The Institute

HEALTH CENTER CLUSTER

COMPREHENSIVE CANCER CENTER PROGRAM AT FOX CHASE

HEALTH CENTER CLUSTER

COAP NETWORK TRAINING AND TECHNICAL ASSISTANCE COORDINATION PROVIDER

HEAD START AND EARLY HEAD START

HEAD START AND EARLY HEAD START

OFFICER SAFETY AND WELLNESS - PREVENTING VIOLENCE AGAINST LAW ENFORCEMENT AND ENSURING OFFICER RESILIENCE AND SURVIVABILITY (VALOR)

INFORMATION TECHNOLOGY SUPPORT AND NATIONAL ISSUES COORDINATION SUPPORT TO THE REGIONAL INFORMATION SHARING SYSTEMS PROGRAM

SAN MATEO HEAD START AND EARLY HEAD START

HEAD START/EARLY HEAD START

OFFICER SAFETY AND WELLNESS (OSW) TRAINING, WHEN PROPERLY CONCEIVED AND EFFECTIVELY EXECUTED, HAS THE POTENTIAL TO DISABLE THE CYCLE OF OFFICER STRESS; OFFICER STRESS, WHEN LEFT UNADDRESSED, CAN WORSEN POLICE-COMMUNITY RELATIONS AND CAN ALSO IMPACT THE RISING CRIME THAT HAS BESET THE WORK OF LAW ENFORCEMENT OFFICERS OVER THE PAST TWO YEARS AND THREATENED PUBLIC SAFETY NATIONWIDE. WELL-TRAINED, SUPPORTED, AND PHYSICALLY AND MENTALLY HEALTHY OFFICERS STAND TO BECOME THE CATALYSTS OF AN ALTERNATIVE CYCLE OF REDUCED STRESS, IMPROVED PERFORMANCE, BETTER OUTCOMES, AND SAFER COMMUNITIES, THEREBY CREATING THE SHORTEST PATH TO HEALTHIER POLICE-COMMUNITY RELATIONS.   THE GOAL OF THE VALOR OSW TRAINING AND TECHNICAL ASSISTANCE (TTA) PROGRAM (VALOR PROGRAM), A COMPONENT OF THE BUREAU OF JUSTICE ASSISTANCE (BJA) VALOR INITIATIVE, IS TO PROVIDE STATE, LOCAL, AND TRIBAL LAW ENFORCEMENT WITH TTA THAT HAS A DIRECT IMPACT ON OSW. THE PROPOSED FUNDING OF $6,700,000 FOR THE PERIOD OF OCTOBER 1, 2022, TO MARCH 31, 2024, WILL ALLOW BJA TO CONTINUE ITS STRONG PRESENCE IN THE LAW ENFORCEMENT FIELD OF OSW WITH THE ONGOING DELIVERY OF THE VALOR PROGRAM, MANAGED BY THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH.   THIS PROPOSAL IS DESIGNED TO CONTINUE IIR’S SUPPORT OF THE VALOR PROGRAM AND INCLUDES THE PROVISION OF ON-SITE AND VIRTUAL TRAININGS, INCLUDING SURVIVE & THRIVE, EXECUTIVE AND MID-LEVEL LEADERSHIP WORKSHOPS, TRAIN-THE-TRAINER SESSIONS TO HELP AGENCIES IMPLEMENT THEIR OWN TRAINING PROGRAMS, AND SUPPLEMENTAL TRAININGS TO PROVIDE AGENCIES WITH A CUSTOMIZED RESPONSE. THIS PROPOSAL ALSO INCLUDES THE DEVELOPMENT OF TRAININGS AND RESOURCES FOR CORRECTIONS AND RURAL, TRIBAL, AND TERRITORIAL LAW ENFORCEMENT; THE CONTINUATION OF IMPLEMENTING TTA AND RESOURCES FOR BJA’S SAFER TOGETHER CAMPAIGN; AND THE ESTABLISHMENT OF PARTNERSHIPS WITH THE INTERNATIONAL ASSOCIATION OF CHIEFS OF POLICE, THE NATIONAL ORGANIZATION OF BLACK LAW ENFORCEMENT EXECUTIVES, THE NATIONAL ASSOCIATION OF WOMEN LAW ENFORCEMENT EXECUTIVES, AND THE NATIONAL POLICING INSTITUTE. ADDITIONAL DELIVERABLES INCLUDE CREATING A TIERED ACHIEVEMENT SYSTEM TO INCENTIVIZE AGENCIES TO PARTICIPATE IN VALOR PROGRAM ACTIVITIES, DEVELOPING PROACTIVE TECHNICAL ASSISTANCE PLANS FOR AGENCIES THAT EXPERIENCE SIGNIFICANT TRAUMATIC EVENTS, AND POTENTIALLY AWARDING MICROGRANTS TO ASSIST IN THE IMPLEMENTATION OR ENHANCEMENT OF AN AGENCY’S WELLNESS PROGRAM.   CURRICULA AND RESOURCES WILL BE UPDATED REGULARLY AND TRANSLATED INTO SPANISH, AS APPLICABLE. THE MOST CURRENT AND ADVANCED TECHNOLOGY WILL BE USED TO DEVELOP EFFECTIVE TTA.    THE ULTIMATE INTENT OF THE TTA PROPOSED AS A PART OF THE VALOR PROGRAM IS TO EFFECT POSITIVE BEHAVIORAL CHANGE IN PARTICIPANTS AND SUPPORT EACH AGENCY’S EFFORT TO MAKE OSW A PRIORITY.

IIR PROPOSES TO CONTINUE TO SUPPORT THE CRITICAL WORK OF THE HAROLD ROGERS PRESCRIPTION DRUG MONITORING PROGRAM (PDMP) TRAINING AND TECHNICAL ASSISTANCE (TTA) PROGRAM THROUGH ITS PDMP TTA CENTER (TTAC) TEAM. THE TTAC TEAM HAS SUPPORTED BJA AND THE PDMP COMMUNITY FOR MORE THAN A DECADE, FACILITATING THE SHARING OF NEW INITIATIVES AND INNOVATIONS AMONG PDMPS AND DISSEMINATING PROVEN, EVIDENCE-BASED, AND EFFECTIVE PRACTICES. BUILDING ON ITS WORK OVER THE PAST 12 YEARS, THE TTAC TEAM WILL CONTINUE TO PROVIDE RESOURCES TO AND COORDINATE INFORMATION SHARING AMONG PDMPS AND OTHER STAKEHOLDERS AND WILL COLLABORATE WITH NATIONAL ORGANIZATIONS, FEDERAL AND STATE AGENCIES, AND OTHER EXPERTS TO PROVIDE THE HIGHEST-QUALITY TTA SERVICE TO BJA GRANTEES, PDMP ADMINISTRATORS, AND OTHER STAKEHOLDERS IN CARRYING OUT THE PROGRAM REQUIREMENTS AND DELIVERABLES. IN COORDINATION WITH BJA, IIR’S TTAC TEAM WILL ASSIST PDMP COMMUNITIES TO PLAN, IMPLEMENT, SUSTAIN, AND ENHANCE THEIR PROGRAMS THROUGH THE EXCHANGE OF INFORMATION AND THE COLLECTION OF DATA AND WILL ALSO WORK TO INCREASE COLLABORATION AMONG LAW ENFORCEMENT, PROSECUTORS, PUBLIC HEALTH OFFICIALS, TREATMENT PROVIDERS, AND/OR DRUG COURTS THROUGH THE STATE PDMPS. THE TTAC TEAM WILL CONTINUE ITS EFFORTS TO ENSURE THE QUALITY AND ACCURACY OF PDMP DATA LOCALLY, REGIONALLY, AND NATIONALLY TO INCREASE THE USE OF PRESCRIBERS AND THE UTILITY TO PRESCRIBERS AND WILL CONTINUE TO SUPPORT THE RXCHECK HUB AS A FULLY OPERATIONAL DATA SHARING SYSTEM TO SECURELY AND EFFICIENTLY SHARE PDMP DATA BETWEEN STATES OR WITH A HEALTH INFORMATION EXCHANGE/ELECTRONIC HEALTH RECORD (HIE/EHR) SYSTEM. THE HAROLD ROGERS PDMP TTA PROGRAM PLAYS A KEY ROLE IN COMBATING THE PRESCRIPTION DRUG EPIDEMIC IN THE UNITED STATES, AND THE TTAC TEAM’S MECHANISMS FOR PDMPS TO COMMUNICATE, SHARE PROMISING PRACTICES, AND ACCESS VALUABLE TOOLS AND RESOURCES ARE FUNDAMENTAL UNDERPINNINGS OF THE PROGRAM’S SUCCESS. IIR, ITS TTAC TEAM, AND IIR’S PARTNER, THE IJIS INSTITUTE, LOOK FORWARD TO MEETING THE GOAL OF THE HAROLD ROGERS PDMP TTA PROGRAM BY SERVING AS A NATIONAL RESOURCE FOR PDMP GRANTEES AND OTHER STAKEHOLDERS; CONDUCTING PDMP ASSESSMENTS AND REVIEWING LEGISLATION; PROVIDING SUBJECT-MATTER EXPERTISE FOR MEETINGS; DEVELOPING ARTICLES, WEBINARS, AND PODCASTS; FACILITATING COMMUNICATION AND PEER-TO-PEER INFORMATION SHARING; SUPPORTING NATIONAL AND FEDERAL PARTNERS; AND SUPPORTING THE RXCHECK HUB.

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

MOLECULAR BASIS FOR GAMMA/DELTA T LINEAGE SPECIFICATION

AMERICAN RESCUE PLAN ACT FUNDING FOR HEALTH CENTERS

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

VALOR OFFICER SAFETY AND WELLNESS TRAINING AND TECHNICAL ASSISTANCE PROGRAM

ACCORDING TO THE CENTERS FOR DISEASE CONTROL AND PREVENTION, 87,203 DRUG OVERDOSE DEATHS OCCURRED IN THE UNITED STATES BETWEEN SEPTEMBER 2019 AND SEPTEMBER 2020. ALTHOUGH OVERDOSE DEATHS WERE ON THE RISE BEFORE THE ONSET OF COVID-19, EVIDENCE POINTS TO AN ACCELERATION DURING THE PANDEMIC. FINAL 2020 DATA HAS NOT YET BEEN REPORTED, BUT THE CDC ESTIMATES THAT THE TOTAL COULD EXCEED 90,000 OVERDOSE DEATHS.   THE INTERSECTING CRISES OF THE PANDEMIC AND THE RISE IN OVERDOSE FATALITIES COMPELLED FEDERAL AGENCIES TO ADOPT MEASURES TO TREAT SUBSTANCE USE DISORDERS (SUD) THROUGH INNOVATIVE STRATEGIES FOR MAINTAINING CONNECTIONS, SUCH AS WIDESPREAD USE OF TELETHERAPY, ALLOWING PATIENTS UNABLE TO VISIT AN OPIOID TREATMENT PROGRAM DAILY TO OBTAIN UP TO 28 DAYS OF TAKE-HOME MEDICATION, AND ALLOWING PRACTITIONERS TO PRESCRIBE BUPRENORPHINE TO NEW PATIENTS WITH OPIOID USE DISORDER FOLLOWING A PHONE EVALUATION.  AS SOME AREAS OF OUR NATION EMERGE FROM THE PANDEMIC, THE BUREAU OF JUSTICE ASSISTANCE’S COMPREHENSIVE OPIOID, STIMULANT, AND SUBSTANCE ABUSE PROGRAM (COSSAP)-SUPPORTED PROJECTS ARE IDEALLY POSITIONED TO SUPPORT THE BIDEN ADMINISTRATION’S VISION TO STEER AMERICAN COMMUNITIES TOWARD EXPANDED, COMPREHENSIVE, AND SUSTAINABLE RESPONSES TO SUD THAT PRIORITIZE PREVENTION, TREATMENT, RECOVERY, AND HARM REDUCTION.  AS THE COSSAP NETWORK HUB FOR TRAINING AND TECHNICAL ASSISTANCE (TTA) SINCE THE PROGRAM’S INCEPTION IN 2017, THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH (IIR) WILL CONTINUE TO SERVE AS THE NEXUS OF A NATIONWIDE COSSAP COMMUNITY OF PRACTICE THAT IS HELPING TO TURN THE TIDE IN THE BATTLE AGAINST SUBSTANCE USE.  IIR WILL CONTINUE TO LEVERAGE INNOVATIVE AND PROVEN COORDINATION PROCESSES AND INFRASTRUCTURE TO MEET THE NEEDS OF THE COSSAP INITIATIVE BY:  •    PROVIDING LOGISTICAL SUPPORT FOR AND DELIVERING WEBINARS, PODCASTS, AND OTHER DISTANCE LEARNING OPPORTUNITIES. •    PRODUCING, EDITING, AND ELECTRONICALLY DISTRIBUTING COSSAP QUARTERLY UPDATES AND OTHER PROGRAM PRODUCTS.  •    COORDINATING ANNUAL APPLICANT WEBINARS, STAKEHOLDER BRIEFINGS, AND NEW GRANTEE ORIENTATION CALLS.  •    COLLECTING, DISTRIBUTING, AND MAINTAINING PROJECT-SPECIFIC COMMUNICATION, ARTICLES OF INTEREST, REPORTS, AND OTHER INFORMATION.  •    DEVELOPING CONTENT FOR, MAINTAINING, AND ENHANCING THE COSSAP RESOURCE CENTER WEBSITE. •    PROVIDING SUPPORT TO ENHANCE EFFORTS TO BUILD PUBLIC HEALTH AND PUBLIC SAFETY PARTNERSHIPS TO ADDRESS OPIOID, STIMULANT, AND OTHER SUBSTANCE USE IN RURAL JURISDICTIONS. A UNIFIED COSSAP NETWORK IS A FUNDAMENTAL UNDERPINNING OF THE PROGRAM’S SUCCESS.  AS THE HUB FOR THE ENTIRE SCOPE OF TTA EFFORTS, IIR WILL CONTINUE TO COORDINATE COSSAP TTA COLLABORATIVE CALLS, COLLABORATE ON PERFORMANCE MEASUREMENT COLLECTION, FACILITATE CONSENSUS-DRIVEN AGENDA DEVELOPMENT FOR VARIOUS COSSAP MEETINGS, AND SUPPORT OTHER TTA TEAM TASKS AND MECHANISMS AS GUIDED BY BJA.

FY 2006 REGIONAL INFORMATION SHARING SUPPORT

SUPPORT FOR RISS PROGRAM AND THE RISS TECHNOLOGY SUPPORT CENTER

SUICIDE IS A LEADING CAUSE OF DEATH AMONG LAW ENFORCEMENT OFFICERS. THE BUREAU OF JUSTICE ASSISTANCE’S (BJA) NATIONAL SUICIDE AWARENESS FOR LAW ENFORCEMENT OFFICERS (SAFLEO) PROGRAM, A VALOR INITIATIVE PROGRAM, PROVIDES NATIONAL, CULTURALLY INFORMED AND SENSITIVE TRAINING AND TECHNICAL ASSISTANCE (TTA) AND RESOURCES TO LAW ENFORCEMENT LEADERS, SUPERVISORS, OFFICERS, FAMILIES, COLLEAGUES, AND OTHERS TO EDUCATE AND INCREASE AWARENESS AND RECOGNITION OF LAW ENFORCEMENT SUICIDE WITH THE AIM OF PREVENTING IT. THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH (IIR) AND ITS PARTNERS IN THIS ENDEAVOR, INCLUDING THE AMERICAN ASSOCIATION OF SUICIDOLOGY, THE MAJOR CITIES CHIEFS ASSOCIATION, THE NATIONAL LAW ENFORCEMENT OFFICERS MEMORIAL FUND, AND THE UNIVERSITY OF KENTUCKY SUICIDE PREVENTION AND EXPOSURE LAB, WILL COLLABORATE AND LEVERAGE OUR RESOURCES TO CONTINUE TO ACCOMPLISH THE SAFLEO PROGRAM’S DELIVERABLES AND THE MISSION TO RAISE AWARENESS AND PROMOTE CHANGE IN THE POLICING CULTURE ABOUT LAW ENFORCEMENT MENTAL HEALTH, INCREASE THE ACCEPTANCE OF HELP-SEEKING BEHAVIOR, AND REDUCE AND PREVENT LAW ENFORCEMENT SUICIDE. THE TEAM WILL UTILIZE ITS MEMBERS’ DIVERSE AND WIDE RANGE OF EXPERIENCE AND EXPERTISE TO CONTINUE TO DEVELOP, ENHANCE, AND DELIVER A COLLECTION OF VIRTUAL AND IN-PERSON TTA AND RESOURCES. TRAINING WILL ADDRESS FACTORS ASSOCIATED WITH THE RISK OF SUICIDAL IDEATION, SUCH AS ORGANIZATIONAL STRESS, CRITICAL INCIDENT TRAUMA, THE NATURE OF SHIFT WORK, RELATIONSHIP ISSUES, AND ALCOHOL USE AND ABUSE. THIS TRAINING SUITE INCLUDES EXECUTIVE, LEADERSHIP AND SUPERVISION, LINE OFFICER, AND TRAIN-THE-TRAINER COURSES. TO FULLY ADMINISTER THIS PROGRAM, THE TEAM WILL PROVIDE TTA TO AGENCIES; DEVELOP AND PUBLISH VIRTUAL OR DISTANCE-LEARNING OPPORTUNITIES; DEVELOP AND PROVIDE TRAINING MATERIALS AND RELATED RESOURCES; MAINTAIN A TRAINING REQUEST DATABASE; LEVERAGE AN EXISTING WEBSITE TO HOUSE MATERIALS; MARKET THE TTA PROGRAM TRAINING AND RESOURCES; CONDUCT EVALUATIONS OF ALL TRAINING; AND CREATE A DIVERSE-MEMBERSHIP ADVISORY BOARD TO GUIDE PROJECT ACTIVITIES AND HELP IDENTIFY EMERGING ISSUES IN SUICIDE AWARENESS AND PREVENTION. IIR WILL UTILIZE A HIGHLY EXPERIENCED, DIVERSE, AND INCLUSIVE TEAM OF SUBJECT-MATTER EXPERTS AND CULTURALLY COMPETENT PRACTITIONERS, INSTRUCTIONAL DESIGNERS, AND INSTRUCTORS. TRAINING AND PRODUCTS WILL BE BASED ON RESEARCH; EVIDENCE-BASED APPROACHES; INNOVATIVE ADULT-LEARNING METHODS; BEHAVIORAL TRENDS; AND PRACTICAL, RELEVANT, AND REALISTIC APPLICATIONS.

SPORE IN OVARIAN CANCER

VALOR OFFICER SAFETY AND WELLNESS TRAINING AND TECHNICAL ASSISTANCE

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

REGIONAL INFORMATION SHARING SYSTEMS (RISS) SUPPORT

THE UNITED STATES IS EXPERIENCING A SURGE IN VIOLENT CRIME, MOST NOTABLY GUN CRIME, HOMICIDES, AND AGGRAVATED ASSAULTS, WHICH FEDERAL BUREAU OF INVESTIGATION (FBI) DEPUTY DIRECTOR PAUL ABBATE RECENTLY NOTED ARE “OCCURRING AT AN APPALLING PACE.” ACCORDING TO FBI DATA, MORE THAN 21,000 HOMICIDES WERE REPORTED IN 2020—4,901 MORE THAN IN 2019—THE BIGGEST LEAP SINCE THE 1960S. OVERALL VIOLENT CRIME—INCLUDING HOMICIDES, RAPE, ROBBERY, AND AGGRAVATED ASSAULT—INCREASED BY 5.6 PERCENT FROM 2019 TO 2020. AS COMMUNITIES RECOVER FROM THE PANDEMIC, MANY ARE COPING WITH COMPLEX SOCIAL ISSUES, INCLUDING CALLS FOR POLICE REFORM IN THE WAKE OF HIGH-PROFILE OFFICER-INVOLVED INCIDENTS, HINDERING COMMUNITY TRUST AND ENGAGEMENT. FOLLOWING ARE OTHER EXAMPLES OF THE CHALLENGES FACING THE CRIMINAL JUSTICE COMMUNITY:   RECRUITMENT AND RETENTION ARE SYSTEMIC PROBLEMS ACROSS THE NATION. GUN CRIME IS AT EPIDEMIC PROPORTIONS, AND GHOST GUNS ARE CONTRIBUTING TO THIS PROBLEM. ADVANCES IN TECHNOLOGY TO AID LAW ENFORCEMENT ARE OF IMMENSE VALUE, BUT THEIR SUCCESSFUL INTEGRATION INTO OPERATIONS REQUIRES COMMITMENT AND ACCESS TO QUALITY TRAINING AND TECHNICAL ASSISTANCE (TTA). POLICE ARE NOT THE ONLY CRIMINAL JUSTICE PROFESSIONALS FACING CHALLENGES. OTHER PROFESSIONALS SUCH AS PROSECUTORS ARE COPING WITH SIMILAR ISSUES DUE TO AN OVERLOAD OF WORK, STRESS, AND TRAUMA.   THE NATIONAL PUBLIC SAFETY PARTNERSHIP (PSP) HAS WORKED WITH MORE THAN 50 CITIES ACROSS THE COUNTRY TO ADDRESS THESE AND OTHER CRITICAL ISSUES RELATED TO VIOLENT CRIME REDUCTION AND IMPROVING COMMUNITY ENGAGEMENT. THE STRESSORS CAUSED BY THE PANDEMIC AND OTHER SOCIOPOLITICAL ISSUES ARE BEST ADDRESSED WITH A SOLID VIOLENCE REDUCTION STRATEGY, EVIDENCE-BASED PRACTICES, AND COMMUNITY ENGAGEMENT. QUALITY, VETTED TTA, ALONG WITH SHARING LESSONS LEARNED AND PROMISING PRACTICES AMONG JURISDICTIONS AND CRIMINAL JUSTICE PROFESSIONALS, CAN IMPROVE STRESS MANAGEMENT PRACTICES WHILE FOCUSING ON CREATING SAFER COMMUNITIES. SOLUTIONS TO THESE CHALLENGES MUST INVOLVE ALL STAKEHOLDERS, FROM POLICE AND PROSECUTORS TO COMMUNITY MEMBERS, CLERGY, SCHOOLS, PUBLIC HEALTH ORGANIZATIONS, VICTIM SERVICE PROVIDERS, PAROLE AND PROBATION, AND CORRECTIONS.    AS THE INCUMBENT TTA PROVIDER RESPONSIBLE FOR THE INFRASTRUCTURE OF PSP, INCLUDING PEER EXCHANGES, COMMUNITIES OF PRACTICE, WEBSITES, DASHBOARDS, THE PSP VIRTUAL ACADEMY, FIELD COMMUNICATIONS TOOLS, AND THE COORDINATION OF ANNUAL SYMPOSIUMS, THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH (IIR) IS THE MOST WELL-POSITIONED TTA PROVIDER TO DELIVER INNOVATIVE PROGRAMMATIC SERVICES ON BEHALF OF THE BUREAU OF JUSTICE ASSISTANCE.

PDMP TRAINING AND TECHNICAL ASSISTANCE PROGRAM

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

IMMUNE MECHANISMS THAT CONTROL ECTROMELIA VIRUS INFECTION

LAW ENFORCEMENT TRAINING

THE PURPOSE OF THIS PROJECT IS TO SUPPORT NEW OR EXISTING LOCAL NONPROFIT PROGRAMS (IN COLLABORATION WITH LAW ENFORCEMENT AND COMMUNITY COALITIONS) IN IMPLEMENTING BEST PRACTICES OR PROMISING APPROACHES FOR DRUG PREVENTION PROGRAMS TARGETED TO YOUTH IN SCHOOL AND EXTRACURRICULAR SETTINGS. SUPPORT FOR PROGRAMS WILL BE ADMINISTERED THROUGH SUBAWARDS TO ADVANCE COMPREHENSIVE APPROACHES TO COMBATING SUBSTANCE USEINCLUDING THROUGH INVESTIGATIONS, TREATMENT, AND EDUCATIONBASED ON IDENTIFIED REGIONAL AND LOCAL NEEDS. INSTITUTE FOR INTERGOVERNMENTAL RESEARCH PROJECT ACTIVITIES INCLUDE, IN COLLABORATION WITH THE OFFICE OF JUVENILE JUSTICE AND DELINQUENCY PREVENTION (OJJDP): DEVELOPING AND EXECUTING A PROCESS FOR SELECTING AND ADMINISTERING SUBAWARDS TO PROJECT SITES TO IMPLEMENT AND/OR EXPAND YOUTH DRUG PREVENTION EDUCATION; DEVELOPING A TECHNOLOGICAL PROGRAM INFRASTRUCTURE; DEVELOPING AND SUPPORTING INDIVIDUALIZED TRAINING AND TECHNICAL ASSISTANCE PLANS FOR EACH SITE; DEVELOPING AND EXECUTING CONVENINGS (VIRTUAL AND IN-PERSON); DATA GATHERING AND REPORTING, INCLUDING QUALITATIVE METRICS SUCH AS SUCCESS STORIES AND THE UPLIFTING OF YOUTH AND FAMILY VOICES WITH LIVED EXPERIENCE; MONITORING SUBAWARDEES FOR PROJECT PROGRESS AS WELL AS FINANCIAL COMPLIANCE; AND STRATEGIC PLANNING MEETINGS WITH OJJDP.

LAW ENFORCEMENT SUICIDE PREVENTION TRAINING PROGRAM

GANG RESISTANCE EDUCATION AND TRAINING (G.R.E.A.T.) PROGRAM TRAINING AND TECHNICAL ASSISTANCE SUPPORT

THE DRIVING PURPOSE FOR THE NASA EARTH SCIENCE EDUCATION COLLABORATIVE NESEC IS TO ADVANCE NASA SMD SCIENCE EDUCATION OBJECTIVES ON NATIONAL, REGIONA

THE BUREAU OF JUSTICE ASSISTANCE’S STATE AND LOCAL ANTI-TERRORISM TRAINING (SLATT) PROGRAM SUPPORTS LAW ENFORCEMENT OFFICERS, ANALYSTS, TRAINING DIRECTORS, PROSECUTORS, AND OTHER CRIMINAL JUSTICE PRACTITIONERS IN UNDERSTANDING AND ADDRESSING DOMESTIC AND INTERNATIONAL TERRORISM AND TARGETED VIOLENCE THROUGH THE DEVELOPMENT AND DELIVERY OF INNOVATIVE TRAINING AND TECHNICAL ASSISTANCE (TTA).  THE PROGRAM, WITH ITS PREVENTION FOCUS, EMPLOYS A MULTIDISCIPLINARY APPROACH THAT BUILDS PARTNERSHIPS AND INTEGRATES EVIDENCE-BASED DATA AND RESEARCH TO EDUCATE PARTICIPANTS; STRENGTHEN COMMUNITY TRUST; ADVOCATE FOR LAW ENFORCEMENT ACCOUNTABILITY AND TRANSPARENCY; AND SAFEGUARD THE PROTECTION OF PRIVACY, CIVIL RIGHTS, AND CIVIL LIBERTIES.  THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH (IIR) AND THE NATIONAL CONSORTIUM FOR THE STUDY OF TERRORISM AND RESPONSES TO TERRORISM (START) PROPOSE TO CONTINUE TO WORK IN PARTNERSHIP TO SOLIDIFY THE SLATT PROGRAM AS THE PREEMINENT PROGRAM FOR ANTI-TERRORISM TTA FOR THE FIELD, SUPPORTING PRESIDENT JOE BIDEN’S NATIONAL STRATEGY FOR COUNTERING DOMESTIC TERRORISM, WHICH RECOGNIZES THAT PREVENTION REQUIRES “A MULTIFACETED RESPONSE ACROSS THE FEDERAL GOVERNMENT . . . THAT INCLUDES WORKING WITH . . . CRITICAL PARTNERS IN STATE, LOCAL, TRIBAL, AND TERRITORIAL GOVERNMENTS AND IN CIVIL SOCIETY, THE PRIVATE SECTOR, ACADEMIA, AND LOCAL COMMUNITIES . . .” THIS PROPOSAL INCLUDES THE CONTINUED DEVELOPMENT AND DELIVERY OF TIMELY AND RELEVANT TTA TO LAW ENFORCEMENT AND CRIMINAL JUSTICE PROFESSIONALS IN THE FIELD, INCLUDING A SUITE OF EVIDENCE-BASED TRAINING COURSES AND WORKSHOPS; ONLINE TRAINING ACCESSED VIA A ROBUST DISTANCE-LEARNING, RESTRICTED-ACCESS PORTAL; ON-DEMAND WEBINARS AND PODCASTS; RESEARCH-BASED PUBLICATIONS AND PRINTABLE RESOURCES; FOCUSED TECHNICAL ASSISTANCE SUPPORT FOR AGENCIES SEEKING TO DEVELOP ANTI-TERRORISM TRAINING; AND THE MAINTENANCE AND ENHANCEMENT OF A DYNAMIC WEBSITE.  TOPICS ADDRESSED AS PART OF THIS COMPREHENSIVE TTA APPROACH WILL CENTER ON IDENTIFYING, REPORTING, INVESTIGATING, AND INTERDICTING POTENTIAL ACTS OF TERRORISM AND TARGETED VIOLENCE AND THE CRITICAL ROLE THAT COMMUNITIES PLAY IN PREVENTION.  THESE DELIVERABLES WILL BE ACCOMPLISHED BY A ROBUST TEAM OF SUBJECT-MATTER EXPERTS (SMES) AND PRACTITIONERS, INSTRUCTIONAL DESIGNERS, AND INSTRUCTORS, INCORPORATING CUTTING-EDGE BEHAVIORAL AND ADULT-LEARNING STRATEGIES TO ENSURE THAT CONCEPTS AND PRINCIPLES INCORPORATED IN THE SLATT PROGRAM ARE IMPLEMENTABLE IN THE FIELD.  THE COLLECTIVE KNOWLEDGE; EXPERIENCE; EXISTING BODY OF WORK; DIVERSITY; AND REPUTATION FOR INTEGRITY, PROFESSIONALISM, AND SUPERIOR NATIONAL-LEVEL SERVICE DELIVERY HELD BY THE IIR AND START TEAM, COUPLED WITH A CADRE OF HIGHLY EXPERIENCED SMES IN THE FIELD OF TERRORISM AND TARGETED VIOLENCE, MAKE IT THE TEAM TO PROVIDE COMPREHENSIVE SUPPORT TO THE SLATT PROGRAM.

NATIONAL OFFICER SAFETY TRAINING AND TECHNICAL ASSISTANCE PROGRAM

PUBLIC SAFETY PARTNERSHIP (PSP) NATIONAL TRAINING AND TECHNICAL ASSISTANCE PROGRAM - PSP LOGISTICAL SUPPORT

JUSTICE INFORMATION SHARING TTA - REGIONAL INFORMATION SHARING SYSTEMS (RISS) TECHNOLOGY SUPPORT CENTER (RTSC)

TRAINING PROGRAM IN CANCER RESEARCH

GLOBAL JUSTICE INFORMATION SHARING INITIATIVE

REGIONAL INFORMATION SHARING SYSTEMS PROGRAM COORDINATION, TRAINING, ANALYSIS, AND TECHNICAL ASSISTANCE SUPPORT

MECHANISM, FUNCTION, AND EXPLOITATION OF INFLUENZA A VIRUS-ACTIVATED CELL DEATH

STATE AND LOCAL TERRORISM PREVENTION TRAINING AND TECHNICAL ASSISTANCE PROGRAM

VIOLENCE REDUCTION NETWORK (VRN): NATIONAL TRAINING AND TECHNICAL ASSISTANCE PROGRAM - VRN LOGISTICAL SUPPORT

A PROPOSAL TO CONTINUE THE ACTIVITIES OF THE NATIONAL GANG CENTER

STRUCTURAL BIOINFORMATICS OF PROTEINS AND PROTEIN COMPLEXES AND APPLICATIONS TO CANCER BIOLOGY

BELIEVE IN YOUTH! LOUISIANA TEEN PREGNANCY PREVENTION PROGRAM (TIER 1B)

SINCE THE PASSAGE OF THE SEX OFFENDER REGISTRATION AND NOTIFICATION ACT (SORNA), THE SMART OFFICE HAS DESIGNED A NATIONAL STRATEGY FOR COMPREHENSIVE SEX OFFENDER REGISTRATION AND PUBLIC NOTIFICATION. THE DRU SJODIN NATIONAL SEX OFFENDER PUBLIC WEBSITE (NSOPW), THE SORNA EXCHANGE PORTAL (THE PORTAL), THE TRIBE AND TERRITORY SEX OFFENDER REGISTRY SYSTEM (TTSORS), AND THE SEX OFFENDER REGISTRY TOOL (SORT) ARE INTEGRAL PARTS OF THIS STRATEGY. THE CHALLENGES OF MANAGING THE RESOURCES ARE NUMEROUS. THEY INCLUDE MANAGING ELABORATE TECHNICAL APPLICATIONS AND SYSTEMS, FOSTERING RELATIONSHIPS WITH MANY DIFFERENT JURISDICTIONS, PROVIDING TECHNICAL SUPPORT FOR A VARIETY OF ISSUES, BUILDING FLEXIBLE APPLICATIONS THAT CAN INTERFACE WITH A VARIETY OF SYSTEMS, AND IDENTIFYING NEW STRATEGIES THAT IMPROVE COLLABORATION. OVER THE PAST 14 YEARS, THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH (IIR) HAS WORKED WITH SORNA JURISDICTIONS TO OVERCOME MANY OF THESE CHALLENGES AND HAS DEVELOPED A STRONG WORKING PARTNERSHIP WITH THE VARIOUS STATES, TRIBES, AND TERRITORIES THAT IT SUPPORTS THROUGH THESE PROGRAMS. SINCE THE INCEPTION OF NSOPW, THE PORTAL, TTSORS, AND SORT, IIR HAS WORKED AT THE DIRECTION OF THE SMART OFFICE TO DEVELOP, ENHANCE, MAINTAIN, AND OPERATE THESE RESOURCES. TO ENSURE THAT THESE TECHNICAL PROGRAMS ARE EFFECTIVELY MANAGED, IIR EMPLOYS A PROJECT STRATEGY THAT INCLUDES DILIGENT PLANNING, CONSTANT EFFECTIVE MONITORING, EXCEPTIONAL CUSTOMER SERVICE, AND EFFICIENT PROBLEM RESOLUTION, ALL TIED TOGETHER WITH IIR’S UNIQUE TECHNICAL EXPERTISE. AS A RESULT OF THIS STRATEGY, NSOPW, THE PORTAL, TTSORS, AND SORT HAVE BECOME INVALUABLE AND TRUSTED RESOURCES FOR THE PUBLIC AND THE ORGANIZATIONS THAT USE THEM. FOR THESE RESOURCES TO CONTINUE TO MEET THE GOALS AND MISSION OF THE SMART OFFICE, IIR WILL FULFILL ONE ALL-ENCOMPASSING GOAL WITH NUMEROUS SUPPORTING DELIVERABLES: GOAL 1— “TO PROVIDE THE PUBLIC WITH INFORMATION ABOUT REGISTERED SEX OFFENDERS AND FACILITATE INFORMATION SHARING AMONG JURISDICTIONS.” THE ACCOMPLISHMENT OF THIS GOAL, THROUGH THE EXECUTION OF THE DELIVERABLES AND TASKS OUTLINED IN THIS APPLICATION, WILL PROVIDE THE SMART OFFICE WITH THE RESOURCES NECESSARY TO PROVIDE THE TRAINING, TECHNICAL ASSISTANCE, AND TECHNICAL SYSTEMS THE SORNA JURISDICTIONS NEED TO EFFECTIVELY MANAGE THEIR REGISTERED SEX OFFENDERS AND SHARE INFORMATION WITH EACH OTHER AND THE PUBLIC.

THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH (IIR) PROPOSES ADMINISTERING A SUBAWARD PROGRAM FOR LOCAL PROJECT SITES AND DEVELOPMENT OF A NATIONAL TRAINING AND TECHNICAL ASSISTANCE (TTA) PROGRAM WITH THE OVERARCHING GOAL TO BUILD CAPABILITY AND CAPACITY OF DIVERSION PROGRAMS SERVING JUSTICE-INVOLVED YOUTH WITH SUBSTANCE USE DISORDER AND CO-OCCURRING MENTAL HEALTH AND SUBSTANCE USE DISORDER NEEDS, PREVENTING THEM FROM ENTERING THE FORMAL JUSTICE SYSTEM BY DIVERTING THEM TO TREATMENT, HEALING, AND HOPE.

THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH (IIR) WILL REDUCE OPIOID USE IN COMMUNITIES THROUGH YOUTH-CENTERED, DATA-DRIVEN TOOLS AND RESOURCES THAT FOCUS ON TRAINING, PROJECT INFRASTRUCTURE DEVELOPMENT, PROGRAM IMPLEMENTATION, AND SUSTAINMENT FOR THE OPIOID AFFECTED YOUTH INITIATIVE (OAYI) GRANT RECIPIENTS. THROUGH STRATEGIC PARTNERSHIPS WITH THE NATIONAL COUNCIL OF JUVENILE AND FAMILY COURT JUDGES (NCJFCJ) AND THE NATIONAL ASSOCIATION OF DRUG COURT PROFESSIONALS (NADCP), THEY PROPOSE TO SUPPORT THE DEVELOPMENT OF TTA RESOURCES AND TOOLS AND ENGAGE YOUTH AND IMPROVE SERVICE DELIVERY IN RESPONSE TO CHALLENGES ASSOCIATED WITH OPIOID USE AND MISUSE. IIR’S SUPPORT, IN COLLABORATION WITH OJJDP, WILL PROVIDE SITE- AND CROSS-SITE-SPECIFIC ASSISTANCE TO THE OAYI GRANTEES THROUGHOUT THE PLANNING AND IMPLEMENTATION PHASES OF THE INITIATIVE, SUPPORTING PROJECT SITES AND THEIR COMMUNITIES AS WELL AS COMMUNITIES ACROSS THE COUNTRY IN THE FOLLOWING AREAS:  (1) CONSISTENTLY EDUCATE AND EMPHASIZE THE IDEA OF EQUAL RIGHTS FOR ALL, INCLUDING THE RIGHT TO BE INFORMED AND TREATED WITH DIGNITY, RESPECT, AND SENSITIVITY; (2) ARE TRAUMA-INFORMED AND VICTIM-CENTERED; AND (3) ENGAGE LAW ENFORCEMENT OFFICERS IN COLLABORATIVE RESPONSES TO ADDRESS THE IMPACT OF OPIOID USE AND MISUSE, IN ALIGNMENT WITH THE IMPLEMENTATION OF PROGRAMS THAT IDENTIFY, RESPOND TO, TREAT, AND SUPPORT IMPACTED YOUTH AND FAMILIES TO ENSURE PUBLIC SAFETY.

CONTINUATION AND EXPANSION OF THE NATIONAL GANG CENTER

THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH (IIR) IS SUBMITTING THIS PROPOSAL TO SUPPORT THE STUDENT, TEACHERS, AND OFFICERS PREVENTING (STOP) SCHOOL VIOLENCE SPECIALIZED TRAINING AND TECHNICAL ASSISTANCE (TTA) PROGRAM CATEGORY 1: TTA FOR LAW ENFORCEMENT WHO WORK IN SCHOOLS AND/OR WITH SCHOOL-AGE POPULATIONS. THIS PROJECT SUPPORTS THE U.S. DEPARTMENT OF JUSTICE’S MISSION TO ASSIST JURISDICTIONS IN REDUCING CRIME; IMPROVING CRIMINAL JUSTICE EFFORTS; ENHANCING INFORMATION SHARING; STRENGTHENING MULTIAGENCY COLLABORATION; AND IMPLEMENTING DATA-DRIVEN, EVIDENCE-BASED STRATEGIES.   WORKING COLLABORATIVELY WITH THE BUREAU OF JUSTICE ASSISTANCE (BJA), IIR WILL UTILIZE ITS COMPREHENSIVE AND PROVEN TTA DELIVERY MODEL TO IMPLEMENT THE FIVE OVERALL PROGRAM GOALS, CATEGORY 1 OBJECTIVE, AND NINE DELIVERABLES FROM OCTOBER 1, 2022, THROUGH SEPTEMBER 30, 2024. IIR IS REQUESTING $2,000,000 TO SUPPORT THIS EFFORT.     IIR WILL WORK WITH AND INCORPORATE PERSPECTIVES AND FEEDBACK FROM STAKEHOLDERS (INCLUDING STUDENTS, PARENTS, SCHOOL OFFICIALS, SCHOOL RESOURCE OFFICERS, AND JUVENILE PROBATION OFFICERS) AND LEVERAGE AND CONTINUE TO BUILD ITS VETTED AND DIVERSE CADRE OF SUBJECT-MATTER EXPERTS TO ENSURE THAT TTA ALIGNS WITH STAKEHOLDER NEEDS AND BJA DIRECTION. IIR WILL:   PROVIDE TTA TO STOP GRANTEES TO SUPPORT EVIDENCE-BASED TRAINING. DEVELOP AND DELIVER ON-SITE AND VIRTUAL TRAINING TO SCHOOL-BASED LAW ENFORCEMENT (I.E., SCHOOL RESOURCE AND PROBATION OFFICERS) AND STAKEHOLDERS (I.E., STUDENTS, PARENTS, TEACHERS). ASSESS, TRIAGE, PRIORITIZE, AND GUIDE STAKEHOLDERS TO TTA BASED ON BEST PRACTICES AND EVIDENCE-BASED STRATEGIES. PROVIDE GUIDANCE AND RESOURCES TO SCHOOLS, SCHOOL SAFETY PRACTITIONERS, AND THE CRIMINAL JUSTICE COMMUNITY. ASSIST SCHOOLS AND LAW ENFORCEMENT IN DEVELOPING AND IMPLEMENTING POLICY AND/OR TRAINING. PARTICIPATE IN ONGOING COLLABORATION, STAY INFORMED OF RELATED ACTIVITIES, SUPPORT CROSS-ORGANIZATION COORDINATION, AND PROMOTE PROGRAM ACTIVITIES AND SUCCESSES. IDENTIFY TRENDS AND EMERGING THREATS AND PROVIDE RECOMMENDATIONS AND INFORMATION TO BJA TO HELP SHAPE FUTURE ACTIVITIES. DEVELOP AND LAUNCH AN INTERACTIVE CLEARINGHOUSE TO HOUSE PROGRAM MATERIALS, REQUEST TTA, AND ENCOURAGE ONGOING DIALOGUE. DEVELOP CUSTOMIZED DASHBOARDS TO COLLECT, ANALYZE, AND REPORT ACTIVITIES TO BJA. SUPPORT WORKING GROUPS, FORUMS, CURRICULUM DEVELOPMENT TEAMS, AND OTHER GROUPS AND MEETINGS. DEVELOP PRODUCTS SUCH AS FACT SHEETS, GUIDES, TOOLKITS, WEBINARS, AND ONLINE RESOURCES. RAISE AWARENESS OF SCHOOL SAFETY PROGRAMS, TRAINING, AND RESOURCES; PRESENT AT EVENTS; AND LEVERAGE BJA AND OTHER PARTNER CHANNELS.   STOP TTA EFFORTS WILL INCREASE THE KNOWLEDGE AND CAPACITY OF GRANTEE SITES, NONGRANTEES SUPPORTING SCHOOL SAFETY INITIATIVES, SCHOOL-BASED LAW ENFORCEMENT, JUVENILE PROBATION OFFICERS, AND OTHER STAKEHOLDERS. IT WILL INCREASE THE ACCESSIBILITY AND VOLUME OF SCHOOL SAFETY INFORMATION AND ULTIMATELY HELP ENHANCE PREVENTION, MITIGATION, AND RESPONSE TO SCHOOL VIOLENCE.

FOX CHASE CLINICAL EPIDEMIOLOGY AND VALIDATION CENTER

STATE AND LOCAL ANTI-TERRORISM TRAINING (SLATT)

STATE, LOCAL, AND TRIBAL TERRORISM PREVENTION TRAINING AND TECHNICAL ASSISTANCE NATIONAL INITIATIVE PROGRAM

NATIONAL TRAINING AND TECHNICAL ASSISTANCE SUPPORT TO THE GANG RESISTANCE EDUCATION AND TRAINING (G.R.E.A.T.) PROGRAM

CANCER PREVENTION-INTERCEPTION TARGETED AGENT DISCOVERY PROGRAM AT FOX CHASE CANCER CENTER - PROJECT SUMMARY - OVERALL HEREDITABLE CANCER-PREDISPOSING MUTATIONS ARE ESTIMATED TO BE AN UNDERLYING CAUSE OF MORE THAN 100,000 ADULT CANCERS IN THE US EACH YEAR. FOR MANY HEREDITARY CANCER SYNDROMES, THE LIFE-TIME RISK OF DEVELOPING CANCER APPROACHES 100%. DESPITE REVOLUTIONARY ADVANCES IN “OMICS” TECHNOLOGIES, OUR UNDERSTANDING OF THE MOLECULAR ALTERATIONS REQUIRED TO SUPPORT THE ESTABLISHMENT OF PRECANCEROUS LESIONS AND PROMOTE EARLY TUMOR DEVELOPMENT REMAINS VERY LIMITED, THUS HINDERING THE DEVELOPMENT OF EFFICACIOUS INTERVENTIONS. A MULTIDISCIPLINARY TEAM OF ACCOMPLISHED INVESTIGATORS AT FOX CHASE CANCER CENTER (FCCC), WITH COMBINED EXPERTISE IN CANCER PREVENTION, HERITABLE CANCER RISK, CANCER BIOLOGY, MOLECULAR MODELING, AND DRUG DISCOVERY HAS BEEN ASSEMBLED TO ADDRESS THIS UNMET IN AN UNPRECEDENTED WAY. THE GOAL OF THE FCCC CAP-IT CENTER IS TO EFFECTIVELY COORDINATE THE DEVELOPMENT OF EFFICACIOUS MOLECULARLY-TARGETED AGENTS FOR PRECISION CANCER PREVENTION AND EARLY INTERCEPTION IN POPULATIONS AT HIGH RISK FOR CANCER. ALL STUDIES ARE FACILITATED BY THE UNIQUE RESOURCES OF THE FCCC RISK ASSESSMENT PROGRAM, WHICH INCLUDES OVER 12,000 FAMILIES AT HIGH RISK FOR CANCER AND 2000 CONFIRMED GERMLINE MUTATION CARRIERS. A COMPREHENSIVE PIPELINE FOR THE DEVELOPMENT OF AGENTS FOR CANCER PREVENTION AND INTERCEPTION IS PROPOSED THAT CONSISTS OF THREE WELL-DEVELOPED RESEARCH DOMAINS: TARGET VALIDATION (AIM 1), AGENT IDENTIFICATION AND SCREENING (AIM 2), AND PILOT IN VIVO EFFICACY STUDIES (AIM 3). EACH DOMAIN WILL BE LED BY A FCCC INVESTIGATOR, WHO IS A NATIONAL LEADER IN THE RESPECTIVE FIELD. TWO HIGHLY INNOVATIVE PROJECTS ARE PROPOSED THAT ILLUSTRATE THE ROBUSTNESS OF THE CAP-IT FRAMEWORK. PROJECT 1 (ENTERING AT TARGET VALIDATION) FOCUSES ON THE DEVELOPMENT OF A NEWLY-IDENTIFIED AGENT THAT REFOLDS MUTANT P53. ITS ABILITY TO TARGET THE TP53 MUTATIONS ASSOCIATED WITH LI- FRAUMENI SYNDROME AND INHIBIT PRECANCEROUS LESIONS IN A SETTING OF MUTANT P53 WILL BE EVALUATED. PROJECT 2 (ENTERING AT AGENT IDENTIFICATION AND SCREENING) UNIQUELY TARGETS THE INITIATED PANCREATIC STROMA AS A STRATEGY FOR EARLY INTERCEPTION IN THE FORMATION OF PANCREATIC CANCER. A NEUTRALIZING ANTIBODY AGAINST THE STROMAL PROTEIN NETRIN G1, THAT CAN REVERT FIBROBLASTS TO A TUMOR-SUPPRESSIVE PHENOTYPE, HAS BEEN DISCOVERED. ANTIBODIES WITH IMPROVED POTENCY WILL BE IDENTIFIED AND TESTED IN VIVO FOR THEIR ABILITY TO INTERCEPT THE PROGRESSION OF PANCREATIC INTRAEPITHELIAL NEOPLASIA. ALL CAP-IT RESEARCH AND TRAINING WILL BE STRONGLY SUPPORTED BY THE LEADERSHIP TEAM AND COORDINATING ACTIVITIES OF THE ADMINISTRATIVE CORE, LED BY DR. CLAPPER. EXPERTISE IN BIOSTATISTICS, BIOINFORMATICS, AND DATA MANAGEMENT WILL BE PROVIDED TO CAP-IT INVESTIGATORS BY AN INFORMATICS CORE, LED BY DR. ROSS. COLLABORATIONS AMONG THE NCI, FCCC AND OTHER CAP-IT CENTERS, AS WELL AS THE SHARING OF DATA AND RESOURCES THROUGH THE DATA AND RESOURCE COORDINATION CENTER, WILL FOSTER PRODUCTIVITY AND INTEGRATION ACROSS THE CAP-IT NETWORK (AIM 4). THE LONG LEGACY OF FCCC IN CLINICAL RISK ASSESSMENT AND PRECLINICAL PREVENTIVE AGENT DEVELOPMENT, WHEN COMBINED WITH EXTENSIVE EXPERTISE IN DRUG DESIGN AND CANCER BIOLOGY, MAKES THIS CENTER UNIQUELY POISED TO BE INSTRUMENTAL IN THE DISCOVERY OF MOLECULARLY-TARGETED AGENTS TO PREVENT OR INTERCEPT EARLY ONCOGENESIS.

INNOVATION FUND

NATIONAL GANG CENTER

TOWARD A HEALTHIER BRONX 2018-2023

TEACHING HEALTH CENTER GRADUATE MEDICAL EDUCATION PROGRAM

NATIONAL VIOLENCE AGAINST WOMEN LAW ENFORCEMENT TRAINING AND TECHNICAL ASSISTANCE CONSORTIUM

NOVEL REGULATORY MECHANISMS UNDERLYING INSIDE-OUT INTEGRIN ACTIVATION

DEVELOPMENT OF COMPREHENSIVE PREVENTION AND INTERVENTION RESPONSES TO GANGS

RYAN WHITE TITLE III FUNDING: EARLY INTERVENTION SERVICES

GANG RESISTANCE EDUCATION AND TRAINING PROGRAM (GREAT), TRAINING AND TECHNICAL ASSISTANCE SUPPORT THROUGHOUT CENTRAL AMERICA.

NATIONAL FUSION CENTER TRAINING AND TECHNICAL ASSISTANCE

INSTITUTE FOR GLOBAL ENVIRONMENTAL STRATEGIES INC. EARTH SCIENCE EDUCATION AND PUBLIC OUTREACH FOR

BELIEVE IN YOUTH! LOUISIANA 2.0

STATE, LOCAL, AND TRIBAL TERRORISM PREVENTION TRAINING AND TECHNICAL ASSISTANCE (SLATT) PROGRAM

REGULATION OF HEMATOPOIESIS BY RIBOSOMAL PROTEIN PARALOGS

EXAMINING MULTILEVEL SYSTEM DYNAMICS AFFECTING HIV COMMUNITY VIRAL LOAD

RYAN WHITE TITLE III FUNDING: EARLY INTERVENTION SERVICES

NATIONWIDE SUSPICIOUS ACTIVITY REPORTING INITIATIVE AND NATIONAL CRIMINAL INTELLIGENCE RESOURCE CENTER

SOUTHWEST BORDER RURAL LAW ENFORCEMENT TRAINING AND TECHNICAL ASSISTANCE

THE ROLE OF P21-ACTIVATED KINASES IN MALIGNANT MESOTHELIOMA

INTEGRATION OF RETROVIRAL DNA: ACCESSING HOST TARGET DNA

STRUCTURE AND FUNCTION OF INTEGRASE

MECHANISMS CONTROLLING EPITHELIAL HOMEOSTASIS

P21-ACTIVATED KINASES AS NEW THERAPEUTIC TARGETS IN NEUROFIBROMATOSIS TYPE 1

IMMIGRANT ENCLAVES: CONFERRING HEALTH ADVANTAGES OR CREATING HEALTH DISPARITIES IN CHINESE IMMIGRANTS?

GLOBAL JUSTICE INFORMATION SHARING INITIATIVE

DRU SJODIN NATIONAL SEX OFFENDER PUBLIC WEBSITE (NSOPW) MAINTENANCE AND OPERATION

TARGETING RIPK3 IN FLU-ASSOCIATED LUNG INJURY

EARTH SYSTEM SCIENCE EDUCATION ALLIANCE (ESSEA) II

EVIDENCE-BASED APPROACH TO EMPOWER ASIAN AMERICAN WOMEN IN CERVICAL CANCER SCREENING

MAINTENANCE AND OPERATION OF THE DRU SJODIN NATIONAL SEX OFFENDER PUBLIC WEBSITE

A BIOBEHAVIORAL MODEL OF DIABETES RISK IN CHINESE IMMIGRANTS

NATIONAL NETWORK OF FUSION CENTERS CAPABILITY AND CAPACITY ENHANCEMENT

RACIAL AND ETHNIC APPROACHES TO COMMUNITY HEALTH US

MAINTENANCE AND OPERATION OF THE DRU SJODIN NATIONAL SEX OFFENDER PUBLIC WEBSITE

UNDERSTANDING THE ROLE OF HISTONE DEMETHYLASES AND HETEROCHROMATIN IN CELL CYCLE

RCT OF AN ONLINE MULTIMEDIA PROGRAM TO BOOST COPING & FUNCTION FOR PCA SURVIVORS

NATIONAL FOCUS AREA ATTC-SCREENING, BRIEF INTERVENTIONS AND REFERRAL TO TREATMENT

ROLE OF ZBP1 IN PATHOGENESIS OF SALMONELLA BIOFILMS - PROJECT SUMMARY INFECTIONS WITH ENTERIC PATHOGENS SUCH AS SALMONELLA, CAMPYLOBACTER, SHIGELLA, OR YERSINIA ARE LEADING CAUSES OF MORBIDITY AND MORTALITY WORLDWIDE. ALTHOUGH IN MOST INDIVIDUALS THE INFECTION RESOLVES, APPROXIMATELY 5% OF PATIENTS SUBSEQUENTLY DEVELOP A PAINFUL CHRONIC INFLAMMATORY CONDITION KNOWN AS REACTIVE ARTHRITIS (REA). HOW SALMONELLA INFECTIONS TRIGGER REA IS NOT WELL UNDERSTOOD. USING SALMONELLA ENTERICA SEROVAR TYPHIMURIUM (STM) AS A MODEL ORGANISM, WE DISCOVERED THAT A SALMONELLA PROTEIN, CURLI, IS A DOMINANT INSTIGATOR OF INFLAMMATION FOLLOWING SALMONELLA INFECTION. CURLI IS A SECRETED PROTEIN AND MAJOR COMPONENT OF THE STM BIOFILM IN THE GASTROINTESTINAL TRACT. CURLI FIBRILS BIND EXTRUDED BACTERIAL DNA WITHIN THE BIOFILM. IT IS THESE CURLI:DNA COMPLEXES, RATHER THAN CURLI ALONE, THAT ARE POTENT TRIGGERS OF TYPE I INTERFERON, IL-17, AND ANTI-DOUBLE STRANDED DNA AUTOANTIBODY PRODUCTION, LEADING TO REA. UNKNOWN, HOWEVER, IS WHY CURLI:DNA COMPLEXES ARE SO INFLAMMATORY. WE REPORT IN THIS PROPOSAL THE REMARKABLE DISCOVERY THAT THE DNA PRESENT WITHIN CURLI:DNA COMPLEXES IS NOT SOLELY B-DNA, THE CLASSIC RIGHT-HANDED (WATSON-CRICK) DOUBLE-HELIX, BUT INCLUDES COPIOUS AMOUNTS OF LEFT-HANDED Z-DNA AS WELL. Z-FORM NUCLEIC ACIDS, SUCH AS Z-DNA AND Z-RNA, WERE THOUGHT NOT TO READILY OCCUR IN NATURE, UNTIL WE SHOWED LAST YEAR THAT Z-RNA IS INDEED PRODUCED DURING VIRUS INFECTIONS AND IS A LIGAND FOR THE NECROPTOSIS-ACTIVATING HOST SENSOR PROTEIN ZBP1. OUR PRELIMINARY RESULTS NOW SHOW THAT THE Z-DNA WITHIN CURLI:DNA COMPLEXES ACTIVATES ZBP1 IN INTESTINAL EPITHELIAL CELLS (IECS) AND FIBROBLASTS, RESULTING IN RIPK3- DEPENDENT NECROPTOSIS OF THESE CELLS. THESE FINDINGS ALLOW US TO PUT FORWARD THE HYPOTHESIS THAT Z-DNA WITHIN CURLI:DNA FIBRILS IN SALMONELLA BIOFILMS ACTIVATES ZBP1 TO INSTIGATE RIPK3-DEPENDENT NECROPTOSIS IN INTESTINAL EPITHELIAL CELLS (IECS) AND OTHER CELL TYPES. NECROPTOSIS, IN TURN, CAUSES CELL LOSS AND DISRUPTS GUT BARRIER INTEGRITY, RELEASING INFLAMMATORY MEDIATORS THAT EVENTUALLY RESULT IN AUTOIMMUNITY AND REA. AS NECROPTOSIS IS A HIGHLY INFLAMMATORY MODE OF CELL DEATH, THESE FINDINGS, AT LONG LAST, SUPPLY A PLAUSIBLE MECHANISM FOR WHY CURLI:DNA COMPLEXES ARE HYPERINFLAMMATORY, AND, THEREFORE, FOR HOW SALMONELLA TRIGGERS REA. THEY ALSO IDENTIFY Z-DNA AS A NEW PAMP, IMPLICATE ZBP1 – UNTIL NOW CONSIDERED AN ANTIVIRAL PROTEIN – AS A SENSOR OF BACTERIAL INFECTIONS, AND POSITION RIPK3 INHIBITORS AS UNANTICIPATED NEW THERAPEUTICS FOR THE TREATMENT OF REA. IN AIM 1, WE WILL DETERMINE HOW Z-DNA FORMS WITHIN CURLI:DNA COMPLEXES, AND HOW Z-DNA ACTIVATES ZBP1. IN AIM 2, WE WILL IDENTIFY THE ZBP1-DRIVEN IMMUNE PATHWAYS THAT PROMOTE CURLI:DNA INDUCED INFLAMMATION AND REA, AND DETERMINE THE CELL TYPES IN WHICH ZBP1 SIGNALING IS IMPORTANT FOR PATHOGENESIS. IN AIM 3, WE WILL EVALUATE WHETHER NECROPTOSIS BLOCKADE WITH RIPK3 KINASE INHIBITORS WILL HAVE PREVENTIVE OR THERAPEUTIC BENEFIT IN REA. A SUCCESSFUL OUTCOME TO THESE STUDIES WILL OUTLINE AN ENTIRELY NEW MECHANISM OF SALMONELLA-TRIGGERED INFLAMMATION. THEY ALSO STAND TO OPEN UP EXCITING NEW THERAPEUTIC AVENUES FOR SALMONELLA-INDUCED REA, WITH POTENTIALLY GAME-CHANGING RAMIFICATIONS FOR THIS CURRENTLY INCURABLE DISEASE.

INVESTIGATING GENETIC ANCESTRY INFLUENCES ON ORAL CAVITY AND LARYNGEAL CANCER SURVIVAL DISPARITIES

EXTENDING A CARIBBEAN BASED COHORT TO PROMOTE US-CARIBBEAN COMPARISONS TO FACILITATE RESEARCH ADDRESSING BLACK HEALTH DISPARITIES

LEGACY: A COHORT OF YOUTH IN FAMILIES FROM THE BREAST CANCER FAMILY REGISTRY

COMPARATIVE EFFECTIVENESS OF VIRTUAL AND OPTICAL COLONOSCOPY FOR CRC SURVEILLANCE

SPECIFICITY OF EFFECTOR ACTIVATION BY RHO FAMILY GTPASES

UNDERSTANDING PSYCHOSOCIAL AND IMMUNOLOGIC RESPONSES IN INDOLENT LYMPHOPROLIFERATIVE DISORDERS

ENHANCING HIV PREVENTION THROUGH A MULTI-LEVEL COMMUNITY INTERVENTION TO PROMOTE

NOVEL ROLE OF THPOK IN MAMMARY CARCINOMA

MATTHEW SHEPARD AND JAMES BYRD, JR. HATE CRIMES TRAINING AND TECHNICAL ASSISTANCE PROGRAM

GLOBAL SUPPORT FOR NATIONAL POLICY, PRACTICE, AND TECHNOLOGY PROJECT

COMPENSATORY MECHANISMS THAT PROMOTE HOMOLOGOUS RECOMBINATION IN BRCA1 MUTANT CANCERS

ADDRESSING SEXUAL CONCERNS IN BREAST CANCER SURVIVORS: RCT OF A NOVEL COUPLE-BASED INTERVENTION

HAPPY BIRTHDAY, LEONARD RIGOROUS EVALUATION STUDY - INSTITUTE OF WOMEN AND ETHNIC STUDIES (IWES) IS A THREE-TIME AWARDEE OF FEDERAL TEEN PREGNANCY PREVENTION (TPP) FUNDING FROM THE HHS OFFICE OF POPULATION AFFAIRS (OPA) TO REPLICATE PROVEN-EFFECTIVE PROGRAMS AND STRATEGIES DESIGNED TO PREVENT UNINTENDED TEEN PREGNANCY AND HIV/STIS IN LOUISIANA (BELIEVE IN YOUTH - NOLA, FY 2010; BELIEVE IN YOUTH - LOUISIANA, FY 2015; AND BELIEVE IN YOUTH - LOUISIANA 2.0, FY 2020). THROUGH THESE AWARDS, IWES HAS IMPLEMENTED EVIDENCE-BASED, TRAUMA-INFORMED, COMPREHENSIVE REPRODUCTIVE HEALTH AND POSITIVE YOUTH DEVELOPMENT PROGRAMS–REACHING OVER 15,000 YOUTH ACROSS LOUISIANA PUBLIC HEALTH REGIONS 1, 2, AND 3 IN URBAN, SUBURBAN, AND RURAL SETTINGS. SINCE ITS FOUNDING IN 1993, IWES HAS INTEGRATED FILM AND OTHER MEDIA PRODUCTS INTO EACH OF ITS COMMUNITY-CENTERED PUBLIC HEALTH INITIATIVES TO ILLUMINATE THE STORIES, EXPERIENCES, AND PERSPECTIVES OF THE COMMUNITIES SERVED. STORYTELLING AND NARRATIVE CHANGE THROUGH MEDIA HAVE BEEN THE CORNERSTONE OF MANY OF IWES’ INITIATIVES, INCLUDING DEVELOPMENT OF ORIGINAL CURRICULA AND INTERVENTION WITH FOCUS ON HEALTH EDUCATION AND PROMOTION, PREVENTION OF ADVERSE HEALTH OUTCOMES, AND STIGMA REDUCTION. IN FALL 2021, IWES RECEIVED A SUBAWARD FROM POLICY & RESEARCH GROUP (PRG), A RECIPIENT OF AN OPA FY 2020 TIER 2 INNOVATION AND IMPACT NETWORK GRANT WHICH FUNDS A JUVENILE JUSTICE INNOVATION & IMPACT NETWORK (JJIIN). PRG HAS PROVIDED TECHNICAL ASSISTANCE AND SUPPORT TO IWES AND FIVE ADDITIONAL NETWORK COLLABORATORS OF THE JJIIN TO DEVELOP AND TEST TPP INTERVENTIONS FOR YOUTH INVOLVED IN THE JUSTICE SYSTEM USING ENTERTAINMENT EDUCATION TO REDUCE SEXUAL RISK BEHAVIORS AND IMPROVE HEALTH. THROUGH THIS OPPORTUNITY, IWES CREATED A NARRATIVE SHORT FILM ENTITLED HAPPY BIRTHDAY, LEONARD AND DEVELOPED A COMPLEMENTARY INTERVENTION PACKAGE WITH A FACILITATION GUIDE AND A WORKBOOK WITH A RESOURCE GUIDE. PILOTING OF THE INTERVENTION IN SPRING 2023 PRODUCED COMPELLING PRELIMINARY RESEARCH DEMONSTRATING THE INTERVENTION IS WELL-RECEIVED BY YOUTH OF THE TARGET POPULATION AND SHOWS PROMISE FOR REDUCING UNINTENDED TEEN PREGNANCY AND STIS. IWES, WITH PRG SERVING AS ITS INDEPENDENT EVALUATOR, WILL RIGOROUSLY EVALUATE THE HAPPY BIRTHDAY, LEONARD INTERVENTION WITHIN A RANDOMIZED CONTROL TRIAL IN THE STATES OF LOUISIANA, ALABAMA, GEORGIA, AND MICHIGAN TO AFFIRM ITS EFFICACY AND DISSEMINATE FINDINGS AND LESSONS LEARNED FROM THE RESEARCH TO CONTRIBUTE TO THE GROWING EVIDENCE BASE OF ENTERTAINMENT EDUCATION INNOVATIONS.

MAKING PROUD CHOICES!-NOLA!

SMALL-MOLECULE EXPLOITATION OF ZBP1-DRIVEN NUCLEAR NECROPTOSIS FOR CANCER IMMUNOTHERAPY - PROJECT SUMMARY/ABSTRACT. IMMUNE CHECKPOINT BLOCKADE (ICB) AND OTHER IMMUNOTHERAPIES HAVE REVOLUTIONIZED CANCER TREATMENT, BUT THE NON-RESPONSIVENESS OF MOST CANCERS TO ICB-BASED MONOTHERAPY REMAINS A SIGNIFICANT PROBLEM. A MAJOR REASON FOR THE NON-RESPONSIVENESS OF THESE SO-CALLED ‘COLD’ TUMORS IS THAT THEY LACK AN IMMUNOGENIC TUMOR MICROENVIRONMENT (TME) AND THUS ESCAPE T-CELL KILLING DESPITE EXPRESSING ICB TARGETS. HOW TO SELECTIVELY INTENSIFY THE IMMUNOGENICITY OF THE TME HAS BEEN AN UNMET CHALLENGE. HERE WE PROPOSE A NEW SMALL-MOLECULE APPROACH THAT ACTIVATES NECROPTOSIS AND TRIGGERS ROBUST INNATE IMMUNE RESPONSES IN THE TME. THIS NEW AVENUE DERIVES FROM OUR WORK ON INFLUENZA A VIRUS (IAV). OUR EARLY FINDINGS SHOWED THAT IAV ACTIVATES NECROPTOSIS IN INFECTED CELLS. NECROPTOSIS KILLS INFECTED CELLS AND IS HIGHLY IMMUNOGENIC. IT IS INITIATED WHEN VIRAL RNAS ACTIVATING THE HOST PROTEIN ZBP1. RECENTLY, AND HIGHLY RELEVANT FOR CANCER IMMUNOTHERAPY, WE FOUND THAT ZBP1 ACTIVATES NECROPTOSIS FROM THE NUCLEUS. SUCH ‘NUCLEAR NECROPTOSIS’ IS SIGNIFICANTLY MORE IMMUNOGENIC THAN CONVENTIONAL (CYTOPLASM-INITIATED) NECROPTOSIS BECAUSE IT RUPTURES THE NUCLEUS AND RELEASES HYPER-INFLAMMATORY NUCLEAR DAMPS INTO THE EXTRACELLULAR SPACE. WE ALSO FOUND THAT THE VIRAL RNAS THAT ACTIVATE ZBP1 ARE Z-RNAS. ALTHOUGH THESE UNIQUE ZBP1 ACTIVATORS SHOULD BE SUPERB ADJUVANTS FOR ICB, Z-RNA IS UNSTABLE AND HARD TO PRODUCE ABSENT VIRUS INFECTION. Z-DNA, HOWEVER, IS STRUCTURALLY ALMOST IDENTICAL TO Z-RNA, BINDS ZBP1 WITH THE SAME AFFINITY, AND CAN BE STABLY PRODUCED IN EUKARYOTIC CELLS BY DISTORTING DNA INTO THE Z-CONFORMATION. THIS SUGGESTED THAT A COMPOUND THAT CAN GENERATE Z-DNA IN CELLS WOULD ACTIVATE ZBP1 AND TRIGGER ON-DEMAND NUCLEAR NECROPTOSIS WITHOUT NEED FOR VIRUS INFECTION. SUCH A COMPOUND WOULD FILL THE LONG-UNMET NEED FOR A NECROPTOSIS AGONIST FOR USE IN CANCER IMMUNOTHERAPY. WE HAVE NOW IDENTIFIED A SMALL MOLECULE, CURAXIN, WHICH INDUCES Z-DNA FORMATION IN LIVE CELLS AND DIRECTLY ACTIVATES ZBP1 TO TRIGGER ‘ON-DEMAND’ NUCLEAR NECROPTOSIS IN CELLS OF THE TME. THESE AND OTHER FINDINGS ALLOW US TO PROPOSE THE HYPOTHESES THAT CURAXIN ALTERS CHROMATIN STRUCTURE AND INDUCES THE FORMATION OF Z-DNA; THAT SUCH Z-DNA RECRUITS ZBP1 TO THE NUCLEUS AND TRIGGERS NUCLEAR NECROPTOSIS; AND THAT CURAXIN-INDUCED NUCLEAR NECROPTOSIS WILL GREATLY IMPROVE ICB TREATMENT OUTCOMES. IN THIS PROPOSAL, WE WILL ASK HOW CURAXIN TRIGGERS Z-DNA FORMATION (AIM 1), HOW Z-DNA ACTIVATES ZBP1 AND NUCLEAR NECROPTOSIS (AIM 2), AND WHETHER INDUCTION OF NUCLEAR NECROPTOSIS BY CURAXIN HAS COMBINATORIAL BENEFIT WITH ICB IN CLINICALLY-RELEVANT MOUSE MODELS OF MELANOMA (AIM 3). THE SUCCESSFUL COMPLETION OF THESE AIMS WILL OUTLINE AN ENTIRELY NEW SMALL- MOLECULE BASED STRATEGY TO ACTIVATE A HIGHLY INFLAMMATORY FORM OF NECROPTOSIS AND POTENTIATE ICB-BASED IMMUNOTHERAPIES, WITH IMPORTANT CLINICAL RAMIFICATIONS.

TREATMENT OF CBS DEFICIENCY WITH PROTEOSTASIS MODULATORS

BRONX FAITH-BASED INITIATIVE TO ELIMINATE RACIAL DISPARITIES IN HEALTH

PROGRAM PURPOSE/AWARD TO MOVE SCSEP PARTICIPANTS INTO UNSUBSIDIZED EMPLOYMENT IN BOTH THE PUBLIC AND PRIVATE SECTORS, PROMOTE PART-TIME WORK EXPERIENCES IN COMMUNITY SERVICE ASSIGNMENTS FOR UNEMPLOYED LOW-INCOME INDIVIDUALS WHO ARE 55 YEARS OF AGE OR OLDER, AND FOSTER SELF-SUFFICIENCY AMONG SUCH INDIVIDUALS. BY STATUTE, SCSEP STATE GRANTS ARE AWARDED TO GOVERNORS (22% OF TOTAL GRANT FUNDING) AND ARE DETERMINED BY FORMULA; NATIONAL NON-PROFITS (NATIONAL GRANTEE) THAT OPERATE IN MULTI-STATE SERVICE AREAS (78% OF TOTAL GRANT FUNDING) ARE AWARDED GRANTS THROUGH A COMPETITION EVERY FOUR YEAR. APPROPRIATION LEVELS DETERMINE THE NUMBER OF TOTAL SLOTS, AND GRANTEES SERVE ALL SLOTS IN THEIR SERVICE AREA. PROGRAMS RUN ON A PROGRAM YEAR (JULY 1 - JUNE 30). ACTIVITIES TO BE PERFORMED PRIMARILY COMMUNITY SERVICE EMPLOYMENT ACTIVITIES, WHERE PARTICIPANTS WORK PART-TIME AT A COMMUNITY SERVICE LOCATION (NOT FOR PROFIT) FOR MINIMUM WAGE. THIS WORK EXPERIENCE PREPARES THEM FOR UNSUBSIDIZED EMPLOYMENT WHILE RECEIVING SERVICES IN THE PROGRAM OR AFTER THEY HAVE COMPLETED THE PROGRAM. PARTICIPANTS ALSO RECEIVE SUPPORT SERVICES, ON-THE-JOB-TRAINING, INDIVIDUAL EMPLOYMENT PLANS, AND CAN RECEIVE CLASSROOM AND SKILLS TRAINING. DELIVERABLES & EXPECTED OUTCOME SCSEP GRANT RECIPIENTS MUST MEET THEIR CORE MEASURES OF PERFORMANCE WHICH REFERS TO HOURS (IN THE AGGREGATE) OF COMMUNITY SERVICE EMPLOYMENT; THE PERCENTAGE OF PROJECT PARTICIPANTS WHO ARE IN UNSUBSIDIZED EMPLOYMENT DURING THE SECOND QUARTER AFTER EXIT FROM THE PROJECT; THE PERCENTAGE OF PROJECT PARTICIPANTS WHO ARE IN UNSUBSIDIZED EMPLOYMENT DURING THE FOURTH QUARTER AFTER EXIT FROM THE PROJECT; THE MEDIAN EARNINGS OF PROJECT PARTICIPANTS WHO ARE IN UNSUBSIDIZED EMPLOYMENT DURING THE SECOND QUARTER AFTER EXIT FROM THE PROJECT; INDICATORS OF EFFECTIVENESS IN SERVING EMPLOYERS, HOST AGENCIES, AND PROJECT PARTICIPANTS; THE NUMBER OF ELIGIBLE INDIVIDUALS SERVED; AND MOST-IN-NEED. INTENDED BENEFICIARY(IES) ADULTS AGE 55 AND OVER WITH INCOME AT OR BELOW 125% OF POVERTY LEVEL AND NOT JOB READY. SUBRECIPIENT ACTIVITIES YES, GRANT RECIPIENTS CAN SUB TO OTHER LOCAL AGENCIES AND NON-PROFIT ORGANIZATIONS.

TEACHING HEALTH CENTER GRADUATE MEDICAL EDUCATION PROGRAM

NEW TOOLS FOR UNDERSTANDING METASTASIS THROUGH TISSUE RESIDENT CELLS: ENABLING AN EXTENSIVE MEDICINE STRATEGY FOR METASTATIC DISEASE

DRU SJODIN NATIONAL SEX OFFENDER PUBLIC WEBSITE (NSOPW) MAINTENANCE AND OPERATION

REDUCING URBAN CERVICAL CANCER DISPARITIES USING A TAILORED MHEALTH INTERVENTION TO ENHANCE COLPOSCOPY ATTENDANCE - PROJECT SUMMARY/ABSTRACT CERVICAL CANCER IS ONE OF THE MOST PREVENTABLE CANCERS AND WHEN DIAGNOSED EARLY AND APPROPRIATELY TREATED, THE LIKELIHOOD OF SURVIVAL IS CLOSE TO 100%. HOWEVER, NONATTENDANCE AT ABNORMAL FOLLOW-UP APPOINTMENTS REACHES 63% AMONG URBAN, UNDERSERVED MINORITY WOMEN. CERVICAL CANCER PREVENTION AND TIMELY DIAGNOSIS REQUIRES THAT PATIENTS BE MONITORED OVER TIME. EXISTING INTERVENTION PROTOCOLS TO PROMOTE ATTENDANCE HAVE SIGNIFICANT LIMITATIONS GIVEN A LIMITED FOCUS ON URBAN, UNDERSERVED MINORITY WOMEN AND REDUCED SUSTAINABILITY IN RESOURCE- LIMITED SETTINGS. TO FILL THIS VOID, WE PROPOSE A TAILORED MHEALTH INTERVENTION AVAILABLE IN BOTH ENGLISH AND SPANISH TARGETING FOLLOW-UP ATTENDANCE FOR ABNORMAL TEST FEEDBACK AT 3 URBAN CLINIC SITES SERVING PREDOMINATELY LOW- INCOME MINORITY WOMEN. WE PROPOSE A HYBRID TYPE 1 EFFECTIVENESS-IMPLEMENTATION TRIAL THAT IS THEORETICALLY- GUIDED BY THE COGNITIVE-SOCIAL HEALTH INFORMATION PROCESSING MODEL AND THE EXPLORATION, PLANNING, IMPLEMENTATION AND SUSTAINMENT IMPLEMENTATION FRAMEWORK TO OPERATIONALIZE AND ASSESS THE EFFICACY OF THE HEALTH ENHANCEMENT RESOURCE SYSTEM (HERS) INTERVENTION. HERS AIMS TO INCREASE PATIENT FOLLOW-UP AFTER ABNORMAL TEST RESULTS THROUGH TEXT MESSAGE-BASED BARRIERS COUNSELING FOR WOMEN AND SUPPLEMENTAL TELEPHONE- BASED HEALTH COACHING FOR WOMEN WHO MISS THEIR APPOINTMENT. USING A SEQUENTIAL, MULTIPLE ASSIGNMENT, RANDOMIZED TRIAL (SMART) DESIGN AND STAKEHOLDER-ENGAGED APPROACH OUR AIMS ARE TO: (1) CONDUCT A RANDOMIZED CONTROL TRIAL (RCT) USING THE SMART DESIGN TO EVALUATE THE EFFICACY OF HERS; (2) QUALITATIVELY ASSESS THE CONTEXTUAL FACTORS (PATIENT FACTORS, HEALTHCARE TEAM RESOURCES, AND ORGANIZATIONAL FACTORS) AFFECTING HERS IMPLEMENTATION OUTCOMES AND POTENTIAL FOR SCALABILITY AND SUSTAINABILITY; AND (3) EXPLORE PATIENT-LEVEL MODERATORS OF THE RELATIONSHIP BETWEEN THE HERS INTERVENTION AND ATTENDANCE AT THE COLPOSCOPY APPOINTMENT. WOMEN (N=546) SCHEDULED FOR INITIAL OR REPEAT COLPOSCOPY FOLLOWING AN ABNORMAL TEST RESULT WILL BE RECRUITED AND RANDOMIZED TO ONE OF 2 CONDITIONS (HERS TEXT MESSAGES OR STANDARD OF CARE) AND, THROUGH THE SMART DESIGN, WILL REMAIN IN THEIR ASSIGNED GROUP OR RE-RANDOMIZED TO HERS OR HERS + HEALTH COACHING, DEPENDING ON INITIAL APPOINTMENT ATTENDANCE. THE PRIMARY OUTCOME IS ATTENDANCE AT THE BASELINE COLPOSCOPY AND THE SECONDARY OUTCOME IS LONG-TERM FOLLOW-UP AT 12-MONTHS. ADDITIONAL RESEARCH QUESTIONS WILL EVALUATE THE BEST INITIAL INTERVENTION (E.G., STANDARD OF CARE OR HERS) FOR INCREASING ATTENDANCE AT THE BASELINE AND 12-MONTH FOLLOW-UP APPOINTMENTS. IN-DEPTH INTERVIEWS WITH HEALTHCARE STAKEHOLDERS AND EXIT INTERVIEWS WITH PATIENTS WILL ASSESS THE IMPACT OF TEAM AND HEALTHCARE SYSTEM CONTEXT ON THE HERS IMPLEMENTATION. FINALLY, EXPLORATORY ANALYSES SEEK TO IDENTIFY MODERATORS OF INTERVENTION EFFECT (E.G., RACE/ETHNICITY, SPANISH OR ENGLISH LANGUAGE, HEALTH LITERACY) AT BASELINE AND 12-MONTH FOLLOW-UP APPOINTMENTS TO EVALUATE WHICH PATIENTS SHOULD RECEIVE THE HERS INTERVENTION AS A FIRST-LINE INTERVENTION RATHER THAN STANDARD OF CARE.

MECHANISM TRANSCRIPT ELONGATION IN CHROMATIN

THE OFFICE ON VIOLENCE AGAINST WOMEN (OVW) TRAINING AND TECHNICAL ASSISTANCE (TA) INITIATIVE PROVIDES OVW GRANTEES AND SUBGRANTEES WITH THE EXPERTISE AND SUPPORT THEY NEED TO DEVELOP AND IMPLEMENT SUCCESSFUL STATE, LOCAL, TRIBAL, AND CAMPUS PROJECTS; INCREASE VICTIM SAFETY; AND BOLSTER OFFENDER ACCOUNTABILITY. THROUGH COOPERATIVE AGREEMENTS, OVW SUPPORTS EDUCATIONAL INITIATIVES, CONFERENCES, PEER-TO-PEER CONSULTATIONS, AND TARGETED ASSISTANCE THAT ALLOW CURRENT AND POTENTIAL GRANTEES AND SUBGRANTEES TO LEARN FROM EXPERTS AND ONE ANOTHER ABOUT HOW TO OVERCOME OBSTACLES AND INCORPORATE PROMISING PRACTICES IN THEIR EFFORTS TO ADDRESS VIOLENCE AGAINST WOMEN. IN ADDITION, OVW IS FOCUSED ON BUILDING THE CAPACITY OF THE CRIMINAL AND CIVIL JUSTICE SYSTEMS AND VICTIM SERVICE ORGANIZATIONS TO RESPOND EFFECTIVELY TO DOMESTIC VIOLENCE, DATING VIOLENCE, SEXUAL ASSAULT, AND STALKING AND TO FOSTER PARTNERSHIPS BETWEEN ORGANIZATIONS THAT HAVE NOT TRADITIONALLY WORKED TOGETHER TO ADDRESS VIOLENCE AGAINST WOMEN. WITH FY 2023 TA INITIATIVE FUNDING, THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH (IIR) WILL CONTINUE TO IMPLEMENT THE NATIONAL VIOLENCE AGAINST WOMEN LAW ENFORCEMENT TRAINING AND TECHNICAL ASSISTANCE CONSORTIUM (LETTAC). LETTAC PROVIDES STREAMLINED TRAINING AND TECHNICAL ASSISTANCE TO LAW ENFORCEMENT AND CRIMINAL JUSTICE SYSTEM PROFESSIONALS TO DELIVER TRAUMA-INFORMED, SURVIVOR-CENTERED, CULTURALLY SPECIFIC RESPONSES TO ADDRESS DOMESTIC VIOLENCE, DATING VIOLENCE, SEXUAL ASSAULT, AND STALKING. OVER THE COURSE OF THE PROJECT PERIOD, IIR WILL PROVIDE TRAINING AND TECHNICAL ASSISTANCE; UPDATE AND MAINTAIN THE LETTAC RESOURCE CENTER; PRESENT IN-PERSON, ON-SITE, AND VIRTUAL TRAININGS AND NATIONAL SUMMITS; CONDUCT PRESENTATIONS AT OTHER OVW AND NON-OVW CONFERENCES; DEVELOP TOOLKITS AND OTHER RESOURCES; PARTICIPATE IN REGIONAL AND NATIONAL CONVENINGS, AND COORDINATE AND DELIVER SPECIAL PROJECTS AS GUIDED BY OVW. THIS PROJECT SUPPORTS FY 2023 TA INITIATIVE PURPOSE AREA 49: COMPREHENSIVE FOR LAW ENFORCEMENT TRAINING AND TECHNICAL ASSISTANCE. THIS AWARD IS FOR YEARS 4 AND 5 OF A FIVE-YEAR COMPREHENSIVE TA PROJECT, AWARDED COMPETITIVELY IN FY 2020, AND IS A CONTINUATION OF 2020-TA-AX-K033

PRIVACY AND CIVIL LIBERTIES PROTECTIONS FOR INFORMATION SHARING PRACTITIONERS IMPLEMENTATION PROJECT

PATHOGENESIS OF MALIGNANT MESOTHELIOMA BY THE HUMAN POLYCOMB COMPLEX BAP1-ASXL

BRONX HEALTH REACH: TOWARDS A HEALTHIER BRONX

HEALTH CENTER CORONAVIRUS AID, RELIEF, AND ECONOMIC SECURITY (CARES) ACT FUNDING

NATIONAL ASHANTI ALERT NETWORK TRAINING AND TECHNICAL ASSISTANCE PROGRAM

FOLIC ACID SUPPLEMENTATION AND COLITIS-ASSOCIATED COLON CARCINOGENESIS - PROJECT SUMMARY/ABSTRACT PATIENTS WITH ULCERATIVE COLITIS, A FORM OF INFLAMMATORY BOWEL DISEASE, FACE AN INCREASED RISK OF DEVELOPING COLORECTAL CANCER. ALTHOUGH ADVANCES HAVE BEEN MADE IN THE THERAPEUTIC MANAGEMENT OF THIS DISEASE, MUCH LESS ATTENTION HAS BEEN GIVEN TO THE DEVELOPMENT OF CANCER PREVENTIVE STRATEGIES FOR THIS HIGH-RISK POPULATION. ULCERATIVE COLITIS PATIENTS OFTEN DEVELOP FOLATE DEFICIENCIES THAT REQUIRE SUPPLEMENTATION WITH FOLIC ACID (FA), A SYNTHETIC FORM OF FOLATE. THE EFFECT OF FA ON RISK FOR COLORECTAL CANCER REMAINS UNCLEAR AND THE RECENT SUGGESTION THAT FA SUPPLEMENTS MAY BE USEFUL IN PREVENTING COLITIS-ASSOCIATED COLORECTAL CANCER IS OF GREAT CONCERN. PRELIMINARY STUDIES FROM THIS GROUP PROVIDE THE FIRST EVIDENCE THAT FA SUPPLEMENTATION (8 MG/KG DIET) CAUSES A DOSE-DEPENDENT INCREASE IN THE FORMATION OF COLORECTAL TUMORS IN MICE WITH AOM/DSS-INDUCED COLITIS. RESULTS FROM ASSOCIATED RNASEQ AND IN VITRO ANALYSES SUGGEST THAT FA PROMOTES TUMORIGENESIS BY ACTIVATING ERK AND INDUCING NF-B SIGNALING IN COLONIC EPITHELIAL CELLS WITH DYSFUNCTIONAL P53, THE GATEKEEPING EVENT IN THE DEVELOPMENT OF COLITIS-ASSOCIATED CANCERS. THE HYPOTHESIS OF THE PROPOSED STUDIES IS THAT FA SUPPLEMENTATION PROMOTES UC-ASSOCIATED CANCER IN CELLS WITH DYSFUNCTIONAL/MUTANT P53, BUT NOT IN CELLS WITH WILD TYPE P53, VIA AN INFLAMMATORY PATHWAY MEDIATED BY ERK AND NF-B. THE MECHANISM BY WHICH FA INDUCES TUMOR FORMATION WILL BE INVESTIGATED IN AIM 1 USING CRISPR ENGINEERED ISOGENIC HUMAN RKO COLON CARCINOMA CELLS WITH VARYING P53 STATUS (P53+/+, P53-/- AND P53+/MUT). THE IMPACT OF FA AND DYSFUNCTIONAL P53 ON ACTIVATION OF ERK, NF-B SIGNALING, AS WELL AS CELL CYCLE PROGRESSION WILL BE EVALUATED. IN VITRO FINDINGS WILL BE VALIDATED IN AIM 2, WHERE COMPLIMENTARY IN VIVO ANALYSES WILL EXAMINE THE COMBINED EFFECT OF FA AND MUTANT P53 ON DSS-INDUCED COLITIS-ASSOCIATED TUMORIGENESIS AND ASSOCIATED BIOMARKERS IN P53+/+ AND P53+/515A (MUTANT) MICE. IN ADDITION, THE IMPACT OF HIGH DOSE FA GIVEN PRIOR TO THE INDUCTION OF COLITIS WILL BE EXAMINED. TUMOR INCIDENCE AND MULTIPLICITY, AS WELL AS DEGREE OF INTESTINAL INFLAMMATION, WILL SERVE AS PRIMARY ENDPOINTS OF THESE STUDIES. BASED ON THE IMPORTANT CONTRIBUTION OF INTESTINAL MICROBIOTA TO COLITIS AND THEIR ABILITY TO SYNTHESIZE FOLATE DE NOVO, THE IMPACT OF FA ADMINISTRATION ON THE DIVERSITY AND RELATIVE ABUNDANCE OF FECAL AND ADHERENT BACTERIA WITHIN THE INTESTINE OF P53+/515A MICE WITH DSS-INDUCED COLITIS WILL BE EXAMINED IN AIM 3. MICE WILL BE TREATED WITH 5-AMINOSALICYLIC ACID (5-ASA), A COMMON MAINTENANCE THERAPY FOR ULCERATIVE COLITIS, FOR THE DURATION OF FA EXPOSURE TO RECAPITULATE THE CLINICAL THERAPY OF A PATIENT FOLLOWING A DIAGNOSIS OF COLITIS. THE COMPOSITION OF THE FECAL AND COLON-ADHERENT MICROBIOMES, DETERMINED FROM 16S RRNA AND METAGENOMIC SEQUENCING DATA, WILL BE CORRELATED WITH COLONIC INFLAMMATION, BARRIER FUNCTION AND TUMOR INCIDENCE/MULTIPLICITY. THE RESULTS ARE EXPECTED TO PROVIDE SIGNIFICANT INSIGHT INTO THE IMPACT OF FA SUPPLEMENTATION ON COLITIS-ASSOCIATED TUMORIGENESIS AND INFORM THE FIRST GUIDELINES FOR THE USE OF FA SUPPLEMENTS BY PATIENTS WITH ULCERATIVE COLITIS.

EARLY HEAD START CHILD CARE PARTNERSHIP

MAINTENANCE AND OPERATION OF THE DRU SJODIN NATIONAL SEX OFFENDER PUBLIC WEBSITE

TOWARD A HEALTHIER BRONX

BAYESIAN STATISTICS AND ALGORITHMS FOR HOMOLOGY MODELING

COOPERATIVE AGREEMENT FOR THE NORTHEAST ADDICTION TECHNOLOGY TRANSFER CENTERS

GANG RESISTANCE EDUCATION AND TRAINING (G.R.E.A.T.) NATIONAL TRAINING AND TECHNICAL ASSISTANCE PROGRAM

NEIGHBORHOOD, SOCIAL CONNECTEDNESS, AND ALLOSTATIC LOAD IN US CHINESE IMMIGRANTS - PROJECT SUMMARY ASIAN AMERICANS ARE THE FASTEST-GROWING RACIAL/ETHNIC GROUP IN THE UNITED STATES (US), AND ASIANS OF CHINESE ORIGIN REPRESENT THE LARGEST SINGLE US ASIAN SUBGROUP. AMONG CHINESE AMERICANS, THE MAJORITY (62%) ARE FOREIGN-BORN. ALTHOUGH CHINESE IMMIGRANTS REPORT BETTER HEALTH THAN THEIR US-BORN COUNTERPARTS, THIS HEALTH AD- VANTAGE DECREASES OVER TIME WITH INCREASING DURATION OF RESIDENCE. THE DOWNWARD HEALTH TRAJECTORY HAS BEEN PRIMARILY ATTRIBUTED TO BEHAVIORAL ACCULTURATION, BUT IMMIGRATION ALSO ENCOMPASSES EXTENSIVE STRESS AND SOCIAL ISOLATION. SOCIAL ISOLATION, IN TURN, MAY INCREASE CHRONIC DISEASE RISK THROUGH DYSREGULATION IN MULTIPLE SYSTEMS – NEUROENDOCRINE, CARDIOVASCULAR, METABOLIC, INFLAMMATORY, IMMUNE – WHICH TOGETHER ARE INDICATIVE OF ALLOSTATIC LOAD (AL). INDEED, STUDIES OF OTHER US IMMIGRANT POPULATIONS (MOSTLY AFRICAN OR LATINX) HAVE NOTED THAT LONGER US RESIDENCE IS ASSOCIATED WITH HIGHER AL. DESPITE THESE FINDINGS, THE QUESTION OF WHETHER IMMIGRANTS’ EXPERI- ENCES OF SOCIAL ISOLATION AFFECT DISEASE RISK AND HEALTH HAS NOT BEEN WELL STUDIED. SOCIAL CONNECTEDNESS, OR THE EXTENT TO WHICH ONE PERCEIVES ONESELF TO BE CLOSELY AND MEANINGFULLY CONNECTED WITH OTHER INDIVIDUALS, GROUPS, AND SOCIETY AS A WHOLE, IS A POSSIBLE STRATEGY TO ADDRESS SOCIAL ISOLATION, BUT THE CONDITIONS AND CONTEXTS THAT FOSTER SOCIAL CONNECTEDNESS ARE NOT WELL UNDERSTOOD. LIVING IN ETHNIC ENCLAVES (I.E. NEIGHBORHOODS WITH A GREATER PROPORTION OF PEOPLE OF THE SAME ETHNICITY) MAY HAVE POSITIVE EFFECTS AMONG CHINESE IMMIGRANTS INCLUDING GREATER SOCIAL SUPPORT AND LESS LONELINESS. IT HAS BEEN SUGGESTED THAT ENCLAVES PROVIDE THE NECESSARY STRUCTURAL CONDITIONS – NAMELY, PHYSICAL AND SOCIAL SPACES – FOR SOCIAL CONNECTEDNESS TO DEVELOP, ALTHOUGH THIS HAS YET TO BE CONFIRMED IN LARGE-SCALE STUDIES. THUS, WE PROPOSE A COMPREHENSIVE INVESTIGATION OF THE FOLLOWING INTERRELATED QUESTIONS: DO POST-MIGRATION EXPERIENCES OF SOCIAL ISOLATION/CONNECTEDNESS HAVE BIOLOGIC CORRELATES AMONG FOREIGN-BORN CHINESE? AND DO ETHNIC ENCLAVES CONTRIBUTE TO SOCIAL CONNECTEDNESS IN THIS POPULATION; IF SO, HOW? TO ADDRESS THESE QUESTIONS, WE WILL RECRUIT A COHORT OF 600 FOREIGN-BORN CHINESE ACROSS THE PHILADELPHIA REGION, INCLUDING RESIDENTS OF ETHNIC ENCLAVES AS WELL AS RESIDENTS OF NEIGHBORHOODS LACKING THE CO-ETHNIC DENSITY AND RESOURCES OF RECOGNIZED ENCLAVES. SPECIFIC AIMS ARE TO: (1) EXAMINE ASSOCIATIONS OF SOCIAL CONNECTEDNESS AND SOCIAL ISOLATION WITH AL IN A COHORT OF US CHINESE IMMIGRANTS; AND (2) EXPLORE WHETHER AND HOW ENCLAVE RESI- DENCE AND ENGAGEMENT WITH ENCLAVE-BASED RESOURCES ARE ASSOCIATED WITH SOCIAL CONNECTEDNESS. DATA COLLECTION WILL INCLUDE QUESTIONNAIRES (E.G., SOCIAL CONNECTEDNESS, ISOLATION, ENGAGEMENT WITH ENCLAVE RESOURCES), BLOOD PRESSURE, ANTHROPOMETRY, AND FASTING BLOOD SAMPLES ANALYZED FOR MARKERS OF AL. ADDRESSES OF RESIDENCES AND LOCATIONS OF ACTIVITIES (E.G., SHOPPING, RELIGIOUS SERVICES) WILL BE GEOCODED. LONGITUDINAL ASSESSMENTS WILL BE OBTAINED AT 2-YEAR FOLLOW-UP TO IDENTIFY CHANGES IN MARKERS OF AL AND CORRELATES OF CHANGES IN THOSE MEASURES. PROJECT FINDINGS WILL IDENTIFY THE MOST VULNERABLE INDIVIDUALS AND NEIGHBORHOODS TO TARGET FOR OUTREACH AND PINPOINT THE CRITICAL COMMUNITY-LEVEL RESOURCES FOR PROMOTING POSITIVE HEALTH TRAJECTORIES IN THIS IMMIGRANT POPULATION.

PANCREATIC CANCER-ASSOCIATED FIBROBLASTS: FUNCTION, DETECTION, AND REGULATION - PROJECT SUMMARY/ABSTRACT PANCREATIC CANCER INDUCES A FIBROUS MICROENVIRONMENT, DESMOPLASIA, WHICH SPANS MOST OF THE TUMOR MASS AND CONTAINS CANCER-ASSOCIATED FIBROBLASTS (CAFS). CAFS SUSTAIN A CANCER HOMEOSTATIC EQUILIBRIUM BY PRODUCING EXTRACELLULAR MATRICES (ECMS) AND SECRETING INFLAMMATORY FACTORS. THE ECM PRODUCED BY CAFS PROMPTS NORMAL FIBROBLASTS TO UNDERGO ACTIVATION AND TRANSITION INTO CAFS, THEREBY PROPAGATING DESMOPLASTIC EXPANSION IN A POSITIVE FEEDBACK LOOP. WHILE THE NORMAL MICROENVIRONMENT SUPPRESSES TUMOR ONSET, DESMOPLASIA CAN EITHER SUPPORT OR AVERT PANCREATIC CANCER. A BETTER UNDERSTANDING OF DESMOPLASTIC EXPANSION AND THE ECM FACTORS THAT CONTROL IT COULD ENABLE US TO FAVOR ITS ANTI-CANCER FUNCTIONS. IN FACT, SEVERAL CLINICAL TRIALS INCLUDING SOME CONDUCTED AT FOX CHASE, AIM AT “NORMALIZING DESMOPLASIA” WITH THE GOAL OF HARNESSING CAF’S ANTI-TUMOR EFFECTS. OF NOTE, WE HAVE DEFINED A SIGNALING AXIS THAT DEPENDS ON CAF-ECM AND INCLUDES ITS MAIN RECEPTORS, INTEGRINS, AND SOME ACTIN BUNDLING, PARTICULAR ENDOCYTIC REGULATORY PROTEINS, AND AN EXTRACELLULARLY TETHERED PRESYNAPTIC PROTEIN KNOWN AS NETRING1. OF NOTE, NETRING1 NECESSITIES CO-RECEPTORS IN CIS AND IN TRANS TO SIGNAL AND WE REVEALED THAT IN RESPONSE TO ECM NETRING1 DRIVES PRO-TUMOR CAF FUNCTION. WE ALSO REPORTED THAT ECM INDUCED PRO-TUMOR CAF ACTIVATION INCLUDES THE ENDOCYTIC LOCALIZATION OF THE ACTIVE CONFORMATION OF AN IMPORTANT ECM RECEPTOR, ACTIVATED A5SS1-INTEGRIN (A-A5), WHICH WE POSIT REGULATES THE PRODUCTION OF TWO UNIQUE EXTRACELLULAR VESICLES. FINALLY, WE SAW THAT THE TRANS CO-RECEPTOR OF NETRING1 IS EXPRESSED IN CAFS AND NEEDED FOR EFFECTIVE FORMATION OF TUMORS WHEN PANCREATIC CANCER CELLS ARE INJECTED INTO THE PANCREATA OF IMMUNE SYSTEM-INTACT MICE. OUR CENTRAL PREMISE PROPOSES THAT CAF PRO-TO-ANTI TUMOR FUNCTION TRANSITION CAN BE ATTAINED VIA BLOCKAGE OF THE ECM-DEPENDENT NETRING1 SIGNALING AXIS, WHICH IS NEEDED TO ACHIEVE THE FUNCTIONAL “DESMOPLASTIC NORMALIZATION” THAT CAN BE DETECTED IN BLOOD. WE PLAN TO TEST THIS HYPOTHESIS IN THREE SPECIFIC AIMS: 1- ASK HOW CAF-ECM REGULATES NETRING1 EXPRESSION AND ENDOCYTIC A-A5 REGULATION AS WELL AS WHAT ARE THE SPECIFIC ECM COMPONENTS THAT ARE RESPONSIBLE FOR NETRING1 EXPRESSION AND CAF’S PRO-TUMOR FUNCTION. 2- INVESTIGATE IF THE UNIQUE EXTRACELLULAR VESICLES GENERATED BY NETRING1 EXPRESSING CAFS COULD BE TRACED SYSTEMICALLY IN PATIENTS’ BLOOD (INCLUDING ARCHIVED SAMPLES AND SAMPLES FROM THE ONGOING TRIAL) AND ASK IF THESE ARE INDICATIVE OF THE TUMOR ASSOCIATED DESMOPLASTIC PRO VS ANTI-PANCREATIC CANCER STATUSES. 3- INQUIRE IF NETRING1’S TRANS RECEPTOR, EXPRESSED IN PRO-TUMORAL FUNCTIONING CAFS, COULD SERVE AS A NEW TARGET. THE STUDY’S ULTIMATE GOAL IS TO CAPITALIZE ON THE NATURAL TUMOR SUPPRESSIVE FUNCTION AND FEATURES OF CAFS AND BLOCK THE TUMOR PROMOTING ONES AS WELL AS TO SYSTEMICALLY INDUCE AND DETECT A PRO-TO-ANTI PANCREATIC CANCER CAF TRANSITION, WHICH COULD BE INDICATIVE OF LOCAL DESMOPLASTIC STATUS, FOR POTENTIAL FUTURE CLINICAL USES.

WERNER SYNDROME PROTEIN, DNA END PROCESSING, AND DOUBLE-STRAND BREAK REPAIR

ARRA - CAPITAL IMPROVEMENT PROGRAM

THE GOAL OF THE CORRECTIONS OFFICER AND STAFF SAFETY AND WELLNESS CENTER (CENTER) IS TO PARTNER WITH THE BUREAU OF JUSTICE ASSISTANCE (BJA) AND IDENTIFY, PRIORITIZE, AND DEVELOP RESOURCES TO ENSURE OFFICER AND STAFF SAFETY, WELLNESS, AND RESILIENCE. THE PROPOSED FUNDING OF $1,500,000 FOR THE PERIOD OF OCTOBER 1, 2022, TO SEPTEMBER 30, 2025, WILL ALLOW FOR THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH (IIR) TO CREATE THE CENTER AND DEVELOP TARGETED TRAININGS AND INNOVATIVE TECHNICAL ASSISTANCE AT THE LEVEL OF EXCELLENCE THAT BJA REQUIRES. THE PROPOSAL IS DESIGNED TO ALLOW IIR TO GENERATE TARGETED TRAININGS FOR CORRECTIONAL WELLNESS AND SAFETY. TRAININGS, PROVIDED ON-SITE OR VIRTUALLY, WILL INCLUDE TOPICS ON PHYSICAL HEALTH AND WELLNESS, MENTAL HEALTH AND EMOTIONAL WELLNESS, AND ENHANCING SAFETY THROUGH SITUATIONAL AWARENESS. THIS PROPOSAL ALSO INCLUDES THE CONTINUED GROWTH OF THE CADRE OF CORRECTIONAL SUBJECT-MATTER EXPERTS WHO CAN ASSIST WITH AND SUPPORT TRAININGS AND TECHNICAL ASSISTANCE. THE CENTER WILL ALSO ACT AS A CLEARINGHOUSE FOR THE MOST RECENT RESEARCH, DATA, AND BEST PRACTICES IN THE CORRECTIONAL SAFETY AND WELLNESS FIELD. ADDITIONAL DELIVERABLES INCLUDE PROVIDING ON-DEMAND TECHNICAL ASSISTANCE TO PRACTITIONERS IN THE FIELD AND CREATING INDIVIDUALIZED TRAINING AND TECHNICAL ASSISTANCE (TTA) PLANS WITH BJA, A PUBLIC-FACING WEBSITE, AND ONLINE WORK TRACKERS AND TRAINING REQUEST DATABASES FOR BJA. ALL CURRICULA, TOOLS, AND RESOURCES WILL BE REGULARLY UPDATED BASED ON RELEVANT RESEARCH AND DATA. EFFECTIVE TTA WILL BE DEVELOPED USING THE MOST CURRENT, USER-FRIENDLY TECHNOLOGY. THE ULTIMATE INTENT OF THE CENTER IS TO BE THE CENTRAL INFORMATION REPOSITORY AND RESOURCE CENTER FOR CORRECTIONAL AGENCIES ACROSS THE NATION.

LUNG CANCER IN NEVER-SMOKERS: ROLE OF ESTROGEN AND ITS METABOLITES

TARGETING THE RAC1 SIGNALING PATHWAY IN MALIGNANT MELANOMA

A-GAME MEASURE WHAT MATTERS: EXPANDING A-GAME TO SCHOOLS, BOARDS, AND AUTHORIZERS

DESIGNING SELECTIVE KINASE INHIBITORS VIA DEEP LEARNING - PROJECT SUMMARY/ABSTRACT MODERN CANCER BIOLOGY LEANS HEAVILY ON KINASE INHIBITORS AS A MEANS TO PROBE THE CONSEQUENCES OF DEACTIVATING A PARTICULAR KINASE, BUT THE MAJORITY OF COMMONLY-USED CHEMICAL PROBES ARE NOT SUFFICIENTLY TARGET- SELECTIVE FOR ROBUST INTERPRETATION OF THE OBSERVED PHENOTYPES. BY ASSEMBLING LARGE PANELS OF KINASES (CORRESPONDING TO MUCH OF THE HUMAN KINOME), IT HAS BECOME POSSIBLE TO DETERMINE THE SELECTIVITY FOR A GIVEN PROBE: HOWEVER, THESE EXPERIMENTS ARE EXPENSIVE AND IMPRACTICAL TO PERFORM AT HIGH THROUGHPUT. WE HAVE RECENTLY DEVELOPED A NEW COMPUTATIONAL APPROACH FOR RAPIDLY AND ACCURATELY BUILDING 3D STRUCTURAL MODELS OF INDIVIDUAL INHIBITOR/KINASE COMPLEXES. AIM 1 OF THIS PROJECT ENTAILS APPLYING DEEP LEARNING TO BUILD MODELS FOR PREDICTING THE BINDING AFFINITY OF INDIVIDUAL INHIBITOR/KINASE PAIRS, USING 3D STRUCTURAL DESCRIPTORS DERIVED FROM THE CORRESPONDING INHIBITOR/KINASE COMPLEXES. AIM 2 OF THIS PROJECT WILL BUILD VERY LARGE COMPUTATIONAL LIBRARIES OF NOVEL CHEMICAL MATTER, ENRICHED IN COMPOUNDS WITH 3D PROPERTIES THAT COMPLEMENT KINASE BINDING SITES. WE WILL FIRST USE THE TOOLS DEVELOPED IN AIM 1 TO RE-EVALUATE THE SELECTIVITY OF CHEMICAL PROBES THAT ARE WIDELY USED BY CELL BIOLOGISTS, THUS INFORMING ON WHICH ONES ARE USEFUL TOOLS AND WHICH ONES SHOULD BE DEPRECATED. TO PROVIDE A REPLACEMENT FOR THE OUTDATED CHEMICAL PROBES, WE WILL COMPUTATIONALLY SCREEN THE LIBRARIES OF AIM 2 FOR MORE SELECTIVE COMPOUNDS, FOCUSING FIRST ON CDK KINASES AND SEVERAL KINASES THAT REPRESENT THERAPEUTIC VULNERABILITIES IN GIST. WE WILL SYNTHESIZE THE TOP-SCORING COMPUTATIONAL HITS, AND CHARACTERIZE THEM USING AN ESCALATION OF BIOCHEMICAL ASSAYS, PROTEOMIC KINOME PROFILING, STRUCTURAL BIOLOGY, AND CELLULAR ASSAYS. IF SUCCESSFUL, THIS PROJECT WILL DELIVER NEW CHEMICAL PROBES FOR SEVERAL HITHERTO UNADDRESSED (“ORPHAN”) KINASES, TO SERVE AS CHEMICAL TOOLS AND AS STARTING POINT FOR DRUG DEVELOPMENT. EQUALLY IMPORTANTLY THOUGH, COMPLETION OF THIS PROJECT WILL PROVIDE A ROBUST AND VALIDATED APPROACH FOR DESIGNING POTENT AND SELECTIVE KINASE INHIBITORS, TO BE SUBSEQUENTLY APPLIED FOR DEVELOPING NEW HIGH-QUALITY PROBES AGAINST EACH OF THE 500 HUMAN KINASES.

DECIPHERING NETWORKS CONTROLLING DNA AMPLIFICATION - PROJECT SUMMARY DNA AMPLIFICATION IS ASSOCIATED WITH PATHOLOGICAL STATES SUCH AS NEUROLOGICAL DISORDERS, CARDIAC DISEASE AND CANCER. AT LEAST 50% OF THE AMPLIFICATIONS IN CANCER ARE TRANSIENT EXTRACHROMOSOMAL DNA (ECDNA). THE TRANSIENT BEHAVIOR CONTRIBUTES TO COPY NUMBER PLASTICITY, RESULTS IN HETEROGENEOUS ONCOGENE EXPRESSION AND ALTERS THERAPEUTIC RESPONSE. THE UNANSWERED QUESTION REMAINS AS TO WHETHER DISTINCT MECHANISMS CONTROL ECDNA COPY GAINS WITHIN CELLS AND HOW THEY IMPACT COPY GAIN EVENTS ASSOCIATED WITH DISEASE. MY OVERALL GOAL IS TO DEFINE THE PRINCIPLES REGULATING SELECTIVE DNA COPY GAINS AND THE ASSOCIATED PLASTICITY, SO WE MAY CONTROL THESE EVENTS. MY LABORATORY WAS THE FIRST TO DISCOVER A MOLECULAR BASIS FOR EXTRACHROMOSOMAL TRANSIENT SITE-SPECIFIC DNA COPY GAINS (TSSGS) IN THE HUMAN GENOME. SPECIFICALLY, WE IDENTIFIED THE FIRST ENZYME CAPABLE OF DRIVING SITE-SPECIFIC ECDNA AMPLIFICATION [THE HISTONE 3 LYSINE 9 AND 36 TRI-DEMETHYLASE (H3K9/36ME3) KDM4A] AND DEMONSTRATED A FUNDAMENTAL ROLE FOR EPIGENETIC STATES IN CONTROLLING THE PREDILECTION OF SPECIFIC DNA REGIONS TO REREPLICATE AND AMPLIFY. WE DISCOVERED SEVEN MORE CHROMATIN ENZYMES- LYSINE METHYLTRANSFERASES (KMTS) AND DEMETHYLASES (KDMS)- THAT FUNCTION IN CONCERT TO CONTROL SITE-SPECIFIC AMPLIFICATION IN BOTH NON-CANCER AND CANCER CELLS. THESE STUDIES ESTABLISHED A CRITICAL ROLE FOR CHROMATIN FACTORS AND THEIR ASSOCIATED STATES IN REGULATING DNA AMPLIFICATIONS. WITH THIS NIGMS R35, MY LABORATORY WILL EXPAND OUR STUDIES IN ORDER TO ELUCIDATE: 1) THE FUNDAMENTAL MECHANISMS CONTROLLING DNA AMPLIFICATION; 2) THE MOLECULAR PROCESSES AND CHARACTERISTICS PROMOTING OR PREVENTING DNA AMPLIFICATION; AND 3) THE RELATIONSHIP BETWEEN ECDNA GENERATION AND THE ASSOCIATED RNA HETEROGENEITY/DNA MUTATION BURDEN. WE WILL ADDRESS THESE POINTS BY LEVERAGING MICROSCOPY- BASED SCREENS USING GENETIC AND CHEMICAL TOOLS IN ORDER TO IDENTIFY KEY AMPLIFIERS, AND IN TURN, GENERATE EPIGENOME PROFILES COUPLED TO GENOME ORGANIZATION MAPS ASSOCIATED WITH THESE PATHWAYS SO THAT MOLECULAR FEATURES CONTROLLING DNA AMPLIFICATION ARE RESOLVED. THESE STUDIES WILL ALSO BE COUPLED TO STATE-OF-THE-ART LONG READ SEQUENCING AND SINGLE CELL (DNA AND RNA) SEQUENCING STRATEGIES SO THAT THE ASSOCIATED HETEROGENEITY WITHIN THE CELL POPULATION AND INDIVIDUAL CELLS CAN BE CORRELATED WITH THE EFFECT OF THE AMPLIFIER ON TSSGS. THESE STUDIES ARE BEING CONDUCTED IN NON-TRANSFORMED CELLS THAT HAVE A NEARLY DIPLOID GENOME SO THAT ADDITIONAL GENOMIC ANOMALIES AND MUTATIONS DO NOT IMPACT THESE STUDIES. COLLECTIVELY, THE DATA GENERATED FROM THESE STUDIES WILL INCREASE OUR KNOWLEDGE ABOUT THE MOLECULAR FEATURES GOVERNING DNA COPY GAINS AND THE ASSOCIATED HETEROGENEITY, WHICH WILL RESOLVE NOVEL BIOMARKERS AND THERAPEUTIC TARGETS IN ORDER TO CONTROL COPY NUMBER- ASSOCIATED DISEASES IN THE YEARS AHEAD.

3D-ADHESION STROMAGENESIS IN CANCER PERMISSIVENESS

ASSESSING DNA POLYMERASE THETA AS A THERAPEUTIC TARGET IN BRCA1 MUTANT CANCER - PROJECT SUMMARY GENETIC DISRUPTION OF DNA POLYMERASE THETA (POL) ACTIVITY HAS BEEN SHOWN TO EFFECTIVELY TARGET BRCA1 MUTATED CELLS, WHILE LEAVING BRCA1 WILD-TYPE (WT) CELLS INTACT. POL FACILITATES THETA-MEDIATED DNA END JOINING (TMEJ) REPAIR BY PROMOTING DNA SYNAPSIS AND REPAIR SYNTHESIS AT BREAK SITES CONTAINING 3' SINGLE STRANDED (SS)DNA OVERHANGS. ALTHOUGH SMALL MOLECULE INHIBITORS OF POL ACTIVITY ARE CURRENTLY UNDER DEVELOPMENT FOR THE TREATMENT OF BRCA1 MUTANT CANCERS, VERY LITTLE IS KNOWN REGARDING THE MECHANISMS THAT ACTIVATE TMEJ AND RESULT IN POL- DEPENDENCY IN BRCA1 MUTANT CELLS. MOREOVER, THE CURRENT PARADIGM ASSUMES THAT HOMOLOGOUS RECOMBINATION (HR)-DEFICIENCY CONFERS POLI SENSITIVITY, THEREFORE PARPI RESPONSIVENESS IS EXPECTED TO BE A BIOMARKER FOR POL INHIBITOR (POLI) SENSITIVITY. IN OUR PRELIMINARY DATA, WE UNEXPECTEDLY IDENTIFIED COMMONLY USED BRCA1 MUTANT CELLS THAT GROW RELATIVELY UNPERTURBED WITH GENETIC POLQ (POL) KNOCKOUT (KO), INDICATING THAT POLI AND PARPI SENSITIVITY MAY NOT NECESSARILY CORRELATE. IN THIS PROPOSAL, WE WILL ELUCIDATE THE MOLECULAR REQUIREMENTS FOR TMEJ ACTIVATION AND IDENTIFY BIOLOGICAL FACTORS THAT DISTINGUISH PARPI AND POLI SENSITIVITY. WE WILL ADDRESS THE FOLLOWING SPECIFIC AIMS: 1) REVEAL THE MOLECULAR BASIS OF TMEJ ACTIVATION IN BRCA1 MUTANT CELLS; 2) UNCOVER GENETIC POL- DEPENDENCIES IN BRCA1 MUTANT CELLS; AND 3) EXAMINE PHARMACOLOGIC POL INHIBITION IN BRCA1 MUTANT CELLS. COLLECTIVELY, THESE STUDIES WILL BE INFORMATIVE FOR FUTURE CLINICAL STUDIES EMPLOYING POLI.

LY-1 B CELLS: DEVELOPMENTAL ORIGINS AND V GENE BIASES

PROJECT ABSTRACT: PROGRAM PURPOSE AWARDTO STRENGTHEN THE ABILITY OF ELIGIBLE MIGRANT AND SEASONAL FARMWORKERS (MSFWS) AND THEIR DEPENDENTS TO OBTAIN OR RETAIN UNSUBSIDIZED EMPLOYMENT, STABILIZE THEIR UNSUBSIDIZED EMPLOYMENT AND ACHIEVE ECONOMIC SELF-SUFFICIENCY, INCLUDING UPGRADED EMPLOYMENT IN AGRICULTURE, AND , HOUSING GRANT RECIPIENTS WORK TO MEET A CRITICAL NEED FOR SAFE AND SANITARY PERMANENT AND TEMPORARY HOUSING. GRANTEES MAY BE ANY ENTITY FAMILIAR WITH THE WORKFORCE CHALLENGES OF MIGRANT AND SEASONAL FARMWORKERS. CONGRESS APPROPRIATES SEPARATE FUNDING FOR NFJP EMPLOYMENT AND TRAINING GRANTS AND FOR NFJP HOUSING GRANTS. GRANTS RUN ON A PROGRAM YEAR FROM JULY 1ST SEPTEMBER 30TH AND A GRANT COMPETITION IS HELD EVERY FOUR YEARS FOR STATE SERVICE AREAS.ACTIVITIES TO BE PERFORMEDTO ENSURE THAT ALL SERVICES ARE FOCUSED ON THE CUSTOMERS NEEDS, SERVICES ARE PROVIDED THROUGH A CASE MANAGEMENT APPROACH EMPHASIZING CUSTOMER CHOICE TO INCLUDE: BASIC AND INDIVIDUALIZED CAREER SERVICES TRAINING SERVICES - ELIGIBLE MSFWS ARE NOT REQUIRED TO RECEIVE CAREER SERVICES PRIOR TO RECEIVING TRAINING SERVICES YOUTH SERVICES, AS AVAILABLE IN THE WIOA YOUTH PROGRAM RELATED ASSISTANCE SERVICES WHICH INCLUDES ALLOWANCE PAYMENTS WHICH INCLUDES SHORT-TERM DIRECT ASSISTANCE THAT HELPS FARMWORKERS AND THEIR FAMILY MEMBERS TO RETAIN THEIR AGRICULTURAL EMPLOYMENT OR TO PARTICIPATE IN CAREER OR TRAINING SERVICES AND SUPPORTIVE SERVICES. NFJP HOUSING GRANTEES PROVIDE FARMWORKERS WITH HOUSING ASSISTANCE, INCLUDING DIRECT PAYMENTS FOR EMERGENCY AND TEMPORARY HOUSING. OTHER INDIRECT ASSISTANCE INCLUDES LEVERAGING SERVICES TO INCREASE OR MAINTAIN HOUSING STOCK AVAILABLE TO FARMWORKERS AND HOUSING DEVELOPMENT DESIGNED TO IMPROVE LIVING CONDITIONS FOR UNDERSERVED FARMWORKER COMMUNITIESDELIVERABLES EXPECTED OUTCOME ALL WIOA ADULT FUNDED PROGRAMS REQUIRE STATES TO COLLECT AND REPORT DATA TO DOL ON PERFORMANCE MEASURES. THE TARGETS FOR THE STATES ARE NEGOTIATED BETWEEN DOL AND THE STATES. WIOA PROGRAMS HAVE PERFORMANCE OUTCOMES OF EMPLOYMENT RATE SECOND QUARTER AFTER EXIT, EMPLOYMENT RATE FOURTH QUARTER AFTER EXIT, MEDIAN EARNINGS SECOND QUARTER AFTER EXIT, MEASURABLE SKILL GAINS, CREDENTIAL ATTAINMENT RATE, AND EFFECTIVENESS IN SERVING EMPLOYERS.INTENDED BENEFICIARY(IES)ELIGIBLE MIGRANT FARMWORKER WHOSE AGRICULTURAL LABOR REQUIRES TRAVEL TO A JOB SITE SUCH THAT THE FARMWORKER IS UNABLE TO RETURN TO A PERMANENT PLACE OF RESIDENCE WITHIN THE SAME DAY AND A LOW INCOME SEASONAL FARMWORKER WHO FOR 12 CONSECUTIVE MONTHS OUT OF THE 24 MONTHS PRIOR TO APPLICATION FOR THE PROGRAM WHO HAS BEEN PRIMARILY EMPLOYED IN AGRICULTURAL OR FISH FARMING INDUSTRIES THATS CHARACTERIZED BY CHRONIC UNEMPLOYMENT OR UNDEREMPLOYMENT. ELIGIBLE MSFW YOUTH IS AGED 1424 WHO IS INDIVIDUALLY ELIGIBLE OR IS A DEPENDENT OF AN ELIGIBLE MSFW.SUBRECIPIENT ACTIVITIESYES, GRANT RECIPIENTS CAN SUB TO OTHER LOCAL AGENCIES AND NON-PROFIT ORGANIZATIONS.

GLOBAL JUSTICE INFORMATION SHARING INITIATIVE

SENIOR COMMUNITY SERVICE EMPLOYMENT PROGRAM

TARGETED CHEMOPREVENTION OF FLAT AND POLYPOID COLITIS-ASSOCIATED DYSPLASIAS

AWARD PURPOSE TO MOVE SCSEP PARTICIPANTS INTO UNSUBSIDIZED EMPLOYMENT IN BOTH THE PUBLIC AND PRIVATE SECTORS, PROMOTE PART-TIME WORK EXPERIENCES IN COMMUNITY SERVICE ASSIGNMENTS FOR UNEMPLOYED LOW-INCOME INDIVIDUALS WHO ARE 55 YEARS OF AGE OR OLDER, AND FOSTER SELF-SUFFICIENCY AMONG SUCH INDIVIDUALS. BY STATUTE, SCSEP STATE GRANTS ARE AWARDED TO GOVERNORS (22% OF TOTAL GRANT FUNDING) AND ARE DETERMINED BY FORMULA; NATIONAL NON-PROFITS (NATIONAL GRANTEE) THAT OPERATE IN MULTI-STATE SERVICE AREAS (78% OF TOTAL GRANT FUNDING) ARE AWARDED GRANTS THROUGH A COMPETITION EVERY FOUR YEAR. APPROPRIATION LEVELS DETERMINE THE NUMBER OF TOTAL SLOTS, AND GRANTEES SERVE ALL SLOTS IN THEIR SERVICE AREA. PROGRAMS RUN ON A PROGRAM YEAR (JULY 1 - JUNE 30). ACTIVITIES PERFORMED PRIMARILY COMMUNITY SERVICE EMPLOYMENT ACTIVITIES, WHERE PARTICIPANTS WORK PART-TIME AT A COMMUNITY SERVICE LOCATION (NOT FOR PROFIT) FOR MINIMUM WAGE. THIS WORK EXPERIENCE PREPARES THEM FOR UNSUBSIDIZED EMPLOYMENT WHILE RECEIVING SERVICES IN THE PROGRAM OR AFTER THEY HAVE COMPLETED THE PROGRAM. PARTICIPANTS ALSO RECEIVE SUPPORT SERVICES, ON-THE-JOB-TRAINING, INDIVIDUAL EMPLOYMENT PLANS, AND CAN RECEIVE CLASSROOM AND SKILLS TRAINING. DELIVERABLES SCSEP GRANT RECIPIENTS MUST MEET THEIR CORE MEASURES OF PERFORMANCE WHICH REFERS TO HOURS (IN THE AGGREGATE) OF COMMUNITY SERVICE EMPLOYMENT; THE PERCENTAGE OF PROJECT PARTICIPANTS WHO ARE IN UNSUBSIDIZED EMPLOYMENT DURING THE SECOND QUARTER AFTER EXIT FROM THE PROJECT; THE PERCENTAGE OF PROJECT PARTICIPANTS WHO ARE IN UNSUBSIDIZED EMPLOYMENT DURING THE FOURTH QUARTER AFTER EXIT FROM THE PROJECT; THE MEDIAN EARNINGS OF PROJECT PARTICIPANTS WHO ARE IN UNSUBSIDIZED EMPLOYMENT DURING THE SECOND QUARTER AFTER EXIT FROM THE PROJECT; INDICATORS OF EFFECTIVENESS IN SERVING EMPLOYERS, HOST AGENCIES, AND PROJECT PARTICIPANTS; THE NUMBER OF ELIGIBLE INDIVIDUALS SERVED; AND MOST-IN-NEED. INTENDED BENEFICIARY ADULTS AGE 55 AND OVER WITH INCOME AT OR BELOW 125% OF POVERTY LEVEL AND NOT JOB READY. SUBRECIPIENT ACTIVITIES YES, GRANT RECIPIENTS CAN SUB TO OTHER LOCAL AGENCIES AND NON-PROFIT ORGANIZATIONS.

THE MED1 PROTEIN IN DNA DAMAGE RESPONSE AND REPAIR

THE A-GAME" - ADVANCING GREAT AUTHORIZING AND MODELING EXCELLENCE"

KINETICS OF EARLY EVENTS IN PROTEIN FOLDING

DEVELOPMENT AND FUNCTION OF NATURAL AUTOREACTIVE B CELLS

TARGETING THE BCL2 IMMUNE CHECKPOINT TO ENHANCE THE IMMUNOSTIMULATORY EFFECTS OF RADIATION IN BREAST CANCER - SUMMARY HORMONE RECEPTOR (HR)+ BREAST CANCER (BC) CAUSES THE MAJORITY OF BC-RELATED DEATHS IN THE US, REFLECTING AN UNMET NEED FOR INNOVATIVE THERAPEUTIC APPROACHES. INDEED, RESISTANCE TO STANDARD TREATMENTS AND METASTATIC SPREAD REMAIN MAJOR CHALLENGES, AND NOVEL APPROACHES SUCH AS IMMUNE CHECKPOINT BLOCKERS (ICBS) HAVE SHOWN LIMITED EFFICACY SO FAR. THE LONG-TERM OBJECTIVE OF THIS PROPOSAL IS TO MECHANISTICALLY DISSECT THE IMPACT OF BCL2, AN ANTIAPOPTOTIC PROTEIN THAT FAVORS THE RESISTANCE OF CANCER CELLS TO DEATH IMPOSED BY CHEMOTHERAPY AND RADIATION THERAPY (RT), ON THE IMMUNOLOGICAL CONFIGURATION OF TREATMENT NAÏVE AND IRRADIATED HR+ BCS. SPECIFICALLY, THIS PROJECT WILL TEST THE HIGHLY INNOVATIVE HYPOTHESIS THAT BCL2 MAY REPRESENT A THERAPEUTICALLY ACTIONABLE IMMUNE CHECKPOINT BECAUSE OF ITS ABILITY TO PRESERVE MITOCHONDRIAL INTEGRITY, BASED ON THESE SPECIFIC AIMS: 1) DETERMINING THE INFLUENCE OF BCL2 LEVELS ON THE IMMUNE MICROENVIRONMENT OF TREATMENT-NAÏVE HUMAN AND MOUSE HR+ BCS; 2) DEFINING THE IMPACT OF BCL2 ON THE IMMUNE MICROENVIRONMENT OF HR+ BCS RESPONDING TO RT IN VITRO AND IN VIVO; AND 3) ELUCIDATING THE VALUE OF BCL2 AS A TARGET TO BOOST THE IMMUNOSTIMULATORY EFFECTS OF RT IN MOUSE MODELS OF HR+ BCS, INCLUDING AN INNOVATIVE MODEL THAT MIMICS KEY FEATURES OF HUMAN HR+ BC. BCL2 IS A PARTICULARLY SIGNIFICANT TARGET BECAUSE ~80% OF HR+ BC CASES OVEREXPRESS BCL2, AND THE BCL2 INHIBITOR VENETOCLAX, IS APPROVED FOR CLINICAL USE. TO ACHIEVE OUR GOALS, DIAGNOSTIC BIOPSIES FROM WOMEN WITH HR+ BC WILL BE EVALUATED BY CODEX FOR BCL2 EXPRESSION, TUMOR INFILTRATION BY KEY IMMUNE CELLS THAT REGULATE ANTICANCER IMMUNITY, AND EXPRESSION OF IMMUNOSUPPRESSIVE PROTEINS LIKE MHC CLASS I AND PD-L1. THE IMPACT OF BCL2 ON THE IMMUNOLOGICAL RESPONSE OF HR+ BC CELLS TO RT WILL BE INTERROGATED IN VITRO, BY GENETIC (DELETION, OVEREXPRESSION) AND PHARMACOLOGICAL (E.G., VENETOCLAX ADMINISTRATION) METHODS COUPLED TO FLOW CYTOMETRY, IF MICROSCOPY AND ELISA FOR THE ASSESSMENT OF KEY REGULATORS OF ANTICANCER IMMUNITY. SIMILAR GENETIC AND PHARMACOLOGICAL APPROACHES WILL BE HARNESSED TO ALTER BCL2 COMPETENCE AND DELINEATE THE INFLUENCE OF BCL2 ON THE IMMUNOLOGICAL TME OF TREATMENT-NAÏVE AND IRRADIATED MOUSE HR+ BCS ESTABLISHED IN IMMUNOCOMPETENT HOSTS, BASED ON IHC, FLOW CYTOMETRY AND SINGLE-CELL RNA SEQUENCING. IN VITRO STUDIES BY FLOW CYTOMETRY AND CLONOGENIC ASSAYS, AS WELL AS IN VIVO STUDIES BASED ON MOUSE HR+ BC CELLS GROWING IN IMMUNODEFICIENT VS IMMUNOCOMPETENT MICE, WILL BE EMPLOYED TO DISSECT THE IMPACT OF BCL2 ON INTRINSIC RADIOSENSITIVITY VS IMMUNE-DEPENDENT TUMOR CONTROL. FINALLY, DIFFERENT COMBINATORIAL REGIMENS INVOLVING RT AND VENETOCLAX WILL BE INVESTIGATED FOR EFFICACY (IN BOTH TREATMENT-NAÏVE AND TREATMENT RESISTANCE SETTINGS) AND POTENTIAL MECHANISMS OF RESISTANCE IN AN ENDOGENOUS MOUSE MODEL OF HR+ BCS THAT MIMICS KEY FEATURES OF HUMAN HR+ BC. OUR FINDINGS WILL ELUCIDATE THE IMPACT OF BCL2 ON THE IMMUNE TME OF HR+ BC AND IDENTIFY THE BEST APPROACH TO INFORM THE INITIATION OF CLINICAL TRIALS TESTING RT PLUS VENETOCLAX IN WOMEN WITH HR+ BC, A DEVASTATING DISEASE THAT STILL AFFECTS >200,000 AND KILLS >25,000 NEW WOMEN EVERY YEAR IN THE US.

INTRA- AND INTER-NEURONAL VIRAL TRAFFICKING

CONTROL OF ALPHA-BETA/GAMMA-DELTA T LINEAGE COMMITMENT

RIP1/3 KINASES AS NEW TARGETS IN MALIGNANT MESOTHELIOMA

EDUCATIONAL PRODUCT EVALUATION PROFESSIONAL DEVELOPMENT AND COMMUNICATION

ANALYSIS AND THERAPEUTIC TARGETING OF THE LINEAR-UBIQUITINATION PATHWAY IN HODGKIN LYMPHOMA - PROJECT SUMMARY HODGKIN LYMPHOMA (HL) IS THE MOST COMMON (6,000 TO 7,000 NEW CASES PER YEAR) LYMPHOMA SUBTYPE IN YOUNG ADULTHOOD. ALTHOUGH THERE HAS BEEN GREAT PROGRESS DURING THE LAST FEW DECADES, THE SURVIVAL RATE FOR PATIENTS DIAGNOSED AT AN ADVANCED STAGE OR WITH RELAPSED/REFRACTORY DISEASE REMAINS LOW. THE CURRENT UNDERSTANDING OF THE BIOLOGY OF THE DISEASE HAS BEEN TRANSLATED INTO THE DEVELOPMENT AND APPROVAL OF THERAPEUTIC AGENTS THAT TARGET HL-SPECIFIC ANTIGENS OR IMMUNE CHECKPOINT PATHWAYS. HOWEVER, THE NUMBER OF PATIENTS IN COMPLETE REMISSION HAS BEEN LOW, AND RELAPSE FREQUENTLY DEVELOPS, LEADING TO POOR OUTCOMES. THUS, A CLEARER UNDERSTANDING OF THE MOLECULAR PATHOLOGY OF HL IS NECESSARY TO DEVELOP NEW TREATMENT STRATEGIES. HL IS CHARACTERIZED BY A MINORITY POPULATION OF MALIGNANT HODGKIN AND REED/STERNBERG (HRS) CELLS IN A BACKGROUND OF DENSE INFLAMMATORY CELLS. HRS CELLS HAVE LOST THEIR B CELL PHENOTYPE, HOWEVER, AND ESCAPED FROM BCR- MEDIATED APOPTOSIS AND IMMUNE ELIMINATION. THEREFORE, TWO MAJOR QUESTIONS REMAIN: (A), HOW DO HRS CELLS ESCAPE THE CONTROL OF THE IMMUNE SYSTEM; (B), HOW DO THEY SURVIVE DESPITE THE ABSENCE OF BCR EXPRESSION? TO ADDRESS THESE GAPS IN KNOWLEDGE, WE APPLIED AN UNBIASED HIGH THROUGHPUT CRISPR SCREENING, AND IDENTIFIED AN ESSENTIAL ROLE FOR THE LINEAR UBIQUITIN CHAIN ASSEMBLY COMPLEX (LUBAC) IN HL PATHOGENESIS. OUR PRELIMINARY STUDIES DEMONSTRATED THAT LUBAC ACTIVITY PROMOTES HRS CELL SURVIVAL AND IMMUNE ESCAPE, WHICH SIGNIFICANTLY OVERLAPS WITH MUTATION STATUS OF THE MOST RECURRENT GENETICALLY ALTERED GENE IN HL, A20. CLINICALLY, LUBAC ACTIVITY IS CONSISTENTLY ELEVATED IN MOST PRIMARY HL CASES, AND THIS IS CORRELATED WITH LOW A20 EXPRESSION. MOREOVER, USING RNA-SEQ ANALYSIS, WE IDENTIFIED A SET OF LUBAC-REGULATED GENES IN HL THAT OVERLAPPED SIGNIFICANTLY WITH SIGNATURES REFLECTING NF-B AND JAK-STAT ACTIVITIES, AS WELL AS TH2 CYTOKINES AND CELL SURFACE IMMUNOSUPPRESSIVE MOLECULES. UNEXPECTEDLY, OUR BIOID PROTEOMIC SCREENING REVEALS A CD30-LUBAC COMPLEX IN HL, SUGGESTING THE ROLE OF LUBAC-A20 AXIS IN THE CD30 MEDIATED NF-B SIGNALING, TH2 CYTOKINE PRODUCTION, AND STAT6 ACTIVATION. FINALLY, A HIGHLY SPECIFIC LUBAC SMALL MOLECULAR INHIBITOR SHOWS PROMISING ACTIVITY AGAINST HL IN VITRO AND IN A MOUSE XENOGRAFT MODEL. ALTOGETHER, THESE FINDINGS PROVIDE STRONG SUPPORT FOR OUR HYPOTHESIS THAT THE LUBAC-A20 AXIS REGULATES HL PATHOGENESIS, AND THAT TARGETING LUBAC COULD BE A NOVEL THERAPEUTIC STRATEGY IN THIS DISEASE. IN THIS STUDY, WE WILL: 1) INVESTIGATE THE MECHANISTIC BASIS BY WHICH THE LUBAC-A20 AXIS SUPPORTS HRS SURVIVAL AND PROLIFERATION; 2) EVALUATE HOW LINEAR-UBIQUITIN-DEPENDENT SIGNALING REGULATES THE MOLECULAR CIRCUITRY THAT DRIVES TUMOR IMMUNE ESCAPE OF HL; AND 3) EXPLOIT THE THERAPEUTIC POTENTIAL OF TARGETING LUBAC TO PROVIDE NOVEL INTERVENTION STRATEGIES FOR BOTH TARGETED AND IMMUNE THERAPIES IN HL. THESE STUDIES PROMISE TO REVEAL CRITICAL INSIGHTS INTO THE MOLECULAR CIRCUITRY THAT DRIVES THIS LYMPHOID CANCER, AS WELL AS PROVIDE UNIQUE OPPORTUNITIES FOR THE DEVELOPMENT OF NOVEL STRATEGIES FOR BOTH TARGETED AND IMMUNE THERAPIES TO TREAT HL.

MTAP, 5'-DEOXY-5'-METHYLTHIOADENOSINE, AND THE DYSREGULATION OF SYMMETRIC DIMETHYLARGININE IN CANCER

EXPLOITING VULNERABILITIES IN GIST USING NOVEL COMBINATION THERAPIES

TARGETING THE KINOME IN K-RAS DRIVEN COLORECTAL CANCERS

DIVERGENT FUNCTIONS OF ERK SUBSTRATE BINDING DOMAINS IN PATHOGENESIS OF MYELOPROLIFERATIVE NEOPLASMS - PROJECT SUMMARY/ABSTRACT THE RAS/MAPK PATHWAY IS ACTIVATED IN 85% OF HUMAN CANCER. NEVERTHELESS, ATTEMPTS TO TARGET RAS/MAPK SIGNALING HAVE PRODUCED ONLY LIMITED EFFICACY. WE HYPOTHESIZE THAT ONE REASON FOR THE FAILURE TO SUCCESSFULLY TARGET THIS PATHWAY IS THAT THE TARGETING EFFORTS HAVE FOCUSED ON THE ACTIVE SITES OF KINASES IN THIS CASCADE, WHICH HAS FAILED TO PROVIDE LONG-LASTING BENEFIT. WE HYPOTHESIZE THAT THE FAILURE OF THIS APPROACH RESULTS FROM TWO CAUSES: 1) ACTIVE SITE INHIBITORS, WHICH RESEMBLE ADENOSINE TRIPHOSPHATE (ATP), MUST OVERCOME THE EXCEEDINGLY HIGH CYTOSOLIC ATP LEVELS IN CANCER CELLS; AND 2) CRITICAL KINASES IN THIS CASCADE (E.G., ERK1/2) HAVE DISTINCT SUBSTRATE INTERACTIONS DOMAINS THAT CAN PERFORM ANTAGONISTIC ROLES IN REGULATING CANCER PROGRESSION. CONSEQUENTLY, ACTIVE-SITE FOCUSED INHIBITION IS AKIN TO SIMULTANEOUS DEPRESSION OF THE ACCELERATOR AND BRAKE PEDALS OF AN AUTOMOBILE. WE HYPOTHESIZE THAT A MORE SUCCESSFUL APPROACH WILL BE TO DEVELOP INHIBITORS WHICH PRESERVE KINASE ACTIVITY, BUT DIVERT IT EXCLUSIVELY TO “BRAKE PEDAL” SUBSTRATES. IN SUPPORT, WE HAVE DEMONSTRATED THAT THE TWO SUBSTRATE BINDING DOMAINS OF ERK2, TERMED THE D AND DPB DOMAINS, PLAY OPPOSING ROLES IN THE PATHOGENESIS OF JAK2-KINASE DRIVEN MYELOPROLIFERATIVE NEOPLASMS (MPN). INDEED, THE DBP AND D DOMAINS ACT LIKE BRAKE AND ACCELERATOR PEDALS, OPPOSING AND PROMOTING DISEASE PROGRESSION, RESPECTIVELY. CONSEQUENTLY, PHARMACOLOGIC ATTENUATION OF THE ACCELERATOR PEDAL (D-DOMAIN) OR ITS SUBSTRATES SHOULD IMPAIR TUMOR PROGRESSION MORE POTENTLY THAN ACTIVE SITE INHIBITION, BECAUSE IT SELECTIVELY INTERFERES WITH THE DISEASE PROMOTING ACTIVITY OF ERK2, WHILE PRESERVING THE TUMOR SUPPRESSIVE FUNCTION OF THE DBP-DOMAIN. WHILE WE HAVE COMPELLING EVIDENCE FOR THE OPPOSING ROLES OF THE ERK2-D AND DBP DOMAINS, THE MOLECULAR BASIS FOR THEIR ACTION REMAINS UNCLEAR AND THIS IS AN IMPEDIMENT TO DEVELOPING EFFECTIVE, PHARMACOLOGIC INTERVENTIONS FOCUSED ON THE ERK2 D DOMAIN. WE NOW SEEK TO ADDRESS THIS GAP IN KNOWLEDGE ACCORDING TO THE FOLLOWING AIMS. WE WILL: 1) ASSESS THE GENERALITY OF THE OPPOSING FUNCTIONS OF THE ERK2-D AND DBP DOMAINS IN THE PATHOGENESIS OF DISTINCT MPN SUBTYPES; 2) UNDERSTAND THE MECHANISTIC BASIS BY WHICH THE ERK2-D AND DBP DOMAINS EXERT THEIR DISTINCT FUNCTIONS; AND 3) ASSESS THE EFFICACY OF PHARMACOLOGIC TARGETING OF THE ERK2-D DOMAIN AND/OR ITS TARGETS IN INHIBITING CANCER PROGRESSION. THROUGH THESE EFFORTS WE EXPECT TO BRING NEW INSIGHTS INTO THE ROLE OF ERK2 SUBSTRATE BINDING MODULES IN REGULATING CANCER PROGRESSION AND HOW TO EXPLOIT THIS INFORMATION THERAPEUTICALLY. WHILE WE BEGIN WITH MPN, THESE FINDINGS MAY HAVE FAR REACHING IMPLICATIONS FOR OTHER RAS/MAPK DRIVEN CANCERS.

SENIOR COMMUNITY SERVICE EMPLOYMENT PROGRAM

BASIS FOR LYMPHOMAGENESIS IN AKT2 TRANSGENIC MICE

RESIDENCY TRAINING IN PRIMARY CARE

INTERACTION OF PROTEIN-TARGETED THERAPEUTICS AND CILIARY DYNAMICS

MECHANISMS REGULATING THE B LYMPHOPOIESIS FETAL/ADULT SWITCH

HIGH-RISK ESTABLISHMENTS AND WOMEN'S HIV PREVENTION IN SOUTHERN CHINA

OLDER WORKERS PROGRAM

REGULATION OF HEMATOPOIESIS BY RIBOSOMAL PROTEIN PARALOGS

INVESTIGATING THE IL-1R PATHWAY IN ANAPLASTIC LARGE CELL LYMPHOMA FOR TARGETED THERAPY - PROJECT SUMMARY ANAPLASTIC LARGE CELL LYMPHOMA (ALCL) COMPRISES A COLLECTION OF MATURE T-CELL NEOPLASMS THAT SHARE ELEVATED EXPRESSION OF CD30 AND ANAPLASTIC CYTOLOGY. ALCL SUBTYPES ARE DIVIDED INTO TWO CLASSES BASED ON THE STATUS OF ANAPLASTIC LYMPHOMA KINASE (ALK), ALK+ AND ALK-. WHILE ALK+ ALCL IS RELATIVELY HOMOGENEOUS, ALK- ALCL REPRESENTS A HETEROGENEOUS GROUP COMPRISING SYSTEMIC ALK NEGATIVE AND PRIMARY CUTANEOUS ALCL (PC-ALCL). THE RECENTLY RECOGNIZED BREAST IMPLANT-ASSOCIATED (BIA) ALCL, WHICH ARISES IN THE SEROMA CAVITY SURROUNDING BREAST IMPLANTS, WAS ACKNOWLEDGED AS A DISTINCT CLINICAL AND PATHOLOGICAL ENTITY THAT SHARES MORPHOLOGIC FEATURES WITH ALK- ALCL. CURRENT THERAPEUTIC STRATEGIES FOR ALCL ARE LARGELY BASED ON AGGRESSIVE B-CELL LYMPHOMA REGIMENS. HOWEVER, THE OUTCOMES ARE GENERALLY MUCH WORSE IN PATIENTS WITH ALK- ALCL THAN IN THOSE WITH ALK+ ALCL. THUS, THERE IS A NEED TO DEVELOP NOVEL, PREFERABLY SMALL MOLECULE-BASED TARGETED THERAPIES FOR THESE LYMPHOID MALIGNANCIES, ESPECIALLY IN ALK- AND BIA ALCL CASES. A MAJOR BARRIER TO THIS GOAL IS THE LACK OF A SYSTEMATIC AND COMPREHENSIVE UNDERSTANDING OF THE DEEP MOLECULAR CHARACTERISTICS OF ALK- AND BIA ALCL PATHOLOGY, WHICH IS CLEARLY NEEDED IN ORDER TO IDENTIFY CRITICAL THERAPEUTIC VULNERABILITIES. TO ADDRESS THE GAPS IN KNOWLEDGE, WE APPLIED AN UNBIASED HIGH THROUGHPUT CRISPR SCREENING IN ALCL, AND IDENTIFIED AN UNEXPECTED ROLE OF THE IL-1R-MYD88 PATHWAY IN SUPPORTING ALK- AND BIA ALCL. THE IL-1R SIGNALING PATHWAY IS A KEY MEDIATOR OF IMMUNITY AND INFLAMMATION AND HAS BEEN SHOWN TO PLAY A CRITICAL ROLE IN MANY SOLID TUMORS; HOWEVER, ITS ROLE IN LYMPHOID MALIGNANCIES HAS NOT BEEN ESTABLISHED. INDEED, OUR PRELIMINARY STUDIES PROVIDE THE FIRST UNEQUIVOCAL EVIDENCE THAT IL-1R1 PATHWAY PLAYS AN ESSENTIAL ROLE IN SUPPORTING ALK- AND BIA ALCL CELL SURVIVAL. CLINICALLY, WE FOUND THAT IL-1 RECEPTOR AND IL-1A EXPRESSION ARE CONSISTENTLY ELEVATED IN PRIMARY ALK- CASES, AND THIS IS CORRELATED WITH IL-1R SIGNALING ACTIVATION (P-IRAK4 LEVEL) IN PRIMARY SAMPLES. MOREOVER, USING RNA-SEQ ANALYSIS, WE IDENTIFIED A SET OF IL-1R PATHWAY REGULATED GENES IN ALK- ALCL THAT OVERLAPPED SIGNIFICANTLY WITH SIGNATURES REFLECTING JAK-STAT3 ACTIVITY AND TH17/TH1 PHENOTYPING. FINALLY, A HIGHLY SPECIFIC IRAK4 INHIBITOR SHOWS PROMISING ACTIVITY AGAINST ALK- AND BIA ALCL IN VITRO AND IN A MOUSE XENOGRAFT MODEL. ALTOGETHER, THESE FINDINGS PROVIDE STRONG SUPPORT FOR OUR HYPOTHESIS THAT THE IL-1R PATHWAY PROMOTES ALK- AND BIA ALCL PATHOGENESIS, AND THAT TARGETING THIS PATHWAY COULD BE A NOVEL THERAPEUTIC STRATEGY IN THESE DISEASES. IN THIS STUDY, WE WILL TEST OUR HYPOTHESIS THROUGH THE FOLLOWING AIMS: 1) ELUCIDATION OF THE EXACT ROLE OF IL-1R PATHWAY IN ALK- AND BIA ALCL, 2) UNDERSTANDING OF MECHANISMS REGULATING THIS PATHWAY AND ITS RELATIONSHIP TO RECURRENT GENETIC LESIONS IN ALCL, AND 3) VALIDATION OF THE IL-1R PATHWAY AS A NOVEL THERAPEUTIC TARGET IN THESE MALIGNANCIES. THE PROPOSED STUDIES SHOULD PROVIDE CRITICAL INSIGHTS INTO THE MOLECULAR CIRCUITRY THAT DRIVES THESE TYPES OF ALCL AND, CONSEQUENTLY, RESULT IN THE DEVELOPMENT OF NOVEL TARGETED THERAPEUTIC STRATEGIES FOR THESE DISTINCT LYMPHOPROLIFERATIVE DISORDERS.

HEF1 FUNCTIONS IN CELL DIVISION-RELATED SIGNALING

OPIOID AFFECTED YOUTH INITIATIVE TECHNICAL ASSISTANCE

OPTIMIZATION OF URINARY DNA DEEP SEQUENCING TESTS TO ENHANCE CLINICAL STAGING OF BLADDER CANCER PATIENTS - PROJECT SUMMARY/ABSTRACT MUSCLE-INVASIVE BLADDER CANCER (MIBC) IS OPTIMALLY TREATED WITH NEOADJUVANT CHEMOTHERAPY FOLLOWED BY RADICAL CYSTECTOMY (RC), WHEREBY ~35% OF PATIENTS WILL HAVE A PATHOLOGIC COMPLETE RESPONSE (PCR). GIVEN THE MORBID, COMPLICATED, AND EXPENSIVE NATURE OF RC AND THE WELL-ESTABLISHED PCR RATE, THERE IS A GROUNDSWELL OF INTEREST IN RC AVOIDANCE FOR PATIENTS ACHIEVING PCR. HOWEVER, IDENTIFYING PCR CLINICALLY (AS OPPOSED TO PATHOLOGICALLY) IS AN INACCURATE PROCESS. IN PUBLISHED STUDIES, PATIENTS WHO AVOID RC AFTER BEING DEEMED CLINICAL COMPLETE RESPONDERS HAVE A 25-60% LIKELIHOOD OF RECURRENCE, METASTASIS, OR BLADDER CANCER MORTALITY. BETTER TOOLS TO ASSESS RESIDUAL DISEASE STATUS ARE NEEDED. TO ADDRESS THIS NEED, WE DEVELOPED A URINE BIOPSY TEST WHICH WE CALL UTERD (URINE TEST FOR RESIDUAL DISEASE). IN UTERD, DNA IS ISOLATED FROM URINE AND SUBJECTED TO NEXT GENERATION SEQUENCING TO DETECT POINT MUTATIONS IN A TARGETED PANEL OF GENES. USING UTERD, MOST MUTATIONS IN TUMOR TISSUE ARE DETECTABLE AS MUTATIONS IN URINE. FURTHER, PRESENCE OR ABSENCE OF RESIDUAL MU AFTER COMPLETION OF CHEMOTHERAPY STRONGLY ASSOCIATES WITH RESIDUAL DISEASE OR PCR AT THE TIME OF RC, RESPECTIVELY. THEREFORE, UTERD COULD BE USED AFTER NEOADJUVANT THERAPY TO BETTER IDENTIFY PATIENTS FOR RC AVOIDANCE. ALTHOUGH UTERD PERFORMS WELL IN DISTINGUISHING PATIENTS WITH PCR FROM RESIDUAL DISEASE, THE NEGATIVE PREDICTIVE VALUE (NPV) OF UTERD IS ONLY 76%, SOME URINE SAMPLES WERE NONDIAGNOSTIC, AND A URINARY DNA PRESERVATION PROTOCOL NEEDS TO BE DEVELOPED IN ORDER FOR THE TEST TO BE WIDELY ADOPTED. PRE-ANALYTICAL FACTORS AND METHODOLOGY IMPROVEMENTS WHICH WE BELIEVE WILL INCREASE THE NPV AND DECREASE NONDIAGNOSTIC RATES WILL BE STUDIED IN AIM 1. IN AIM 2, WE WILL DETERMINE IF URINE PRESERVATIVES CAN BE USED TO FACILITATE SHIPPING TO A CENTRALIZED LAB WITHOUT LOSS OF FIDELITY OF THE TEST. LASTLY, IN AIM 3, WE WILL DETERMINE IF THE ABSENCE OF MUTATIONS FROM A URINE BIOPSY IS ASSOCIATED WITH PCR REGARDLESS OF THE PRE-SURGICAL THERAPY. TO ANSWER THIS QUESTION, SAMPLES OBTAINED ON 5 PROSPECTIVE MIBC CLINICAL TRIALS FROM MULTIPLE INSTITUTIONS WILL BE STUDIED USING THE OPTIMIZED PROTOCOLS IDENTIFIED THROUGH THIS RESEARCH. THE RESEARCH TEAM IS COMPRISED OF A UROLOGIST, MEDICAL ONCOLOGISTS, A RADIATION ONCOLOGIST, A STATISTICIAN, A COMPUTATIONAL BIOLOGIST WHO ARE EXPERTS IN THEIR FIELDS. THE SKILLS AND CONTRIBUTIONS OF THE TEAM ARE COMPLIMENTARY AND WILL CULMINATE IN THE DEVELOPMENT OF A UNIQUE AND ROBUST BIOMARKER THAT ADDRESSES A SIGNIFICANT CLINICAL NEED USING A ONE-OF-A-KIND SAMPLE COHORT. UTERD MAY ENHANCE THE ABILITY OF A BLADDER CANCER CLINICIAN TO ANSWER HIGHLY RELEVANT CLINICAL QUESTION, NAMELY, “DOES THIS PATIENT HAVE RESIDUAL DISEASE AFTER PRE- SURGICAL THERAPY, AND THEREFORE, WILL HE/SHE BENEFIT FROM RC?”

ITCLA UNITED HOUMA NATION NACTEP PROGRAM

OPTIMIZING VIRTUAL CARE

REGIONAL INFORMATION SHARING SYSTEMS (RISS) INFORMATION TECHNOLOGY AND NETWORK INFRASTRUCTURE SUPPORT

THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH (IIR) PROPOSES TO PROVIDE COMPREHENSIVE OPIOID, STIMULANT, AND SUBSTANCE USE PROGRAM (COSSUP) OVERDOSE FATALITY REVIEW (OFR) TRAINING AND TECHNICAL ASSISTANCE (TTA) OVER A 24-MONTH PERIOD FOR A TOTAL OF $2,000,000. THE PROJECT WILL ADDRESS THE OVERARCHING GOAL OF SUPPORTING STATE, LOCAL, AND TRIBAL JURISDICTIONS WITH EFFORTS TO PREVENT AND REDUCE OVERDOSE DEATHS THROUGH DEVELOPMENT OR ENHANCEMENT OF OFRS THAT INCREASE ACCESS TO AND USE OF DATA AND INFORMATION SHARING TO ENHANCE PREVENTION OF AND RESPONSES TO OVERDOSES. TO ADDRESS THIS GOAL, THIS PROPOSAL SEEKS TO EXPAND, EQUIP, AND ENHANCE OFRS BY IMPLEMENTING FOUR OBJECTIVES: (1) BUILD THE CAPACITY OF OFR MULTIDISCIPLINARY TEAMS TO ANALYZE AND REVIEW AGGREGATE DATA TO UNDERSTAND OVERDOSE TRENDS AND GAPS IN STRATEGIES AND SERVICES; (2) DEVELOP NEW RESPONSES AND DEPLOY RESOURCES THROUGH AN ACCOUNTABLE IMPLEMENTATION FRAMEWORK TO ADDRESS OVERDOSE PREVENTION STRATEGY GAPS AND NEEDS; (3) ENHANCE THE QUALITY AND REACH OF SERVICES FOR THE FIELD THROUGH COLLABORATIVE APPROACHES TO PROMOTE AND ADVANCE THE WORK OF THE COSSUP TTA PROVIDERS; AND (4) TRACK TRENDS AND BUILD TOOLS TO SUPPORT TRANSLATION OF KNOWLEDGE OF EFFECTIVE OFR STRATEGIES. IIR OFR TTA STAFF HAVE EXTENSIVE PROFESSIONAL EXPERIENCE IN COLLECTING AND ANALYZING DATA TO UNDERSTAND THEMES AND IDENTIFY NEEDS AND TRENDS AND IN BUILDING AND COORDINATING MULTIDISCIPLINARY TEAMS TO FACILITATE A SERIES OF CONFIDENTIAL, INDIVIDUAL DEATH REVIEWS AT THE STATE AND LOCAL LEVELS TO EFFECTIVELY IDENTIFY SYSTEM GAPS AND INNOVATIVE COMMUNITY-SPECIFIC OVERDOSE PREVENTION AND INTERVENTION STRATEGIES. THE OFR STAFF HAVE PROVIDED INNOVATIVE, TIMELY, AND RESPONSIVE OFR TTA SINCE THE FORMAL INCEPTION OF THE COSSUP OFR TTA SUPPORT IN 2019 AND HAVE AUTHORED THE PINNACLE RESOURCE, OVERDOSE FATALITY REVIEW: A PRACTITIONERS GUIDE TO IMPLEMENTATION, THAT IS THE FOUNDATION FOR THE WORK HAPPENING THROUGHOUT THE COUNTRY. IIR PROPOSES TO PARTNER WITH OTHER COSSUP TTA PROVIDERS, SUBJECT-MATTER EXPERTS, THE MEDICAL COLLEGE OF WISCONSIN, AND THE LEGISLATIVE ANALYSIS AND PUBLIC POLICY ASSOCIATION. THESE PARTNERSHIPS, ALONG WITH THE OFR STAFFS EXPERTISE AND SUPPORT, WILL SIGNIFICANTLY ADVANCE THE OFR FIELDS STANDARDS OF PRACTICE AND ULTIMATELY PREVENT AND REDUCE OVERDOSE DEATHS.

TARGETING THE ONCOGENIC MUTANT P53 SIGNALING IN COLORECTAL CANCER THERAPY

THE INSTITUTE FOR INTERGOVERNMENTAL RESEARCH (IIR) BRINGS TOGETHER TECHNICAL, SUBJECT MATTER, AND LIVED EXPERIENCE EXPERTISE TO STRENGTHEN CAPACITIES OF OFFICE OF JUVENILE JUSTICE AND DELINQUENCY PREVENTION (OJJDP) GRANTEES AND THE FIELD AS THEY CONDUCT DATA-DRIVEN STRATEGIC PLANNING THAT INVESTS IN COMMUNITY-BASED CONTINUUMS OF DEVELOPMENTALLY APPROPRIATE CARE AND REDUCES RELIANCE ON YOUTH INCARCERATION/DETENTION. THESE CONTINUUMS OF CARE WILL ENSURE THAT YOUTH CAN BE SERVED IN THEIR COMMUNITIES, AT HOME WITH THEIR FAMILY, IN SCHOOL, AND WITH FRIENDS, WHICH WILL PREVENT YOUTH FROM ENTERING THE JUVENILE JUSTICE SYSTEM AND REDUCE DEEPER INVOLVEMENT FOR YOUTH WHO HAVE ALREADY COME IN CONTACT WITH THE SYSTEM. IIR AND ITS PARTNERS, NEIGHBORHOOD RESILIENCE PROJECT, CARTERS CREW, AND COLLABORATIVE SOLUTIONS FOR COMMUNITIES, HAVE JOINED AS A TRAINING AND TECHNICAL ASSISTANCE (TTA) TEAM TO SERVE AND PROMOTE FIELD INNOVATIONS IN PLANNING FOR YOUTH, FAMILY, AND COMMUNITY SUCCESS. PRIMARY ACTIVITIES PROPOSED INCLUDE: IDENTIFICATION AND DISSEMINATION OF STRATEGIES THAT SUPPORT PROMISING AND EVIDENCE-BASED APPROACHES THAT ADVANCE THE LONG-TERM WELL-BEING OF YOUTH AND THEIR FAMILIES; DEVELOPMENT OF TTA PLANS BASED ON CAPACITY ASSESSMENTS OF EACH PROJECT SITES CURRENT STATE, NEEDS, AND GOALS; PROVISION OF TRAININGS FOCUSED ON ASSET MAPPING, STAKEHOLDER ENGAGEMENT, AND SUSTAINABILITY CONSIDERATIONS; DELIVERY OF CULTURALLY RESPONSIVE TTA; FACILITATION OF STRATEGIC OPPORTUNITIES TO BUILD ONGOING RELATIONSHIPS AMONG GRANTEES AND MODEL PROGRAM SITES; ASSISTANCE IN IDENTIFYING COST SAVINGS THAT CAN BE REINVESTED IN EFFECTIVE DELINQUENCY PREVENTION AND INTERVENTION PROGRAMS; PROMOTION OF BEST PRACTICE OUTCOMES; AND DEVELOPMENT OF ADDITIONAL TOOLS, DISSEMINATED NATIONALLY, BASED ON RECOMMENDATIONS FROM COMMUNITY STAKEHOLDER LISTENING SESSIONS. TTA IS EXPECTED TO ENHANCE CAPACITIES OF PROJECT PLANNING SITES THAT WILL PRODUCE AND SUSTAIN BETTER AND MORE EQUITABLE OUTCOMES FOR YOUTH. IIR WILL LAUNCH A LEADERSHIP CENTER FOR YOUTH JUSTICE INNOVATIONS TO SERVE AS A PROFESSIONAL SPACE FOR YOUNG PEOPLE WITH JUSTICE-IMPACTED EXPERIENCES WHO EXPRESS A PASSION FOR BEING AGENTS OF CHANGE AND AN INTEREST IN ADVANCING PROFESSIONAL SKILLS. THESE PAID FELLOWS WILL BE PROVIDED OPPORTUNITIES TO ENGAGE STAKEHOLDERS, GAIN A NATIONAL PERSPECTIVE, AND SHARPEN SKILLS AND COMPETENCIES POSITIONING THEM FOR FUTURE CAREER POSSIBILITIES. THE TTA TEAM INCLUDES A BLEND OF EXPERTISE IN JUVENILE JUSTICE REFORM PRACTICES, POSITIVE YOUTH DEVELOPMENT, RACIAL AND ETHNIC DISPARITIES, QUANTITATIVE AND QUALITATIVE ANALYSIS, STRATEGIC PLANNING, TRAUMA-INFORMED SERVICE DELIVERY, YOUTH AND FAMILY ENGAGEMENT PRACTICES, IMPLEMENTATION AND SUSTAINMENT SCIENCE, NONPROFIT FUND DEVELOPMENT, AND CHANGE MANAGEMENT. THE TEAM WILL ESTABLISH COLLABORATIVE RELATIONSHIPS WITH PROGRAM SITE REPRESENTATIVES TO ENSURE THAT SUPPORT IS TAILORED. OF CHANGE AND AN INTEREST IN ADVANCING PROFESSIONAL SKILLS. THESE PAID FELLOWS WILL BE PROVIDED OPPORTUNITIES TO ENGAGE STAKEHOLDERS, GAIN A NATIONAL PERSPECTIVE, AND SHARPEN SKILLS AND COMPETENCIES POSITIONING THEM FOR FUTURE CAREER POSSIBILITIES. THE TTA TEAM INCLUDES A BLEND OF EXPERTISE IN JUVENILE JUSTICE REFORM PRACTICES, POSITIVE YOUTH DEVELOPMENT, RACIAL AND ETHNIC DISPARITIES, QUANTITATIVE AND QUALITATIVE ANALYSIS, STRATEGIC PLANNING, TRAUMA-INFORMED SERVICE DELIVERY, YOUTH AND FAMILY ENGAGEMENT PRACTICES, IMPLEMENTATION AND SUSTAINMENT SCIENCE, NONPROFIT FUND DEVELOPMENT, AND CHANGE MANAGEMENT. THE TEAM WILL ESTABLISH COLLABORATIVE RELATIONSHIPS WITH PROGRAM SITE REPRESENTATIVES TO ENSURE THAT SUPPORT IS TAILORED.

SENIOR COMMUNITY SERVICE EMPLOYMENT PROGRAM

TRANSCRIPTIONAL CONTROL OF TH-POK, A KEY REGULATOR OF LINEAGE CONTROL

PEMBROLIZUMAB MAINTENANCE AFTER ENFORTUMAB VEDOTIN/PEMBROLIZUMAB INDUCTION IN FRONT-LINE METASTATIC UROTHELIAL CARCINOMA.

A NEW VIEW OF PAH ALLOSTERY - CORRELATION WITH DISEASE-ASSOCIATED ALLELES

CONTROL OF LINEAGE COMMITMENT IN DEVELOPING THYMOCYTES

SENIOR COMMUNITY SERVICE EMPLOYMENT PROGRAM

PREVENTING HIV INFECTION IN WOMEN THROUGH EXPANDED INTIMATE PARTNER VIOLENCE PREVENTION, SCREENING, AND RESPONSE SERVICES PROGRAM

NATIONAL GANG CENTER

NEW METHODS FOR HIGH-RESOLUTION COMPARATIVE MODELING

DISSECTING BRCA1-PALB2 ACTIVITY IN DNA REPAIR AND DEVELOPMENT

PROGRAM PURPOSE AWARDTO MOVE SCSEP PARTICIPANTS INTO UNSUBSIDIZED EMPLOYMENT IN BOTH THE PUBLIC AND PRIVATE SECTORS, PROMOTE PART-TIME WORK EXPERIENCES IN COMMUNITY SERVICE ASSIGNMENTS FOR UNEMPLOYED LOW-INCOME INDIVIDUALS WHO ARE 55 YEARS OF AGE OR OLDER, AND FOSTER SELF-SUFFICIENCY AMONG SUCH INDIVIDUALS. BY STATUTE, SCSEP STATE GRANTS ARE AWARDED TO GOVERNORS (22% OF TOTAL GRANT FUNDING) AND ARE DETERMINED BY FORMULA NATIONAL NON-PROFITS (NATIONAL GRANTEE) THAT OPERATE IN MULTI-STATE SERVICE AREAS (78% OF TOTAL GRANT FUNDING) ARE AWARDED GRANTS THROUGH A COMPETITION EVERY FOUR YEAR. APPROPRIATION LEVELS DETERMINE THE NUMBER OF TOTAL SLOTS, AND GRANTEES SERVE ALL SLOTS IN THEIR SERVICE AREA. PROGRAMS RUN ON A PROGRAM YEAR (JULY 1 - JUNE 30).ACTIVITIES TO BE PERFORMEDPRIMARILY COMMUNITY SERVICE EMPLOYMENT ACTIVITIES, WHERE PARTICIPANTS WORK PART-TIME AT A COMMUNITY SERVICE LOCATION (NOT FOR PROFIT) FOR MINIMUM WAGE. THIS WORK EXPERIENCE PREPARES THEM FOR UNSUBSIDIZED EMPLOYMENT WHILE RECEIVING SERVICES IN THE PROGRAM OR AFTER THEY HAVE COMPLETED THE PROGRAM. PARTICIPANTS ALSO RECEIVE SUPPORT SERVICES, ON-THE-JOB-TRAINING, INDIVIDUAL EMPLOYMENT PLANS, AND CAN RECEIVE CLASSROOM AND SKILLS TRAINING.DELIVERABLES EXPECTED OUTCOMESCSEP GRANT RECIPIENTS MUST MEET THEIR CORE MEASURES OF PERFORMANCE WHICH REFERS TO HOURS (IN THE AGGREGATE) OF COMMUNITY SERVICE EMPLOYMENT THE PERCENTAGE OF PROJECT PARTICIPANTS WHO ARE IN UNSUBSIDIZED EMPLOYMENT DURING THE SECOND QUARTER AFTER EXIT FROM THE PROJECT THE PERCENTAGE OF PROJECT PARTICIPANTS WHO ARE IN UNSUBSIDIZED EMPLOYMENT DURING THE FOURTH QUARTER AFTER EXIT FROM THE PROJECT THE MEDIAN EARNINGS OF PROJECT PARTICIPANTS WHO ARE IN UNSUBSIDIZED EMPLOYMENT DURING THE SECOND QUARTER AFTER EXIT FROM THE PROJECT INDICATORS OF EFFECTIVENESS IN SERVING EMPLOYERS, HOST AGENCIES, AND PROJECT PARTICIPANTS THE NUMBER OF ELIGIBLE INDIVIDUALS SERVED AND MOST-IN-NEED.INTENDED BENEFICIARY(IES)ADULTS AGE 55 AND OVER WITH INCOME AT OR BELOW 125% OF POVERTY LEVEL AND NOT JOB READY.SUBRECIPIENT ACTIVITIESYES, GRANT RECIPIENTS CAN SUB TO OTHER LOCAL AGENCIES AND NON-PROFIT ORGANIZATIONS.

TARGETING THE SRPK1-AKT SIGNALING AXIS IN ENDOMETRIAL CANCER

SYNERGISTIC TARGETING OF CHOLESTEROL METABOLISM AND EGFR SIGNALING IN CANCER

LEUKOTRIENE-INDUCED NESTIN EXPRESSION PROMOTES MEDULLOBLASTOMA TUMORIGENESIS

INTERFERON ACTIVATED NECROPTOSIS AS A NEW THERAPEUTIC AVENUE FOR KIDNEY CANCER

THE ROLE OF MICROHOMOLOGY-MEDIATED END JOINING IN FANCONI ANEMIA PATHOGENESIS

HEPATITIS B VIRUS CCCDNA

ANE - NURSE PRACTITIONER RESIDENCY PROGRAM

FY 2020 EXPANDING CAPACITY FOR CORONAVIRUS TESTING (ECT)