Rector & Visitors Of The University Of Virginia

CANCER CENTER SUPPORT GRANT

MULTIMODAL DEVELOPMENTAL NEUROGENETICS OF FEMALES WITH ASD

CARES ACT HIGHER ED EMERGENCY RELIEF FUND PART 2 FOR THE UNIVERSITY OF VIRGINIA

CARES ACT GRANT US DEPT OF EDUCATION FOR THE UNIVERSITY OF VIRGINIA

PANNEXIN CHANNELS IN VASCULAR PHYSIOLOGY & INFLAMMATION

DOPAMINE/ANGIOSTENSIN RECEPTORS IN GENETIC HYPERTENSION

THE STROKE HYPERGLYCEMIA INSULIN NETWORK EFFORT (SHINE) TRIAL

CARES ACT - RADFORD UNIVERSITY

CELL MIGRATION CONSORTIUM

PROVISION OF CLINICAL DATA TO SUPPORT A NATIONWIDE COVID-19 COHORT COLLABORATIVE

DESCRIPTION:THIS AGREEMENT PROVIDES FUNDING UNDER THE INFLATION REDUCTION ACT (IRA) TO THE UNIVERSITY OF VIRGINIA. SPECIFICALLY, THE PROJECT WILL ALLOW THE UNIVERSITY OF VIRGINIA, WORKING IN UTQIAGVIK, AK, TO IMPROVE STORM- AND MELT-WATER INFRASTRUCTURE AND MANAGEMENT; PRESERVE INUPIAT TRADITIONS AND CULTURAL SITES; ENHANCE BARROW LOCAL UTILITIES' READINESS AND PREPAREDNESS, AND STRENGTHEN LOCAL CAPACITY; IMPROVE RESIDENTIAL SANITATION BY CONNECTING UNSERVICED HOMES TO MODERN WATER/SEWER SYSTEMS; AND PROTECT THE COMMUNITY'S DRINKING WATER LAGOON. ACTIVITIES:THE ACTIVITIES INCLUDE A COMPREHENSIVE DRAINAGE STUDY OF THE CITY TO INFORM INFRASTRUCTURE UPGRADES AND SUSTAINABLE WATER, SNOW AND PERMAFROST MANAGEMENT, AND IMPLEMENTING IDENTIFIED UPGRADES TO BETTER RESPOND TO INCREASED PRECIPITATION, FLOODING AND ASSOCIATED PERMAFROST DEGRADATION; INSTALLING THERMOSIPHONS IN TRADITIONAL ICE CELLARS WITH UPGRADED DRILLING EQUIPMENT, AND INSTALLING AND IMPROVING DRAINAGE AND RESTORING DISTURBED TUNDRA VEGETATION TO REDUCE FLOODING AT THE COMMUNITY'S CEMETERY; UPGRADING OR EXPANDING CRITICAL HEAVY-DUTY MAINTENANCE VEHICLES THAT ARE BETTER EQUIPPED FOR THE ARCTIC CONDITIONS TO ENHANCE THE LOCAL UTILITY'S READINESS AND PREPAREDNESS, AND STRENGTHENING LOCAL WORKFORCE CAPACITY WHILE REDUCING GREENHOUSE GAS EMISSIONS AND OCCUPATIONAL HAZARDS, AND CREATING AND EXPANDING PROGRAMS THAT BUILD KNOWLEDGE AND JOBS IN SUSTAINABLE WATER, SNOW AND PERMAFROST MANAGEMENT; CONNECTING UNSERVICED HOMES TO MODERN WATER/SEWER SYSTEMS, ELIMINATING OR REDUCING THE USE OF HONEY BUCKETS, HUMAN WASTE SPILLAGE, AND ASSOCIATED ENVIRONMENTAL AND HUMAN HEALTH RISKS; AND PROTECTING THE COMMUNITY'S DRINKING WATER LAGOON BY CONDUCTING COMPREHENSIVE FEASIBILITY STUDIES FOR PER-AND POLYFLUOROALKYL (PFAS) SUBSTANCES REMEDIATION/REMOVAL AND ALGAE BLOOM MITIGATION. SUBRECIPIENT:THE SUBAWARD WITH BARROW UTILITIES AND ELECTRIC COOPERATIVE, INC. (BUECI) WILL COVER WATER AND SEWER CONNECTIONS FOR UNSERVICED HOMES, UPGRADE OF HEAVY-DUTY VEHICLES TO IMPROVE READINESS AND REDUCE GREENHOUSE GAS EMISSIONS AND OCCUPATIONAL HAZARDS, FEASIBILITY STUDIES FOR PER- AND POLYFLUOROALKYL SUBSTANCES (PFAS) AND ALGAL GROWTH MITIGATION IN THE COMMUNITY DRINKING WATER LAGOON, MATERIAL COSTS TO STABILIZE SUBSIDING BUECI STRUCTURES DUE TO PERMAFROST DEGRADATION, AND CONTINUING EDUCATION FOR BUECI LEADERSHIP AND MEMBERS. THE SUBAWARD WITH NORTH SLOPE BOROUGH (NSB) WILL COVER IMPROVEMENTS TO DRAINAGE INFRASTRUCTURE AND COVER MATERIALS, AND CIVIL WORKS TO STABILIZE PERMAFROST AND REDUCE MELTWATER FLOODING, IMPROVE PUMPING OPERATION OF NEWLY ADDED SEWER TANKS, CONDUCT A COMMUNITY-WIDE DRAINAGE ASSESSMENT AND PRODUCE AN ACTION PLAN FOR STORMWATER/MELTWATER MANAGEMENT, CONTINUING EDUCATION FOR NSB LEADERSHIP AND PUBLIC WORKS OPERATORS, AND INTERNSHIPS / APPRENTICESHIPS BETWEEN DEPARTMENT OF PUBLIC WORKS AND I#7735;ISA#289;VIK COLLEGE'S WORKFORCE DEVELOPMENT PROGRAM. THE SUBAWARD WITH THE CITY OF UTQIA#289;IVK (COU) WILL ALLOW FOR IMPROVEMENTS TO THE CULTURAL SITE OF IMAIQSAUN CEMETERY AND COVER DRAINAGE DESIGN, DRAINAGE INSTALLATION AND EXPANSION, IMPROVED SNOW AND MELTWATER MANAGEMENT, GRAVESITE REVEGETATION, AND REPATRIATION OF GRAVESITES INCLUDING NEW COFFINS AND CULTURAL RE-BURIAL CEREMONY. THE SUBAWARD WITH THE INUPIAT COMMUNITY OF ARCTIC SLOPE (ICAS) WILL COVER THE PURCHASE AND SHIPPING OF THERMOSIPHONS AND AN AUGER DRILL TO BE USED FOR THEIR ICE CELLAR PRESERVATION PROJECT. THE SUBAWARD WITH THE ARCTIC INFRASTRUCTURE DEVELOPMENT CENTER AT THE UNIVERSITY OF ALASKA FAIRBANKS WILL ALLOW THE AIDC TO PROVIDE ON-SITE ASSESSMENTS, AND REVIEW AND CONSULTATION ON FEASIBILITY STUDIES AND ICE CELLAR PRESERVATION. OUTCOMES:THE ANTICIPATED DELIVERABLES INCLUDE INCLUDE A STORM(MELT)WATER INFRASTRUCTURE AND MANAGEMENT STUDY/ACTION PLAN, AND IMPLEMENTATION OF THE RECOMMENDATIONS IDENTIFIED IN THE PLAN; ACQUISITION OF THERMOSIPHON INSTALLATION EQUIPMENT AND INSTALLATION OF THERMOSIP

TARGETED SPHINGOLIPID METABOLISM FOR TREATMENT OF AML

DESCRIPTION:THIS AGREEMENT PROVIDES FUNDING UNDER THE INFLATION REDUCTION ACT (IRA) TO RECTOR AND VISITORS OF THE UNIVERSITY OF VIRGINIA (UVA). SPECIFICALLY, THE PROJECT WILL IMPLEMENT CLIMATE RESILIENCE PLANNING IN TEN COMMUNITIES THROUGH SOUTHWEST (APPALACHIAN) VIRGINIA AND ADVANCE PROJECTS THAT REDUCE POLLUTION AND CARBON EMISSIONS WHILE SIMULTANEOUSLY ADVANCING CRITICAL COMMUNITY NEEDS: CLIMATE-RESILIENT AFFORDABLE HOUSING, ENERGY-EFFICIENT AND CARBON-NEUTRAL CHILDCARE AND WORKFORCE TRAINING, AND CLIMATE-RESILIENT GATHERING SPACES THAT DOUBLE AS COMMUNITY CAPACITY BUILDING SPACES AND HEALTHCARE ACCESS POINTS. ACTIVITIES:THE ACTIVITIES INCLUDE 1) PARTNER WITH UNITED WAY OF SOUTHWEST VIRGINIA/ENDLESS OPPORTUNITIES (UW/EO), BUCHANAN COUNTY, AND DICKENSON COUNTY TO SUPPORT ELECTRIC VEHICLE TRANSPORTATION OPTIONS AS WELL AS EV CHARGING UNITS; 2) PARTNER WITH BUCHANAN COUNTY AND THE SOUTHERN GAP DEVELOPMENT AREA TO BUILD ENERGY-EFFICIENT, HEALTHY AND CLIMATE-RESILIENT WORKFORCE HOUSING; 3) PARTNER WITH UW/EO TO INCREASE THE ENERGY EFFICIENCIES OF THEIR WORKFORCE AND CHILDCARE CENTERS; 4) PARTNER WITH THE UW/EO TO SUPPORT THE INSTALLATION OF COMMUNITY SOLAR ON THEIR AFFILIATED WORKFORCE DEVELOPMENT AND CHILDCARE CENTERS; 5) PARTNER WITH DICKENSON COUNTY AND THE TOWN OF HAYSI TO DEVELOP A COMMUNITY RESILIENCE HUB THAT CAN ALSO BE A CENTER FOR COMMUNITY ENGAGEMENT AND CAPACITY; 6) PARTNER WITH HEALTHY APPALACHIA INSTITUTE TO RENOVATE 10 LOCATIONS TO DOUBLE AS COMMUNITY RESILIENCE HUBS AND HEALTHCARE OUTPOSTS; 7) CONDUCT FEASIBILITY STUDIES OF ADVANCING MIXED RENEWABLE ENERGY DEVELOPMENTS ON BROWNFIELD SITES IN BUCHANAN AND DICKENSON COUNTIES; AND 8) PARTNER WITH JAMES MADISON UNIVERSITY'S CENTER FOR THE ADVANCEMENT OF SUSTAINABLE ENERGY AND THE NETWORK OF LOCAL COMMUNITY COLLEGES TO ADVANCE CLEAN ENERGY CAREER DEVELOPMENT. SUBRECIPIENT:SUBAWARD OF $4,594,245 TO UNITED WAY (FORMERLY EO) FOR THE DECARBONIZATION AND CARBON MITIGATION OF CHILDCARE CENTERS. THIS PROJECT INCLUDES SOLAR INSTALLATION AND ENERGY EFFICIENCY UPGRADES TO CHILDCARE FACILITIES, OUTDOOR CLASSROOMS, AND BUILDING OUT PROGRAMMING FOR THE RENEWABLE ENERGY SECTOR WORKFORCE. SUBAWARD OF $1,757,708 TO DICKENSON COUNTY FOR BUILDING A CLIMATE RESILIENCE HUB IN THE TOWN OF HAYSI OUTSIDE OF THE FLOODPLAIN. THIS PROJECT INCLUDES ENGINEERING AND ARCHITECTURAL DESIGN AND PERMITS, CONSTRUCTION OF THE FACILITY, AND INSTALLATION OF EV FAST CHARGER. SUBAWARD OF $4,847,841 TO BUCHANAN COUNTY FOR THE BUILDING OF CLIMATE RESILIENT HOUSING IN SOUTHERN GAP OUTSIDE OF THE FLOODPLAIN. THIS PROJECT INCLUDES CONSTRUCTION EXTENSION OF INFRASTRUCTURE (WATER, SEWER, POWER AND TELCOM) TO SUBDIVISION LOTS, CONSTRUCTION OF INTERIOR ROADWAYS AND WALKWAYS, CONSTRUCTION OF TWO SINGLE FAMILY DWELLING UNITS, CONSTRUCTION OF MULTI-FAMILY TOWN HOUSE RENTAL UNITS, AND AN EV CHARGING STATION AT THE REGIONAL OFFICE PARK OFFICE BUILDING. SUBAWARD OF $132,000 TO VIRGINIA TECH FOR A COMMUNITY ENGAGEMENT PROJECT ON CLIMATE RESILIENCE STRATEGIC PLANNING. THIS COMMUNITY-BASED CLIMATE RESILIENCE PLANNING PROCESS INVOLVES THE RAFT (RESILIENCE ADAPTATION FEASIBILITY TOOL). SUBAWARD OF $1,973,797 TO JAMES MADISON UNIVERSITY (JMU) CENTER FOR THE ADVANCEMENT OF SUSTAINABLE ENERGY FOR DEVELOPING CLEAN ENERGY CAREERS. THIS PROJECT INCLUDES BUILDING OR EXPANDING A REGIONAL ENERGY WORKFORCE HUB IN ABINGDON IN PARTNERSHIP WITH VIRGINIA HIGHLANDS COMMUNITY COLLEGE (VHCC) AND NEW RIVER COMMUNITY COLLEGE (NRCC) TO DEVELOP GREEN JOBS PIPELINE, FROM ENTRY LEVEL INSTALLATION, TO PROJECT MANAGEMENT, TO ADVANCED MANAGERIAL AND LEADERSHIP IN RENEWABLE ENERGY CAREERS. PROGRAMS SUPPORTED AT THE REGIONAL HUB WILL ADDRESS RENEWABLE ENERGY SKILL DEVELOPMENT FOR K-12 STUDENTS, TEACHER TRAININGS FOR K-12 FACULTY, RENEWABLE ENERGY KIT AND CURRICULUM DISTRIBUTION, SUMMER CAMPS, AND SUPPORT FOR KIDWIND CHALLENGE TEAMS. OUTCOMES:THE ANTICIPATED DELIVERABLES INCLUDE SOLAR INSTALLATION, ENERGY EFFICIENCY UPGRADES,

NEW: CENTER FOR CATALYTIC HYDROCARBON FUNCTIONALIZATION -- EFRC; PI - BRENT GUNNOE

ESTABLISHED STATUS EPILEPTICUS TREATMENT TRIAL (ESETT)

BASIC CARDIOVASCULAR RESEARCH TRAINING GRANT

STRUCTURAL DYNAMICS OF PRESYNAPTIC MEMBRANE FUSION

HCMR NOVEL MARKERS OF PROGNOSIS IN HYPERTROPHIC CARDIOMYOPATHY

GENERAL CLINICAL RESEARCH CENTER

APPALACHIAN SUPPORT FOR SPECIALIZED EDUCATION TRAINING (ASSET)

ELECTRON INTERACTIONS WITH NUCLEI

CLINICAL ACCEPTANCE OF THE ARTIFICIAL PANCREAS: THE INTERNATIONAL DIABETES CLOSED LOOP (IDCL) TRIAL

SIGNALING AND PROGRESSION IN PROSTATE CANCER

IMMUNOBIOLOGY OF TRANSFUSION

KIDNEY DEVELOPMENT CELL FATE AND PRECURSORS OF DISEASE IN THE YOUNG AND ADULT

PROTEIN SEQUENCING BY TANDEM MASS SPECTROMETRY

INFECTIOUS DISEASES TRAINING PROGRAM

EPIDEMIOLOGY OF OVARIAN CANCER IN AFRICAN-AMERICAN WOMEN

MODULAR BIO-BEHAVIORAL CLOSED-LOOP CONTROL OF TYPE 1 DIABETES

CELEBRATING THE 250TH ANNIVERSARY OF THE UNITED STATES OF AMERICA: CREATING AND SUSTAINING ACCESS TO FOUNDING ERA / EARLY REP [THE COLLABORATIVE PROJECT, CELEBRATING THE 250TH ANNIVERSARY OF THE UNITED STATES OF AMERICA: CREATING AND SUSTAINING ACCESS TO FOUNDING ERA / EARLY REPUBLIC PRIMARY SOURCES, REPRESENTS A TIMELY AND TRANSFORMATIVE INVESTMENT IN RESEARCHING, EDITING, PUBLISHING, AND PROMOTING THE DOCUMENTARY HERITAGE OF THE FOUNDING ERA AND EARLY REPUBLIC. WITH SUPPORT FROM THIS GRANT, THE UNIVERSITY OF VIRGINIA AND ITS PARTNERS WILL ACHIEVE FOUR CRITICAL OUTCOMES: INCREASING OUR UNDERSTANDING OF THE FOUNDING ERA AND EARLY REPUBLIC; REFINING AND STRENGTHENING THE TECHNICAL AND INSTITUTIONAL INFRASTRUCTURE; CREATING A DYNAMIC, FREELY-ACCESSIBLE WEBSITE; AND PROVIDING HANDS-ON TRAINING AND KNOWLEDGE-SHARING OPPORTUNITIES. BY UNITING EDITORIAL EXPERTISE, TECHNOLOGICAL INNOVATION, AND PUBLIC OUTREACH, THIS INITIATIVE ENSURES THAT THE IDEAS, VOICES, AND EXPERIENCES THAT SHAPED THE FOUNDING OF THE UNITED STATES OF AMERICA REMAIN AVAILABLE, UNDERSTANDABLE, AND ENDURING FOR FUTURE GENERATIONS.]

MEDICAL SCIENTIST TRAINING PROGRAM

CANCER RESEARCH TRAINING IN MOLECULAR BIOLOGY

KETAMINE ADD-ON FOR ESTABLISHED STATUS EPILEPTICUS TREATMENT TRIAL (KESETT) - THE KETAMINE ADD-ON THERAPY FOR ESTABLISHED STATUS EPILEPTICUS TREATMENT TRIAL (KESETT) IS A PHASE III RANDOMIZED, DOUBLE-BLIND CLINICAL TRIAL TO TEST WHETHER KETAMINE (KET) (1 OR 3 MG/KG) ADDED TO THE STANDARD THERAPY, LEVETIRACETAM (LEV), IS MORE EFFECTIVE THAN LEVETIRACETAM (60 MG/KG) ALONE IN TREATING STATUS EPILEPTICUS AFTER BENZODIAZEPINES HAVE FAILED. GENERALIZED CONVULSIVE STATUS EPILEPTICUS (SE) IS A DANGEROUS BUT COMMON NEUROLOGIC EMERGENCY; IT CAN CAUSE RESPIRATORY DEPRESSION AND PERMANENT BRAIN DAMAGE. BENZODIAZEPINES ARE AN EFFECTIVE FIRST-LINE THERAPY, BUT APPROXIMATELY ONE-THIRD OF CHILDREN AND 40% OF ADULTS DO NOT RESPOND. PATIENTS WHO FAIL BENZODIAZEPINES ARE IN ESTABLISHED STATUS EPILEPTICUS. THEY ARE TREATED WITH SECOND-LINE AGENTS SUCH AS LEVETIRACETAM, WHICH SUCCESSFULLY TERMINATES STATUS EPILEPTICUS IN ONLY 47% OF SUBJECTS. WE PROPOSE THAT ADDING KETAMINE TO LEVETIRACETAM WILL INCREASE EFFICACY TO 62%. PRECLINICAL AND CLINICAL EVIDENCE SUPPORTS THIS TRIAL. KETAMINE, AN NMDA RECEPTOR ANTAGONIST, TERMINATES BENZODIAZEPINE REFRACTORY SE IN EXPERIMENTAL ANIMALS. NMDA RECEPTOR ACTIVATION TRIGGERS SELF-REINFORCING SEIZURE MECHANISMS UNDERLYING SE. IT ABROGATES INHIBITORY PLASTICITY, PREVENTS EXCITOTOXICITY AND NEURONAL DEATH, AND PREVENTS EPILEPTOGENESIS ACCOMPANYING SE IN EXPERIMENTAL ANIMALS. RECENT CLINICAL STUDIES IN CHILDREN AND ADULTS SHOWED THAT KETAMINE TERMINATED ESTABLISHED STATUS EPILEPTICUS IN 23 OF 24 SUBJECTS. KETAMINE IS USED EXTENSIVELY IN EMERGENCY SETTINGS FOR SEDATION, INTUBATION, AGITATION, AND PAIN MANAGEMENT; IT IS ON THE WHO ESSENTIAL MEDICATIONS LIST BECAUSE IT IS SAFELY USED EXTENSIVELY. CLINICIANS USE IT EFFECTIVELY TO TREAT REFRACTORY AND SUPER-REFRACTORY SE, AND MANY EXPERTS RECOMMEND IT. ED PHYSICIANS HAVE USED IT FOR DECADES FOR PROCEDURAL SEDATION. WE PROPOSE TO TEST 1 AND 3 MG/KG KETAMINE DOSES BASED ON RECENT HUMAN STUDIES, EXTENSIVE PHARMACOKINETIC MODELING, ANIMAL-TO-HUMAN DOSE CONVERSION AS SUGGESTED BY THE FDA, AND DATA ON THE SAFETY OF KETAMINE. OUR OVERALL HYPOTHESIS IS THAT KETAMINE ADDED TO LEV WILL IMPROVE THE OUTCOME OF ESTABLISHED STATUS EPILEPTICUS COMPARED TO TREATMENT WITH LEVETIRACETAM ALONE BY CLINICALLY MEANINGFUL 15%. WE WILL TEST THIS HYPOTHESIS BY ACCOMPLISHING THE FOLLOWING SPECIFIC AIMS IN A BAYESIAN-ADAPTIVE RANDOMIZED CLINICAL TRIAL: AIM 1: DETERMINE WHETHER PARTICIPANTS RANDOMIZED TO LEVETIRACETAM +3 MG/KG KETAMINE OR LEVETIRACETAM +1 MG/KG KETAMINE WILL HAVE MORE DESIRABLE OUTCOMES THAN THOSE RECEIVING LEVETIRACETAM +PLACEBO. WE RANK THE OUTCOMES ON A SCALE RANGING FROM 1 TO 5. AIM 2: TO ENSURE THAT THE TRIAL IS INFORMATIVE FOR TREATING ESTABLISHED STATUS EPILEPTICUS IN CHILDREN BY DESCRIBING THE EFFECTIVENESS AND RATE OF ADVERSE REACTIONS OF THESE DRUGS. AIM 3: MEASURE DIFFERENCES BETWEEN TREATMENT ARMS IN SECONDARY OUTCOMES. THIS TRIAL CAN CHANGE THE TREATMENT PARADIGM FOR SE BY SUPPLEMENTING CURRENT SECOND-LINE AGENTS WITH KETAMINE TO IMPROVE THE TIMELINESS OF SEIZURE TERMINATION.

SYSTEMS ANALYSIS OF STRESS-ADAPTED CANCER ORGANELLES (SASCO) CENTER - PROJECT SUMMARY/ABSTRACT ONCOGENE ACTIVATION IS MODULATED BY NORMAL SUBCELLULAR COMPARTMENTS THAT EXECUTE SPECIALIZED FUNCTIONS RELATED TO HALLMARK CANCER PHENOTYPES. THESE ORGANELLES MUST ADAPT TO ONCOGENIC STRESS IN ORDER FOR TUMORS TO INITIATE AND PROGRESS, BUT THERE IS LITTLE TO NO SYSTEMS-LEVEL UNDERSTANDING OF HOW SUCH ADAPTATIONS OCCUR AND WHAT VULNERABILITIES MIGHT BE CREATED. THE SYSTEMS ANALYSIS OF STRESS-ADAPTED CANCER ORGANELLES (SASCO) CENTER AT THE UNIVERSITY OF VIRGINIA WILL ADDRESS THIS CHALLENGE BY MECHANISTIC MODELING OF ORGANELLAR PROCESSES THAT ITERATES WITH QUANTITATIVE EXPERIMENTS IN DISEASE-RELEVANT CELL CULTURES AND PRIMARY TUMORS. THE WORKING SASCO CENTER HYPOTHESIS IS THAT ORGANELLE-SPECIFIC ADAPTATION TO ONCOGENIC STRESS OCCURS THROUGH A FEW CRITICAL BOTTLENECKS, WHICH BECOME IDENTIFIABLE ONCE THE RELEVANT SIGNALING, METABOLIC, AND TRANSPORT PATHWAYS HAVE BEEN PROPERLY INTEGRATED. THE CENTER BRINGS TOGETHER 14 INVESTIGATORS WITH PRIMARY AND COLLABORATIVE TRACK RECORDS IN CANCER BIOLOGY, SYSTEMS BIOLOGY, GENETICALLY ENGINEERED MOUSE MODELS OF CANCER, AND CLINICAL PRACTICE. THREE RESEARCH PROJECTS AND ONE SHARED RESEARCH CORE WILL PURSUE A COMMON RESEARCH STRATEGY, WHICH LEVERAGES MECHANISTIC MODELS TO TEST COMPETING ALTERNATIVE HYPOTHESES ABOUT HOW ORGANELLES ADAPT TO STRESSES FROM PROXIMAL ONCOGENES THAT DRIVE SPECIFIC TYPES OF CANCER. THE PROJECTS ARE ORGANIZED HIERARCHICALLY AS ORGANELLE STRESSES DOWNSTREAM OF PROLIFERATION-INDUCING ONCOGENES. PROJECT 1 WILL EXAMINE THE CHROMOSOME PASSENGER COMPLEX AND ITS REGULATED PHASE SEPARATION DURING METAPHASE AS AN ORGANELLE THAT SENSES AND REPAIRS SPINDLE DEFECTS TO SUPPRESS BREAST CANCER ANEUPLOIDY DRIVEN BY MITOTIC TRANSCRIPTION FACTORS. PROJECT 2 WILL EVALUATE THE METABOLIC CONSEQUENCES OF CHRONIC MITOCHONDRIAL FRAGMENTATION CAUSED BY MUTANT KRAS IN PRIMARY COLORECTAL CANCERS AND SECONDARY LIVER METASTASES. PROJECT 3 WILL INVESTIGATE LOCALIZED SIGNAL-TRANSDUCTION REBALANCING AS A MECHANISM FOR ALLEVIATING PLASMA-MEMBRANE STRESS CAUSED BY EGFR AMPLIFICATION IN GLIOBLASTOMA. ALL RESEARCH PROJECTS WILL RELY ON THE HIGH-CONTENT IMAGING & ANALYSIS CORE TO OBTAIN ITERATIVE MULTICHANNEL IMMUNOFLUORESCENCE DATA WITH ORGANELLE-LEVEL RESOLUTION AND QUANTIFICATION. THE SASCO OUTREACH CORE AMPLIFIES ONGOING PROGRAMS AT THE UNIVERSITY OF VIRGINIA TO PROVIDE SUMMER RESEARCH EXPERIENCES FOR UNDERGRADUATES AND FACULTY SCHOLARS FROM HISTORICALLY UNDERREPRESENTED BACKGROUNDS AS WELL AS INTRODUCTORY SYSTEMS BIOLOGY MODELING MATERIALS FOR CLINICIANS ACROSS THE COMMONWEALTH OF VIRGINIA. THE SASCO CENTER WILL THUS CREATE A NATIONAL HEADQUARTERS FOR SUBCELLULAR CANCER SYSTEMS BIOLOGY WITHIN THE BROADER CANCER SYSTEMS BIOLOGY CONSORTIUM.

THE UNIVERSITY OF VIRGINIA EXPERIMENTAL HIGH ENERGY PHYSICS AT THE ENERGY FRONTIER

CLINICAL AND BASIC STUDIES IN POLYCYSTIC OVARIAN SYNDROME

CLINICAL & BASIC STUDIES IN POLYCYSTIC OVARIAN SYNDROME

"CENTER FOR HYPERSONIC COMBINED CYCLE FLOW PHYSICS"

MEDIUM ENERGY SPIN PHYSICS WITH LASERS

FUNCTIONAL ANALYSIS OF GENOME WIDE ASSOCIATIONS IN COLORECTAL CANCER

HIGH ENERGY PHYSICS

IMMUNE REGULATION OF VIRUS CLEARANCE AND TISSUE INJURY AT SITES OF INFECTION

PROJECT ENGAGE: THE IMPACT OF CARE FOR TEACHERS ON STUDENTS' SUCCESS

UNIVERSITY TRANSPORTATION CENTER

PREDICTIVE INFORMATICS MONITORING IN THE NEONATAL INTENSIVE CARE UNIT

COMPREHENSIVE MAGNETIC RESONANCE IN PAD

IGE ANTIBODIES TO THE MAMMALIAN OLIGOSACCHARIDE GALACTOSE-ALPHA-1, 3-GALACTOSE (ALPHA-GAL): IMMUNOLOGY, EPIDEMIOLOGY AND RELEVANCE TO ALLERGIC AND INFLAMMATORY DISEASE

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH SUPPORTING THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCY DARPA DEFENSE SCIENCES OFFICE DSO MULTIOBJECTIVE ENGINEERING AND TESTING OF ALLOY STRUCTURES METALS PROGRAM. THIS EFFORT SHALL BE CARRIED OUT GENERALLY AS SET FORTH IN EXHIBIT B, RESEARCH DESCRIPTION DOCUMENT, DATED JANUARY 30, 2024, AND IN THE RECIPIENTS REVISED PROPOSAL TITLED, OPTIMAL MULTI MATERIAL DESIGN VIA TOMOGRAPHIC CHARACTERIZATION AND DATA DRIVEN MODELS, DATED JUNE 8, 2023, COPIES OF WHICH ARE IN THE POSSESSION OF BOTH PARTIES.

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) -THE NATIONAL SCIENCE FOUNDATION (NSF) GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP) IS A HIGHLY COMPETITIVE, FEDERAL FELLOWSHIP PROGRAM. GRFP HELPS ENSURE THE VITALITY AND DIVERSITY OF THE SCIENTIFIC AND ENGINEERING WORKFORCE OF THE UNITED STATES. THE PROGRAM RECOGNIZES AND SUPPORTS OUTSTANDING GRADUATE STUDENTS WHO ARE PURSUING RESEARCH-BASED MASTER'S AND DOCTORAL DEGREES IN SCIENCE, TECHNOLOGY, ENGINEERING, AND MATHEMATICS (STEM) AND IN STEM EDUCATION. THE GRFP PROVIDES THREE YEARS OF FINANCIAL SUPPORT FOR THE GRADUATE EDUCATION OF INDIVIDUALS WHO HAVE DEMONSTRATED THEIR POTENTIAL FOR SIGNIFICANT RESEARCH ACHIEVEMENTS IN STEM AND STEM EDUCATION. THIS AWARD SUPPORTS THE NSF GRADUATE FELLOWS PURSUING GRADUATE EDUCATION AT THIS GRFP INSTITUTION. 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.

CRYO-EM OF HELICAL PROTEIN AND NUCLEOPROTEIN POLYMERS AT NEAR ATOMIC RESOLUTION

LTER: CLIMATE DRIVERS, DYNAMICS, AND CONSEQUENCES OF ECOSYSTEM STATE CHANGE IN COASTAL BARRIER SYSTEMS

RESEARCH IN THE INTENSITY FRONTIER: NOVA AND MU2E

A MICRO-CELLULAR SOLIDS APPROACH TO THERMO-STRUCTURAL MATERIALS WITH CONTROLLED ARCHITECTURES

ROLE OF TH17 IN SEVERE AND RECURRENT C. DIFFICILE INFECTION

AN INTEGRATED CELLUAR MATERIALS APPROACH TO FORCE PROTECTION (TOPIC# 7)

BASIC AND TRANSLATIONAL MECHANISMS OF ALLOIMMUNIZATION TO RBC TRANSFUSION - ALLOIMMUNIZATION TO TRANSFUSED RBCS REMAINS A MAJOR PROBLEM FOR THE LARGE NUMBER OF PATIENTS WHO REQUIRE TRANSFUSION (APPROXIMATELY 1 OUT OF 70 PEOPLE (~5,000,000 PATIENTS) ANNUALLY IN THE USA ALONE). ALTHOUGH A BARRIER TO TRANSFUSION IN MULTIPLE SETTINGS, ALLOIMMUNIZATION IS PARTICULARLY PROBLEMATIC FOR PATIENTS WITH SICKLE CELL DISEASE (SCD) DUE TO 1) THE INCREASED RATE OF ALLOIMMUNIZATION (UP TO 30%), 2) THE NEED FOR CHRONIC TRANSFUSION, AND 3) THE RISK OF UNDETECTED (OR NEW) ALLOANTIBODIES CAUSING POTENTIALLY CATASTROPHIC HYPERHEMOLYSIS. THERE ARE VERY FEW EFFECTIVE THERAPEUTIC INTERVENTIONS TO PREVENT RBC ALLOIMMUNIZATION (E.G., EXTENSIVE ANTIGEN MATCHING). FOR ALL TRANSFUSION INDICATIONS, PATIENTS TEND TO BE EITHER “RESPONDERS” THAT DEVELOP ALLOANTIBODIES OVER TIME WITH ONGOING TRANSFUSION OR “NON-RESPONDERS” WITH NO DETECTABLE ALLOANTIBODIES EVEN AFTER MANY TRANSFUSIONS. CURRENTLY, WE CANNOT PREDICT WHICH PATIENTS ARE LIKELY TO BE RESPONDERS AND BECOME ALLOIMMUNIZED. THIS P01 FOCUSES ON ADDRESSING THE PERSISTENT PROBLEM OF RBC ALLOIMMUNIZATION FOR THE LARGE NUMBER OF PATIENTS WHO REQUIRE TRANSFUSIONS AND ARE AT RISK FOR ALLOIMMUNIZATION. THE PROGRAM IS STRUCTURED AROUND A CENTRAL CORE (CORE A) THAT WILL COLLECT LONGITUDINAL SAMPLES FROM A COHORT OF 2000 PATIENTS WITH SCD (AT STEADY STATE, AT TIME OF TRANSFUSION, AND ONE-MONTH POST-TRANSFUSION) LINKED TO DETAILED CLINICAL INFORMATION, INCLUDING RBC ALLOIMMUNIZATION. PROJECTS 1-3 COMBINE NOVEL TRANSLATIONAL MURINE MODELS WITH CLINICAL SAMPLES FROM CORE A WHILE PROJECT 4 USES SAMPLES FROM CORE A TO TEST HYPOTHESES THROUGH AN OMICS-BASED APPROACH AND GENERATES DATA ON PATHWAYS STUDIED IN PROJECTS 1-3. IN THIS WAY, THE PROPOSED PROGRAM CREATES A SYNERGY OF APPROACHES WITH THE ABILITY TO TRANSLATE MURINE FINDINGS INTO HUMANS AND MODEL HUMAN FINDINGS IN MICE. USING THE SAMPLES FROM CORE A AS A COMMON RESOURCE, FOUR PROJECTS ARE PROPOSED. PROJECT 1 BUILDS ON A NOVEL OBSERVATION THAT A MOUSE MODEL OF SLE RECAPITULATES INCREASED RBC ALLOIMMUNIZATION OBSERVED IN HUMANS WITH SLE AND UTILIZES THE MODEL AND SAMPLES FROM CORE A TO TEST THE MECHANISTIC ROLE OF TLR7, TLR9 AND ANTI-NUCLEIC ACID ANTIBODIES IN RBC ALLOIMMUNIZATION. PROJECT 2 BUILDS ON OUR NOVEL OBSERVATION THAT MULTIPLE PURINERGIC SIGNALING PATHWAYS REGULATE RBC ALLOIMMUNIZATION IN MICE AND UTILIZES MOUSE MODELS AND SAMPLES FORM CORE A TO TEST THE MECHANISTIC ROLE OF CD73, AMP, ADORA1, ADENOSINE AND ADORA2B IN RBC ALLOIMMUNIZATION. PROJECT 3 PROPOSES MECHANISTICALLY DRIVEN STUDIES IN PRE-CLINICAL MODELS AND HUMAN STUDIES TO EXPAND UPON OUR NOVEL FINDING THAT RETICULOCYTES (IN DONOR RBC UNITS OR IN TRANSFUSION RECIPIENTS) ARE A RISK FACTOR FOR RBC ALLOIMMUNIZATION. PROJECT 4 WILL INVESTIGATE THE UNDERLYING GENETIC RISK FACTORS THAT PREDISPOSE A GIVEN PATIENT WITH SCD THROUGH ANALYSIS OF WHOLE GENOME SEQUENCING AND THE SPECIFIC MOLECULAR DRIVERS OF ALLOIMMUNIZATION TO A GIVEN TRANSFUSION THROUGH ANALYSIS OF SINGLE CELL RNASEQ DATA. THIS P01 IS DESIGNED TO HAVE NEAR-TERM BENEFITS OF GUIDING CLINICAL PRACTICE BY DISCOVERING PREDICTORS OF RESPONDER/NON-RESPONDER PATIENTS AND LONGER-TERM BENEFITS OF ELUCIDATING MECHANISMS OF RBC ALLOIMMUNIZATION TO ALLOW RATIONAL TARGETS FOR THERAPY DEVELOPMENT.

AN INTERDISCIPLINARY TRAINING PROGRAM IN IMMMUNOLOGY

SYSTEM-LEVEL APPROACH FOR MULTI-PHASE, NANOTECHNOLOGY-ENHANCED COOLING OF HIGH-POWER MICROELECTRONIC SYSTEMS

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

NETWORK FOR CARDIOTHORACIC SURGICAL INVESTIGATIONS IN CARDIOVASCULAR MEDICINE

EXPRESSION AND PROTEOMIC CHARACTERIZATION OF RISK LOCI IN TYPE 1 DIABETES

BIOSPECIMEN PROCUREMENT AND TISSUE MICROARRAY MANUFACTURE FOR THE CHTN

TOWARDS A MISSION CONFIGURABLE STEALTH UNDERWATER BATOID

BIO-BEHAVIORAL FEEDBACK AND CONTROL OF TYPE 1 DIABETES

IGE ANTIBODY RESPONSES TO THE OLIGOSACCHARIDE GALACTOSE-ALPHA-1,3-GALACTOSE (ALPHA-GAL) IN MURINE AND HUMAN ATHEROSCLEROSIS - PROJECT ABSTRACT INCREASED TOTAL SERUM IGE LEVELS ARE ASSOCIATED WITH CORONARY ARTERY DISEASE (CAD). HOWEVER, THE CAUSAL ROLE OF ANTIGEN-SPECIFIC IGE IN CAD REMAINS LARGELY UNEXPLORED. RECENT WORK FROM OUR GROUP AND OTHERS PROVIDE EVIDENCE THAT HUMANS WITH IGE SENSITIZATION TO THE MAMMALIAN OLIGOSACCHARIDE ALLERGEN A-GAL HAVE LARGER CORONARY ARTERY PLAQUES AND UNSTABLE PLAQUE FEATURES SIGNIFYING INCREASED CAD COMPARED TO THOSE WITHOUT IGE TO A-GAL. YET, WHETHER IGE TO A-GAL DIRECTLY PROMOTES ATHEROSCLEROTIC PLAQUE DEVELOPMENT AND THE MOLECULAR AND CELLULAR MECHANISMS MEDIATING IGE SENSITIZATION TO A-GAL LINKED TO ATHEROSCLEROSIS FORMATION ARE UNKNOWN. BITES FROM THE LONE STAR TICK INDUCE IGE SENSITIZATION TO A-GAL AND A SUBSEQUENT SEVERE ALLERGIC RESPONSE WHEN THE SUBJECT INGESTS A-GAL-CONTAINING FOODS SUCH AS RED MEAT. HOWEVER, THE VAST MAJORITY OF INDIVIDUALS WITH IGE TO A-GAL DO NOT MANIFEST WITH DELAYED ANAPHYLAXIS AND FREQUENTLY HAVE NO OUTWARD IDENTIFYING SYMPTOMS. AS SUCH, THEY CONTINUE TO CONSUME A-GAL-CONTAINING FOOD PRODUCTS (MEAT, DAIRY, ETC.) WHICH HAVE THE CAPACITY TO CONTINUE TO STIMULATE IGE RESPONSES AND INFLAMMATION IN THE VESSEL WALL. PRELIMINARY DATA PROVIDE THE FIRST EVIDENCE THAT HUMANS WITH IGE SENSITIZATION TO A-GAL HAD A HIGHER FREQUENCY OF CCR6+ SWITCHED MEMORY (SWM) B CELLS. NOTABLY, CONSISTENT WITH THE ASSOCIATION OF THE IGE SENSITIZATION TO A-GAL AND CAD, THE AMOUNT OF CCR6 ON SWM B CELLS WAS ASSOCIATED WITH CAD SEVERITY. TRANSCRIPTOMIC ANALYSIS DEMONSTRATED THAT CCR6+ SWM B CELLS EXPRESSED HIGHER IL-4R AND STAT6 IN SUBJECTS THAT WERE IGE A-GAL+ COMPARED TO IGE A- GAL-. INTERESTINGLY, IL-4 AND STAT6 ARE IMPORTANT FOR B CELL CLASS SWITCH RECOMBINATION TO IGE, SUGGESTING THAT CELLS THAT MAKE IL-4 MAY BE IMPORTANT IN IGE A-GAL PRODUCTION. STUDYING IGE SENSITIZATION TO A-GAL IN CONVENTIONAL MURINE MODELS OF ATHEROSCLEROSIS IS NOT FEASIBLE AS MICE, LIKE ALL LOWER MAMMALS BUT UNLIKE HUMANS, EXPRESS THE ENZYME GALACTOSYLTRANSFERASE, PRODUCE A-GAL AND DO NOT DEVELOP AN IGE RESPONSE TO A- GAL. WE HAVE OBTAINED A NOVEL A-GAL-/- MOUSE THAT MIMICS THE HUMAN CONDITION TO STUDY THE ROLE OF IGE SENSITIZATION TO A-GAL IN ATHEROSCLEROSIS. COMPARING A-GAL-/- MICE TO MICE WILDTYPE (WT) FOR A-GAL, WE SHOW A SIGNIFICANT INDUCTION OF IGE TO A-GAL AFTER EXPOSURE TO LONE STAR TICK-DERIVED LIPIDS IN THE A-GAL-/- BUT NOT THE WT MOUSE. MOREOVER, PRELIMINARY DATA FROM MICE DEFICIENT IN NKT CELLS IMPLICATES INKT CELLS IN THE REGULATION OF IGE ANTIBODY PRODUCTION TO LIPIDS FROM LONE STAR TICKS. BASED ON THESE HUMAN AND MURINE DATA, THE OVERARCHING OBJECTIVE OF THIS PROPOSAL IS TO INVESTIGATE WHETHER THESE FACTORS AND CELLS PLAY A CAUSAL ROLE IN ATHEROSCLEROSIS DEVELOPMENT DUE TO IGE SENSITIZATION TO A-GAL. WE WILL USE LOSS AND GAIN OF FUNCTION STUDIES IN MURINE ATHEROSCLEROSIS MODELS TO DEFINE NOVEL MECHANISMS OF A-GAL IGE PRODUCTION AND THE IMPACT OF TICK-INDUCED A- GAL SENSITIZATION ON DIET-INDUCED ATHEROSCLEROSIS, AND TEST A LARGER COHORT OF HUMANS WITH CAD QUALITATIVELY AND QUANTITATIVELY BY INTRAVASCULAR ULTRASOUND VIRTUAL HISTOLOGY (IVUS-VH), ALLOWING FOR MORE ROBUST MULTIVARIATE ANALYSIS AND DEEPER INTERROGATION OF IMMUNE CELL PHENOTYPES THAT MARK THOSE AT GREATEST RISK.

THE ROLE OF COPY NUMBER VARIANTS (CNV) IN TYPE 1 DIABETES

DEVELOPMENTAL ORIGINS AND HOMEOSTATIC MECHANISMS UNDERLYING ADULT PHENOTYPES

FIELD STUDIES OF HUMAN IMMUNITY TO AMEBIASIS IN BANGLADESH

URINE COLORIMETRY FOR TUBERCULOSIS PHARMACOKINETICS EVALUATION IN CHILDREN AND ADULTS

NEW START GRANT

SOCIAL RELATIONSHIP QUALITIES AS PREDICTORS OF HEALTH & AGING FROM ADOLESCENCE THROUGH EARLY MIDLIFE

CELLULAR AND GENETIC BASIS OF SYSTEMIC LUPUS

STUDY OF THE NUCLEON STRUCTURE AT JEFFERSON LAB HALL A

CARDIOVASCULAR SURGERY RESEARCH TRAINING GRANT

DOPAMINERGIC AND GLUTAMATERGIC MECHANISMS OF COCAINE ADDICTION: SEX DIFFERENCES

ONTOGENY OF CENTRAL NEURAL TASTE RESPONSES

LTER: DRIVERS, DYNAMICS AND CONSEQUENCES OF NON-LINEAR CHANGE IN COASTAL BARRIER SYSTEMS

CRITICAL PERIOD PLASTICITY AND BINOCULAR MATCHING IN THE VISUAL CORTEX

MOLECULAR MECHANISMS OF MEMBRANE TRANSPORT

REAL-TIME MEASUREMENTS OF NEUROTRANSMISSION IN DROSOPHILA MELANOGASTER

TARGETED CEU IMAGING OF ATHEROSCLEROSIS AND ANGIOGENESIS

CELLULAR/MOLECULAR MECHANISMS OF RESPIRATORY NEURONAL CHEMOSENSITIVITY

BFGF LOW AFFINITY RECEPTORS AND HIVAN

MINIMALLY INVASIVE CEREBRAL BLOOD FLOW AND OXYGENATION MONITORING FOR INTRACRANIAL HYPERTENSION - ABSTRACT/PROJECT SUMMARY TRAUMATIC BRAIN INJURY, ACUTE ISCHEMIC STROKE, AND INTRACEREBRAL HEMORRHAGE ARE FREQUENTLY COMPLICATED BY INTRACRANIAL HYPERTENSION LEADING TO PROGRESSIVE ISCHEMIA AND SECONDARY BRAIN INJURY. RECENT EFFORTS FOCUSED ON IMPROVING OUTCOMES HAVE THEREFORE BEEN FOCUSED UPON IMPROVING CEREBRAL OXYGENATION AND THE DEVELOPMENT OF MONITORING DEVICES TO GUIDE THERAPY. CURRENT DEVICES DESIGNED TO MEASURE TISSUE OXYGENATION ARE, HOWEVER, SEVERELY LIMITED IN THEIR SCOPE OF SURVEILLANCE AND ACCURACY. SURFACE OXIMETRY MONITORS INTERROGATE ONLY SUPERFICIAL BRAIN TISSUE, WITH CONTAMINATION FROM INTERVENING SKIN AND SKULL. INTRAPARENCHYMAL BRAIN TISSUE OXYGEN PROBES SURVEY RELATIVELY METABOLICALLY LESS ACTIVE WHITE MATTER (COMPARED TO GRAY MATTER), A VOLUME OF LESS THAN 3 MM3, AND AT A SINGLE LOCATION. LASTLY, INTRAPARENCHYMAL TISSUE OXYGEN MONITORS ARE BULKY, INCOMPATIBLE WITH MAGNETIC RESONANCE IMAGING, AND HAVE YET TO DEMONSTRATE CLINICAL EFFICACY. TO FILL THIS NEED, WE WILL FINALIZE THE DEVELOPMENT OF A BRAIN-SPECIFIC, MINIMALLY INVASIVE, OPTICAL BLOOD FLOW AND OXYGENATION MONITORING SYSTEM (FLOXBR), THEN TRANSLATE THIS DEVICE TO HUMANS. THE FLOXBR, EMPLOYING DIFFUSE OPTICAL AND CORRELATION SPECTROSCOPIES VIA A BRAIN SURFACE PROBE, MAY OFFER IMPROVED SENSITIVITY AND SPECIFICITY COMPARED TO NON-INVASIVE PROBES AND WILL PROBE LARGER VOLUMES THAN CURRENTLY AVAILABLE INVASIVE PROBES, SUCH AS THE LICOXTM TISSUE PO2 PROBE. UNLIKE INTRAPARENCHYMAL PROBES, THIS DEVICE CAN LIE ABOVE OR BELOW THE DURA AND WILL BE MORE SENSITIVE TO HIGHLY METABOLICALLY ACTIVE GRAY MATTER. ITS SMALL SIZE AND FLEXIBILITY WILL PERMIT MULTIPLE PROBES TO BE PLACED THROUGH A SINGLE BURR HOLE, THUS ALLOWING FOR THE MONITORING OF REGIONAL DIFFERENCES IN FLOW AND OXYGENATION. UNLIKE SURFACE OXIMETRY, THE FLOXBR IS NOT IMPACTED BY SUPERFICIAL TRAUMA OR EDEMA, IMPROVING RELIABILITY AND SENSITIVITY. CONTINUOUS, EASILY INTERPRETED, AND RELIABLE MINIMALLY INVASIVE MONITORING OF CEREBRAL OXYGEN DELIVERY MAY ENHANCE MANAGEMENT AND OUTCOMES IN PATIENTS SUFFERING FROM INTRACRANIAL HYPERTENSION. OUR AIMS ARE SUCCINCTLY SUMMARIZED BELOW. AIM 1) FINALIZE DEVELOPMENT & MANUFACTURE THE FLOXBR BRAIN FLOW AND OXIMETRY MONITORING DEVICE. AIM 2) PRE-CLINICAL DEVICE EVALUATION, MEASUREMENT VALIDATION, AND SAFETY TESTING OF FLOXBR. AIM 3) COMPLETE REGULATORY AND SAFETY REQUIREMENTS TO SUPPORT FLOXBR FIRST-IN-HUMANS FEASIBILITY TESTING. AIM 4) CONDUCT FIRST-IN-HUMANS FEASIBILITY TESTING.

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH SUPPORTING THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCY DARPA MICROSYSTEMS TECHNOLOGY OFFICE MTO FOR THE INTENSITY SQUEEZED PHOTONIC INTEGRATION FOR REVOLUTIONARY DETECTORS INSPIRED PROGRAM. THIS EFFORT SHALL BE CARRIED OUT GENERALLY AS SET FORTH IN EXHIBIT B, RESEARCH DESCRIPTION DOCUMENT, DATED JUNE 12, 2024, AND IN THE RECIPIENTS PROPOSAL TITLED, SQUEEZED INTEGRATED NITRIDE TECHNOLOGY SQUINT, DATED DECEMBER 17, 2023, COPIES OF WHICH ARE IN THE POSSESSION OF BOTH PARTIES.

LONG-TERM DRIVERS, STATE CHANGE AND DISTURBANCE ON THE VIRGINIA COAST RESERVE: LTER V

FOCUSED ULTRASOUND INTERVENTIONS FOR NONINVASIVE PRECISION THERAPY IN PRIMARY AND METASTATIC BREAST CANCERS

TRAINING IN CELL AND MOLECULAR BIOLOGY

AUGMENTATION OF TISSUE PERFUSION IN PAD WITH ULTRASOUND-MEDIATED CAVITATION

THE ROLE OF ION TRANSPORT IN GLIOMA MIGRATION, PROLIFERATION, AND APOPTOSIS

ROLE OF EOSINOPHILS IN INNATE PROTECTION FROM C. DIFFICILE

GROWTH AND REGENERATION IN THE INNER EAR

MOLECULAR MECHANISMS OF VIRAL MEMBRANE FUSION

MOLECULAR MECHANISMS OF RHOA-MEDIATED CA2+SENSITIZATION IN VASCULAR SMOOTH MUSCLE

ELECTRON INTERACTIONS WITH NUCLEI

ADOLESCENT PEER AND FAMILY PRECURSORS OF ADULT PSYCHOSOCIAL FUNCTIONING

AN EVALUATION OF TREATMENT WITH OMALIZUMAB TO IMPROVE THE ASTHMATIC RESPONSE TO A

MOLECULAR STUDY OF MOUSE VIRAL RESISTANCE MECHANISMS

DYNAMIC REGULATION OF ALTERNATIVE SPLICING IN THE INITIATION AND PROGRESSION OF ISLET AUTOIMMUNITY IN THE ENVIRONMENTAL DETERMINANTS OF DIABETES IN THE YOUNG (TEDDY) STUDY - PROJECT SUMMARY / ABSTRACT TYPE 1 DIABETES (T1D) IS AN AUTOIMMUNE DISEASE FROM AN IMMUNE-MEDIATED ATTACK ON THE PANCREATIC BETA CELLS. AS ~5% OF THOSE DEVELOPING T1D HAVE A POSITIVE FAMILY HISTORY, THERE IS LITTLE AWARENESS OF SYMPTOMS. T1D IS MOST VIRULENT IN CHILDREN, YET IT AFFECTS ALL AGE AND ANCESTRY GROUPS. THE BETA CELL DESTRUCTION IN T1D IS IDENTIFIED ONLY THROUGH PRESENCE OF ISLET AUTOANTIBODIES TO INSULIN (IAA), GLUTAMIC ACID DECARBOXYLASE (GADA), INSULINOMA- ASSOCIATED PROTEIN 2 (IA-2A), AND ZINC TRANSPORTER 8 (ZNT8A), ALTHOUGH THEIR PREVALENCE CAN VARY DEPENDING ON AGE, SEX, AND ANCESTRY. GENETIC FACTORS ACCOUNT FOR ~50% OF T1D RISK, AND WE (AND OTHERS) HAVE IDENTIFIED OVER 100 LOCI CONTAINING DISEASE-ASSOCIATED VARIANTS. THE VAST MAJORITY OF T1D VARIANTS RESIDE IN THE NON-CODING GENOME AND MAP TO ENHANCER REGIONS IN IMMUNE-RELEVANT CELL TYPES (E.G., CD4+ T CELLS). THE MECHANISMS UNDERLYING THE TRANSITION FROM AN INDIVIDUAL’S GENETIC RISK TO ISLET AUTOIMMUNITY AND DEVELOPMENT OF T1D HAVE NOT BEEN RESOLVED. THE PROPOSED RESEARCH IS AN ANCILLARY PROJECT OF THE ENVIRONMENTAL DETERMINANTS OF DIABETES IN THE YOUNG (TEDDY) STUDY. TEDDY IS A LONGITUDINAL COHORT STUDY DESIGNED TO DISCOVER TRIGGERS OF ISLET AUTOIMMUNITY BY FOLLOWING NEWBORNS AT HIGH GENETIC RISK WITH FREQUENT FOLLOW-UP AND COLLECTION OF SAMPLES FOR DEEP PHENOTYPING AND BIOLOGICAL PROFILING. THIS PROJECT PROPOSES TO USE TEDDY DATA AND PBMC SAMPLES TO EXAMINE AN UNDER-STUDIED MECHANISM IN T1D, THE ROLE OF ALTERNATIVE SPLICING. ALTERNATIVE SPLICING OF PRE-MRNA GENERATES DIVERSITY IN GENE EXPRESSION (REGULATION) AND PROTEIN IN A TISSUE-SPECIFIC MANNER. ERRORS IN ALTERNATIVE SPLICING CAN RESULT IN ERRORS IN GENE REGULATION AND HAS BEEN SHOWN TO LEAD TO HUMAN DISEASE, INCLUDING AUTOIMMUNE DISEASES. FURTHER, GENETIC VARIATION ALSO IMPACTS PROPER SPLICING OF MRNA, GENERATING ABERRANT VARIANTS. WE HAVE SHOWN THAT ALTERNATIVE SPLICING IS ASSOCIATED WITH T1D IN KNOWN T1D LOCI USING SHORT-READ RNA SEQUENCING. IN ADDITION, RNA-BINDING PROTEINS (RBPS) WITH ROLES IN ALTERNATIVE SPLICING CAN GENERATE DIFFERENT MRNA AND PROTEIN ISOFORMS WITH CHANGE OR LOSS OF PROTEIN FUNCTION. WE HAVE IDENTIFIED 12 GENES IN KNOWN T1D LOCI THAT ENCODE RBPS OF RELEVANCE TO GENE EXPRESSION AND T1D SUSCEPTIBILITY. TO GAIN A COMPREHENSIVE UNDERSTANDING OF THE ROLE OF THESE RBP-REGULATED ALTERNATIVE SPLICING EVENTS ON INITIATION AND PROGRESSION OF ISLET AUTOIMMUNITY LEADING TO T1D, WE PROPOSE TO FOCUS ON A RELEVANT CELL TYPE (CD4+ T CELLS) OBTAINED FROM TEDDY PARTICIPANTS AT MULTIPLE TIME POINTS DURING THE TRANSITION PERIODS OF ISLET AUTOIMMUNITY. WE WILL OBTAIN LONG-READ RNA SEQUENCING (FOR FULL ISOFORM DETECTION) AND SHORT-READ RNA SEQUENCING (FOR ISOFORM ABUNDANCE) TO DEFINE DIFFERENTIAL ALTERNATIVE SPLICING EVENTS, CONSTRUCT RBP NETWORKS, AND UTILIZE DEEP LEARNING TIME SERIES MODELS TO MAP T1D RISK OVER TIME. WE WILL EXPERIMENTALLY VALIDATE ALTERNATIVELY SPLICED GENES, THEIR RBPS, AND BIOLOGICAL MECHANISMS THAT LEAD TO ISLET AUTOIMMUNITY AND T1D. TOGETHER, THE OUTCOME OF THE PROPOSED RESEARCH WILL ENABLE BETTER PREDICTION OF ISLET AUTOIMMUNITY AND T1D RISK TRAJECTORY, THE TIMING FOR MONITORING, AND NOVEL THERAPEUTIC INTERVENTIONS IN T1D.

IRON DEFICIENCY: MOLECULAR AND CELLULAR CONSEQUENCES

THE INFLUENCE OF SOCIAL NETWORKS ON DISPARITIES IN POSTNEONATAL INFANT MORTALITY

HIGH-THROUGHPUT ASSAYS FOR IMAGING HUMAN INTRACELLULAR PATHOGEN INFECTIONS

ARP ECONOMIC DEVELOPMENT GRANT FOR RURAL HEALTH CARE FACILITIES

FOCUSED COPE: ENHANCING RESILIENCE AND EQUITY IN URBAN COASTAL COMMUNITIES THROUGH THE CO-GENERATION OF COMMUNITY CAPITALS -2209139 (GOODALL). THE OVERARCHING GOAL OF THIS PROJECT IS TO CREATE TRANSFERABLE METHODS FOR ENHANCING RESILIENCE AND EQUITY IN URBAN COASTAL COMMUNITIES. WHILE THE GOAL IS TO PRODUCE TRANSFERABLE METHODS, THE PROJECT FOCUSES ON COMMUNITIES IN HAMPTON ROADS REGION OF VIRGINIA ? ONE OF THE MOST VULNERABLE POPULATIONS TO SEA LEVEL RISE IN THE UNITED STATES ? AS COMMUNITY PARTNERS. THE HUB STRUCTURE OF THE PROJECT EMPHASIZES THE CO-GENERATION OF COMMUNITY CAPITALS AMONG A DIVERSE TEAM OF RESEARCHERS IN PARTNERSHIP WITH COMMUNITY STAKEHOLDERS. COMMUNITY CAPITALS IS A TERM INCLUSIVE OF BOTH NATURAL-BUILT CAPITALS, SUCH AS SEA WALLS, LIVING SHORELINES, AND GREEN STORMWATER INFRASTRUCTURE, AND HUMAN-SOCIAL CAPITALS, SUCH AS HEALTH, WELL-BEING, AGENCY, AND EMPOWERMENT. THE OVERARCHING HYPOTHESIS IS THAT BOTH FORMS OF COMMUNITY CAPITALS MUST BE ADVANCED IN SYNERGY IN ORDER TO HAVE RESILIENT AND EQUITABLE URBAN COASTAL COMMUNITIES. THE RESEARCH PLAN OPERATES ON TWO SPATIAL SCALES, REGIONAL AND LOCAL, BECAUSE BOTH SCALES ARE CRITICAL FOR BUILDING COMMUNITY CAPITALS. ON THE REGIONAL SCALE, THE RESEARCH TASKS ARE TO CREATE A GEOSPATIAL DATA INVENTORY, A SYSTEM-WIDE FLOOD MODEL, AND EQUITABLE POLICIES FOR REGIONAL CLIMATE RESILIENCE IN URBAN COMMUNITIES. ON THE LOCAL SCALE, THE RESEARCH TASKS ARE TO EMPOWER AND ENGAGE COMMUNITIES THAT HAVE BEEN HISTORICALLY MARGINALIZED IN THE CLIMATE RESILIENCE CONVERSATION, BUILD COMMUNITY CAPITAL THROUGH WORKSHOPS THAT RESULT IN CO-DESIGNED STORMWATER INFRASTRUCTURE, AND MEASURE THE CO-BENEFITS OF GREEN STORMWATER INFRASTRUCTURE FOR MENTAL HEALTH AND WELL-BEING. WORK ACROSS THE TWO SCALES IS CONNECTED THROUGH SHARED RESOURCES AND FEEDBACK BETWEEN THE LOCAL COMMUNITY AND BROADER-SCALE REGIONAL EFFORTS. A KEY INTELLECTUAL FEATURE OF THIS RESEARCH IS THE SYNERGISTIC ADVANCEMENT OF COMMUNITY CAPITALS FOR CLIMATE RESILIENCE. MANY PROJECTS FOCUS ON ONE OF THESE COMMUNITY CAPITALS, BUT FEW SEEK TO ADVANCE BOTH IN SYNERGY WITH ONE ANOTHER. TO ADVANCE THE HUMAN-SOCIAL CAPITAL LIKE WELL-BEING, EMPOWERMENT, AND AGENCY CRITICAL TO FOSTERING EQUITABLE AND RESILIENT COMMUNITIES, THIS PROJECT ADVANCES EQUITABLE PUBLIC POLICIES THAT CAN HAVE A LASTING IMPACT ON HOW COASTAL URBAN CITIES APPROACH THE CHALLENGE OF ADDRESSING CLIMATE RESILIENCE. FOR EXAMPLE, THE CONCEPT OF CO-DESIGNED GREEN STORMWATER INTERVENTIONS THAT CAN BE IMPLEMENTED BY COMMUNITY MEMBERS CAN CONTRIBUTE TO BOTH ENHANCING NATURAL-BUILT CAPITAL AND SOCIAL-HUMAN CAPITAL. TO ENCOURAGE INCLUSION, THE PROJECT ALSO HAS A STRONG FOCUS ON REMOVING BARRIERS TO PARTICIPATION FACING UNDERREPRESENTED AND MARGINALIZED COMMUNITIES IN THE COASTAL RESILIENCE CONVERSATIONS AND ACTIVITIES. TO STRENGTHEN HOW NATURAL-BUILT CAPITALS CAN BE ASSESSED AND STRENGTHENED, THE RESEARCH ADVANCES THE STATE OF ART FOR MODELING COMPLEX URBAN STORMWATER SYSTEMS AT A REGIONAL SCALE. THE STRATEGY IS TO BUILD FROM WIDELY USED MODELS FOR ENGINEERING DESIGN, SO THAT PRODUCTS OF THE RESEARCH CAN BE MORE EASILY ADOPTED BY COASTAL COMMUNITIES, AND TO INTEGRATE THEM INTO A MORE HOLISTIC MODELING SYSTEM. LASTLY, THE HUB STRUCTURE OF THIS PROJECT PROVIDES THE OPPORTUNITY TO FOSTER CONVERGENCE ACROSS THE PROJECT TEAM?S EXPERTISE THAT RANGES FROM HYDROLOGIC ENGINEERING AND OCEAN SCIENCE, TO ARCHITECTURE AND LANDSCAPE DESIGN, TO ENVIRONMENTAL JUSTICE AND ENVIRONMENTAL PSYCHOLOGY, TO SOCIAL WORK AND COMMUNITY ENGAGEMENT. THE PROJECT HAS THREE PRIMARY BROADER IMPACT GOALS. THE FIRST IS TO BROADEN PARTICIPATION IN SCIENCE, TECHNOLOGY, ENGINEERING, AND MATH (STEM). TO ACHIEVE THIS GOAL, THE PROJECT TEAM WILL PROVIDE OPPORTUNITIES FOR EIGHT UNDERGRADUATE STUDENTS AND ONE GRADUATE STUDENT AT NORFOLK STATE UNIVERSITY (NSU) ? A HISTORICALLY BLACK UNIVERSITY LOCATED IN NORFOLK, VIRGINIA ? A PARTNER COMMUNITY FOR THE PROJECT. THE PROJECT AIMS TO CREATE A LONG-TERM PARTNERSHIP BETWEEN NSU AND THE UNIVERSITY OF VIRGINIA TO CAPITALIZE ON THEIR SHARED INTEREST IN CLIMATE RESILIENCE, AND TO CREATE AUTHENTIC AND MEANINGFUL CONNECTIONS WITH THE LOCAL COMMUNITY. THE SECOND BROADER IMPACT GOAL IS OUTREACH AND EDUCATION. THE PROJECT TEAM WILL STRENGTHEN EXISTING EFFORTS IN STEM EDUCATION TO REACH PUBLIC K-12 STUDENTS: A LEARNING BARGE CO-DEVELOPED BETWEEN UVA AND THE ELIZABETH RIVER PROJECT (ERP) AND THE SCHOOLYARD-LONG TERM ECOLOGICAL RESEARCH (SLTER), A PROJECT THAT LEVERAGES NSF SUPPORT TO TEACH STUDENTS LIVING ON VIRGINIA?S COAST ABOUT CLIMATE RESILIENCE. THE THIRD BROADER IMPACT GOAL OF THE PROJECT IS TO HAVE A POSITIVE EFFECT ON THE WELL-BEING OF THE LOCAL PARTNER COMMUNITIES. ONE WAY THIS WILL BE ASSESSED IS THROUGH STUDYING MENTAL HEALTH AND WELL-BEING CO-BENEFITS OF GREEN INFRASTRUCTURE INTERVENTIONS CO-DESIGNED AND IMPLEMENTED THROUGH THE PROJECT 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.

ROLE OF CREM IN AMEBIC COLITIS AND INFLAMMATORY BOWEL DISEASE

PRORENIN RECEPTORS MEDIATE HYPERTENSION AND KIDNEY DISEASE IN DIABETES

RENAL AT2 RECEPTORS IN HYPERTENSION

SPHINGOLIPIDS IN ACUTE KIDNEY INJURY

VIRGINIA-NORTH CAROLINA LOUIS STOKES ALLIANCE FOR MINORITY PARTICIPATION, 2017-2022

ORGANIZATION OF CENTRAL SYMPATHETIC PATHWAYS

2007 LSAMP: VIRGINIA-NORTH CAROLINA ALLIANCE FOR MINORITY PARTICIPATION (PHASE I)

DUST MITE, COCKROACH AND CAT ALLERGENS IN ASTHMA

SPIN TRANSITIONS, PHASE COMPETITION AND ORDERING IN PEROVSKITE OXIDES

POST-DOCTORAL RESEARCH FELLOWSHIPS

NOVEL ROLE OF HEPATIC SEL1L-HRD1 ERAD IN FGF21 GENE TRANSCRIPTION

EVALUATION OF STATE AND DISTRICT EDUCATION PROGRAMS AND POLICIES

FOCUSED COPE: BUILDING CAPACITY FOR ADAPTATION IN RURAL COASTAL COMMUNITIES

PROCESSED ANTIGEN CHARACTERIZATION BY MASS SPECTROMETRY

COPASI: BIOCHEMICAL NETWORK MODELING AND SIMULATION SOFTWARE

NEUROVASCUALAR REGENERATION

RESEARCH NETWORKS FOCUSED ON CRITICAL PROBLEMS OF EDUCATION POLICY AND PRACTICE (NETWORKS)

FUNCTIONAL MECHANISMS OF T1D RISK VARIANTS AND THEIR TARGET GENES USING 3D EPIGENOMICS AND SINGLE CELL APPROACHES

THE REACH INTERVENTION FOR CAREGIVERS OF VETERANS AND SERVICE MEMBERS WITH TBI: EFFICACY AND IMPLEMENTATION PLANNING ACROSS THE VA POLYTRAUMA SYSTEM OF CARE

BALANCING PROTECTIVE IMMUNITY AND CHRONIC SEQUELAE BY RESIDENT CD8 T CELLS

HERCULES: HARDWARE-ENHANCED RESILIENT COMPARTMENTALIZATION AND PROGRAM ANALYSIS FOR UPGRADED LEGACY ENVIRONMENT SECURITY

ORGANIZATION AND FUNCTION OF NEURONAL ENDOSOMES

"(MURI-07) HELIX: A SELF-REGENERATIVE ARCHETECTURE FOR THE INCORRUPTIBLE ENTERPRISE" DATED 11/10/06

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

UNIVERSITY OF VIRGINIA - ICDDR,B RESEARCH UNIT FOR WOMEN'S AND CHILDREN'S HEALTH RESEARCH

PURINERGIC REGULATION OF VEINOUS ENDOTHELIAL PERMEABILITY

RETROTRAPEZOID NUCLEUS AND CENTRAL CHEMORECEPTION

POSTDOCTORAL TRAINING GRANT FOR MDS IN SURGICAL ONCOLOGY RESEARCH

THE VIRGINIA EDUCATION SCIENCES PRE-DOCTORAL TRAINING PROGRAM

SURVIVAL OF NEISSERIA GONORRHOEAE AFTER PRIMARY HUMAN NEUTROPHIL CHALLENGE

THIS IS A CONTINUATION OF N00014-14-1-0533 MULTI-OBJECTIVE OPTIMIZATION AND MIXED-HORIZON DECISION-MAKING FOR AUTONOMOUS VEHICLES

MECHANISMS OF TUMOR ESCAPE FROM ANTI-ANGIOGENIC THERAPY

MOLECULAR ANALYSIS OF A YEAST TRANSCRIPTIONAL REGULATOR

MICROTUBULE-MEDIATED MECHANISMS UNDERLYING HAIR CELL DEVELOPMENT AND DEAFNESS

LONG-TERM IMPACT AND INTERVENTION FOR DIARRHEA IN BRAZIL

50 MW SEGMENTED ULTRALIGHT MORPHING ROTORS FOR WIND ENERGY

IRF4 AND IMMUNITY TO INFLUENZA INFECTION

IDENTIFYING CELL-TYPE SPECIFIC GENETIC CONTROL OF T1D RISK VARIANTS IN TEDDY - TYPE 1 DIABETES (T1D) IS A COMPLEX DISORDER THAT ARISES FROM THE ACTION OF MULTIPLE GENETIC AND ENVIRONMENTAL RISK FACTORS WITH POPULATION CUMULATIVE RISK APPROACHING 1 IN 300 CHILDREN. THE DISEASE PROCESS FOR T1D CONSISTS OF INITIATION OF AN IMMUNE ATTACK TARGETED TO INSULIN SECRETING BETA CELLS IN THE ISLETS, MODIFYING, IMPAIRING, AND (ULTIMATELY) DESTROYING THE BETA CELLS. GENOME- WIDE ASSOCIATION STUDIES (GWAS), PERFORMED BY OURSELVES AND OTHERS, IDENTIFIED MORE THAN 100 CHROMOSOMAL LOCI WHERE THERE IS SIGNIFICANT, REPLICATED EVIDENCE OF ASSOCIATION WITH T1D. AS SHOWN BY US IN THE TYPE 1 DIABETES GENETIC CONSORTIUM IMMUNOCHIP FINE-MAPPING ANALYSIS, AND OTHER STUDIES, ~ 98-99% OF T1D CREDIBLE SET OF SNPS ARE IN THE NON-CODING REGION OF THE GENOME AND PREFERENTIALLY MAP IN ENHANCER REGIONS ACTIVE IN IMMUNE CELLS. THE PROPOSED STUDY IS AN ANCILLARY RESEARCH PROJECT OF THE ENVIRONMENTAL DETERMINANTS OF DIABETES IN THE YOUNG (TEDDY) STUDY. TEDDY WAS DESIGNED TO DISCOVER ENVIRONMENTAL TRIGGERS OF T1D IN A PROSPECTIVE COHORT OF NEWBORNS AT GENETIC RISK, FOLLOWED MULTIPLE TIMES PER YEAR WITH COLLECTION OF SAMPLES FOR DEEP PHENOTYPIC AND BIOMARKER PROFILING. THIS PROJECT WILL UTILIZE LONGITUDINAL SAMPLES AND THEIR RICH DEMOGRAPHIC, GENETIC, AND IMMUNE MARKERS COLLECTED ON TEDDY PARTICIPANTS. WE WILL USE SINGLE-CELL SEQUENCING TECHNOLOGY TO MONITOR IMMUNE MARKERS AT THE PROTEIN AND TRANSCRIPTION LEVELS TO GENERATE PROFILES FOR DIFFERENT STAGES OF ISLET AUTOIMMUNITY. TO GAIN A COMPREHENSIVE UNDERSTANDING OF THE T1D RISK GENES THAT FUNCTION IN INITIATION AND PROGRESSION OF ISLET AUTOIMMUNITY, WE PROPOSE TO APPLY SINGLE-CELL SEQUENCING TO MAP T1D RISK VARIANTS THAT ALTER GENE EXPRESSION IN CIRCULATING IMMUNE CELLS; WE WILL USE IMMUNE CELL-SURFACE MARKERS FOR CELL TYPE IDENTIFICATION AND EXAMINE IMMUNE PROFILES AT INITIATION AND PROGRESSION TO T1D. TO IDENTIFY BIOLOGICAL PATHWAYS, THAT T1D GENES FUNCTION IN, WE WILL CONSTRUCT A REFERENCE CO-EXPRESSION NETWORK AND REFINE PREDICTED GENE-GENE INTERACTIONS WITH BAYESIAN NETWORKS.

GENOMIC ARCHITECTURE OF LGL LEUKEMIA

BIOTECHNOLOGY TRAINING PROGRAM

GENETIC CONTRIBUTORS TO DIABETES AND DYSLIPIDEMIA IN AFRICAN AMERICANS

VISUAL SIGNAL TRANSFORMATION IN THE RETINOCOLLICULAR PATHWAY

AKAP150-TRPV4 REGULATION OF ENDOTHELIAL FUNCTION IN OBESITY

RESEARCH FOR APPROVED HATCH (HATCH ACT REGULAR RESEARCH) PROJECTS AT VIRGINIA TECH

NEW PHARMACOTHERAPY FOR ALCOHOL AND CO-MORBID DISORDERS

TRANSLATION OF THE UVA ADVANCED AUTOMATED INSULIN DELIVERY SYSTEMS TO CLINICAL CARE IN YOUNG CHILDREN: GLYCEMIC CONTROL, REGULATORY ACCEPTANCE AND OPTIMIZATION OF DAY TO DAY USE

TRAINING IN THE PHARMACOLOGICAL SCIENCES

EXPEDITIONS: COLLABORATIVE RESEARCH: GLOBAL PERVASIVE COMPUTATIONAL EPIDEMIOLOGY

A MEDICAL CENTER NETWORK FOR OPTIMIZED LUNG CANCER BIOSPECIMEN BANKING

NEW START MURI COOPERATIVE AGREEMENT ENTITLED, "PLANETARY- AND GEOLOGICALLY-INSPIRED DISCOVERY OF REFRACTORY MATERIALS"

RYAN WHITE PART C OUTPATIENT EIS PROGRAM

PAPILLOMAVIRUS E6 STRUCTURAL CONSORTIUM

CONTROL OF SIR2 BY NUCLEAR NAD SALVAGE PATHWAYS

CIS-REGULATORY ARCHITECTURE OF CORONARY VASCULAR WALL LOCI

MECHANISMS OF MATERNAL BRAIN CHANGES WITH BIRTH INTERVENTIONS

DETERMINANTS OF MYOGENIC AND NEURONAL MEMBRANE PHENOMENA

GAP JUNCTIONAL PATTERNING IN ARRHYTHMIC HEART

ASTHMA AND ALLERGIC DISEASE CENTER

HALLMARKS OF PROTECTIVE IMMUNITY IN SEQUENTIAL RHINOVIRUS INFECTIONS IN HUMANS

LEVERAGING COMMUNITY PHARMACISTS TO OPTIMIZE SMOKING CESSATION SERVICES FOR RURAL SMOKERS IN APPALACHIA - RURAL APPALACHIAN POPULATIONS HAVE THE HIGHEST RATES OF CIGARETTE SMOKING IN THE U.S. AND ARE DISPROPORTIONATELY AFFECTED BY TOBACCO-RELATED CANCERS. PUBLICLY AVAILABLE SMOKING CESSATION RESOURCES (E.G., STATE QUITLINES, TEXT-BASED INTERVENTIONS, NICOTINE REPLACEMENT THERAPY [NRT]) ARE UNDER-UTILIZED BY RURAL APPALACHIAN SMOKERS. FURTHERMORE, RURAL APPALACHIA IS MEDICALLY UNDERSERVED; THUS, SMOKING CESSATION SERVICES WITHIN PRIMARY CARE SETTINGS FACE ADDITIONAL BARRIERS. COMMUNITY PHARMACISTS, WITH THEIR CENTRALIZED PLACEMENT IN LOCAL COMMUNITIES AND CLINICAL EXPERTISE, ARE IDEALLY SITUATED TO BUILD CAPACITY IN UNDERSERVED AREAS SUCH AS RURAL APPALACHIA TO ENHANCE EXISTING SMOKING CESSATION RESOURCES FOR SMOKERS. RESEARCH ON PHARMACIST-DELIVERED SMOKING CESSATION INTERVENTIONS IS LIMITED AND DOES NOT PROVIDE FOR DOCUMENTATION AND BILLING TO COMPENSATE PHARMACISTS FOR THEIR TIME SPENT COUNSELING PATIENTS. MEDICATION THERAPY MANAGEMENT (MTM), A PHARMACIST-DELIVERED MEDICATION ADHERENCE APPROACH THAT ALLOWS PHARMACISTS TO RECEIVE COMPENSATION FOR PROVIDING MEDICATION EXPERTISE, COULD BE LEVERAGED TO PROMOTE SMOKING CESSATION. TO ADDRESS THIS GAP, WE DEVELOPED AN MTM INTERVENTION, QUITAID, TO INCREASE SMOKING CESSATION AMONG RURAL SMOKERS. QUITAID WAS BASED ON A MEDICATION ADHERENCE INTERVENTION SHOWN TO BE EFFICACIOUS IN A QUITLINE SETTING. THE PURPOSE OF THE PROPOSED STUDY IS TO USE A PRAGMATIC APPROACH, GUIDED BY THE REACH, EFFECTIVENESS, ADOPTION, IMPLEMENTATION, AND MAINTENANCE (RE-AIM) FRAMEWORK, TO IDENTIFY THE ESSENTIAL COMPONENTS OF AN EFFECTIVE SMOKING CESSATION PROGRAM THAT CAN EASILY INTEGRATE WITHIN COMMUNITY PHARMACIES IN UNDERSERVED RURAL AREAS. SMOKERS (N=768) RECRUITED THROUGH 14 COMMUNITY PHARMACIES IN RURAL APPALACHIA WILL BE RANDOMIZED IN A 25 FULL FACTORIAL EXPERIMENT TO THE FOLLOWING FIVE TREATMENTS: (1) QUITAID (YES VS. NO), (2) TOBACCO QUITLINE (YES VS. NO), (3) SMOKEFREETXT (YES VS. NO), (4) COMBINATION NRT GUM + NRT PATCH (VS. NRT PATCH ALONE), AND/OR (5) 8 WEEKS OF NRT (VS. STANDARD 4 WEEKS). THE PRIMARY OUTCOME IS BIOCHEMICALLY- CONFIRMED POINT PREVALENCE ABSTINENCE AT THE 6-MONTH FOLLOW-UP. WE WILL ALSO ASSESS IMPLEMENTATION, INCLUDING RELATIVE COST, AS WELL AS FACILITATORS AND BARRIERS OF REACH, ADOPTION, AND MAINTENANCE OF QUITAID AND STANDARD, EVIDENCE-BASED TOBACCO TREATMENTS THROUGH AN ASK-ADVISE-CONNECT METHOD IN COMMUNITY PHARMACIES. OUR MAIN HYPOTHESIS IS THAT A SMOKING CESSATION MTM WILL INCREASE SMOKING CESSATION AND ENHANCE REACH AND ADHERENCE TO PUBLICLY AVAILABLE SMOKING CESSATION RESOURCES IN MEDICALLY UNDERSERVED RURAL AREAS. THE PROPOSED STUDY WILL: (1) PROVIDE FOUNDATIONAL EVIDENCE FOR LEVERAGING COMMUNITY PHARMACISTS IN UNDERSERVED AND RURAL AREAS TO PROMOTE UTILIZATION OF EXISTING EVIDENCE-BASED TOBACCO CESSATION RESOURCES THROUGH ENHANCED MTM SUPPORT, (2) INFORM UPDATED NATIONAL GUIDANCE ON TREATING RURAL SMOKERS, AND (3) AID STATE LEGISLATION EFFORTS RELATED TO PHARMACY SMOKING CESSATION PROGRAMS AND POLICIES. ULTIMATELY, THIS RESEARCH WILL INFORM STRATEGIES FOR SMOKING CESSATION IN RURAL AREAS, SUCH THAT CANCER RATES ACHIEVE PARITY WITH URBAN AREAS.

MRI OF MYOCARDIAL FUNCTION IN POST-INFARCT KNOCKOUT MICE

SYSTEMATIC IDENTIFICATION OF FUNCTIONAL T1D-ASSOCIATED NON-CODING SNPS USING GENETIC, TRANSCRIPTOMIC AND EPIGENETIC METHODS

TUBERCULOSIS SECOND LINE DRUG SUSCEPTIBILITY CHIP

EXTRINSIC MECHANISMS GOVERNING INJURY-INDUCED AXON DEGENERATION

PROJECT CATALYZE: THE IMPACT OF CARE + PATHS ON STUDENTS’ SUCCESS

ITERATIVE REPLICATION OF READ WELL IN FIRST GRADE

ALANYL-GLUTAMINE SUPPLEMENTATION OF STANDARD TREATMENT FOR C. DIFFICILE INFECTION

CCAM - UNIV. OF VIRGINIA

FORM AND FUNCTION OF OUR JANUS FACED GENOME

OBSERVATION OF YOUNG CHILDREN'S COMPETENCE IN CLASSROOM

EXTRACELLULAR SPACE AS MODULATOR OF GAP JUNCTION-CONDUCTION VELOCITY RELATIONSHIP

INSTITUTIONAL CAREER DEVELOPMENT CORE

EDUCATION RESEARCH TRAINING

HYPERPOLARIZED XENON-129 MRI: A NEW MULTI-DIMENSIONAL BIOMARKER TO DETERMINE PULMONARY PHYSIOLOGIC RESPONSES TO COPD THERAPEUTICS

RESEARCH NETWORKS FOCUSED ON CRITICAL PROBLEMS OF EDUCATION POLICY AND PRACTICE (NETWORKS)

TARGETING SUCCINATE SIGNALING FOR INNOVATIVE PAIN RELIEF IN ORAL CANCER. - CURRENT PAIN MANAGEMENT STRATEGIES FOR PATIENTS WITH ORAL OR HEAD AND NECK CANCER CONDITIONS OFTEN RELY ON HIGH-DOSE OPIOID ANALGESICS, WHICH CAN BE INEFFECTIVE. SUCCINATE IS A DICARBOXYLIC ACID METABOLITE IN THE KREBS CYCLE, AND EMERGING EVIDENCE HIGHLIGHTS ITS PRO-INFLAMMATORY ROLE THROUGH THE ACTIVATION OF ITS G-PROTEIN COUPLED RECEPTOR, SUCNR1. NOTABLY, ORAL CANCER PATIENTS SHOW ELEVATED CIRCULATING SUCCINATE LEVELS AND INCREASED SUCNR1 EXPRESSION IN TUMOR TISSUES. WE HAVE BEEN AT THE FOREFRONT OF INVESTIGATING SUCCINATE/SUCNR1 SIGNALING AND HAVE DEMONSTRATED THAT SUCNR1 ACTIVATION PROMPTS PRO-INFLAMMATORY SIGNALING IN MYELOID CELLS. OUR PRELIMINARY FINDINGS INDICATE THAT PATIENTS WITH ORAL CANCER EXPERIENCING HIGHER PAIN SCORES HAVE ELEVATED PLASMA SUCCINATE LEVELS. ADDITIONALLY, SUCNR1 EXPRESSION HAS BEEN OBSERVED IN BOTH HUMAN AND MOUSE GANGLIA, WITH SUCCINATE INCREASING INFLAMMATION AND NOCICEPTION IN WILDTYPE (WT) MICE BUT NOT IN SUCNR1 KNOCKOUT (KO) MICE. IN AN MOC2 ORTHOTOPIC XENOGRAFT MODEL OF ORAL CANCER, KO MICE EXHIBITED REDUCED FACIAL NOCICEPTION AND FEWER TUMOR- INFILTRATING MYELOID CELLS. WE HYPOTHESIZE THAT INHIBITING SUCNR1 ACTIVATION COULD ALLEVIATE ORAL CANCER PAIN BY REDUCING INFLAMMATION AND NOCICEPTION. TO TEST THIS HYPOTHESIS, WE PROPOSE TWO SPECIFIC AIMS. IN AIM 1, WE WILL INVESTIGATE SUCCINATE SIGNALING AND ASSESS SUCNR1 AS A POTENTIAL TARGET FOR ALLEVIATING ORAL CANCER PAIN USING CLINICAL SAMPLES AND PRECLINICAL MODELS. THE ANALGESIC EFFECTS OF A NOVEL SUCNR1 ANTAGONIST WE HAVE DEVELOPED WILL BE EVALUATED IN 4NQO-INDUCED ORAL CANCER MICE. WE WILL MEASURE TUMOR GROWTH, ORAL FUNCTION, AND REFERRED MECHANICAL AND THERMAL HYPERSENSITIVITIES, ALONG WITH ASSOCIATED COMORBIDITIES. ADDITIONALLY, WE WILL EXPLORE THE DISTRIBUTION AND NEUROMODULATORY FUNCTION OF SUCNR1 IN HUMAN ORAL CANCER TISSUES, AND THE GANGLIA OF BOTH HUMAN AND MOUSE. IN AIM 2, WE WILL EVALUATE THE ROLE OF MYELOID SUCNR1 IN ORAL CANCER PAIN WITH GLOBAL AND MYELOID-SPECIFIC KNOCKOUT MICE, ALONGSIDE THEIR LITTERMATE CONTROLS. THREE ORAL CANCER MODELS—MOC1 AND MOC2 ORTHOTOPIC XENOGRAFTS AND 4NQO-INDUCED ORAL CANCER—WILL BE DEVELOPED IN THESE MICE. WE WILL MEASURE TUMOR GROWTH AND NOCICEPTION WHILE CHARACTERIZING VARIOUS MYELOID POPULATIONS IN TUMOR, PERIPHERAL BLOOD, AND TUMOR- DRAINING LYMPH NODES THROUGH FLOW CYTOMETRY. LASTLY, WE WILL ASSESS SUCCINATE AND CYTOKINE LEVELS IN SERUM, AND TUMOR TISSUES USING SUCCINATE ASSAYS, MESO SCALE DISCOVERY MULTIPLEX IMMUNOASSAYS, AND SEMI- QUANTITATIVE PCR.

MEDIUM ENERGY SPIN PHYSICS WITH LASERS

BEHAVIORAL ROLES OF SEROTONIN

INVESTIGATION OF INJURIES TO ARMORED VEHICLE PERSONNEL SUBJECT TO BLAST: PRELIMINARY STUDY WITH EMPHASIS ON LOWER EXTREMEITY FACTORS

KIDS SIPSMARTER: A MULTI-LEVEL BEHAVIORAL AND HEALTH LITERACY INTERVENTION TO REDUCE SUGAR-SWEETENED BEVERAGES AMONG APPALACHIAN MIDDLE-SCHOOL STUDENTS

CAV-1.TRPV4 REGULATION OF ENDOTHELIAL FUNCTION IN SMALL PULMONARY ARTERIES

THE FUNCTIONAL ORGANIZATION OF MAMMALIAN MEMBRANES

MIDBRAIN CIRCUITS FOR PERCEPTUAL DECISION-MAKING - ABSTRACT PERCEPTUAL DECISION-MAKING IS A FUNDAMENTAL COGNITIVE ABILITY THAT IS VITAL TO HEALTHY, DAILY FUNCTIONING AND IS IMPAIRED IN MANY DISEASES. ALTHOUGH MANY BRAIN REGIONS ARE KNOWN TO BE INVOLVED, THERE IS NO CLEAR BRAIN-WIDE MODEL OF HOW PERCEPTUAL DECISIONS ARE FORMED AND EXECUTED AND THE UNDERLYING CIRCUIT MECHANISMS ARE STILL LARGELY UNKNOWN. HERE, A TEAM OF INVESTIGATORS PROPOSE A SERIES OF EXPERIMENTS THAT WILL USE BEHAVIORAL MEASURES, IMAGING, PHYSIOLOGY, CIRCUIT DISSECTION, AND COMPUTATIONAL MODELING TO STUDY HOW THE MIDBRAIN SUPERIOR COLLICULUS (SC) PARTICIPATES IN VISUAL DECISION-MAKING. SPECIFICALLY, THIS NEW TEAM OF INVESTIGATORS WILL PROBE THE CONTRIBUTION OF TWO SC NEURONAL CELL TYPES, WIDE FIELD VERTICAL (WFV) CELLS IN THE VISUOSENSORY LAYERS AND PREDORSAL BUNDLE (PDB) CELLS IN THE MOTOR LAYERS. THESE EXPERIMENTS WILL BE DONE IN MICE AND TREE SHREWS, TO REVEAL THE UNDERLYING CIRCUITS AND COMPUTATIONAL PRINCIPLES ACROSS SPECIES AND TO LAY THE FOUNDATION FOR FUTURE EXPERIMENTS DESIGNED TO DISSECT DECISION-MAKING CIRCUITS IN PRIMATES. IN AIM 1, THE INVESTIGATORS WILL ESTABLISH AND PERFORM PSYCHOPHYSICAL EXPERIMENTS TO ASSESS PERCEPTUAL DECISION-MAKING IN BOTH SPECIES. THE BEHAVIORAL DATA WILL BE FITTED WITH COMPUTATIONAL MODELS TO ARBITRATE BETWEEN DIFFERENT THEORIES OF DECISION-MAKING. IN AIM 2, TWO PHOTON CALCIUM IMAGING AND/OR PHYSIOLOGICAL RECORDING WILL BE PERFORMED IN MICE AND TREE SHREWS TO DETERMINE THE ACTIVITY OF WFV AND PDB NEURONS DURING THE PSYCHOPHYSICAL MEASURES ESTABLISHED IN AIM 1. IN ADDITION, WFV AND PDB NEURONS WILL BE SILENCED OPTOGENETICALLY DURING THE BEHAVIORAL TASKS TO REVEAL THEIR SPECIFIC ROLES IN DECISION-MAKING. IN AIM 3, THE INVESTIGATORS WILL USE INTERSECTIONAL MONOSYNAPTIC VIRAL TRACING TECHNIQUES, MULTIPLEXED PEROXIDASE LABELING FOR CONFOCAL AND ULTRASTRUCTURAL ANALYSIS OF SYNAPTIC CONNECTIONS AND AND OPTOGENETICS-ASSISTED BRAIN SLICE RECORDING TO INVESTIGATE THE INTRINSIC AND EXTRINSIC CIRCUITS THAT LINK WFV AND PDB CELLS. TOGETHER, THESE EXPERIMENTS WILL GENERATE NOVEL KNOWLEDGE OF THE SYNAPSE TO CIRCUIT MECHANISMS UNDERLYING PERCEPTUAL DECISION-MAKING, AND PROVIDE TECHNICAL AND THEORETICAL FOUNDATIONS FOR FUTURE MECHANISTIC STUDIES OF COGNITIVE FUNCTION IN HIGHER MAMMALIAN SPECIES DIRECTLY RELEVANT TO HUMANS.

MRI: DEVELOPMENT OF ACCORD, A COMMUNITY CYBERINSTRUMENT FOR BROADENING ACCESS TO RESEARCH ON SENSITIVE DATA

PREVENTION OF ALCOHOL RELATED INCIDENTS IN THE US AIR FORCE

TARGETING NEUROBLASTOMA WITH ARMED T CELLS

ROLE OF JAK2V617F IN THE PATHOGENESIS OF MYELOPROLIFERATIVE DISORDERS.

MENINGES-TO-ASTROCYTE COMMUNICATION IN COGNITIVE FUNCTION

MECHANISMS OF HETEROCELLULAR SIGNALING AT THE MYOENDOTHELIAL JUNCTION

STRUCTURE AND FUNCTION OF E. HISTOLYTICA ADHERENCE LECTIN

PREMATURITY-RELATED VENTILATORY CONTROL: LEADERSHIP DATA AND COORDINATION CENTER (LDCC)

MECHANISM OF CELLULOSE SYNTHESIS AND TRANSPORT ACROSS BIOLOGICAL MEMBRANES

NEURAL SUBSTRATES OF REINFORCEMENT LEARNING AND ITS TRAINING IN MAJOR DEPRESSION

STRUCTURE AND FOLDING OF INTEGRAL MEMBRANE PROTEINS

THE ROLES OF TUMOR MICROENVIRONMENT IN NEUROFIBROMA DEVELOPMENT AND THERAPEUTICS

FUNDAMENTAL STUDIES OF CATALYTIC SITES AND CATALYST/MEMBRANE INTEGRATIONS FOR ADVANCED HYDROXIDE EXCHANGE MEMBRANE ELECTROLYZERS