Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1383&sort=end_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=end_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=end_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=end_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1382&sort=end_date" }, "data": [ { "type": "Grant", "id": "14678", "attributes": { "award_id": "1R01NS136197-01", "title": "Evaluating SARS-CoV-2 spike antigen-induced coagulopathy and neuroinflammation as mechanistic drivers of neurologic PASC", "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": 9314, "first_name": "LUMY", "last_name": "Sawaki-Adams", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-04-01", "end_date": "2029-03-31", "award_amount": 664976, "principal_investigator": { "id": 31372, "first_name": "Michael Joseph", "last_name": "Peluso", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Post-acute sequelae of SARS-CoV-2 infection (PASC) can affect multiple organ systems and result in functional impairment. Neurologic PASC symptoms (neuro-PASC) including cognitive impairment, headache, and neuropathy are among the most debilitating. Structural and functional brain changes – as defined by changes in cerebral blood flow, white and gray matter morphology, and neurocognitive performance – have been observed post-COVID and have variably been associated with neuro-PASC. Data from our group and others have implicated virus persistence, coagulation dysfunction, and inflammation as potential causes. Based on these data, we hypothesize that the persistence of SARS-CoV-2 spike protein drives downstream clot pathology, microcirculatory dysfunction, and neuroinflammation, leading to damage to neuronal tissues and resulting in neuro-PASC. To test this mechanistic model, we will leverage one of the longest prospective studies of Long COVID (Long-term Impact of Infection with Novel Coronavirus cohort; LIINC; NCT04362150), which includes detailed clinical data and biological specimens on 700 individuals following mostly mild-to-moderate COVID-19, over 250 of whom report neuro-PASC symptoms. In Aim 1, we will use banked specimens and data from individuals followed for up to 4 years post-COVID to conduct both a cross-sectional analysis and a longitudinal study of three well-defined groups: (1) neuro-PASC (n=200), (2) non-neuro-PASC (n=200), and (3) fully recovered (n=100). We will determine whether spike persistence is present among those with neuro-PASC, whether it drives fibrin dysregulation and microclotting, and whether it causes systemic and/or neurologic inflammation. In a subset, we will determine whether the primary determinants of neuro-PASC emerge during the acute phase (first 10 days) and how they evolve over 4 years. In Aim 2, we will conduct a prospective, intensive characterization of individuals with and without evidence of SARS-CoV-2 persistence (n=75 per group). These cohorts will be characterized clinically by neurocognitive testing and a suite of state-of-the-art MRI studies. Lumbar punctures and gut biopsies will be performed. Multiple biologic studies will be conducted, including assessment of SARS-CoV-2 blood, cerebrospinal fluid (CSF), and tissue reservoirs, characterization of microclots, and assessment of inflammation. We will determine the effect of spike persistence on neurocognitive performance and on MRI parameters of cerebral blood flow, neuroinflammation, axonal loss, and tissue atrophy. Finally, we will determine whether spike persistence drives changes in CSF profiles including fibrin dysregulation, neuroinflammation and blood-brain barrier disruption. In Aim 3, we will study specimens from a separately funded randomized trial of an anti-SARS-CoV-2 monoclonal antibody (AER002; NCT05877508) to test whether disruption of tissue reservoirs of SARS-CoV-2 spike antigen in the post-acute phase alters the pathway proposed in our model. Our proposed studies provide the unprecedented ability to examine in detail how virus persistence, coagulopathy, and immune dysfunction cause neurologic injury and result in neuro-PASC.", "keywords": [ "2019-nCoV", "Acute", "Affect", "Antigens", "Atrophic", "Automobile Driving", "Axon", "Binding", "Biological", "Biological Markers", "Biological Specimen Banks", "Biopsy", "Blood", "Blood Coagulation Disorders", "Blood Vessels", "Body System", "Brain", "COVID-19", "Cerebrospinal Fluid", "Cerebrovascular Circulation", "Clinical", "Clinical Data", "Clinical Trials", "Coagulation Process", "Coronavirus", "Cox Proportional Hazards Models", "Cross-Sectional Studies", "Data", "Deposition", "Diagnosis", "Diffusion Magnetic Resonance Imaging", "Early identification", "Emerging Technologies", "Enrollment", "Fibrin", "Fibrinogen", "Functional disorder", "Functional impairment", "Funding", "Headache", "Health", "Image", "Immune System Diseases", "Impaired cognition", "Individual", "Infection", "Inflammation", "Inflammatory", "Infrastructure", "Laboratories", "Link", "Longitudinal Studies", "Longterm Follow-up", "Macrophage Activation", "Magnetic Resonance Imaging", "Measures", "Mediation", "Mediator", "Methods", "Modeling", "Monoclonal Antibodies", "Morphology", "Nervous System Trauma", "Neurocognitive", "Neurocognitive Deficit", "Neurologic", "Neurologic Symptoms", "Neurons", "Neuropathy", "Outcome", "Outpatients", "Paper", "Parents", "Pathology", "Pathway interactions", "Performance", "Persons", "Phase", "Pilot Projects", "Plasma", "Polymers", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Prospective Studies", "Proteins", "Publishing", "RNA", "Reporting", "Research Infrastructure", "Research Personnel", "Role", "SARS-CoV-2 antigen", "SARS-CoV-2 spike protein", "Sampling", "Specimen", "Spinal Puncture", "Susceptibility Gene", "Symptoms", "Testing", "Tissues", "United States National Institutes of Health", "Viral", "Virus", "arterial spin labeling", "biomarker identification", "blood-brain barrier disruption", "cohort", "cytokine", "glial activation", "gray matter", "improved", "multimodality", "neurocognitive test", "neuroinflammation", "neurologic sequelae of COVID-19", "neuropathology", "novel coronavirus", "performance tests", "polymerization", "programs", "prospective", "proteomic signature", "randomized trial", "reduce symptoms", "repository", "single molecule", "symptomatology", "tool", "white matter" ], "approved": true } }, { "type": "Grant", "id": "14682", "attributes": { "award_id": "1U19AI181105-01", "title": "Project 3: Evolution, dynamics and durability of B cell and antibody responses in lung transplantation", "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": [], "start_date": "2024-04-16", "end_date": "2029-03-31", "award_amount": 380387, "principal_investigator": { "id": 31376, "first_name": "Troy D", "last_name": "Randall", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 612, "ror": "https://ror.org/008s83205", "name": "University of Alabama at Birmingham", "address": "", "city": "", "state": "AL", "zip": "", "country": "United States", "approved": true }, "abstract": "Project 3: Evolution, dynamics and durability of B cell and antibody responses in lung transplantation Emerging data suggest that, like lung-resident memory T cells, memory B cells can reside in the lung without recirculating and act as first responders to pulmonary pathogens like influenza and SARS-CoV-2. We termed these cells lung-resident memory B cells or BRM cells. We also showed that lung-resident memory B cells require contact with antigen within the lung in order to initiate their residency program. Taken together, these data suggest that BRM cells are an important component of immunity to pulmonary pathogens. However we have only a rudimentary understanding of where BRM cells come from, how they are selected, what antigens they react with and how they are recalled (or not) after vaccination or secondary infection. Although lung-resident memory B cells are clearly generated in response to pulmonary infection, it is less clear whether they are generated in response to other types of antigens like auto-antigens or allo-antigens. Interestingly, many pulmonary diseases, like COPD, IPF and ILD, have an autoimmune component in some patients, perhaps as a consequence of persistent inflammation. Moreover, allo-reactive antibodies are often observed in lung transplant patients. Given that auto-antigens and allo-antigens are widely expressed in the lung tissue, it makes sense that lung-resident B cells will respond to these antigens in the lung. Our overall hypothesis is that allo-reactive, auto- reactive and pathogen-reactive B cells in lung allografts are primed and selected locally in the lung, and that the signals and cellular interactions involved in this process are different than those in conventional secondary lymphoid organs. To test this hypothesis, we will take advantage of single cell methods that allow us to define (and compare) individual B cells in blood, bronchalveolar lavage (BAL) fluid and lung tissue by a combination of transcriptome (single cell RNseq), BCR clonotype (single cell BCRseq), DNA-barcoded antibodies to surface markers (CITEseq) and affinity/specificity/cross-reactivity of BCRs cloned and expressed as recombinant antibodies (single cell cloning). We will also use high-dimensional antigen arrays of HLA alleles, auto-antigens, and virus-derived antigens to quantify the reactivity of antibodies in the blood and BAL fluid of lung transplant patients. Using these methods to compare populations of auto-reactive, allo-reactive and virus-reactive-specific B cells in the lung, BAL and blood over time and, in some cases, after infection, we will be able to determine how memory B cells in the lung are related to one another, the depth of their selection, the extent of their cross- reactivity and their ability to respond to local antigens. This information will be informative about the evolution of donor-specific antibodies in the context of lung transplant, the potential role of auto-antibodies in the lungs of transplant patients and the ability of pre-formed, virus-reactive (DONOR) B cells retained in donor lungs as they respond to infection.", "keywords": [ "2019-nCoV", "Affinity", "Alleles", "Alloantigen", "Allografting", "Antibodies", "Antibody Response", "Antigens", "Appearance", "Autoantibodies", "Autoantigens", "Autoimmune", "B-Lymphocytes", "B-cell receptor repertoire sequencing", "Bar Codes", "Binding", "Blood", "Cells", "Cellular Indexing of Transcriptomes and Epitopes by Sequencing", "Chronic Obstructive Pulmonary Disease", "Clone Cells", "DNA", "Data", "Development", "Epitopes", "Evolution", "Functional disorder", "Genetic Transcription", "Human", "Immunity", "Immunoglobulin A", "Immunoglobulin G", "Individual", "Infection", "Inflammation", "Influenza", "Lavage", "Liquid substance", "Location", "Longevity", "Lung", "Lung Diseases", "Lung Lavage Fluid", "Lung Transplantation", "Lung infections", "Memory B-Lymphocyte", "Methods", "Monitor", "Mus", "Pathology", "Patients", "Population", "Process", "Reaction", "Recombinant Antibody", "Residencies", "Respiratory Tract Infections", "Role", "Serum", "Signal Transduction", "Site", "Specificity", "Structure of parenchyma of lung", "Surface", "T-Lymphocyte", "Testing", "Time", "Tissues", "Transplant Recipients", "Transplantation", "Vaccination", "Variant", "Virus", "antibody-mediated rejection", "autoreactive B cell", "autoreactivity", "cross reactivity", "donor-specific antibody", "experimental study", "first responder", "high dimensionality", "influenzavirus", "insight", "lung allograft", "lung pathogen", "migration", "pathogen", "programs", "respiratory virus", "response", "secondary infection", "secondary lymphoid organ", "self-renewal", "single-cell RNA sequencing", "tissue resident memory T cell", "transcriptome", "transcriptome sequencing" ], "approved": true } }, { "type": "Grant", "id": "14687", "attributes": { "award_id": "1R01CA289295-01", "title": "Strategies for Reaching and Impacting Our Communities Sustainably (NWP-ROCS Program)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [ { "id": 31381, "first_name": "ELIZABETH ANNE", "last_name": "Sarma", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-04-01", "end_date": "2029-03-31", "award_amount": 542964, "principal_investigator": { "id": 31382, "first_name": "Rachel C", "last_name": "Shelton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 781, "ror": "", "name": "COLUMBIA UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Widespread implementation, scale-up, and sustainability of culturally-appropriate, evidence-based programs is critical to reducing the significant and disproportionate burden of cancer among Black women. Community- engaged Lay Health Advisor (LHA) programs are highly successful in reducing health inequities for cancer. One of the most robust evidence-based and nationally disseminated LHA cancer prevention/screening programs is The National Witness Project (NWP). NWP is one of the few equity-focused LHA programs with both longevity and evidence of impact in Black communities nationally. Despite its impact, NWP continues to face challenges to sustainability and the long-term delivery of the program. Advancing the science of sustainability is urgent, as inequities in cancer and challenges to the sustainability of evidence-based programs were exacerbated during the COVID pandemic. Research is critically needed on sustainability, particularly among low-resource settings and communities that face historical and ongoing structural and systemic barriers to health, to make progress towards racial equity for cancer screening and outcomes. Our team is uniquely poised to lead and advance research in this area. Building off of our work on sustainability and a long-term partnership with NWP, we propose a national mixed-methods prospective study with the following aims. First, in aim 1 we will refine, with a sub-sample of NWP sites nationally (n=6), a package of sustainability strategies to support the ongoing delivery of NWP at scale, with the long-term goal of addressing cancer screening inequities among Black women. We will focus on strategies for building capacity and partnerships to enhance sustained impact and delivery of NWP and support retention of LHAs (e.g. novel curricula/training; tailored technical assistance; Community of Practice model to share lessons across sites), with the goal of enhancing capacity for: 1) building partnerships/identifying champions at academic/healthcare centers to leverage organizational resources; 2) building business case for program’s value; 3) adapting to local community needs and context. In Aim 2, we propose to deliver and examine the impact of this refined package of sustainability strategies on multiple sustainability outcomes annually over four years across 16 NWP sites nationally using a pre-post cluster prospective design. Finally, in aim 3, we plan to apply a concurrent mixed-methods approach (n=200 surveys and 50-65 in-depth interviews) to examine the uptake, acceptability, appropriateness, feasibility and impact of sustainability strategies among 16 NWP sites to explore the processes through which strategies build capacity for and influence sustainability of equity-focused EBIs in community settings over the 4 years. This research is timely, providing a key opportunity to advance scientific understanding of strategies to promote sustainability among a generalizable, nationally disseminated program. Findings lay the groundwork for enhancing sustainability of trusted community-led programs and making progress towards racial equity in cancer and cancer screening.", "keywords": [ "Accountability", "Address", "Area", "Behavior", "Black race", "Breast", "Businesses", "COVID-19 pandemic", "Cancer Burden", "Cancer Center", "Cancer Control", "Cancer Model", "Cancer Survivor", "Cervical Cancer Screening", "Collaborations", "Communities", "Community of Practice", "Diagnostic", "Discrimination", "Early Diagnosis", "Education", "Educational Curriculum", "Entrepreneurship", "Equity", "Evaluation", "Evidence based program", "Face", "Goals", "Health", "Healthcare", "Inequity", "Infrastructure", "Institution", "Institutionalization", "Interview", "Knowledge", "Lead", "Longevity", "Malignant Neoplasms", "Malignant neoplasm of cervix uteri", "Medical", "Methods", "Modeling", "National Cancer Institute", "Outcome", "Participant", "Play", "Process", "Prospective Studies", "Racial Equity", "Research", "Resource-limited setting", "Resources", "Science", "Scientific Advances and Accomplishments", "Screening for cancer", "Services", "Site", "Surveys", "Testing", "Time", "Training", "Trust", "Underserved Population", "Woman", "Work", "black women", "cancer prevention", "community partnership", "community setting", "design", "evidence base", "experience", "follow-up", "health equity", "health inequalities", "implementation science", "improved", "novel", "programs", "prospective", "racial disparity", "scale up", "screening program", "skills", "social", "sustainability framework", "systemic barrier", "theories", "uptake" ], "approved": true } }, { "type": "Grant", "id": "14819", "attributes": { "award_id": "1R01MH135915-01", "title": "Societal stressors, adaptive factors, and developmental timing: Influences on Latinx mental health from early childhood through young adulthood", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 6363, "first_name": "Julia L", "last_name": "Zehr", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-06-01", "end_date": "2029-03-31", "award_amount": 811056, "principal_investigator": { "id": 31498, "first_name": "ESTHER J", "last_name": "CALZADA", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 24693, "first_name": "Kathleen M", "last_name": "Roche", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 174, "ror": "https://ror.org/00y4zzh67", "name": "George Washington University", "address": "", "city": "", "state": "DC", "zip": "", "country": "United States", "approved": true } ] }, { "id": 31499, "first_name": "MARGARET O", "last_name": "CAUGHY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 174, "ror": "https://ror.org/00y4zzh67", "name": "George Washington University", "address": "", "city": "", "state": "DC", "zip": "", "country": "United States", "approved": true }, "abstract": "In 2021, the US Surgeon General issued an advisory warning of a youth mental health crisis, exacerbated by the COVID-19 pandemic. Latinx youth, a group marginalized by race, ethnicity, class, and culture, have exceedingly high rates of internalizing symptoms such as depression and anxiety. Ecosocial theory posits that historical, societal, and ecological conditions over the life course have critical impacts on later mental health. This research will examine how distal and proximal societal stressors influence mental health trajectories for a diverse sample of US Latinx youth followed from early childhood into young adulthood. Distal societal stressors, such as the pandemic, anti-immigrant rhetoric, and neighborhood ethnic marginalization, may increase Latinx youth’s internalizing symptoms directly and indirectly through proximal societal stressors, such as families’ COVID-related economic, health, and social problems and individuals’ perceptions of immigrant threats and ethnic discrimination. These kinds of societal stressors also may have direct and indirect effects on increased internalizing symptoms through family stress processes, including maternal depression and harsh parenting. The nature of youth’s exposure to these stressors (for how long, when in history and development) and the presence of protective adaptive factors (e.g., parents’ cultural socialization; youth self-regulation) can moderate stressor impacts on internalizing symptoms. This research will leverage advances in Integrated Data Analysis (IDA) to pool data from five longitudinal Latinx cohort studies to obtain a single, aggregated data set with 2,515 Latinx mother-youth dyads following youth from age 2 to 22 (2010-26). IDA increases statistical power, sample heterogeneity and generalizability, and measurement breadth and depth in ways not possible with a single data set. The application will support 1) collecting cross-sectional data for 500 Latinx individuals to establish standard measurement scaling across the five studies; 2) integrating data across all five studies; and 3) extracting data from Twitter and the US Census to assess anti-immigrant rhetoric and neighborhood factors, respectively. Analyses will utilize a general latent variable modeling framework that includes multilevel modeling, structural equation modeling, item response modeling, and finite mixture modeling. We hypothesize a cascade of effects from distal societal stressors to increased internalizing symptoms through greater proximal societal stressors and increased family stress processes. We expect that pathways linking societal stressors to youth’s internalizing symptoms will vary depending upon the presence of adaptive factors, the developmental timing and cumulative effects of youth experiences, and sociodemographic characteristics (e.g., youth biological sex, family national origin). This study offers an unparalleled opportunity to understand Latinx mental health in relationship to multi-level stressors, adaptive factors, and sensitive periods of development. As Latinx youth comprise more than one-in-four US youth, findings from this research will help guide new preventive interventions and refine existing ones for a large and growing segment of the US population.", "keywords": [ "Address", "Affect", "Age", "Anxiety", "COVID-19", "COVID-19 pandemic", "Censuses", "Characteristics", "Child", "Child Rearing", "Cohort Studies", "Data", "Data Aggregation", "Data Analyses", "Data Pooling", "Data Set", "Depressed mood", "Development", "Distal", "Early identification", "Economics", "Equation", "Ethnic Origin", "Event", "Exposure to", "Family", "Feeling hopeless", "Goals", "Health", "Heterogeneity", "High School Student", "Immigrant", "Immigration", "Individual", "Informal Social Control", "Intervention", "Knowledge", "Latinx", "Latinx population", "Life Cycle Stages", "Light", "Link", "Longevity", "Longitudinal cohort study", "Measurement", "Measures", "Mediating", "Mental Depression", "Mental Health", "Mental disorders", "Modeling", "Mothers", "National Institute of Mental Health", "National origin", "Nature", "Neighborhoods", "Parents", "Pathway interactions", "Perception", "Policies", "Population", "Process", "Race", "Recording of previous events", "Reporting", "Research", "Research Personnel", "Sampling", "Shapes", "Signal Transduction", "Social Problems", "Socialization", "Strategic Planning", "Stress", "Surgeon", "Surveys", "Symptoms", "Twitter", "Youth", "biological sex", "cost effective", "course development", "data integration", "early childhood", "early experience", "ethnic discrimination", "ethnic identity", "experience", "marginalization", "marginalized population", "maternal depression", "multilevel analysis", "pandemic disease", "preventive intervention", "response", "sex", "social", "sociodemographics", "socioeconomic disadvantage", "stress management", "stressor", "theories", "young adult" ], "approved": true } }, { "type": "Grant", "id": "14824", "attributes": { "award_id": "1R01AI181618-01", "title": "HIV-1 membrane fusion and inhibition", "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": 10594, "first_name": "Gerard", "last_name": "Lacourciere", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-05-20", "end_date": "2029-03-31", "award_amount": 696910, "principal_investigator": { "id": 8930, "first_name": "Bing", "last_name": "Chen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 798, "ror": "https://ror.org/00dvg7y05", "name": "Boston Children's Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 798, "ror": "https://ror.org/00dvg7y05", "name": "Boston Children's Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Virus entry begins with the first encounter between the virus and the cell surface and ends with delivery of the contents of the virus into the host cell. HIV-1 membrane fusion is the first key delivery step, mediated by the virus-encoded envelope glycoprotein [Env; trimeric (gp160)3 cleaved to (gp120/gp41)3], which belongs to the group of class I viral fusion proteins including influenza hemagglutinin, SARS-CoV-2 spike protein and Ebola glycoprotein. A mature Env spike has three copies each of noncovalently-associated receptor-binding subunit gp120 and fusion subunit gp41. Sequential binding of gp120 to the primary receptor CD4 and a coreceptor (chemokine receptor CCR5 or CXCR4) leads to large, irreversible structural rearrangements in gp41, which drive fusion. This picture, derived largely from structural studies of the soluble fragments and from cellular studies with inhibitors and antibodies, is still incomplete because it lacks extension to a high-resolution picture of the complete Env trimer in the context of a lipid-bilayer membrane, which is the substrate of the fusion reaction. We have determined by NMR the structures of the HIV-1 Env transmembrane domain (TMD), membrane proximal external region (MPER), and cytoplasmic tail (CT) in bicelles that mimic lipid bilayers. These regions all form well-ordered, trimeric clusters in a lipid bilayer. Disruption of any of them can reduce membrane fusion efficiency and alter the antigenic structure of the entire Env, suggesting that they have structural and functional roles in fusion and in trimer conformational stabilization. Very recently, we have completed a high-resolution structure of the intact SARS-CoV-2 postfusion spike in membrane, showing how the functionally critical membrane-interacting regions interact with membrane and with each other. These findings are the basis of our overall hypothesis that that structures of the HIV-1 fusion complex either alone or bound with fusion inhibitors in membrane will reveal new structural features of the membrane-interacting regions and substantially advance our mechanistic understanding of the viral fusion and its inhibition, thereby informing future development of intervention strategies. We will apply advanced technologies in cryogenic electron microscopy (cryo-EM) and tomography (cryo-ET) to study structural and functional properties of the HIV-1 fusion complex, as reconstituted in membranes and on the surface of a virus particle. We will also investigate molecular mechanisms of HIV-1 inhibition by two distinct types of fusion inhibitors. Our goal is a \"molecular movie\" of HIV-1 fusion, to inform development of new intervention strategies. We propose the following Specific Aims to address our hypothesis: 1) We will determine structure of the HIV-1 fusion complex containing intact Env, CD4 and CCR5 in the context of a lipid bilayer. 2) We will investigate molecular mechanism of HIV-1 fusion inhibition by anti-CD4 antibody ibalizumab. 3) We will dissect mechanism of action of small-molecule fusion inhibitors targeting the MPER of HIV-1 Env.", "keywords": [ "2019-nCoV", "Address", "Antibodies", "Binding", "Binding Sites", "CCR5 gene", "CD4 Antigens", "CXCR4 gene", "Cell surface", "Cells", "Complex", "Cryo-electron tomography", "Cryoelectron Microscopy", "Cytoplasmic Tail", "Detergents", "Development", "Ebola", "Electron Microscopy", "FDA approved", "Future", "Glycoproteins", "Goals", "HIV Envelope Protein gp120", "HIV-1", "Human", "Infection", "Infection prevention", "Influenza Hemagglutinin", "Intervention", "Length", "Lipid Bilayers", "Lipids", "Mediating", "Membrane", "Membrane Fusion", "Micelles", "Molecular", "Molecular Conformation", "Molecular Mechanisms of Action", "Monoclonal Antibodies", "Pilot Projects", "Process", "Property", "Reaction", "Resolution", "Role", "SARS-CoV-2 spike protein", "Series", "Structure", "Surface", "System", "Technology", "Therapeutic", "Therapeutic Agents", "Transmembrane Domain", "Viral", "Viral Fusion Proteins", "Viral Vaccines", "Virion", "Virus", "Virus Inhibitors", "Visualization", "chemokine receptor", "design", "electron tomography", "env Gene Products", "glycosylation", "gp160", "improved", "inhibitor", "insight", "membrane assembly", "movie", "nanodisk", "neutralizing antibody", "novel", "particle", "receptor", "receptor binding", "reconstitution", "small molecule", "structural biology", "therapy development", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "14891", "attributes": { "award_id": "1R01HD113529-01", "title": "A Multisite RCT of a Daily Living Skills Intervention for Autistic Adolescents Prior to the Transition to Adulthood", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 9289, "first_name": "Alice S", "last_name": "Kau", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-06-19", "end_date": "2029-03-31", "award_amount": 690880, "principal_investigator": { "id": 31582, "first_name": "Amie Marie", "last_name": "Duncan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 897, "ror": "", "name": "CINCINNATI CHILDRENS HOSP MED CTR", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary/Abstract: Daily living skills (DLS), which are the tasks (e.g., hygiene, cooking, laundry, managing money) that individuals do to take care of themselves at home, school, work, and in the community, are impaired in autistic adolescents without an intellectual disability (ID) such that their skills are 6-8 years behind same-aged peers. Age appropriate DLS have been linked to achieving better adult outcomes in employment, college, independent living, and overall quality of life. In the recent Lancet Commission on the future of care and clinical treatment in ASD there was a call to action to address DLS in adolescence as a potential intervention target to increase the likelihood of attaining positive adult outcomes. However, until our team began developing and evaluating the Surviving and Thriving in the Real World (STRW) intervention, there were no known comprehensive, evidence-based DLS interventions for autistic adolescents at this critical developmental period. In two recent pilot randomized clinical trials (RCTs), STRW demonstrated statistically significant and clinically meaningful gains in DLS (i.e., gains of 2-4 years of DLS over the course of a 14-week intervention) compared to a control condition (i.e., PEERS social skills intervention). In our two pilot RCTs, STRW was converted to telehealth due to COVID-19. There were equal DLS gains between in-person STRW and STRW-telehealth (STRW-T) and there were numerous benefits to telehealth delivery. The next step in this line of work is to assess the efficacy of STRW-T in a fully powered Phase 3 RCT compared to an attention control condition (PEERS-telehealth; PEERS-T) and examine the impact of improved DLS on early adult outcomes by following adolescents 6-months after high school graduation. We will enroll 192 autistic teens without ID in the 11th/12th grades and randomize them to receive STRW-T (n = 96) or PEERS-T (n = 96). Caregivers and adolescent participants will complete a comprehensive multi-method DLS battery (i.e., interview, survey, daily phone diaries, goal attainment scaling) at baseline, post-treatment, and 6-month follow- up. Young adult outcomes in work, college, and quality of life will be assessed 6-months post-high school graduation for all participants. The current proposal has the following aims: (1) examine the efficacy of STRW- T on DLS compared to PEERS-T; (2) evaluate whether the improvement in DLS outcomes by STRW-T are sustained at 6-month follow-up; (3) examine the effects of STRW-T intervention on outcomes in college, work, and QoL after high school graduation compared to PEERS. We will also explore the mediating role of improved DLS on young adult outcomes. If the aims of the proposed study are achieved, STRW-T would fill the gap in the current evidence base for treating DLS in autistic adolescents and would be the first study to examine whether a DLS intervention impacts work, college, and QoL outcomes after graduation from high school. Our long term goal is to narrow the gap between age and DLS, and also fill the existing treatment gap by disseminating and implementing this intervention into routine clinical practice for autistic teens.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15674", "attributes": { "award_id": "1I01BX006818-01", "title": "Regulation of T cell immunity", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2025-04-01", "end_date": "2029-03-31", "award_amount": null, "principal_investigator": { "id": 32517, "first_name": "John T", "last_name": "Chang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2485, "ror": "https://ror.org/00znqwq11", "name": "VA San Diego Healthcare System", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Background and Innovation: Mortality from infectious diseases remains the second leading cause of death worldwide, a fact highlighted by 4 years of a global pandemic, making the understanding of host responses, development of new vaccines, and improving existing vaccines important priorities of biomedical research. Memory T cells mediate protection from reinfection with previously encountered pathogens, and a large number of these cells, termed tissue-resident memory cells (TRM), do not recirculate throughout the body, reside within tissues, and provide essential sentinel protection at body surfaces. Using a murine infection model that is well established in the field for studying CD8 TRM, this application will investigate the context- and tissue-specific roles of the transcription factor Foxo1. Conceptual innovations include the study of Foxo1, the role of which is poorly understood in TRM biology. Technical innovations include the use of numerous cutting- edge approaches, including Cellular Indexing of Transcriptomes and Epitopes (CITE-seq) which enables proteomic and transcriptomic (scRNA-seq) analyses in the same single-cells, to identify consequences of Foxo1-deficiency in TRM. Bioinformatic innovations include the application of Taiji, a state-of-the-art bioinformatic analysis algorithm integrating transcriptomic and epigenomic data, to reveal Foxo1-transcription factor networks and identify putative regulatory factors and pathways controlled by Foxo1. Significance and Impact to Veterans Healthcare: Infectious diseases have a substantial public health and economic burden on the Veteran population. These include diseases for which we have vaccines, such as SARS-CoV-2 and influenza, as well as diseases that we do not yet have vaccines for, such as Hepatitis C (HCV) and HIV. A major gap in knowledge is that current vaccines generate neutralizing antibodies but do not generate a robust memory T cell response, including TRM, which are crucial for optimal protection at barrier surfaces. Another gap in knowledge is a comprehensive molecular understanding of the tissue-specific requirements for the generation and persistence of TRM, which will be addressed by this project. This research will address the VHA/ORD research priority of exploring fundamental biologic principles in pre-clinical models with the ultimate goal of improving the well-being of the nation’s Veterans specifically in the area of infectious diseases. Path to translation/implementation: Current vaccination regimens aim to generate protective antibodies but do not generate TRM. A detailed understanding of regulatory programs and transcriptional networks that govern T cell adaptation to tissues and barrier sites must be gained in order to provide the foundation and rational scientific basis to develop “tissue-tailored” immune responses. In this way, immune cells that promote or regulate inflammation can be transcriptionally engineered for trafficking to, retention in, and function within a particular tissue. Next steps to move this research along the translational pathway will involve testing whether modulation of Foxo1-mediated pathways enhances vaccine-generated immune memory.", "keywords": [ "2019-nCoV", "Address", "Adoptive Transfer", "Algorithmic Analysis", "Antibodies", "Area", "Bioinformatics", "Biological", "Biology", "Biomedical Research", "Blood", "Body Surface", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "CRISPR/Cas technology", "Categories", "Cause of Death", "Cell Differentiation process", "Cells", "Cellular Indexing of Transcriptomes and Epitopes by Sequencing", "Cellular biology", "Circulation", "Colon", "Communicable Diseases", "Computer Analysis", "Data", "Development", "Disease", "Economic Burden", "Engineering", "Epitopes", "Exhibits", "FOXO1A gene", "Foundations", "Generations", "Genetic", "Genetic Transcription", "Goals", "HIV/HCV", "Health", "Health Care", "Homologous Gene", "Human", "Immune", "Immune response", "Immunity", "Immunologic Memory", "Infection", "Infectious Skin Diseases", "Inflammation", "Influenza", "Integrins", "Kidney", "Knowledge", "Liver", "Lymphocytic choriomeningitis virus", "Lymphoid Tissue", "Maintenance", "Mediating", "Memory", "Modeling", "Molecular", "Morbidity - disease rate", "Mucous Membrane", "Mus", "Neoplasm Metastasis", "Organ", "Pathogenesis", "Pathway interactions", "Personal Satisfaction", "Play", "Population", "Pre-Clinical Model", "Proteins", "Proteomics", "Public Health", "RUNX3 gene", "Regimen", "Repression", "Research", "Research Priority", "Residencies", "Respiratory Mucosa", "Role", "Salivary Glands", "Sentinel", "Site", "Skin", "Small Intestines", "Sphingosine-1-Phosphate Receptor", "Surface", "System", "T cell regulation", "T cell response", "T memory cell", "T-Cell Receptor", "T-Lymphocyte", "Tai Ji", "Tamoxifen", "Testing", "Therapeutic", "Tissue Differentiation", "Tissues", "Transcription Repressor", "Transgenic Organisms", "Translations", "Vaccination", "Vaccines", "Veterans", "adaptive immunity", "chemokine receptor", "design", "epigenomics", "field study", "first responder", "improved", "indexing", "innovation", "military veteran", "mortality", "neutralizing antibody", "novel vaccines", "pandemic disease", "pathogen", "pathogenic microbe", "programs", "response", "trafficking", "transcription factor", "transcriptome", "transcriptomics", "tumor growth" ], "approved": true } }, { "type": "Grant", "id": "15675", "attributes": { "award_id": "1R01EB037031-01", "title": "Point-of-care DNA diagnostics from raw samples", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Biomedical Imaging and Bioengineering (NIBIB)" ], "program_reference_codes": [], "program_officials": [ { "id": 32518, "first_name": "KRISTIN HEDGEPATH", "last_name": "GILCHRIST", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-04-05", "end_date": "2029-03-31", "award_amount": 257807, "principal_investigator": { "id": 32519, "first_name": "Robert M", "last_name": "Cooper", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 760, "ror": "https://ror.org/0168r3w48", "name": "University of California, San Diego", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The proposed project will develop living biosensors for detecting and analyzing DNA at the single- base level, without requiring sample purification or any equipment. DNA is the prime information carrier for life, and DNA analysis provides valuable information for, e.g., diagnosing microbial infections or tracking disease outbreaks. Many techniques exist for detecting and analyzing DNA, but these generally require processing steps to extract and purify samples, and most require expensive equipment and significant training and expertise. This proposal will transfer that complexity into the biosensor itself, harnessing functions that evolved into living bacteria over billions of years to pull DNA out of raw samples, analyze it, and produce easily read output. The biosensors will pull in DNA using natural competence, and analyze it with single-base precision using their endogenous CRISPR-Cas system. Upon detecting a target sequence, the living biosensors will release thousands of signal molecules that can be detected using a lateral flow assay, similar to a consumer pregnancy or Covid-19 test. Several target DNA sequences will be used for demonstrations: urinary tract pathogens, E. coli, and Salmonella. The target uropathogens are difficult to diagnose with standard culture tests. Using single-base sequence analysis, the biosensors will subtype E. coli as likely pathogenic or likely commensal. A similar strategy will be employed to detect single-base mutations responsible for the majority of fluoroquinolone-resistant Salmonella isolates. DNA biosensing will be demonstrated in clinically relevant human samples, without the extensive purification required by other methods. The result will be a hybrid living biosensor / lateral flow assay that requires minimal sample preparation, produces rapid results, and can achieve single-base resolution. The biosensors developed in this project could find applications any time DNA monitoring is needed that is inexpensive, requires minimal sample preparation, equipment, and expertise, or takes place at the point of care. Examples include clinical diagnostics, monitoring disease outbreaks for public health, or environmental monitoring, with particular benefits where resources are limited.", "keywords": [ "Antibiotic Resistance", "Architecture", "Bacteria", "Base Sequence", "Binding", "Biological", "Biological Assay", "Biosensing Techniques", "Biosensor", "Blood", "Buffers", "COVID-19 test", "Clinic", "Clinical", "Clustered Regularly Interspaced Short Palindromic Repeats", "Colon", "Colorectal Neoplasms", "Competence", "Complex", "Coupled", "Custom", "DNA", "DNA Sequence", "DNA analysis", "Detection", "Diagnosis", "Diagnostic", "Disease Outbreaks", "Engineering", "Ensure", "Environment", "Environmental Monitoring", "Epitopes", "Equipment", "Escherichia coli", "Genetic", "Genomic DNA", "Goals", "Human", "Hybrids", "In Situ", "In Vitro", "Infection", "Lateral", "Life", "Medical", "Methods", "Monitor", "Mus", "Mutation", "Mutation Detection", "Oncogenic", "Output", "Pathogenicity", "Performance", "Pregnancy Tests", "Preparation", "Proteins", "Public Health", "Publishing", "RNA", "Rapid diagnostics", "Readability", "Reporter", "Resolution", "Resource-limited setting", "Resources", "Salmonella", "Salmonella enterica", "Sampling", "Scheme", "Science", "Sensitivity and Specificity", "Sequence Analysis", "Signal Transduction", "Signaling Molecule", "Source", "Specificity", "Sputum", "Synthetic Genes", "System", "Techniques", "Testing", "Time", "Training", "Urinary tract", "Urinary tract infection", "Urine", "Uropathogen", "Work", "base", "cancer cell", "clinical diagnostics", "clinically relevant", "cost", "diagnostic platform", "fluoroquinolone resistance", "improved", "in vivo", "interest", "lateral flow assay", "microbial", "nanoshell", "pathogen", "point of care", "point-of-care diagnostics", "screening", "tumor" ], "approved": true } }, { "type": "Grant", "id": "15678", "attributes": { "award_id": "1I01BX006894-01", "title": "NCOA7 deficiency worsens brain damage after stroke", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2025-04-01", "end_date": "2029-03-31", "award_amount": null, "principal_investigator": { "id": 32523, "first_name": "Dandan", "last_name": "Sun", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1477, "ror": "https://ror.org/05eq41471", "name": "Veterans Health Administration", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Background and Innovation: Lysosomes (with an acidic milieu of pH around 4.5) contain numerous acidic hydrolases for maintaining cellular homeostasis via the degradation of unwanted cellular components. NCOA7 (nuclear receptor coactivator 7), a member of the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) protein family, was initially implicated in the oxidative stress as oxidation resistance proteins. However, new research demonstrates that NCOA7 directly binds and modulates vacuolar H+- ATPase (V-ATPase) assembly and activity to control endolysosomal acidification. Our pilot data from SNP- edited, human stem cell-derived endothelial cells have demonstrated that allele-specific binding of the inflammatory transcription factor NF-κB to a common intronic variant SNP rs11154337 in NCOA7 controls gene expression. Namely, we found that a C/C genotype, present in ~25% of the population, promoted lower NCOA7 expression and less lysosomal acidification (Prelim Data). Global Ncoa7 transgenic knockout mice (Ncoa7-/-, KO) are viable up to 18 months of age, with comparable gross brain structure to wild-type littermate (WT). However, upon ischemic stroke, compared to WT mice, we found that Ncoa7 KO mice exhibited worsened ischemic stroke outcomes (higher mortality, worsened blood-brain barrier impairment, increased astrogliosis and microglial activation, and abnormal accumulation of myelin basic protein, MBP) (Prelim Data). Whether the above worsened ischemic stroke outcomes resulted from V-ATPase dysfunction and lysosomal de-acidification remains unknown. In this proposal, we will test our hypotheses: 1). NCOA7 plays an important role in V-ATPase activity and lysosomal function in stroke brain in a cell-specific manner; 2). NCOA7 deficient in neurons and in oligodendrocytes drives lysosomal dysfunction and oxysterol/bile acid- specific inflammation, as well as abnormal cholesterol and MBP accumulation; 3). Post-stroke administration of NCOA7 activator Compound 958 will stimulate NCOA7 activity and reduce stroke brain damage. Significance and Impact to Veterans Healthcare: Cardiovascular diseases such as hypertension and pre- hypertension are common in active US military personnel. Moreover, post-traumatic stress disorder is associated with different cardiovascular and cerebrovascular diseases in older veterans. Collectively, these are well-established risk factors for stroke. The goal of this proposal is to study cellular mechanisms underlying the worsened ischemic stroke outcomes in NCOA7 deficient conditions and to determine whether pharmacological stimulation of NCOA7 is a novel therapeutic strategy for improving acute ischemic stroke outcomes. Therefore, our proposal is closely relevant to Veterans and the VA mission. Path to translation/implementation: completion of this study will directly address our knowledge gap about role of NCOA7 in regulating lysosome function and cholesterol metabolism in the stroke brains. To explore pharmacological tools, utilizing computational modeling, we developed a novel small molecule activator of NCOA7, Compound 958, which reduced pulmonary endothelial immunoactivation and robustly improved survival of a mouse model of acute COVID-19 (Prelim Data). Our findings from this study will reveal potentials of NCOA7 as a therapeutic target for attenuating V-ATPase dysfunction in stroke brain, and efficacy of NCOA7 activator Compound 958 in stroke therapy.", "keywords": [ "Acute", "Address", "Age Months", "Alleles", "Axon", "Bile Acids", "Binding", "Blood - brain barrier anatomy", "Blood Vessels", "Brain", "Brain Diseases", "Brain Injuries", "Cardiovascular Diseases", "Catalytic Domain", "Cause of Death", "Cells", "Cerebral Ischemia", "Cerebrovascular Disorders", "Cholesterol", "Cholesterol Homeostasis", "Computer Models", "Data", "Demyelinations", "Drug Kinetics", "Endothelial Cells", "Endothelium", "Endowment", "Exhibits", "Functional disorder", "Gene Expression", "Generations", "Genotype", "Goals", "Health Care", "Heterozygote", "Homeostasis", "Hydrolase", "Hydrolysis", "Hydroxylation", "Hypertension", "Impairment", "Inflammation", "Inflammatory", "Institute of Medicine (U.S.)", "Ischemic Stroke", "Knockout Mice", "Knowledge", "Lung", "Lysosomes", "Medicine", "Military Personnel", "Mission", "Mus", "Myelin Basic Proteins", "Nerve Degeneration", "Neuroglia", "Neurological outcome", "Neurons", "Nuclear Receptors", "Oligodendroglia", "Oxidative Stress", "Pathogenesis", "Play", "Population", "Post-Traumatic Stress Disorders", "Production", "Protein Family", "Proteins", "Pulmonary Hypertension", "Recovery", "Research", "Resistance", "Risk Factors", "Role", "Scientist", "Sterols", "Stroke", "Structure", "Testing", "Transgenic Organisms", "Translations", "USP6 gene", "Variant", "Vascular Diseases", "Veterans", "acute COVID-19", "astrogliosis", "career", "cholesterol trafficking", "design", "efficacy evaluation", "glial activation", "human stem cell-derived", "improved", "innovation", "lysin", "member", "mortality", "mouse model", "neuron loss", "novel", "novel therapeutic intervention", "oxidation", "pharmacologic", "post stroke", "prehypertension", "professor", "small molecule", "stroke outcome", "stroke recovery", "stroke therapy", "therapeutic target", "tool", "transcription factor", "vacuolar H+-ATPase", "white matter" ], "approved": true } }, { "type": "Grant", "id": "14580", "attributes": { "award_id": "1R35GM153478-01", "title": "Integrating opportunistic data into respiratory disease models to enhance surveillance, explain seasonality, and reveal spatial transmission landscapes", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 12060, "first_name": "Han", "last_name": "Nguyen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-05-01", "end_date": "2029-04-30", "award_amount": 426660, "principal_investigator": { "id": 21228, "first_name": "Shweta", "last_name": "Bansal", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 181, "ror": "https://ror.org/05vzafd60", "name": "Georgetown University", "address": "", "city": "", "state": "DC", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 181, "ror": "https://ror.org/05vzafd60", "name": "Georgetown University", "address": "", "city": "", "state": "DC", "zip": "", "country": "United States", "approved": true }, "abstract": "My research program addresses fundamental questions about population-scale infectious disease dynamics and brings to light the role of social factors in these dynamics. The impact that carefully formulated and extensively validated models can have in predicting spatio-temporal disease dynamics and providing a rational assessment of alternative intervention strategies is understood by policymakers and clinical practitioners alike. However, as the COVID-19 pandemic has demonstrated, continuing to neglect socio-behavioral processes presents a critical barrier to future model development: behavioral surveillance gaps jeopardize our ability to predict pathogen emergence; a poor understanding of the feedback loops between behavior and disease hampers the forecasting of disease dynamics; and a limited appreciation of the nonlinear impacts of anti-mitigation behavior reduces hope of eliminating diseases before they take hold. At the same time, public health inequities fueled by income inequality and systemic racism pose a dire and urgent threat. To address these pressing gaps, my research team uses a multi-scale socio-behavioral disease modeling approach to integrate interacting elements of health, physical and socially-constructed environments, and community and individual behavior to predict social and spatial heterogeneities in respiratory disease burden. We develop generative and inferential models for a systematic understanding of the constant, compounding socio-behavioral processes that give rise to disease heterogeneities across individuals, communities, and systems. We also leverage opportunistic datasets to characterize behavior and disease across geography and time to resolve questions that have eluded explanation without socio-behavioral data. Our future work will advance the theory of respiratory disease dynamics with a focus on two case studies, SARS- CoV-2 and influenza, in the United States. The work will make significant contributions to our understanding of respiratory virus epidemiology, seasonality, spatial epidemiology, health inequities, and public health policy and will spur innovation for integrating large data streams into infectious disease models. These advances will generalize to improve our understanding of other respiratory, partially immunizing viruses that cause epidemics or pandemics. Our focus on the US public health system also serves as a crucial case study to characterize the consequences of intense variation across social, environmental, economic, and demographic dimensions and inform the impact of heterogeneity on data collection, model complexity, disease outcomes, and management strategies. Our work has broad implications at a time when heterogeneities will be amplified by future perturbations, including emerging diseases, climate change, and sociopolitical unrest. Understanding the mechanisms underlying the causes of epidemiological heterogeneity across space, time, and the landscape of vulnerability will help inform resource allocation, design outbreak intervention, optimize disease surveillance, strengthen health systems, and improve access to healthcare.", "keywords": [ "2019-nCoV", "Address", "Awareness", "Behavior", "Behavior Therapy", "Behavioral", "COVID-19", "COVID-19 pandemic", "Case Study", "Clinical", "Communicable Diseases", "Communities", "Data", "Data Collection", "Data Set", "Dimensions", "Disease", "Disease Outbreaks", "Disease Outcome", "Disease Surveillance", "Economics", "Effectiveness", "Elements", "Environment", "Epidemic", "Epidemiology", "Feedback", "Future", "Geography", "Health", "Health Policy", "Health system", "Heterogeneity", "Immunize", "Improve Access", "Incidence", "Income", "Individual", "Inequality", "Infection", "Influenza", "Institutional Racism", "Intervention", "Methods", "Modeling", "Monitor", "Play", "Policy Maker", "Politics", "Population", "Process", "Public Health", "Readiness", "Research", "Resource Allocation", "Respiratory Disease", "Role", "Seasons", "Severities", "Social Behavior", "System", "Time", "United States", "Variant", "Virus", "Work", "burden of illness", "climate change", "data modeling", "data streams", "design", "disease heterogeneity", "disease model", "emerging pathogen", "health care availability", "health inequalities", "improved", "infectious disease model", "innovation", "large datasets", "mathematical model", "model development", "neglect", "pandemic disease", "pathogen", "programs", "respiratory", "respiratory virus", "social", "social factors", "spatial epidemiology", "spatiotemporal", "theories", "tool", "transmission process" ], "approved": true } } ], "meta": { "pagination": { "page": 1383, "pages": 1405, "count": 14046 } } }