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Department of Health and Human Services

MATERNAL, INFANT AND EARLY CHILDHOOD HOMEVISITING GRANT PROGRAM - PURPOSE: THE PURPOSE OF THE MIECHV GRANT IS TO CONTINUE TO SUPPORT THE DELIVERY OF COORDINATED AND COMPREHENSIVE HOME VISITING SERVICES TO FAMILIES RESIDING IN HIGH- RISK COMMUNITIES. IN FY25 ,NINETEEN COMMUNITY AGENCIES WILL IMPLEMENT HOME VISITING PROGRAMS, USING EVIDENCE-BASED MODELS WITHIN ALL EIGHT COUNTIES ACROSS THE STATE. GOALS & OBJECTIVES: FOR THE FUNDING PERIOD OF SEPTEMBER 30, 2025 – SEPTEMBER 29, 2027, THE OFFICE OF EARLY CHILDHOOD WILL: 1. IMPLEMENT VOLUNTARY, HIGH QUALITY, HOME VISITING PROGRAMS, USING EVIDENCE-BASED MODELS THAT HAVE SHOWN EFFECTIVENESS AROUND OEC- IDENTIFIED OUTCOMES AND THE STATUTORILY MANDATED BENCHMARKS. 2. PROVIDE VOLUNTARY HOME VISITING PROGRAMS TO FAMILIES RESIDING IN AT-RISK COMMUNITIES THAT WERE IDENTIFIED IN A STATEWIDE NEEDS ASSESSMENT. 3. SEEK COORDINATION AND COLLABORATION WITH COMMUNITY PARTNERS AND SERVICES THROUGH THE LEGISLATIVELY MANDATED CONNECTICUT HOME VISITING CONSORTIUM. 4. CONTINUE TO USE ACTIVE CONTRACT MANAGEMENT CONSISTING OF HIGH FREQUENCY, DATA-INFORMED, COLLABORATION BETWEEN OEC PROGRAM STAFF AND LIA STAFF TO ACHIEVE TARGETED OUTCOMES SPECIFIED IN THE AUTHORIZING LEGISLATION THAT IMPROVE THE WELL-BEING OF CHILDREN AND FAMILIES INCLUDING IMPROVED HEALTH, SAFETY, CHILD DEVELOPMENT, SCHOOL READINESS. 5. CONTINUE IMPLEMENTATION OF RATE CARD CONTRACTING. THE RATE CARD PROVIDES INCENTIVE PAYMENTS TO PROVIDERS FOR THE ACHIEVEMENT OF OUTCOMES THAT 1.) GENERATE SIGNIFICANT VALUE TO FAMILIES, COMMUNITIES, AND GOVERNMENT, 2.) ARE MEASURABLE AND CAN BE LINKED TO ADMINISTRATIVE DATA SYSTEMS, 3.) FOCUS ON TWO- GENERATIONAL IMPACTS, AND 4.) OFFER ALL PROVIDERS AN EQUAL AND FAIR OPPORTUNITY TO EARN INCENTIVE PAYMENTS. 6. CONTINUE TO WORK WITH INCARCERATED PARENTS TO REDUCE THE IMPACT OF THEIR ABSENCE ON THEIR CHILDREN. 7. SUPPORT AND RETAIN A HIGHLY SKILLED AND COMPETENT HOME VISITING WORKFORCE METHODOLOGY: USING THE EVIDENCE BASED MODELS OF CHILD FIRST, HEALTHY FAMILIES AMERICA, NURSE-FAMILY PARTNERSHIP AND PARENTS AS TEACHERS, THE OEC WILL SERVE FAMILIES RESIDING IN THE FOLLOWING 21 HIGH-NEED COMMUNITIES IDENTIFIED BY THE 2020 STATEWIDE NEEDS ASSESSMENT; BRIDGEPORT, ANSONIA, DERBY, NEW HAVEN, KILLINGLY, NEW LONDON, PLAINFIELD, NORWICH, PUTNAM, WINDHAM, EAST HARTFORD, VERNON, MANCHESTER, BLOOMFIELD, HARTFORD, DANBURY, TORRINGTON, CANAAN, WINCHESTER, SHARON, WATERBURY, NEW BRITAIN AND MERIDEN. SERVICES WILL PRIORITIZE ENROLLMENT TO THE MIECHV POPULATIONS AS WELL AS THE OEC TARGET POPULATIONS OF PRENATAL FAMILIES, TEEN PARENTS AND WOMEN AT HIGHEST RISK FOR POOR PREGNANCY OUTCOMES AND LOW BIRTH WEIGHT BABIES. CURRENT CAPACITY OF MIECHV PROGRAMS, AS OF DECEMBER 31, 2024, IS 96% (793 OF 826 FAMILY SLOTS) AND FY23, CT MIECHV CAPACITY WILL INCREASE A BY 24 FAMILIES FROM 826 TO 850. KEY ACTIVITIES TO ENSURE APPROPRIATE LINKAGES AND REFERRALS NETWORKS; CT WILL: 1) CONTINUE TO SUPPORT REGIONAL NETWORKS AND PARTNERSHIPS FOR RECRUITMENT AND REFERRAL AGREEMENTS WITH COMMUNITY PARTNERS; 2) MAINTAIN AND FULFIL MEMORANDUM OF AGREEMENTS (MOAS) WITH SEVERAL STATE AGENCIES TO FOSTER REFERRALS AND THE COORDINATION OF SERVICES. WITH THE INCREASE OF MATCHING FUNDS, OEC WILL EXPAND SERVICES IN THE HIGH-NEED COMMUNITY OF NEW HAVEN BY AT A MINIMUM OF 24 FAMILIES. NON-FEDERAL MATCHING FUNDS ARE STATE GENERAL FUND DOLLARS THAT FUND A PORTION OF FTE FOR STATE-LEVEL STAFF.

Department of Health and Human Services

MATERNAL, INFANT AND EARLY CHILDHOOD HOMEVISITING GRANT PROGRAM - REQUESTING $1,669,091 BASE & $1,140,234 MATCH. THE PURPOSE OF THE N-MIECHV PROGRAM IS THE PREVENTION OF CHILD MALTREATMENT, TOXIC STRESS, & POOR LIFE COURSE OUTCOMES THROUGH VOLUNTARY, EVIDENCE-BASED HOME VISITING SERVICES IN PRIORITY COUNTIES IDENTIFIED THROUGH NEEDS ASSESSMENT, BY LOCAL IMPLEMENTING AGENCIES SPECIFICALLY TARGETING AT-RISK POPULATIONS. N-MIECHV WILL USE THE MATCH OPPORTUNITY TO ENHANCE NETWORK CAPACITY BY UTILIZING THE HOME VISITOR PERSONNEL COST METHOD & BRAIDING FEDERAL MIECHV FUNDING WITH TANF & STATE GENERAL FUNDS. FY2025 GOALS & OBJECTIVES: 1. BY 09/29/2027, N-MIECHV WILL ASSURE DOCUMENTATION OF HIGH-FIDELITY DELIVERY OF VOLUNTARY, EVIDENCE-BASED HOME VISITING TO FAMILIES THAT ARE AT GREATER RISK OF POOR LIFESPAN HEALTH OUTCOMES DUE TO POVERTY, TEEN PARENTS, INVOLVEMENT IN CHILD WELFARE, EXPOSURE TO RELATIONSHIP VIOLENCE, EXPOSURE TO SUBSTANCE OR TOBACCO USE, PARENTS WITH LOW STUDENT ACHIEVEMENT OR DEVELOPMENTAL DISABILITIES, OR HAVE ONE OR BOTH PARENTS IN THE MILITARY WITH MULTIPLE DEPLOYMENTS. OBJ. 1.1: BY 09/29/26, EVERY NETWORK PROGRAM WILL HAVE THE CHILD WELFARE PROTOCOL PLAN APPROVED OR MAINTAIN PART OF THEIR ENROLLMENT TARGET WITH CHILD WELFARE-REFERRED FAMILIES. OBJ. 1.2: BY 9/29/27, N-MIECHV WILL PROVIDE INTENSIVE & TARGETED TECHNICAL ASSISTANCE TO INDIVIDUAL PROGRAM SITES TO ASSURE QUALITY DELIVERY OF SERVICES. OBJ. 1.3: BY 9/29/27, N-MIECHV WILL ASSURE LIAS DEMONSTRATE FIDELITY, ACCURACY, & COMPLETION OF THE DATA TO PRODUCE POSITIVE RESULTS ON THE FEDERAL BENCHMARKS. OBJ. 1.4: BY 9/29/27, ALL LIAS WILL EITHER MAINTAIN ACCREDITATION IN GOOD STANDING OR ACHIEVE SATISFACTORY FIDELITY ASSESSMENTS (NEW PROGRAMS) WITH THE HEALTHY FAMILIES AMERICA NATIONAL MODEL. 2. BY 09/29/2027, N-MIECHV WILL DEMONSTRATE A SIGNIFICANT INCREASE OF CAPACITY FROM 704 TO 947 IN 30 OF 31 IDENTIFIED PRIORITY COUNTIES STATEWIDE, COMPLETING THE EXPANSION PROJECT. OBJ. 2.1: BY 9/29/26, N-MIECHV WILL REACH THE ANTICIPATED ENROLLMENT CAPACITY PROJECTED LAST YEAR BY RESOLUTION OF STAFFING PRIORITIES AND THE EXPANSION OF SEVERAL PROGRAM SITES, INCREASING NUMBERS FROM 704 TO 832. OBJ. 2.2: BY 09/29/27, N-MIECHV WILL EXPAND CAPACITY IN THREE PREVIOUSLY UNSERVED PRIORITY COUNTIES, BY IMPLEMENTING A NEW PROGRAM WITH SOUTHWEST NEBRASKA DISTRICT PUBLIC HEALTH DEPARTMENT AND EXPANDING SERVICES WITH NEBRASKA CHILDREN’S HOME SOCIETY INTO SAUNDERS COUNTY. OBJ. 2.3: BY 09/29/27, N-MIECHV WILL COMPLETE THE EXPANSION PROJECT BY INCREASING CAPACITY IN THE SUBAWARDS FROM 832 TO 947. 3. BY 09/29/27 N-MIECHV WILL ENHANCE A WELL-TRAINED & COMPETENT WORKFORCE. OBJ. 3.1: BY 09/29/27, N-MIECHV WILL POLL NETWORK STAFF FOR ADDITIONAL TRAINING INTERESTS & OFFER AT LEAST ONE NEW PROFESSIONAL DEVELOPMENT OPPORTUNITY TO THE NETWORK EACH YEAR OF THE PERIOD OF PERFORMANCE. OBJ. 3.2: BY 09/27/27, N-MIECHV WILL CONTRACT WITH THE UNL NEBRASKA CENTER FOR REFLECTIVE STRATEGIES FOR ON-GOING REFLECTIVE SUPERVISION TRAINING OPPORTUNITIES FOR NEW SUPERVISORS. 4. BY 09/29/2027, N-MIECHV WILL ENGAGE CROSS-SECTOR SYSTEMS-LEVEL COLLABORATIONS TO PROMOTE SUSTAINABILITY OF EVIDENCE-BASED HOME VISITING FOR AT-RISK FAMILIES, TO IMPROVE FAMILY & LIFE COURSE OUTCOMES. OBJ. 4.1: BY 9/29/27, N-MIECHV WILL CONTRIBUTE FUNDING TO A COORDINATED INTAKE PROJECT IN DOUGLAS COUNTY, WITH SEVERAL DIFFERENT HOME VISITING RESOURCES AVAILABLE TO INCREASE BOTH COLLABORATION AND REFERRALS INTO LOCAL N-MIECHV-FUNDED PROGRAMS. OBJ. 4.2: BY 9/29/27, N-MIECHV WILL ACTIVELY PARTICIPATE ON THE NATIONAL ASTHVI GROUP AND/OR WITH THE MATERNAL CHILD HEALTH BUREAU DESIGNATED ORGANIZATION FOR LEADERSHIP DEVELOPMENT AND COLLABORATION ACROSS MATERNAL CHILD HEALTH PROGRAMS, BUILDING CAPACITY OF MCH LEADERS THROUGH COORDINATED AND COLLABORATIVE SUPPORT TO ACHIEVE THE LONG-TERM GOAL TO IMPROVE NATIONAL MCH HEALTH OUTCOMES AND REDUCE ASSOCIATED DISPARITIES BY BETTER SERVING SPECIFIC POPULATIONS AND AWARDEES.

Department of Health and Human Services

MATERNAL, INFANT AND EARLY CHILDHOOD HOMEVISITING GRANT PROGRAM - SOUTH DAKOTA DEPARTMENT OF HEALTH 600 CAPITOL AVE., PIERRE, SD 57501 PROJECT DIRECTOR: CARRIE CHURCHILL, RN 605-394-2495 CARRIE.CHURCHILL@STATE.SD.US HTTPS://DOH.SD.GOV/PROGRAMS/BRIGHT-START/ TOTAL OF GRANT FUNDS REQUESTED: $2,033,254 ($1,307,361 BASE FUNDING AND $725,893 MATCHING FUNDS) ANNOTATION: THE SOUTH DAKOTA HOME VISITING PROGRAM SEEKS TO IMPROVE PREGNANCY OUTCOMES, CHILD HEALTH AND DEVELOPMENT, AND EARLY CHILDHOOD SYSTEMS COORDINATION BY IMPLEMENTING THE NURSE FAMILY PARTNERSHIP AND PARENTS AS TEACHERS EVIDENCE-BASED HOME VISITING MODELS. SERVICES ARE PROVIDED IN THE FOLLOWING IDENTIFIED AT RISK COUNTIES: BEADLE, BENNETT, BUTTE, DAY, FALL RIVER, JACKSON, LAWRENCE, MARSHALL, OGLALA LAKOTA, PENNINGTON, AND ROBERTS. IN THE FY 2024 GRANT YEAR, THE PROGRAM PLANS TO EXPAND SERVICES TO HUGHES COUNTY AND UP TO THREE ADDITIONAL COUNTIES YET TO BE DETERMINED. GOALS: 1. INCREASE CAPACITY OF THE SOUTH DAKOTA HOME VISITING PROGRAM TO IMPLEMENT EFFECTIVE, EVIDENCE-BASED HOME VISITING SERVICES TO MORE ELIGIBLE FAMILIES. 2. ADVANCE EARLY CHILDHOOD COMPREHENSIVE SYSTEM DEVELOPMENT IN IDENTIFIED AT-RISK COMMUNITIES. 3. CREATE A DATA-DRIVEN SYSTEM TO IMPROVE THE QUALITY OF HOME VISITING SERVICES. METHODOLOGY: THE SOUTH DAKOTA HOME VISITING PROGRAM IMPLEMENTS THE NURSE FAMILY PARTNERSHIP MODEL USING DEPARTMENT OF HEALTH AND SUBRECIPIENT PARTNER STAFF. PARENTS AS TEACHERS SERVICES ARE DELIVERED BY ONE SUBRECIPIENT LOCAL IMPLEMENTING AGENCY PARTNER. THE PROPOSED CASELOAD OF MIECHV FAMILY SLOTS FOR THE PROJECT PERIOD IS 266 IN YEAR 1 AND 302 IN YEAR 2. GROWTH IN PROPOSED FAMILY SLOTS WILL OCCUR WITH EXPANSION OF PARENTS AS TEACHERS INTO ADDITIONAL COUNTIES AND INCLUSION OF ADDITIONAL NURSE FAMILY PARTNERSHIP FAMILIES INTO MIECHV FUNDED SERVICES. COMMUNITIES WILL BE IDENTIFIED BASED ON NUMBERS OF POTENTIALLY ELIGIBLE FAMILIES, FIT OF HOME VISITING WITH OTHER EARLY CHILDHOOD INITIATIVES, AND COMMUNITY READINESS FOR SUCH SERVICES. THE DEPARTMENT OF HEALTH WORKS WITH STATE AGENCY PARTNERS, NONPROFIT AND SOCIAL SERVICE AGENCIES, AND TRIBAL ENTITIES TO COORDINATE SERVICES FOR FAMILIES. SOUTH DAKOTA HOME VISITING IS AN ACTIVE PARTNER IN EARLY CHILDHOOD COMPREHENSIVE SYSTEMS WORK. HOME VISITING STAFF BUILD NETWORKS IN LOCAL COMMUNITIES TO MAINTAIN A BASE OF REFERRALS, PROGRAM GROWTH, AND SERVICE COORDINATION.

Department of Health and Human Services

MATERNAL, INFANT AND EARLY CHILDHOOD HOMEVISITING GRANT PROGRAM - SOUTH DAKOTA DEPARTMENT OF HEALTH 600 E CAPITOL, PIERRE, SD 57501 PROJECT DIRECTOR: LEXI PUGSLEY, MS, RN 605-626-2660 LEXI.PUGSLEY@STATE.SD.US HTTPS://DOH.SD.GOV/PROGRAMS/BRIGHT-START/ TOTAL OF FEDERAL GRANT FUNDS REQUESTED: $2,384,514 ($1,307,361 BASE FUNDING AND $1,077,153 MATCHING FUNDS) PURPOSE: THE SOUTH DAKOTA DEPARTMENT OF HEALTH, OFFICE OF HOME VISITING (OHV) SEEKS TO IMPROVE PREGNANCY OUTCOMES, CHILD HEALTH AND DEVELOPMENT, AND EARLY CHILDHOOD SYSTEMS COORDINATION BY IMPLEMENTING THE NURSE FAMILY PARTNERSHIP (NFP) EVIDENCE-BASED HOME VISITING MODEL. SERVICES ARE PROVIDED IN 62 IDENTIFIED AT-RISK COUNTIES. MATCHING FUNDS WILL EXPAND PROGRAM ELIGIBILITY AND INCREASE THE NUMBER OF PARTICIPANTS AND HOUSEHOLD SERVED. GOALS AND OBJECTIVES: 1. INCREASE CAPACITY OF THE SD OFFICE OF HOME VISITING TO IMPLEMENT HOME VISITING SERVICES TO MORE ELIGIBLE FAMILIES. A. INCREASE ENROLLMENT AND CASELOAD CAPACITY IN IDENTIFIED AT-RISK COMMUNITIES. 2. ADVANCE EARLY CHILDHOOD COMPREHENSIVE SYSTEM DEVELOPMENT. A. SUPPORT FAMILY ENGAGEMENT AND SYSTEM COORDINATION EFFORTS. APPROACH: THE PROPOSED CASELOAD OF MIECHV FAMILY SLOTS FOR THE PROJECT PERIOD IS 265 IN YEAR 1 AND 346 IN YEAR 2. GROWTH IN PROPOSED FAMILY SLOTS WILL OCCUR WITH EXPANSION OF NFP INTO ADDITIONAL AT-RISK COUNTIES AND EXPANDED PROGRAM ELIGIBILITY THROUGH THE NFPX MODEL ENHANCEMENT. OHV IS PROPOSING TO SERVE THE FOLLOWING AT-RISK COUNTIES IN FY 2025: AURORA, BEADLE, BENNETT, BON HOMME, BRULE, BUFFALO, BUTTE, CAMPBELL, CHARLES MIX, CLARK, CLAY, CODINGTON, CORSON, CUSTER, DAVISON, DAY, DEUEL, DEWEY, DOUGLAS, EDMUNDS, FALL RIVER, FAULK, GRANT, GREGORY, HAAKON, HAMLIN, HAND, HANSON, HARDING, HUGHES, HUTCHINSON, HYDE, JACKSON, JERAULD, JONES, KINGSBURY, LAKE, LAWRENCE, LINCOLN, LYMAN, MARSHALL, MCCOOK, MCPHERSON, MEADE, MELLETTE, MINER, MINNEHAHA, MOODY, OGLALA LAKOTA, PENNINGTON, PERKINS, POTTER, ROBERTS, SANBORN, SPINK, STANLEY, SULLY, TODD, TURNER, UNION, WALWORTH, AND ZIEBACH. OHV IMPLEMENTS THE NURSE FAMILY PARTNERSHIP MODEL USING DEPARTMENT OF HEALTH STAFF AND STAFF FROM THREE SUBRECIPIENT/LOCAL IMPLEMENTING AGENCY (LIA) PARTNERS. OHV WILL USE MATCHING FUNDS TO EXPAND PROGRAM ELIGIBILITY AND SERVICE DELIVERY FOR NFP HOME VISITING SERVICES. NON-FEDERAL MATCHING FUNDS INCLUDE STATE GENERAL FUNDS.

Department of Health and Human Services

MATERNAL, INFANT AND EARLY CHILDHOOD HOMEVISITING GRANT PROGRAM - THE NEW JERSEY (NJ) MATERNAL, INFANT, AND EARLY CHILDHOOD HOME VISITING (MIECHV) PROGRAM, ADMINISTERED BY THE NEW JERSEY DEPARTMENT OF HEALTH (NJ DOH) IN PARTNERSHIP WITH THE NEW JERSEY DEPARTMENT OF CHILDREN AND FAMILIES (DCF), IS DEDICATED TO IMPROVING MATERNAL AND CHILD HEALTH OUTCOMES AND SUPPORTING FAMILIES ACROSS THE STATE. THE NJ MIECHV PROGRAM HAS MADE SIGNIFICANT PROGRESS IN EXPANDING SERVICES, STRENGTHENING ITS WORKFORCE, AND ENHANCING DATA SYSTEMS TO ENSURE THE HIGHEST QUALITY SERVICE DELIVERY. IN FY24, THE PROGRAM EXPANDED SERVICES BY ADDING 281 SLOTS ACROSS FOUR COUNTIES, REACHING 1,811 FAMILIES IN 16 AT-RISK COUNTIES. IN YEAR 2 OF FY25, UTILIZING NON-FEDERAL MATCHING FUNDS, MIECHV WILL EXPAND TO FIVE ADDITIONAL COUNTIES—CAPE MAY, CUMBERLAND, GLOUCESTER, SALEM, AND MONMOUTH—ADDING 288 NEW SLOTS THROUGH THE PARENTS AS TEACHERS (PAT) MODEL VIA FOUR EXISTING LOCAL IMPLEMENTING AGENCIES (LIAS). WITH THIS EXPANSION, NJ MIECHV WILL OFFER A TOTAL OF 2,099 HOME VISITING SLOTS, ACHIEVING FULL COVERAGE ACROSS ALL 21 NJ COUNTIES. TO ACHIEVE THESE EXPANSION GOALS, NJ MIECHV IS CONTINUING TO STRENGTHEN ITS WORKFORCE THROUGH ONGOING PROFESSIONAL DEVELOPMENT AND PARTICIPATION IN COHORTS 1 AND 2 OF THE COORDINATED STATEWIDE EVALUATION (CSE). IN ADDITION, THE PROGRAM REMAINS FOCUSED ON IMPROVING DATA SYSTEMS AND PERFORMANCE MONITORING. RECENT ENHANCEMENTS TO DATA TRACKING AND REPORTING HAVE RESULTED IN A REDUCTION IN DATA MISSINGNESS AND IMPROVED SERVICE DELIVERY OUTCOMES. THESE IMPROVEMENTS ENABLE BETTER ALIGNMENT WITH PERFORMANCE STANDARDS AND SUPPORT DATA-DRIVEN DECISION-MAKING TO OPTIMIZE SERVICE COORDINATION AND CLIENT OUTCOMES. WHILE PROGRESS HAS BEEN SIGNIFICANT, CHALLENGES REMAIN, SUCH AS FLUCTUATIONS IN HOME VISITOR STAFFING AND THE INTEGRATION OF DATA SYSTEMS ACROSS VARIOUS HOME VISITING MODELS. THE PROGRAM IS COMMITTED TO ADDRESSING THESE THROUGH TARGETED RECRUITMENT AND RETENTION STRATEGIES. NJ MIECHV WILL CONTINUE MEETING THE GROWING DEMAND FOR SERVICES AND FOCUS ON CONTINUOUS QUALITY IMPROVEMENT TO ENSURE THAT FAMILIES RECEIVE THE SUPPORT NEEDED FOR POSITIVE MATERNAL AND CHILD HEALTH OUTCOMES. NJ’S GOALS AND OBJECTIVES: GOAL 1: EXPAND ACCESS TO HIGH-QUALITY MIECHV HOME VISITING SERVICES FOR AT-RISK FAMILIES ACROSS NEW JERSEY. OBJECTIVE 1.1: ADD 281 NEW SERVICE SLOTS UTILIZING FOUR EXISTING LIAS. OBJECTIVE 1.2: MONITOR SERVICE DELIVERY IN EXPANDED AREAS AND ENSURE CASELOAD TARGETS ARE MET (85%). OBJECTIVE 1.3: CONDUCT ONGOING MONITORING AND ADJUSTMENTS TO SUPPORT FAMILIES IN NEWLY EXPANDED COUNTIES. GOAL 2: STRENGTHEN AND RETAIN A WELL-TRAINED, COMPETENT HOME VISITING WORKFORCE. OBJECTIVE 2.1: PROVIDE ONGOING PROFESSIONAL DEVELOPMENT AND FOCUSED TRAINING. OBJECTIVE 2.2: ENHANCE WORKFORCE SATISFACTION AND RETENTION THROUGH COORDINATED STATE EVALUATION COHORTS 1 & 2. OBJECTIVE 2.3: RECRUIT AND RETAIN QUALIFIED STAFF WITH A FOCUS ON COMMUNITY ALIGNMENT AND UTILIZING HOME VISITING DASHBOARD DATA. GOAL 3: ENHANCE COORDINATION AND COMMUNICATION ACROSS THE MIECHV SYSTEM. OBJECTIVE 3.1: CONTINUE TO STRENGTHEN INTERAGENCY COLLABORATION AND STREAMLINE MIECHV SERVICE DELIVERY. OBJECTIVE 3.2: ENSURE ADEQUATE INCOMING REFERRALS. OBJECTIVE 3.3: IMPLEMENT INTEGRATED HOME VISITING DATA DASHBOARDS TO MONITOR PARTICIPANT DEMOGRAPHICS AND REFERRALS. GOAL 4: IMPROVE DATA QUALITY AND USE OF APR AND PERFORMANCE METRICS TO ENHANCE MATERNAL AND CHILD HEALTH OUTCOMES. OBJECTIVE 5.1: MONITOR HRSA ANNUAL PERFORMANCE REPORT (APR) AND KEY MATERNAL AND CHILD HEALTH MEASURES. OBJECTIVE 5.2: DISAGGREGATE DATA BY SOCIO-DEMOGRAPHIC FACTORS TO IDENTIFY NEEDS. OBJECTIVE 5.3: UPDATE DATA MISSINGNESS GUIDES TO REDUCE DATA MISSINGNESS. GOAL 5: IMPLEMENT THE FY25 CQI PLAN TO ENHANCE SERVICE DELIVERY AND INCREASE FAMILY INVOLVEMENT. OBJECTIVE 6.1: PARTNER WITH JOHNS HOPKINS UNIVERSITY FOR DATA ANALYSIS AND PROGRAM ASSESSMENT. OBJECTIVE 6.2: COLLABORATE WITH FHI AND SUBJECT MATTER EXPERTS TO BETTER COORDINATE SERVICES.

Department of Health and Human Services

MATERNAL, INFANT AND EARLY CHILDHOOD HOMEVISITING GRANT PROGRAM - THE OKLAHOMA STATE DEPARTMENT OF HEALTH (OSDH) PROPOSES TO STRENGTHEN OKLAHOMA’S COMPREHENSIVE EARLY CHILDHOOD SYSTEM BY SUPPORTING THE DELIVERY OF COORDINATED, HIGH-QUALITY, AND VOLUNTARY EARLY CHILDHOOD HOME VISITING SERVICES TO ELIGIBLE FAMILIES IN HIGH-RISK COMMUNITIES IDENTIFIED THROUGH THE UPDATED NEEDS ASSESSMENT. UTILIZING EVIDENCE-BASED HOME VISITING PROGRAMS (EBHVPS), THE PROJECT WILL FOCUS ON COMANCHE, OKLAHOMA, AND TULSA COUNTIES. THE INITIATIVE WILL ADDRESS GAPS IN SERVICES FOR AT-RISK POPULATIONS, IMPROVE COORDINATION, AND INCREASE FAMILY ENGAGEMENT. OSDH IS REQUESTING $7,187,025 IN BASE FUNDS AND $1,512,949 IN FEDERAL MATCHING FUNDS, FOR A TOTAL OF $8,699,973. MATCHING FUNDS WILL BE USED TO EXPAND AND SUPPORT SERVICE DELIVERY ACROSS PARTICIPATING COMMUNITIES, INCREASING THE PROGRAM’S CAPACITY AND IMPACT. GOALS AND OBJECTIVES GOAL 1: IMPROVE COORDINATION AND COLLABORATION OBJECTIVE: ESTABLISH AND SUSTAIN LOCAL HOME VISITING COALITIONS LED BY COMMUNITY CONNECTORS TO STRENGTHEN COORDINATION BETWEEN EBHVPS AND OTHER COMMUNITY RESOURCES. GOAL 2: INCREASE OUTREACH, ENGAGEMENT, AND RETENTION OBJECTIVES: ENHANCE THE PARENTPRO CENTRAL INTAKE SYSTEM AND SUPPORT COMMUNITY CONNECTORS IN RECRUITMENT EFFORTS AND COMMUNITY ENGAGEMENT ACTIVITIES. GOAL 3: ENHANCE THE QUALITY OF EBHVP SERVICES OBJECTIVES: IMPLEMENT NEW STRATEGIES WITHIN LOCAL IMPLEMENTING AGENCIES (LIAS) AND SUPPORT LOCAL QUALITY IMPROVEMENT PROJECTS TO ENSURE EFFECTIVE SERVICE DELIVERY. APPROACH TO ACHIEVE THESE GOALS, OSDH WILL IMPLEMENT THE FOLLOWING INNOVATIVE STRATEGIES: 1. COMMUNITY CONNECTORS: SPECIALLY TRAINED INDIVIDUALS WHO PROMOTE HOME VISITING SERVICES, IDENTIFY SERVICE GAPS, AND FOSTER PARTNERSHIPS WITH LOCAL STAKEHOLDERS—ESPECIALLY TO REACH UNDERSERVED OR SPECIAL POPULATIONS. 2. PARENTPRO CENTRAL INTAKE SYSTEM: A CENTRALIZED INTAKE AND REFERRAL SYSTEM SUPPORTED BY A TARGETED MARKETING CAMPAIGN DESIGNED TO IMPROVE OUTREACH AND STREAMLINE ENROLLMENT INTO APPROPRIATE HOME VISITING SERVICES. 3. INTEGRATED FAMILY SUPPORT SERVICES: STRENGTHEN REFERRAL PATHWAYS TO COMPLEMENTARY SERVICES SUCH AS CIRCLE OF PARENTS, CHILD GUIDANCE, SOONERSTART, AND DEVELOPMENTAL SCREENINGS. OSDH WILL IMPLEMENT THREE EBHV MODELS ACROSS THE THREE AT-RISK COUNTIES: NURSE-FAMILY PARTNERSHIP, PARENTS AS TEACHERS, AND SAFECARE. THESE EVIDENCE-BASED MODELS WILL BE DELIVERED BY 10 LOCAL IMPLEMENTING AGENCIES (LIAS) IN FFY 2025. • CASELOAD: O CURRENT AS OF 04/10/2025: 560 FAMILY SLOTS O PROPOSED FFY 2025: 786 FAMILY SLOTS O PROPOSED FFY 2026: 786 FAMILY SLOTS O PROPOSED FFY 2027: 786 FAMILY SLOTS • MIECHV COMMUNITIES SERVED: COMANCHE COUNTY, OKLAHOMA COUNTY, AND TULSA COUNTY • LOCAL IMPLEMENTING AGENCIES (LIAS): A TOTAL OF 10 LIAS WILL RECEIVE FY 2025 MIECHV FUNDING TO DELIVER SERVICES IN THE IDENTIFIED HIGH-RISK COMMUNITIES. • MATCHING FUNDS: OSDH IS APPLYING FOR $1,512,949 IN FEDERAL MATCHING FUNDS. THESE FUNDS WILL BE USED TO ENHANCE OUTREACH EFFORTS THROUGH THE COMMUNITY CONNECTORS AND EXPAND QUALITY AND CAPACITY OF LIAS TO SERVE ADDITIONAL FAMILIES. THE MATCH WILL BE SUPPORTED BY NON-FEDERAL STATE FUNDS. ENHANCED COORDINATION EFFORTSOKLAHOMA’S EBHVP SYSTEM IS SUPPORTED BY A ROBUST INFRASTRUCTURE, INCLUDING: • THE OKLAHOMA PARTNERSHIP FOR SCHOOL READINESS (THE STATE’S EARLY CHILDHOOD ADVISORY COUNCIL), WHICH PROVIDES STRATEGIC OVERSIGHT. • MIECHV EVALUATION AND MANAGEMENT TEAMS, WHICH MEET REGULARLY TO GUIDE IMPLEMENTATION AND CONTINUOUS IMPROVEMENT. • THE FAMILY SUPPORT PROFESSIONAL COMMUNITY OF PRACTICE AND THE PARENT PARTNERSHIP BOARD, WHICH FOSTER COLLABORATION, REDUCE DUPLICATION, AND ENSURE FAMILY VOICE IN DECISION-MAKING. THIS COMPREHENSIVE AND COMMUNITY-DRIVEN APPROACH WILL STRENGTHEN OKLAHOMA’S CAPACITY TO DELIVER EQUITABLE, HIGH-QUALITY HOME VISITING SERVICES AND IMPROVE LONG-TERM OUTCOMES FOR VULNERABLE FAMILIES.

Somers

MBA Seurity System Upgrade

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary Food and environmental allergies are a significant health burden in developed countries. However, it remains still unclear why some allergy patients develop systemic, potentially fatal anaphylactic responses even after a local allergen exposure (e.g., acute hypothermia upon bee sting), while others experience localized reactions in the areas not directly exposed to the allergen (e.g., skin manifestations of food allergy). Numerous studies indicate the critical involvement of allergen-specific IgE antibodies in acute allergy and anaphylaxis, but high levels of IgE against a particular allergen do not always induce anaphylaxis or an ectopic reaction in a remote site upon exposure to that allergen. Thus, in addition to the dose of IgE and the allergen, there appears to be unknown factors affecting the severity and organ specificity of allergic responses. However, the host’s mechanism responsible for the systemic and ectopic dissemination of allergic reaction remains unclear. One of the current limitations to address this question is the lack of animal models, as most animal models of severe allergy requires systemic or repeated challenge with a high dose of allergen, making it often challenging to definitively address how the allergic response is originated. Proteases are a common type of allergens. Papain, a cysteine protease in papaya and a known occupational allergen, is widely used as an experimental adjuvant to induce type 2 inflammation in mice, but papain-specific allergic response has not been well-characterized. We recently found that a second exposure to papain in previously exposed animals induces prolonged edema and hypothermia, a hallmark of local and systemic anaphylaxis, respectively. In contrast to most animal models of systemic anaphylaxis in which the allergen is systemically administered, the systemic response is induced by local sensitization and a single challenge in our model, making it an ideal model to study how the local challenge leads to disseminated responses. We here propose to use this new model in combination with cutting-age mouse genetic and transcriptomic approaches to dissect how a local challenge induces systemic anaphylactic response and ectopic inflammation in a remote site. We hypothesize that local MCs and neurons coordinately trigger systemic and ectopic responses in allergic reactions. In this application, we aim to understand (1) how local challenge develops into a systemic allergic response, and (2) how the allergen-specific immunity modulates local immune responses to protease allergens. If successful, future studies will follow to investigate the molecular mechanism and therapeutic intervention, to examine its relevance in responses to other allergens, and to extend the knowledge to other clinically relevant organ systems such as food and airborne allergies.

NIA - National Institute on Aging

Abstract Protein synthesis is a vital biological process, important for neuronal development, synaptic plasticity, and cognitive functions such as learning and memory. In contrast, dysregulated translation is a feature of many neurodegenerative disorders, including Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Pathogenic changes to the microtubule associated protein tau are thought to cause neurotoxicity and dysfunction in both AD and FTD in part by disrupting several molecular processes, including protein synthesis. However, the molecular mechanisms by which pathogenic tau disrupts protein synthesis remain elusive. In this application, we will determine how FTD-associated heterozygous mutations in tau impact protein synthesis in human neurons. We will use human induced pluripotent stem cell (iPSC)-derived neurons carrying FTD-associated tau mutations as a model. The iPSCs will be differentiated into neurons using Neurogenin-2, a master transcription factor capable of inducing differentiation into excitatory neurons in under two weeks. Using this platform, in the first aim we will determine the impact of FTD-associated tau mutations on translation elongation rates and will perform ribosome profiling to determine the translatome and translational efficiency associated with the FTD- associated tau mutations. In the second aim, we will determine whether the tau mutations alter tau- ribosome interactions and if they cause ribosome collisions. These studies will provide insight concerning the mechanisms by which FTD-associated mutations in tau alters protein synthesis, as well as the biology and subsequent pathobiology of tau in tauopathies such AD and FTD.

NIA - National Institute on Aging

SUMMARY Pathological aggregation of the protein tau is a hallmark of Alzheimer’s disease and several related dementias, collectively referred to as tauopathies. Familial tauopathies caused by coding mutations in tau and experimental model systems support a causal role for tau aggregation in these diseases. Based on these findings, tau-lowering therapies using anti-sense oligonucleotides or antibodies are currently in clinical trials. However, potential drawbacks of these approaches are that the therapeutic modalities are expensive and would therefore be challenging to deploy in the large population of AD and tauopathy patients. Furthermore, therapies lowering total tau levels have the caveat that we insufficiently understand the physiological roles of tau, and lowering total tau may have detrimental effects. Therefore, therapies selectively targeting pathological forms of tau using small- molecule drugs remain a significant unmet need. Endogenous protein homeostasis mechanisms that lower pathological tau species may represent an attractive therapeutic target in AD and tauopathies. In previous work, the lab of MPI Dr. Kampmann used a genome-wide CRISPRi screen in human neurons to systematically uncover such mechanisms. The UFMylation pathway was an important class of hits in this screen, where knockdown reduced tau oligomers. In follow-up studies, Kampmann and collaborator Dr. Li Gan confirmed that inhibition of the UFMylation pathway lowers pathological tau species in different human neuron and mouse models of tauopathy. However, the underlying molecular mechanisms that link UFMylation to tau proteostasis are unknown. MPI Dr. Kopito has previously elucidated the mechanisms and targets of the UFMylation pathway using biochemical and structural approaches. His work established that the 60S ribosomal subunit is the target of UFMylation and that this modification is essential to dislodge terminated ribosomes from SEC61 translocons in the endoplasmic reticulum (ER). In unpublished findings, his lab uncovered that failure of UFMylation to recycle ribosomal subunits specifically activates adaptive signaling through the ER proteostasis sensor IRE1 and activation of the transcription factor XBP1s to drive a transcriptional program of protective stress response effectors. We hypothesize that this response serves as a feedback loop to ensure levels of available SEC61 translocons, while also upregulating other protein homeostasis factors that facilitate clearance of pathological states of tau. The proposed research will (1) Define the molecular mechanism by which disruption of UFMylation and translocon homeostasis activates protective IRE1 signaling in the absence of unfolded proteins, (2) Elucidate the mechanism by which protective IRE1 signaling suppresses tau aggregation, and (3) Validate the mechanism and therapeutic potential of IRE1 activation in tauopathy mouse models.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ABSTRACT Many emerging zoonotic viruses (animal viruses that transmit to humans) are highly pathogenic, having the potential to cause deadly epidemics or even global pandemics. The risks zoonotic viruses pose are highlighted by the emergence of the SARS/MERS coronaviruses, Ebola virus, and HIV-1, all of which are related to animal viruses that were unknown before they caused substantial cases of disease in humans. Given the risk animal viruses pose to humans, many researchers have turned to viral discovery—using genome sequencing tools and metagenomic analyses, researchers hope to identify novel animal viruses before they emerge in humans. We've developed a pipeline that integrates viral surveillance with molecular investigations in the laboratory to identify pre-emergent viruses with epidemic potential. Using this approach, we've provided compelling evidence suggesting that simian arteriviruses (SAVs)—understudied and neglected pathogens of African monkeys—are poised for spillover, posing a threat to human health. We demonstrate key biological features that poise SAVs for zoonosis, including: (1) compatibility with human receptors; (2) high titer propagation in human cells; and (3) potential for evasion of human innate immunity. Further interrogation of the biology of SAV infection is crucial for future epidemic preparedness efforts. The objective of this proposal is to uncover mechanisms of cell entry, immune evasion, and zoonotic potential for these highly concerning viral pathogens. In Aim 1, we employ a series of molecular, biochemical, structural, and functional approaches to define SAV-receptor interactions and establish proof-of-concept strategies for future therapeutics—an essential step in outbreak preparedness. In Aim 2, we will identify SAV proteins that antagonize the human innate immune response, with the goal of revealing vulnerabilities that may help develop safe and effective antiviral approaches. In Aim 3, we will thoroughly evaluate the zoonotic potential of diverse SAVs. This includes: (1) identifying novel SAVs through whole virome sequencing of wild African primate biomaterials; (2) the development and application of non-human primate induced-pluripotent stem cell (iPSC)-derived macrophages to isolate novel SAVs in cell targets from natural host species; and (3) detailed infection studies in human cells to evaluate human compatibility. Further, we will perform the first in-depth serosurvey for SAV exposure history using banked sera from a Ugandan case-control cohort. When taken together, this proposal will lead to a deeper understanding of the molecular biology and pathogenesis of these understudied viruses, as well as a greater appreciation for the zoonotic risk that they pose. It is imperative that we invest in characterizing the biology and pathogenesis of SAVs now so that we may begin to develop platform technologies (i.e., diagnostics, vaccines, therapeutics) in case they do emerge in the future.

NIGMS - National Institute of General Medical Sciences

ABSTRACT Regulation of mRNA translation is vital for cells to acclimate and respond to changing environments and stress. A paradoxical mechanism of protein synthesis regulation is the modulation of translational fidelity. Mounting evidence shows that organisms, from bacteria to humans, regulate errors during translation to resist and acclimate to cellular stresses. Despite recent progress and exciting discoveries, our understanding of how trans- lational fidelity is regulated remains incomplete. The long-term objective of my research program is to determine how and why changes in translational fidelity occur and the molecular mechanisms underlying its regulation. In this MIRA proposal, we focus on the function of two families of translation factors: a rare tryptophanyl-tRNA synthetase (TrpRS) and an aminoacyl-tRNA deacylase (CtdA). Our preliminary and published results indicate that these protein factors coordinate translational fidelity in response to environmental and physiological changes. TrpRS is a universal and essential enzyme that ligates tryptophan to tRNAs during protein synthesis. TrpRS’s substrate specificity is critical in translational fidelity as ligation of non-cognate amino acids causes translation errors. Our preliminary data show that some organisms, including pathogens of public health interest, such as Salmonella enterica and Klebsiella pneumoniae, encode an unconventional TrpRS (named TrpRS-B2) with relaxed specificity that confers resistance against oxidative stress. TrpRS-B2 is predominantly found in organisms encoding an additional TrpRS (TrpRS-B1) that lacks the characteristics of TrpRS-B2. CtdA is a newly discovered family of aminoacyl-tRNA deacylases that maintain translational fidelity of Arg codons. CtdA hydrolyzes canavanyl-tRNAArg resulting from the ligation of canavanine, a toxic non-standard amino acid, to tRNAArg by arginyl-tRNA synthetase, which confuses canavanine with Arg. However, little else is known about the potential involvement of CtdA in other cellular functions and its diversification during evolution. The emphasis of our proposed research is to establish how TrpRS-B2 and CtdA contribute to the biology of several human-associated bacteria by regulating translation. In the next five years, we will address several fundamental questions using Salmonella enterica as a model organism because it offers a facile and established system to interrogate diverse environmental, physiological, and host-interaction conditions. We will investigate the molecular and biochemical differences between TrpRS-B2 and TrpRS-B1 and how TrpRS-B2 confers toler- ance to oxidative stress and promotes virulence. Moreover, we will examine the role(s) of CtdA beyond canavanine detoxification and the function of newly identified CtdA paralogs. These studies will shed light on the diverse regulatory mechanisms of translational fidelity and expand our understanding of the survival strategies of bacteria. Ultimately, this knowledge can help develop new approaches to treating human bacterial diseases.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY/ABSTRACT Nuclear-cytoplasmic transport governs communication between the cytoplasm and the nucleus and thus plays a pivotal role in the regulation of many fundamental cellular processes, including cell signaling, gene regulation, and cell cycle control. The nuclear pore complex (NPC) is one of the core components of the transport machinery and serves as the permeability barrier for macromolecular trafficking across the nuclear envelope. Given its housekeeping role as the gateway for nuclear-cytoplasmic transport, the NPC has been viewed as a relatively invariant structure across cell types. However, emerging evidence, including our own work, challenges this view and shows that NPCs exhibit profound variation in their number, post-translational modifications, and protein composition in different cellular and developmental contexts. Yet, we do not currently understand the mechanistic basis for how these changes in NPC state are regulated, nor how they influence cellular processes and cell physiology. The research proposal in this MIRA application will focus on the following three questions to define the emerging regulatory dimension of NPC function and their functional consequences on cell physiology. Over the next five years, we will: 1) determine how changes in NPC number modulate the kinetics and specificity of nuclear- cytoplasmic transport and control early embryogenesis; (2) define how NPC phosphorylation during interphase serves as part of cell signaling pathways to control nuclear-cytoplasmic transport and cell proliferation; and (3) dissect the mechanisms for assembly and regulation of cell type-specific NPC compositions during cell differentiation. Varied systems will be employed, including Drosophila embryos, mammalian tissue culture cells, and in vitro reconstitution systems, to best address the questions at hand. These projects will further the long- term goal of defining the role of the NPC as more than just a housekeeping transport apparatus but as an active regulator of cellular processes and physiology.

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary/Abstract Signaling through the B cell antigen receptor (BCR) is indispensable for B lymphocyte maturation, activation and differentiation as it governs the initiation of transcriptional programs associated with B cell activation and fate decisions, as well as the BCR-dependent processing of antigen and presentation of antigen to T cells. The dysregulation of BCR signaling results in immunodeficiency, autoimmunity or tumorigenesis. However, despite its pivotal relevance to health and disease, the mechanisms by which antigen binding initiates BCR signaling are still incompletely understood. Upon maturation, naïve B cells express both IgM and IgD isotypes of BCR, which have identical specificity and affinity for antigen. Yet, the functional advantage to co-express two BCR isotypes with equal affinities on every mature B cell remains puzzling. After antigen stimulation in the germinal center (GC), B cells differentiate and undergo somatic hypermutation as well as class switch recombination, by which their BCRs greatly increase affinity for antigen and change isotypes to IgG, IgE, and IgA. It has been shown that GC B cells have intrinsically higher-affinity thresholds for BCR signaling and pull on BCRs to extract from dendritic cells bound antigens mechanically. However, it is not known how the affinity threshold translates into force threshold and how mechanical force modulates BCR signaling. Using a set of mechanoimmunological concepts, ideas, approaches, and tools, we propose to investigate these fundamental questions under two specific aims, Aim 1 will test the B cell mechanosensory hypothesis at the single-cell and single-bond level by characterizing the Ig isotype-dependent in situ affinities and force-dependent lifetimes of BCR–antigen bonds and by correlating concurrently measured calcium (Ca2+) fluxes in B cells with the biophysical measurements. Aim 2 will test the B cell mechanosensory hypothesis at the cell population level by characterizing the Ig isotype-dependent B cell endogenous forces on BCR–antigen bonds, by measuring the Ig isotype-dependent calcium fluxes in B cells induced by BCR–antigen engagement, and by determining the force requirement for Ig isotype-dependent calcium fluxes in B cells. The proposed research holds the promise to provide the conceptual framework, design principles, and engineering strategies to harness the power of the B cell adaptive immune system to combat diseases ranging from viral infections, auto-immune disorders, to cancer.

Federal Communications Commission

In this document, the Federal Communications Commission's Media Bureau (Bureau) announces that due to prospective applicants' inability to access the Commission's Licensing and Management System (LMS) during the recent partial lapse in government funding and therefore prepare and file applications as previously scheduled, it is revising the dates for the Class A, LPTV, and TV translator major modification and LPTV/TV translator new station filing opportunities previously announced in its (public notice), DA 25-792, released September 3, 2025 (September 2025 PN).

Medina Memorial Health Care System - Community Partners

Program to assist low income homeowners and renters reduce lead hazards in their homes by providing education, lead screenings, materials and supplies.

Michigan Department of Agriculture and Rural Development

MDARD provides grants to farmers, agribusinesses, food banks, and rural organizations for agricultural development, local food systems, food safety, and rural community economic development across Michigan.

NINDS - National Institute of Neurological Disorders and Stroke

PROJECT SUMMARY / ABSTRACT Alzheimer’s disease (AD) is a neurodegenerative disorder affecting nearly five million Americans. Treatments are limited treatments and provide only modest benefits. Genome-wide association studies have identified TREM2 as one of the top AD risk genes. In particular, the TREM2R47H variant increases disease risk four-fold. How TREM2R47H affects risk for AD is currently unknown, but our preliminary observations in a mouse model indicate that it triggers hypersynchrony of thalamocortical circuits. TREM2 is expressed principally in microglia, and emerging evidence links microglial dysfunction and disrupted synapse remodeling to AD pathogenesis. My central hypothesis is that TREM2R47H causes thalamocortical hypersynchrony in AD mice by disrupting electrical properties of microglia that are essential for synaptic remodeling. To address this hypothesis, I will use a combination of advanced techniques spanning electrophysiology in human iPSC-derived cultures, brain slices and behaving mice, transcriptomics, and behavioral analysis. I will determine how TREM2R47H affects microglial electrical properties and transcriptional states by integrating electrophysiology with single-cell transcriptomics using Patch-seq and transcriptomic analyses in mouse and human iPSC-derived microglia (Aim 1). I will assess how these changes disrupt glutamatergic and GABAergic synaptic function in the thalamocortical system using patch-clamp recordings, circuit-level electrophysiology, and synapse reconstruction to identify synaptic mechanisms underlying thalamocortical hypersynchrony (Aim 2). Finally, I will test whether optogenetic manipulation of microglial membrane voltage can restore synaptic balance, reduce hypersynchrony, and improve behavioral deficits in mouse models of AD, providing critical proof-of- concept for therapeutic strategies (Aim 3). This integrated approach will yield a detailed understanding of how TREM2R47H microglia contribute to AD pathogenesis and identify novel therapeutic targets. This proposal will provide me with mentored training in advanced innovative techniques, including microglial optogenetics, circuit electrophysiology, machine-learning-based behavioral testing, and humanized rodent models of AD, which are essential for investigating microglial control of network dysfunction. Alongside the excellent training environment at Gladstone Institutes, my mentoring and advising teams expertise in defining the mechanisms of AD and network dysfunction driven by microglia, as well as advanced methods for circuit dissection, behavioral analysis, and thalamocortical oscillatory rhythms in cognition. This work will build upon my prior research into the molecular mechanisms of circuit hyperexcitability in neurodegenerative and neurodevelopmental disorders and form the foundation for my independent research program aimed at studying microglial contributions to thalamocortical circuit dysfunction and guiding the development of novel therapeutic strategies for neurodegenerative disorders.

Middletown

Military Museum Fire & Alarm System Upgrade

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY This application is submitted in response to RFA-DA-26-001: SCORCH Data Mining and Functional Validation. Human immunodeficiency virus (HIV) infects non-neuronal cells in the brain, particularly microglia, which serve as reservoirs of latent infection. HIV has deleterious effects on both non-neuronal and neuronal cell function in brain regions involved in reward, emotion, and cognition. Many of these same regions, including the nucleus accumbens (NAc), also regulate the motivational properties of opioids and other drugs of abuse. Opioid use disorder (OUD) is more prevalent in people living with HIV than in the general population, and HIV and OUD reciprocally interact, with each exacerbating the severity of the other. EcoHIV is a modified HIV strain capable of infecting microglia, macrophages, and CD4+ T cells in mice, and recapitulating key pathobiological features of chronic HIV infection in humans. As part of the SCORCH consortium, we have generated single-nucleus RNA sequencing (snRNA-seq), two-dimensional (2D) single-cell spatial transcriptomic (Spatial-seq), and 3D single- cell Spatial-seq data from the NAc of control and EcoHIV-infected mice that remained drug-naïve or had a history of intravenous (IV) opioid (oxycodone) self-administration. Sequencing data were also collected from the same groups of mice that received antiretroviral therapy (ART). Here, we will mine this unique dataset to investigate the cellular and molecular mechanisms of HIV and opioid interactions in the NAc. In AIM 1, we will analyze our sequencing data to define the genetic phenotypes and spatial organizations of the medium spiny neurons (MSNs) in the NAc that undergo the most robust transcriptional remodeling in response to HIV infection alone and in combination with opioid self-administration. This analysis will enable us to distinguish between D1- and D2-expressing MSNs, identify novel subtypes, and determine their distributions within the NAc according to established (e.g., core versus shell) or novel spatial architectures. We will also integrate our mouse sequencing data with similar datasets collected from HIV-infected and drug-experienced rats, non-human primates (NHPs), and humans, available through the SCORCH-Neuroscience Multi-omics (SCORCH-NeMO) Archive. By constructing a cross-species cell atlas of the NAc, we can prioritize HIV and opioid-responsive MSN subtypes for further analyses. In AIM 2, we will employ cutting-edge circuit mapping, electrophysiological, and molecular approaches to characterize functional adaptations in the genetically defined and spatially organized MSN subtypes that exhibit the most robust transcriptional responses to HIV infection and opioid exposure. In AIM 3, we will use the CRISPR-Cas9 system to target high-priority genes dysregulated by HIV and opioids in genetically defined and spatially organized MSN subtypes in the NAc. The effects of CRISPR-mediated gene cleavage in MSNs on IV opioid self-administration and other NAc-mediated behaviors relevant to HIV/opioid interactions will be evaluated in EcoHIV-infected mice. This highly innovative research program promises to fundamentally advance our understanding of the pathobiological interactions between HIV and opioids.

Minnesota Department of Agriculture

The MDA provides grants to farmers, food system organizations, and rural communities for sustainable agriculture, local food systems, beginning farmer support, agricultural marketing, and rural economic development across Minnesota.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Dengue, chikungunya, and Zika are diseases transmitted by Aedes aegypti. One strategy to reduce Ae. aegypti populations is to release non-biting male mosquitoes that pass female killing genes to their progeny. Over time and with many releases, this can lead to a significant suppression of the mosquito population, decreasing transmission of the pathogens they vector. Some female-killing technologies are available for this vector, but these technologies have some challenges that support the development of additional control technologies. To address this need, we aim to build new tools to generate female-killing technologies in Ae. aegypti. We focus on developing novel mitochondrial-targeted restriction endonucleases (mtREs) and CRISPR systems to kill females with flexible designs and components amenable for future development in a wide variety of mosquito vectors. As part of these efforts, we will explore switch-like cis-regulatory polycomb response elements (PREs) to modulate the transcriptional activity of the mtREs and Cas9. In Aim 1, we will selectively express the small mtRE, PacI, in female mosquitoes. Female-specific expression of PacI will be achieved by driving PacI expression with a female-specific promoter or by encoding a female-specific intron of the highly conserved doublesex (dsx) gene into the coding sequence of PacI. These expression systems will be further optimized by integrating the PRE upstream of the PacI promoter. In Aim 2, we will also use PREs to develop high precision heat shock-inducible and female-specific Cas9 expression systems. Heat shock promoters can still have activity at low temperatures, and Cas9 often has high activity, which can interfere with strain survival and the desired female-killing phenotype, so we aim to use PREs to minimize the issues. To achieve female specificity, the heat shock Cas9 will be designed to target female-specific essential genes, or the Cas9 will be engineered to encode a female-specific dsx intron in its coding sequence, ensuring Cas9 is only expressed in females. To optimize these Cas9 systems, they will be engineered first to target an easily screenable gene and then to target essential genes. The tools developed in Aims 1 and 2 will be evaluated in preliminary fitness and population cage studies, which will be used to prioritize their future development in Ae. aegypti and other mosquito vectors. These expression systems also have other applications for mosquito control and as a research tool to explore mosquito biology and genetics.

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary Prior research from our groups and others has shown that Psl and Pel exopolysaccharides (EPS) play important roles within Pseudomonas aeruginosa (Pa) biofilms. These include initiating and maintaining cell-to-cell interactions, maintaining the structure of the biofilm via interactions with extracellular proteins and DNA (eDNA), conferring tolerance of antibiotics and antimicrobial peptides, enabling colonization of lung epithelia, and persistence against the host immune response. While Psl and Pel are known to exist in two distinct forms: a cell- associated and a cell-released form, the role(s) each variant of the polymer may play within biofilms has typically not been considered separately. Distinct roles for cell-associated and cell-released Psl/Pel suggest that these two forms of the polymers are likely chemically or structurally different. Little is known about how these polymers are retained on the cell surface and whether chemical modifications such as deacetylation of Pel may impact this association. In this proposal, we will test the hypothesis that Psl and Pel exist in several different isoforms of variable length and/or chemical modification. The first specific aim will examine these EPS for modifications. The Sia system positively influences the amount of cell-associated Psl and Pel in a c-di-GMP dependent manner but the mechanism by which it does so is unknown. Experiments in this proposal will explore how the Sia system controls Pel/Psl localization to the cell surface. Finally, we hypothesize that the cellular distribution of Psl/Pel controlled by the Sia system will impact adhesion and biofilm biomechanics, interaction of polymers with matrix proteins and eDNA, the susceptibility of Pa to antimicrobial and host defenses as well as pathogenesis. Thus, we will dissect the biological consequences of EPS localization and the contribution(s) each form of the polymer plays within the biofilm.

NIAID - National Institute of Allergy and Infectious Diseases

Aberrant inflammation drives the development of autoimmune diseases and cancer. The incomplete understanding of molecular mechanisms controlling inflammatory activation and resolution remains a significant obstacle to developing effective treatments for inflammatory disorders. Therefore, the main objective of this proposal is to identify and characterize novel molecular pathways that regulate inflammatory responses. MicroRNAs (miRNAs) have emerged as essential regulators that fine-tune immune homeostasis through both activating and inhibitory functions. Among these, miR-146a serves as a paradigmatic example of an immunomodulatory miRNA that functions primarily as a negative feedback regulator of NFκB signaling. The indispensable role of miR-146a in immune homeostasis is demonstrated by miR-146a-deficient mice, which develop systemic autoimmunity, hematological malignancies, and bone marrow failure. Similarly, altered miR-146a expression in humans is associated with inflammatory diseases and cancer. Despite its clinical significance, the mechanisms controlling miR-146a biogenesis remain poorly understood. Our preliminary studies revealed an unexpected post-transcriptional mechanism regulating miR-146a production. We discovered that active protein synthesis is specifically required for miR-146a maturation, as translation inhibition arrests miR-146a processing at the precursor stage while other miRNAs are unaffected. Through an unbiased biochemical approach, we identified the tRNA synthetase EPRS1 as a specific pre-miR- 146a binding protein that recognizes its conserved apical loop. EPRS1 depletion significantly impairs miR-146a processing without affecting other miRNAs, establishing a novel regulatory axis linking protein synthesis machinery to inflammatory control. Our central hypothesis is that miR-146a biogenesis is controlled post- transcriptionally by EPRS1 and additional, yet-to-be-identified, translation-dependent factors. In Aim 1, we will define how EPRS1 regulates miR-146a biogenesis by characterizing their molecular interaction and identifying short-lived proteins required for EPRS1-dependent processing. In Aim 2, we will leverage CRISPR screen methodology to identify additional regulators of miR-146a biogenesis and determine their functional relationship to EPRS1. The proposed research is significant because it will reveal previously unappreciated mechanisms controlling miR-146a production and potentially explain its dysregulation in inflammatory and hematological diseases. Understanding these regulatory mechanisms may enable the development of innovative therapeutic strategies to restore miR-146a levels in patients, circumventing the limitations of direct miRNA therapeutics.