUND INTEGRATION OF TREATMENT OF OPIOID USE DISORDER (OUD) AND OTHER SUBSTANCE USE DISORDERS WITH HIV TREATMENT AND PREVENTION. THROUGH OVER 20 YEARS OF DIRECT CLINICAL CARE AS AN INFECTIOUS DISEASE AND ADDICTION MEDICINE PHYSICIAN COMBINED WITH SUBSTANTIAL CLINICAL RESEARCH EXPERTISE INVOLVING PWUD LIVING WITH AND AT RISK OF HIV, I KNOW THE BLIND SPOTS IN THE EHE PLAN AND I CAN FILL THEM IN WITH THIS PIONEER AWARD. MY PIONEERING AWARD VISION IS TO: 1) TRAIN PERSONS WHO LIVE IN THE COMMUNITIES AFFECTED BY HIGH LEVELS OF OVERDOSE TO BE COMMUNITY HEALTH WORKERS (CHWS) TO PROVIDE THE HIV TESTING AND RAPID DIAGNOSIS OF OUD; 2) CREATE MOBILE HUBS THAT ARE PHARMACIES AND CLINICS ON WHEELS THAT CAN BE DEPLOYED TO IMMEDIATELY DISPENSE PRE-EXPOSURE PROPHYLAXIS (PREP), ANTIRETROVIRAL THERAPY (ART), AND MEDICATION TREATMENT FOR OUD (MOUD) ANYWHERE; 3) DEVELOP RAPIDLY DEPLOYABLE MOBILE RAPID RESPONSE TEAMS (THE MOBILE SPOKES) COMPRISED OF THE CHWS AND PHARMACISTS WITH 24 HOUR ACCESS TO ONLINE CLINICIANS THAT DEPLOY OUT FROM THE MOBILE HUBS TO WHERE THE CHWS IDENTIFY TO BRING THE MEDICATIONS (PREP/ART BASED ON THE RAPID HIV TESTING RESULTS, AND MOUD TO PEOPLE WHO HAVE A DIAGNOSIS OF OUD) TO WHERE PEOPLE ‘LIVE’; AND 4) COLLABORATE WITH RESEARCHERS, INCLUDING MODELERS, TO PRIORITIZE WHERE OUTBREAKS OF HIV ARE MOST LIKELY TO OCCUR AND PROVIDE A COLLABORATION HUB FOR OTHERS WORKING IN THE FIELDS OF HIV AND SUBSTANCE USE DISORDERS TO HELP INFORM THIS PROPOSED CARE MODEL. THROUGH THIS AWARD, I WILL ALSO ENSURE THAT THE MOBILE RAPID RESPONSE TEAMS CONTINUE TO FOLLOW PEOPLE AND HELP THEM RETAIN ON THE MEDICATIONS AND ADDRESS COMPETING NEEDS TO ELIMINATE BARRIERS TO ACCESSING SERVICES. THUS, THE OVERALL IDEA IN THIS PIONEER AWARD IS PROVIDING LOW BARRIER SERVICES AT MULTIPLE ACCESS POINTS IN LINE WITH THE EHE PLANS WHERE WE WOULD BE BRINGING THE TESTING AND TREATMENT PLANS (MOUD, PREP/ART) TO PWUD AND RETAINING THEM VIA NON- TRADITIONAL METHODS WHERE THEY LIVE. THROUGH USING TRAINED PERSONS WHO LIVE IN THE COMMUNITIES (CHWS) WITH SHARED LIVING EXPERIENCES OF THEIR COMMUNITY MEMBERS WHO USE DRUGS AND ARE AT RISK OR LIVING WITH HIV, WE CAN PROVIDE THE TESTING AND DIAGNOSIS SERVICES COMBINED WITH PHARMACISTS TO DISPENSE THE MEDICATIONS IN REAL-TIME TO PEOPLE WHO TYPICALLY DO NOT HAVE ACCESS TO OUR NORMAL CLINICAL OR RESEARCH VENUES INCLUDING WOMEN, JUSTICE-INVOLVED PERSONS, IMMIGRANTS, THE UNINSURED, AND UNDERREPRESENTED MINORITIES. I HAVE THE EXPERIENCE, THE PASSION, THE WORK ETHIC AND THE COLLABORATIVE TEAM TO HELP END HIV IN PWUD THROUGH THIS PIONEER AWARD.

(MURI) HIGH COHERENCE QUANTUM PHONONIC CIRCUITS

(MURI) HIGH COHERENCE QUANTUM PHONONIC CIRCUITS

MECHANISM AND INHIBITION OF HIV REVERSE TRANSCRIPTASE

MECHANISM AND INHIBITION OF HIV REVERSE TRANSCRIPTASE

8/8-PREDICTORS AND MECHANISMS OF CONVERSION TO PSYCHOSIS

8/8-PREDICTORS AND MECHANISMS OF CONVERSION TO PSYCHOSIS

CELLULAR AND MOLECULAR ANALYSIS OF B LYMPHOCYTE DEVELOPMENT AND SELECTION

COMPUTER-AIDED DESIGN OF ANTI-HIV DRUGS

COMPUTER-AIDED DESIGN OF ANTI-HIV DRUGS

SOMATIC MOSAICISM IN THE BRAIN OF TOURETTE SYNDROME

SOMATIC MOSAICISM IN THE BRAIN OF TOURETTE SYNDROME

GRADUATE RESEARCH FELLOWSHIP PROGRAM

GRADUATE RESEARCH FELLOWSHIP PROGRAM

REGULATION OF EXOCYTOSIS STUDIES WITH FLIPPED SNARES

REGULATION OF EXOCYTOSIS STUDIES WITH FLIPPED SNARES

YALE CANCER CENTER NCTN LAPS

RNA METABOLISM IN TRYPANOSOMES

DEFINING THE ROLE OF MUTATIONAL BURDEN IN SUSTAINING NORMAL HOMEOSTASIS DURING AGING

GENOMIC ANALYSIS OF TISSUE AND CELLULAR HETEROGENEITY IN IPF

NOVEL INSIGHTS INTO THE MOLECULAR AND CELLULAR MECHANISM REGULATING LIPID METABOLISM AND ATHEROSCLEROSIS

PROTECTING PRIVACY AND FACILITATING SHARED ACCESS OF CLINICAL AND GENETIC DATA OF SPECIAL POPULATIONS

CENTER FOR CARDIOVASCULAR OUTCOMES RESEARCH AT YALE UNIVERSITY

POWERING THE BRAIN: THE CELL BIOLOGY OF NEUROENERGETICS

FUNCTIONAL RELEVANCE OF CFTR TRAFFICKING IN VIVO TO INTESTINAL DISEASE

NEUROGENETIC PROCESSES IN THE FETAL BRAIN

IDENTIFYING ENHANCERS WITH HUMAN-SPECIFIC DEVELOPMENTAL FUNCTIONS

FUNCTIONAL CIRCUITRY OF VISUAL ADAPTATION

STRUCTURAL CORRELATES OF PRESTIN ACTIVITY.

THE IMPACT OF HIV INFECTION ON IMMUNOLOGIC, TRANSCRIPTOMIC, AND METABOLOMIC SIGNATURES OF MEDICATION-ASSISTED THERAPY FOR OPIOID ADDICTION

ION PUMP PARTNERS: REGULATORS OF SORTING AND FUNCTION

DEVELOPMENT AND ORGANIZATION OF THE HUMAN FRONTAL CORTEX

EASTERN CARIBBEAN HEALTH OUTCOMES RESEARCH NETWORK (ECHORN

INTRACRANIAL MULTIMODAL PHYSIOLOGICAL MONITORING IN ACUTE BRAIN INJURY - PROJECT SUMMARY PRESENT DAY MULTIMODAL MONITORING FOR TRAUMATIC BRAIN INJURY (TBI) IS LIMITED IN ITS IMPLEMENTATION AS IT NECESSITATES MULTIPLE INVASIVE PROBES TO MEASURE INTRACRANIAL PRESSURE (ICP), INTRACRANIAL EEG (ICEEG), INTRACRANIAL TEMPERATURE (ICT), AND BRAIN TISSUE OXYGEN (PBTO2), THE MAJORITY OF WHICH REQUIRE THEIR OWN INSTRUMENTATION AND MONITORS. WHILE THERE IS INCREASING EVIDENCE TO SUPPORT MULTIMODAL MONITORING IN TBI AND OTHER ACUTE BRAIN INJURIES, THE PRESENT CUMBERSOME SYSTEMS MAKE IT NEARLY IMPOSSIBLE TO USE OUTSIDE OF MAJOR LEVEL 1 TRAUMA CENTERS. THE CHALLENGES INCLUDE THE NEED FOR EXPERTISE WITH BOTH PROBE PLACEMENT AND DATA INTERPRETATION AS WELL AS THE INTEGRATION OF MULTIPLE ELECTRONIC UNITS FROM DIFFERENT VENDORS WITH DIVERSE SOFTWARE SYSTEMS, EACH REQUIRING TRAINING, IT AND BIOMEDICAL ENGINEERING SUPPORT. COUPLED WITH THIS IS AN INCREASED RISK OF BLEEDING AND INFECTION FROM THE MULTIPLE ENTRY POINTS INTO BRAIN PARENCHYMA. OUR OBJECTIVE IS TO DEVELOP A SINGLE SOURCE BRAIN MONITORING SOLUTION FOR THE MANAGEMENT OF SEVERE TBI. WE WILL INTEGRATE THE MODALITIES INDICATED FOR SEVERE TBI (ICP, ICEEG, ICT, PBTO2) IN A BRAIN IMPLANTABLE DEVICE CALLED THE NEUROPROBE WITH A TARGET DIAMETER WHICH IS EQUIVALENT TO, OR SMALLER THAN, INDIVIDUAL CURRENT PROBES. WE WILL DEVELOP A SINGLE INTERFACE DEVICE CALLED THE NEUROLINK TO ACQUIRE THE MULTI-MODAL INTRACRANIAL DATA FROM THE NEUROPROBE AS WELL AS SCALP EEG AND PATIENT PHYSIOLOGICAL DATA INCLUDING SYSTEMIC BLOOD PRESSURE (SBP), HEART RATE (HR), MEAN ARTERIAL PRESSURE (MAP) AND BLOOD OXYGEN (SPO2) AND TRANSMIT THESE SENSOR SIGNALS TO MONITORS AS A TIME- LOCKED SINGLE DIGITAL DATA STREAM. WE WILL DEVELOP A DISPLAY UNIT CALLED THE NEUROMONITOR TO ANALYZE AND DISPLAY THE ACQUIRED MULTIMODAL DATA IN A SYNCHRONIZED REAL-TIME MANNER. WE CALL THE COMPOSITE SOLUTION CREATED BY THE NEUROPROBE, NEUROLINK, AND NEUROMONITOR DEVICES THE NEUROPROBE SOLUTION. THE TECHNOLOGICAL DEVELOPMENT OF THE NEUROPROBE SOLUTION DRAMATICALLY EXPANDS THE CAPABILITIES OF THE EXISTING ICEEG DEPTH ELECTRODES DEVELOPED AT YALE UNIVERSITY AND MULTIMODAL PROBES CURRENTLY ON THE MARKET. THE KEY INNOVATIONS OF THE NEUROPROBE SOLUTION ARE: 1. INTEGRATION OF MULTIPLE PHYSIOLOGIC SENSORS ON A SINGLE INTRACRANIAL PROBE (NEUROPROBE). 2. SIMPLIFICATION OF NEUROPROBE TO ALLOW PLACEMENT AT BEDSIDE IN A CIVILIAN OR MILITARY FACILITY. 3. DEVELOPMENT OF A MULTIMODAL INTERFACE DEVICE (NEUROLINK) TO STORE AND RELAY TIME-LOCKED DIGITAL DATA ACQUIRED FROM THE NEUROPROBE AND EXTRACRANIAL SENSORS TO THE NEUROMONITOR AND OTHER CLINICAL MONITORS. 4. DEVELOPMENT OF AN IPAD SIZED MONITOR (NEUROMONITOR) TO ANALYZE AND DISPLAY MULTIMODAL DATA. 5. TIME-LOCKED MULTI-STREAM DATA TRANSFER WHICH ALLOWS FOR REAL-TIME AND POST-HOC DATA REVIEW AND ANALYSIS. THIS INNOVATIVE SOLUTION ALLOWS ACQUISITION AND INTEGRATION OF DATA FROM MULTIPLE PHYSIOLOGICAL PARAMETERS THROUGH A STANDARD SMALL TABLET CREATING A SIMPLE SINGLE END-TO-END SOLUTION FROM SENSORS TO MULTIMODAL DATA ANALYSIS AND DISPLAY IN AN OTHERWISE FRAGMENTED AND COMPLEX DOMAIN.

STUDIES OF TRANSFER RNA

EXPLOITING RIBOSWITCH SENSORS TO REVEAL ANTIBIOTICS UPTAKE AND RETENTION IN GRAM NEGATIVE BACTERIA

CENTER FOR POLYCYSTIC KIDNEY DISEASE RESEARCH AT YALE

HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR YOUNG ADULTS WITH SICKLE CELL DISEASE - CLINICAL COORDINATING CENTER

YALE TRAINING PROGRAM IN HEALTH SERVICES RESEARCH