Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=2&sort=-start_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-start_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=-start_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-start_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-start_date" }, "data": [ { "type": "Grant", "id": "15948", "attributes": { "award_id": "1R21AI196828-01", "title": "N Protein Nexus: Rewiring Host Translation Machinery for SARS-CoV-2's Early Replicative Advantage", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-04-01", "end_date": "2028-03-31", "award_amount": 213048, "principal_investigator": { "id": 23292, "first_name": "Rong", "last_name": "Hai", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1190, "ror": "", "name": "UNIVERSITY OF CALIFORNIA RIVERSIDE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 44391, "first_name": "Sean E", "last_name": "O'Leary", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3407, "ror": "", "name": "UNIVERSITY OF CALIFORNIA RIVERSIDE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "ABSTRACT: Dependence on host-cell machinery for protein synthesis poses a significant challenge to coronavirus replication, particularly at the onset of infection when viral genomic RNA must compete with an abundance of host mRNAs for translation. To overcome this hurdle, viruses have evolved sophisticated strategies to commandeer the host translation machinery. While multiple mechanisms by which SARS-CoV-2 hijacks host translation have been elucidated, almost all involve non-structural viral proteins. This raises a fundamental question: how does SARS- CoV-2 establish a translational foothold during the early stages of infection, before non-structural proteins are synthesized? The viral nucleocapsid (N) protein is the primary viral factor present at this early stage of infection and has been shown to manipulate cell machinery to facilitate infection. We have found that N protein physically and functionally interacts with the human translation machinery, facilitating preferential viral translation. Moreover, our results suggest that the viral genome's 5ʹ untranslated region exploits high-affinity N protein binding to potentiate selective viral RNA recognition for translation. We hypothesize that N protein is a key mediator of viral translational hijacking in early SARS-CoV-2 infection, establishing a new paradigm within the N- protein functional repertoire. This proposal now seeks to elucidate the molecular mechanisms of host protein- synthesis modulation by N protein for viral benefit during early infection. Through two specific aims, we will (1) identify the viral determinants responsible for the impact of N protein on viral RNA translation and (2) delineate the roles of host factors in N protein viral-translation enhancement. By combining biochemical, biophysical, and genetic approaches, we will establish a comprehensive understanding of unanticipated host-virus interactions that govern SARS-CoV-2 pathogenesis, uncovering novel viral vulnerabilities that can be exploited to develop targeted antiviral therapy. Ultimately, this study will provide new insights for innovative therapeutic strategies that can be extended to other viruses with RNA-binding proteins, offering a promising avenue for smothering infection at its onset. 3", "keywords": [ "2019-nCoV", "Affinity", "Amino Acids", "Anti-viral Therapy", "Binding Proteins", "Biochemical", "Biology", "Biophysics", "COVID-19", "COVID-19 treatment", "Cells", "Communicable Diseases", "Coronavirus", "Dependence", "Elements", "Elongation Factor", "Face", "Genomic approach", "Human", "Infection", "Integration Host Factors", "Knowledge", "Life Cycle Stages", "Maps", "Mediating", "Mediator", "Messenger RNA", "Methods", "Molecular", "Nonstructural Protein", "Nucleocapsid", "Nucleocapsid Proteins", "Peptide Initiation Factors", "Phase", "Preparation", "Protein Biosynthesis", "Proteins", "RNA Viruses", "RNA-Binding Proteins", "RNA-Protein Interaction", "Recombinants", "Ribosomes", "Role", "SARS-CoV-2 genome", "SARS-CoV-2 infection", "SARS-CoV-2 pathogenesis", "Site", "Therapeutic", "Translations", "Untranslated RNA", "Untranslated Regions", "Viral", "Viral Genome", "Viral N Protein", "Viral Nonstructural Proteins", "Viral Proteins", "Virus", "antiviral drug development", "biophysical analysis", "biophysical techniques", "combat", "functional genomics", "genetic analysis", "genetic approach", "genomic RNA", "influenzavirus", "innovation", "insight", "mRNA Translation", "new therapeutic target", "novel", "pathogen", "pathogenic virus", "protein expression", "therapy development", "translational impact", "viral RNA", "viral genomics", "virus host interaction" ], "approved": true } }, { "type": "Grant", "id": "15947", "attributes": { "award_id": "1I01RD001550-01A1", "title": "A systems biology approach to identifying mechanisms underlying enhanced reactogenicity after mRNA-based vaccination", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2026-04-01", "end_date": "2030-03-31", "award_amount": null, "principal_investigator": { "id": 8775, "first_name": "DAVID H", "last_name": "CANADAY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 497, "ror": "https://ror.org/051fd9666", "name": "Case Western Reserve University", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3406, "ror": "", "name": "LOUIS STOKES CLEVELAND VA MEDICAL CENTER", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Significance to the VA: Vaccine hesitancy toward COVID-19 mRNA vaccines remains a significant challenge. Identifying ways to reduce hesitancy is a key objective of these studies. Reactogenicity refers to adverse events (AEs) that occur shortly after vaccination as a physical manifestation of the inflammatory response. Understanding which reactogenic mechanisms are most closely linked to enhanced immunogenicity is crucial for designing interventions that mitigate negatively perceived side eKects without compromising the protective immune response. The veteran population includes a high proportion of older, multimorbid individuals who are particularly susceptible to severe morbidity and mortality from SARS-CoV-2 and RSV, both of which have approved mRNA vaccines, and influenza, for which an mRNA vaccine is anticipated soon. As the use of mRNA vaccine platforms increases, eKorts to facilitate their acceptance and utilization are essential for veteran health. Innovation and Impact: To our knowledge, no NIH-supported studies are investigating mRNA vaccine reactogenicity using systems biology approaches, particularly in VA priority cohorts, as indicated by NIH RePORTER and ClinicalTrials.gov. No comprehensive systems biology studies have focused on identifying specific pathways and molecules associated with AEs from mRNA vaccines. This innovative approach can help VA providers explain vaccine use and AEs, increasing uptake. Additionally, our findings could inform strategies to reduce AEs while maintaining protective immune responses. Specific Aims: Aim 1: Determine the mechanisms underlying reactogenicity by assessing local and systemic AEs following mRNA COVID-19 vaccination. Hypothesis: The development of AEs is associated with interferome and inflammasome pathway activation, leading to increased inflammatory cytokine and chemokine levels and enhanced immune activation. Additionally, pre-existing metabolic pathway perturbations may exacerbate AEs and serve as potential therapeutic targets. Aim 2: Identify mechanisms specific to reactogenicity versus protective immune response or those common to both. Hypothesis: Some mechanisms linked to severe AEs are also associated with stronger vaccine-induced immune responses. Aim 3: Model the impact of age and sex on mRNA COVID-19 vaccine-induced reactogenicity and immune response. Hypothesis: Older individuals, due to higher baseline inflammatory signatures, exhibit altered AE development and vaccine-specific immune responses following mRNA vaccination. Methodology: Veterans and, if necessary, some non-veterans will be enrolled to meet study targets. Participants will receive standard-of-care Pfizer or Moderna mRNA COVID-19 vaccines. Reactogenicity will be assessed clinically, and blood samples will be analyzed for cellular and transcriptomic changes, as well as vaccine-specific immune responses. Comprehensive systems biology analysis will compare individuals with high versus low AEs. Path to Translation/Implementation: Vaccine education interventions enhance trust in CDC recommendations and address concerns about rapid vaccine development and side eKects. Understanding the mechanisms driving reactogenicity will provide essential information to health care providers for patient education. Additionally, our findings may inform therapies or vaccine modifications to reduce AEs while preserving immune protection.", "keywords": [ "Ache", "Activities of Daily Living", "Address", "Adverse event", "Age", "Antigens", "Automobile Driving", "Bioinformatics", "Biological", "Biological Assay", "Blood specimen", "COVID-19", "COVID-19 mortality", "COVID-19 vaccination", "COVID-19 vaccine", "Cells", "Cellular Immunity", "Characteristics", "Chills", "Clinical", "Communities", "Data Set", "Development", "Disease", "Dose", "Educational Intervention", "Enrollment", "Event", "Exhibits", "FDA Emergency Use Authorization", "Fatigue", "Fright", "Headache", "Health", "Health Personnel", "Hour", "Immune", "Immune response", "Immunological Models", "Individual", "Inflammasome", "Inflammatory", "Inflammatory Response", "Influenza", "Injections", "Insecta", "Link", "Messenger RNA", "Metabolic", "Metabolic Pathway", "Methodology", "Modeling", "Moderna COVID-19 vaccine", "Modification", "Morbidity", "Muscle", "Mutate", "Older Population", "Outcome", "Pain", "Participant", "Pathway interactions", "Patient Education", "Patients", "Persons", "Phase", "Phase III Clinical Trials", "Population", "Predisposition", "Production", "Provider", "Publishing", "RNA vaccination", "RNA vaccine", "Reaction", "Recommendation", "Reporter", "Reporting", "Resources", "Respiratory Syncytial Virus Vaccines", "Role", "Serious Adverse Event", "Serology", "Serum", "Severities", "Side", "Site", "Systems Biology", "Technology", "Therapeutic", "Translations", "Trust", "United States National Institutes of Health", "Vaccination", "Vaccines", "Variant", "Veterans", "Work", "age effect", "chemokine", "cohort", "cytokine", "egg", "flu", "high dimensionality", "immune activation", "immunogenicity", "improved", "in vivo", "influenza virus vaccine", "innovation", "life span", "military veteran", "open label", "pathogen", "preservation", "prevent", "response", "sex", "standard of care", "therapeutic target", "therapy design", "transcriptomics", "uptake", "vaccination outcome", "vaccine acceptance", "vaccine development", "vaccine efficacy", "vaccine hesitancy", "vaccine immunogenicity", "vaccine platform", "vaccine reaction", "vaccine response", "vaccine side effects" ], "approved": true } }, { "type": "Grant", "id": "15956", "attributes": { "award_id": "1R01AI189721-01A1", "title": "Decoding cellular networks governing respiratory mucosal IgA immunity", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 44403, "first_name": "HARIHARAN", "last_name": "SUBRAMANIAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-04-01", "end_date": "2031-03-31", "award_amount": 773388, "principal_investigator": { "id": 20818, "first_name": "Jie", "last_name": "Sun", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1426, "ror": "", "name": "MAYO CLINIC ROCHESTER", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3413, "ror": "", "name": "UNIVERSITY OF VIRGINIA", "address": "", "city": "", "state": "VA", "zip": "", "country": "United States", "approved": true }, "abstract": "Abstract/summary The factors and mechanisms driving robust respiratory mucosal immunity, particularly respiratory IgA responses, post-infection or vaccination are largely unknown. This represents a significant gap in our understanding necessary for designing future vaccination strategies aimed at providing enhanced mucosal protection against respiratory viral infections including new SARS-CoV-2 variants. This RO1 grant proposal aims to address this critical knowledge gap. Our central hypothesis is that the generation of mucosal IgA and respiratory protective immunity is contingent upon the localized interactions among pulmonary macrophages, CD4 T cells, and B cells within the respiratory tract. Three specific aims (SA) are proposed. Aim 1: Identify the associated mechanisms by which respiratory CD4+ T cells promote IgA production in situ. Aim 2: Elucidate TGFβ-dependent macrophages and B cell interactions in mucosal IgA production. Aim 3: Define the molecular and functional signatures of mucosal cross-reactive IgA-producing B cells. We believe that the insights obtained will be crucial in developing next-generation mucosal vaccines designed to effectively counter SARS-CoV-2 variants and other respiratory pathogens, significantly enhancing public health prevention strategies against respiratory infections. .", "keywords": [ "2019-nCoV", "Address", "Adenoviruses", "Alveolar Macrophages", "Animals", "Antibodies", "Applications Grants", "Area", "Automobile Driving", "B-Lymphocytes", "B-cell receptor repertoire sequencing", "Blood", "CD4 Positive T Lymphocytes", "Cell Communication", "Circulation", "Clinical Research", "Cloning", "Exhibits", "Future", "Generations", "Goals", "Hybrids", "Immune Evasion", "Immune response", "Immunity", "Immunoglobulin A", "Immunoglobulin G", "Immunologics", "In Situ", "Individual", "Infection", "Inhalation", "Intramuscular", "Knowledge", "Link", "Macrophage", "Maintenance", "Molecular", "Morbidity", "Mucosal Immunity", "Mucous Membrane", "Plasma Cells", "Prevention strategy", "Production", "Public Health", "RNA vaccination", "RNA vaccine", "Research", "Respiratory Mucosa", "Respiratory System", "Respiratory Tract Infections", "Role", "SARS-CoV-2 exposure", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "Sea", "Secondary Immunization", "Severity of illness", "Shapes", "Signal Transduction", "Testing", "Th1 Cells", "Transforming Growth Factor beta", "Vaccinated", "Vaccination", "Vaccine Design", "Viral Respiratory Tract Infection", "Virus", "booster vaccine", "cross reactivity", "design", "dimer", "influenzavirus", "insight", "interleukin-21", "mortality", "mucosal vaccination", "mucosal vaccine", "next generation", "novel vaccines", "pathogenic virus", "pulmonary", "recruit", "respiratory", "respiratory pathogen", "response", "single-cell RNA sequencing", "transmission process", "vaccination strategy", "variants of concern", "viral transmission" ], "approved": true } }, { "type": "Grant", "id": "15949", "attributes": { "award_id": "1UG3NS143075-01A1", "title": "miR-10b Gene Editing Therapy for Glioblastoma", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 44392, "first_name": "KELLY WILL", "last_name": "SHEPPARD", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-04-01", "end_date": "2028-03-31", "award_amount": 790474, "principal_investigator": { "id": 44393, "first_name": "Anna M.", "last_name": "Krichevsky", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3408, "ror": "", "name": "BRIGHAM AND WOMEN'S HOSPITAL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Malignant glioma, particularly glioblastoma (GBM), remains among the most lethal forms of cancer and represents a significant unmet need in current medicine. The median survival of GBM patients is approximately 15-20 months with highly aggressive standard care, and the five-year survival rate is about 5%. There are no effective therapies for the disease. Over the years, we accumulated evidence that GBM growth and invasiveness are closely regulated by microRNAs, small regulatory molecules that control gene expression and strongly contribute to gliomagenesis. We demonstrated that this class of molecules holds great promise as therapeutic targets for neuro-oncology. Our work led us to focus on miR-10b, a unique growth and invasion-promoting miRNA and common molecular target for GBM in adults (otherwise a highly heterogeneous class of brain malignancies). We identified miR-10b, essential for glioma growth, as a top and common therapeutic target for GBM. Inhibition of miR-10b using different strategies reduced tumor growth in all tested glioma cell and animal models. CRISPR/Cas9 gene-editing of miR-10b emerged as the most potent therapeutic strategy in mice, and it holds great promise for GBM patients. We developed potent and safe lipid nanoparticle (LNP) -based miR-10b editing formulation as a new class of precision medicine for GBM. Our objective is to advance this miR-10b editing drug (called miRTED) into a “first-in-human” clinical trial in subjects with GBM. The Specific Aims of this project are, in UG3 component (Discovery phase): 1) Finalize the efficacy of miRTED administration using diverse orthotopic GBM models, 2) Assess the toxicity and off-target effects of miRTED administration using human and rodent neuroglial cells, brain organoids, and mouse models to establish dosing guidelines, and during UH3 component (Development phase): 3) Partner with BPN team and selected contract research organization to manufacture preclinical and then GMP-grade clinical lots of the LNP, 4) Partner with BPN team and selected contract research organization to conduct IND-enabling mouse toxicology and biodistribution studies, and 5) Finalize the writing and filing of the IND application with the FDA. Due to glioma “addiction” to miR-10b, the new strategy is expected to be highly efficacious for most, if not all, GBM patients despite the heterogeneity of the disease. This approach is principally different from other gene therapies proposed for the GBM- that all target only a subpopulation of patients. It can be used in combination with, or ultimately replace, the current standard care. In addition, the LNP formulations developed in this project could provide a platform technology for precision medicine targeting other tumor vulnerabilities. Notably, the recent success of COVID mRNA vaccines and in vivo gene editing trials provide POCs for the efficacy, safety, and scalability of mRNA/LNPs and CRISPR/Cas9 components in humans.", "keywords": [ "Adult", "Allografting", "Angiogenesis Inhibitors", "Animal Model", "Animals", "Antisense Oligonucleotide Therapy", "Antisense Oligonucleotides", "Apoptosis", "BCL2L11 gene", "Biodistribution", "Brain", "Brain Neoplasms", "CDKN1A gene", "CDKN2A gene", "COVID-19", "CRISPR/Cas technology", "Cell Cycle", "Cell Differentiation process", "Cell model", "Cells", "Clinical Pathways", "Clinical Trials", "Cytoprotection", "Development", "Diagnosis", "Disease", "Dose", "Drug Formulations", "EGFRvIII Peptide", "Epidermal Growth Factor Receptor", "Excision", "Exhibits", "FDA approved", "FDA-approved drug", "Formulation", "Gene Expression", "Genes", "Gliadel", "Glioblastoma", "Glioma", "Gliomagenesis", "Growth", "Guidelines", "Human", "Immunocompetent", "Immunotherapy", "Invaded", "Investigational New Drug Application", "Lead", "Malignant Glioma", "Malignant Neoplasms", "Mediating", "Medicine", "Messenger RNA", "MicroRNAs", "Modeling", "Molecular Target", "Mus", "Mutation", "Neuroglia", "Neurons", "Newly Diagnosed", "Organoids", "Patients", "Peptide Vaccines", "Pharmaceutical Preparations", "Phase", "Play", "RNA Splicing", "RNA delivery", "RNA vaccine", "Recurrence", "Regimen", "Research Contracts", "Resistance", "Rodent", "Role", "Safety", "Schedule", "Signal Pathway", "Survival Rate", "System", "Testing", "Therapeutic", "Toxic effect", "Toxicology", "Transcriptional Activation", "Tumor Cell Nuclei", "Tumor Subtype", "U6 small nuclear RNA", "Work", "Writing", "Xenograft procedure", "addiction", "bevacizumab", "checkpoint inhibition", "chemoradiation", "chemotherapy", "clinical lot", "disease heterogeneity", "drug development", "effective therapy", "first-in-human", "gene therapy", "in vivo", "inhibitor", "lipid nanoparticle", "manufacture", "mouse model", "mutational status", "nerve stem cell", "neuro-oncology", "neurosurgery", "oligonucleotide therapeutics", "patient subsets", "pharmacokinetics and pharmacodynamics", "pre-clinical", "precision medicine", "pro-apoptotic protein", "standard care", "standard of care", "success", "symptomatic improvement", "targeted therapy trials", "targeted treatment", "technology platform", "temozolomide", "therapeutic genome editing", "therapeutic target", "tumor", "tumor growth", "uncontrolled cell growth", "uptake" ], "approved": true } }, { "type": "Grant", "id": "15951", "attributes": { "award_id": "1K99HL183741-01", "title": "Modeling the Effect of Apolipoprotein LI Risk Variants on CVD Risk in African American E-cigarette Users Using Human Induced Pluripotent Stem-Cell-Derived Endothelial Cells", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 44395, "first_name": "KAREN MARY", "last_name": "NEILSON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-04-01", "end_date": "2028-03-31", "award_amount": 127168, "principal_investigator": { "id": 44396, "first_name": "Jelena", "last_name": "Mustra Rakic", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2635, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "African American individuals face a disproportionately higher risk of tobacco-related cardiovascular diseases (CVD) than other races, a disparity not fully explained by traditional and socioeconomic risk factors. Despite lacking approval from the U.S. Food and Drug Administration (FDA) for their safety, e-cigarettes (e-cigs) have become increasingly popular, particularly among youth, and are now among the most commonly used tobacco products alongside traditional cigarettes. Approximately half of African American individuals carry at least one of two genetic variants (G1 and G2) of the apolipoprotein L1 (APOL1) gene, which are exceedingly rare in other populations. APOL1 is widely expressed, particularly in the vasculature. We have shown that carriers of APOL1 G1 and G2 variants have increased susceptibility to tobacco-related CVD, including stroke and coronary heart disease. Dysfunction of vascular endothelial cells (ECs) is a critical precursor to CVD. EC dysfunction also plays a key role in APOL1-associated pathology, including exacerbated renal issues and increased susceptibility to sepsis and severe COVID-19. Recent research indicates that, similar to cigarettes, both e-cigs and menthol—a flavor popular in the African American community—independently impair endothelial function. While studies, including those using induced pluripotent stem cell (iPSC)-derived ECs, demonstrate these effects, the specific impact of APOL1 risk variants on vascular health in African American tobacco product users remains unknown. The goal of the proposed research is to determine the effects of e-cigs, with and without menthol, on endothelial health, compare them to the effects of cigarettes, and identify potential molecular markers and pathways associated with CVD in African American users, with a focus on the APOL1 genotype. As such, this application aims to expand my background and expertise in modeling the CVD risk from tobacco products and to provide specific training in tobacco product-related in vitro assays, iPSC methodology, gene editing, and computational techniques. Building on my prior work in human studies, this research extends to the cellular level to address significant gaps in knowledge regarding the adverse effects of the most popular tobacco products, with and without menthol, among the African American population—a demographic long targeted by the tobacco industry marketing. To achieve this goal, I will use a robust in vitro platform of human iPSC-ECs to address the following aims: Aim K1) to determine the effect of e-cigs and cigarettes on markers of EC dysfunction in G1/G1 iPSC-ECs, Aim R1) to determine the effect of e-cigs and cigarettes on endothelial function in G2/G2 iPSC-ECs, and Aim R2) to determine the effect of e-cigs and cigarettes on inflammatory markers and lipid mediators of inflammation in G1/G1 and G2/G2 iPSC-ECs. This project will deepen our understanding of the adverse effects of widely used tobacco products on vascular health in the CVD-burdened African American population. It also aims to identify molecular markers of cardiovascular injury in this high-risk group, providing insights into the mechanisms of tobacco-related cardiovascular damage and supporting the development of targeted interventions.", "keywords": [ "Address", "Adverse effects", "African American", "African American population", "Aftercare", "Apolipoproteins", "Blood Vessels", "CCL2 gene", "CRISPR/Cas technology", "CXCL10 gene", "CXCR3 gene", "Cardiovascular Diseases", "Cardiovascular Models", "Cardiovascular system", "Cell Culture Techniques", "Cell Line", "Cell Physiology", "Cigarette", "Communities", "Computational Technique", "Coronary heart disease", "Development", "Disease", "Disease Management", "Disparity", "Electronic cigarette", "Endothelial Cells", "Endothelium", "Exhibits", "Exposure to", "Face", "Functional disorder", "Genes", "Genetic Markers", "Genotype", "Goals", "Health", "Human", "Impairment", "In Vitro", "Inflammation Mediators", "Inflammatory", "Interferon Type II", "Interleukin-1 beta", "Interleukin-6", "Intervention", "Ischemic Stroke", "Kidney", "Kidney Diseases", "Knowledge", "Link", "Marketing", "Menthol", "Mentors", "Modeling", "Molecular", "Molecular Target", "Pathology", "Pathway interactions", "Pattern", "Phase", "Phenotype", "Play", "Polyunsaturated Fatty Acids", "Population", "Predisposition", "Race", "Recording of previous events", "Research", "Risk", "Risk Factors", "Role", "Safety", "Sepsis", "Signal Transduction", "Smoker", "Smoking", "Stroke", "Study models", "TNF gene", "Tobacco", "Tobacco Industry", "Tobacco use", "Training", "United States Food and Drug Administration", "Variant", "Vascular Endothelial Cell", "Work", "Youth", "burden of illness", "cardiovascular disorder risk", "cardiovascular health", "cardiovascular injury", "cardiovascular risk factor", "cell injury", "cigarette smoking", "cigarette user", "clinically relevant", "combustible cigarette", "electronic cigarette use", "electronic cigarette user", "endothelial dysfunction", "genetic variant", "genome editing", "health disparity", "high risk", "high risk population", "human induced pluripotent stem cells", "improved", "in vitro Assay", "in vivo", "induced pluripotent stem cell", "inflammatory marker", "insight", "interest", "lipid mediator", "marginalized community", "molecular marker", "racial population", "risk variant", "severe COVID-19", "socioeconomics", "stem cell based approach", "tobacco products", "transcriptomics", "trend", "vaping", "vascular endothelial dysfunction", "vascular injury" ], "approved": true } }, { "type": "Grant", "id": "15954", "attributes": { "award_id": "1R01AG092810-01A1", "title": "The Impact of Changes in Primary Care Clinicians' Work Effort on the Health of Older Adults", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 44399, "first_name": "MARCEL", "last_name": "SALIVE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-04-01", "end_date": "2031-01-31", "award_amount": 680086, "principal_investigator": { "id": 44400, "first_name": "Bruce E.", "last_name": "Landon", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44401, "first_name": "Lisa", "last_name": "Rotenstein", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2635, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "There are demonstrated benefits of comprehensive, continuous, and coordinated primary care for older adults, ranging from higher rates of appropriate preventive care receipt to lower rates of hospitalization and mortality. However, the benefits of strong primary care are threatened by an impending primary care workforce crisis, exacerbated by prevalent trends of primary care physician (PCP) workforce attrition and clinical effort reduction. Partly in response to these trends, there is increasing representation of NPs and PAs, collectively referred to as advanced practice clinicians (APCs), in the primary care workforce. However, burnout, intent to leave, and intent to reduce clinical effort are also prevalent among primary care APCs. These trends across primary care clinicians (PCCs; comprising physicians, NPs, and PAs) may significantly threaten quality of and access to care for older adults. At present, there is limited evidence to inform healthcare leaders and policy makers about how primary care workforce disruptions impact access to and quality of primary care received by older adults. There is additionally insufficient information on the actionable factors associated with PCC turnover and PCC reductions in clinical effort. In this grant, we will leverage data from Medicare fee-for-service and Medicare Advantage, which together provide coverage for 93% of older adults, in order to: 1) quantify the number of Medicare patients impacted by PCC turnover and sustained reductions in billed clinical effort and identify factors associated with these work effort changes; 2) assess the impact of PCC turnover and PCCs’ sustained reductions in billed clinical effort on patterns of primary care receipt and non-primary care utilization, including emergency department visits and hospitalizations; and 3) assess the impact of PCC turnover and sustained reductions in billed clinical effort on quality of care for older adults. All analyses will be conducted for the overall population of older adults as well as for subgroups of more vulnerable older adults, including those with dementia, multiple chronic conditions, and from underserved groups (e.g., dually eligible for Medicaid). Additionally, analyses will be conducted for physicians and APCs separately, and for the overall study period and comparing the pre- and post-COVID periods. The results from this study will elucidate how changes in PCCs’ work patterns influence the care of the growing US population of older adults. They will provide actionable insights for leaders seeking to design clinical systems and policies that enhance primary care for older adults. Overall, this proposal will enhance the ability of clinical, operational, and policy leaders to maintain the effort of the primary care workforce and optimize care for older adults.", "keywords": [ "Accident and Emergency department", "Address", "Affect", "COVID-19 pandemic", "Caring", "Clinical", "Complex", "Continuity of Patient Care", "Counseling", "Data", "Dementia", "Documentation", "Educational process of instructing", "Emergency department visit", "Fee-for-Service Plans", "Grant", "Health", "Health Care", "Health Services Accessibility", "Hospitalization", "Investments", "Left", "Location", "Measures", "Medicaid eligibility", "Medical Students", "Medicare", "Modeling", "Occupations", "Older Population", "Outcome", "Patients", "Pattern", "Physicians", "Policies", "Policy Maker", "Preventive care", "Primary Care", "Primary Care Physician", "Process", "Quality of Care", "Reporting", "Specialist", "Subgroup", "System", "Testing", "Time", "Underserved Population", "United States", "Visit", "Work", "acute care", "beneficiary", "burnout", "care delivery", "care providers", "care systems", "care utilization", "cost", "demographics", "design", "dual eligible", "hospitalization rates", "improved outcome", "insight", "large scale data", "mortality", "multiple chronic conditions", "older adult", "post-COVID-19", "primary care clinician", "response", "screening", "social", "trend" ], "approved": true } }, { "type": "Grant", "id": "15959", "attributes": { "award_id": "1R21AI196878-01", "title": "A Microfluidic-Free Droplet Technology for Rapid and Quantitative Airborne Pathogen Monitoring", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32597, "first_name": "BROOKE ALLISON", "last_name": "BOZICK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-04-01", "end_date": "2028-03-31", "award_amount": 451000, "principal_investigator": { "id": 44406, "first_name": "Daniel", "last_name": "Weisgerber", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2635, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Pathogen transmission via indirect routes such as fomite, waterborne, and airborne transmission are hallmarks of both endemic and pandemic spread. Viruses such as Influenza, SARS-CoV-2, and measles are notable examples, in addition to deadly microbes such as Bordetella pertussis, Mycobacterium tuberculosis, and Coccidioides species. However, the rapid detection and analysis of airstreams as part of biosurveillance, public health monitoring, or epidemiological research remains challenging. Current state-of-the-art methods rely on bulky apparatuses for both the collection and detection of airborne agents; most of these methods are ill suited to rapid response point-of-testing within medical facilities, workplace locals, or public spaces. Further, these technologies are based on bulk Polymerase Chain Reaction (PCR) and Loop-mediated isothermal amplification (LAMP) methods that have limited quantitative accuracy. Thus, more portable and accurate platforms are needed to address the types of rapid response and ubiquitous monitoring that is required to minimize outbreaks in the 21st century. Towards this objective, this grant will address the need for an improved method of airborne pathogen detection through the development of the digital droplet Aerosol Capture & Quantification (ddACQ) system. The ddACQ system consists of two novel technologies, a filter particle array and a droplet buoyancy counter. The filter particle array allows for the capture of airborne pathogens or biological agents and generation of microfluidic droplets when mixed with an oil and water reagent solution. A phone-powered heat block then drives a one-step isothermal digital droplet reaction. Digital techniques have several key advantages over classical quantitative PCR and LAMP techniques, namely single molecule detection and direct quantification without a standard curve. Finally, the droplet buoyancy counter allows for smartphone based read out of the reaction immediately at the testing site in under an hour. Together, the innovations within and implementation of the ddACQ system represents a novel application of microfluidic principles and an enabling technology for both pathogen transmission research and public health monitoring applications.", "keywords": [ "2019-nCoV", "Address", "Aerosols", "Air", "Air Movements", "Biological Assay", "Biological Monitoring", "Biological Products", "Bordetella pertussis", "COVID-19", "Cellular Phone", "Characteristics", "Coccidioides", "Collection", "Complex", "Detection", "Development", "Devices", "Disease Outbreaks", "Elements", "Epidemiologic Research", "Etiology", "Generations", "Goals", "Grant", "Heating", "Hour", "Human Resources", "Hydrogels", "Individual", "Influenza", "Influenza A virus", "Influenza B Virus", "Lighting", "Measles", "Measurement", "Measures", "Mediating", "Medical", "Methods", "Microbe", "Microfluidics", "Microscope", "Modeling", "Modernization", "Monitor", "Mycobacterium tuberculosis", "Oils", "Pathogen detection", "Polymerase Chain Reaction", "Public Health", "Quarantine", "Reaction", "Reagent", "Recovery", "Research", "Route", "Running", "Sampling", "Site", "Stream", "Structure", "Surface", "Syndrome", "System", "Techniques", "Technology", "Telephone", "Testing", "Training", "Virus", "Water", "Workplace", "aerosolized", "air sampling", "biosecurity", "contaminated water", "cost", "design", "detection platform", "digital", "experience", "improved", "innovation", "instrumentation", "isothermal amplification", "method development", "new technology", "novel", "pandemic disease", "particle", "pathogen", "pathogenic bacteria", "pathogenic fungus", "portability", "rapid detection", "rapid testing", "respiratory", "respiratory virus", "response", "risk stratification", "single molecule", "targeted agent", "transmission process", "waterborne" ], "approved": true } }, { "type": "Grant", "id": "15963", "attributes": { "award_id": "1R01AG083894-01A1", "title": "Longitudinal MRI Measures of Cerebrovascular Injury and AD Atrophy in a Study of Latinos (SOL-INCA-MRI Long)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 44413, "first_name": "MARYAM X", "last_name": "GHALEH", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-03-15", "end_date": "2030-11-30", "award_amount": 3517625, "principal_investigator": { "id": 44414, "first_name": "Charles", "last_name": "DeCarli", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44415, "first_name": "Hector M", "last_name": "Gonzalez", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3418, "ror": "", "name": "UNIVERSITY OF CALIFORNIA AT DAVIS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Latinos constitute a heterogeneous population which accounted for slightly more than 50% of the United States (US) population growth for 2010 to 2020. Latinos are also becoming a larger proportion of older individuals in the US. Despite this, biomarker studies of normal aging and cognitive impairment remain limited, and the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) constitutes the only known representative sample. Moreover, epidemiological data indicate that Latinos have a higher prevalence of vascular risk factors, lower cardiovascular health metrics, and a greater likelihood of having mild cognitive impairment (MCI) or dementia due non-Alzheimer’s disease processes that differ by heritage. Consequently, diagnosis and treatment of Latino persons with cognitive impairment may be more challenging, but more amenable to prevention through reduction of vascular risk factors than non-Hispanic White persons where vascular risk and disease is less prevalent. The first cycle of “MRI Measures of Cerebrovascular Injury and Alzheimer’s disease Atrophy in a Study of Latinos (RF1 AG054548; AKA SOL-INCA-MRI)” was designed to identify biological underpinnings of normal cognitive aging, MCI and Alzheimer’s disease and related dementias (ADRD) in a representative subgroup of the HCHS/SOL 62 + 9 years of age on average. Despite restrictions imposed by the COVID pandemic, our investigators successfully obtained brain MRI from 2668 individuals or >95% of the proposed study cohort. From these data we have published on 1) differences in brain structure from ages 35-85; 2) the impact of vascular risk and sleep on brain structure; 4) the association of cognition with subsequent MRI measures; and 4) genetic influences on select brain measures. These early results, while of scientific value, are cross- sectional and do not reflect ongoing degeneration or incident vascular injury, limiting inferential power that might extend scientific knowledge of brain aging and ADRD in this unique cohort. For this application, we propose to extend our work to include longitudinal MRI analysis, leveraging longitudinal biomarker and clinical data from 3 visits, spanning approximately 12 years of HCHS/SOL and its cognitive ancillary study (SOL-INCA- AD; R01 AG075758, Gonzalez, DeCarli Co-PIs) on a deeply characterized and diverse Hispanic/Latino cohort. Adding longitudinal image analysis in combination with longitudinal lifestyle, medical risk factors, plasma ATN biomarkers, genetics and cognitive assessment in this Latino cohort will address multiple ADRD research milestones and priorities while enabling stronger statistical inference of risk and resilience factors amongst representative, yet relatively young-old members of diverse Latino communities, creating the opportunity to identify modifiable risk factors, potentially reducing societal burden due to later-life ADRD in this rapidly growing portion of the older US population.", "keywords": [ "9 year old", "Age", "Aging", "Alzheimer's Disease", "Alzheimer's disease related dementia", "Amyloid beta-Protein", "Ancillary Study", "Atrophic", "Biological", "Biological Markers", "Blood Vessels", "Brain", "Brain Injuries", "COVID-19 pandemic", "Cerebrovascular Trauma", "Clinical Data", "Cognition", "Cognitive", "Cognitive aging", "Communities", "Data", "Dementia", "Diagnosis", "Disease", "Funding", "Genetic", "Genetic Risk", "Growth", "Hemorrhage", "High Prevalence", "Hispanic", "Hispanic Community Health Study/Study of Latinos", "Image Analysis", "Impaired cognition", "Individual", "Infarction", "Intercept", "K-Series Research Career Programs", "Knowledge", "Latino", "Latino Population", "Life", "Life Style", "Magnetic Resonance Imaging", "Measures", "Mediating", "Medical", "Nerve Degeneration", "Not Hispanic or Latino", "Older Population", "Participant", "Pathologic", "Persons", "Plasma", "Population", "Population Growth", "Population Heterogeneity", "Prevention", "Process", "Publishing", "Research", "Research Personnel", "Risk", "Risk Factors", "Sampling", "Sleep", "Structure", "Study of Latinos", "Subgroup", "Time", "United States", "United States National Institutes of Health", "Vascular Diseases", "Visit", "Water", "White Matter Hyperintensity", "Work", "aging brain", "brain magnetic resonance imaging", "cardiovascular health", "cerebral microbleeds", "cognitive performance", "cognitive testing", "cohort", "cohort research", "design", "disparity reduction", "endophenotype", "epidemiologic data", "gray matter", "magnetic resonance imaging biomarker", "member", "mild cognitive impairment", "modifiable risk", "morphometry", "normal aging", "resilience factor", "serial imaging", "social culture", "sociocultural determinant", "tau-1", "vascular injury", "vascular risk factor", "white matter" ], "approved": true } }, { "type": "Grant", "id": "15967", "attributes": { "award_id": "1R21DA062030-01A1", "title": "Understanding trajectories of cannabis use frequency across the lifespan based on routine screening in a large outpatient population", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)" ], "program_reference_codes": [], "program_officials": [ { "id": 44419, "first_name": "KEVA WONTORIA", "last_name": "COLLIER KIDEMU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-03-15", "end_date": "2028-02-29", "award_amount": 470979, "principal_investigator": { "id": 44420, "first_name": "Gwen", "last_name": "Lapham", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3421, "ror": "", "name": "KAISER FOUNDATION RESEARCH INSTITUTE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Cannabis use is prevalent and increasing in the US, with growth in older adult use outpacing increases in all other age groups. Cannabis use increases risk of cannabis use disorder (CUD) and other adverse health outcomes, with up to 33% of people who use cannabis having a CUD. In the context of legalized, more frequent and higher potency cannabis use, longitudinal studies examining the long-term risks of cannabis use are critically needed. Latent class trajectory modeling is an established approach to modeling cannabis use patterns among adolescent and young adult research participants. Few studies have included middle-aged or older adults, for whom cannabis morbidity may be most concerning due to risks of drug interactions, diminished health, falls and injuries, and impaired cognition. The proposed study responds to NIDA’s call for research on the health effects of cannabis, particularly among older adults, and trajectories of substance use and adverse health outcomes. This study will use 10 years of electronic health record data from a large health system that screens patients annually with a valid practical, single-item cannabis screen. The sample includes more than 331,000 adult patients (≥ 18 years)—including large samples of middle aged and older adults—who have completed the cannabis screen on 3 or more occasions as part of routine clinical care (2016 – 2025). The screen asks about the frequency of cannabis use (none to daily), with frequency of use being the most important predictor of CUD and adverse health conditions, even when accounting for heterogeneity of cannabis products. Specific aims are to conduct developmental research to inform a future R01 that will assess the extent to which different longitudinal cannabis use patterns predict subsequent adverse health outcomes. Aim 1 is to conduct preliminary analyses to understand sample biases, cohort effects (e.g., COVID- 19) and data missing. Aim 2 is to apply multistep trajectory modeling to identify groups of patients, separately for 4 age groups (18-34, 35-49, 50-64, ≥ 65), who follow similar trajectories of cannabis use and characterize patients in each trajectory group by demographics, health conditions, medication use, health care utilization and diagnosed CUD. Aim 3 is to describe, for each age-based trajectory group, the year-by-year prevalence of concurrent adverse health outcomes associate with cannabis use (i.e., depression, psychotic disorder, chronic pain, polysubstance use, cognitive impairment, diagnosed CUD) over the study period. Secondarily, by age group, we will repeat Aims 2 and 3 separately in women and men and in 4 subgroups defined by race and ethnicity: Black, Hispanic, Asian and White. Public Health Impact: More than 59 million US adults use cannabis, yet little is known about the long-term patterns of cannabis use and associated adverse health outcomes, particularly for middle-aged and older adults. Results will have direct clinical implications for care of patients whose cannabis use is associated with adverse outcomes and build the foundation for future research to predict subsequent adverse health outcomes by trajectory group.", "keywords": [ "Accounting", "Adolescent and Young Adult", "Adult", "Age", "Anxiety", "Anxiety Disorders", "Asian", "Black race", "COVID-19", "Cannabis", "Cessation of life", "Characteristics", "Chronic", "Clinical", "Cohort Effect", "Cohort Studies", "Data", "Data Sources", "Development", "Diagnosis", "Drug Interactions", "Electronic Health Record", "Epidemiology", "Ethnic Origin", "Foundations", "Frequencies", "Future", "Growth", "Health", "Health Insurance", "Health system", "Heterogeneity", "Hispanic", "Impaired cognition", "Individual", "Injury", "Legal", "Link", "Longitudinal Studies", "Medical", "Mental Depression", "Modeling", "Mood Disorders", "Morbidity", "National Institute of Drug Abuse", "Outcome", "Outpatients", "Pain", "Participant", "Patient Care", "Patients", "Pattern", "Perception", "Persons", "Pharmaceutical Preparations", "Population", "Prevalence", "Psychoses", "Psychotic Disorders", "Public Health", "Race", "Recreation", "Reporting", "Research", "Risk", "Risk Factors", "Route", "Sampling", "Sampling Biases", "Sleep", "Subgroup", "Substance Use Disorder", "Suicide attempt", "Surveys", "Testing", "Warfarin", "Washington", "Woman", "acute care", "adverse outcome", "age group", "alcohol risk", "automobile accident", "cannabis use behavior", "care utilization", "chronic pain", "clinical care", "cohort", "demographics", "falls", "health care service utilization", "human old age (65+)", "insurance claims", "life span", "marijuana legalization", "marijuana use", "marijuana use disorder", "men", "middle age", "mortality", "older adult", "patient screening", "polysubstance use", "primary care patient", "risk perception", "routine care", "routine screening", "screening", "sex", "substance use", "young adult" ], "approved": true } }, { "type": "Grant", "id": "15969", "attributes": { "award_id": "1UG3NS141843-01A1", "title": "Low-dose naltrexone (LDN) for the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 44422, "first_name": "LINA FERNANDA", "last_name": "GARCIA", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-03-06", "end_date": "2028-02-28", "award_amount": 556686, "principal_investigator": { "id": 44423, "first_name": "Jarred W.", "last_name": "Younger", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3422, "ror": "", "name": "UNIVERSITY OF ALABAMA AT BIRMINGHAM", "address": "", "city": "", "state": "AL", "zip": "", "country": "United States", "approved": true }, "abstract": "In this UG3/UH3 Exploratory Clinical Trial, we will test low-dose naltrexone (LDN) as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). ME/CFS affects approximately 1 million people in the United States, with incidence rates increasing with the SARS-CoV-2 pandemic. ME/CFS is characterized by profound fatigue, cognitive issues, pain sensitivity, and post-exertional malaise (PEM). Several studies support the hypothesis that ME/CFS involves chronic inflammatory activity in the central nervous system (CNS) that is driven by hyperactive microglia. More than 35 years since recognizing ME/CFS as a distinct medical condition, there is still no FDA-approved medications and no consensus on optimal treatment of the disorder. There is an urgent need to identify treatments that are safe and effective in reducing the severity of ME/CFS. Low dose naltrexone (LDN) involves daily doses of naltrexone in the 0.5mg to 6.0mg range. LDN crosses the blood-brain barrier, pushes microglia from an inflammatory to a resting state, and reduces the production of pro-inflammatory chemicals in the brain. LDN reduces fatigue severity in conditions such as ME/CFS, fibromyalgia, and Long-COVID. LDN is an ideal first treatment for ME/CFS because it is generically available, inexpensive, safe, and well-tolerated. LDN also has no abuse potential. In this Phase II trial, several questions will be answered to optimize a future Phase III efficacy trial of LDN for ME/CFS. This trial uses a remote design where individuals can enroll from anywhere in the United States and can complete all study tasks from their home. This approach allows individuals who are homebound or bedbound to participate in the clinical trial. Study 1 is a dose-finding study where 75 ME/CFS participants will receive LDN at 1.5mg/day, 3.0mg/day, 4.5mg/day, and 6.0mg/day for 2 months each, in blinded order. This study will be used to determine the best dose of LDN to be used in future trials. Study 2 is a randomized controlled trial (RCT) in 150 individuals with ME/CFS. Participants will be randomized to receive LDN or placebo. This study will be used to test safety and tolerability, determine the likely side-effects, determine the best measure to use as a primary outcome, identify predictors of a positive LDN response, and preliminarily measure the strength of the LDN effect. A subgroup of participants (25 LDN and 25 placebo) will be recruited close to the University of Alabama at Birmingham (UAB) to complete advanced neuroimaging and blood tests of neuroinflammation, neurodegeneration, and oxidate stress. These tests may yield biomarkers of LDN response for predicting who is a good LDN candidate, or for tracking improvement with the treatment. Neuroimaging will focus on brain lactate and temperature, two measures of brain inflammation. Study 3 is an extended-duration study where participants may be switched between placebo and LDN, in order to collect additional safety, tolerability, efficacy, and durability information. 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