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Cape Cod Foundation

Cape Cod Foundation ($75M in assets) supports nonprofits in MA through grants focused on education, environment, health, arts. Awards range from $1,000 to $25,000.

Capital Region Community Foundation (Lansing)

Capital Region Community Foundation (Lansing) ($100M in assets) supports nonprofits in MI through grants focused on education, community development, health, arts. Awards range from $1,000 to $50,000.

Capoeira Life

The South Seattle Capoeira Academy, located at 2909 Rainier Ave S #103 will be rebuilt after sustaining damage due to a flood. The project will allow the rebuilding of their homebase into an even greater serving cultural art center that will improve safety, have a greater capacity for events and provide health and wellness to the community, and increase the impact to public benefit. The project is free and open to public participation. The project will be completed in summer of 2026.

NHLBI - National Heart Lung and Blood Institute

Project Summary Angina is one of the most common symptoms prompting coronary angiography, yet up to 50% of patients are found to have no significant obstructive coronary artery disease (CAD). Many of these individuals continue to experience chest pain without a clear diagnosis. In a substantial proportion of cases, symptoms are attributable to coronary microvascular dysfunction (MVD), an increasingly recognized contributor to myocardial ischemia, heart failure with preserved ejection fraction (HFpEF), obesity, and diabetes. Despite its high prevalence, MVD remains underdiagnosed and challenging to monitor noninvasively. Invasive coronary function testing (CFT) is the gold standard but is technically complex, carries procedural risk, and is limited to specialized centers. While positron emission tomography (PET) enables non-invasive quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR), its utility is constrained by cost, limited availability, radiation exposure, and moderate spatial resolution. Cardiac magnetic resonance (CMR) offers a promising, widely accessible alternative. Recent advances in quantitative perfusion mapping, Artificial Intelligence-driven image enhancement, and multiparametric tissue characterization have transformed stress CMR into a powerful tool for assessing perfusion and myocardial health with high spatial resolution. These capabilities position CMR to play a central role in the diagnosis and monitoring of MVD. This proposal leverages state-of-the-art CMR technology, cross-modality validation, invasive testing, and mechanistic phenotyping to: • Define and validate CMR-based diagnostic criteria for MVD using invasive CFT as the reference standard. • Evaluate the correlation and comparative diagnostic accuracy of CMR- versus PET-derived MBF and MPR for detecting MVD. • Assess whether GLP-1 receptor agonist (GLP-1RA) therapy improves coronary microvascular function independent of weight loss, using bariatric surgery as a comparator and serial quantitative CMR for longitudinal assessment. This work addresses a critical unmet need for non-invasive diagnostic tools and treatment monitoring in MVD, with the potential to expand precision cardiovascular care for an overlooked yet high-risk population.

Cartier Foundation

Funds contemporary art, environmental programs, and cultural projects globally.

NCI - National Cancer Institute

PROJECT SUMMARY CD8 T cells are powerful adaptive immune cells that have the ability to eradicate cancer cells. However, despite the presence of tumor-specific CD8 T cells (CD8 TST) tumors progress, suggesting that CD8 T cells become dysfunctional. While direct cytotoxic activity against cancer cells generally resides within the CD8 T cell compartment, CD4 T cells play important roles in priming and activation of naïve CD8 T cells in lymphoid tissues and enhancing CD8 T cell mobilization into peripheral tissues, including tumors. We recently investigated if and how tumor-specific CD4 T cells (CD4 TST) could be enlisted to overcome CD8 TST dysfunction/exhaustion in tumors (Espinosa et al., (2024)). Employing preclinical cancer models as well as human samples, we discovered that CD4 TST are critical during the effector phase within tumors: CD4 TST must co-engage with CD8 TST on the same dendritic cell (DC), forming a three-cell-cluster (triad) to license CD8 TST cytotoxicity and tumor destruction. Triad formation reprograms CD8 TST, preventing and even reversing CD8 TST dysfunction/exhaustion, ultimately leading to the elimination of large established tumors and long-term protection from recurrence. We showed that when triad formation is prevented in settings of immunotherapies, tumors progress even when equal numbers of CD8 and CD4 TST are present within tumors. Strikingly, we found that the presence of triads in tumors of patients treated with immune checkpoint blockade was associated with clinical responses. Thus, the unique spatial positioning and cell-cell interactions of CD4 T cells, CD8 T cells, and DC are critical for anti-tumor responses. These intriguing findings have now led us to ask how CD4 TST in immune cell triads license CD8 TST to kill cancer cells. Which transcription factors (TF) and polarization state(s) are required for CD4 TST effector function within triads? Which receptor/ligand and/or cytokine/chemokine signals mediate CD8 TST cytotoxicity? Which signals do DC provide to CD4 TST and/or CD8 TST? Are specialized DC subsets, phenotypes, or maturation states needed? In this application, we will leverage the power of preclinical cancer models and unique human samples, employ state-of-the-art technologies, and design and test innovative strategies to identify the critical molecular factors and signals within triads and test how they can be enforced for the treatment of cancer. This work will provide mechanistic insights into the immune cell interactions critical for tumor control and inform strategies to enhance immunotherapy responses.

NCI - National Cancer Institute

ABSTRACT Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative cellular therapy strategy for pediatric patients with high-risk B-cell ALL but is associated with significant complications, the most consequential of which are relapse, GVHD and the devasting consequences of use of total body irradiation (TBI) as conditioning therapy. CAR T cell therapy has emerged as a novel, powerful cellular therapy for the treatment of relapsed/refractory B- ALL. We now propose to combine these two powerful cellular therapies, namely allo-HCT and transplant donor- derived allogeneic CAR T cell therapy to minimize the risk of relapse and eliminate TBI. In addition, we will use graft engineering approaches to minimize GVHD by select use of immune effectors. We will use for : i) The transplant platform : TCRαβ T cell depletion approach as TCRαβ T cells are key mediators of GVHD and ii) the CART platform : a naïve T-cell depleted product as naïve T cells are key mediators of GVHD leaving behind memory T cells which do not cause GVHD, to manufacture our CAR T cell product, (CD19-CAR(Mem) T cells). We hypothesize that combining allogeneic transplant donor-derived CD19-CAR(Mem) T cells infusion prophylactically after TCRαβ+ T cell depleted alloHCT will provide complimentary and augmented immune-mediated graft-versus-leukemia effects which will decrease risk of relapse and allow for the use of a TBI- free conditioning regimen while maintaining low rates of GVHD. A secondary hypothesis is that that carefully orchestrated correlative studies are needed to decipher the mechanisms of response and resistance of our approach to enable future innovation. We will test these hypotheses in two aims: Aim 1: To assess feasibility, safety, and clinical outcomes of prophylactic CD19-CAR(Mem) T cell infusion after TCRαβ+ depleted transplant and reduced-toxicity TBI-free conditioning. Aim 2: To characterize the fate and function of infused CAR T cells, their impact on immune reconstitution, and mechanisms of response and resistance using advanced state-of-the art correlative testing including TCR analysis and 10x scRNAseq analysis of immune cells and malignant blasts. If successful, this strategy could enable powerful, TBI-free transplant strategies that will lead to long-term remissions with minimal morbidity and mortality for pediatric B-ALL. Extensive correlative data generated will provide critical information for the field of transplantation and cell therapy. While this application is focused on pediatric B-ALL, these findings could be readily applied to broader pediatric and adult populations enabling novel, innovative, combinatorial cell-therapy based approaches across the spectrum of high-risk hematological malignancies.

Black and Tan Project

The Black and Tan community group will mark the celebration of Black History with a play, `Reparations: A Musical Which Centers on the Fictional Trial of Thomas Jefferson`. The play will be held at Langston Hughes Performing Arts Institute located at 104 17th Ave S. The Company will perform a series of 3 Shows starting Friday evening at (LHPAI) over 3 days. There will be a peer panel following Friday's premiere. Saturday- doors open at 6:00pm, followed by a performance of the Play at 7:30pm, a reception with Food, Afro-Centric vendors and Music Entertainment. Closing night is the Sunday matinee, Doors open at 3:00pm Show starts at 4:30pm. The event is free and open to the public.

Friends of Latinx Essential Workers

On May 10, 2020 the Friends of Dia de las Madres group will be hosting an event at Langston Hughes Performing Arts Institute located at 104 17th Ave S from 2pm-4pm. A celebration of women and mothers on Mexico's Mother's Day, Latina artistic leaders, professional musicians, and volunteers will join with Friends of Dia des Madres and Orquesta Northwest to present a concert with performances of original music by María José Félix, in a world-premiere collaboration with Washington State Poet Laureate Claudia Castro Luna and of Mexican composer Manuel Ponce's first piano concerto by Daniela Liebman.

Capitol Hill Housing Foundation

The LGBTQ Senior Celebration will be held on September 21, 2017 from 5pm to 8pm at the Calamus Auditorium located at 517 E Pike St. The goal of this celebration is to catalyze a conversation on affordable housing and healthcare for LGBTQ seniors on Capitol Hill. There will be Queer art, food, and storytelling that will bring generations together to create a strong foundation for Capitol Hill Housing's plans to create a low-income LGBTQ senior affirming apartment building.

National Endowment for the Humanities

CELEBRATION OF AMERICA THROUGH THE ARTS [YOUNG AUDIENCES OF HOUSTON CELEBRATES AMERICA THROUGH A CULTURAL ARTS EVENT SERIES OF HUMANITIES FOCUSED LECTURES AND WORKSHOPS FOR PK-12 YOUTH, HIGHLIGHTING KEY HISTORICAL FIGURES AND MOMENTS HONORING THE UNITED STATES OF AMERICA. PROGRAMS INCLUDE COMMUNITY EVENTS AND FAMILY PROGRAMS THAT ARE FREE AND OPEN TO THE PUBLIC AND PROVIDE KNOWLEDGE OF AMERICA'S HISTORICAL EVENTS.]

NIA - National Institute on Aging

ABSTRACT This proposal presents an innovative and interdisciplinary approach to accelerate the development of effective, precision therapeutics for Alzheimer’s disease (AD), a complex and heterogeneous neurodegenerative disorder with limited treatment options. Recognizing the critical role of neuroimmune and vascular dysfunction in AD pathogenesis—particularly within the perivascular spaces, the we will leverage state-of-the-art single-nucleus transcriptomic profiling (VINE-seq) and integrative computational drug repositioning to identify and test repurposed compounds capable of modulating disease-relevant gene expression signatures at the cell type level. The project builds on extensive preliminary data identifying key AD-related transcriptional signatures across neurons, glia, and vascular/perivascular cells, revealing both known and novel therapeutic targets. Using publicly available and lab-generated transcriptomic datasets, the team employs tools like Connectivity Map and LINCS to predict drug candidates that reverse pathogenic gene networks in distinct brain cell types. Early analyses have already nominated over 80 potential compounds, including letrozole, irinotecan, sirolimus, and vorinostat, several of which show multi-compartment activity and strong preclinical promise. These candidates will be rigorously validated in vitro using iPSC-derived neurons, glia, and assembloid models, and in vivo using mouse models of AD with tools like longitudinal bioluminescent imaging and plasma biomarkers to assess efficacy, target engagement, and safety. Aim 1 seeks to validate and optimize repurposed drugs targeting neuron-glial dysfunction by integrating computational predictions with functional studies in co-culture systems, chronic mouse dosing models (e.g., 5xFAD, hTAU), and multi-omic readouts of parenchymal pathology, including amyloid burden, neuroinflammation, and synaptic loss. Aim 2 focuses on the vascular-perivascular axis of AD by using single-cell signatures from VINE-seq to identify and test compounds that reverse vascular dysfunction and immune dysregulation in CAA-associated AD models (e.g., TgAPP23), with endpoints including cerebral amyloid angiopathy, blood-brain barrier integrity, and perivascular inflammation. Together, these complementary aims form a robust platform to evaluate and prioritize sex- and cell-type-specific therapies that address both neuronal and vascular drivers of AD. The collaboration brings together a world-class team with expertise in AD genomics, drug repurposing, systems immunology, mouse modeling, and human cell-based models. By uniting cutting-edge transcriptomic technologies with in vivo pharmacology and a precision medicine framework, this work has the potential to deliver impactful therapeutic strategies that can be rapidly translated into clinical trials for patients with Alzheimer’s disease.

NIH

Significance to VA. Disrupted sleep occurs in many conditions common in Veterans, including VA research priorities such as post-traumatic stress disorder (PTSD), substance abuse, major depression and neurodegenerative disorders. Insomnia is associated with an increased risk for suicide and increases the risk for relapse in opioid use disorder. Furthermore, disrupted sleep and abnormal sleep spindles are common in expensive, hard-to-treat conditions such as dementia and schizophrenia. Increasing evidence suggests that sleep spindles are needed for memory consolidation. Deep sleep is vital in clearing the toxic proteins which are increased by traumatic brain injury and cause neurodegeneration. Accordingly, novel strategies to promote deep restorative sleep are needed for a wide variety of disorders affecting Veterans. Cognitive treatments have utility but exert a relatively modest effect and the most widely used existing pharmacological treatments may disrupt deep restorative sleep and be habit-forming. Thus, alternative treatments are needed. Innovation and Impact. Here, in mice we evaluate for the first time whether deep restorative sleep can be enhanced through cell-type specific modulation of an important basal ganglia structure, the globus pallidus, pars externa (GPe). Our data suggest inhibition of GPe neurons which express the calcium-binding protein parvalbumin (PV+) shortens sleep latency and strongly increases the depth and consolidation of sleep. Our novel data show that another group of neurons which express the transcription factor neuronal PAS domain 1 (Npas1+) regulate sleep spindles, important in memory consolidation. Thus, pharmacological or brain stimulation strategies which inhibit GPe PV+ neurons may be a novel strategy to treat insomnia, whereas inhibition of Npas1+ neurons may promote memory consolidation. Our new data in Aim3 identify a safe natural pharmacological agent which opens potassium channels to inhibit GPe PV+ neurons and promote sleep. Specific Aims. Here, experiments focus on two major, non-overlapping neuronal-types of the GPe, PV+ and Npas1+, which make up 50 % and 30 % of GPe neurons, respectively. Aims 1 and 2 will use state-of-the- art neuromodulatory approaches in genetically-modified mice to test the effects of exciting or inhibiting these neurons on sleep. Aims 1 and 2 will also extend our approach to wild-type mice and identify the downstream neuronal targets. In Aim 3 we will test whether we can enhance sleep via systemic or local application of a safe natural compound which preferentially inhibits GPe PV+ neurons by opening potassium channels. Methodology. All aims investigate the effects of GPe manipulations on sleep and cortical electrical oscillations using electroencephalographic and electromyogram recordings in mice. Aim 1 uses chemogenetics to excite or inhibit GPe PV+ or NPas1+ neurons. Chemogenetics allows a prolonged increase or decrease in neuronal activity through the cell-type specific expression of G-protein activated receptors which respond selectively to an otherwise inert drug. Aim 2 will use closed-loop optogenetics to specifically inhibit (Aim2a) or excite (Aim2b) PV+ or Npas1+ during non-rapid-eye-movement sleep. Optogenetics allows fast and precise manipulation by applying light to neurons expressing light-activated ion channels or pumps. Aim 3 will use a pharmacological approach to inhibit GPe PV+ neurons by opening the potassium channels they express. Path to translation/implementation: Potentially the fastest translational application of this research is to use a pharmacological approach, as in Aim3, to enhance sleep by inhibiting GPe PV+ neurons via opening of the potassium channels they express. Several potassium channel openers, including the natural one we test here are safe and approved for use in humans and proposed as therapeutic agents. Another approach could be to modify existing electrical deep brain stimulation protocols or non-invasive stimulation approaches to target GPe to promote healthy sleep and daytime alertness. Ultimately, in the longer-term, we believe that cell- type specific approaches such as optogenetics or chemogenetics could be applied.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY Opioid use disorder (OUD) is common among people living with HIV, and the combination produces more severe neurobehavioral impairments than either condition alone. Both HIV and opioids remodel neural circuits through inflammatory and neuromodulatory pathways, with brain region specific effects. Microglia, the resident immune cells of the brain, are central to these processes, yet it is unknown how HIV and opioid signals converge at the protein level to influence microglial function over time and across circuits. While single-cell RNA sequencing has revealed microglial heterogeneity, transcript levels often correlate poorly with protein abundance. Because proteins are the functional effectors of cellular processes, direct proteomic measurement provides a more accurate view of activity. However, bulk proteomics masks cell- type-specific responses, and targeted protein assays limit discovery of novel effectors. This project employs a state-of-the-art, cell-type-specific proteomic strategy using a Cre-dependent mutant methionyl-tRNA synthetase (MetRS*) system. This approach labels nascent proteins in microglia in vivo with the noncanonical amino acid azidonorleucine (ANL), enabling selective enrichment and mass spectrometry based profiling. It provides unprecedented temporal and spatial resolution of microglial proteomic changes across brain regions and disease stages. Using models of EcoHIV infection and fentanyl exposure, we will define distinct and overlapping microglial protein networks that emerge in each condition and during comorbidity. We hypothesize that HIV and opioids drive both unique and convergent proteomic programs in a brain region and time-specific manner, contributing to behavioral adaptations relevant to addiction and neuroimmune dysfunction. The phased R61/R33 design first validates and optimizes microglial proteomics across brain regions and labeling windows (Aim 1), then identifies EcoHIV-induced proteomic signatures in behaviorally relevant regions (Aim 2). In the R33 phase, we will map microglial proteomic dynamics across the addiction cycle in fentanyl, EcoHIV, and combined models (Aim 3). Finally, we will integrate mouse proteomic data with human single-cell RNA-seq datasets and validate high-priority targets using multiplexed imaging in both mouse and human brain tissue (Aim 4). Impact: This work will produce the first spatiotemporal atlas of microglial proteomic adaptations to HIV, opioids, and their combination. By identifying conserved molecular signatures that link microglial plasticity to behavioral outcomes, the project will yield mechanistic insight into neuroimmune dysregulation in comorbid HIV & OUD and lay the groundwork for targeted therapeutic strategies.

OD - NIH Office of the Director

PROJECT SUMMARY This application requests funds to purchase a cellenONE X1 Neo single-cell isolation and liquid dispenser system from Cellenion. The proposed instrument will be located in the Mass Spectrometry Proteomics Core at Baylor College of Medicine. The cellenONE X1 Neo is essential for establishing ultra-low-input proteomics capabilities at BCM and will be primarily used to isolate single cells and subcellular structures from clinical samples, pre-clinical patient-derived xenograft models, and various animal- and cell-based model specimens. Configured with protein sample processing workflows for bottom-up mass spectrometry, this platform will meet critical sample preparation needs for picogram- and nanogram-level starting materials, which demand extremely precise, low-volume, and contamination-free sample handling not adequately supported by our standard core protocols. Single-cell and spatial proteomics is a novel and rapidly advancing area of biomedical research with the potential to transform our understanding of cellular heterogeneity and disease mechanisms. However, despite BCM’s extensive research infrastructure, this capability is currently lacking at our institution. The addition of the cellenONE X1 Neo represents a significant leap forward, enabling our core to offer a complete, automated solution for ultra-sensitive proteomic analysis. Importantly, this instrument will leverage a recent acquisition of the Bruker timsTOF Ultra2 in the Mass Spectrometry Core – a $1.2 million investment in state-of-the-art mass spectrometry instrumentation capable of measuring ultra-small-scale proteomes. Although this Bruker timsTOF is already used for other challenging applications, the absence of a suitable single-cell preparation platform remains a critical barrier to adopting true single-cell and spatial proteomics workflows. The unifying aim of the projects supported by the cellenONE X1 Neo is to explore the molecular mechanisms driving normal physiology and disease at the level of individual cells or rare cell populations. This instrument will provide the precision, scalability, and operational robustness necessary to meet the evolving needs of our growing user base. Its integration into the Mass Spectrometry Proteomics Core aligns with BCM’s strategic plan to expand and share cutting-edge proteomics capabilities and will directly enhance research initiatives in cancer, metabolic disease, neuroscience, immunology, and beyond. The cellenONE X1 Neo will position the Core, and BCM more broadly, as a regional leader in ultra-sensitive proteomics by providing a comprehensive, accessible sample processing solution.

NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases

Project Summary/Abstract Psoriatic arthritis is a chronic and progressive inflammatory arthritis closely linked with psoriasis. Blockade of the IL-17 signaling pathway shows impressive efficacy and excellent safety for treatment of psoriasis but less so for PsA. Tissue penetrance limits the bioavailability of monoclonal antibodies to the joint and fibrocartilaginous enthesis and IL-17A signaling is diversified by local immune cells in tissues rendering IL-17A inhibition less effective. A higher dosage poses the risks of serious infections and certain types of cancer as all IL-17 inhibitors are immunosuppressive therefore to improve clinical outcomes in PsA more selective targeting is required. Herein, we have developed a novel animal model of IL-17A gene transfer where mice develop joint and skin inflammation associated with enthesitis, fingernail psoriasis and onycholysis hallmarks of PsA pathology. We will interrogate our murine model to define the early cellular and molecular pathways that dictate IL-17A-induced pathologies using state-of-the-art transgenic mice and molecular tools. Our work will uncover the pathogenic mechanisms of IL-17A and uncover novel molecular targets that can be exploited for therapeutic intervention and directly benefit PsA patients worldwide.

NIGMS - National Institute of General Medical Sciences

PROJECT SUMMARY / ABSTRACT Endosymbiotic events have driven the evolution of dramatic and consequential biological traits, however most known examples occurred billions of years ago, resulting in deeply integrated associations that mask early steps in the evolution of these associations. “Solar powered, sap sucking” Sacoglossan sea slugs represent a recent and incompletely established endosymbiosis in which stolen, functional chloroplasts are stored in slug tissues. Here, I propose to leverage this unique organism to understand the mechanistic basis of stolen chloroplast (kleptoplast) retention and integration into host cell physiology as a model for understanding endosymbiosis more broadly. To accomplish this, I will: (Aim 1) use organellar proteomics to identify proteins critical for establishment and maintenance of this endosymbiosis (often called “functional kleptoplasty”), (Aim 2) determine the function of those proteins using a combination of pharmacology, patch clamp experiments, and heterologous expression studies, and finally (Aim 3) expand these experiments in a comparative approach using different species of Sacoglossan slugs with different retention abilities. Thus, this study will employ rigorous methodology combining state-of-the-art sequencing technology and multi-omics approaches with physiological approaches, functional assays, and a diverse set of imaging techniques. Further, I will leverage the incredible biodiversity of sea slugs to empower a comparative approach for a comprehensive understanding of a truly unique biological phenomenon: the maintenance of functional photosynthetic chloroplasts within animal tissues. This project will take place at host institution Harvard Medical School (HMS, Cell Biology) and builds on my expertise in transcriptomics, evolutionary biology, and bioinformatics with training in new skills from my primary sponsor, Dr. Corey Allard (HMS, Cell Biology), in electrophysiology, biochemistry, and molecular techniques. I will be aided by an interdisciplinary advisory team composed of my co-sponsor, Dr. Wade Harper (HSM, Cell Biology), an expert in organelle proteomics, Dr. Steven Gygi (HMS, Cell Biology), a world leader in proteomics, and Dr. Amy Lee (HMS, Cell Biology/Dana Farber Cancer Institute), an expert in transcription and RNA biology. Investigation of functional kleptoplasty in Sacoglossan sea slugs will fill a critical gap in our understanding of the evolution of endosymbiosis and the integration of novel organelles into host cells. Completion of these aims will reveal mechanisms used by slugs for sequestration and maintenance of chloroplasts, and thus advance our understanding of the origins and functions of organelles and the fundamental processes that drive the evolution of novel traits. These insights may have broad applications in biotechnology, and could serve as a blueprint to engineer other types of cells to perform photosynthesis, or to take up different foreign cargoes for applications in agriculture, medicine, or even space travel.

NIEHS - National Institute of Environmental Health Sciences

PROJECT SUMMARY Numerous environmental agents (hereafter, genotoxins) induce DNA lesions or create other types of barriers that stall replication forks. This can lead to replication stress, and failure to alleviate this stress and restart stalled forks can cause genome instability. Elevated replication stress and the replication-associated mutations that result from genotoxin-induced fork stalling contribute to aging, inflammation, cancer, and numerous other chronic diseases in humans. This project aims to advance understanding of the cellular responses to replication stress. One crucial aspect of the replication stress response involves replication fork reversal, a process that remod- els both the nascent and parental DNA strands to form a four-way junction structure. Fork reversal is carried out by a family of ATP-dependent translocases. Why multiple enzymes with similar activities are involved in this process is not understood. We showed that one of these translocases, HLTF, prevents a remarkably DNA dam- age-tolerant mode of replication by promoting fork reversal and preventing alternative and potentially error-prone modes of DNA synthesis. The unanticipated resilience of the replication fork to various genotoxins in HLTF’s absence may drive mutagenesis and promote the survival of damaged cells. We will investigate the cellular responses to genotoxic and oxidative damage, focusing on the mechanism of replication fork reversal and the impact of loss of fork reversal on genome stability and cell fitness. By combining molecular, biochemical, genomic and proteomic approaches, as well as state-of-the-art single-molecule ap- proaches, we will address the following broad questions: What are the functions of fork reversal and how does it occur in response to environmentally relevant forms of genotoxic damage? What are the specific functions of a central regulator of fork reversal, HLTF, in the face of oxidative and genotoxic DNA damage? Does loss of HLTF and fork reversal increase mutation (rates) in the context of environmental stressors? Our strategy will initially focus in large part on HLTF, elucidating its unique roles. As the project evolves, we will phase in further studies on other remodelers so as to understand, over the long-term, the overall fork reversal process and the unique contributions of each protein to the replication stress response. The knowledge we gain from this research will ultimately facilitate the development of new strategies that i) alleviate the pathological states observed in the absence of the replication stress response, and ii) prevent cancer cells' ability to tolerate DNA damage and develop drug resistance.

NIGMS - National Institute of General Medical Sciences

Montana State University (MSU) is the alma mater of Maurice Hilleman, the most prolific vaccine scientist of the 20th century. The Hilleman legacy is important to MSU and a point of pride in the state of Montana. Beyond the Hilleman Scholars program and the Hilleman Research Symposium, MSU prioritizes “consequential” biomedical research aimed at understanding the molecular basis of disease. This research is supported by a BSL-3 (select agent capable) laboratory, a large animal BSL-2 facility, the only contemporary cryo-electron microscope capable of high-resolution structure determination the region, state of the art confocal and chemical imaging labs, and new investments in a cell analysis core. This existing infrastructure helps support the long-term goal of this Phase 1 Center of Biomedical Research Excellence (COBRE) to establish a sustainable Center for Advanced Molecular Pathogenesis (CAMP) that fosters recruitment, development, and retention of investigators who share a common interest in translating new discoveries in pathogenesis into new treatments, vaccines, and cures. The theme of this application is intended to be broad enough to cultivate and maintain a pipeline of new faculty with diverse model systems, techniques, and scientific perspectives, while maintaining a unified research goal that focuses on understanding mechanisms and developing treatments for disease. Significantly, this application takes advantage of a talented pool of COBRE-eligible investigators in three departments from two Montana campuses and anticipates the recruitment of additional cohorts of early-stage investigators that will benefit from professional mentoring, instrumentation, and infrastructure essential to advancing biomedical excellence at Montana State University. To achieve this long-term goal, we propose three specific aims: 1) Recruit, develop, and retain a critical mass of investigators necessary to sustain a rigorous, productive, and merit-based research Center focused on Advance Molecular Pathogenesis (CAMP), 2) Improve capacities to translate basic research discoveries into tangible benefits for individuals and society, and 3) Establish core facilities that advance the aims of early-stage investigators, and simultaneously expands the biomedical research infrastructure in Montana and the surrounding IDeA-eligible states. To accomplish these aims, we propose three initial research projects, supported by two cores: The Administrative Core and the Advanced Biological Imaging and Cell Analysis Core. The rigor and feasibility of this application is enhanced by the leadership team (which includes two former COBRE investigators), the prior training and track record of our Research Project Leaders, tailormade mentorship teams, the research infrastructure supported by this award, and active engagement with world-renowned members of our advisory committee. Success of the current cohort will create a syphon, pulling new investigators into a high-priority career development program, thereby building a critical mass of investigators with the necessary momentum to sustain a unified research Center that focuses on understanding mechanisms and developing treatments for disease.

NIGMS - National Institute of General Medical Sciences

UNIVERSITY OF NORTH DAKOTA HOST PATHOGEN INTERACTIONS OVERALL SUMMARY The goal of this COBRE 3 application is to continue to sustain research in host-pathogen interactions at the University of North Dakota by providing ongoing support to host-pathogen researchers. In COBREs 1 and 2, we made significant progress towards development of a host-microbe interactions program through support of individual projects, building our core group by recruitment of immunology and microbial pathogenesis experts, and supporting faculty development through mentoring programs. We established four Cores to meet the needs of the host-pathogen interactions community and provided technical and financial support that increased the number of researchers in our community utilizing state-of-the art imaging, histology, flow cytometry, and computational approaches. In Phases 1 and 2, our COBRE Investigators and Core users made important discoveries that resulted in 106 papers published in high impact journals, and the awarding of more than $30 million in external funding from NIH grants alone. In this proposal, we seek to maintain this momentum and move our group towards sustainability through the following strategies: (1) Supporting our Cores to enable performance of cutting-edge research, transition to financial sustainability, and empower researchers through training and educational workshops; (2) Promote high- quality research, expand the reach of the group through collaborations with experts in other fields, and support innovative, cross-disciplinary research through a Pilot Project Program; (3) Promote long-term sustainability of the group through building partnerships with other IDeA state groups and cohorts through our successful seminar series and annual regional Host-Pathogen Interactions Symposium. Our long-term goal is to transition the HPI group into a sustainable, well-organized academic center which will serve as a conduit for increased interaction between investigators from multiple scientific backgrounds with a thematic interest in pursuing research on various aspects of host-microbe interactions. This center will continue attract top talent, train the next generation of scientists, and become a national hub for cutting edge esearch.

National Institute of Standards and Technology

The National Institute of Standards and Technology (NIST) Center for Nanoscale Science and Technology (CNST) is soliciting applications from eligible applicants to develop and implement with the CNST a Postdoctoral and Student Researcher and Visiting Fellow Measurement Science and Engineering Program. This program is intended to promote research, training, and practical experience in nanoscale science and technology on-site at the CNST, and to support collaboration in advancing the CNST s mission to support the development of nanotechnology through research on measurement and fabrication methods, standards and technology, and by operating a state-of-the-art nanofabrication facility.

National Institute of Standards and Technology

The National Institute of Standards and Technology (NIST) Center for Nanoscale Science and Technology (CNST) is establishing a financial assistance program for awardees to develop and implement with the CNST a Postdoctoral Researcher and Visiting Fellow Measurement Science and Engineering Program. This program is intended to promote research, training, and practical experience in nanoscale science and technology on-site at the CNST, and to advance the CNST s mission to support the development of nanotechnology through research on measurement and fabrication methods, standards and technology, and by operating a state-of-the-art nanofabrication facility, the NanoFab. The primary program objectives are: 1.To advance, through cooperative efforts with one or more universities, research consistent with the mission of NIST, and CNST specifically. See http://www.nist.gov/cnst/ and 15 U.S.C. Sec. 271 et seq. 2.To provide training for the next generation of nanotechnologists by providing recent Ph.D. recipients postdoctoral positions ( Postdoctoral Researchers ) to perform research at the CNST under the mentorship of a CNST Project Leader. The Postdoctoral Researchers must show promise as contributors to the mission of the CNST, and be selected on the basis of ability and of the relevance of the proposed work to the mission of the CNST. 3.To provide advanced training and access to the CNST s expertise and instrumentation by providing practicing scientists and engineers in the public and private sectors visiting senior research positions ( Visiting Fellows ) to perform research at the CNST in collaboration with a CNST Project Leader. The Visiting Fellows must be selected on the basis of ability and on the relevance of the proposed work to the mission of the CNST. 4.To provide Postdoctoral Researchers and Visiting Fellows under this program with professional development opportunities, including travel to relevant workshops and conferences. 5.To encourage U.S. industrial, university, and government scientists to participate in research at the CNST, either in collaboration with the CNST research program or by using the NanoFab, by providing support for travel and local expenses for participants traveling beyond a normal commuting distance to the CNST in Gaithersburg, Maryland.

National Institutes of Health

The National Institute of Neurological Disorders and Stroke (NINDS) is interested in supporting ambitious research projects to elucidate mechanisms of neurodegeneration in Alzheimer s disease-related dementias (ADRD) organized as a Center without Walls consortium. NINDS Centers without Walls are collaborative research networks that bring together diverse expertise from different institutions to tackle complex neurological problems that are not tractable by individual research projects.This program is considering using an activity code, such as the RM1, that enables interdisciplinary research consortia capable of identifying and characterizing novel ADRD mechanisms. Teams may include cross-disciplinary and cross-specialty expertise to address the complex co-pathologies, mixed etiologies, and disease heterogeneity in ADRD.This program is anticipated to support teams that can combine multiple approaches, such as state-of-the-art technologies, disease-relevant models, clinical science, and human specimens, to investigate unique disease mechanisms and identify new therapeutic targets, biomarkers, and other factors influencing ADRD susceptibility, resilience, and pathology. One awardee team would serve as a coordinating center for all awardees to facilitate recurring meetings, data harmonization and sharing, cross-site communication, and support the implementation of inter-laboratory rigor and reproducibility plans.This program is informed by key priorities from the ADRD Summit 2025, including embracing ADRD complexity and breaking down topic- and disease-based silos, and is intended to provide a mechanistic foundation for future translational and clinical ADRD research.Applications are not being solicited at this time. Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. Investigators with complementary expertise in ADRD mechanisms, clinical phenotypes, and advanced technologies are encouraged to contact agency staff listed below for additional information.

National Institutes of Health

<p>The National Institute of Neurological Disorders and Stroke (NINDS) is interested in supporting ambitious research projects to elucidate mechanisms of neurodegeneration in Alzheimer’s disease-related dementias (ADRD) organized as a “Center without Walls” consortium. NINDS Centers without Walls are collaborative research networks that bring together diverse expertise from different institutions to tackle complex neurological problems that are not tractable by individual research projects.</p><p>This program is considering using an activity code, such as the RM1, that enables interdisciplinary research consortia capable of identifying and characterizing novel ADRD mechanisms. Teams may include cross-disciplinary and cross-specialty expertise to address the complex co-pathologies, mixed etiologies, and disease heterogeneity in ADRD.</p><p>This program is anticipated to support teams that can combine multiple approaches, such as state-of-the-art technologies, disease-relevant models, clinical science, and human specimens, to investigate unique disease mechanisms and identify new therapeutic targets, biomarkers, and other factors influencing ADRD susceptibility, resilience, and pathology. One awardee team would serve as a coordinating center for all awardees to facilitate recurring meetings, data harmonization and sharing, cross-site communication, and support the implementation of inter-laboratory rigor and reproducibility plans.</p><p>This program is informed by key priorities from the ADRD Summit 2025, including embracing ADRD complexity and breaking down topic- and disease-based silos, and is intended to provide a mechanistic foundation for future translational and clinical ADRD research.</p><p>Applications are not being solicited at this time. Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. Investigators with complementary expertise in ADRD mechanisms, clinical phenotypes, and advanced technologies are encouraged to contact agency staff listed below for additional information.&nbsp;</p>