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9873 documents

Replication Fork Repair

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

SUSAN THOMAS LOVETT · BRANDEIS UNIVERSITY · 2024 · $504,582 — Project Summary Replication fork repair is essential for cell survival and stability of genetic material. In humans, inefficiency of repair is associated with cancer proneness, neurological, immunological, developmental defects and premature aging. For microbial pathogens, the ability to repair DNA …

Resolving Spatiotemporal Dynamics of Recombinant Poliovirus Immunotherapy

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Matthias Gromeier · DUKE UNIVERSITY · 2024 · $358,773 — Priming of antitumor immunity relies on a specialized subset of conventional Dendritic Cells (cDC1s), CD103+ DCs, that have unique capabilities of trafficking tumor antigens to lymph nodes for cross-presentation. The critical role of cDC1s in cancer immune surveillance make them highly coveted targe…

Delineating the Genetic Susceptibility of Smoking-Induced Vascular Dysfunction

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Hongchao Guo · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $249,000 — PROJECT SUMMARY This proposal describes a five-year career development program to prepare Dr. Hongchao Guo for a career as an independent investigator. This program will build on Dr. Guo’s background as a molecular stem cell biologist by providing him expertise in bioinformatics, secretomics, and dr…

Endothelial tip cell-mediated angiogenesis and repair after neonatal stroke

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Fernando Francisco Gonzalez · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $460,447 — PROJECT SUMMARY/ABSTRACT Neonatal stroke is an important cause of death and disability, and diagnosis is often delayed. There is insufficient knowledge regarding repair mechanisms that occur in response to focal ischemia-reperfusion injury that is the most common cause of early stroke. Angiogenesis,…

Functional Genomics of High Grade Glioma

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

KWANHA YU · BAYLOR COLLEGE OF MEDICINE · 2024 · $152,274 — Glioma is the most common and deadly disease affecting the CNS. Current projections suggest 22,000 new cases annually, of which 13,000 will be Glioblastoma Multiforme, which is universally fatal. Despite over 60 years of research, there have been no significant improvements to patient outcome. More …

Identification of predictive biomarkers for severe acute leptospirosis and its long-term sequelae

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Nattachai Srisawat · CHULALONGKORN UNIVERSITY · 2024 · $137,229 — Leptospirosis is a potentially life-threatening zoonosis with protean manifestations and a leading cause of acute febrile illness (AFI) in the tropics. The acute phase of leptospirosis can trigger a systemic inflammatory response, leading to multiorgan failure, including liver failure, acute kidney …

The Pacific Cancer Research Consortium (PCRC), an NCORP Community Site

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Alison Katherine Conlin · SWEDISH MEDICAL CENTER, FIRST HILL · 2024 · $2,632,282 — In 2013, the Pacific Cancer Research Consortium (PCRC) was created to bring clinical trials and cancer care delivery research to community cancer treatment centers in the Western United States as an NCI Community Oncology Research Program (NCORP) Community Site. Under a multiple PI/PD structure, the…

Risk and Resilience in Urban Black American Acute Trauma Survivors

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Christine L Larson · UNIVERSITY OF WISCONSIN MILWAUKEE · 2024 · $713,411 — PROJECT ABSTRACT Trauma is common and increases risk for a host of negative health outcomes, most notably posttraumatic stress disorder (PTSD). Given the potential harmful sequelae of trauma exposure, it is crucial to identify acute post-trauma risk factors that predict chronic PTSD. Moreover, urban…

Functional Characterization of Mitochondrial Genome Nonsense Mutations

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Dan E Arking · JOHNS HOPKINS UNIVERSITY · 2024 · $245,625 — Mitochondria play an essential role in cellular function and impact human health through varied mechanisms, including energy metabolism, cell signaling, and apoptosis. Many aging-related diseases have a mitochondrial (MT) component, with studies highlighting associations with cardiovascular disease,…

High resolution inflammatory networks induced by HIV reservoirs in adolescents

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Catherine A Blish · STANFORD UNIVERSITY · 2024 · $815,573 — ABSTRACT Antiretroviral treatment (ART) for HIV infection effectively blocks viral replication, but fails to eradicate the virus, which can be a source of persistent inflammation. The pathways by which chronic, treated HIV infection drives inflammation are poorly defined, particularly in children an…

Inter-metastatic divergency in small cell lung cancer; implications for the design of future immunotherapies

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Jose R Conejo-Garcia · DUKE UNIVERSITY · 2024 · $367,057 — Abstract Aggressive malignant progression and spreading has limited a clear understanding of the pathophysiology of SCLC. The overarching goal of this “bedside to bench” project is to elucidate the role of inter-metastatic divergence in therapeutic resistance in small cell lung cancer (SCLC), with a…

ImpleMEntation of a Digital-first care deLiverY model for heart failure in Uganda (MEDLY Uganda)

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Joseph Antony Cafazzo · YALE UNIVERSITY · 2024 · $542,296 — PROJECT SUMMARY/ABSTRACT In sub-Saharan Africa, heart failure (HF), a clinical syndrome that causes multiple debilitating symptoms and results in poor health-related quality of life, has a 34% 1-year mortality rate, the highest of any region globally. Major care gaps and sociodemographic disparities…

Chemical tools for developmental biology

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

JAMES K CHEN · STANFORD UNIVERSITY · 2024 · $625,036 — Developmental biology is now both a molecular and systems-level science. Forward- and reverse-genetic technologies have identified individual genes that regulate tissue formation and contribute to their oncogenic transformation later in life. High-throughput sequencing has revealed the “omic” featur…

Underlying Mechanisms in CADASIL

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Manfred Boehm · NORTHWESTERN UNIVERSITY AT CHICAGO · 2024 · $658,626 — Brain microvascular ischemic disease is a common cause of leukoencephalopathy, leading to cognitive impairment, dementia, and stroke. CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is the most frequent mendelian cause of cerebral small vessel dis…

Structural Mechanisms of DNA Damage Sensing and Activation of the ATR, Fanconi Anemia, and ATM Checkpoints

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

NIKOLA P PAVLETICH · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $672,595 — Genetic instability is a hallmark of cancer. The cell has evolved an intricate set of pathways that sense and repair DNA damage, which is an inevitable consequence of cellular metabolism and the environment. Failure of a repair pathway, due to either overwhelming DNA damage or pathway inactivation b…

Genetic interactions among targets of master regulator genes as drivers of complex behavior in Drosophila intestinal stem cells

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Mariano A Loza Coll · CALIFORNIA STATE UNIVERSITY NORTHRIDGE · 2024 · $147,500 — PROJECT SUMMARY Several master regulator (MR) genes have been characterized in tissue stem cells across organs and species. However, they remain poor candidates for therapeutic manipulation because they are highly pleiotropic, affecting hundreds of targets and operating across many organ systems. Th…

Bridging the gap: joint modeling of single-cell 1D and 3D genomics

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

YE ZHENG · FRED HUTCHINSON CANCER CENTER · 2024 · $12,355 — PROJECT SUMMARY/ABSTRACT Advances in single-cell technologies have enabled three-dimensional (3D) genome structure profiling and simultaneous capture of the transcriptome and epigenome within a cell. Quantitative tools are, however, still unable to fully leverage the unprecedented resolution of sing…

Therapeutic and mechanistic significance of altered metabolism of HIV medicines by alcohol- or alcohol/synthetic opioid combination

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

JASON T BLACKARD · UNIVERSITY OF CINCINNATI · 2024 · $697,172 — Abstract HIV/AIDS continues to be a major global health issue, and chronic liver disease has become a major cause of HIV-mortality. Several contributing factors are recognized including hepatotoxicity of anti-HIV drugs, coinfection of hepatitis viruses and widespread alcohol use. The likelihood of c…

Interrogating and Targeting Microglia Phagocytosis in Alzheimer’s Disease

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Brandon Blake Holmes · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $210,306 — Alzheimer's disease (AD) is an intractable neurodegenerative disorder that devastates approximately 6.2 million Americans nationwide. Emerging evidence now establishes a central role for microglia in AD pathogenesis and reveals that transcriptional and epigenetic level changes in these cells tightly…

Mentoring Scientists for Careers in HIV Translational Clinical Research

NIH Pandemic-Era Grants · Pandemic Era Grants / 2024

Timothy Jensen Henrich · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $191,388 — ABSTRACT/SUMMARY The primary goals of this K24 award are to identify and cultivate diverse, highly motivated, young investigators with a propensity for independent thinking, and increase their involvement in collaborative, patient-oriented HIV pathogenesis and cure research. Specifically, junior inv…