Northwestern University

THE ROBERT H. LURIE COMPREHENSIVE CANCER CENTER

TAS::89 0227::TAS RECOVERY; NEW: RECOVERY ACT - CENTER FOR INTEGRATED TRAINING IN FAR-FROM-EQUILIBRIUM AND ADAPTIVE MATERIALS (CITFAM) -- EFRC; PI -

NORTHWESTERN UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE (NUCATS)

MULTICENTER AIDS COHORT STUDY

ECHO PRO RESEARCH RESOURCE: A DEVELOPMENTALLY-BASED MEASUREMENT SCIENCE FRAMEWORK FOR ASSESSING ENVIRONMENTAL EXPOSURE AND CHILD HEALTH

ARGONNE-NORTHWESTERN SOLAR ENERGY RESEARCH (ANSER) CENTER -- EFRC

THIRD COAST CENTER FOR AIDS RESEARCH

THE MOBILETOOLBOX FOR MONITORING COGNITIVE FUNCTION

MULTILEVEL INFLUENCES ON HIV AND SUBSTANCE USE IN A YMSM COHORT

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

NORTHWESTERN CORE CLINICAL RESEARCH SITE: TRANS-OMICS FOR HIV/AIDS RESEARCH

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.

THE AMERICAN LUNG ASSOCIATION (ALA) LUNG HEALTH COHORT

ADVANCED MATERIALS CENTER FOR EXCELLENCE: CENTER FOR HIERARCHICAL MATERIALS DESIGN (CHIMAD)

ADVANCED MATERIALS CENTER OF EXCELLENCE

MULTIDISCIPLINARY CLINICAL AND TRANSLATIONAL SCIENCE (MCTS) PROGRAM (UL1)

NORTHWESTERN UNIVERSITY CLINICAL TRIAL UNIT

STUDY IN PARKINSON DISEASE OF EXERCISE PHASE 3 CLINICAL TRIAL: SPARX3

PATHOPHYSIOLOGY OF ALVEOLAR EPITHELIAL LUNG INJURY

SUCCESSFUL CLINICAL RESPONSE IN PNEUMONIA THERAPY (SCRIPT) SYSTEMS BIOLOGY CENTER

THIS COOPERATIVE AGREEMENT SHALL BE PERFORMED IN ACCORDANCE WITH STATEMENT OF WORK, ENTITLED "NORMALIZING TIMING OF RHYTHMS ACROSS INTERNAL NETWORKS O

AFFORDABLE CARE ACT TEACHING HEALTH CENTER (THC) GRADUATE MEDICAL EDUCATION (GME) PAYMENT PROGRAM

DISORDERED PROTEOSTASIS AS A DRIVER OF DISEASE IN THE AGING LUNG

ALTERATIONS OF CIRCADIAN TIMING IN SLEEP AND AGING

ALZHEIMER'S DISEASE CORE CENTER

GRADUATE RESEARCH FELLOWSHIP PROGRAM (GRFP)

THE CENTER FOR INNOVATION IN POINT-OF-CARE TECHNOLOGIES FOR HIV/AIDS AT NORTHWESTERN UNIVERSITY (C-THAN)

SPORE IN PROSTATE CANCER

CENTER FOR MOLECULAR QUANTUM TRANSDUCTION (CMQT)

HEARTSHARE DECODE-HF: DATA TRANSLATION CENTER TO COMBINE OMICS, DEEP PHENOTYPING, AND ELECTRONIC HEALTH RECORDS FOR HEART FAILURE SUBTYPES AND TREATMENT TARGETS - PROJECT SUMMARY THE OVERARCHING AIM OF THE NORTHWESTERN HEARTSHARE DECODE-HF: DATA TRANSLATION CENTER TO COMBINE OMICS, DEEP PHENOTYPING, AND ELECTRONIC HEALTH RECORDS FOR HEART FAILURE SUBTYPES AND TREATMENT TARGETS IS TO PROVIDE OVERALL MANAGEMENT AND OVERSIGHT FOR HEARTSHARE, INCLUDING COORDINATION AND COMMUNICATION ACROSS ALL SUBSECTIONS AND CORES OF THE PROGRAM, AND WITH THE 4 HEARTSHARE CLINICAL CENTERS (CCS). THE DATA TRANSLATION CENTER (DTC) WILL NEED TO ENSURE TIMELY COMPLETION OF THE RETROSPECTIVE AND PROSPECTIVE COMPONENTS OF HEARTSHARE. IN OUR APPLICATION, WE DEMONSTRATE THE ABILITY AND PRIOR EXPERIENCE OF OUR MULTI-PI TEAM AND CORE LEADERS IN THE CONDUCT AND LEADERSHIP OF LARGE-SCALE, MULTI-CENTER STUDIES, PARTICULARLY IN THE REALMS OF HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF), ELECTRONIC HEALTH RECORD (EHR)-BASED INVESTIGATION, DEEP PHENOTYPING, MACHINE LEARNING, AND BIOREPOSITORIES. FOR BOTH THE RETROSPECTIVE AND PROSPECTIVE HEARTSHARE COMPONENTS, THE NORTHWESTERN DTC WILL LEVERAGE ITS CONSIDERABLE EXPERIENCE IN: (1) COHORTS AND TRIALS THAT HAVE DATA ON ADJUDICATED HF PATIENTS, AND (2) ITS LEADERSHIP AND TRACK RECORD AS THE TOP ENROLLER IN HFPEF TRIALS/STUDIES TO ENSURE OPTIMAL RECRUITMENT BY THE HEARTSHARE CCS. WE WILL ALSO LEVERAGE OUR EXPERTISE IN HFPEF, DATA COORDINATION/MANAGEMENT, BIODATA CATALYST, EHR-BASED RESEARCH, BIOSTATISTICS, MACHINE LEARNING, MULTI-OMICS, HUMAN-COMPUTER INTERACTION, AND MOBILE HEALTH DATA MONITORING TO (1) SUCCESSFULLY EXECUTE THE HEARTSHARE PROGRAM AND (2) MEET THE HEARTSHARE DTC GOALS OF PROVIDING A RICH RESOURCE TO THE RESEARCH COMMUNITY TO ADVANCE THE SCIENCE OF NEXT-GENERATION PHENOMICS TO IDENTIFY HFPEF SUBTYPES AND THERAPEUTIC TARGETS. OUR HEARTSHARE DTC WILL CARRY OUT EACH OF ITS 4 PRIMARY RESPONSIBILITIES. (1) THE ADMINISTRATIVE AND OUTREACH CORE WILL OVERSEE HEARTSHARE PROGRAM OPERATIONS, RESEARCH SKILLS DEVELOPMENT, AND CAPITATION TO CCS FOR DEEP PHENOTYPING COSTS; SUPPORT A CALL CENTER TO FOLLOW PATIENT OUTCOMES; AND PROMOTE RAPID AND BROAD DATA-SHARING OF CLINICAL AND MOLECULAR DATA. (2) THE DATA PORTAL CORE WILL SERVE AS THE PRIMARY ACCESS POINT (VIA A WEB-BASED INTERFACE) AND COORDINATING CENTER FOR ALL HEARTSHARE DATA; AND TO DEVELOP AN INTERACTIVE PATIENT-FACING WEB-BASED INTERFACE FOR REMOTE CONSENT, COMPLETION OF FORMS, AND COLLECTION OF MOBILE HEALTH DATA USING BIODATA CATALYST TOOLS. (3) THE DATA MANAGEMENT CORE WILL OVERSEE ENSURE DATA QUALITY, INTEGRATION AND HARMONIZATION OF VARIOUS DATA TYPES; PERFORM ADVANCED ANALYTICS; COORDINATE BIOSPECIMEN AND IMAGING BIOREPOSITORIES; AND INTEGRATE WITH TOPMED FOR OMICS ANALYSES. (4) THE COHORT CORE WILL AGGREGATE DATA ON HF PATIENTS FROM COMPLETED EPIDEMIOLOGY COHORTS AND HF TRIALS AND WILL COMBINE DATA WITH FURTHER BIOPROFILING OF EXISTING SAMPLES TO ALLOW DISCOVERY/VALIDATION OF NOVEL TARGETS.

AFFORDABLE CARE ACT TEACHING HEALTH CENTER (THC) GRADUATE MEDICAL EDUCATION (GME) PAYMENT PROGRAM

HYPERGLYCEMIA AND PREGNANCY OUTCOME (HAPO) FOLLOW UP STUDY

SUSTAINED LONG ACTING PREVENTION AGAINST HIV PROGRAM OPERATION

SPORE FOR TRANSLATIONAL APPROACHES TO BRAIN CANCER

NORTHWESTERN ADRC NON COMPETING SUPPLEMENT APPLICATION - ON BEHALF OF THE NORTHWESTERN ADRC, WE ARE SUBMITTING THIS SUPPLEMENT APPLICATION TO REQUEST FUNDING FOR EXPENSES THAT WERE NOT REQUESTED IN OUR P30 BUDGET TO SUPPORT OUR BRAIN AUTOPSY PROGRAM, BECAUSE THEY WERE NOT REQUIRED AT THE TIME OF OUR INITIAL APPLICATION. AS OF JANUARY 2022, THE NORTHWESTERN MEMORIAL HOSPITAL (NMH) DEPARTMENT OF PATHOLOGY CHANGED THEIR BILLING POLICY FOR ALL HOSPITAL-INCURRED AUTOPSIES. UP TO THAT DATE, ALL AUTOPSIES ON ANY PATIENT WHO WAS AFFILIATED WITH A NORTHWESTERN MEDICINE PHYSICIAN WERE COMPLIMENTARY, INCLUDING THOSE OBTAINED FOR THE RESEARCH PARTICIPANTS ENROLLED IN THE NORTHWESTERN ADRC CLINICAL CORE. ALL COSTS WERE COVERED INCLUDING THOSE FOR BRAIN REMOVAL AND STORAGE AND TISSUE PROCESSING. FROM JANUARY 2022 ONWARD, THIS POLICY HAS CHANGED SUCH THAT FREE AUTOPSIES ARE PROVIDED ONLY ON THOSE PATIENTS WHO EXPIRE WHILE THEY ARE INPATIENTS ADMITTED TO THE HOSPITAL AT NMH. SINCE MOST OF OUR PARTICIPANTS DIE AT HOME OR IN HOSPICE OR AT ANOTHER HOSPITAL, WE WILL REQUIRE ADDITIONAL FUNDING THAT WAS NOT REQUESTED IN OUR PRIOR APPLICATIONS, PARTICULARLY IN THE LAST 5 YEAR COMPETING RENEWAL, FUNDED IN 2021. AS A RESULT, THE CURRENT APPLICATION IS REQUESTING A SUPPLEMENT TO COVER THE COSTS OF BRAIN AUTOPSIES CARRIED OUT IN THE DEPARTMENT OF PATHOLOGY AT NMH FOR THE NORTHWESTERN ADRC CLINICAL CORE. OUR CENTER ESTIMATES TO CONDUCT 50 BRAIN AUTOPSIES PER YEAR AT NMH. THE REQUEST (SEE BUDGET JUSTIFICATION) INCLUDES THE COST FOR BRAIN REMOVAL AND STORAGE, TISSUE PROCESSING, AND CHEMICALS AND REAGENTS REQUIRED FOR STORAGE AND PROCESSING. IN ADDITION, ON OCCASION, OUR ADRC NEUROPATHOLOGY CORE IS ASKED TO ASSIST IN BRAIN REMOVAL FOR A PARTICIPANT AT ANOTHER ADRC WHO LIVES CLOSE TO OUR FACILITY. WE ARE THUS ALSO ASKING FOR COSTS TO COVER BRAIN REMOVAL, STORAGE AND SHIPPING FOR THOSE INSTANCES. OUR BRAIN AUTOPSY PROGRAM HAS BEEN HIGHLY SUCCESSFUL AND EVEN DURING THE PANDEMIC BENEFITTED FROM THE DEPARTMENT OF PATHOLOGY'S CAREFUL ADJUSTMENTS TO ALLOW SAFE BRAIN REMOVAL OF PARTICIPANTS WHO HAVE DIED SINCE THE PANDEMIC BEGAN.

INSTITUTE FOR CATALYSIS IN ENERGY PROCESS

GLYCEMIC PROFILE OF PREGNANCY CONSORTIUM BIOSTATISTICS RESEARCH CENTER

REGULATION AND FUNCTION OF INTERMEDIATE FILAMENTS IN CELL MECHANICS

THE RHYTHM EVALUATION FOR ANTICOAGULATION WITH CONTINUOUS MONITORING OF ATRIAL FIBRILLATION TRIAL (REACT-AF) - PROJECT SUMMARY / ABSTRACT PURPOSE: THE RHYTHM EVALUATION FOR ANTICOAGULATION WITH CONTINUOUS MONITORING OF ATRIAL FIBRILLATION (REACT AF) CLINICAL TRIAL WILL COMPARE THE EFFICACY AND SAFETY OF TWO TREATMENT STRATEGIES FOR STROKE PREVENTION IN ATRIAL FIBRILLATION (AF): THE CURRENT STANDARD OF CONTINUOUS DIRECT ORAL ANTICOAGULATION (DOAC) VERSUS A NOVEL STRATEGY OF PRECISION, TIME-DELIMITED DOAC INITIATED ONLY IN RESPONSE TO A = 1-HOUR AF EPISODE DETECTED BY AN AF-SENSING SMARTWATCH (AFSW (APPLE WATCH)). RATIONALE: STROKE RISK IS OFTEN TEMPORALLY RELATED TO AF ONSET AND DURATION, BUT BLEEDING RISK CONTINUES AS A CONSTANT RISK OF ANTICOAGULATION EXPOSURE EVEN DURING LONG AF-FREE PERIODS WHEN STROKE RISK MAY BE LOW. REACT- AF WILL EVALUATE THE BENEFITS AND RISKS OF WITHHOLDING ANTICOAGULATION DURING PROLONGED PERIODS OF SINUS RHYTHM AS GUIDED BY AN AFSW. COMPARED WITH CONTINUOUS DOAC, AFSW-GUIDED, TIME-DELIMITED DOAC TREATMENT MAY REDUCE BLEEDING EVENTS WHILE MAINTAINING STROKE PROTECTION. THIS HAS POTENTIAL TO IMPROVE IMPORTANT MAJOR CLINICAL OUTCOMES AND QUALITY OF LIFE WHILE REDUCING HEALTH CARE UTILIZATION. DESIGN: REACT-AF IS A MULTICENTER PROSPECTIVE, RANDOMIZED, OPEN LABEL, BLINDED ENDPOINT (PROBE DESIGN) TRIAL COMPARING THE CURRENT STANDARD OF CARE OF CONTINUOUS DOAC ADMINISTRATION VERSUS TIME-DELIMITED DOAC TREATMENT GUIDED BY AN AFSW IN PATIENTS WITH A HISTORY OF PAROXYSMAL OR PERSISTENT AF AND LOW-TO-MODERATE STROKE RISK (CHA2DS2-VASC SCORE 1-4). THE STUDY WILL HAVE AN INITIAL EXPLANATORY PHASE I FOLLOWED BY AN EXPLANATORY PHASE II WITH PRAGMATIC ELEMENTS. PRIMARY AIM 1 (EFFICACY OBJECTIVE): TO ASSESS WHETHER AFSW-GUIDED, TIME-DELIMITED DOAC THERAPY IS NON- INFERIOR TO CONTINUOUS DOAC THERAPY FOR A COMPOSITE ENDPOINT THAT INCLUDES: (1) ISCHEMIC STROKE; (2) SYSTEMIC EMBOLISM; (3) ALL-CAUSE MORTALITY. HYPOTHESIS: TIME-DELIMITED DOAC THERAPY IS NON-INFERIOR TO CONTINUOUS DOAC THERAPY FOR THE COMPOSITE ENDPOINT OF ISCHEMIC STROKE, SYSTEMIC EMBOLISM, AND ALL-CAUSE MORTALITY. PRIMARY AIM 2 (SAFETY OBJECTIVE): TO ASSESS WHETHER AFSW-GUIDED, TIME-DELIMITED DOAC THERAPY SIGNIFICANTLY REDUCES MAJOR BLEEDING EVENTS COMPARED TO CONTINUOUS DOAC THERAPY. HYPOTHESIS: MAJOR BLEEDING EVENTS WILL BE SIGNIFICANTLY LOWER IN PARTICIPANTS RANDOMIZED TO AFSW-GUIDED, TIME- DELIMITED DOAC THERAPY COMPARED WITH PARTICIPANTS RECEIVING CONTINUOUS DOAC THERAPY. EXPLORATORY AIM 1: TO COMPARE OVERALL PARTICIPANT SATISFACTION WITH ANTICOAGULATION MANAGEMENT BETWEEN THE TWO STUDY ARMS. EXPLORATORY AIM 2: TO COMPARE ESTIMATES OF HEALTH-RELATED RESOURCE UTILIZATION IN PARTICIPANTS RANDOMIZED TO CONTROL VERSUS EXPERIMENTAL ARMS.

CEMRI: MULTIFUNCTIONAL NANOSCALE MATERIAL STRUCTURES

MRSEC: CENTER FOR MULTIFUNCTIONAL MATERIALS

NUCATS CTSA UM1 AT NORTHWESTERN UNIVERSITY - PROJECT SUMMARY/ABSTRACT OVER PRIOR FUNDING CYCLES, THE NORTHWESTERN UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCES (NUCATS) INSTITUTE HAS DEVELOPED AND DELIVERED A ROBUST INSTITUTIONAL INFRASTRUCTURE TO SUPPORT CLINICAL AND TRANSLATIONAL RESEARCH. OUR MATURE CTSA HUB HAS MADE EXCEPTIONAL CONTRIBUTIONS TO THE CONSORTIUM, ATTAINING NATIONAL PROMINENCE FOR IGNITING CROSS-DISCIPLINARY TEAM SCIENCE AND BOUNDARY-CROSSING PARTNERSHIPS. THESE STRENGTHS NOW ENABLE NUCATS TO PIVOT AND FOCUS ON CLINICAL AND TRANSLATIONAL SCIENCE (CTS). THIS PROPOSAL ADDRESSES THREE OF THE MOST URGENT AND FUNDAMENTAL PRIORITIES TO ACCELERATE AND CATALYZE TRANSLATION: (A) CULTIVATING A CULTURE OF INCLUSIVE EXCELLENCE TO BETTER CAPITALIZE ON OUR FULL RANGE OF TALENT AND ENABLE EFFECTIVE TRANSLATION FOR DIVERSE POPULATIONS; (B) ACCELERATING DISCOVERY AND DEVELOPMENT OF INNOVATIONS IN INTERVENTIONS AND PROCESSES TO IMPROVE EFFICIENCY OF TRANSLATION; AND (C) INFUSING IMPLEMENTATION SCIENCE (IS) METHODS INTO WORK ACROSS THE TRANSLATIONAL CONTINUUM TO INCREASE THE DEMAND FOR AND SUPPLY OF EFFECTIVE HEALTH SERVICES TO IMPROVE PUBLIC HEALTH. NUCATS WILL DEVELOP, EVALUATE, AND DISSEMINATE MORE EFFECTIVE HEALTH INTERVENTIONS TO MORE PATIENTS MORE QUICKLY THROUGH TEAMWORK WITH OUR EXCEPTIONAL COALITION OF COMMUNITY, HEALTH SYSTEM, AND CTSA PARTNERS VIA THREE SPECIFIC AIMS: INCLUDE, INNOVATE, AND IMPLEMENT. FOR OUR INCLUDE AIM, WE WILL WORK TO CULTIVATE A CULTURE OF INCLUSIVE EXCELLENCE AS WE EXPAND OUR WORKFORCE, PARTNERSHIPS, AND RESEARCH PARTICIPANTS, INCLUDING THOSE HISTORICALLY UNDERREPRESENTED IN BIOMEDICAL SCIENCE, TO OPTIMIZE THE BENEFICIAL IMPACTS OF TRANSLATION ON THE HEALTH OF ALL. FOR OUR INNOVATE AIM, WE WILL CATALYZE INNOVATION ACROSS ALL STAGES OF THE TRANSLATIONAL CONTINUUM TO PROMOTE ENTREPRENEURSHIP AS WELL AS THE RIGOR AND REPRODUCIBILITY OF TRANSLATIONAL RESEARCH. FOR OUR IMPLEMENT AIM, WE WILL INFUSE IMPLEMENTATION SCIENCE METHODS INTO CLINICAL RESEARCH ACROSS THE TRANSLATIONAL CONTINUUM TO ACCELERATE PUBLIC HEALTH IMPACT. EACH SPECIFIC AIM WILL BE ATTAINED VIA A SET OF STRATEGIES, WHICH IN TURN CONSIST OF A SET OF INITIATIVES. PURSUIT OF THE SPECIFIC AIMS WILL BE OVERSEEN BY A HIGHLY INTERACTIVE MULTIPLE PRINCIPAL INVESTIGATOR (MPI) TEAM IDEALLY SUITED TO PROVIDE STRONG OVERSIGHT OF THE SPECIFIC AIMS, WITH EACH MPI HAVING PRIMARY OVERSIGHT OF ONE AIM. THE MPIS WILL TIGHTLY COORDINATE A TEAM- BASED LEADERSHIP STRUCTURE EMPHASIZING INTEGRATION ACROSS HUB AND APPLICATION COMPONENTS, SUPPORTED BY ADVISORY COMMITTEES. THIS PROPOSAL IS FURTHER ENABLED BY OUR RENOWNED EVALUATION INFRASTRUCTURE, OUR LONGSTANDING LEADERSHIP IN OPEN SCIENCE PRINCIPLES (INCLUDING FINDABLE, ACCESSIBLE, INTEROPERABLE, REUSABLE (FAIR) DATA) AND OUR TRACK RECORD OF LEADERSHIP ACROSS THE CTSA CONSORTIUM. BY THE END OF THE PROPOSED UM1, NUCATS WILL BECOME A NATIONAL CHAMPION AND CONSORTIUM RESOURCE FOR TRANSDISCIPLINARY RESEARCH TEAMS SEEKING TO CONTINUOUSLY IMPROVE CTS PERFORMANCE TO MORE EFFICIENTLY DELIVER INCLUSIVE, INNOVATIVE, AND IMPLEMENTABLE SOLUTIONS THAT IMPROVE HEALTH FOR ALL.

MEDICAL SCIENTIST TRAINING PROGRAM

STUDENT AID PORTION FOR PUBLIC AND NONPROFIT INSTITUTIONS-NORTHWESTERN UNIVERSITY

LUNG FUNCTION DECLINE AND DISEASE RISK FROM YOUNG ADULTHOOD TO MIDDLE AGE

MIDWEST SMALL PRACTICE CARE TRANSFORMATION RESEARCH ALLIANCE

PROTEOSTASIS IN AGING AND NEURODEGENERATIVE DISEASE

CENTER: NSF ENGINEERING RESEARCH CENTER FOR HUMAN AUGMENTATION VIA DEXTERITY (HAND) -THE WORK OF THE NSF ENGINEERING RESEARCH CENTER FOR HUMAN AUGMENTATION VIA DEXTERITY (HAND) WILL LEAD TO VERSATILE, DEXTEROUS ROBOTIC ARMS AND HANDS THAT ADDRESS A BROAD RANGE OF HUMAN, INDUSTRY, AND SOCIETAL NEEDS. THE PURPOSE IS TO CREATE ROBOT MANIPULATORS THAT ARE WIDELY USEFUL ?OUT OF THE BOX.? TODAY, ROBOT ARMS BECOME USEFUL ONLY AFTER AN EXPENSIVE INTEGRATION PROCESS, MAKING THEM INACCESSIBLE TO MANY WHO MIGHT BENEFIT, INCLUDING MOST OF THE COUNTRY?S QUARTER-MILLION SMALL AND MEDIUM ENTERPRISES (SMES). TO BE USEFUL OUT OF THE BOX, ROBOTS MUST HAVE TRULY VERSATILE END-EFFECTORS (?HANDS?), AI-POWERED DEXTEROUS SKILLS, AND INTUITIVE INTERFACES THAT TRAINED WORKERS CAN USE IMMEDIATELY. TRAINING MUST BE WIDELY ACCESSIBLE AND CAREER PATHS MUST BE AVAILABLE TO LEARNERS FROM A YOUNG AGE. FIRMS OF ALL SIZES MUST BE ABLE TO ADOPT THESE ROBOTS, AND WORKERS OF ALL EDUCATION LEVELS, HIGH SCHOOL THROUGH POSTGRADUATE, MUST BE ABLE TO USE THEM. THE BREADTH AND STRUCTURE OF THE ERC PROGRAM WILL ENABLE HAND TO ADDRESS THESE TECHNICAL, WORKFORCE, AND ECOSYSTEM CHALLENGES, ULTIMATELY DEMOCRATIZING ACCESS TO ROBOT DEXTERITY. ROBOTS WILL NO LONGER BE LIMITED TO HIGH-VOLUME, HIGHLY REPEATABLE OPERATIONS; THEY WILL FIND APPLICATION IN LOW-VOLUME HIGH-MIX MANUFACTURING, FOOD PROCESSING, REMOTE HANDLING OF PRECIOUS OR DANGEROUS MATERIALS, ASSISTANCE FOR INDIVIDUALS WITH MOTOR IMPAIRMENTS, AND MANY OTHER AREAS. WIDESPREAD ACCESS TO ROBOTIC MANIPULATION WILL BE VITALLY IMPORTANT AS THE U.S. ADDRESSES LABOR SHORTAGES IN FIELDS SUCH AS MANUFACTURING AND CAREGIVING, AND AS DEMOGRAPHICS INEXORABLY CHANGE, LEADING TO A SHRINKING POOL OF WORKERS SUPPORTING AN AGING POPULATION. WHILE SOME AREAS OF ROBOTICS HAVE SEEN DRAMATIC ADVANCES IN RECENT YEARS, DEXTEROUS MANIPULATION HAS PROVEN TO BE A MORE CHALLENGING PROBLEM, REQUIRING A VERY HIGH LEVEL OF CONVERGENCE. HAND WILL PROVIDE THIS WITH A CONVERGENT RESEARCH PROGRAM ORGANIZED INTO THREE THRUSTS: HANDS (SENSING, ACTUATION, DESIGN), INTELLIGENT DEXTERITY (SIMULATION, REPRESENTATION, CONTROL), AND HUMAN INTERFACE (MULTIMODAL INTERFACE, PROGRAMMING, SOCIAL/LEGAL/INDUSTRIAL STUDIES). THE CENTER WILL BRING TOGETHER EXPERTS IN MATERIALS, MANUFACTURING, MANIPULATION, SOFT ROBOTICS, ARTIFICIAL INTELLIGENCE, MACHINE PERCEPTION, MODELING, HAPTICS, HUMAN-ROBOT INTERACTION, PARTICIPATORY DESIGN AND RESEARCH, TEAM SCIENCE, EDUCATION, LAW, AND THE SOCIAL SCIENCES TO OVERCOME FUNDAMENTAL BARRIERS TO DEXTERITY. THESE INCLUDE ACHIEVING LARGE SCALE INTEGRATION OF ACTUATORS AND SENSORS, BUILDING ROBUST VISUO-TACTILE-MOTOR SKILLS THAT ARE COMPOSABLE INTO COMPLEX BEHAVIORS, AND LOW-CODE PROGRAMMING BY NON-ROBOTICISTS. THE RESULT WILL BE AN ENGINEERED SYSTEM ? HANDS, SKILLS, INTERFACE, AND TRAINING MATERIALS ? THAT DRAMATICALLY ADVANCES ROBOTIC MANIPULATION AND ITS ACCESSIBILITY TO DIVERSE USER POPULATIONS. HAND?S DEXTEROUS MANIPULATORS WILL BE WHERE AI LEARNS ABOUT THE PHYSICAL WORLD, AND WHERE AI IS TRANSFORMED TO USEFUL PHYSICAL WORK. ADDITIONALLY, THROUGH ENGINEERING WORKFORCE DEVELOPMENT EFFORTS, HAND WILL PROVIDE A NOVEL EDUCATION PLATFORM FOR INTRODUCING LEARNERS TO AI AND DEXTERITY; AN ACCELERATOR PROGRAM TO HELP SMES SUCCEED WITH ROBOTS; REU AND RET PROGRAMS THAT INCREASE DIVERSITY; AND UNDERGRADUATE AND GRADUATE CERTIFICATES BUILT ON A FOUNDATION OF DEXTERITY, SOCIAL IMPACTS OF AUTOMATION, AND PARTICIPATORY RESEARCH AND DESIGN METHODS. HAND WILL USE THOSE METHODS TO ENGAGE DIVERSE INDIVIDUALS, ENSURE THAT THE BENEFITS OF DEXTERITY ARE EQUITABLY SHARED, AND PROMOTE DIVERSITY AND A CULTURE OF INCLUSION. HAND?S INNOVATION ECOSYSTEM WILL SUPPORT STRONG ENGAGEMENT WITH SMALL, MEDIUM, AND LARGE MANUFACTURERS, ROBOTICS COMPANIES, NATIONAL LABS, CIVIC ORGANIZATIONS, AND EDUCATORS VIA TESTBEDS, ADVISORY BOARDS, A ROBUST PROCESS FOR TECHNOLOGY TRANSFER, AND A PUBLIC INTEREST INITIATIVE. TOGETHER WITH THIS ECOSYSTEM, HAND WILL IMPACT THE FUTURE OF WORK BY DEMOCRATIZING ACCESS TO HUMAN AUGMENTATION VIA DEXTERITY AND FRAMING THE ASSOCIATED SOCIAL, ECONOMIC, AND ETHICAL IMPLICATIONS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

RHYTHMICITY AND SYNCHRONY IN THE BASAL GANGLIA

NATIONAL RESOURCE FOR TRANSLATIONAL AND DEVELOPMENTAL PROTEOMICS

NUTRITION PRECISION HEALTH FOR ALL OF US (CHICAGO CENTER) - PROJECT SUMMARY EPIDEMIOLOGICAL AND CLINICAL STUDIES SUPPORT AN IMPORTANT ROLE OF NUTRITION IN HEALTH. HOWEVER, NUTRITION RESEARCH IS LIMITED BY BIAS DUE TO SELF-REPORTED DIET DATA AND INTER- AND INTRA-INDIVIDUAL VARIATION. HIGH-THROUGHPUT `OMIC' PROFILING TECHNIQUES COMBINED WITH ADVANCED REMOTE REAL-TIME DATA COLLECTION NOW ENABLE COMPREHENSIVE STUDIES OF INDIVIDUAL RESPONSES TO DIET THEREBY CREATING OPPORTUNITIES FOR PERSONALIZED NUTRITION ADVICE. OUR OVERALL GOAL IS TO FACILITATE THE NUTRITION FOR PRECISION HEALTH (NPH) CONSORTIUM BY LEVERAGING OUR EXISTING ILLINOIS PRECISION MEDICINE CONSORTIUM (IPMC) INFRASTRUCTURE TO ENROLL ALL OF US RESEARCH PROGRAM (AOURP) PARTICIPANTS IN THE DISCOVERY NUTRITION SCIENCE STUDY INVOLVING THREE DIET MODULES. PROPOSED IS INVESTIGATION OF SPECIFIC ELEMENTS OF A DIETARY APPROACHES TO STOP HYPERTENSION (DASH) DIET WITH BLOOD PRESSURE (BP) AS THE PRIMARY OUTCOME. BP IS REGULATED BY A COMPLEX NETWORK OF MECHANISMS UNDER THE INFLUENCE OF GENETIC AND ENVIRONMENTAL FACTORS, AND HIGH BP IS RECOGNIZED AS THE LEADING MODIFIABLE RISK FACTOR FOR CARDIOVASCULAR DISEASE, CEREBROVASCULAR DISEASE, KIDNEY DISEASE AND ALL-CAUSE MORTALITY WORLDWIDE. DASH DIET ADHERENCE HAS CONSISTENTLY DOCUMENTED REDUCED BP, INDEPENDENT OF BASELINE CALORIE OR SODIUM INTAKE. ALTHOUGH OLDER, HYPERTENSIVE AND BLACK PERSONS SHOW GREATER BP RESPONSES TO DASH ADHERENCE AND REDUCED DIETARY SODIUM INTAKE, INTER-INDIVIDUAL VARIABILITY IS OBSERVED AND REMAINS UNEXPLAINED. IN MODULE 1, WE WILL FOLLOW 2,000 AOURP PARTICIPANTS FOR 14 DAYS TO EXAMINE BASELINE DIET AND PHYSIOLOGICAL RESPONSES TO TEST-MEAL CHALLENGES HYPOTHESIZED TO ELICIT VARIABLE PHYSIOLOGICAL AND METABOLOMIC RESPONSES BASED ON INDIVIDUAL CARDIOMETABOLIC, GENETIC AND GUT MICROBIAL STATUS. WE THEN EXAMINE RESPONSES TO THREE 14-DAY INTERVENTION PERIODS INVOLVING DASH-TYPE DIETS AMONG 400 CONSENTING MODULE 1 PARTICIPANTS IN A FREE-LIVING CONTROLLED FEEDING STUDY (MODULE 2) AND IN 200 MODULE 1 PARTICIPANTS IN A DOMICILE CONTROLLED FEEDING STUDY (MODULE 3). THE THREE INTERVENTION DIETS ARE ISOCALORIC, SODIUM EQUIVALENT AND INCLUDE: I) DASH-STANDARD, II) DASH-FFF, SPECIFYING FRUITS, FLAVONOIDS AND FAT AND DASH-PP, EMPHASIZING PLANT PROTEIN. EACH DIET HAS DISTINCTIVE NUTRITIVE PROPERTIES THAT INFLUENCE BP REGULATION AND EACH WILL ELUCIDATE DIVERSE PHYSIOLOGICAL, METABOLOMIC, AND MICROBIOMIC RESPONSES THAT ARE MODIFIED BY CARDIOMETABOLIC AND GENETIC STATUS. OUR THREE IPMC CLINICAL SITES INCLUDING NORTHWESTERN UNIVERSITY, THE UNIVERSITY OF CHICAGO, AND THE ILLINOIS INSTITUTE OF TECHNOLOGY SPAN WIDE YET GEOGRAPHICALLY DISTINCT SERVICE AREAS IN ETHNICALLY AND SOCIOECONOMICALLY DIVERSE CHICAGO COMMUNITIES, THEREBY OFFERING TARGETED ENROLLMENT OF DEMOGRAPHICALLY DIVERSE PARTICIPANTS. THIS RESEARCH IN COLLABORATION WITH THE NPH CONSORTIUM INITIATES FUNDAMENTAL CAUSAL AND MECHANISTIC INSIGHT INTO THE ROLE OF THE DASH-TYPE DIET IN BP REGULATION WITH POTENTIAL TO DISCOVER NOVEL BIOLOGICAL PATHWAYS UNDERLYING RISKS FOR DEVELOPING HIGH BP. THIS ADVANCED KNOWLEDGE CAN INFORM UNPRECEDENTED PERSONALIZED DIET RECOMMENDATIONS TO PREVENT AND TREAT THE MASSIVE PUBLIC HEALTH BURDEN OFF HYPERTENSION.

MECHANISMS OF RECOVERY FROM VIRAL PNEUMONIA - PROJECT SUMMARY_OVERALL RECOVERY FROM VIRAL PNEUMONIA IS A CLINICALLY IMPORTANT YET UNDERSTUDIED PROCESS. SEVERE INFLUENZA A VIRUS AND SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 CAUSE SEVERE VIRAL PNEUMONIA, WHICH DAMAGES THE LOWER RESPIRATORY TRACT TO INDUCE ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS). MOST ARDS DEATHS OCCUR DAYS-TO-WEEKS AFTER ARDS ONSET—A TIME WHEN PATIENTS ARE RECOVERING FROM THE INCITING INSULT, YET STUDIES IN MURINE MODELS TYPICALLY FOCUS ON THE EARLY DEVELOPMENT OF ACUTE LUNG INJURY AND DEATH FROM OVERWHELMING INFECTION. OTHER THAN AVOIDANCE OF ADDITIONAL LUNG INJURY, VIA LOW TIDAL VOLUME VENTILATION AND A HANDFUL OF OTHER SUPPORTIVE THERAPIES, THERE ARE NO SPECIFIC THERAPIES FOR PATIENTS WITH VIRAL PNEUMONIA INDUCED ARDS. A CENTRAL HYPOTHESIS OF THIS PPG IS THAT THE PERSISTENCE OF RESPIRATORY FAILURE AND THE DEVELOPMENT OF MULTIPLE ORGAN DYSFUNCTION IN PATIENTS WITH ARDS IS A CONSEQUENCE OF THE FAILURE OF NORMAL MECHANISMS OF INFLAMMATION RESOLUTION AND LUNG TISSUE REPAIR. THIS HYPOTHESIS IS CLINICALLY SUPPORTED BY A RECENT ANALYSIS OF PATIENTS ENROLLED IN THE ARDSNET WHERE A “HYPERINFLAMMATORY” ENDOTYPE OF ARDS PATIENTS WAS ASSOCIATED WITH WORSE CLINICAL OUTCOMES, INCLUDING DEATH. WE PROPOSE TO INVESTIGATE THE PROCESS OF RECOVERY FROM VIRAL PNEUMONIA WITH A FOCUS ON MECHANISMS THAT PROMOTE RESOLUTION OF LUNG INFLAMMATION AND HEALTHY REPAIR OF LUNG DAMAGE. THE PPG INVESTIGATORS WILL TEST THIS CENTRAL HYPOTHESIS THROUGH A HIGHLY INTEGRATED AND INNOVATIVE SET OF EXPERIMENTS BY FOCUSING ON FOUR SPECIFIC AIMS: SPECIFIC AIM 1. TO DETERMINE WHETHER VIMENTIN REGULATES PERSISTENT INFLAMMATION DURING RECOVERY FROM SEVERE INFLUENZA A VIRUS–INDUCED PNEUMONIA BY PROMOTING A PRO-INFLAMMATORY PHENOTYPE IN MONOCYTE-DERIVED ALVEOLAR MACROPHAGES AND BY LIMITING THE PRO-REPAIR CAPACITY OF REGULATORY T CELLS. SPECIFIC AIM 2. TO DETERMINE WHETHER MITOCHONDRIAL ELECTRON TRANSPORT CHAIN COMPLEX I OR III, AND LACTATE PRODUCTION, DRIVES PERSISTENT NLRP3 INFLAMMASOME-DEPENDENT INFLAMMATION DURING RECOVERY FROM SEVERE INFLUENZA A VIRUS–INDUCED PNEUMONIA. SPECIFIC AIM 3. TO DETERMINE WHETHER PERSISTENT ACTIVATION OF LUBAC-MEDIATED NF-KB SIGNALING IN THE LUNG EPITHELIUM DRIVES MACROPHAGE ACTIVATION AND INHIBITS LUNG REPAIR FOLLOWING VIRAL PNEUMONIA. SPECIFIC AIM 4. TO DETERMINE WHETHER DNA METHYLTRANSFERASE ACTIVITY AND UHRF1 INDUCE DNA HYPERMETHYLATION IN TREG CELLS DURING AGING TO IMPAIR TREG CELL REPARATIVE FUNCTION FOLLOWING SEVERE VIRAL PNEUMONIA IN OLDER HOSTS.

CONSEQUENCES OF INCARCERATION ON HEALTH, AGE-RELATED CONDITIONS, AND RISK FACTORS FOR ADRD - PROJECT SUMMARY ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (ADRD) DISPROPORTIONATELY AFFECT BLACK AND HISPANIC ADULTS, ATTRIBUTABLE, IN PART, TO DISPARITIES IN SOCIOECONOMIC STATUS AND AGE-RELATED HEALTH CONDITIONS. ADRDS ARE AMONG THE COSTLIEST DIS- EASES TO TREAT, POSING A PROFOUND BURDEN FOR PEOPLE ALREADY EXPERIENCING HEALTH DISPARITIES. MASS INCARCERATION, WHICH DISPROPORTIONATELY AFFECTS BLACK AND HISPANIC PEOPLE, MAY PLAY A KEY ROLE. WE PROPOSE TO EXTEND OUR CURRENT 28-YEAR LONGITUDINAL STUDY, THE NORTHWESTERN JUVENILE PROJECT (NJP), TO CONDUCT THE FIRST COMPREHENSIVE, PROSPECTIVE STUDY OF HOW THE DOSE OF INCARCERATION—FREQUENCY AND DURATION OF STAYS, TYPE OF FACILITY (JUVENILE DETENTION, JAIL, PRISON), AGE(S), AND RECENCY—AFFECTS HEALTH, AGE-RELATED CONDITIONS, AND RISK FACTORS FOR ADRD. LEVERAGING OUR ORIG- INAL SAMPLE (N=1829 (NOW 1492), WHO WILL BE AGES 39-49 IN THE PROPOSED STUDY), WE WILL USE A MIXED-METHODS AP- PROACH, FOCUSING ON MODIFIABLE, MIDLIFE RISK FACTORS FOR ADRD AS NOTED IN THE LANCET COMMISSION 2020 REPORT ON ADRD PREVENTION AND OTHER RISK INDEXES: HYPERTENSION, SMOKING, OBESITY, DEPRESSION, EXERCISE, DIABETES, SOCIAL CON- TACT, AND ALCOHOL ABUSE. MIDDLE ADULTHOOD (40+ YEARS) IS A CRITICAL DEVELOPMENTAL PERIOD FOR TARGETING ADRD RISK FACTORS. WE HAVE ALREADY CONDUCTED A PILOT STUDY (N=65) THAT DEMONSTRATES THE FEASIBILITY OF THE PROPOSED METHODS AND THE NEED TO STUDY HEALTH, AGE-RELATED CONDITIONS, AND RISK FACTORS FOR ADRD IN PEOPLE WHO HAVE BEEN INCARCER- ATED. WE WILL: (1) INTERVIEW PARTICIPANTS TO ASSESS PHYSICAL AND MENTAL HEALTH, PSYCHOLOGICAL WELL-BEING, AND COGNI- TION USING THE NIH TOOLBOX (CRYSTALLIZED AND FLUID INTELLIGENCE) AND THE UNIFORM DATA SET (MEMORY); (2) COLLECT BLOOD-BASED BIOMARKERS OF HEALTH (GLUCOSE METABOLISM, LIPID RATIOS, KIDNEY FUNCTION, INFLAMMATION, AND BIOLOGICAL AGING); (3) COLLECT PHYSIOLOGICAL MEASUREMENTS OF HEALTH (HEIGHT, WEIGHT, WAIST CIRCUMFERENCE, BLOOD PRESSURE, REST- ING HEART RATE); AND (4) USE DETAILED DATA ON DOSE OF INCARCERATION AND THE FRAMEWORK OF DOSE-RESPONSE MODELS TO AS- SESS HOW INCARCERATION AFFECTS HEALTH, AGE-RELATED CONDITIONS, AND RISK FACTORS FOR ADRD. WE HAVE 3 SPECIFIC AIMS: (1) TO ASSESS HEALTH, AGE-RELATED CONDITIONS, AND ADRD RISK FACTORS AMONG PARTICIPANTS AT MEDIAN AGE 45 AND COM- PARE THEM TO PARTICIPANTS IN THE ADD HEALTH STUDY, AN NIA-FUNDED STUDY WITH A SIMILARLY AGED SAMPLE; (2) TO EXAM- INE THE RELATIONSHIP BETWEEN THE DOSE OF INCARCERATION AND HEALTH, AGE-RELATED CONDITIONS, AND RISK FACTORS FOR ADRD; AND (3) TO IDENTIFY RISK AND PROTECTIVE FACTORS—INCLUDING GEOCODED ADDRESSES TO DETERMINE ENVIRONMENTAL RISKS— THAT MODERATE THE RELATIONSHIP BETWEEN DOSE OF INCARCERATION AND HEALTH, AGE-RELATED CONDITIONS, AND ADRD RISK FAC- TORS. WE HYPOTHESIZE, FOR EXAMPLE: THAT OUR PARTICIPANTS WILL HAVE WORSE HEALTH THAN THOSE IN ADD HEALTH; THAT PER- SONS WHO CYCLE IN AND OUT OF JAIL WILL DEMONSTRATE POORER HEALTH AND GREATER RISK FOR ADRD THAN PERSONS WITH LONG PRISON STAYS, EVEN AFTER CONTROLLING FOR DAYS INCARCERATED; AND THAT LIMITED EXERCISE IN CORRECTIONS AND UNSTABLE HOUS- ING UPON RELEASE WILL EXACERBATE INCARCERATION’S CONSEQUENCES. BY ELUCIDATING HOW THE DOSE OF INCARCERATION AND SUB- SEQUENT REENTRY EXPERIENCES INFLUENCE RISK FOR ADRD, THE PROPOSED STUDY WILL ESTABLISH THE EMPIRICAL FOUNDATION NEEDED TO REDUCE DISPARITIES IN HEALTHY AGING AND MITIGATE RISK FOR ADRD IN PERSONS WHO HAVE BEEN INCARCERATED.

SPORE IN PROSTATE CANCER

THE CODING DECODING TRANSFER AND TRANSLATION OF INFORMATION IN CANCER

NSF-SIMONS NATIONAL INSTITUTE FOR THEORY AND MATHEMATICS IN BIOLOGY -LIVING ORGANISMS EXHIBIT MYRIAD CAPABILITIES THAT ALLOW THEM TO FLOURISH AND TO ADJUST AND ADAPT TO THEIR VARIABLE CONDITIONS OF EXISTENCE. THESE CAPABILITIES HAVE EMERGED UNDER A SET OF CONSTRAINTS THAT ARE PHYSICAL, CHEMICAL, ENVIRONMENTAL, AND EVOLUTIONARY IN NATURE. FOR THIS REASON, FIELDS OF MATHEMATICS THAT ARE ADEPT AT INCORPORATING CONSTRAINTS ARE PARTICULARLY WELL-SUITED TO ILLUMINATING THE ROLES OF CONSTRAINTS IN BIOLOGY. AN UNDERSTANDING OF CONSTRAINTS FROM BOTH MATHEMATICAL AND BIOLOGICAL PERSPECTIVES PROVIDES A UNIQUE BRIDGE FOR INTERDISCIPLINARY RESEARCH, WITH MATHEMATICAL RESEARCH THAT WILL ADVANCE KNOWLEDGE OF BIOLOGY, AND BIOLOGY RESEARCH THAT WILL CATALYZE NEW MATHEMATICS. THIS PROJECT FUNDS THE ESTABLISHMENT OF A NATIONAL INSTITUTE FOR THEORY AND MATHEMATICS IN BIOLOGY (NITMB) IN CHICAGO LED BY NORTHWESTERN UNIVERSITY AND THE UNIVERSITY OF CHICAGO. THE MISSION OF THIS PROJECT IS THE CREATION OF A NATIONWIDE COLLABORATIVE RESEARCH COMMUNITY THAT WILL GENERATE NEW MATHEMATICAL RESULTS AND WILL UNCOVER THE FUNDAMENTAL PRINCIPLES GOVERNING LIFE THROUGH THEORIES, DATA-INFORMED MATHEMATICAL MODELS, AND COMPUTATIONAL AND STATISTICAL TOOLS. THE RESEARCH DONE BY THE NITMB WILL SUPPORT ADVANCES IN AREAS AS DIVERSE AS THE ENVIRONMENT, BIOMEDICINE, AND TECHNOLOGY DEVELOPMENT. THE NITMB WILL USE AN INTERLOCKING SET OF STRATEGIES AND INITIATIVES THAT WILL HELP DEVELOP A DIVERSE WORKFORCE WHILE ENSURING BROAD IMPACTS ON THE RESEARCH COMMUNITY. GEOGRAPHICALLY CO-LOCATED NITMB MEMBERS WILL SHARE SPACE IN DOWNTOWN CHICAGO THAT IS READILY ACCESSIBLE TO COLLABORATORS ACROSS THE US AND THE WORLD. THE NITMB WILL REALIZE THIS VISION VIA AN INNOVATIVE RESEARCH PROGRAM ORGANIZED AROUND FIVE INTERRELATED THEMES, SELECTED BECAUSE THEY REFLECT KEY CAPABILITIES OF BIOLOGICAL SYSTEMS AND INTERCONNECT WITH OPEN MATHEMATICAL PROBLEMS. THESE THEMES - FIDELITY AND VARIATION, FITNESS AND OPTIMIZATION, INFORMATION PROCESSING, LEARNING AND ADAPTATION, AND PREDICTION AND ANTICIPATION - ESTABLISH BRIDGES ACROSS SUBDISCIPLINES OF BIOLOGICAL AND MATHEMATICAL SCIENCES, ENSURING THAT RESEARCH IN ONE DOMAIN WILL SUPPORT ADVANCES IN THE OTHERS. THE THEMES ALSO REFLECT THE CROSS-DISCIPLINARY ORGANIZATIONAL STRUCTURE OF THE NITMB, ENSURING THAT TRAINING AND COMMUNITY-BUILDING ACTIVITIES FOSTER DEEP INTERACTIONS ACROSS DISCIPLINES. THE NITMB WILL ACHIEVE NUMEROUS FOUNDATIONAL ADVANCES, INCLUDING: A NEW MATHEMATICAL UNDERSTANDING OF DYNAMICAL SYSTEMS IN BIOLOGICALLY RELEVANT NON-AUTONOMOUS SETTINGS; NEW TOOLS FOR EXTRACTING GLOBAL MATHEMATICAL MODELS FROM LOCAL BEHAVIOR; NEW THEORY FOR DEFINING VARIABLES GOVERNING FITNESS AND FUNCTION; RIGOROUS DEFINITIONS OF CELL STATES AND STATE TRANSITIONS IN DEVELOPMENT; AND QUANTITATIVE MODELS OF THE EMERGENCE OF BEHAVIOR FROM COLLECTIVE NEURAL ACTIVITIES. NITMB PROGRAMS WILL CREATE A VIBRANT INTERNATIONAL COMMUNITY THAT WILL ENDURE FOR DECADES AND GENERATE FOUNDATIONAL ADVANCES IN BIOLOGY AND MATHEMATICS THAT WILL INFORM FURTHER DEVELOPMENTS IN PUBLIC HEALTH, THE ENVIRONMENT, AND OTHER APPLICATIONS. TARGETED RESEARCH PROJECTS WILL BRING TOGETHER MATHEMATICIANS AND BIOLOGISTS TO COLLABORATE AND TRAIN STUDENTS AND POST-DOCTORAL FELLOWS TO BECOME FUTURE LEADERS AT THE DISCIPLINARY INTERFACE. THE NITMB WILL ENGAGE IN A BROAD ARRAY OF EDUCATION, WORKFORCE DEVELOPMENT, AND BROADENING PARTICIPATION ACTIVITIES THAT WILL INCLUDE DIVERSE COMMUNITIES. ITS EDUCATION INITIATIVES WILL REACH STUDENTS FROM THE K-12 LEVEL, USING A PROVEN STRATEGY TO PAIR MIDDLE-SCHOOLERS WITH GRADUATE STUDENT MENTORS IN LASTING PARTNERSHIPS. THE NITMB WILL ALSO DEVELOP TRAINING FOR UNDERGRADUATES, GRADUATES, AND POST-BACCALAUREATE STUDENTS AND TEACHERS WITH COMMUNITY PARTNERS IN A HIGHLY DIVERSE CITY. INCLUSION IS A CORE VALUE INTEGRATED INTO ALL NITMB EDUCATION AND TRAINING ACTIVITIES. A WIDE VARIETY OF SCIENTIFIC LONG PROGRAMS, WORKSHOPS, AND CONFERENCES WILL ENHANCE COLLABORATION BETWEEN MATHEMATICS AND BIOLOGY AND ENSURE THAT THE SCIENTIFIC OUTCOMES OF THE NITMB?S RESEARCH IMPACT WIDE-RANGING SECTORS OF BASIC AND APPLIED RESEARCH. IN ADDITION TO FUNDING FROM THE NATIONAL SCIENCE FOUNDATION THIS PROJECT IS GENEROUSLY SUPPORTED BY THE SIMONS FOUNDATION. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

CLINICAL COORDINATION CENTER FOR STEADY-PD3

1/3: THE CHICAGO COLLABORATIVE TO PROMOTE AND ADVANCE CANCER HEALTH EQUITY

UTERINE LEIOMYOMA RESEARCH CENTER PROGRAM

CHANNELOPATHY-ASSOCIATED EPILEPSY RESEARCH CENTER

INTEGRATING MECHANISTIC INSIGHTS FROM DIVERSE MODELS TO PREVENT CMV REACTIVATION FOLLOWING TRANSPLANTATION

THE NATIONAL PERSON-CENTERED ASSESSMENT RESOURCE (PCAR)

NEUROBIOLOGY OF LANGUAGE RECOVERY IN APHASIA: NATURAL HISTORY AND TREATMENT-IND*

NUCLEIC ACID-BASED NANOCONSTRUCTS FOR THE TREATMENT OF CANCER

INTEGRATING CELL-FREE SYSTEMS AND GENOME ENGINEERING TO ACCELERATE BIOSYSTEMS DESIGN FOR CARBON-NEGATIVE BIOMANUFACTURING

NANOMATERIALS FOR CANCER DIAGNOSTICS AND THERAPEUTICS

RESEARCH IN THE ENERGY, COSMIC AND INTENSITY FRONTIERS AND THEORETICAL PHYSICS AT NORTHWESTERN UNIVERSITY

CENTER FOR PREVENTION IMPLEMENTATION METHODS FOR DRUG ABUSE & SEX RISK BEHAVIOR

CELLULAR AND MOLECULAR BASIS OF DISEASE TRAINING PROGRAM

HEALTH LITERACY AND COGNITIVE FUNCTION AMONG OLDER ADULTS

GRADUATE RESEARCH FELLOWSHIP PROGRAM

LIVER CIRRHOSIS NETWORK: SCIENTIFIC AND DATA COORDINATION CENTER - PROJECT SUMMARY LIVER CIRRHOSIS POSES A SIGNIFICANT PUBLIC HEALTH BURDEN IN THE UNITED STATES (US) AS IT IS ASSOCIATED WITH SUBSTANTIAL MORBIDITY, MORTALITY AND COST. AN ESTIMATED ONE-THIRD OF PATIENTS DEVELOP DECOMPENSATING EVENTS SUCH AS GASTROINTESTINAL VARICEAL BLEEDING, ASCITES, HEPATIC ENCEPHALOPATHY (HE), JAUNDICE, AND RENAL IMPAIRMENT. FURTHER, THESE POOR OUTCOMES ARE ALSO ASSOCIATED WITH DEVELOPMENT OF HEPATOCELLULAR CARCINOMA (HCC) IN THE CIRRHOTIC LIVER, THE NINTH LEADING CAUSE OF DEATH AMONG CANCERS WITHIN THE US. WHILE TRANSPLANTATION IS A CURATIVE TREATMENT FOR CIRRHOSIS, PATIENTS ARE OFTEN INELIGIBLE FOR TRANSPLANTATION DUE TO LACK OF AVAILABLE ORGANS AND ADDITIONAL RISKS INVOLVED. THUS, PATIENTS AND PROVIDERS FREQUENTLY FOCUS ON SYMPTOMATIC TREATMENT OPTIONS SUCH AS LIFESTYLE/NUTRITION MODIFICATIONS TO INITIATE WEIGHT LOSS AND OPTIMIZE PROTEIN ABSORPTION, NONSELECTIVE BETA- BLOCKERS TO REDUCE THE RISK OF GASTROINTESTINAL BLEEDING, AND TREATMENT FOR HE TO IMPROVE CONFUSION. A RECENT META-ANALYSIS SUGGESTS STATIN THERAPY AS A PROMISING TREATMENT FOR CIRRHOSIS AS STATINS TEND TO DECREASE OXIDATIVE STRESS AND INFLAMMATION AND INCREASE ENDOTHELIAL CELL FUNCTION, WITH DOWNSTREAM EFFECTS INCLUDING REDUCTION OF HEPATIC INFLAMMATION, FIBROSIS, AND VASCULAR TONE. ALTHOUGH THIS REVIEW REPRESENTS OVER 120 THOUSAND PATIENTS, TRUE EFFICACY DATA IN THE SETTING OF A RANDOMIZED CONTROLLED TRIAL (RCT) ARE PRESENTLY LIMITED TO JUST FOUR RCTS FROM OUTSIDE OF THE US, REPRESENTING LESS THAN 300 PATIENTS WITH CIRRHOSIS. TO BETTER UNDERSTAND THE NATURAL HISTORY OF THE DISEASE AND ALSO TO FURTHER EVALUATE THE USE OF STATINS IN THE TREATMENT OF CIRRHOSIS, THE LIVER CIRRHOSIS NETWORK (LCN), CONSISTING OF UP TO 10 CLINICAL CENTERS (CCS) AND ONE SCIENTIFIC AND DATA COORDINATION CENTER (SDCC) WILL BE CHARGED WITH DEVELOPING (A) A PROSPECTIVE COHORT AND (B) AN RCT TO EVALUATE STATIN EFFICACY IN PATIENTS WITH CIRRHOSIS. NORTHWESTERN UNIVERSITY DATA ANALYSIS AND COORDINATING CENTER (NUDACC) AND ITS PARTNERS PROPOSE TO SERVE AS THE SDCC--THE CENTRAL SCIENTIFIC AND LEADERSHIP CORE FOR THE LCN--COORDINATING ALL OPERATIONAL AND DATA-RELATED ACTIVITIES USING CUTTING-EDGE RESOURCES FOR STUDY DESIGN, PLANNING AND CONDUCT, ONGOING MONITORING, AND STATISTICAL ANALYSES. NUDACC UNITES AN INTERDISCIPLINARY TEAM WITH WIDE-RANGING EXPERIENCE INCLUDING COLLABORATIVE AND METHODOLOGIC BIOSTATISTICIANS, HEPATOLOGISTS, DATA MANAGERS, PROJECT MANAGERS, AND MULTIPLE SUPPORTING STUDY STAFF. TOGETHER WE PROPOSE TO COLLABORATE WITH THE LCN TO LEAD THE DESIGN, CONDUCT, COORDINATION, OVERSIGHT, MANAGEMENT, ADMINISTRATION, ANALYSES, AND DISSEMINATION FOR THE LCN-RELATED STUDIES.

BARRIER DAMAGE AND THE IMMUNE CASCADENORTHWESTERN UNIVERSITY COUNTERACT CENTER OF EXCELLENCE (NUCCX) - NORTHWESTERN UNIVERSITY (NU) IS RECOGNIZED FOR ITS STRONG INTERDISCIPLINARY CUTANEOUS, OCULAR, NANOTECHNOLOGY AND IMMUNOLOGY RESEARCH PROGRAMS WITH PARTICULAR STRENGTH IN INVESTIGATIONS RELATED TO WOUND REPAIR AND INFLAMMATION. LEVERAGING THESE STRENGTHS, THE THEME OF THE NU COUNTERACT CENTER OF EXCELLENCE (NUCCX) IS THE “BARRIER DAMAGE AND THE IMMUNE CASCADE”, WITH ITS GOAL TO PROMOTE OUTSTANDING TRANSLATIONAL RESEARCH IN THE TREATMENT OF SULFUR MUSTARD (SM) INJURY. THE NUCCX, WITH ITS 12 SENIOR RESEARCH SCIENTISTS, ENCOMPASSES 7 UNIVERSITY DEPARTMENTS WITHIN THE FEINBERG MEDICAL SCHOOL AND THE WEINBERG COLLEGE OF ARTS AND SCIENCES. INFORMATION GENERATED THROUGH THE NUCCX WILL IMPROVE PATIENT CARE TO THOSE SUFFERING FROM SM INJURY. TO ACCOMPLISH THIS GOAL, THE NUCCX HAS THE FOLLOWING RESEARCH PROJECTS AND CORES: (I) TOPICAL AND SYSTEMIC INTERVENTIONS FOR MUSTARD-INDUCED SKIN INJURY (PROJECT 1); (II) REVERSING THE OCULAR IMPACT OF NM AND SM THROUGH NOVEL THERAPIES (PROJECT 2); (III) TRANSLATION AND TRIALS: ADVANCING MEDICAL COUNTERMEASURE DEVELOPMENT (PROJECT 3); (IV) ADMINISTRATIVE CORE (CORE A); (V) LIPID-BASED MATERIALS SYNTHESIS AND CHARACTERIZATION CORE (CORE B); (VI) POLYMERIC MATERIALS SYNTHESIS AND CHARACTERIZATION CORE (CORE C); AND (VII) EDUCATION AND ENRICHMENT CORE (CORE D). PROJECT 1 WILL EXAMINE THE CLINICAL POTENTIAL OF SYSTEMICALLY ADMINISTERED PLGA-IMPS IN CONJUNCTION WITH VITAMIN D3 TO MITIGATE IMMUNE ACTIVATION FOLLOWING NM AND SM SKIN EXPOSURE. A SIMILAR NANOPARTICLE-BASED STRATEGY WILL BE USED TO EVALUATE REDUCTION OF SKIN INFLAMMATION WITH TOPICAL HDL NP AND/OR SYNTHETIC MELANIN PDA NP. PROJECT 2 WILL DEFINE THE CLINICAL POTENTIAL OF TOPICAL HDL NP-BASED EYE DROPS IN THE CONTEXT OF ACUTE AND DELAYED PHASES RESULTING FROM NM AND SM EXPOSURE IN THE CORNEA. A SIMILAR APPROACH WILL BE TAKEN TO EVALUATE SYSTEMICALLY ADMINISTERED VITAMIN D3 AND PLGA-IMPS IN OCULAR NM/SM INJURY. PROJECT 3 WILL USE NON-INVASIVE TESTING IN HUMANS TO DEFINE THE SIGNATURE INFLAMMATORY BIOMARKERS THAT WILL BE EVALUATED IN CLINICAL TRIALS TESTING OF VITAMIN D3 AND PLGA-IMP. THE TRANSLATIONAL STUDIES ARE HIGHLY RELEVANT TO MUSTARD AS THEY ARE BASED ON MULTI-OMICS ANALYSIS DATA OF ARCHIVED SKIN SAMPLES FROM IN VIVO SM (NON-HUMAN PRIMATE) AND NM (HUMAN) MUSTARD EXPOSURE. THE ADMIN CORE WILL BE A FOCAL POINT FOR ALL UNIVERSITY-WIDE SM-RELATED ACTIVITIES AND WILL BE RESPONSIBLE FOR COORDINATING ALL ACTIVITIES OF THE NUCCX. CORE B WILL SYNTHESIZE A SUITE OF ORGANIC CORES TO BE USED AS TEMPLATES TO PRODUCE A LIBRARY OF NANOPARTICLES FORMULATED TO BE TOPICALLY APPLIED TO THE EYE AND SKIN. CORE C WILL SYNTHESIZE SYNTHETIC MELANIN, POLYMER-PEPTIDE HYBRID MATERIALS AND PLGA-IMPS TO BE USED FOR THERAPEUTIC DEVELOPMENT. CORE D WILL FOSTER EDUCATION AND TRAINING, AS WELL AS ADVANCE PERSONAL AND PROFESSIONAL DEVELOPMENT OF NUCCX TRAINEES AND INVESTIGATORS. THIS CORE WILL ALSO PROMOTE INCLUSIVITY AND DIVERSITY WITHIN THE MUSTARD INJURY FIELD. PROJECTS 1-3 AND CORES A-D INTERDIGITATE WITH EACH OTHER AND HAVE STRONG TRANSLATIONAL COMPONENTS. THE NUCCX IS WELL POSITIONED TO TAKE BASIC FINDINGS INTO A CLINICAL SETTING, WHICH WILL FACILITATE OUR UNDERSTANDING AND TREATING SM INJURY OF THE SKIN AND EYES.

DISTRIBUTED CELL-FREE MANUFACTURING OF BIOLOGICS-BASED MEDICAL COUNTERMEASURES

UTILITY OF BIOMARKERS OF REJECTION AND KIDNEY INJURY IN TAILORING LIVER TRANSPLANT IMMUNOSUPPRESSION - PROJECT SUMMARY/ABSTRACT THE ADVENT OF MOLECULAR BIOMARKERS HOLDS GREAT PROMISE, BOTH FROM A DIAGNOSTIC PERSPECTIVE AS WELL AS THE ABILITY TO PREDICT A DISEASE STATE EARLY ENOUGH TO INFORM THERAPY AND CHANGE CLINICAL OUTCOMES. IN THE LAST SEVERAL YEARS, STUDIES HAVE SUGGESTED A ROLE FOR BIOMARKER PROFILING IN THE MANAGEMENT OF IMMUNOSUPPRESSION IN LIVER TRANSPLANT RECIPIENTS. FROM OUR CTOT-14 STUDY DATA, WE HAVE DEVELOPED KEY BIOMARKERS THAT CAN DETECT EARLY SIGNS OF UNDER- (REJECTION) AND OVER- (CHRONIC KIDNEY DISEASE) IMMUNOSUPPRESSION, PARTICULARLY WITH USE OF STANDARD CALCINEURIN-INHIBITOR THERAPY. BUT AS THE ACCURACY OF MOLECULAR DIAGNOSTICS IMPROVES, AND AS TECHNOLOGY PLATFORMS EVOLVE, TWO IMPORTANT QUESTIONS HAVE SURFACED REGARDING THEIR VALUE IN THE MANAGEMENT OF LIVER TRANSPLANT RECIPIENTS. FIRST, CAN BIOMARKERS INFORM PATIENT MANAGEMENT AND OPTIMIZE THE ABILITY TO PERSONALIZE IMMUNOSUPPRESSIVE THERAPY? SECOND, CAN WE CHARACTERIZE KEY PATHWAYS OF IMMUNE ACTIVATION AND KIDNEY INJURY TO FURTHER OPTIMIZE THE USE OF BIOMARKERS AND IDENTIFY NEW THERAPEUTIC TARGETS? WE BELIEVE THAT THESE QUESTIONS COMPRISE THE NEXT FRONTIER IN BIOMARKER RESEARCH, AND WE HAVE THEREFORE FORMULATED THIS PROPOSAL TO TEST A SET OF HYPOTHESES THAT RELATE DIRECTLY TO THESE QUESTIONS. FIRST, IN A PROSPECTIVE MULTI-CENTER CLINICAL TRIAL OF LIVER TRANSPLANT RECIPIENTS, WE WILL CHALLENGE THE `STANDARD OF CARE' AND TEST THE HYPOTHESIS THAT SERIAL BLOOD BIOMARKER PROFILING CAN IDENTIFY PATIENTS AT RISK OF KIDNEY INJURY AFTER LIVER TRANSPLANTATION AND ALSO GUIDE THE REMOVAL OF NEPHROTOXIC CALCINEURIN-INHIBITOR THERAPY SAFELY WITHOUT ADVERSELY INCREASING ACUTE REJECTION. TO ACHIEVE THIS OBJECTIVE, WE WILL LEVERAGE THESE IMMUNE AND KIDNEY BIOMARKERS DEVELOPED IN OUR CTOT-14 VALIDATION STUDY TO DETECT EARLY SIGNS OF REJECTION AND KIDNEY INJURY TO ENHANCE PROACTIVE, SAFE WITHDRAWAL OF CALCINEURIN-INHIBITORS IN FAVOR OF NON-NEPHROTOXIC MTOR-INHIBITORS. THIS BIOMARKER-GUIDED INTERVENTIONAL APPROACH WILL BE TESTED AGAINST CURRENT STANDARD MANAGEMENT AND ALSO RISK-STRATIFY PATIENTS INTO THOSE NEEDING OR NOT NEEDING SUCH INTERVENTIONS. SECOND, WE WILL LEVERAGE THE CLINICAL TRIAL SAMPLE COLLECTIONS TO GAIN DEEPER UNDERSTANDING OF WHAT LEADS TO REJECTION OR ALTERNATIVELY WHAT IS PROTECTIVE OF REJECTION. WE WILL ACCOMPLISH THIS BY PERFORMING AN EXTENSIVE BATTERY OF BLOOD IMMUNE CELL, ANTIBODY, GENOMIC AND PROTEOMIC PROFILING DURING THE INTERVENTIONS TO BEST IDENTIFY THE PATHWAYS LEADING TO OUR OUTCOMES. IN ADDITION, WE WILL SIMULTANEOUSLY PERFORM NOVEL KIDNEY IMAGING BIOMARKERS TO ASK WHAT LEADS TO KIDNEY INJURY VS. PROTECTION IN OUR UNIQUE COHORTS. TOGETHER, THE CLINICAL TRIAL AND ACCOMPANYING MECHANISTIC STUDIES WILL ALLOW US TO CROSS THE NEXT FRONTIER IN BIOMARKER RESEARCH IN TRANSPLANTATION, NAMELY THE ABILITY TO USE BIOMARKERS TO MONITOR THE STATE OF IMMUNE RESPONSIVENESS AND DRUG TOXICITY TO INFORM THERAPEUTIC DECISIONS. OUR CLINICAL DATA AND BIO-BANKED SAMPLES WILL CREATE A NEW RESOURCE FOR THE COMMUNITY AND FACILITATE A NEW GENERATION OF MOLECULAR DIAGNOSTICS TRANSLATABLE INTO CLINICAL PRACTICE.

NANOSCALE SCIENCE & ENGINEERING CENTER FOR INTEGRATED NANOPATTERNING AND DETECTION TECHNOLOGIES

MULTI-SCALE EVALUATION AND MITIGATION OF TOXICITIES FOLLOWING INTERNAL RADIONUCLIDE CONTAMINATION - OVERALL: ABSTRACT HISTORY HAS TAUGHT US THAT EXPOSURES TO RADIONUCLIDES CAN HAPPEN ANY DAY ALMOST ANYWHERE IN THE US AND ELSEWHERE AND WE HAVE DONE LITTLE TO PREPARE OURSELVES. OUR ABILITY TO PERFORM DOSIMETRY MODELING FOR SUCH SCENARIOS AND EFFORTS INTO BIOMARKER AND MITIGATION DISCOVERY ARE ARCHAIC AND OUR TENDENCY TO RELY ON EXTERNAL BEAM RADIATION TO MODEL THESE IS UTTERLY MISPLACED. WE SHOULD AND WE CAN DO MUCH BETTER. THIS PROGRAM CENTERS ON THE HYPOTHESIS THAT RADIATION FROM INTERNAL EMITTERS IS VERY UNEVENLY DISTRIBUTED WITHIN A BODY, AMONGST ORGANS, AND EVEN WITHIN ORGANS, TISSUES AND CELLS. THE HALF-LIFE AND DECAY SCHEMA OF THE RADIONUCLIDE, ITS ACTIVITY AND CONCENTRATION, PARTICLE SIZE AND MORPHOLOGY, AND ITS CHEMICAL FORM AND SOLUBILITY ARE ALL CRITICAL, AS ARE THE ROUTE OF UPTAKE, TISSUE STRUCTURE, GENETIC MAKEUP, PHYSIOLOGY, DANGER SIGNALING AND THE CROSSTALK WITH THE IMMUNE SYSTEM. CONCEPTUALLY THIS SUGGESTS THAT THE ANALYSIS OF RADIONUCLIDE DISTRIBUTION REQUIRES MEASUREMENTS AT THE MESO, MICRO AND NANO LEVEL FOR ACCURATE DOSIMETRY MODELING AND BIOKINETICS ANALYSES, THAT WILL MUCH BETTER ALIGN WITH BIOLOGICAL ENDPOINTS, AND THEREFORE WITH MEANINGFUL COUNTERMEASURE DEVELOPMENT. IN MANY WAYS OUR PROGRAM INTEGRATES THE THREE MAIN PILLARS OF RADIATION SCIENCE, NAMELY RADIATION PHYSICS, RADIATION CHEMISTRY AND RADIATION BIOLOGY, TAKING INTO ACCOUNT PHARMACOKINETICS AND PHARMACODYNAMICS ASPECTS OF PARTICLE DISTRIBUTION AT SUBCELLULAR, CELLULAR, AND TISSUE LEVELS. IN OTHER WORDS, TO UNDERSTAND THE BIOLOGICAL EFFECTS OF INTERNAL EMITTERS AND FIND THE BEST POSSIBLE MITIGATION STRATEGIES A SYSTEMATIC STUDY IS CALLED FOR, ONE THAT INCLUDES BUT IS NOT LIMITED TO: A) RADIONUCLIDE PHYSICAL AND CHEMICAL FORM AND INTRAVITAL MIGRATION, B) PROTRACTED EXPOSURE TIMES, C) RADIATION QUALITY PARAMETERS, D) NOVEL VIRTUAL PHANTOM MODELING BEYOND FEW MACRO REFERENCE MODELS ; E) NOVEL BIOKINETICS WITH SEX- AND AGE- SPECIFICITY; F) MESO, MICRO AND NANO SCALE HISTOLOGY AND IMMUNOHISTOCHEMISTRY WITH INTEGRATED RADIONUCLIDE DISTRIBUTION INFORMATION; G) EXPLORATION OF MOLECULAR BIOMARKERS OF RADIONUCLIDE INTAKE AND CONTAMINATION AND H) COUNTERMEASURES THAT MODULATE RADIONUCLIDE DISTRIBUTION AND POSSIBLY ALSO IMPROVE DNA, CELL AND TISSUE REPAIR. WE HAVE ASSEMBLED A TEAM WITH DIVERSE SCIENTIFIC EXPERTISE THAT CAN TACKLE THESE CHALLENGES WITHIN AN INTEGRATED PROGRAM. THERE IS AN INCREDIBLY IMPRESSIVE TECHNOLOGICAL TOOLBOX AT OUR DISPOSAL AND OUR GOAL IS TO GENERATE A MEANINGFUL BLUEPRINT FOR UNDERSTANDING AND PREDICTING BIOLOGICAL CONSEQUENCES OF EXPOSURE TO RADIONUCLIDES. THE POSSIBLE BENEFITS OF THIS PROGRAM TO THE RADIATION RESEARCH COMMUNITY AND THE GENERAL POPULATION ARE IMMENSE.

ARMADA: ADVANCING RELIABLE MEASUREMENT IN ALZHEIMER'S DISEASE AND COGNITIVE AGING

CARDIOVASCULAR REGENERATIVE MEDICINE

FOOD ALLERGY OUTCOMES RELATED TO WHITE AND AFRICAN AMERICAN RACIAL DIFFERENCES (FORWARD)

GENES, ANDROGENS AND INTRAUTERINE ENVIRONMENT IN PCOS

INTERACTIVE MECHANISMS OF PELVIC PAIN

NEW; TITLE: EFFECTS OF LOW-DOSE IRRADIATIONON NFKB SIGNALING NETWORKS AND MITOCHONDRIA; PI-GAYLE WOLOSCHAK

SPATIO-TEMPORAL ORGANIZATION OF CHROMATIN AND INFORMATION TRANSFER IN CANCER

ASYMMETRIC NEURODEGENERATION AND LANGUAGE IN PRIMARY PROGRESSIVE APHASIA - PROJECT SUMMARY / ABSTRACT PRIMARY PROGRESSIVE APHASIA (PPA) IS A DEMENTIA OF LANGUAGE THAT EMERGES ON A BACKGROUND OF PRESERVED MEMORY. IT CAN BE CAUSED BY MULTIPLE NEUROPATHOLOGIC ENTITIES, INCLUDING ALZHEIMER'S DISEASE (AD) AND FRONTOTEMPORAL LOBAR DEGENERATIONS (FTLD). THE ONE CORE FEATURE OF ALL PPA VARIANTS IS THE SELECTIVE AND ASYMMETRIC NEURODEGENERATION OF THE LANGUAGE-DOMINANT (USUALLY LEFT) HEMISPHERE. FOR THE PAST 15 YEARS, THE NORTHWESTERN PPA PROGRAM HAS ENROLLED PATIENTS FOR BIENNIAL COGNITIVE EVALUATION, MULTIMODAL IMAGING, AND GENETIC CHARACTERIZATION. BIOFLUIDS ON ALL PATIENTS AND BRAIN TISSUE FROM THOSE WHO HAVE COME TO AUTOPSY HAVE BEEN BANKED, CURATED, AND SHARED WITH THE NATIONAL ALZHEIMER'S COORDINATING CENTER (NACC) AND THE NATIONAL CENTRALIZED REPOSITORY FOR ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (NCRAD). THIS COHORT REPRESENTS WHAT IS ARGUABLY THE WORLD'S LARGEST REGISTRY OF DEEPLY PHENOTYPED PPA PATIENTS. DURING THE NEXT CYCLE OF THIS PROJECT, PPA GROUPS WILL BE STRATIFIED BY NEUROPATHOLOGY RATHER THAN CLINICAL VARIANT. THE THREE INTERACTIVE SPECIFIC AIMS ARE TO CHARACTERIZE NEUROPATHOLOGY-SPECIFIC FINGERPRINTS OF ASYMMETRY THROUGH MULTIMODAL IMAGING; TO IDENTIFY NEUROPATHOLOGY-SPECIFIC CORRELATES OF NEUROSYNAPTIC DISRUPTION, INFLAMMATORY MARKERS, GENE EXPRESSION, AND THEIR HEMISPHERIC ASYMMETRY; AND TO EXPLORE MOLECULAR SIGNATURES OF SELECTIVE LEFT HEMISPHERE SUSCEPTIBILITY AND MEMORY RESILIENCE THROUGH GENETIC ANALYSES. WE WILL CONTINUE PROSPECTIVE ENROLLMENT INTO EXISTING AND NEW PROJECTS AND DEVELOP RESEARCH METHODOLOGY FOR SINGLE-SUBJECT RATHER THAN GROUP STUDIES SO THAT INDIVIDUAL DIFFERENCES IN BRAIN ORGANIZATION CAN BE TAKEN INTO ACCOUNT. AN OVERARCHING THEME WILL BE THE CLINICOPATHOLOGY OF ASYMMETRY, WHICH IS THE SINGLE UNIVERSAL CORE FEATURE OF PPA, AND WHICH OFFERS A UNIQUE SETTING FOR INVESTIGATING THE MECHANISMS OF SELECTIVE VULNERABILITY. THE INNOVATIVE ASPECTS INCLUDE ACCESS TO A UNIFORMLY INVESTIGATED UNIQUE PPA COHORT, AVAILABILITY OF AUTOPSY TISSUE FROM BOTH HEMISPHERES SO THAT ASYMMETRY CAN BE QUANTITATED, GRAPH THEORY APPROACHES TO NETWORK ARCHITECTURE, GENETIC EXPLORATIONS OF ASYMMETRIC HEMISPHERIC VULNERABILITY, AND DEVELOPMENT OF PERSONALIZED SINGLE-SUBJECT MAPPING OF THE DISEASED LANGUAGE NETWORK. THE NORTHWESTERN PPA RESEARCH PROGRAM HAS MADE KEY CONTRIBUTIONS TO RESEARCH ON THE NEUROBIOLOGY AND COGNITIVE CHARACTERISTICS OF PPA BY SHOWING THAT THE SAME SYNDROME (E.G., PPA) CAN BE CAUSED BY MULTIPLE NEUROPATHOLOGIC ENTITIES, THAT A SINGLE DISEASE (E.G., AD) CAN CAUSE MULTIPLE SYNDROMES, AND THAT CLINICAL MANIFESTATIONS ARE DETERMINED BY NETWORK ANATOMY RATHER THAN MOLECULAR PATHOLOGY. THROUGH THIS WORK PPA HAS BECOME A PARADIGMATIC ENTITY FOR ESTABLISHING PRINCIPLES OF PATHOPHYSIOLOGIC HETEROGENEITY IN DEMENTIA. THE AIMS IN THIS PROPOSAL WILL HELP TO SHED ADDITIONAL LIGHT ON THE ANATOMICAL TROPISMS OF NEURODEGENERATIVE DISEASES, THE FOUNDATIONS OF HEMISPHERIC ASYMMETRY IN NEURODEGENERATION, THE INTERNAL ARCHITECTURE OF THE LANGUAGE NETWORK, AND THE MECHANISMS THAT MEDIATE THE RESILIENCE OF MEMORY FUNCTION IN PPA WITH AD NEUROPATHOLOGY.

HYDROGEN IN ENERGY AND INFORMATION SCIENCES (HEISS)

PROTEOGENOMICS FOR ORGAN TRANSPLANTATION: PREDICTION, DIAGNOSIS, INTERVENTION

MULTIDISCIPLINARY CLINICAL AND TRANSLATIONAL SCIENCE (MCTS) PROGRAM (UL1)

A FAMILY-GENETIC STUDY OF AUTISM AND FRAGILE X SYNDROME

TAS::57 3600::TAS "(MURI 13) ELECTROCHEMICAL IMAGING AND MECHANISTIC STUDIES ON THE NANOMETER SCALE"

NORTHWESTERN CANCER PREVENTION CONSORTIUM

HYPERBARIC OXYGEN THERAPY FOR ULCERATIVE COLITIS PATIENTS HOSPITALIZED FOR MODERATE TO SEVERE FLARES: A PHASE 3 MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, SHAM-CONTROLLED TRIAL - PROJECT SUMMARY ULCERATIVE COLITIS IS ONE OF THE MOST EXPENSIVE MEDICAL CONDITIONS IN THE UNITED STATES, WITH A CONSIDERABLE AMOUNT OF THESE COSTS BEING INCURRED DURING HOSPITALIZATIONS FOR ACUTE FLARES. A SUBSTANTIAL PROPORTION OF ULCERATIVE COLITIS PATIENTS HOSPITALIZED FOR ACUTE FLARES WILL FAIL TO RESPOND TO INTRAVENOUS STEROIDS AND REQUIRE SECOND LINE THERAPIES SUCH AS BIOLOGICS AND/OR COLECTOMY, WHICH CAN BE ASSOCIATED WITH SIGNIFICANT MORBIDITY AND MORTALITY. ULCERATIVE COLITIS PATIENTS WHO ARE HOSPITALIZED OR HAVE RECENTLY BEEN HOSPITALIZED FOR ACUTE FLARES ARE EXCLUDED FROM TRADITIONAL PHASE 2 AND 3 DRUG DEVELOPMENT TRIALS BECAUSE OF HOW HIGH RISK THEY ARE FOR PROGRESSION TO COLECTOMY OR RE-ADMISSION. NOVEL, SAFE, AND EFFECTIVE TREATMENTS ARE NEEDED TO OPTIMIZE OUTCOMES IN THIS HIGH-RISK ORPHAN POPULATION. A HALLMARK OF ULCERATIVE COLITIS IS CHRONIC INTESTINAL MUCOSAL HYPOXIA AND INFLAMMATION, WITH AN ACCOMPANYING DYSFUNCTION IN HYPOXIA RESPONSE PATHWAYS AND PREFERENTIAL ACTIVATION OF PATHOGENIC IMMUNE CELLS INCLUDING NEUTROPHILS. HYPERBARIC OXYGEN THERAPY INVOLVES BREATHING 100% OXYGEN UNDER INCREASED ATMOSPHERIC PRESSURE TO INCREASE TISSUE OXYGENATION. IN A PHASE 2 TRIAL PROGRAM WE DEMONSTRATED THAT THIS INCREASED OXYGENATION OF MUCOSAL TISSUE LEADS TO IMPROVEMENTS IN DISEASE ACTIVITY IN ULCERATIVE COLITIS, REDUCTIONS IN INFLAMMATORY MARKERS, AND PREVENTION OF PROGRESSION TO BIOLOGICS OR COLECTOMY DURING HOSPITALIZATIONS FOR ACUTE FLARES. IN THE CURRENT PROPOSAL WE AIM TO 1) CONFIRM THE IMPACT OF HYPERBARIC OXYGEN THERAPY ON DISEASE OUTCOMES IN ULCERATIVE COLITIS PATIENTS HOSPITALIZED FOR ACUTE FLARES THROUGH A MULTI-CENTER, DOUBLE-BLIND, SHAM- CONTROLLED, CLINICAL TRIAL. WE FURTHER AIM TO EXPLORE THE MECHANISMS THROUGH WHICH HYPERBARIC OXYGEN THERAPY IMPROVES DISEASE ACTIVITY BY STUDYING THE HYPERBARIC OXYGEN SPECIFIC EFFECTS ON 2) NEUTROPHILS AND EPITHELIAL CELLS, AND 3) THE MICROBIOME. CONFIRMATION OF TREATMENT EFFICACY FOR HYPERBARIC OXYGEN THERAPY WOULD BRING FORWARD A NOVEL THERAPY FOR A HIGH-RISK POPULATION OF ULCERATIVE COLITIS PATIENTS WHO ARE TRADITIONALLY EXCLUDED FROM TRADITIONAL CLINICAL TRIAL PROGRAMS, WHILE ALSO ADVANCING OUR UNDERSTANDING OF DISEASE PATHOGENESIS AND THE INTERPLAY BETWEEN HYPOXIA, THE IMMUNE SYSTEM, AND THE MICROBIOME.

MUTATIONS OF CHROMATIN AND ITS MODIFYING MACHINERIES IN MALIGNANCIES

CONTROL OF SYNAPTIC CIRCUITS BY SMALL GTPASE PATHWAYS - SUMMARY – OVERALL A MAJOR GOAL OF NIMH IS TO UNDERSTAND THE NEUROBIOLOGY UNDERLYING COMMON COGNITIVE AND BEHAVIORAL DEFICITS ASSOCIATED WITH MENTAL DISORDERS. SUCH BEHAVIORAL DEFICITS, AS WELL AS ACTION PLANS EXECUTED IN RESPONSE TO NOVEL SENSORY EXPERIENCES, ARE GATED BY COGNITIVE PROCESSING WITHIN NEOCORTICAL CIRCUITS. IT IS EXPECTED THAT A MECHANISTIC AND MULTI-LEVEL BIOLOGICAL UNDERSTANDING OF HOW CORTICAL CIRCUITS ARE BUILT AND REFINED DURING DEVELOPMENT WILL REVEAL MOLECULAR TARGETS FOR FUTURE THERAPEUTIC STRATEGIES TO TREAT MENTAL DISORDERS. THUS, THE GOAL OF THIS CENTER IS TO UNDERSTAND HOW GENE EXPRESSION AND ASSOCIATED GENE FUNCTION WITHIN KEY NEURONAL SUBTYPES REGULATES NEUROBIOLOGICAL SUBSTRATES REQUIRED TO FORM CORTICAL CIRCUITS THAT ENABLE DECISION-MAKING AND BEHAVIORAL ADAPTATIONS. A CONTE CENTER WILL PROVIDE RAPID AND EFFICIENT BIDIRECTIONAL FLOW OF INFORMATION AND TOOLS, AS WELL AS SYNERGY AND INTEGRATION THAT COULD NOT BE ACHIEVED USING INDIVIDUAL GRANTS. RAS AND RHO-LIKE SMALL GTPASES PLAY FUNDAMENTAL BIOLOGICAL ROLES WITHIN NEURONS BY CONTROLLING CELL- AUTONOMOUS GROWTH-RELATED SIGNALING PATHWAYS AND ORCHESTRATING NEURONAL CIRCUIT ASSEMBLY AND FUNCTION. GEFS AND GAPS ARE DIRECT UPSTREAM REGULATORS OF SMALL GTPASE SIGNALING, AND WITHIN NEURONS, ORCHESTRATE CELLULAR MIGRATION, NEURONAL MORPHOGENESIS, SYNAPTIC CONNECTIVITY, SYNAPTIC PLASTICITY TRIGGERED IN RESPONSE TO NOVEL SENSORY EXPERIENCE, IN VIVO NEURAL CIRCUIT FUNCTION, AND ASSOCIATED BEHAVIORAL ADAPTATIONS. GEFS AND GAPS AS EXEMPLAR BIOLOGICAL ENTRY POINTS FOR UNDERSTANDING HOW CELLULAR GTPASE SIGNALING SHAPES NEURAL CIRCUITS THAT FACILITATE ADAPTIVE BEHAVIORS. HOWEVER, IT IS UNKNOWN HOW THEIR EXPRESSION AND FUNCTION WITHIN SPECIFIC NEURONAL SUBTYPES AND DEFINED DEVELOPMENTAL WINDOWS DRIVE CORTICAL CIRCUIT REFINEMENT TO IMPACT COGNITIVE PROCESSING AND ASSOCIATED BEHAVIORS. TO CLOSE THIS KNOWLEDGE GAP, OUR TEAM IS PROPOSING AN INTEGRATED, INTERDISCIPLINARY, MULTI-LEVEL “CENTER FOR GTPASE REGULATION OF NEURONAL CELL BIOLOGY AND BEHAVIOR” TO STUDY THE ROLES OF GTPASE SIGNALING IN CORTICAL NEURAL CIRCUIT WITH THE GOAL OF UNDERSTANDING FUNDAMENTAL PRINCIPLES THAT DRIVE THE HIERARCHICAL ORGANIZATION OF BRAIN CIRCUITS THAT UNDERLIE COMPLEX BEHAVIORS. COMPRISED OF INVESTIGATORS WITH EXPERTISE THAT SPANS ALL MAJOR LEVELS OF BRAIN FUNCTION – MOLECULAR, SYNAPTIC, CELLULAR, CIRCUIT, SYSTEM, AND BEHAVIOR – THE IMPACT OF OUR CENTER WILL BE TO MECHANISTICALLY CONNECT THE REGULATION OF GTPASE SIGNALING WITHIN DISTINCT NEURONAL SUBTYPES TO THE ASSEMBLY AND FUNCTION OF BEHAVIORAL CIRCUITS ASSOCIATED WITH MENTAL DISORDERS.

A PRAGMATIC TRIAL OF AN ADAPTIVE EHEALTH HIV PREVENTION PROGRAM FOR DIVERSE ADOLESCENT MSM

NORTHWESTERN UNIVERSITY CLINICAL TRIAL UNIT

AFRICAN AMERICAN CARDIOVASCULAR PHARMACOGENETIC CONSORTIUM (ACCOUNT): DISCOVERY AND TRANSLATION

DRUG ABUSE INCARCERATION & HEALTH DISPARITIES IN HIV/AIDS: A LONGITUDINAL STUDY

IDENTIFICATION OF THE INITIAL TARGETS OF TRANSMISSION

SAGE GRANDE: AN OPEN ARTIFICIAL INTELLIGENCE TESTBED FOR EDGE COMPUTING AND INTELLIGENT SENSING -LANGUAGE-BASED GENERATIVE ARTIFICIAL INTELLIGENCE (AI) IS TRANSFORMING SCIENTIFIC RESEARCH, OPENING NEW OPPORTUNITIES TO EMPOWER DISCOVERY AND BROADER PARTICIPATION THROUGH THE USE OF NATURAL LANGUAGE INTERFACES TO SCIENTIFIC WORKFLOWS AND AI-ENABLED CYBERINFRASTRUCTURE. TO FULLY EXPLOIT NSF?S INVESTMENTS IN CYBERINFRASTRUCTURE, THERE IS A CRITICAL NEED TO DEVELOP AND UNDERSTAND THE INTEGRATION, PROGRAMMING, AND USE OF AI ACROSS SCIENTIFIC COMPUTING RESOURCES AND HIGH-RESOLUTION ENVIRONMENTAL SENSORS AND INSTRUMENTS SUCH AS CAMERAS, MICROPHONES, AND WEATHER SENSORS. THIS NEW AI-ENABLED CYBERINFRASTRUCTURE WILL ACCELERATE DATA ANALYSIS AND SOFTWARE GENERATION WITH POWERFUL MULTI-MODAL LARGE LANGUAGE MODELS (LLMS). IT HARNESSES LLMS TO DEMOCRATIZE ACCESS TO AI, ENABLING INDIVIDUALS WITHOUT PROGRAMMING SKILLS TO CONDUCT EXPERIMENTS AND ALLOWING THE SCIENTIFIC COMMUNITY TO DEVELOP NATURAL LANGUAGE INTERFACES, EMPOWERING A NEW GENERATION OF SCIENTISTS, BROADENING PARTICIPATION IN AI RESEARCH THROUGH OUTREACH PROGRAMS, AND ENHANCING REPRESENTATION. HANDS-ON TRAINING AND EDUCATIONAL RESOURCES FOR STUDENTS WILL PROVIDE TECHNICAL SKILLS AND ENHANCE THE NATION?S AI WORKFORCE DEVELOPMENT. THE SAGE GRANDE TESTBED (SGT) IS DESIGNED TO REVOLUTIONIZE THE INTEGRATION OF LLMS AND EDGE COMPUTING IN SCIENTIFIC RESEARCH, EXTENDING NSF?S CYBERINFRASTRUCTURE TO SUPPORT ADVANCED AI APPLICATIONS ACROSS VARIOUS DOMAINS. IT BUILDS ON SAGE, AN AI-ENABLED PLATFORM DEVELOPED THROUGH NSF?S MID-SCALE RESEARCH INFRASTRUCTURE PROGRAM TO INTEGRATE NATURAL LANGUAGE PROCESSING CAPABILITIES WITH CLOUD-BASED SOFTWARE ENVIRONMENTS, ENABLING SEAMLESS SCIENTIFIC INQUIRIES AND REDUCING THE COMPLEXITY OF USING ADVANCED CYBERINFRASTRUCTURE. SGT SUPPORTS A LIBRARY OF LLMS TO SUPPORT NATURAL LANGUAGE QUERIES, FOSTERING BREAKTHROUGH RESEARCH AND HANDS-ON EDUCATION. THE TESTBED ADDRESSES GENERATIVE AI, THE COMPUTING CONTINUUM, AND SCIENTIFIC MEASUREMENT AND OBSERVATION, AND PROVIDES CYBERINFRASTRUCTURE TO EVALUATE AI TRUST FACTORS, INCLUDING HALLUCINATIONS, BIAS, AND SAFETY AS WELL AS AI-GENERATED AND AI-CONTROLLED CYBER-PHYSICAL SYSTEMS NECESSARY FOR FIELD MEASUREMENTS AND REAL-TIME DATA ANALYSIS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

FUNCTION OF DESMOGLEIN 1/PEMPHIGUS FOLIACEUS ANTIGEN

CHRONIC RHINOSINUSITIS INTEGRATIVE STUDIES PROGRAM 2 (CRISP2)

SILICON TRACKER PROPOSAL FOR THE DO UPGRADE-OUTSTANDING JUNIOR INVESTIGATOR PROGRAM.

UNIVERSITY TRANSPORTATION CENTERS - TRANSPORTATION AND ECONOMIC DEVELOPMENT IN MOUNTAIN REGIONS

MID-SCALE RI-1: SAGE: A SOFTWARE-DEFINED SENSOR NETWORK

CENTER FOR CHRONIC PAIN AND DRUG ABUSE

MEDICAL SCIENTIST TRAINING PROGRAM - THE MD/PHD PROGRAM AT NORTHWESTERN UNIVERSITY WAS ESTABLISHED IN 1964 AND HAS BEEN SUPPORTED BY AN NIH TRAINING GRANT FROM 1964-1969 AND FROM 1987-PRESENT. THE MISSION OF THE NORTHWESTERN MSTP IS TO TRAIN THE NEXT GENERATION OF COMPETENT, COMMITTED, AND DIVERSE PHYSICIAN-SCIENTISTS IN AN INCLUSIVE TRAINING ENVIRONMENT THAT ALLOWS ALL STUDENTS TO FLOURISH. TO ACCOMPLISH THIS MISSION, OUR TRAINING CURRICULUM EMPHASIZES AND INTEGRATES TWO PARALLEL PURSUITS: TRAINING STUDENTS TO EXCEL IN BIOMEDICAL RESEARCH, AND INSTILLING THE VALUES, KNOWLEDGE, AND ART OF CLINICAL MEDICINE. EXCELLENCE IN MEDICINE BEGINS IN THE PRECLINICAL PHASE OF THE PROGRAM WITH A COMPREHENSIVE MEDICAL EDUCATION CENTERED ON EARLY EXPOSURE TO PATIENT CARE, AND IT IS REINFORCED WITH REQUIRED INPATIENT AND OUTPATIENT EXPOSURE THROUGHOUT THE RESEARCH PHASE OF THE PROGRAM. DURING THE RESEARCH PHASE, MSTP STUDENTS BENEFIT FROM NORTHWESTERN'S WELL-FUNDED RESEARCH ENTERPRISE THAT PROVIDES RICH OPPORTUNITIES TO PURSUE INTERDISCIPLINARY TRANSLATIONAL RESEARCH IN LIFE SCIENCES, BIOMEDICAL ENGINEERING, BIOINFORMATICS, AND MANY OTHER AREAS ACROSS OUR EVANSTON AND CHICAGO CAMPUSES. AFTER THE SUCCESSFUL DEFENSE OF THEIR DOCTORAL DISSERTATIONS, MSTP STUDENTS COMPLETE HOSPITAL-BASED CLERKSHIPS AS PART OF THE CLINICAL PHASE OF THEIR MEDICAL SCHOOL EDUCATION AND RECEIVE THE MD DEGREE. THE MSTP HAS DEVELOPED A ROBUST SET OF PROGRAM-SPECIFIC COURSES AND ACTIVITIES TO CONTINUOUSLY INTEGRATE MEDICAL AND RESEARCH TRAINING THROUGHOUT THE PROGRAM AND HELP CREATE A SENSE OF COMMUNITY AMONG STUDENTS. THESE ACTIVITIES ARE COMPLIMENTED BY A STRONG MENTORING STRUCTURE THAT ENSURES ALL STUDENTS RECEIVED INDIVIDUALIZED SUPPORT FROM PROGRAM LEADERSHIP AS THEY MOVE THROUGH THE PHASES OF TRAINING AND WORK TO ACHIEVE THEIR UNIQUE PROFESSIONAL GOALS. THE PROGRAM'S LONG-STANDING SUCCESS IN MEETING ITS TRAINING OBJECTIVES IS EVIDENCED IN A NUMBER OF AREAS: OUR STUDENTS RECEIVE GRANT FUNDING AT EXCELLENT SUCCESS RATES, GRADUATE WITH STRONG PUBLICATION RECORDS, AND SECURE RESIDENCY POSITIONS THAT ARE AMONG THE VERY BEST IN THE NATION. OUR PROGRAM ALSO HOLDS DIVERSITY AS A CENTRAL PART OF OUR TRAINING MISSION, AND THE DIVERSITY OF OUR COHORTS SPEAKS TO THE PROGRAM'S COMMITMENT TO FOSTERING A TRAINING ENVIRONMENT THAT SUPPORTS ALL STUDENTS AS THEY WORK TOWARDS THE DUAL DEGREE. SIZE LEADERSHIP, THE OVER THE PAST TWO DECADES, THE AND QUALITY OF THE MSTP HAVE GROWN STEADILY THANKS TO STRONG INSTITUTIONAL SUPPORT, AND SUBSTANTIAL GROWTH IN BIOMEDICAL SCIENCE RESEARCH AT NORTHWESTERN UNIVERSITY. PROGRAM CURRENTLY SUPPORTS 121 STUDENTS, WITH PLANS FOR CONTINUED EXPANSIONAND IMPROVEMENT OVER THE NEXT FIVE YEARS.

A PRAGMATIC TRIAL OF TWO STRATEGIES FOR IMPLEMENTING AN EFFECTIVE EHEALTH HIV PREVENTION PROGRAM

MRSEC: MULTIFUNCTIONAL NANOSCALE MATERIAL STRUCTURES

ENGINEERING THE TRANSLATION APPARATUS FOR THE SYNTHESIS OF ELECTRONICALLY ACTIVE SEQUENCE-DEFINED POLYMERS

NORTHWESTERN UNIVERSITY MATERIALS RESEARCH SCIENCE AND ENGINEERING CENTER -NONTECHNICAL DESCRIPTION: THE NORTHWESTERN UNIVERSITY MATERIALS RESEARCH SCIENCE AND ENGINEERING CENTER (NU-MRSEC) ADVANCES WORLD-CLASS MATERIALS RESEARCH, EDUCATION, AND OUTREACH VIA ACTIVE INTERDISCIPLINARY COLLABORATIONS WITHIN THE CENTER AND WITH EXTERNAL PARTNERS IN ACADEMIA, INDUSTRY, NATIONAL LABORATORIES, AND MUSEUMS, BOTH DOMESTICALLY AND ABROAD. THE INTELLECTUAL MERIT OF THE NU-MRSEC RESIDES PRIMARILY WITHIN ITS INTERDISCIPLINARY RESEARCH GROUPS (IRGS) AND SEED-FUNDED PROJECTS THAT EXPLORE THE FRONTIERS OF MATERIALS RESEARCH. IRG-1 ENTITLED ?BIOPROGRAMMABLE MATERIALS VIA CELL-FREE SYNTHETIC BIOLOGY? DEVELOPS SOFT COMPOSITE MATERIALS THAT INCORPORATE BIOLOGICAL MACHINERY IN A CELL-FREE PLATFORM, THUS REMOVING THE NOURISHMENT AND CARE DEMANDS OF LIVING TISSUE. IN THIS MANNER, THE FUNCTIONALITY OF LIVING BIOLOGICAL SYSTEMS ARE ACHIEVED IN AN AUTONOMOUS MATERIAL WITH DIRECT IMPLICATIONS FOR SUSTAINABLE AGRICULTURE, WATER TREATMENT, SMART CLOTHING, AND WOUND HEALING. IRG-2 ENTITLED ?ORCHESTRATED IONTRONICS VIA DYNAMIC HYBRID IONIC/ELECTRONIC CONDUCTORS? DESIGNS MATERIALS THAT CONCURRENTLY CONDUCT IONS AND ELECTRONS, BEHAVING IN A MANNER THAT MIMICS BIOLOGICAL NEURONS. THESE HYBRID IONIC/ELECTRONIC CONDUCTORS THUS ENABLE BRAIN-INSPIRED COMPUTATION THAT IS ACCELERATING ADVANCES IN ARTIFICIAL INTELLIGENCE, ROBOTICS, AND BIOELECTRONICS. BY INCORPORATING THESE RESEARCH ADVANCES INTO INNOVATIVE PEDAGOGY, THE NU-MRSEC ACHIEVES BROAD IMPACT THROUGH PROFESSIONAL DEVELOPMENT OF GRADUATE STUDENTS AND POSTDOCS, RESEARCH EXPERIENCES FOR UNDERGRADUATES AND TEACHERS, AND OUTREACH TO K-12 STUDENTS AND THE GENERAL PUBLIC. THESE ACTIVITIES ARE ENHANCED BY PARTNERSHIPS WITH ARGONNE NATIONAL LABORATORY, ART INSTITUTE OF CHICAGO, CHICAGO MUSEUM OF SCIENCE AND INDUSTRY, CHICAGO FIELD MUSEUM OF NATURAL HISTORY, CHICAGO PUBLIC SCHOOLS, AND CHICAGO CITY COLLEGES. TECHNICAL DESCRIPTION: THE NORTHWESTERN UNIVERSITY MATERIALS RESEARCH SCIENCE AND ENGINEERING CENTER (NU-MRSEC) INTEGRATES MATERIALS RESEARCH, EDUCATION, AND OUTREACH THROUGH TWO INTERDISCIPLINARY RESEARCH GROUPS (IRGS) AND WITH EXTERNAL PARTNERS IN ACADEMIA, INDUSTRY, NATIONAL LABORATORIES, AND MUSEUMS, BOTH DOMESTICALLY AND ABROAD. IRG-1 ENTITLED ?BIOPROGRAMMABLE MATERIALS VIA CELL-FREE SYNTHETIC BIOLOGY? DEVELOPS SOFT ACTIVE MATERIALS THAT INCORPORATE BIOLOGICAL MACHINERY INTO ARTIFICIAL CELLS THAT ELIMINATE THE NEED FOR, AND CONSTRAINTS OF, LIVING CELLS. THESE BIOPROGRAMMABLE MATERIALS POSSESS AUTONOMOUS PROPERTIES SUCH AS SELF-HEALING, ON-DEMAND CARGO RELEASE, DYNAMIC MECHANICAL PROPERTY MODULATION, BIOMINERALIZATION, AND SHAPE-MORPHING. BY ACHIEVING THE ADAPTIVE MULTI-FUNCTIONALITY OF BIOLOGICAL SYSTEMS IN A CELL-FREE SYNTHETIC MATERIAL, IRG-1 ACCELERATES ADVANCES IN SUSTAINABLE AGRICULTURE, SOFT ROBOTICS, WATER TREATMENT, SMART CLOTHING, AND WOUND HEALING. IRG-2 ENTITLED ?ORCHESTRATED IONTRONICS VIA DYNAMIC HYBRID IONIC/ELECTRONIC CONDUCTORS? DESIGNS MATERIALS WITH MIXED IONIC AND ELECTRONIC TRANSPORT PHENOMENA THAT REALIZE NEUROMORPHIC FUNCTIONALITY FOR EFFICIENTLY IMPLEMENTING ARTIFICIAL INTELLIGENCE. BY UNDERSTANDING AND CONTROLLING THE INTERPLAY BETWEEN ORGANIC MATERIALS AND INORGANIC LAYERED MATERIALS, IRG-2 ACHIEVES SYNERGISTIC IONTRONIC ATTRIBUTES INCLUDING MULTI-TIMESCALE SYNAPTIC POTENTIATION AND PLASTICITY, NON-LINEAR RESPONSES THAT EMULATE NEURONAL SPIKING, AND STIMULI-INDUCED STRUCTURE MODULATION TO PROVIDE SENSORY TRANSDUCTION, SELECTIVITY, AND ADAPTATION. THE RESEARCH OF THE NU-MRSEC INFORMS A COMPREHENSIVE SET OF EDUCATION AND OUTREACH ACTIVITIES THAT ARE NOT ONLY DESIGNED FOR SPECIFIC COHORTS (GENERAL PUBLIC, K-12, UNDERGRADUATES, GRADUATE STUDENTS, POSTDOCS) BUT ALSO BRIDGE PROGRAMS THAT SHEPHERD STUDENTS ALONG THE DEVELOPMENT PATHWAY, THEREBY INCREASING THE NUMBER AND DIVERSITY OF PARTICIPANTS AT ALL LEVELS. THESE EFFORTS ARE AUGMENTED BY CORPORATE PARTNERSHIPS AND STARTUP COMPANIES, EXTENSIVE SHARED FACILITIES, AND REGULAR INTERACTIONS WITH ARGONNE NATIONAL LABORATORY, ART INSTITUTE OF CHICAGO, CHICAGO MUSEUM OF SCIENCE AND INDUSTRY, CHICAGO FIELD MUSEUM OF NATURAL HISTORY, CHICAGO PUBLIC SCHOOLS, AND CHICAGO CITY COLLEGES. 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.

HIT EXTENSION CENTERS - 3012 - THE CHICAGO HIT REGIONAL EXTENSION CENTER

TAS::57 3600::TAS "(MURI-15) A 4D NANOPRINTER FOR MAKING AND MANIPULATING MACROSCOPIC MATERIALS"

MECHANISMS OF GONOCOCCAL PILIN ANTIGENIC & PHASE VARIATION

NANOMATERIALS FOR CANCER DIAGNOSTICS AND THERAPEUTICS

NORTHWESTERN UNIVERSITY CENTER FOR CHROMATIN NANOIMAGING IN CANCER (NU-CCNIC) - OVERALL: PROJECT SUMMARY CANCER STEM CELLS (CSCS) PLAY A CRITICAL ROLE IN FOSTERING TUMOR RESISTANCE TO THERAPIES AND RELAPSE AFTER TREATMENT. THIS PRESENTS A CRUCIAL BARRIER TO THE DEVELOPMENT OF SUCCESSFUL ANTI-CANCER THERAPEUTICS. TRANSCRIPTIONAL REPROGRAMMING AND PLASTICITY PLAY A CRITICAL ROLE IN AND OUT OF THE CSC STATE, WHICH IN TURN ARE INTERDEPENDENT ON THE REGULATORY FUNCTION OF THE THREE-DIMENSIONAL (3D) STRUCTURE OF CHROMATIN, EPIGENETIC STATES, AND OTHER MOLECULAR EVENTS. OUR UNDERSTANDING OF FUNDAMENTAL CSC BIOLOGY HAS BEEN HAMPERED BY THE NEED FOR CELLULAR NANOSCALE IMAGING TECHNOLOGIES THAT PROVIDE BOTH HIGHLY DETAILED STRUCTURAL INFORMATION REGARDING 3D CHROMATIN ORGANIZATION AND HIGHLY MULTIPLEXED MOLECULAR IMAGING OF THE MANY MOLECULAR REGULATORS AND EVENTS INVOLVED IN CSC PROCESSES. WE PROPOSE TO ESTABLISH THE NORTHWESTERN UNIVERSITY CENTER FOR CHROMATIN NANOIMAGING IN CANCER (NU-CCNIC) TO ADDRESS THIS FUNDAMENTAL TECHNOLOGY GAP IN CELLULAR NANOSCALE IMAGING AND DEPLOY THE NEW TECHNOLOGIES TO ADDRESS THE FUNDAMENTAL KNOWLEDGE GAP IN CSC BIOLOGY. THE CENTER CONVERGES EXPERTS IN CELLULAR NANOSCALE IMAGING, COMPUTATIONAL IMAGING, MOLECULAR MODELING, COMPUTATIONAL GENOMICS, CSC BIOLOGY, AND ONCOLOGY. THE CENTER WILL DEVELOP, TEST, VALIDATE, ITERATE, AND DEPLOY AN INTEGRATED AND CO-REGISTERED MULTI-SCALE CHROMATIN NANOIMAGING PLATFORM THAT WILL COMPRISE THREE “NESTED-DOLL” IMAGING TECHNIQUES: CHROMATIN SCANNING TRANSMISSION ELECTRON MICROSCOPY, OPTICAL SPECTROSCOPIC SUPER-RESOLUTION NANOSCOPY, AND OPTICAL SPECTROSCOPIC NANOSENSING. THE NANOIMAGING PLATFORM WILL ENABLE QUANTITATIVE IMAGING OF CHROMATIN STRUCTURE AND HIGHLY MULTIPLEXED MOLECULAR AND GENE-SPECIFIC LOCALIZATION, AT THE MOST FUNDAMENTAL LENGTH-SCALE APPROACHING 1 NM RESOLUTION, INCLUDING THE IMAGING OF STATISTICALLY SIGNIFICANT CELL POPULATIONS AND LIVE CELLS WITH HIGH TEMPORAL RESOLUTION OVER PROLONGED TEMPORAL FOLLOW-UP TIMES. THE NANOIMAGING PLATFORM WILL BE BRIDGED TO COMPUTATIONAL GENOMICS, EPIGENOMICS, GENOME MAPPING, AND PREDICTIVE TRANSCRIPTIONAL MODELING DATASETS. THESE TECHNOLOGIES WILL BE DEPLOYED TO ANSWER SEVERAL LONG-STANDING OPEN QUESTIONS IN CSC BIOLOGY. WE WILL ELUCIDATE WHETHER CSCS CAN ORIGINATE FROM NON-CSCS VIA TRANSCRIPTIONAL REPROGRAMMING, TEST THE ROLE OF CHROMATIN STRUCTURE IN FOSTERING TRANSCRIPTIONAL PLASTICITY IN CSC PROCESSES, AND EXPLORE THE POSSIBILITY OF TRANSCRIPTIONALLY REPROGRAMMING CSCS TO EXIT THE STEM-STATE AS A NEW THERAPEUTIC STRATEGY. ALL ASPECTS OF THE TECHNOLOGY DEVELOPMENT WILL BE GUIDED BY THE NEEDS OF THE CSC BIOLOGY TESTBED THROUGH A SERIES OF RESEARCH FEEDBACK LOOPS. IN THE LONG TERM, SUCH SINGLE-CELL NANOIMAGING TECHNOLOGIES WILL HELP COMPREHENSIVE UNDERSTANDING OF THE COMPLEX INTERPLAY BETWEEN STRUCTURAL, PHYSICO-CHEMICAL, AND MOLECULAR GENOMIC EVENTS. WE ANTICIPATE THAT THESE CONVERGENCE STUDIES WILL PROVIDE NEW INSIGHTS INTO CSC BIOLOGY, WHICH ARE IMPOSSIBLE TO REVEAL WITH THE USE OF ANY SINGLE METHOD, AND OPEN NEW OPPORTUNITIES FOR IDENTIFYING THERAPEUTIC STRATEGIES.

ESTABLISHING A CLOSTRIDIA FOUNDRY FOR BIOSYSTEMS DESIGN BY INTEGRATING COMPUTATIONAL MODELING, SYSTEMS-LEVEL ANALYSES, AND CELL-FREE ENGINEERING TECHNOLOGIES

OPTIMIZING PREDICTION OF PRESCHOOL PSYCHOPATHOLOGY FROM BRAIN: BEHAVIOR MARKERS OF EMOTION DYSREGULATION FROM BIRTH: A COMPUTATIONAL, DEVELOPMENTAL COGNITIVE NEUROSCIENCE APPROACH

LANGUAGE IN PRIMARY PROGRESSIVE APHASIA

ALIGNING DOSIMETRY AND BIOMARKERS OF LUNG INJURY WITH PROPHYLAXIS AND MITIGATION OF DAMAGE FROM RADIONUCLIDES AND METALS

HORMONAL SIGNALS THAT REGULATE OVARIAN DIFFERENTIATION

APTO: MEASURING, UNDERSTANDING, PREDICTING, AND ACCELERATING TECHNOLOGY OUTCOMES -SCIENTIFIC AND TECHNOLOGICAL (S&T) ADVANCES ARE KEY DRIVERS OF ECONOMIC GROWTH AND RISING STANDARDS OF LIVING AND ARE CENTRAL TO IMPROVING HEALTH, MAINTAINING A COMPETITIVE WORKFORCE, AND ENSURING ROBUST NATIONAL SECURITY. YET, DESPITE GAINS IN OUR QUANTITATIVE UNDERSTANDING OF S&T PROGRESS, OUR ABILITY TO ASSESS AND PREDICT HOW, WHEN, AND WHICH RESEARCH IDEAS AND INVESTMENTS LEAD TO SUCCESSFUL APPLICATIONS REMAINS ELUSIVE. THE PRIMARY CHALLENGE STEMS FROM LONGSTANDING EMPIRICAL BLIND SPOTS ALONG THE RESEARCH-TO-MARKET PIPELINE. AS A RESULT, MANY CRUCIAL QUESTIONS REMAIN OPEN. FOR EXAMPLE, WHICH SPECIFIC RESEARCH INSIGHTS WILL ACTUALLY PENETRATE THE MARKET AND PROPEL DOWNSTREAM TECHNOLOGICAL CAPABILITY, PRODUCTION, AND USE? WHAT ARE THE CHARACTERISTICS OF SPECIFIC GRANTS, IDEAS, RESEARCHERS, AND ORGANIZATIONS THAT BEST PREDICT TANGIBLE ADVANCES? WHAT SPECIFIC HURDLES OBSTRUCT PROGRESS, AND WHERE AND HOW CAN THESE HURDLES AND SLOWDOWNS BE OVERCOME? TO ADDRESS THESE CHALLENGES, NORTHWESTERN UNIVERSITY, TOGETHER WITH ITS PARTNERS, WILL PURSUE TWO LINES OF EFFORT (LOE): DATA AND MODELS. THE DATA LOE CREATES A DATA PIPELINE LINKING RESEARCH FUNDING IN SCIENCE AND TECHNOLOGY TO MARKETPLACE USES IN WIDE-RANGING APPLICATION AREAS. THE MODEL LOE BUILDS ON THE DATA LOE AS WELL AS PRIOR WORK ON THE SCIENCE OF SCIENCE TO DEVELOP PREDICTIVE AND CAUSAL MODELS OF TECHNOLOGY OUTCOMES. TOGETHER, THESE DATASETS AND MODELS WILL PROVIDE THE RESEARCH COMMUNITY WITH TOOLS TO BROADEN THE IMPACT OF FEDERAL R&D INVESTMENT, ACCELERATE APPLICATIONS AND SOCIAL IMPACT, AND DIRECT ATTENTION TO DIVERSE SOURCES OF BREAKTHROUGH IDEAS. THE ABILITY TO PREDICT TECHNOLOGICAL PROGRESS AND PINPOINT UNTAPPED OPPORTUNITIES FOR ADVANCING TARGETED TECHNOLOGY OUTCOMES IS EXPECTED TO OPEN NEW DOORWAYS TO NATIONAL PROGRESS. IN ADDITION TO INFORMING HOW INVESTMENTS IN PEOPLE, IDEAS, AND ORGANIZATIONS PREDICT AND PROMOTE ADVANCES IN SPECIFIC APPLICATION AREAS, OUR MODELS WILL LEVERAGE WIDE-RANGING SOURCES OF VALUABLE RESEARCH IDEAS, REMOVE BARRIERS FOR UNDERREPRESENTED GROUPS, AND HELP LESS RESEARCH-INTENSIVE INSTITUTIONS ENGAGE IN SUCCESSFUL COMMERCIALIZATION. THE GOAL OF THIS FIVE-YEAR RESEARCH PROGRAM IS TO ESTABLISH A SYSTEMATIC, QUANTITATIVE FOUNDATION FOR MEASURING, UNDERSTANDING, PREDICTING, AND ACCELERATING TECHNOLOGY OUTCOMES. DESPITE RAPID ADVANCES IN OUR UNDERSTANDING OF SCIENTIFIC AND TECHNOLOGICAL PROGRESS, QUANTIFYING AND PREDICTING WHAT, WHEN, AND HOW WE REALIZE ADVANCES IN SPECIFIC APPLICATION AREAS REMAINS ELUSIVE. KEY CONSTRAINTS INVOLVE DATA. THIS RESEARCH PROGRAM FILLS LONGSTANDING GAPS THROUGH FIVE INTERCONNECTED RESEARCH THRUSTS, BUILDING AN INTEGRATED RESEARCH-TO-MARKET DATA PIPELINE AND CREATING NEW MODELS THAT TRANSFORM OUR ABILITY TO ASSESS, PREDICT, AND ACCELERATE TECHNOLOGICAL PROGRESS. THRUST 1 UNLOCKS THE RESEARCH-TO-MARKET PATHWAY VIA TECH BRIDGE, A BOLD INITIATIVE TO AGGREGATE, INTEGRATE, AND ANALYZE UNIVERSITY DATASETS, INCLUDING TECHNOLOGY TRANSFER, HUMAN RESOURCES, AND RESEARCH OFFICES. LINKING DATA ACROSS A NETWORK OF OVER 20 RESEARCH INSTITUTIONS WILL CREATE UNPARALLELED OPPORTUNITIES FOR INSIGHT, BRIDGING MAJOR GAPS IN THE RESEARCH-TO-MARKET PATHWAY. THRUST 2 ILLUMINATES THE JOURNEY FROM R&D TO MARKET IMPACT. A DATA LAKE WILL BE CONSTRUCTED THAT LEVERAGES THE POWER OF LICENSING AND STARTUP DATA FROM THRUST 1 AND BUILDS MACHINE LEARNING MODELS TO PREDICT THE MARKET IMPACT OF UPSTREAM R&D INVESTMENTS. THRUST 3 INTEGRATES THE DATA IN THRUST 2 WITH DEEP DIVES INTO FIVE TECHNOLOGY AREAS -- ADDITIVE MANUFACTURING, SYNTHETIC BIOLOGY, ADVANCED MATERIALS, ARTIFICIAL INTELLIGENCE ALGORITHMS, AND THERAPEUTICS. TECHNOLOGY-SPECIFIC OUTCOMES WILL BE TRACED TO ENABLE DOWNSTREAM PREDICTIONS OF TECHNOLOGY CAPABILITIES, PRODUCTION, AND USE. THRUST 4 BUILDS MODELS FOR TECHNOLOGY OUTCOMES. THE RESEARCH TEAM WILL FIRST EXPLORE MECHANISMS GOVERNING THE EVOLUTION OF TECHNOLOGICAL FRONTIERS, THEN LEVERAGE MACHINE LEARNING MODELS TO TRAIN AND TEST A SERIES OF INTER-RELATED MODULES ALONG THE RESEARCH-TO-MARKET PIPELINE. FINALLY, THRUST 5 ACCELERATES KEY TECHNOLOGY OUTCOMES THROUGH TWO FRAMEWORKS: A PREDICTIVE FRAMEWORK IDENTIFIES IDEAS, PEOPLE, AND ORGANIZATIONS THAT HAVE THE POTENTIAL TO ACCELERATE OUTCOMES, AND AN INTERVENTION FRAMEWORK PINPOINTS UNTAPPED OPPORTUNITIES FOR FEDERAL R&D TO HAVE A WIDER AND FASTER IMPACT. THE RESEARCH TEAM WILL LINK OUTCOMES AND THEIR PREDICTORS UPSTREAM TO ALL PHASES OF RESEARCH AND DEVELOPMENT AND ESTIMATE THE MARKET IMPACT OF SPECIFIC IDEAS, INVESTMENTS, INDIVIDUALS, TEAMS, AND ORGANIZATIONS. PARTNERS INCLUDE 21 PUBLIC AND PRIVATE UNIVERSITIES ACROSS 13 STATES, 1 NATIONAL LAB, 2 PRIVATE ORGANIZATIONS, AND 1 ASSOCIATION. OVERALL, THIS INTEGRATED RESEARCH-TO-MARKET DATA PIPELINE AND NEW MODELS AIMS TO TRANSFORM THE ABILITY TO ASSESS, PREDICT, AND ACCELERATE TECHNOLOGICAL PROGRESS. NEW KNOWLEDGE OF HOW UPSTREAM R&D AND INVESTMENTS ADVANCE DOWNSTREAM TECHNOLOGY OUTCOMES WILL BE REALIZED ALONGSIDE NEW ABILITIES TO IDENTIFY BOTTLENECKS AND OPPORTUNITIES TO MULTIPLY AND ACCELERATE THE SOCIETAL IMPACT OF R&D AND INVESTMENTS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

PATHOGENESIS OF REBOUND SIV/HIV VIREMIA AFTER ANTIRETROVRAL THERAPY

CENTRAL PAIN MECHANISMS, PAIN INTENSITY AND DRUG RESPONSE IN RHEUMATOID ARTHRITIS

CHRONIC RHINOSINUSITIS INTEGRATIVE STUDIES PROGRAM (CRISP)

MULTI-INSTITUTIONAL PHASE 2/3 TRIAL OF FRESH FROZEN PLASMA (FFP) IN PATIENTS WITH MODERATE TO SEVERE TRAUMATIC BRAIN INJURY (TBI)

ARMCADA - ADVANCING RELIABLE MEASUREMENT IN COGNITIVE AGING AND DECISION-MAKING ABILITY - WITH AGE COMES INCREASING EMPHASIS ON MAKING HIGHLY CONSEQUENTIAL, LONG TERM AND VARIED DECISIONS, RANGING FROM MEDICAL TO FINANCIAL TO LEGAL, AND BEYOND. THESE DECISIONS UNDERLIE THE BASIC COMPETENCIES FOR INDEPENDENT LIVING. COGNITIVE IMPAIRMENT OFTEN HINDERS BASIC DECISION-MAKING CAPACITIES, SIGNIFICANTLY IMPACTING QUALITY OF LIFE. DEFICITS IN DECISION-MAKING CAPACITY SADLY OFTEN LEAD TO HARMFUL CONSEQUENCES INCLUDING FINANCIAL LOSS, INCAPACITY TO CONSENT TO MEDICAL PROCEDURES, AND EVEN VULNERABILITY FOR ELDER ABUSE. THERE IS GROWING EVIDENCE THAT EARLY SCREENING OF DECISION-MAKING CAPACITY CAN BE AN IMPORTANT INDICATOR OF EARLY AGE-RELATED COGNITIVE IMPAIRMENT RELATED TO ALZHEIMER’S DISEASE AND ALZHEIMER’S DISEASE-RELATED DEMENTIAS (AD/ADRD). YET, DESPITE A 2020 UNITED STATES PREVENTIVE SERVICES TASK FORCE REPORT POINTING TO THE IMPORTANCE OF EARLY ASSESSMENT AND DETECTION OF SUCH FUNCTIONAL OUTCOMES FOR OLDER ADULTS, CAREGIVERS, AND FAMILIES, COGNITIVE IMPAIRMENT SCREENING TYPICALLY DOES NOT INCLUDE SYSTEMATIC AND COMPREHENSIVE ASSESSMENT OF DECISION-MAKING CAPACITY. WE WILL ESTABLISH THE ADVANCING RELIABLE MEASUREMENT IN COGNITIVE AGING AND DECISION-MAKING ABILITY (ARMCADA) RESEARCH NETWORK AND INTEGRATE EFFORTS TO ADAPT, DEVELOP, VALIDATE AND NORM MEASURES TO ASSESS DECISION-MAKING FUNCTIONALITY IN AN AGING POPULATION. OUR NORTHWESTERN UNIVERSITY TEAM HAS EXTENSIVE EXPERIENCE IN DEVELOPING NATIONAL RESEARCH NETWORKS FOR THE PURPOSE OF ASSESSMENT SYSTEM DEVELOPMENT, VALIDATION AND DISTRIBUTION, INCLUDING THE ORIGINAL NIH NEUROSCIENCE BLUEPRINT CONTRACT TO CREATE THE NIH TOOLBOX FOR ASSESSMENT OF NEUROLOGICAL AND BEHAVIORAL FUNCTION® (NIHTB). WE WILL LEVERAGE THIS EXPERTISE TO COMPLETE THREE SPECIFIC AIMS: THE PROPOSED PROJECT WILL 1) CREATE THE ARMCADA RESEARCH NETWORK WITH THE GOAL OF ADVANCING A THEORETICAL TAXONOMY OF DECISION-MAKING SKILLS FOR SUCCESSFUL AGING; 2) IDENTIFY, SYNTHESIZE, CREATE, AND VALIDATE NEW MEASURES OF DECISION-MAKING IN AN AGING SAMPLE REPRESENTATIVE OF THE ENTIRE RANGE OF DECISION-MAKING CAPACITY LEVELS AND OLDER ADULTS FROM MINORITY BACKGROUNDS; 3) FACILITATE SCALABLE NATIONWIDE PUBLIC DISSEMINATION OF THESE MEASURES, INCLUDING INTEGRATION INTO ELECTRONIC HEALTH RECORD SYSTEMS, TO BENEFIT THE EARLY IDENTIFICATION OF OLDER ADULTS WITH COGNITIVE IMPAIRMENT AND EVALUATE THE EFFICACY OF POTENTIAL INTERVENTIONS AIMED TO MITIGATE COGNITIVE DECLINE COMMONLY ASSOCIATED WITH AD/ADRD.

TRAINING PROGRAM IN LUNG BIOLOGY

UNRAVELING THE MECHANISMS OF HIV PERSISTENCE AND REBOUND - PROJECT SUMMARY/ABSTRACT (OVERALL) THE PERSISTENCE OF HIV INFECTION DESPITE LONG TERM SUPPRESSION OF VIREMIA BY CART CONSTITUTES THE MAJOR OBSTACLE TO HIV CURE. THIS IS UNFORTUNATELY TRUE EVEN FOR PATIENTS INITIATED ON CART DURING ACUTE INFECTION. THUS, LONG-TERM PERSISTENT HIV RESERVOIRS ARE SEEDED RAPIDLY POST INFECTION, AND THIS WAS CONFIRMED IN THE NONHUMAN PRIMATE (NHP) MODEL OF HIV. IN ADDITION, DATA FROM SEVERAL GROUPS AND OURS STRONGLY SUGGEST THAT RESIDUAL VIRAL REPLICATION IS ONGOING DESPITE IN TISSUES DESPITE FULL SUPPRESSION OF VIREMIA BY CART. OUR ON-GOING STUDIES INVESTIGATE THE “ECLIPSE PHASE” OF VIRAL REBOUND IN THE NHP MODEL AFTER CART INTERRUPTION. THIS “ECLIPSE PHASE” IS KEY TO UNDERSTAND THE REBOUND PROCESS SINCE THE VIRUS IS SPREADING IN TISSUES BEFORE VIREMIA AND IT IS INFLUENCED BY ADAPTIVE AND INNATE RESPONSES AS WELL AS THE HOST MICROENVIRONMENT. IN OUR STUDIES OF EARLY (4 DAYS POST- INFECTION) CART INITIATION, OUR INNOVATIVE SIV-ENV IMMUNOPET-CT GUIDED ANALYSIS AND SAMPLING LED TO SEVERAL IMPORTANT, SOMETIMES UNEXPECTED FINDINGS: 1) WE DETECTED SIV EXPANSION THROUGHOUT THE ENTIRE HOST FOR >1 WEEK POST CART INITIATION, WITH SIGNAL DECREASING THEREAFTER; 2) EVEN AFTER 6-8 MONTHS OF CART, IMMUNOPET/CT WAS SENSITIVE ENOUGH TO DETECT RESIDUAL VIRAL (PROTEIN) SIGNAL IN TISSUES IN SPITE OF UNDETECTABLE VIREMIA IN THE BLOOD; 3) UPON ART INTERRUPTION, VIRAL SIGNALS REBOUNDED AS EARLY AS 4 DAYS POST CART INTERRUPTION (ATI) BUT ALSO 2 WEEKS BEFORE DETECTION OF VIRUS IN PLASMA; 4) ANALYSIS OF THE TISSUES COLLECTED AT REBOUND THROUGH OUR PET-CT GUIDED NECROPSY WORKFLOW SURPRISINGLY SHOWED THAT THE MAJORITY OF INFECTED CELLS WERE OF MYELOID CELLS. AFTER EXTENSIVE ANALYSIS, THESE CELLS REVEALED TO BE MAST CELLS (MC), A PREDOMINANTLY TISSUE RESIDENT GRANULOCYTES THAT WE DEMONSTRATE EXPRESSES CD4 AND CCR5. BY TEAMING UP WITH A LOCAL MC EXPERT, WE WERE ABLE TO DEMONSTRATE THAT PRIMARY TISSUE MC ARE SUSCEPTIBLE TO HIV INFECTION IN VITRO AND THEIR SUSCEPTIBILITY AND ABILITY TO SUPPORT VIRAL REPLICATION IS HEAVILY INFLUENCED BY ENVIRONMENTAL STIMULI. IN THIS PPG, WE WILL LEVERAGE SEVERAL IMPORTANT INSIGHTS AND INNOVATIVE TECHNIQUES DEVELOPED DURING OUR CURRENT PPG TO INVESTIGATE THE HYPOTHESIS THAT MC CONTRIBUTE TO HIV PERSISTENCE IN TISSUES DURING CART AND/OR CONTRIBUTE TO VIRAL REBOUND UPON CART INTERRUPTION. MOREOVER, WE WILL CLARIFY VIRUS-HOST DYNAMICS THROUGH PHYLOANATOMICAL ANALYSIS OF VIRAL POPULATIONS IN TISSUES USING TISSUES AND CELLS ISOLATED THROUGH OUR INNOVATIVE PET-CT GUIDED SAMPLING WORKFLOW. THESE TISSUES WILL BE IDENTIFIED ALSO THROUGH THE ANALYSIS OF ADDITIONAL FEATURES OF “REBOUND TISSUES” THAT WE HAVE RECOGNIZED THROUGH OUR CURRENT STUDIES. THIS PPG COMPRISES OF 3 INDEPENDENT, ALTHOUGH HIGHLY INTERCONNECTED PROJECTS, 1 SCIENTIFIC NHP CORE AND 1 ADMINISTRATIVE CORE. THE 3 PROJECTS WILL ALL USE IN DIFFERENT WAYS TISSUES FROM THE NHP STUDIES AS WELL AS RESOURCES UNIQUE TO EACH PROJECT AND WILL ADDRESS DIFFERENT ALTHOUGH COMPLEMENTARY QUESTIONS WITH THE ULTIMATE GOAL TO DISSECT THE MECHANISMS OF HIV PERSISTENCE AND REBOUND.

IMPLEMENTATION AND EVALUATION OF AN EXPANDED BILINGUAL ELECTRONIC SYMPTOM MANAGEMENT PROGRAM ACROSS A MULTI-SITE, FULLY-INTEGRATED COMPREHENSIVE CANCER CENTER

INSTITUTE FOR ENVIRONMENTAL CATALYSIS

MECHANISMS OF AGING AND DEMETINA TRAINING PROGRAM

NCLT: A CENTER TO DEVELOP NANOSCALE SCIENCE AND ENGINEERING EDUCATORS WITH LEADERSHIP CAPABILITIES

THE MECHANICAL BASIS OF PRIMARY OPEN ANGLE GLAUCOMA

USING SIGLECS AND THEIR LIGANDS TO TREAT ALLERGIC DISEASES SALTAD

CONDUCTIVE DNA SYSTEMS AND MOLECULAR DEVICES

CREATING AND INTERFACING DESIGNER CHEMICAL QUBITS

ENGINEERING CAREER DEVELOPMENT CENTER IN MOVEMENT AND REHABILITATION SCIENCES

A NOVEL TOOLBOX FOR RAPID, ON DEMAND, IN VITRO GLYCOPROTEIN SYNTHESIS

NORTHWESTERN GENOMIC RISK ASSESSMENT AND MANAGEMENT PROGRAM

DISORDERED TISSUE BIOMECHANICS AS A DRIVER OF ESOPHAGEAL DISEASE

CENTER OF EXCELLENCE FOR ADVANCED BIOPROGRAMMABLE NANOMATERIALS (C-ABN)

NOVEL BIOPHOTONICS METHODOLOGY FOR COLON CANCER SCREENING

NORTHWESTERN UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE (NUCATS)

9/24- HEALTHY BRAIN AND CHILD DEVELOPMENT NATIONAL CONSORTIUM - PROJECT SUMMARY/ABSTRACT NEURODEVELOPMENTAL PROCESSES ARE SHAPED BY DYNAMIC INTERACTIONS BETWEEN GENES AND ENVIRONMENTS. MALADAPTIVE EXPERIENCES EARLY IN LIFE CAN ALTER DEVELOPMENTAL TRAJECTORIES, LEADING TO HARMFUL AND ENDURING DEVELOPMENTAL SEQUELAE. PRE- AND POSTNATAL HAZARDS INCLUDE MATERNAL SUBSTANCE EXPOSURE, TOXICANT EXPOSURES IN PREGNANCY AND EARLY LIFE, MATERNAL HEALTH CONDITIONS, PARENTAL PSYCHOPATHOLOGY, MALTREATMENT, STRUCTURAL RACISM, AND EXCESSIVE STRESS. TO ELUCIDATE HOW VARIOUS ENVIRONMENTAL HAZARDS IMPACT CHILD DEVELOPMENT, IT IS IMPERATIVE THAT A NORMATIVE TEMPLATE OF DEVELOPMENTAL TRAJECTORIES OVER THE FIRST 10 YEARS OF LIFE BE ESTABLISHED BASED ON A SUFFICIENTLY LARGE AND DEMOGRAPHICALLY DIVERSE SAMPLE OF THE US POPULATION. TO ACCOMPLISH THIS, THE HEALTHY BRAIN AND CHILD DEVELOPMENT NATIONAL CONSORTIUM (HBCD-NC) HAS BEEN FORMED TO DEPLOY A HARMONIZED, OPTIMIZED, AND INNOVATIVE SET OF NEUROIMAGING (MRI, EEG) MEASURES COMPLEMENTED BY AN EXTENSIVE BATTERY OF BEHAVIORAL, PHYSIOLOGICAL, AND PSYCHOLOGICAL TOOLS, AND BIOSPECIMENS TO UNDERSTAND NEURODEVELOPMENTAL TRAJECTORIES IN A SAMPLE OF 7,500 MOTHERS AND INFANTS ENROLLED AT 24 SITES ACROSS THE UNITED STATES (US). THE HBCD-NC WILL CARRY OUT A COMMON RESEARCH PROTOCOL UNDER DIRECTION OF THE HBCD-NC ADMINISTRATIVE CORE (HCAC) AND WILL ASSEMBLE AND DISTRIBUTE A COMPREHENSIVE AND WELL-CURATED RESEARCH DATASET TO THE SCIENTIFIC COMMUNITY AT LARGE UNDER THE DIRECTION OF THE HBCD-NC DATA COORDINATING CENTER (HDCC). THE OVERARCHING GOAL OF THE HBCD-NC IS TO CREATE A COMPREHENSIVE, HARMONIZED, AND HIGH- DIMENSIONAL DATASET THAT WILL CHARACTERIZE TYPICAL NEURODEVELOPMENTAL TRAJECTORIES IN US CHILDREN AND THAT WILL ASSESS HOW BIOLOGICAL AND ENVIRONMENTAL EXPOSURES AFFECT THOSE TRAJECTORIES. A SPECIAL EMPHASIS WILL BE PLACED ON UNDERSTANDING THE IMPACT OF PRE- AND POSTNATAL EXPOSURE TO OPIOIDS, MARIJUANA, ALCOHOL, TOBACCO AND/OR OTHER SUBSTANCES. TO ADDRESS THESE BROAD OBJECTIVES, THE SAMPLE OF WOMEN ENROLLED WILL INCLUDE: 1) A RACIALLY, ETHNICALLY, AND SOCIOECONOMICALLY DIVERSE COHORT THAT IS REPRESENTATIVE OF THE US POPULATION; 2) PREGNANT WOMAN WITH USE OF TARGETED SUBSTANCES (OPIOIDS, MARIJUANA, ALCOHOL, TOBACCO); AND 3) DEMOGRAPHICALLY AND BEHAVIORALLY SIMILAR WOMEN WITHOUT SUBSTANCE USE IN PREGNANCY TO ENABLE VALID CAUSAL INFERENCES. IN ADDITION, THE HBCD-NC WILL IDENTIFY KEY DEVELOPMENTAL WINDOWS DURING WHICH BOTH HARMFUL AND PROTECTIVE ENVIRONMENTS HAVE THE MOST INFLUENCE ON LATER NEURODEVELOPMENTAL OUTCOMES. THE LARGE, MULTI-MODAL, LONGITUDINAL, AND GENERALIZABLE DATASET THAT WILL BE PRODUCED FOR THE FIRST TIME BY THIS STUDY WILL PROVIDE NOVEL INSIGHTS INTO CHILD DEVELOPMENT USING STATE- OF-THE-ART METHODS. THE HBCD-NC STUDY WILL INFORM PUBLIC POLICY TO IMPROVE THE HEALTH AND DEVELOPMENT OF CHILDREN ACROSS THE NATION.

METALLOENZYMES AND METAL HOMEOSTASIS

A FAMILY-GENETIC STUDY OF LANGUAGE IN AUTISM

ILLINOIS PRECISION MEDICINE CONSORTIUM (IPMC)

STIMULI-RESPONSIVE CONTROL OF PROTEIN-BASED MOLECULAR STRUCTURE

THE CLAUDE D. PEPPER OLDER AMERICANS INDEPENDENCE CENTER (OAIC) AT NORTHWESTERN UNIVERSITY

GMP PRODUCTION AND EXTENDED TOXICOLOGY OF AN ORAL FORMULATION DRUG FOR ALZHEIMER'S DISEASE - ABSTRACT ALZHEIMER’S DISEASE (AD) AND RELATED DEMENTIAS ARE A MAJOR GLOBAL PUBLIC HEALTH PROBLEM, PREDICTED TO INCREASE DRAMATICALLY OVER THE NEXT DECADES. EFFECTIVE THERAPIES TO PREVENT, CURE, OR SLOW THE DISEASE PROGRESSION ARE LACKING. A DIVERSIFIED PORTFOLIO OF NEW THERAPEUTIC STRATEGIES WITH DISCRETE PHARMACOLOGICAL FUNCTION IS URGENTLY NEEDED. WE PROPOSE REPOSITIONING OF AN EXISTING ACUTE BRAIN INJURY CLINICAL CANDIDATE, MW189, NOW IN PHASE 2 CRITICAL CARE MEDICINE TESTING FOR HEMORRHAGIC STROKE. REPOSITIONING OF THERAPEUTIC CANDIDATES IN CLINICAL DEVELOPMENT, OR REPURPOSING OF APPROVED DRUGS, ARE GENERALLY CONSIDERED FASTER AND MORE EFFICIENT APPROACHES THAN DE NOVO CNS DRUG DISCOVERY AND DEVELOPMENT. CAVEATS INCLUDE THE LOWER SUCCESS RATES WHEN DONE ACROSS DISEASE INDICATIONS (E.G., ONCOLOGY TO NEUROLOGY) VS WITHIN THE SAME DISEASE INDICATION. REPOSITIONING OF MW189 WILL USE AN EXISTING CNS DRUG DEVELOPMENT PORTFOLIO AND RESEARCH INFRASTRUCTURE. DELIVERABLES WILL ALLOW RAPID TRANSITION TO CLINICAL EVALUATION IN AD PATIENTS. MW189 IS A CNS-PENETRANT, SMALL MOLECULE THAT SELECTIVELY ATTENUATES STRESSOR-INDUCED CHANGES IN DYSREGULATED CYTOKINE PRODUCTION. THE RESULTANT PATHOPHYSIOLOGY CONTRIBUTES TO SYNAPTIC DYSFUNCTION, NEURODEGENERATION AND COGNITIVE DECLINE IN DIVERSE DISEASES. MW189 HAS NO LIABILITIES IN IND-ENABLING PRECLINICAL SAFETY PHARMACOLOGY AND TOXICOLOGY AND SUCCESSFULLY COMPLETED THREE PHASE 1 CLINICAL STUDIES OF SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMIC END POINT ENGAGEMENT. MW189’S EXCELLENT PROFILE IN FDA GUIDED PRECLINICAL AND CLINICAL STUDIES PROVIDES A STRONG FOUNDATION FOR CONTINUED MW189 CLINICAL DEVELOPMENT IN OTHER CNS DISEASE AREAS. WE HYPOTHESIZE THAT MW189 IS A VIABLE CANDIDATE FOR DAILY ORAL TREATMENT OF DEMENTIA PATIENTS. WE PROPOSE STUDIES TO REMOVE THE REMAINING TECHNICAL AND REGULATORY BARRIERS TO MW189 ENTRY INTO FUTURE AD CLINICAL INVESTIGATIONS. AIM 1: PRODUCE GMP CLINICAL DRUG SUBSTANCE, DRUG PRODUCT, REFERENCE STANDARD AND INTERNAL STANDARD. GMP CLINICAL DRUG FOR ORAL ADMINISTRATION WILL BE FDA QUALITY COMPLIANT FOR PHASE 2 INDS AND WILL ADDRESS RECENT FDA NEW GUIDANCES ON ENHANCED DRUG QUALITY. AIM 2: PERFORM EXTENDED GLP TOXICOLOGY STUDIES IN RATS (6 MO) AND DOGS (9 MO) WITH RECOVERY PHASE AND TOXICOKINETICS. OUTCOMES WILL ALLOW FUTURE DAILY ORAL ADMINISTRATION TO AD PATIENTS AND PROVIDE REFINED DOSING PARAMETERS FOR LONGER TERM ADMINISTRATION. AIM 3: OBTAIN A PHASE 2 IND FOR FUTURE CLINICAL TRIALS IN EARLY AD AND RELATED DEMENTIAS. THIS FINAL MILESTONE WILL POSITION US TO IMMEDIATELY PROCEED TO A FUTURE PHASE 2A CLINICAL STUDY OF AD PATIENTS. SUCCESSFUL OUTCOMES FROM THE PROPOSED INVESTIGATIONS AND THE FOLLOW-ON CLINICAL TRIALS WILL IMPACT A NUMBER OF CNS DISORDERS WHERE CYTOKINE DYSREGULATION IS PART OF THE DISEASE PROGRESSION OR SUSCEPTIBILITY MECHANISM.

THE NEU-LUNG CONSORTIUM: NEUTROPHILIC MECHANISMS OF INFLAMMATION, INJURY, AND REPAIR IN LUNG AND AIRWAYS DISEASES - PROJECT SUMMARY/ABSTRACT – OVERALL NEUTROPHILS ARE ABUNDANT IMMUNE CELLS THAT ARE RECRUITED FROM THE CIRCULATION IN RESPONSE TO INFLAMMATION, INFECTION, AND INJURY. IN THE LUNG AND AIRWAYS, NEUTROPHILS SERVE AS CRITICAL INNATE IMMUNE EFFECTORS OF THE HOST DEFENSE AGAINST PATHOGENS YET ALSO DRIVE SERIOUS AND IMPORTANT DISEASES WITH ENORMOUS

"ULTRAHIGH PERFORMANCE NANOANTENNAS FOR SURFACE ENHANCED RAMAN SPECTROSCOPY"

INTEGRATION OF FEEDING AND GLUCOSE METABOLISM BY THE CIRCADIAN GENE NETWORK

SLOW OUTWARD CURRENTS AND LEARNING IN AGING HIPPOCAMPUS

NEW COOPERATIVE AGREEMENT TITLED: THE ARMY SYNTHETIC BIOLOGY CENTER FOR PREDICTIVE MATERIALS DESIGN (PREMADE)

FUNCTIONALLY DEFINING HIV-HOST INTERACTIONS DURING THE EARLY HIV-1 LIFECYCLE

CORE CENTER FOR CLINICAL RESEARCH AT NORTHWESTERN UNIVERSITY

MECHANISTIC ANALYSIS OF GENETIC MODIFIERS IN PARKINSON'S DISEASE - SUMMARY I BELIEVE THAT COMBINING DISEASE GENE DISCOVERY APPROACHES WITH IN-DEPTH FOLLOW-UP MECHANISTIC AND FUNCTIONAL STUDIES IS A UNIQUE ASPECT OF MY RESEARCH PROGRAM. OUR RECENT DISCOVERY OF “HUMAN-SPECIFIC” PATHWAYS AND PHENOTYPES (COMPARED TO MICE) IN MIDBRAIN DA NEURONS HAS LED US TO FOCUS ON PATIENT-DERIVED DA NEURONS TO EXAMINE THE FUNCTION OF PD-LINKED GENES. BY EMPLOYING CO-CULTURES OF IPS-DERIVED NEURONS, MICROGLIA AND ASTROCYTES, WE WILL EXAMINE THE INTERPLAY OF CELL-AUTONOMOUS AND NO-CELL AUTONOMOUS PATHWAYS THAT LEAD TO DYSFUNCTION OF MIDBRAIN DA NEURONS IN PD. MOREOVER, WE WILL USE INNOVATIVE TECHNOLOGY TO SIMULTANEOUSLY EXAMINE A LARGE NUMBER OF GENETIC VARIANTS IN A POOLED IPS APPROACH THAT HAS NOT BEEN POSSIBLE PREVIOUSLY. FINALLY, OUR RECENT DISCOVERY OF DIRECT CONTACTS BETWEEN LYSOSOMES AND MITOCHONDRIAL HAS OPENED A COMPLETELY NEW OPPORTUNITY TO EXAMINE INTER- AND INTRA-ORGANELLAR DYNAMICS IN NEURODEGENERATION. THE R35 AWARD WOULD PROVIDE ME THE TIME, FREEDOM AND STABILITY TO BE EVEN MORE ADVENTUROUS AND, AS ALWAYS, FOLLOW THE MOST INTERESTING BIOLOGY TO HAVE A HIGH IMPACT ON THE FIELD.

NON-CODING RNAS AND THEIR MECHANISMS AND FUNCTIONS

COBOGLOBINS-COBALT-SUBSTITUTED HEMOGLOBINS AND MYOGLOBIN

CELLULAR MECHANISMS OF HIPPOCAMPAL NETWORK NEUROPLASTICITY GENERATED BY BRAIN STIMULATION

SPHERICAL NUCLEIC ACIDS FOR IN VIVO THERAPEUTICS

TRAINING GRANT IN SLEEP RESEARCH

FUNCTION OF BASAL SYNAPSES AT MAMMALIAN PHOTORECEPTORS

VASCULAR GROWTH AND REGENERATION

CENTER FOR REPRODUCTIVE RESEARCH AT NORTHWESTERN UNIVERSITY

MOLECULAR AND CELLULAR CHARACTERIZATION OF ESSENTIAL HUMAN GENES. - WE PROPOSE TO GENERATE BARCODED AND CONDITIONAL NULL ALLELES IN A CELLULAR SYSTEM THAT CAN MODEL EARLY HUMAN DEVELOPMENT AND A BROAD RANGE OF HUMAN DISEASES. WE WILL ESTABLISH A DATA PRODUCTION RESEARCH AND DEVELOPMENT CENTER IN RESPONSE TO THE RFA-HG-21-029: MOLECULAR PHENOTYPES OF NULL ALLELES IN CELLS (MORPHIC) PHASE 1, WHICH AIMS TO ESTABLISH A CATALOG OF MOLECULAR AND CELLULAR PHENOTYPES OF NULL ALLELES FOR ULTIMATELY EVERY HUMAN GENE, USING IN VITRO MULTICELLULAR SYSTEMS. OUR CENTER WILL UTILIZE A CHEMICALLY INDUCIBLE AND REVERSIBLE SYSTEM THAT ENABLES THE RAPID DEPLETION OF TARGET PROTEINS. THE APPROACH PERMITS TEMPORAL CONTROL OF PROTEIN LEVELS TO STUDY THE CONSEQUENCES OF NULL ALLELES. WE WILL UTILIZE A SUPER SENSITIVE DEGRON THAT RAPIDLY DEGRADES THE TARGET PROTEIN OF INTEREST IN RESPONSE TO A LOW DOSE OF AUXIN, A CELL MEMBRANE DIFFUSIBLE SMALL CHEMICAL PLANT HORMONE. WE WILL COMBINE CRISPR-BASED TARGETED LOCUS ENGINEERING TO HOMOZYGOUS KNOCK-IN A MINI AUXIN-INDUCIBLE DEGRON (MAID) AT THE END OF THE TARGE GENE TO CREATE A CHEMICALLY CONTROLLABLE SWITCH TO CREATE NULL-ALLELES IN AN OPEN-ACCESS HUMAN INDUCED PLURIPOTENT STEM (HIPSC) CELL, WHICH CAN BE DIFFERENTIATED INTO VARIOUS CELL LINEAGES AND MULTICELLULAR ORGANOIDS TO MODEL HUMAN DEVELOPMENT AND DISEASES. NOTABLY, EACH AID-DEGRON WILL ALSO CONTAIN GENE-SPECIFIC BARCODES, ALLOWING TRACKING THE FATE OF HUNDREDS OF THOUSANDS OF NULL ALLELES WHEN THESE ENGINEERED NULL ALLELES ARE POOLED. THE PROPOSED APPROACH IS GENERALIZABLE AND CAN RAPIDLY DEPLETE TARGET PROTEINS CODDED BY VARIOUS CLASSES OF HUMAN GENES. OUR STRATEGY WILL BE PARTICULARLY ADVANTAGEOUS AND CRITICAL TO STUDY THE NULL PHENOTYPES OF ESSENTIAL GENES, WHICH CANNOT BE STUDIED BY CHRONIC DEPLETION USING GENETIC APPROACHES (SUCH AS CRISPR KO) BECAUSE THE KNOCK-IN RESULTS IN CELL DEATH. THEREFORE, TO HIGHLIGHT THE UTILITY OF OUR STRATEGY, WE PRIORITIZE CREATING NULL ALLELES BY CRISPR MEDIATED KNOCK-IN PROCESS TO INTRODUCE BARCODED AID DEGRON IN 250 ESSENTIAL GENES. WE CHOSE GENES IMPLICATED IN HUMAN DISEASES AND SUBVIABLE PHENOTYPES IN THE INTERNATIONAL MOUSE PHENOTYPING CONSORTIUM (IMPC). WE PROPOSE TO CATALOG THE CELLULAR PHENOTYPES (SURVIVAL, PROLIFERATION, MITOTIC FUNCTION, AND DIFFERENTIATION) AND MOLECULAR PHONOTYPES, INCLUDING GENE EXPRESSION AND CHROMATIN ACCESSIBILITY FOR SELECT NULL ALLELES. THIS INFORMATION WILL PROVIDE UNIQUE INSIGHTS INTO THE BIOLOGICAL FUNCTION OF THESE DEVELOPMENTALLY CRITICAL GENES. IT WILL HIGHLIGHT THE UTILITY OF ESTABLISHING THE CHEMICALLY INDUCIBLE DEGRON SYSTEM AS A GENERALIZABLE STRATEGY FOR THE GOALS OF THE MORPHIC CONSORTIUM. THE CREATED BARCODED AND CONDITIONAL NULL ALLELE RESOURCE WILL PROVIDE A UNIQUE OPPORTUNITY TO TEMPORALLY CONTROL THE TIMING OF NULL ALLELES IN PLURIPOTENT STEM STATE AND VARIOUS TERMINALLY DIFFERENTIATED CELL TYPES OR MULTICELLULAR ORGANOID SYSTEMS THAT CAN BE GENERATED FROM THE PLURIPOTENT STEM CELLS.

INTEGRATED EMPIRICAL AND TRANSLATIONAL RESEARCH TO DIVERSIFY THE SCIENTIFIC WORKFORCE

A PRIMATE MODEL OF AN INTRA-CORTICALLY CONTROLLED FES PROSTHESIS FOR GRASP

TOOLBOX DETECT: LOW COST DETECTION OF COGNITIVE DECLINE IN PRIMARY CARE SETTINGS

CONTRIBUTIONS OF STRESS REACTIVITY TO RISK OF ALZHEIMER'S DISEASE AND RELATED DEMENTIA'S IN A COMMUNITY-BASED COHORT - RACIAL/ETHNIC MINORITY ADULTS ARE AT HIGHER RISK FOR ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (ADRD). MOREOVER, MINORITY ADULTS ARE NOT ONLY EXPOSED TO MORE INTENSE AND FREQUENT STRESSFUL SITUATIONS IN THEIR DAILY LIVES BUT THEY ALSO HAVE FEWER RESOURCES TO MANAGE THESE SITUATIONS IN HEALTHY WAYS. LIMITED RESOURCES AMONG THESE ADULTS MAY LEAD TO IMPAIRED PHYSIOLOGIC STRESS RESPONSES (I.E., STRESS REACTIVITY), SPECIFICALLY DYSREGULATION OF THE SYMPATHETIC NERVOUS SYSTEM AND THE HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL (HPA) AXIS. OUR UNDERSTANDING OF THE IMPACT OF STRESS REACTIVITY ON ADRD RISK COMES FROM ANIMAL STUDIES AND EXPERIMENTS IN HUMANS USING CONTROLLED, LABORATORY STRESSORS. THIS IS A MAJOR LIMITATION BECAUSE LABORATORY STRESSORS CANNOT CAPTURE THE VARIETY, SEVERITY, OR DURATION OF STRESSORS THAT INDIVIDUALS FACE IN THEIR DAILY LIVES. THUS, THERE REMAINS A NEED TO MORE RIGOROUSLY EVALUATE RELATIONSHIPS OF STRESS REACTIVITY WITH ADRD RISK IN NATURAL SETTINGS. WE PROPOSE TO FILL THIS CRITICAL GAP IN THE LITERATURE BY ADDING MORE PERSONALIZED AND OBJECTIVE INDICATORS OF STRESS AND STRESS REACTIVITY TO A LONGSTANDING COMMUNITY-BASED COHORT, THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA). WE WILL USE EXISTING GENE EXPRESSION DATA TO CALCULATE A MOLECULAR MARKER OF THE PHYSIOLOGIC RESPONSE TO CHRONIC EXPOSURE TO ADVERSITY. WE WILL ALSO COLLECT REPEATED MEASUREMENTS OF STRESSFUL EXPERIENCES, NEGATIVE AFFECT (EMOTIONS), AND HEART RATE IN ORDER TO DEVELOP PARTICIPANT-SPECIFIC MARKERS OF AFFECTIVE AND AUTONOMIC STRESS REACTIVITY, RESPECTIVELY. OUR OVERALL GOAL IS TO USE THESE MEASURES TO EXAMINE ASSOCIATIONS OF THE BODY'S RESPONSE TO STRESSFUL EXPERIENCES WITH RISK OF ADRD IN A NATURAL SETTING. WE WILL LEVERAGE EXISTING AND ONGOING REPEATED ASSESSMENTS OF COGNITIVE FUNCTION AS WELL AS ONGOING ASSESSMENTS OF NEUROIMAGING BIOMARKERS OF BOTH VASCULAR AND AD PATHOLOGY INCLUDING CEREBRAL BLOOD FLOW (CBF), WHITE MATTER HYPERINTENSITIES, ASS DEPOSITION, AND GRAY MATTER VOLUME LOSS. OUR PROPOSED STUDY WILL ALLOW US TO BEGIN TO DISENTANGLE THE PATHWAYS THROUGH WHICH STRESS EXPOSURE AND STRESS REACTIVITY IMPACT VASCULAR DEMENTIA PATHOLOGY AND/OR AD POSITIVITY. FINDINGS WILL INFORM STRESS MANAGEMENT INTERVENTIONS AND PRECISION MEDICINE INITIATIVES DESIGNED TO PREVENT ADRD AND/OR SLOW ITS PROGRESSION.

MENTORING FOR SUCCESS: DEVELOPING FUNDAMENTAL SKILLS FOR BIOMEDICAL RESEARCH

MICROTUBULE MOTORS, CYTOSKELETAL ORGANIZATION AND CELL POLARITY

EFFECTIVENESS OF RELATIONSHIP EDUCATION FOR REDUCING HIV INCIDENCE IN MEN WHO HAVE SEX WITH MEN - MEN WHO HAVE SEX WITH MEN (MSM) ARE DISPROPORTIONATELY IMPACTED BY HIV IN THE UNITED STATES. YOUNG MSM (YMSM), PARTICULARLY YMSM OF COLOR, HAVE THE HIGHEST HIV INCIDENCE OF ANY GROUP. DESPITE THE PERCEIVED SAFETY OF ROMANTIC RELATIONSHIPS, MAIN PARTNERSHIPS ACCOUNT FOR A LARGE PROPORTION OF NEW HIV INFECTIONS IN MSM (35-68%), AND THIS PROPORTION IS MUCH HIGHER AMONGST YMSM. MSM SUBSTANTIALLY REDUCE CONDOM AND PREP USE UPON ENTRY INTO A RELATIONSHIP, DESPITE CONTINUED HIGH RISK FOR MANY COUPLES. HOWEVER, HEALTHY ROMANTIC RELATIONSHIPS PROVIDE MYRIAD BENEFITS TO INDIVIDUAL HEALTH AND WELLBEING. THUS, WE CREATED 2GETHER, WHICH INTEGRATES EVIDENCE-BASED RELATIONSHIP EDUCATION (E.G., COMMUNICATION, CONFLICT RESOLUTION) AND HIV PREVENTION (E.G., MONOGAMY/NON-MONOGAMY AGREEMENTS, BEHAVIORAL/BIOMEDICAL PREVENTION), TO OPTIMIZE RELATIONSHIP FUNCTIONING AND REDUCE HIV RISK IN MALE COUPLES. 2GETHER DEMONSTRATED EVIDENCE OF FEASIBILITY AND ACCEPTABILITY, AS WELL AS PRELIMINARY EFFECTS ON HIV RISK BEHAVIORS AND RELATIONSHIP FUNCTIONING, IN A PILOT TRIAL. WE HAVE ALSO ADAPTED 2GETHER FOR ONLINE ADMINISTRATION, CONSISTING OF 3 ONLINE DIDACTIC SKILLS MODULES AND 2 VIDEOCONFERENCE-BASED SKILLS COACHING SESSIONS, AND ARE EVALUATING ITS EFFICACY IN A RANDOMIZED TRIAL. DESPITE ITS PROMISE, WE HAVE IDENTIFIED SEVERAL CRITICAL GAPS IN COUPLE-BASED HIV PREVENTION: 1) LIVE SKILLS COACHING IS BURDENSOME AND NOT COST-EFFECTIVE, 2) MANY PARTNERED MSM ARE UNABLE TO ENROLL PARTNERS AND ARE THUS EXCLUDED, AND 3) NEWER, HIGH RISK RELATIONSHIPS RARELY ENROLL IN TRIALS, SO WE NEED TO DELIVER RELATIONSHIP SKILLS TO SINGLE MSM BEFORE RELATIONSHIP INITIATION. OUR GOAL IS TO UPGRADE 2GETHER INTO A SCALABLE AND TAILORED INTERVENTION PACKAGE FOR BOTH SINGLE AND PARTNERED MSM, CONSISTING OF: 1) A STANDALONE RELATIONSHIP EDUCATION AND HIV PREVENTION EHEALTH PROGRAM (“ERE”) FOR SINGLE AND PARTNERED MSM, AND 2) TWO ADDITIONAL DYADIC SKILLS COACHING SESSIONS (FOR MSM PARTICIPATING AS DYADS ONLY). AIM 1: EVALUATE THE IMPACT OF THE TAILORED 2GETHER INTERVENTION PACKAGE ON HIV INCIDENCE IN MSM. WE WILL ENROLL 5,000 HIV-NEGATIVE MSM TO TEST EFFECTIVENESS OF THE ENTIRETY OF THE 2GETHER TAILORED INTERVENTION PACKAGE ON HIV INCIDENCE AT 24-MONTHS POST-INTERVENTION RELATIVE TO CONTROL. WE WILL ALSO EXPLORE EFFECTS OF PARTICULAR TAILORED ELEMENTS: (A) EXAMINE DIFFERENTIAL EFFECTIVENESS BETWEEN SINGLE AND PARTNERED MSM; (B) AMONG PARTNERED MSM, ANALYZE THE ADDITIVE BENEFIT OF DYADIC SKILLS COACHING SESSIONS BEYOND THE AUTOMATED ERE PROGRAM. AIM 2: EXPLORE DIFFERENTIAL EFFECTS ACROSS TREATMENT ARMS AMONG SUBGROUPS OF MSM. WE WILL EXPLORE DIFFERENTIAL EFFECTS ACROSS TREATMENT ARM BY AGE, RACE/ETHNICITY, RURALITY, AND TRANSGENDER EXPERIENCE. AIM 3: RESEARCH THE IMPLEMENTATION OF 2GETHER NATIONALLY TO INFORM SCALE OUT AND DETERMINE COST. EMPLOYING A HYBRID TYPE 1 EFFECTIVENESS–IMPLEMENTATION TRIAL DESIGN, WE WILL USE MIXED METHODS TO IDENTIFY FACILITATORS AND BARRIERS TO IMPLEMENTATION. WE WILL MEASURE KEY IMPLEMENTATION DETERMINANTS AND OUTCOMES THROUGH IN-DEPTH INTERVIEWS WITH NATIONAL STAKEHOLDERS TO INFORM FUTURE IMPLEMENTATION STRATEGIES, AND CONDUCT COST ANALYSIS TO ESTIMATE COST OF PROGRAM IMPLEMENTATION.

COMPREHENSIVE CARDIAC STRUCTURE-FUNCTION ANALYSIS IN HEART TRANSPLANTATION

USING TEMPORAL PHASE SIGNATURES TO PREDICT AND CONTROL BIOLOGICAL TIMING

ROLE OF KALIRIN-7 AND RAC1 IN SYNAPTIC PLASTICITY

MITOCHONDRIAL METABOLISM AND ROS REGULATE CANCER

RESEARCH CAREER DEVELOPMENT IN OBSTETRICS AND GYNECOLOGY

APPROACHES TO INTERGRATED PHOTOCHEMICAL SYSTEMS FOR SOLAR ENERGY CONVERSION

IMPROVING PATIENT REPORTED OUTCOME DATA FOR RESEARCH THROUGH SEAMLESS INTEGRATION OF THE PROMIS TOOLKIT INTO EHR WORKFLOWS

UNDERSTANDING THE CELLULAR BASIS OF MOVEMENT DISORDERS

CARCINOGENESIS TRAINING PROGRAM

PRECLINICAL ALZHEIMERS DISEASE DRUG DEVELOPMENT OF NOVEL MAPK INHIBITORS

PRIMARY CARE DETECTION OF COGNITIVE IMPAIRMENT LEVERAGING HEALTH AND CONSUMER TECHNOLOGIES IN UNDERSERVED COMMUNITIES: THE MYCOG TRIAL - WE SEEK TO RENEW OUR CURRENT AWARD (UH3NS105562) AS PART OF THE DETECT CID CONSORTIUM AND CONDUCT A PRAGMATIC TRIAL TO TEST THE EFFECTIVENESS + FIDELITY OF OUR NIH TOOLBOX-DERIVED PARADIGM TO IMPROVE EARLY DETECTION AND MANAGEMENT OF COGNITIVE IMPAIRMENT/DEMENTIA IN PRIMARY CARE SETTINGS SERVING HEALTH DISPARATE PATIENT POPULATIONS. EARLY IDENTIFICATION OF COGNITIVE IMPAIRMENT (CI), INCLUDING ALZHEIMER’S DISEASE (AD) AND RELATED DEMENTIAS (ADRD), IS A TOP PUBLIC HEALTH PRIORITY. YET IN PRIMARY CARE SETTINGS THAT MANAGE THE HEALTH OF THE MAJORITY OF COMMUNITY-DWELLING OLDER ADULTS, LESS THAN HALF OF PATIENTS WITH ANY CI ARE DETECTED AND/OR DIAGNOSED. AMONG COMMUNITY HEALTH CENTERS THAT SERVE MARGINALIZED PATIENTS - BY LOW SOCIOECONOMIC STATUS (SES), MINORITY RACE OR ETHNICITY - RATES OF DETECTION MAY BE FAR LOWER. THIS IS OF GREAT CONCERN, AS HISPANIC/LATINO (H/L) AND BLACK OLDER ADULTS ARE 1.5 TO 2 TIMES MORE LIKELY TO DEVELOP ADRD AND TO GO UNDETECTED/UNDIAGNOSED COMPARED TO NON-H/L WHITES. PRACTICAL, SCALABLE STRATEGIES ARE NEEDED TO HELP PRIMARY CARE PRACTICES BETTER DETECT AND MANAGE CI, ESPECIALLY THOSE CARING FOR MEDICALLY UNDERSERVED, LOW SES COMMUNITIES. SINCE 2017, OUR TEAM HAS BEEN A MEMBER OF THE NINDS DETECT CID CONSORTIUM; A NETWORK DEDICATED TO IMPROVING CLINICAL PARADIGMS FOR EARLY DETECTION OF CI AND ADRD AND ITS SUBSEQUENT MANAGEMENT IN EVERYDAY CLINICAL SETTINGS. HAVING DEVELOPED THE NIH TOOLBOX FOR ASSESSMENT OF NEUROLOGICAL AND BEHAVIORAL FUNCTION (CO-I: GERSHON, MPI: NOWINSKI) AND WITH EXPERTISE IN HEALTH SYSTEM RE-DESIGN FOR PATIENT-CENTERED CARE (MPI: WOLF), WE VALIDATED OUR OWN CLINICAL PARADIGM, KNOWN AS MYCOG. THIS INCLUDES A BRIEF, IPAD-BASED, SELF- ADMINISTERED, ELECTRONIC HEALTH RECORD (EHR)-LINKED STRATEGY TO ASSESS FOR CI DURING PRIMARY CARE VISITS WHEN CONCERNS ARE IDENTIFIED. IN RESPONSE TO RFA-NS-22-009, WE WILL PARTNER WITH A NATIONAL PRIMARY CARE PROVIDER (OAK STREET HEALTH) AND CONDUCT A 2-ARM, CLINIC-RANDOMIZED, PRAGMATIC TRIAL COMPARING MYCOG TO USUAL CARE. WE WILL FOCUS ON POPULATIONS EXPERIENCING CI/ADRD DISPARITIES: BLACK, H/L, AND LOW SES OLDER ADULTS. OUR SPECIFIC AIMS ARE TO: 1) TEST THE EFFECTIVENESS OF THE MYCOG PARADIGM TO IMPROVE EARLY DETECTION OF CI AND DEMENTIAS AMONG LOW SES, BLACK AND HISPANIC OLDER ADULTS; 2) INVESTIGATE THE PRESENCE OF DISPARITIES IN EARLY DETECTION OF CI, ITS DIAGNOSIS, AND RATE OF REFERRALS BY RACE AND ETHNICITY; 3) DETERMINE THE FIDELITY AND RELIABILITY OF MYCOG AND IDENTIFY ANY PATIENT, CAREGIVER, CLINICIAN, AND/OR HEALTH SYSTEM BARRIERS TO ITS OPTIMAL, SUSTAINED IMPLEMENTATION; 4) ASSESS THE COST-EFFECTIVENESS OF THE MYCOG PARADIGM FROM A PRIMARY CARE PERSPECTIVE. IMPACT: OUR FINDINGS WILL ADDRESS KNOWN DISPARITIES AND OFFER NEW EVIDENCE ON A COMPREHENSIVE, EHR-ENABLED, BILLABLE, SCALABLE, PRIMARY CARE PROTOCOL FOR EARLY DETECTION OF CI - INFORMING FUTURE WIDESPREAD DISSEMINATION.

CENTER FOR REPRODUCTIVE HEALTH AFTER DISEASE

THERAPEUTIC TARGETING OF MALIGNANT GLIOMA STEM CELLS

DICE - A NATURAL CANCER SURVEILLANCE MECHANISM - A NEW ROAD TO CANCER THERAPY

NOVEL PROTEIN AGGREGATION INHIBITORS AND UPPER MOTOR NEURON STABILIZERS FOR ALS AND OTHER NEURODEGENERATIVE DISEASES

NONINVASIVE TOOLS FOR ASSESSING MUSCLE STRUCTURE AND FUNCTION

PRECLINICAL DEVELOPMENT OF A NOVEL SMALL MOLECULE INHIBITOR OF ALZHEIMER'S DISEASE-RELATED COGNITIVE IMPAIRMENT

REGULATING FIBROSIS AND MUSCLE GROWTH IN THE MUSCULAR DYSTROPHIES

TECHNOLOGY ENABLED SERVICES FOR COORDINATED CARE OF DEPRESSION IN HEALTHCARE SETTINGS

SIGNAL PROCESSING IN THE INNER RETINA

TAS::57 3600::TAS 'RECONFIGURABLE MATTER FROM PROGRAMMABLE ATOM EQUIVALENTS'

MULTISCALE DESIGN AND MANUFACTURING OF HYBRID DWCNT-POLYMER FIBERS

MOLECULAR MECHANISMS OF ABNORMAL DENDRITIC SPINE PLASTICITY IN SCHIZOPHRENIA

IDENTIFICATION OF GENETIC AND BRAIN MOLECULAR AND BIOCHEMICAL MECHANISMS THAT REGULATE THE RESPONSES TO PHYSICAL AND EMOTIONAL STRESSORS IN THE MOUSE

SYNAPTIC CODING IN THE CEREBELLAR CORTICONUCLEAR CIRCUIT