Regents Of The University Of California

CANCER CENTER SUPPORT GRANT

GRADUATE RESEARCH FELLOWSHIP PROGRAM

CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

CARES ACT: INSTITUTION ALLOCATION OF HEER FUNDS

CARES ACT FUNDING IN SUPPORT OF UC BERKELEY - INSTITUTIONAL PORTION

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

UCSF-GIVI CENTER FOR AIDS RESEARCH

CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE

CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE

UZ-UCSF CLINICAL TRIALS UNIT

CARES ACT FUNDING IN SUPPORT OF UC BERKELEY

HIGHER EDUCATION EMERGENCY FUNDS TO STUDENTS

QCRG PANDEMIC RESPONSE PROGRAM - QCRG PANDEMIC RESPONSE PROGRAM OVERALL SUMMARY THE QCRG (QUANTITATIVE BIOSCIENCES INSTITUTE CORONAVIRUS RESEARCH GROUP) PANDEMIC RESPONSE PROGRAM IS AN INTERDISCIPLINARY PROGRAM THAT AIMS TO IDENTIFY NEW DIRECT-ACTING ANTIVIRALS FOR SARS-COV-2 AND 19 OTHER VIRUSES. THE PROPOSAL BRINGS TOGETHER A TEAM OF 45 INVESTIGATORS FROM 14 DIFFERENT INSTITUTIONS WITH A HISTORY OF COLLABORATION; 31 OF THESE HAVE CO-PUBLISHED TOGETHER ON 25 PAPERS ON SARS-COV-2,1–25 EFFORTS THAT HAVE LAID A STRONG FOUNDATION FOR THE QCRG PANDEMIC RESPONSE PROGRAM. INITIALLY, WE WILL FOCUS ON EIGHT TARGET CLASSES FROM EIGHT VIRAL FAMILIES (CORONAVIRIDAE, PICORNAVIRIDAE, TOGAVIRIDAE, FLAVIVIRIDAE, HANTAVIRIDAE, ARENAVIRIDAE, NAIROVIRIDAE AND PARAMYXOVIRIDAE), INCLUDING SEVEN CORONAVIRUSES, WITH A FOCUS ON SARS-COV-2, WHERE THE VIRAL RNA AND 12 PROTEINS WILL BE TARGETED. IN ADDITION TO THE SARS-COV-2 RNA (PROJECT 1), WE WILL TARGET THE NSP3 PLP AND NSP5 MPRO PROTEASES (PROJECT 2); THE NSP3 MACRODOMAIN (PROJECT 5); THE RDRP POLYMERASE, NSP7, NSP8 AND NSP12 (PROJECT 2) THE STRUCTURAL PROTEINS E (PROJECT 3), N (PROJECT 6) AND M (PROJECTS 3 AND 6); THE METHYLTRANSFERASES NSP10/16 AND NSP14 (PROJECT 4); AND THE ACCESSORY PROTEIN INVOLVED IN REGULATING THE IMMUNE RESPONSE, ORF9B (PROJECT 6). ALTHOUGH WE WILL FOCUS ON SARS-COV-2, RELATED PROTEINS FROM 19 OTHER VIRUSES WILL ALSO BE TARGETED. USING THE QCRG DRUG DISCOVERY PLATFORM, WE WILL PERFORM SCREENS ON THESE TARGETS, INVOLVING FRAGMENT CAMPAIGNS, VIRTUAL LIBRARY DOCKING, AND HIGH-THROUGHPUT SCREENS, TO DISCOVER INHIBITORS, WHICH WILL BE OPTIMIZED USING CYCLES OF DESIGN, STRUCTURE DETERMINATION, AND TESTING. IN VITRO AND IN VIVO PHARMACOKINETICS AS WELL AS ACTIVITY IN CELLULAR AND MOUSE MODELS OF INFECTION WILL BE CARRIED OUT, FOLLOWED BY STUDIES INVOLVING ORAL BIOAVAILABILITY, CLEARANCE, PERMEABILITY, SOLUBILITY, METABOLIC LIABILITIES, TOXICITY AND EFFICACY. THE FINAL GOAL OF EACH PROJECT IS AN OPTIMIZED LEAD READY FOR CLINICAL DEVELOPMENT AT ROCHE (SEE LETTER OF SUPPORT FROM DR. JOHN YOUNG, HEAD OF INFECTIOUS DISEASES) AND OTHER INDUSTRY PARTNERS. THROUGHOUT, WE WILL EXPLOIT AN INTEGRATED SUITE OF EXPERIMENTAL AND COMPUTATIONAL TECHNOLOGIES PROVIDED BY EIGHT CORES. THE BIOCHEMISTRY CORE WILL PROVIDE PURIFIED MATERIAL FOR THE SCREENING CORE, WHILE THE STRUCTURES OF TARGETS AND COMPOUNDS WILL BE DETERMINED THROUGH THE CRYO-EM, CRYO-ET AND CRYSTALLOGRAPHY CAPABILITIES OF THE STRUCTURAL BIOLOGY CORE. STATE-OF-THE-ART MASS SPECTROMETRY IN THE PROTEOMICS CORE WILL PROVIDE MECHANISTIC INSIGHT INTO THE EFFECTS OF COMPOUNDS ON THEIR TARGETS. THE MEDICINAL CHEMISTRY CORE WILL OPTIMIZE POTENT ON- TARGET COMPOUNDS AND WORK CLOSELY WITH THE IN VITRO VIROLOGY CORE AND IN VIVO VIROLOGY CORE TO MEASURE AND OPTIMIZE ANTIVIRAL ACTIVITY. THE INTEGRATIVE MODELING CORE WILL PROVIDE COMPUTATIONAL SUPPORT TO STRUCTURE DETERMINATION AND INHIBITOR DISCOVERY THROUGHOUT THE QCRG DRUG DISCOVERY PLATFORM. THE ADMINISTRATIVE CORE WILL PROVIDE LEADERSHIP, HELP TO FOSTER A COLLABORATIVE ENVIRONMENT, AND MANAGE THE MENTORED PROJECTS AND THE DEVELOPMENTAL RESEARCH PROJECTS, WHICH WILL BRING IN NEW INVESTIGATORS.

THE ALZHEIMER'S DISEASE TAU PLATFORM CLINICAL TRIAL - PROJECT SUMMARY / ABSTRACT TAU PROTEIN IS AN ATTRACTIVE AD THERAPEUTIC TARGET BECAUSE THE AMOUNT AND ANATOMICAL DISTRIBUTION OF INSOLUBLE TAU AT AUTOPSY IS STRONGLY CORRELATED WITH THE SYMPTOMS AND SEVERITY OF DISEASE DURING LIFE. MULTIPLE TAU THERAPIES ARE NOW IN CLINICAL TRIALS FOR AD, WITH MANY NEW AGENTS ENTERING THE CLINIC. NEW APPROACHES TO ACCELERATING THEIR CLINICAL DEVELOPMENT ARE URGENTLY NEEDED. A VARIETY OF AD BIOMARKERS NOW EXIST, INCLUDING CSF AND PLASMA BETA AMYLOID RATIOS AND PHOSPHORYLATED TAU (P-TAU) LEVELS, AND AMYLOID AND TAU PET TRACERS, PROVIDING TOOLS TO MEASURE PHARMACODYNAMIC EFFECTS OF AMYLOID AND TAU THERAPIES ON THE CORE BIOLOGY OF AD. THE GOAL OF THE ALZHEIMER’S TAU PLATFORM (ATP) TRIAL IS TO CONDUCT A RANDOMIZED, PLACEBO CONTROLLED, PHASE 2 PLATFORM TRIAL IN PRECLINICAL-PRODROMAL AD THAT WILL SIMULTANEOUSLY TEST AT LEAST TWO DIFFERENT TAU-DIRECTED THERAPIES, ALONE OR IN COMBINATION WITH AN ANTI-AMYLOID THERAPY, TO DETERMINE SAFETY, TOLERABILITY, AND BIOLOGICAL BASED PROOF OF CONCEPT BASED ON THE TAU PET TRACER 18F MK6240 AND OTHER TAU BIOMARKERS. PLATFORM TRIALS CREATE EFFICIENCIES THROUGH GENERATION OF A COMMON CLINICAL TRIAL PROTOCOL AND SHARED PLACEBO GROUPS TO ALLOW A GREATER NUMBER OF THERAPIES TO BE TESTED IN LESS TIME WITH LESS EXPENSE THAN BY CONDUCTING MULTIPLE INDEPENDENT TRIALS. THIS TRIAL WILL TEST 5 THERAPEUTIC HYPOTHESES INVOLVING COMBINATIONS OF 3 DRUGS VERSUS PLACEBO: TWO TAU THERAPIES WILL BE STUDIED IN A 2 X 3 FACTORIAL DESIGN (PLACEBO VS. ANTI-AMYLOID [N=2] X TWO TAU THERAPIES OR PLACEBO [N=3]) FOR 24 MONTHS, IN SIX PARALLEL ARMS. THE KEY INCLUSION CRITERIA FOR ATP WILL BE >20 CENTILOIDS OF AMYLOID PET UPTAKE, 18F MK6240 TEMPORAL ROI SUVR >1.25, WITH A GLOBAL CLINICAL DEMENTIA RATING (CDR) OF 0 OR 0.5 AND MMSE >23. USING THESE CRITERIA, WE ESTIMATE THAT 150 PARTICIPANTS PER ARM WILL BE NECESSARY TO HAVE 80% POWER TO DETECT A 30% SLOWING IN THE ACCUMULATION 18F MK6240 SIGNAL OVER 24 MONTHS OF BLINDED THERAPY. KEY SECONDARY ENDPOINTS WILL BE CHANGES IN PLASMA P-TAU SPECIES (-217, ETC.) AND NEUROFILAMENT LIGHT CHAIN (NFL), CLINICAL RATING SCALES AND VOLUMETRIC MRI. LEVERAGING THE EXPERIENCE AND RESOURCES OF THE NIH AD CLINICAL TRIAL CONSORTIUM (ACTC), WE PROPOSE TO ENROLL 900 PARTICIPANTS AT ~100 ACTC SITES OVER 24 MONTHS, RANDOMIZE THEM 5:1 DRUG:PLACEBO FOR 24 MONTHS OF BLINDED TREATMENT, FOLLOWED BY A 24 MONTH OPEN LABEL EXTENSION. WE AIM TO: 1) TEST THE ABILITY OF TWO TAU-DIRECTED THERAPIES, EITHER ALONE OR IN COMBINATION WITH AN ANTI-AMYLOID THERAPY, TO SLOW THE ACCUMULATION OF TAU PET SIGNAL OVER 24 MONTHS AS COMPARED TO PLACEBO OR ANTI-AMYLOID THERAPY ALONE; 2) TEST THE SAFETY AND TOLERABILITY OF 24 MONTHS OF BLINDED THERAPY FOLLOWED BY AN OPTIONAL 24 MONTH OPEN LABEL EXTENSION OF COMBINATION TAU/ANTI-AMYLOID THERAPY; AND 3) EXPLORE THE ABILITY OF EACH OF TWO TAU DIRECTED THERAPIES TO SLOW DISEASE PROGRESSION AS MEASURED BY CSF AND PLASMA BIOMARKERS (PLASMA P-TAU, NFL), VOLUMETRIC MRI AND CLINICAL ASSESSMENTS (PRECLINICAL ALZHEIMER’S COMPOSITE [PACC], ETC.). IF SUCCESSFUL, THE ATP WILL PROVIDE DATA FOR DECISION-MAKING ABOUT WHICH TAU THERAPIES OR COMBINATIONS TO PURSUE IN LARGER EFFICACY STUDIES, AN ONGOING RESOURCE TO TEST NEW THERAPEUTIC APPROACHES BEYOND TAU, AND WILL IMPROVE UNDERSTANDING OF AD BIOLOGY.

SUPPORTING THE IMPLEMENTATION AND EXPANSION OF HIGH QUALITY HIV

STRUCTURAL CELL BIOLOGY OF DNA REPAIR MACHINES

CENTER FOR ENERGY EFFICIENT ELECTRONICS SCIENCE (CENTER FOR E3S)

US POINTER NEUROIMAGING ANCILLARY STUDY

FRONTOTEMPORAL DEMENTIA: GENES, IMAGES AND EMOTIONS

CENTER FOR CELLULAR CONSTRUCTION

UZ-UCSF CLINICAL TRIALS UNIT

TOXIC SUBSTANCES IN THE ENVIRONMENT

HARC CENTER: HIV ACCESSORY AND REGULATORY COMPLEXES

GH16-1619: SUPPORTING THE IMPLEMENTATION AND EXPANSION OF HIGH QUALITY, SUSTAINABLE AND COMPREHENSIVE

DEVELOPING THE PRELIMINARY DESIGN FOR THE DEEP UNDERGROUND SCIENCE AND ENGINEERING LABORATORY (DUSEL)

GRADUDATE RESEARCH FELLOWSHIP PROGRAM

THE CONNIE WOFSY WOMEN'S HIV STUDY

REDUCING FAILURE-TO-INITIATE ART: STREAMLINED ART START STRATEGY (START)

MECHANISMS OF INITIATION AND PERSISTENCE OF ALLERGIC ASTHMA

BRAIN TUMOR SPORE GRANT

CENTER FOR AIDS PREVENTION STUDIES

INTRACELLULAR PATHOGENS AND INNATE IMMUNITY

IMAGING AND TISSUE BIOMARKERS IN THE TREATMENT OF BRAIN TUMORS

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH SUPPORTING THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCY BIOLOGICAL TECHNOLOGIES OFFICE PANACEA PROGRAM.

NDC FOR THE OPTICAL CONTROL OF BIOLOGICAL FUNCTION

SYNTHETIC BIOLOGY ENGINEERING RESEARCH CENTER (SYNBERC)

AIDS EDUCATION TRAINING CENTER

UCSF CORE CENTER FOR PATIENT-CENTRIC MECHANISTIC PHENOTYPING IN CHRONIC LOW BACK PAIN

TEAM FOR RESEARCH IN UBIQUITOUS SECURE TECHNOLOGY (TRUST)

SF BAY AREA MACS/WIHS COMBINED COHORT STUDY

DEGENERATIVE AND DEMENTING DISEASES OF AGING

NEW APPROACHES TO DEMENTIA HETEROGENEITY

QLCI-CI: NSF QUANTUM LEAP CHALLENGE INSTITUTE FOR PRESENT AND FUTURE QUANTUM COMPUTING

NUCLEAR SCIENCE & SECURITY CONSORTIUM (NNSC)

AUTOIMMUNITY CENTER OF EXCELLENCE CLINICAL RESEARCH PROGRAM

CELL THERAPIES FOR NEUROINFLAMMATION AND NEURODEGENERATION PROGRAMMABLE PLATFORM FOR TARGETING THERAPIES TO THE BRAIN

GH19-1951 TARGETED HIV/TB STRATEGIC INFORMATION TECHNICAL ASSISTANCE FOR PRESIDENT'S EMERGENCY PLAN FOR AIDS RELIEF (PEPFAR) AND GLOBAL FUND TO FIGHT AIDS, TUBERCULOSIS AND MALARIA (GFATM) COUNTRIES

UCSF-STANFORD CENTER OF EXCELLENCE IN REGULATORY SCIENCE

THE PROGRESSIVE SUPRANUCLEAR PALSY CLINICAL TRIAL PLATFORM (PTP) - PROJECT SUMMARY / ABSTRACT PROGRESSIVE SUPRANUCLEAR PALSY (PSP) IS A SEVERE NEURODEGENERATIVE DISEASE OF AGING THAT USUALLY LEADS TO DEATH WITHIN 5-7 YEARS OF DIAGNOSIS. THERE ARE NO EFFECTIVE TREATMENTS FOR PSP, BUT THERAPEUTIC APPROACHES BEING TESTED IN CLINICAL TRIALS FOR OTHER NEURODEGENERATIVE DISEASES, SUCH AS ALZHEIMER’S (AD) AND AMYOTROPHIC LATERAL SCLEROSIS MAY BE EVEN MORE PROMISING FOR PSP. DESPITE EXCELLENT FEASIBILITY OF LARGE MULTICENTER PSP CLINICAL TRIALS, THERE ARE FEW NEW STUDIES, LIMITING OPTIONS FOR PATIENTS TO ACCESS EXPERIMENTAL THERAPIES AND SEVERELY DELAYING THE IDENTIFICATION OF EFFECTIVE TREATMENTS. NEW, EFFICIENT CLINICAL PSP TRIAL PROGRAMS AND FOCUSED EFFORTS TO IDENTIFY PSP BIOMARKERS ARE URGENTLY NEEDED. THE OVERARCHING GOAL OF THE PSP TRIAL PLATFORM (PTP) IS TO CONDUCT A RANDOMIZED, PLACEBO-CONTROLLED, PHASE 2 PLATFORM TRIAL IN MILD-MODERATE PSP THAT WILL SIMULTANEOUSLY TEST AT LEAST THREE DIFFERENT TAU-RELATED OR NEUROPROTECTIVE THERAPIES TO DETERMINE SAFETY, TOLERABILITY AND CLINICAL PROOF OF CONCEPT BASED ON A MULTIMODAL CLINICAL RATING SCALE, THE MODIFIED PSP RATING SCALE-15 (MPSPRS-15). PLATFORM TRIALS CREATE ECONOMIES OF SCALE THROUGH GENERATION OF A COMMON CLINICAL TRIAL PROTOCOL AND THE ABILITY TO SHARE PLACEBO GROUP INFORMATION TO ALLOW A GREATER NUMBER OF THERAPIES TO BE TESTED IN A SHORTER AMOUNT OF TIME AND WITH LESS EXPENSE THAN MULTIPLE INDEPENDENT CLINICAL TRIALS. THREE THERAPIES WILL BE COMPARED FOR 12 MONTHS, IN FOUR PARALLEL ARMS, WITH A 3:1 (DRUG:PLACEBO) RANDOMIZATION RATIO TO ENCOURAGE RECRUITMENT, FOLLOWED BY AN OPTIONAL, 12-MONTH OPEN-LABEL EXTENSION. KEY INCLUSION CRITERIA WILL BE A DIAGNOSIS OF MILD-MODERATE PSP, WITH SYMPTOMS < 5 YEARS IN DURATION, PRESERVED ABILITY TO AMBULATE WITH MINIMAL COGNITIVE IMPAIRMENT (MINI MENTAL STATE EXAM > 25). ALL INDIVIDUALS WILL BE SCREENED WITH A VALIDATED MRI DIAGNOSTIC TOOL TO RULE OUT NON-PSP ETIOLOGIES. USING THESE CRITERIA, WE ESTIMATE THAT 110 PARTICIPANTS PER GROUP (3 DRUG, 1 PLACEBO) WILL BE NECESSARY TO HAVE 80% POWER TO DETECT A 33% SLOWING IN DECLINE ON THE MPSPRS-15 OVER 12 MONTHS, ACCOUNTING FOR 20% ATTRITION. KEY SECONDARY ENDPOINTS WILL INCLUDE INCLUDING CHANGES IN THE TOTAL PSPRS, ACTIVITIES OF DAILY LIVING (SCHWAB AND ENGLAND ADL), GLOBAL STATUS (CLINICAL GLOBAL IMPRESSION OF DISEASE SEVERITY), THE PSP QUALITY OF LIFE SCALE, A NEWLY VALIDATED PSP COGNITIVE COMPOSITE, AND VOLUMETRIC MRI BIOMARKERS INCLUDING MIDBRAIN VOLUME. EXPLORATORY CSF BIOMARKER DISCOVERY EFFORTS WILL FOCUS ON CHANGES IN PSP-ASSOCIATED TAU FRAGMENTS, AXON GUIDANCE NETWORK PROTEINS, AND LYSOSOMAL PROTEINS AND LIPIDS OVER 12 MONTHS. LEVERAGING THE EXPERIENCE AND RESOURCES OF THE CUREPSP CENTERS OF CARE, THE PARKINSON’S STUDY GROUP, THE NIH-FUNDED ALLFTD RESEARCH NETWORK, AND THE NIH AD CLINICAL TRIALS CONSORTIUM (ACTC), WE PROPOSE TO ENROLL 440 PARTICIPANTS AT ~50 SITES IN NORTH AMERICA OVER 24 MONTHS. LIKE OTHER PLATFORM TRIALS, ADDITIONAL THERAPEUTIC ARMS MAY BE ADDED AFTER INITIAL PROGRAM LAUNCH. IF SUCCESSFUL, THE PTP WILL PROVIDE KEY DATA FOR DECISION-MAKING ABOUT WHICH THERAPIES TO PURSUE IN LARGER EFFICACY TRIALS, CREATE A NEW INFRASTRUCTURE TO EFFICIENTLY EVALUATE PSP THERAPIES, AND A NEW RESOURCE FOR LONGITUDINAL PSP CLINICAL AND BIOMARKER DATA, AND BIOSAMPLES, TO BE SHARED WITH OTHER RESEARCHERS.

OCCUPATIONAL SAFETY AND HEALTH EDUCATION AND RESEARCH CENTERS

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

DARE: DELANEY AIDS RESEARCH ENTERPRISE TO FIND A CURE.

DECONSTRUCTING AND RECONSTRUCTING THE T CELL SIGNALING NETWORK

PROGRAM FOR RESISTANCE IMMUNOLOGY SURVEILLANCE & MODELING OF MALARIA IN UGANDA

PROTECTIVE IMMUNITY FOLLOWING DENGUE VIRUS NATURAL INFECTIONS AND VACCINATION

DELANEY AIDS RESEARCH ENTERPRISE TO CURE HIV

SPIROMICS II: BIOLOGICAL UNDERPINNINGS OF COPD HETEROGENEITY AND PROGRESSION

DELANEY AIDS RESEARCH ENTERPRISE TO CURE HIV - PROJECT SUMMARY/ABSTRACT THE GOALS OF THE DARE COLLABORATORY ARE TO DEVELOP A VIABLE COMBINATION REGIMEN THAT REDUCES THE REBOUND- COMPETENT HIV/SIV RESERVOIR DURING ANTIRETROVIRAL THERAPY (ART) AND/OR INDUCES DURABLE CONTROL OF HIV/SIV IN THE ABSENCE OF THERAPY. OUR PROPOSED WORK IS BASED ON TWO OBSERVATIONS MADE OUR GROUP. FIRST, WE FOUND THAT VIRUS- SPECIFIC CD8+ T CELLS CONTRIBUTE TO CONTROL OF THE VIRUS AT STEADY-STATE. THESE CELLS, HOWEVER, HAVE LIMITED EFFECT DURING AND IMMEDIATELY POST-ART. WE BELIEVE AND WILL SEEK TO PROVE THAT EFFECTIVE REMISSION STRATEGIES WILL REQUIRE ORGANIZATION OF A ROBUST INNATE AND ADAPTIVE IMMUNE RESPONSE DURING THE EARLIEST STAGES OF VIRUS REBOUND, EFFECTIVELY INTERCEPTING AND SUPPRESSING VIRAL REBOUND PRIOR TO THE MASSIVE SYSTEMIC GROWTH OF SIV/HIV THAT OVERWHELMS, DAMAGES AND/OR EVADES THE IMMUNE SYSTEM. SECOND, WE AND OTHERS HAVE FOUND THAT DESPITE VIRUS EXPRESSION DURING ART (EITHER NATURALLY OR IN RESPONSE TO A LATENCY REVERSAL AGENT), THE FREQUENCY OF INFECTED CELLS REMAINS STABLE. WE HAVE FOUND THAT INFECTED CELLS ARE RELATIVELY RESISTANT TO CELL DEATH PROGRAMS. WE WILL DEVELOP THERAPIES THAT RENDER THESE CELLS TO HOST-MEDIATED CLEARANCE MECHANISMS, THUS RESULTING IN THEIR REDUCTION AND PERHAPS ELIMINATION. TO ACHIEVE OUR GOALS, WE WILL (1) CHARACTERIZE IN PEOPLE TRANSCRIPTIONALLY ACTIVE CELLS AND PROLIFERATING INFECTED CELLS, FOCUSING ON IDENTIFYING MECHANISMS FOR PERSISTENCE, (2) DEFINE IN PEOPLE THE EARLIEST IMMUNOLOGIC AND VIROLOGIC EVENTS POST-INTERRUPTION OF ART, FOCUSING ON POST-TREATMENT CONTROLLERS, (3) DEVELOP IN NON-HUMAN PRIMATES (NHPS) A COMBINATION REGIMEN THAT TARGETS THE REACTIVATING VIRUS DURING THE IMMEDIATE POST-ART PERIOD AND RESULTS IN SUSTAINED CONTROL AT SET-POINT AND (4) DEVELOP IN VITRO AND IN ANIMAL MODELS THERAPIES THAT RENDER THE RESERVOIR MORE SUSCEPTIBLE TO DEATH THROUGH THE ACTIVATION OF INTRINSIC (CELLULAR) AND/OR EXTRINSIC (VIRUS-SPECIFIC) PRO-APOPTOTIC PATHWAYS. THIS WORK WILL LEVERAGE OUR DEEP INVESTMENT IN (1) THE OPTIMIZATION OF THE SIV NHP MODEL AND A HUMANIZED MOUSE MODEL, BOTH DEVELOPED SPECIFICALLY TO SUPPORT THE TYPES OF STUDIES WE WILL PURSUE, (2) THE DEVELOPMENT OF A ROBUST CLINICAL COHORT (SCOPE) DESIGNED TO SUPPORT INTENSIVE, BIOLOGIC STUDIES OF PEOPLE LIVING WITH HIV (PWH), AND (3) THE IMPLEMENTATION AND CONDUCT OF SEVERAL CLINICAL TRIALS DESIGNED IN PART TO TEST OUR HYPOTHESES IN PEOPLE AND FROM WHICH SAMPLES WILL BE MADE AVAILABLE TO OUR TEAM FOR EX VIVO STUDIES. WE ANTICIPATE MEETING THE FOLLOWING MILESTONES AND DELIVERABLES: (1) DEFINITION OF THE ACTIVE RESERVOIR IN LYMPHOID TISSUES FROM SIV-INFECTED MONKEYS AND HIV-INFECTED HUMANS ON EFFECTIVE ART, (2) DETERMINATION OF WHETHER RESERVOIR CELLS ARE RESISTANT TO INTRINSIC AND EXTRINSIC CELL KILLING, (3) DEVELOPMENT OF A VIABLE AND TRANSLATABLE REMISSION STRATEGY IN NHPS, AND (4) IDENTIFICATION AND PRE-CLINICAL DEVELOPMENT OF INTERVENTIONS AIMED AT ENHANCING THE CELL DEATH, EITHER BY MAKING CELLS MORE SUSCEPTIBLE TO CELL DEATH AND/OR BY OPTIMIZING THE EFFICACY OF THE VIRUS-SPECIFIC T CELL RESPONSE.

UNLEARNING NEURAL SYSTEMS DYSFUNCTION IN NEUROPSYCHIATRIC DISORDERS

RECENT INFECTION SURVEILLANCE CONSORTIUM

NUCLEAR SCIENCE AND ENGINEERING NONPROLIFERATION RESEARCH CONSORTIUM

CENTER TO ADDRESS DISPARITIES IN CHILDREN'S ORAL HEALTH

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

HARC: HIV ACCESSORY AND REGULATORY COMPLEXES - THE HARC CENTER: HIV ACCESSORY AND REGULATORY COMPLEXES OVERALL SUMMARY THE HARC CENTER IS AN INTERDISCIPLINARY PROGRAM THAT AIMS TO IMPROVE OUR UNDERSTANDING OF THE INTERACTIONS BETWEEN HIV ACCESSORY AND REGULATORY PROTEINS AND HOST CELLULAR SYSTEMS, WITH THE ULTIMATE GOAL TO EXPAND ON THERAPEUTIC TARGETS AND TREATMENT MODALITIES FOR HIV/AIDS. THE HARC CENTER WILL FOCUS ITS EFFORTS ON THE DETERMINATION OF STRUCTURES OF THE ACCESSORY AND REGULATORY PROTEINS OF HIV-1, WITH A FOCUS ON TAT, VIF AND REV, IN COMPLEX WITH THEIR CELLULAR PARTNERS, WHICH HAVE NOT BEEN TARGETS OF HIV THERAPEUTIC MODALITIES UNTIL NOW. A BETTER MOLECULAR UNDERSTANDING OF THE FUNCTIONS AND MECHANISMS OF VIRUS-HOST COMPLEXES MAY REVEAL NEW THERAPEUTIC STRATEGIES FOR INTERVENTION, INCLUDING STRATEGIES OF HOST-DIRECTED THERAPIES, WHICH MAY ESCAPE THE LIMITATIONS OF CURRENT DRUG REGIMENS WHERE MUTATIONS IN THE TARGETED HIV ENZYMES CAN DIMINISH DRUG EFFICACY. THE HARC CENTER WILL DETERMINE THE STRUCTURES OF THESE VIRUS-HOST COMPLEXES USING AN INTEGRATED “SYSTEMS-TO- STRUCTURE” PLATFORM THAT INCLUDES (1) DISCOVERY, THROUGH NOVEL METHODS OF FUNCTIONAL PROTEOMICS AND GENETICS BEING DEVELOPED IN THE HARC CENTER, (2) VALIDATION THROUGH BREAKTHROUGH CRISPR METHODS IN PRIMARY T CELLS AS WELL AS TARGETED BIOCHEMICAL AND FUNCTIONAL ASSAYS, AND (3) STRUCTURE DETERMINATION USING A SYNTHESIS OF INNOVATIVE STRUCTURAL TECHNIQUES DEVELOPED IN PREVIOUS ITERATIONS OF THE HARC CENTER TO ADDRESS THE LARGE, FLEXIBLE, HETEROGENEOUS AND SOMETIMES MEMBRANE-ASSOCIATED SYSTEMS WE STUDY. THE PROPOSED RESEARCH PROJECTS ARE CENTERED AROUND THREE THEMES THAT SERVE THE CENTER’S GOAL. WE WILL EXPLORE HOW HIV INHIBITS HOST RESTRICTION FACTORS (THEME 1), STUDY THE FACTORS REGULATING HIV TRANSCRIPTION AND LATENCY (THEME 2) AND INVESTIGATE VIRUS-HOST EVOLUTION (THEME 3) ACROSS THREE PROJECTS: STRUCTURE AND EVOLUTION OF VIF AND APOBEC3 (PROJECT 1), REGULATION OF HIV TRANSCRIPTION AND LATENCY (PROJECT 2), AND GENETICS AND EVOLUTION (PROJECT 3). THE HARC CENTER PROJECTS ARE SUPPORTED BY 4 TECHNOLOGY CORES COVERING PROTEOMIC APPROACHES (CORE 1 - PROTEOMICS), CRISPR SCREENS AND ENDOGENOUS TAGGING IN PRIMARY CELLS TO STUDY VIRUS- HOST FUNCTION (CORE 2 - GENETICS), STRUCTURAL BIOLOGY USING CRYO-ELECTRON MICROSCOPY, X-RAY SCREENING AND ANTIBODY TECHNOLOGIES TO DETERMINE THE STRUCTURES OF HIV VIRUS-HOST COMPLEXES (CORE 3 - STRUCTURAL BIOLOGY), AND INTEGRATIVE MODELING OF VIRUS-HOST COMPLEXES (CORE 4 - COMPUTATIONAL). THE OVERALL GOALS, PROGRESS, AND ADMINISTRATION AS WELL AS OUTREACH ACTIVITIES AND COMMUNICATIONS WILL BE OVERSEEN BY THE ADMINISTRATIVE CORE (CORE 5). THE DEVELOPMENTAL CORE (CORE 6) WILL PROVIDE TRAINING OPPORTUNITIES TO YOUNG INVESTIGATORS AND HARC CENTER MEMBERS AND AWARD THE COLLABORATIVE OPPORTUNITY FUND TO ENHANCE THE CENTER’S OVERALL RESEARCH THEME.

TO CONDUCT NONPROLIFERATION RESEARCH IN NUCLEAR SCIENCE AND ENGINEERING AND DEVELOP HUMAN CAPITAL FOR THE NATION'S NATIONAL AND NUCLEAR SECURITY MISSIONS IN SUPPORT OF DNN R&D.

ALS EFFICIENTLY NETWORKING ADVANCED BEAM LINE EXPERIMENTS (ALS-ENABLE)

A MULTISECTORAL STRATEGY TO ADDRESS PERSISTENT DRIVERS OF THE HIV EPIDEMIC IN EAST AFRICA

INNATE AND ADAPTIVE IMMUNE RESPONSES IN TH2-HIGH ASTHMA

PRIMARY IMMUNE DEFICIENCY TREATMENT CONSORTIUM

PHENIX: NEW METHODS FOR AUTOMATION IN MACROMOLECULAR CRYSTALLOGRAPHY

RESEARCH COORDINATING CENTER TO REDUCE DISPARITIES IN MULTIPLE CHRONIC DISEASES (RCC RD-MCD) - SUMMARY SIGNIFICANT DISPARITIES IN PREVENTION, TREATMENT, AND MANAGEMENT OF MULTIPLE CHRONIC DISEASES EXIST ALONG INTERSECTING RACIAL, CULTURAL, SOCIO-ECONOMIC, AND VULNERABLE POPULATION CONTEXTUAL LINES; COMMUNITY ENGAGEMENT AND CULTURALLY INFORMED MULTILEVEL APPROACHES ARE REQUIRED TO EFFECTIVELY REDUCE THESE DISPARITIES. THE UCSF RESEARCH COORDINATING CENTER WILL LEVERAGE AND PIVOT OUR SIGNIFICANT EXPERTISE, EXPERIENCE, AND CAPACITY IN COMMUNITY-ENGAGED RESEARCH, DISPARITIES RESEARCH, PROGRAM IMPLEMENTATION EXPERIENCE WITH UNDERSERVED AND VULNERABLE POPULATIONS, DATA SCIENCE, AND MAJOR CHRONIC DISEASES TO SERVE AND SUPPORT A NATIONWIDE RESEARCH COORDINATING AND TECHNICAL ASSISTANCE CENTER. THE SPECIFIC AIMS OF THE PROJECT ARE TO: 1) DEVELOP THE NIMHD RD-MCD RESEARCH CONSORTIUM AND ITS OVERSIGHT MECHANISMS: THROUGH THE ORGANIZATIONAL AND MANAGEMENT UNIT’S CONVENING, SECURE COMMUNICATION, INTERNAL AND EXTERNAL RESOURCE SHARING, STANDARDIZATION, PROGRESS, SITE, AND STUDY MONITORING, AND DISSEMINATION FUNCTIONS VIA A 508- COMPLIANT CONSORTIUM WEBSITE IN COOPERATION WITH PROGRAM OFFICIALS, REPRESENTATIVE STEERING COMMITTEE, NETWORKED COMMUNITY ADVISORY BOARDS, AND AN INDEPENDENT DATA AND SAFETY MONITORING BOARD (DSMB). 2) IMPLEMENT RD-MCD CONSORTIUM-WIDE COMMON DATA ELEMENT DEVELOPMENT, COLLECTION, INTEGRATION, CURATION, ANALYSIS, AND SHARING USING EXISTING WELL-DEVELOPED NATIONAL DATA COORDINATING AND COLLECTION CENTER RESOURCES AND EXPERTISE FORMING A RESEARCH COORDINATION & DATA MANAGEMENT (RCDM) UNIT PROVIDING A SECURE AND ACCESSIBLE DATA WAREHOUSE HUB FOR RD-MCD CONSORTIUM DATA, AND TECHNICAL ASSIST- ANCE AND GUIDANCE ON: IMPLEMENTING MULTIPLE DATA STANDARDS AND CROSS-STUDY INSTRUMENTS INCLUDING PHENX TOOLKIT COLLECTIONS (E.G. SOCIAL DETERMINANTS OF HEALTH (SDOH)); AND UP-TO-DATE RD-MCD INFORMATION, TOOLS, AND RESOURCES VIA SECURED INVESTIGATOR-FACING AND COMMUNITY-FACING WEBSITE RESOURCE PAGES. 3) ESTABLISH A MULTIPLE CHRONIC DISEASES DISPARITIES (MCD) RESEARCH EDUCATIONAL DEVELOPMENT NETWORK: FACILITATED BY THE SKILLS DEVELOPMENT UNIT COMBINING SCIENTIFIC, NETWORKING, AND SKILLS BUILDING EXPERTISE ACROSS THE P50 MCD RESEARCH CONSORTIUM TO IMPLEMENT AND MAINTAIN DIVERSE DEVELOPMENT OPPORTUNITIES FOR ACADEMIC RESEARCHERS, MINORITY-SERVING INSTITUTIONS, HEALTH WORKERS, AND OTHER COMMUNITY PARTNERS. THE RCC WILL DELIVER AND COORDINATE: A) MONTHLY WEBINARS, B) YEARLY SKILLS DEVELOPMENT WORKSHOPS, C) ACCESS TO MENTORS ACROSS THE MCD CONSORTIUM AND THE NIH NATIONAL RESEARCH MENTORING NETWORK, AND D) TRACK THE IMPACT OF THE RCC AND CENTER’S DEVELOPMENT ACTIVITIES. 4) FACILITATE AND MONITOR VIBRANT COMMUNITY-ENGAGED RESEARCH AMONG NIMHD RD-MCD P50 RESEARCH CONSORTIUM MEMBERS AND COMMUNITY PARTNERS THROUGH A COMMUNITY ENGAGEMENT (CE) UNIT PROVIDING ACCESS TO UNDERSERVED/VULNERABLE POPULATION-SPECIFIC TECHNICAL ASSISTANCE (TA) TEAMS, STRUCTURAL AND ORGANIZATIONAL SUPPORT FOR A COMMUNITY OF PRACTICE, AND COLLABORATIVE SCIENTIFIC WORKING GROUPS.

POISON CONTROL STABILIZATION AND ENHANCEMENT PROGRAM

CENTER FOR GAS SEPARATIONS RELEVANT TO CLEAN ENERGY TECHNOLOGIES -- EFRC

NOVEL STRATEGIES TO PREVENT MALARIA AND IMPROVE HIV OUTCOMES IN AFRICA

THE MOLECULAR BASIS OF CELL FUNCTION

TBI ENDPOINTS DEVELOPMENT (TED)

UCSF LIVER CORE CENTER

ATLANTA HQ UCSF TECHNICAL ASSISTANCE TO SUPPORT PRESIDENTS EMERGENCY PLAN FOR AID

NEW APPROACHES TO DEMENTIA HETEROGENEITY

PRECLINICAL DESIGN AND CLINICAL TRANSLATION OF TB REGIMENS (PREDICTR) CONSORTIUM - PROJECT SUMMARY THE LONG DURATION AND MULTIDRUG NATURE OF TUBERCULOSIS (TB) TREATMENT REGIMENS POSE OBSTACLES TO TREATMENT COMPLETION FOR PATIENTS AND PROVIDERS, BUT ALSO CHALLENGE RESEARCH EFFORTS TO DEVELOP NEW AND IMPROVED REGI- MENS. WITHOUT A VALIDATED EARLY BIOMARKER ABLE TO DISCRIMINATE REGIMENS WITH DIFFERENT CURATIVE POTENTIAL, THE FIELD DEPENDS HEAVILY ON PRECLINICAL MODELS. HOWEVER, TB REGIMEN DEVELOPMENT HAS BEEN SLOW, OFTEN HINDERED AND MISLED BY POOR PRECLINICAL-TO-CLINICAL TRANSLATION. ANIMAL MODELS AND PHARMACOMETRIC MODELING PLAYED KEY ROLES IN DEVELOPING GROUNDBREAKING NOVEL REGIMENS CAPABLE OF SHORTING TREATMENT DURATIONS FOR DRUG-SUSCEPTIBLE AND MULTIDRUG-RESISTANT TB TO 4 AND 6 MONTHS, RESPECTIVELY. HOWEVER, THESE TOOLS ARE STILL NOT UTILIZED TO THEIR FULL POTENTIAL. RECENT SUCCESSES IN TB DRUG DISCOVERY HAVE PRODUCED ADDITIONAL CLINICAL AND PRECLINICAL DRUG CANDI- DATES, WHICH HAVE REVEALED A NEW CHALLENGE: WITH MANY POSSIBLE COMBINATIONS, HOW TO PRIORITIZE MULTIDRUG REGI- MENS TO TEST IN RESOURCE-INTENSIVE CLINICAL TRIALS? THE MOST EFFICIENT “CRITICAL PATH” OF PRECLINICAL EXPERIMENTS AND MODELING TO FOLLOW TO IDENTIFYING AND OPTIMIZING THE BEST REGIMENS FOR ADVANCEMENT TO CLINICAL TRIALS REMAINS UNCERTAIN. THE PROPOSED PROJECT WILL ESTABLISH A COMPREHENSIVE, COLLABORATIVE, MULTIDISCIPLINARY CONSORTIUM OF SCIENTIFIC LEADERS, DRUG DEVELOPERS AND OTHER STAKEHOLDERS TO DEVELOP AND PURSUE A PRECLINICAL AND TRANSLATIONAL RESEARCH AGENDA TO IDENTIFY NOVEL REGIMENS WITH THE GREATEST POTENTIAL FOR CLINICAL SUCCESS IN ADULTS AND CHILDREN WITH TB. THE OVERARCHING HYPOTHESIS IS THAT INTEGRATION AND ANALYSIS OF SPECIFIC PRECLINICAL AND EARLY CLINICAL DATA USING VALIDATED MODELS AND TOOLS WILL ENABLE DATA-DRIVEN CLINICAL TRIAL SIMULATIONS THAT YIELD QUANTITATIVE PREDICTIONS OF PHASE 2 AND PHASE 3 TRIAL ENDPOINTS USEFUL TO IDENTIFY AND RANK REGIMENS WITH THE HIGHEST PROBABILITY OF CLINICAL SUCCESS IN PATIENTS ACROSS THE AGE AND DISEASE SPECTRUM OF PULMONARY TB. INITIAL EFFORTS WILL BE AIMED AT REFINING AND VALIDATING PRECLINICAL IN VIVO (BALB/C AND C3HEB/FEJ MOUSE) AND IN VITRO MODELS AND TRANSLATIONAL TOOLS BY LEVERAGING THE LARGEST DATA WAREHOUSE ON TB DRUGS AND REGIMENS EVER ASSEMBLED, WITH DATA SPANNING FROM EARLY PRECLINICAL STAGES TO PHASE 3 CLINICAL TRIALS, FOR BOTH BACK TRANSLATION AND FORWARD PREDICTION APPROACHES TO VALIDATION. THE OVERALL GOAL IS TO DEVELOP A FULLY DATA- AND KNOWLEDGE-DRIVEN APPROACH TO EVALUATE, PRIORITIZE AND OPTIMIZE NOVEL DRUG REGIMENS FOR CLINICAL TRIALS REQUIRING ONLY PRECLINICAL AND EARLY CLINICAL TRIAL DATA. IN ADDITION TO ENDPOINTS BASED ON BACTERIAL BURDEN AND RELAPSE (IN MICE), THE RS RATIO, A NEW PORTABLE BIOMARKER OF BACTERIAL “HEALTH”, WILL BE EVALUATED AS A COMPLEMENTARY PHARMACODYNAMIC (PD) BIOMARKER TO INCREASE EFFICIENCY AND PREDICTIVE ACCURACY OF PRECLINICAL STUDIES. THE EXPECTED OUTCOMES ARE NOVEL METHODOLOGIES OF COMBINING PRE- CLINICAL AND EARLY CLINICAL DATA, A DEFINED SET OF CRITICAL PATH EXPERIMENTS WITH PREDICTIVE VALUE, AND A FRAMEWORK FOR MODEL-INFORMED DECISION-MAKING BASED ON QUANTITATIVE PREDICTIONS OF CLINICAL OUTCOMES FOR EMERGING REGI- MENS PRIOR TO INITIATION OF PHASE 2/3 TRIALS. THE PREDICTIONS WILL BE USED TO RANK ORDER CANDIDATE REGIMENS FOR ADVANCEMENT TO CLINICAL TRIALS.

THE EPILEPSY PHENOME/ GENOME PROJECT (EPGP)

GENERATION OF AN IN VIVO HUMAN GENOME TRANSCRIPTIONAL ENHANCER DATASET

BRAIN VASCULAR MALFORMATION CONSORTIUM: PREDICTORS OF CLINICAL COURSE

A MULTIDISCIPLINARY CENTER FOR DEVELOPING HUMAN AND NON-HUMAN PRIMATE BRAIN CELL ATLASES - PROJECT SUMMARY THE ULTIMATE PRODUCT OF OUR CENTER WILL BE A SERIES OF COMPREHENSIVE DEVELOPING HUMAN AND NON-HUMAN PRIMATE (NHP) BRAIN ATLASES OF UNPRECEDENTED CELLULAR, SPATIAL, AND ANATOMICAL RESOLUTION. IN AIM 1, WE WILL CHARACTERIZE TRANSIENT CELL POPULATIONS, ESTABLISH THE DIVERSITY OF CELL TYPES PRESENT IN SPECIFIC BRAIN REGIONS, UNRAVEL COMPLEX DEVELOPMENTAL TRAJECTORIES, AND REVEAL CONSERVED AND DIVERGENT CELL-TYPE SPECIFIC FEATURES. WE WILL JOINTLY PROFILE OF SINGLE NUCLEUS RNA (SNRNA-SEQ) AND ACCESSIBLE CHROMATIN (SNATAC-SEQ) USING THE 10X GENOMICS SNMULTIOME PLATFORM. ALL AIMS WILL INCLUDE 30 ANATOMICALLY DISTINCT REGIONS OF FRESH FROZEN DEVELOPING HUMAN, RHESUS MACAQUE, AND MARMOSET BRAINS AT FOUR DEVELOPMENTAL EPOCHS: MID-GESTATION, NEONATAL, CHILDHOOD, AND ADOLESCENCE AND PERFORM PROBE-BASED VALIDATION. IN AIM 2, WE WILL CONDUCT SPATIAL TRANSCRIPTOMIC AND EPIGENOMIC MAPPING OF CELL TYPES IN FRESH-FROZEN DEVELOPING HUMAN AND NHP BRAINS USING DBIT SPATIAL-RNA-SEQ AND SPATIAL-ATAC-SEQ PLATFORMS. THIS APPROACH WILL ALLOW US TO DISCOVER SPATIAL AND TEMPORAL FEATURES, INCLUDING THE DEVELOPMENTAL NICHE, PROXIMITY OF CELL TYPES TO EACH OTHER, AND REGIONAL ABUNDANCE. IN AIM 3 WE WILL CREATE COMMON COORDINATE FRAMEWORKS FOR THE DEVELOPING HUMAN AND NHP BRAIN USING HIGH RESOLUTION (9.4T AND 7T) MRI-BASED DEVELOPMENTAL STRUCTURAL ATLASES AND LEVERAGING EXISTING DEVELOPING HUMAN MRI DATA. OUR FINAL AIM WILL CREATE A CROSS SPECIES MOLECULAR AND SPATIAL ATLAS OF BRAIN DEVELOPMENT IN HUMAN AND NHP. THIS INTEGRATION WILL ENABLE US TO IDENTIFY CONSERVED AND DIVEREGENT ASPECTS OF THE HUMAN BRAIN AND IDENTIFY THE DEVELOPMENTAL STAGES, SPATIAL DISTRIBUTION, GENE REGULATORY ELEMENTS AND CELL TYPES VULNERABLE TO NEURODEVELOPMENTAL AND NEUROPSYCHIATRIC DISORDERS. WE WILL COORDINATE TO ENSURE THAT OUR DEVELOPMENTAL ATLASES MERGE WITH ADULT HUMAN, MACAQUE AND MARMOSET ATLASES THAT OTHER BICAN CENTERS CREATE. THE DATA COLLECTED BY OUR CENTER WILL BE PERFECTLY ALIGNED WITH THE OVERARCHING GOAL OF THE BICCN IN GENERATING A COMPREHENSIVE CENSUS OF BRAIN CELL TYPES ACROSS THE LIFESPAN THAT INTEGRATES MOLECULAR, ANATOMICAL, FUNCTIONAL, AND CELL LINEAGE DATA FOR DESCRIBING CELL TYPES IN HUMAN AND NHP BRAINS. BY LEVERAGING INNOVATIONS IN CELL CAPTURE AND SPATIAL MAPPING TECHNOLOGIES, THE CURRENT PROPOSAL WILL HAVE BROAD IMPLICATIONS FOR UNDERSTANDING THE CELLULAR ORIGINS OF DISEASES AND FOR HIGHLIGHTING PATTERNS OF SELECTIVE CELL TYPE VULNERABILITY IN NEURODEVELOPMENTAL DISORDERS SUCH AS AUTISM AND SCHIZOPHRENIA. ADDITIONALLY, OUR PLANS TO CREATE DEVELOPMENTAL CELLULAR AND MOLECULAR RESOLUTION MAPS OF MARMOSET AND MACAQUE WILL PROVIDE FOUNDATIONAL DATA FOR ESTABLISHING PRIMATE MODELS OF HUMAN DISEASE. FINALLY, OUR ATLAS OF CONSERVED MOLECULAR, EPIGENETIC, AND SPATIAL PROPERTIES WILL SUPPORT THE PRECISE MONITORING, TARGETING, AND REPLACEMENT OF SPECIFIC CELL TYPES AND THE IMPROVEMENT OF IN VITRO MODELS.

INTEGRATED HEALTH, BEHAVIORAL AND ECONOMIC RESEARCH ON CURRENT AND EMERGING TOBACCO PRODUCTS

MEDICAL SCIENTIST TRAINING PROGRAM

IMPROVED MODELS TO INFORM TOBACCO PRODUCT REGULATION

NSF CENTER FOR GENETICALLY ENCODED MATERIALS

INSTITUTIONAL CAREER DEVELOPMENT CORE

AIDS EDUCATION AND TRAINING CENTERS PROGRAM

THE PSYCHIATRIC CELL MAP INITIATIVE: CONNECTING GENOMICS, SUBCELLULAR NETWORKS, AND HIGHER ORDER PHENOTYPES

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

RAPID RESEARCH FOR DIAGNOSTICS DEVELOPMENT IN TB NETWORK (R2D2 TB NETWORK)

ADMINSUPP:TRANSFORMING RESEARCH AND CLINICAL KNOWLEDGE IN TRAUMATIC BRAIN INJURY

HPMI: HOST PATHOGEN MAPPING INITIATIVE

EXPLORING DESIGN PRINCIPLES OF CELLULAR CONTROL CIRCUITS

ELECTRON MICROSCOPY OF BIOLOGICAL MACROMOLECULES

HYPERPOLARIZED MRI TECHNOLOGY RESOURCE CENTER

POISON CONTROL STABILIZATION AND ENHANCEMENT PROGRAM

I-SPY2 +: EVOLVING THE I-SPY 2 TRIAL TO INCLUDE MRI-DIRECTED, ADAPTIVE SEQUENTIAL TREATMENT TO OPTIMIZE BREAST CANCER OUTCOMES

FOUR REPEAT TAUOPATHY NEUROIMAGING INITIATIVE

NSEC: CENTER FOR SCALABLE AND INTEGRATED NANOMANUFACTURING (SINAM)

DEEP UNDERGROUND SCIENCE AND ENGINEERING LABORATORY (DUSEL) SITE SELECTION AND TECHNICAL DESIGN DEVELOPMENT

MULTIDISCIPLINARY TRAINING PROGRAM IN LUNG DISEASE

IRACDA SCHOLARS IN SCIENCE (ISIS) PROGRAM

AIDS EDUCATION AND TRAINING CENTERS PROGRAM

SYSTEMS-BASED PREDICTIONS OF RESPONSES TO CANCER THERAPY

DIABETES ENDOCRINOLOGY RESEARCH CENTER

UCSF OLDER AMERICANS INDEPENDENCE CENTER

ORIGINS AND BIOLOGICAL CONSEQUENCES OF HUMAN INFERTILITY

PHARMACOGENOMICS OF MEMBRANE TRANSPORTERS

GENOMIC SEQUENCING TO AID DIAGNOSIS IN PEDIATRIC AND PRENATAL PRACTICE: EXAMINING CLINICAL UTILITY, ETHICAL IMPLICATIONS, PAYER COVERAGE, AND DATA INTEGRATION IN A DIVERSE POPULATION.

MULTICENTER OSTEOARTHRITIS STUDY (MOST) RENEWAL

CALIFORNIA-ARIZONA CLINICAL TRIALS NETWORK NODE

HEALTH DISPARITIES RESEARCH AT UCR

NAT'L AND INTERN'L AIDS EDUCATION AND TRAINING CENTERS

STRUCTURALLY ENABLING THE "AVOID-OME" TO ACCELERATE DRUG DISCOVERY

NC4: CENTER FOR NETWORKED CONFIGURABLE COMMAND, CONTROL AND COMMUNICATIONS FOR RAPID SITUATIONAL AWARENESS

TREATMENTS FOR COMPLEX PATIENTS IN NEW SETTINGS

NOVEL SMALL-MOLECULE THERAPIES FOR CF

COMPREHENSIVE CHARACTERIZATION OF THE DROSOPHILA TRANSCRIPTOME

WE PROPOSE THE CENTER FOR THE UTILIZATION OF BIOLOGICAL ENGINEERING IN SPACE (CUBES) TO SUPPORT BIOMANUFACTURING FOR DEEP SPACE EXPLORATION THAT REALIZES THE INHERENT MASS POWER AND VOLUME ADVANTAGES OF SPACE BIOTECHNOLOGY OVER TRADITIONAL ABIOTIC APPROACHES. CUBES WILL ADVANCE THE PRACTICALITY OF AN INTEGRATED MULTI-FUNCTION MULTI-ORGANISM BIOMANUFACTURING SYSTEM ON A MARS MISSION. HIGHLY MULTIDISCIPLINARY RESEARCH WILL CULMINATE IN A CONTINUOUS BIOMANUFACTURING DEMONSTRATION OF FUEL MATERIALS PHARMACEUTICALS AND FOOD. OUR TEAM CAN EXECUTE THIS VISION BECAUSE OF OUR DEEP EXPERIENCE IN HYBRID BIOINORGANICS FOR LIGHT-DRIVEN CARBON AND NITROGEN FIXATION ENZYMOLOGY POLYMER CHEMISTRY SYNTHETIC BIOLOGY EXTREMOPHILE ENGINEERING ADDITIVE MANUFACTURING AEROSPACE ENGINEERING PLANT/MICROBIOME FOOD AND CHEMICAL MANUFACTURE AND SPACE CROP PHYSIOLOGY. CUBES ENDEAVORS WILL INCLUDE (1) MEDIA GENERATION: ARTIFICIAL PHOTOSYNTHESIS THAT TURNS CARBON DIOXIDE INTO METHANE AND ACETATE; NITROGENASE-CATALYZED CONVERSION OF NITROGEN INTO AMMONIA AND CARBON DIOXIDE TO OTHER C1 COMPOUNDS; AMMONIA NITRIFICATION; REGOLITH DETOXIFICATION AND ENRICHMENT; RECYCLING MISSION MATERIALS; (2) FUEL PRODUCTION: THE AFOREMENTIONED METHANE; C2/C3 ALKANES; NITROUS OXIDE FROM NITRITE AND ACETATE; DIESELLIKE FUELS FROM RECYCLED INEDIBLE PLANT MASS; HYDRAZINE VIA ANAMMOX BACTERIA FROM AMMONIA; (3) BIOPOLYMER PRODUCTION USE AND RECYCLING: GENERATION FROM METHANE AND C1 SUBSTRATES; ADDITIVES PRODUCTION; TESTING IN ADDITIVE MANUFACTURING DEVICES; CHEMICAL/ BIOLOGICAL RECYCLING; (4) PROCESS ENGINEERING: OPTIMIZATION OF PLATFORM ORGANISMS FOR MAXIMAL YIELD AND TOLERANCE INCLUDING MESOPHILIC AND EXTREMOPHILE BIOPROCESSING IN NOVEL BIOREACTORS; PLATFORM CHEMICALS FOR DOWNSTREAM BIOLOGICAL PROCESSES; (5) PHARMACEUTICAL SYNTHESIS BY MICROBES AND PLANTS FOR ANALGESICS BONE REGENERATION AND ANTICANCER; (6) INCREASED FOOD PRODUCTION BY MICROBES AND PLANTS THROUGH SELECTION PLANT/MICROBE SYNERGIES IN RESTRICTED ROOT-ZONE VOLUMES GENETIC ENGINEERING PLANT-MICROBIOME ENHANCEMENT AND INNOVATIVE LIGHT DELIVERY SYSTEMS FOR PHOTOSYNTHESIS IN EFFICIENT SPACE-READY PLANT GROWTH CHAMBERS; (7) PLANT SYSTEM WASTE RECYCLING AND PLANT CELL WALL DECONSTRUCTION; AND (8) DEMONSTRATION SYSTEM INTEGRATION TESTING SEEDING AND INCORPORATION OF AUTONOMY. OUR INNOVATIONS INCLUDE: NOVEL ARTIFICIAL PHOTOSYNTHETIC SUBSTRATES COUPLED TO MICROBES AND ENZYMES TO EFFECTIVELY HARVEST LIGHT AND SPLIT WATER TO FIX BOTH CARBON DIOXIDE AND NITROGEN INTO CRITICAL FEEDSTOCKS FOR MICROBIAL AND PLANT BIOMANUFACTURING; THE DESIGN OF EFFECTIVE MICROBIAL COMMUNITIES AND BIOPROCESSING TECHNIQUES FOR A RANGE OF MICROBIALLY-PRODUCED PLASTICS WITH TUNABLE PROCESSING AND MECHANICAL PROPERTIES DERIVABLE FROM AVAILABLE FEEDSTOCKS AND RECYCLING MATERIALS; THE LEVERAGING OF A UNIQUE REPRODUCIBLE MARS ENVIRONMENT-SIMULATION CHAMBER TO EXPLORE THE BOUNDS OF OPERATION OF MESOPHILIC AND EXTREMOPHILIC MICROBES TO REDUCE COST FOR CONDITIONING IN MARS ENVIRONMENTS; CHARACTERIZING ENGINEERING AND OPTIMIZING DIVERSE NON-MODEL MICROBES THAT WILL SUPPORT BENEFICIAL PLANT PHENOTYPES; CUTTING-EDGE TECHNIQUES IN USING PLANTS AND INEDIBLE PLANT BIOMASS TO QUICKLY AND EFFICIENTLY PRODUCE IMPORTANT CLASSES OF HUMAN DRUGS THAT REQUIRE CHEMISTRIES UNAVAILABLE IN MICROBIAL CELLS; OPTIMIZED PLANTS AND PLANT GROWTH CHAMBERS THAT ADDRESS THE AVAILABILITY OF LIGHT STRESSORS AND ENERGY LIKELY TO BE ENCOUNTERED IN A DEEP SPACE CULTIVATION ENVIRONMENT; AND NOVEL COMPUTATION SYSTEMS TO CAPTURE MODEL ANALYZE TEST AND DISSEMINATE BIOLOGICAL DATA ACROSS CUBES INTEGRATED PROCESSES AND SUBSYSTEM MODULES. CUBES' INDIVIDUAL APPROACHES TO MEDIA PRODUCTION MISSION PRODUCT MANUFACTURE AND FOOD AND PHARMACEUTICAL SYNTHESIS AMPLIFIED BY A FOCUS ON INTEGRATION AND OPTIMIZATION WILL LEAD TO A STRONG DATA-DRIVEN TECHNOLOGICALLY-BACKED PLATFORM FOR SPACE BIOMANUFACTURING.

THE PURPOSE OF USAID DIGITAL FUTURE CAMBODIA IS TO CREATE A COHORT OF CAMBODIAN YOUTH WITH ENTERPRISE-DRIVEN SKILLS, TRAINING, AND QUALIFICATIONS THAT WILL HELP THEM CONTRIBUTE TO CAMBODIAN SOCIETY AND SUCCEED IN A MODERN DIGITAL ECONOMY, AND SUPPORT AN OPEN INTERNET AND FREEDOM OF INFORMATION EXCHANGE IN ORDER TO ENCOURAGE COMPETITION, INNOVATION, AND PROMOTE INTERNATIONAL STANDARDS FOR IT CERTIFICATION IN ORDER TO ADVANCE CAMBODIA’S SELF-RELIANCE IN THE DIGITAL AGE.

HARC CENTER: HIV ACCESSORY AND REGULATORY COMPLEXES

NOVEL THERAPEUTICS FOR PRION DISEASES

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH IN SUPPORT OF BTO IN THE AMOUNT OF 389,469 ON CONTRACT HR0011-17-2-0047.

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH SUPPORTING THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCY (DARPA) BIOLOGICAL TECHNOLOGIES OFFICE (BTO) PANACEA PROGRAM.

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

GRADUATE RESEARCH FELLOWSHIP PROGRAM

CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE

PHARMACOGENOMICS OF STATIN THERAPY

SPINS AND HEAT IN NANOSCALE ELECTRONIC SYSTEMS (SHINES)

ALCOHOL CENTER FOR TRANSLATIONAL GENETICS (ACTG)

CENTER ON THE ECONOMICS AND DEMOGRAPHY OF AGING

NOVEL THERAPIES TO MODULATE THE INFLAMMATORY ALLORESPONSE IN RENAL GRAFTS

CORRECTION OF NEUROLOGICAL DISEASE VIA ALLELE SPECIFIC EXCISION OF PATHOGENIC REPEATS - PROJECT SUMMARY / ABSTRACT A CENTRAL PROMISE OF GENOME EDITING IS ITS POTENTIAL TO TREAT MONOGENIC DISEASE. DESPITE EARLY-STAGE CLINICAL PROGRESS FOR CRISPR-CAS BASED APPROACHES, MONOGENIC NEURODEGENERATIVE CONDITIONS AND NUCLEOTIDE TRIPLET EXPANSION DISORDERS HAVE NOT BEEN A FOCUS OF ANY BIOTECHNOLOGY COMPANY IN THIS SPACE. OUR PROPOSAL BRINGS TOGETHER A TEAM OF ACADEMIC INVESTIGATORS TO DEVELOP A SYNERGISTIC SUITE OF FIRST-IN-CLASS CRISPR-CAS BASED THERAPEUTICS FOR HUNTINGTON'S DISEASE (HD) AND C9ORF72 AMYOTROPHIC LATERAL SCLEROSIS (ALS). WE WILL ENGINEER AND DEPLOY AN EDITING APPROACH THAT EXCISES, WITH IND-GRADE POTENCY AND MUTANT ALLELE-SELECTIVITY, THE DISEASE- CAUSING EXPANSION REPEAT FROM HUMAN HTT AND C9ORF72 LOCI, RESPECTIVELY. OUR STRATEGY IS BASED ON IDENTIFYING ALLELES OF COMMONLY HETEROZYGOUS SNPS THAT RESIDE ON THE SAME HAPLOTYPE AS THE DISEASE-CAUSING REPEAT EXPANSION, AND THEN ENGINEERING CRISPR-CAS9 FOR HIGH SELECTIVITY OF CLEAVAGE, ON ONE OR BOTH SIDES OF THE MUTANT ALLELE REPEAT, TO DRIVE ITS EXCISION, WITH TWO TIERS OF DELIVERY INNOVATION. OUR TRAILBLAZER PROJECT (RESEARCH PROJECT 1, RP1) WILL DEVELOP AN HD THERAPEUTIC BY PACKAGING MUTANT HTT-SPECIFIC CRISPR-CAS9 INTO A NEWLY DEVELOPED SEROTYPE OF ADENO-ASSOCIATED VIRUS (AAV) WITH ROBUST AND BROAD BIODISTRIBUTION IN THE BRAIN PARENCHYMA OF NONHUMAN PRIMATES (NHP). WE WILL IMPLEMENT AN INNOVATIVE STRATEGY IN WHICH THE CRISPR-CAS9 CASSETTE TEMPORALLY LIMITS ITS OWN EXPRESSION. WE WILL IDENTIFY AND ADVANCE THE PRECLINICAL LEAD COMPOSITION THROUGH IND-ENABLING STUDIES LEVERAGING 3 DEDICATED RESOURCE CORES TO (I) ASSESS MOLECULAR OUTCOMES AT THE GENETIC LEVEL, (II) ADMINISTER REAGENTS TO ANIMALS AND OBSERVE THEIR BEHAVIOR, AND (III) ASSESS MOLECULAR AND HISTOLOGICAL OUTCOMES FROM CELLS AND ANIMAL TISSUES. AN ADMINISTRATIVE CORE LED BY EXPERIENCED DEVELOPERS OF GENOME EDITING-BASED THERAPEUTICS, WILL PROVIDE PROJECT-MANAGEMENT SUPPORT AND LEAD ON PREPARATION OF REGULATORY SUBMISSIONS, AIMING TO FILE AN HD IND BY PROGRAM END. IN RP2, WE WILL APPLY THE AAV-BASED EXCISION APPROACH TO BUILD A COGNATE EXPERIMENTAL THERAPEUTIC FOR C9ORF72-DRIVEN ALS. SYNERGIES WITH RP1 INCLUDE CMC INNOVATION TO MANUFACTURE NOVEL AAV, RE-USE OF THE SELF-REGULATING CRISPR-CAS CASSETTE AND VIRUS HARBORING IT, AND REGULATORY FEEDBACK ON IND-ENABLING PHARMACOLOGY, TOXICOLOGY, AND BIODISTRIBUTION STUDIES. WE WILL ADVANCE RP2 THROUGH PRE-IND. FOR RP3, WE WILL ESTABLISH A FIRST-IN-CLASS, TRANSFORMATIVE PARADIGM FOR IN VIVO GENOME EDITING THERAPY BY REFORMULATING THE PRECLINICAL LEAD CRISPR-CAS9 COMBINATION USED IN RP1 INTO A HIGHLY INNOVATIVE “CAS9 RNP MONOPARTICLE” IN WHICH AMPHIPHILIC PEPTIDES DELIVER THE GENE EDITOR TO NEURONS UPON INJECTION. WE WILL DEVELOP APPROACHES FOR MONOPARTICLE MANUFACTURE TO ENABLE EX VIVO AND IN VIVO EFFICACY STUDIES IN HD MODELS. EXTENSIVE SYNERGIES WITH RP1 PROJECT AND COMPREHENSIVE SUPPORT BY THE RCS WILL ENABLE US TO ADVANCE THIS APPROACH TO PRE-IND BY PROGRAM END. THE SUM TOTAL OF THIS EFFORT WILL ESTABLISH A FUNDAMENTALLY NEW PARADIGM FOR IN VIVO GENOME EDITING APPLICABLE TO ALL NUCLEOTIDE REPEAT EXPANSION DISORDERS, AND ADVANCE PRECLINICAL LEAD FORMULATIONS FOR ONE DISEASE, HD, TO IND, AND ANOTHER SUCH DISEASE, C9ORF ALS, TO PRE-IND.

SUPERCDMS SNOLAB

UNIVERSITY OF CALIFORNIA GLOBAL HEALTH INSTITUTE PROGRAM FOR FELLOWS AND SCHOLARS

GH20-2036 HQ SUPPORT OF IMPROVED INTEROPERABLE HIS TOWARDS HIV/AIDS AND TB CONTROL THROUGH IMPROVED HIS POLICY, GOVERNANCE, WORKFORCE CAPACITY, AND SYSTEMS UNDER PEPFAR

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

MRI CORTICOGRAPHY: DEVELOPING NEXT GENERATION MICROSCALE HUMAN CORTEX MRI SCANNER

CARBOHYDRATE-BASED THERAPY FOR LUNG DISEASE

MESENCHYMAL STEM CELLS FOR TREATMENT OF ARDS FOLLOWING TRAUMA

NATURAL HAZARDS ENGINEERING RESEARCH INFRASTRUCTURE: COMPUTATIONAL MODELING AND SIMULATION CENTER 2021-2025

MOLECULAR PATHOGENESIS OF AGE-DEPENDENT CNS DEGENERATION

AIDS EDUCATION AND TRAINING CENTERS PROGRAM

DRUG DEPENDENCE CLINICAL RESEARCH PROGRAM

AREA HEALTH EDUCATION CENTERS POINT OF SERVICE MAINTENANCE AND ENHANCEMENT

ILLUMINATING DRUGGABLE DARK MATTER

NEW START COOPERATIVE AGREEMENT

REGULATION OF CELLULAR PATHWAYSIN HUMAN BRAIN DEVELOPMENT

TARGETING EPITHELIAL CELLS TO TREAT PULMONARY FIBROSIS

CENTER FOR INNOVATION:MEMBRANE PROTEIN PRODUCTION (RMI)

CENTER FOR AGING IN DIVERSE COMMUNITIES (CADC)

GH13-1328 TECHNICAL ASSISTANCE TO COUNTRIES SUPPORTED BY THE PEPFAR AND GLOBAL

US/CHINA CLEAN ENERGY RESEARCH CENTER FOR WATER-ENERGY SOLUTIONS AND TECHNOLOGIES (CERC-WEST)

CHILDHOOD LEUKEMIA AND ENVIRONMENTAL EXPOSURES

WESTERN REGIONAL ALLIANCE FOR PEDIATRIC EMERGENCY MANAGEMENT (WRAP-EM)

THE CENTER OF INTEGRATED NANOMECHANICAL SYSTEMS (COINS) RENEWAL YRS 6-10

UCSF NUTRITION OBESITY RESEARCH CENTER

P30 - CORE GRANT FOR VISION RESEARCH

MARINE ECOSYSTEM SENSING, OBSERVATION AND MODELING LABORATORY

ALGORITHMS AND SPECIALIZERS FOR PROVABLY-OPTIMAL IMPLEMENTATIONS WITH RESILIENCY AND EFFICIENCY (ASPIRE) (PERFECT)

CLINICAL AND TRANSTIONAL SCIENCE INSTITUTE

GRANT

COORDINATING CENTER TO HELP ELIMINATE/REDUCE ORAL HEALTH INEQUALITIES IN CHILDREN

CENTER FOR DENTAL, ORAL, AND CRANIOFACIAL TISSUE AND ORGAN REGENERATION (C-DOCTOR)

THE BIOLOGY OF HIV TRANSMISSION

CORE GRANT FOR VISION RESEARCH

GH20-2042: STRATEGIC USE OF SURVEILLANCE AND EPIDEMIOLOGY TO SUPPORT HIV EPIDEMIC CONTROL IN KENYA UNDER THE PRESIDENT'S EMERGENCY PLAN FOR AIDS RELIEF (PEPFAR)

HIGH-DOSE ERYTHROPOIETIN FOR ASPHYXIA AND ENCEPHALOPATHY (HEAL) CCC

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH IN SUPPORT OF BTO IN THE AMOUNT OF 5,990,885 ON CONTRACT HR0011-19-2-0007.

SPORE IN BREAST CANCER

CELLULAR CONTROL:SYNTHETIC SIGNALING/MOTILITY (RMI)

CRYPTOCOCCUS NEOFORMANS GENE KNOCKOUT RESOURCE

INHERITED T CELL DEFECTS: DIAGNOSIS, MECHANISMS AND TREATMENTS

ADVANCED TECHNOLOGY TO STUDY VISUAL FUNCTION ON A CELLULAR SCALE

CELL BIOLOGY, GENETICS, AND BIOCHEMISTRY TRAINING PROGRAM

GH15-1543: ENHANCING STRATEGIC INFORMATION CAPACITY FOR HIV/AIDS PROGRAMS IN KENYA THROUGH SURVEILLANCE AND EPIDEMIOLOGY, MONITORING AND EVALUATION UNDER THE U.S. PEPFAR (PROGRAM AREA A AND AREA B)

CENTER FOR INTEGRATED PRECISION AND QUANTUM MEASUREMENT

NATURAL HAZARDS ENGINEERING RESEARCH INFRASTRUCTURE: COMPUTATIONAL MODELING AND SIMULATION CENTER

DE NOVO COPY NUMBER VARIATION AND GENE DISCOVERY IN HUMAN BRAIN MALFORMATIONS

NETWORK FOR NEUTRINOS, NUCLEAR ASTROPHYSICS, AND SYMMETRIES

RESEARCH CENTER FOR CANCER SYSTEMS BIOLOGY: CANCER CELL MAP INITIATIVE

ACTIN ASSEMBLY AND CLATHRIN-MEDIATED ENDOCYTOSIS IN YEAST AND MAMMALS

DEVELOPMENT AND CONTROL OF PULMONARY ALVEOLAR STABILITY

HIV TREATMENT FOR RESEARCH SUBJECTS OR BY RESEARCHERS IN KENYA

POPULATION GENOMIC ANALYSIS OF GUT MICROBIAL COLONIZATION IN PREMATURE INFANTS

IMMUNOSUPPRESSION WITHDRAWAL FOR STABLE PEDIATRIC LIVER TRANSPLANT RECIPIENTS

IMPACT OF CCR5 BLOCKADE IN HIV+ KIDNEY TRANSPLANT RECIPIENTS

BAY AREA TEAM AGAINST RESISTANCE

DARPA MSC PROGRAM - MESS: MODEL BUILDING, EXPLORATION AND SOCIAL LEARNING SYSTEM

PROTEIN HOMEOSTASIS MECHANISMS UNDERLYING ENTEROVIRUS REPLICATION AND EVOLUTION

GENETIC AND MOLECULAR EPIDEMIOLOGY OF ADULT GLIOMA

BIOMEDICAL SCIENCE RESEARCH CAREER ENHANCEMENT PROGRAM

TRAINEESHIP IN AIDS PREVENTION STUDIES

CELLULAR DECISION MAKING

BIOSPHERES OF MARS: ANCIENT AND RECENT STUDIES

THE HEALTH EPEOPLE RESOURCE FOR MOBILIZED RESEARCH