Grants

Town of Roxbury

Certified Local Government

City of New Haven

Certified Local Government

Town of Salisbury

Certified Local Government

City of Stamford

Certified Local Government

New Milford

Certified Local Government

Town of Roxbury

Certified Local Government

City of Norwich

Certified Local Government

City of Norwich

Certified Local Government

Town of Enfield

Certified Local Government

City of Stamford

Certified Local Government

Town of Enfield

Certified Local Government

New Milford

Certified Local Government

Automated Confirmations, Inc

Office Equipment and Accessories and Supplies

Office of Addiction Services and Supports

The goals of the project are to increase the number of CRPAs and CRPA-Ps; increase the number of bilingual CRPAs; assist with any barriers to obtaining the CRPA/CRPA-P; connect individuals who have obtained the CRPA/CRPA-P to a job and help them to remain in the job; increase the number of individuals obtaining the Veterans Supported Recovery (VSR) designation as a CRPA to assist with the many veterans who are struggling with substance use disorder; and assist in transitioning CRPA-Ps to the full CRPA and obtaining renewals.

NSF

This grant provides three years of funding to the Northeast National Ion Microprobe Facility (NENIMF) at Woods Hole Oceanographic Institution (WHOI). The NENIMF operates a Secondary Ion Mass Spectrometer (SIMS) as a resource for earth, ocean, and planetary science research. SIMS measurements analyze solid materials with great precision. The NENIMF SIMS measures the concentration and isotopic composition of light elements (hydrogen, lithium, boron, carbon, nitrogen, and oxygen). It supports research in two areas relevant to society, volcanoes and climate change. The SIMS can study the volatiles (dissolved gasses) found in magmas and examine climate signals in biogenic carbonates. The NENIMF trains and assists users with performing analyses. Fifty-six scientists from 32 institutions used the NENIMF from 2022 to 2024, and over the last three decades NENIMF instrumentation has supported almost 400 studies. The NENIMF uses a Cameca IMS 1280 double focusing mass spectrometer with a large radius magnetic sector (585 mm) and ion optics optimized to attain a mass resolving power (MRP=M/ΔM) of 6,000 without significant loss of secondary ion intensity. The IMS 1280 was recently upgraded with NSF support from single to multicollection with enhanced UV imaging capabilities. In addition to the specialized microanalytical capabilities of the NENIMF, SIMS users are investigating B isotopes in Mid-Ocean Ridge Basalt glasses and subduction zone minerals, Zr in rutile geospeedometry, Ti diffusion in quartz, and U-Th-Pb dating of monazite and zircon. New analytical protocols recently developed at the NENIMF include measuring the concentrations of low abundance volatile elements in nominally anhydrous minerals, characterization of the isotopic composition of B at very low concentrations, measurement of volatiles in very small (< 10 µm diameter) melt inclusions, and development of isotope and concentration reference materials. The NENIMF emphasizes student learning and training of undergraduates, graduate students, and post-doctoral researchers. It will continue to involve WHOI’s Undergraduate Summer Student Fellows, Post-doctoral Scholars, and WHOI/MIT Joint Program graduate students in SIMS-focused research projects. The NENIMF will run annual workshops to engage young scientists in SIMS-based research focused on magma volatiles, and it will conduct community outreach at scientific meetings. The NENIMF will strive to make its analytical platforms accessible to many different users, and it will select and support a visiting summer student during each year of these operations. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIA - National Institute on Aging

Abstract Misfolded/dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein causes multiple health related issues including lung disease and diabetes in cystic fibrosis (CF). Scientific advancements have significantly prolonged the life span of CF patients. But aging promotes endothelial dysfunction. Importantly, CF patients are known to have impaired endothelial function. Therefore, it is likely that endothelial dysfunction will worsen with age in CF patients. However, how CFTR regulates endothelial function and thereby vascular tone is not known. It is not known whether CFTR modulators are effective against CF-associated endothelial dysfunction. Therefore, it is important to understand the significance of CFTR in endothelial function and to assess the impact of aging on endothelial function in CF patients. Our preliminary data suggests that like CF patients, deletion of CFTR or expression of dysfunctional CFTR exhibit impairment of endothelium-dependent relaxation of coronary arteries in pigs. Even acute pharmacological inhibition of CFTR in mice aortic rings leads to endothelial dysfunction. We have also noted that genetic deletion of CFTR or pharmacological inhibition of CFTR downregulates endothelial nitric oxide synthase (eNOS) expression in endothelial cells. As aging promotes endothelial dysfunction and downregulation of eNOS levels, we propose to evaluate the changes in endothelial function and examine the mechanism involved in CFTR-mediated regulation of NO production with aging. We will use a novel mouse model of CF disease with endothelial deletion of CFTR (e-CFTR-/-) to determine: 1) whether aging-induced endothelial dysfunction accelerates with endothelial deletion of CFTR and 2) the eNOS- CFTR regulation as a mechanism mediating the CFTR-dependent regulation of endothelial function. We will examine vascular function in aged mice having endothelial deletion of CFTR. We will also use cell biology-based assays to determine the functional changes in the endothelial cells due to CFTR and possible ways to modulate such effect. This study will demonstrate the impact of aging on endothelial dysfunction due to loss of CFTR function.

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY Cystic fibrosis (CF) is a life-threatening genetic disorder that affects >120,000 individuals worldwide. Mutations in the CFTR gene cause CF, with 10% of people with CF (pwCF) having two copies of mutations that are unre- sponsive to FDA-approved CFTR modulators. Exon 12 contains the most common modulator-ineligible mutations, affecting nearly one in five pwCF who are not able to receive modulator therapies. This subpopulation of pwCF urgently needs a corrective gene editing therapy to restore CFTR function. Gene editing the endogenous CFTR presents a promising path to cure CF by correcting the pathogenic mutations. However, current approaches face significant limitations: they target only one or few mutations at a time, demonstrate low efficiency and risk unintended off-target effects. To overcome these barriers, this proposal aims to develop a new gene editing strategy that replaces the entire exon 12 without a DNA break, termed retron editing. Successful completion of the proposed aims will establish a retron editor that can safely and efficiently replace CFTR exon 12. More broadly, successful retron-mediated exon replacement will transform the lives of pwCF and those with other rare monogenic diseases.

Regional Council Capital Fund - RC4

CG Meaker Redevelopment Capital

Cgh Health Foundation

Cgh Health Foundation is an active grantmaking foundation based in Sterling, IL. Focus: general. Contact the foundation directly for current funding opportunities.

NIA - National Institute on Aging

Project Summary Apolipoprotein E4 (E4) is the predominant genetic risk factor for Alzheimer’s disease (AD). Recent studies demonstrate that E4 contributing to tau-induced neurodegeneration. However, the mechanisms by which E4 contributes to tau toxicity remain poorly understood. The GAS-STING-Interferon (IFN) signaling pathway is known to exacerbate the immuno-inflammatory response, worsening the procession neurodegenerative diseases. In AD, pathogenic tau can induce cGAS-STING-IFN signaling in microglia. Importantly, inflammatory responses, such as IFN, are heightened in microglia expressing E4, suggesting a potential mechanistic association between E4 and IFN pathway. Cholesterol 25-hydroxylase (CH25H) is an interferon inducible gene (ISG) predominantly expressed in disease associated microglia, where it produces 25-hydroxycholesterol (25- HC), a bioactive lipid involved in immune regulation. We previously showed that 25-HC exacerbates, while deletion of Ch25h suppresses, microglial inflammatory response. Notably, E4 promotes a stronger 25-HC- dependent IL1b/a cleavage compared to E3 or E2. Our preliminary studies suggest that Ch25h deletion mitigates tau pathology, reduces neurodegeneration, and improves cognitive function in tauopathy mouse models. These protective effects are linked to suppressed microglial inflammatory signaling and reduced STING expression in vivo and in vitro. These results suggest that 25-HC may regulate cGAS-STING signaling, a pathway implicated in tauopathy in our previous studies. Based on these observations on 25-HC and APOE, we hypothesize that CH25H acts with APOE4 to activate microglial STING-IFN signaling and promote Tau toxicity and neurodegeneration in AD. Aim 1 will investigate how 25-HC promotes cGAS-STING-Inflammasome signaling in microglia, by characterize the dose-dependent effects of exogeneous 25-HC in cGAS-STING-IFN activation, investigating whether 25-HC activates the STING-inflammasome pathway and exploring alternative mechanisms involving cytosolic dsDNA accumulation using unbiased multi-omics approaches. Aim 2 will determine if E4 activates cGAS-STING-IFN via an CH25H-dependent mechanism by characterizing the effects of E4 on tau- induced IFN responses in microglia and assess if E4 activates cGAS-STING signaling at baseline and under tau fibrils stimulation, investigating whether CH25H mediates E4-induced IFN response in microglia, and determining if intracellular cholesterol dysregulation is the convergent mechanism for Ch25h and E4. Aim 3 will investigate if CH25H enzymatic activity is required for E4-induced toxicity in tauopathy mice and assess the therapeutic potential of CH25H inhibition using antisense oligonucleotides (ASOs) by leveraging newly established mouse models with enzyme-active and enzyme-inactive CH25H overexpression to examine the role of 25-HC in tauopathy mice expressing E4 (TE4). We have assembled a highly complementary and collaborative research team to address these aims. We anticipate that our study will identify novel cellular mechanisms, uncover innovative pathways, and provide new models that have therapeutic implications.

Department of Family and Support Services

CHA FAMILY SUPPORTIVE SERVICES

Chaddock Childrens Foundation

Chaddock Childrens Foundation is an active grantmaking foundation based in Quincy, IL. Focus: social services. Contact the foundation directly for current funding opportunities.

Chaffey College Foundation

Chaffey College Foundation is an active grantmaking foundation based in Rch Cucamonga, CA. Focus: education. Contact the foundation directly for current funding opportunities.

NSF

A goal of the Tribal Colleges and Universities Program (TCUP) is to increase the science, technology, engineering and mathematics (STEM) instructional and research capacities of specific institutions of higher education that serve the Nation's indigenous students. Expanding the instructional, research, and development capacity at these institutions expands the opportunities for students to pursue challenging yet rewarding careers in STEM fields, provides for research studies in areas that may be locally relevant, and encourages a faculty community to look beyond the traditional classroom for intellectual and professional growth. This project aligns directly with that goal by strengthening the STEM cyberinfrastructure for instructional and research activities. The project aims to enhance cyberinfrastructure and cybersecurity necessary to facilitate development of the institution in STEM fields and for the protection of sensitive data. The project upgrades specific STEM IT resources at Lac Courte Oreilles Ojibway University to improve the resiliency and security of STEM operations, data management as well as the teaching and research enterprises. Improvements to the university’s network and cybersecurity, fosters its ability to implement advances in STEM instruction and research. The activities for developing STEM cyberinfrastructure directly support current and future projects, including the ability to expand STEM instruction through distance education. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.