Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=2&sort=-id
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-id", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1419&sort=-id", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-id", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-id" }, "data": [ { "type": "Grant", "id": "15933", "attributes": { "award_id": "3U19AI118626-11S1", "title": "Respiratory pathogen-specific T cell signatures following vaccination, natural infection, and treatment", "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": 32843, "first_name": "JOSEPH J", "last_name": "BREEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-06-01", "end_date": "2027-05-31", "award_amount": 93590, "principal_investigator": { "id": 20714, "first_name": "Alessandro", "last_name": "Sette", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 777, "ror": "", "name": "LA JOLLA INSTITUTE FOR IMMUNOLOGY", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 777, "ror": "", "name": "LA JOLLA INSTITUTE FOR IMMUNOLOGY", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "– Overall The La Jolla HIPC team will focus on pathogens causing infectious diseases of the upper and lower respiratory tract that lead to substantial mortality and morbidity. Our approach is unique and innovative, as it focuses on defining immune signatures (IMS) of antigen-specific CD4 and CD8 T cells generated in response to natural infection with important respiratory pathogens such as SARS-CoV-2, Common Cold Coronaviruses (CCC), influenza, Respiratory Syncytial Virus (RSV) and Mycobacterium tuberculosis (Mtb). Likewise, our Program will investigate IMS of antigen-specific T cells generated following vaccination against a diverse array of pathogens in different platforms like attenuated pathogens (BCG, yellow fever (YF)), purified proteins (acellular Bordetella pertussis (PT) vaccines), viral vectors (J&J, SARS-CoV-2) and mRNA (Moderna and Pfizer). In Project 1, we will perform longitudinal analysis to determine persistence and plasticity of antigen-specific T cell responses following natural SARS-CoV-2 infection and vaccination. We will study T cell responses specific to SARS-CoV-2 following vaccination with different vaccine platforms in previously-unvaccinated donors, and in a longitudinal cohort of vaccinated individuals previously naturally-infected with SARS-CoV-2. In parallel studies, we will analyze T cell responses to SARS-CoV-2 in naturally-infected unvaccinated donors. We will also analyze T cell responses in two previously-enrolled cohorts who received YF and PT vaccinations; in both cohorts the natural evolution and persistence of T cell responses to CCC viruses will be investigated. In Project 2, we will perform longitudinal analysis of the IMS of Mtb-specific T cells. Here, we will build on our progress made during the previous HIPC funding period to characterize the IMS associated with latent and active TB disease as well as BCG vaccination. Specifically, we will characterize the longitudinal IMS of both active and latent TB during treatment. In parallel, we will characterize the longitudinal IMS of adults (re)vaccinated with BCG, and characterize the IMS of Mtb-specific T cells in the lung. In Project 3, we will determine the molecular properties of pathogen-specific lung tissue-resident memory T cells (TRM). Our goal is to establish a single-cell atlas of the transcriptome, epigenome, and T cell receptor (TCR) of antigen-specific lung TRM targeting common pathogens that infects the lungs such as: viral (influenza, RSV, para influenza, meta pneumovirus, SARS-CoV-2, CCC), bacterial (pneumococcus, PT, Mtb) and fungal pathogens. The longitudinal study design will enable assessment of plasticity and persistence of lung TRM cells following natural infection and vaccination. The synergy between Projects will allow the generation of cross- comparable large-scale single-cell T cell signatures for respiratory pathogens/vaccines.", "keywords": [ "2019-nCoV", "Address", "Adult", "Antigens", "Atlases", "Attenuated", "Bacille Calmette-Guerin vaccination", "Bacteria", "Blood", "Bordetella pertussis", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "Cells", "Cellular Assay", "Clinical", "Common Cold", "Communicable Diseases", "Communication", "Coronavirus", "Disease", "Enrollment", "Ensure", "Epitopes", "Evolution", "Flow Cytometry", "Funding", "Generations", "Goals", "Immune", "Immune response", "Infection", "Influenza", "Longitudinal cohort", "Lower respiratory tract structure", "Lung", "Molecular", "Morbidity - disease rate", "Mycobacterium tuberculosis", "National Institute of Allergy and Infectious Disease", "Pertussis", "Pertussis Vaccine", "Phenotype", "Play", "Pneumovirus", "Property", "Recurrence", "Resources", "Respiratory Tract Infections", "Respiratory syncytial virus", "Risk", "Role", "SARS-CoV-2 infection", "Services", "Severity of illness", "Sorting", "Streptococcus pneumoniae", "Structure of parenchyma of lung", "Systems Biology", "T cell response", "T memory cell", "T-Cell Receptor", "T-Lymphocyte", "T-Lymphocyte Subsets", "T-cell receptor repertoire", "Technology", "Time", "Tissues", "Upper respiratory tract", "Vaccinated", "Vaccination", "Vaccinee", "Vaccines", "Viral", "Viral Vector", "Virus", "Yellow Fever", "adaptive immunity", "antigen-specific T cells", "biomarker panel", "burden of illness", "cohort", "cost effective", "current pandemic", "data management", "design", "epigenome", "innovation", "longitudinal analysis", "longitudinal design", "mortality", "pathogen", "pathogenic fungus", "programs", "protein purification", "respiratory pathogen", "response", "single cell ATAC-seq", "success", "synergism", "tissue resident memory T cell", "transcriptome", "transcriptomics", "unvaccinated", "vaccine platform" ], "approved": true } }, { "type": "Grant", "id": "15932", "attributes": { "award_id": "3U24DK112340-08S1", "title": "A biochemical roadmap of exercise signal", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 44377, "first_name": "PADMA", "last_name": "MARUVADA", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-06-01", "end_date": "2027-05-31", "award_amount": 500000, "principal_investigator": { "id": 44378, "first_name": "Clary B", "last_name": "Clish", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 24074, "first_name": "ROBERT E", "last_name": "GERSZTEN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 771, "ror": "https://ror.org/04drvxt59", "name": "Beth Israel Deaconess Medical Center", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 1003, "ror": "", "name": "BROAD INSTITUTE, INC.", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Exercise is an effective intervention for both the prevention and treatment of cardiometabolic diseases, but the mechanistic underpinnings of the health benefits of exercise remain incompletely defined. Recent work highlights the importance of inter-organ circuits in mediating healthful exercise responses. We identified β- aminoisobutyric acid (BAIBA) as a novel small molecule “myokine” that increases the expression of brown adipocyte-specific genes in vitro and improves glucose disposal and decreases weight gain in mice. In humans, plasma BAIBA concentrations are increased with chronic exercise and demonstrate a strong inverse association with metabolic risk factors. Further, related efforts by our group have positioned us as leaders in characterizing within- and between-tissue molecular responses to exercise and dietary interventions. These experiences, coupled with the high translational relevance of the research problem, motivated our participation in the MoTrPAC initiative. Our team was built upon existing collaborations between Duke, Harvard and the Broad Institute with complementary strengths in metabolomics and proteomics technologies and decades of experience in cardiometabolic research. To date, we have provided a deep menu of analytical tools for targeted and non-targeted metabolomics, protein profiling, and the analysis of key protein post-translational modifications. Group members have been deeply involved in the animal and pre-COVID biochemical profiling efforts, in collaborations with other Chemical Analysis Sites (CAS) and the Bioinformatics Core to harmonize workflows, and in the working groups necessary to integrate the data. We have also played key roles in associated scholarly activities and in developing the next generation of translational investigators focused on exercise science. An additional distinction of our team is the ability to integrate new findings from MoTrPAC with ongoing genomic, proteomic and metabolomic analyses in large human cohorts and other exercise studies led by our investigators. We hypothesize that integrating the metabolomic and proteomic profiles of human tissues and blood during exercise with genetics and detailed human phenotyping will provide novel insights into the interorgan circuits and within-organ responses that mediate its salutary effects. We are deeply committed to the notion that all data generated by this multi-disciplinary consortium will be made rapidly available to the scientific community.", "keywords": [ "Adipocytes", "Aminoisobutyric Acids", "Animals", "Biochemical", "Bioinformatics core", "Blood", "COVID-19", "Cardiometabolic Disease", "Chemicals", "Chronic", "Collaborations", "Communities", "Coupled", "Data", "Dietary Intervention", "Exercise", "Genes", "Genetic", "Genomics", "Goals", "Health", "Health Benefit", "Heart Diseases", "Human", "In Vitro", "Individual", "Longevity", "Mediating", "Metabolic", "Metabolic Diseases", "Molecular", "Mus", "Organ", "Phenotype", "Plasma", "Play", "Positioning Attribute", "Post-Translational Protein Processing", "Prevention", "Proteomics", "Research", "Research Personnel", "Risk Factors", "Science", "Signal Transduction", "Site", "Technology", "Therapeutic Intervention", "Tissues", "Weight Gain", "Work", "analytical tool", "cardiometabolism", "cohort", "data integration", "effective intervention", "exercise intervention", "experience", "glucose disposal", "human tissue", "improved", "insight", "member", "metabolomics", "multidisciplinary", "next generation", "novel", "novel therapeutics", "protein profiling", "response", "small molecule", "translational scientist", "working group" ], "approved": true } }, { "type": "Grant", "id": "15931", "attributes": { "award_id": "1K99AI193238-01", "title": "Investigating the role of T cells in promoting post-acute memory deficits after COVID-19 in mice", "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": 32599, "first_name": "MICHELLE MARIE", "last_name": "ARNOLD", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-07", "end_date": "2027-06-30", "award_amount": 107995, "principal_investigator": { "id": 26728, "first_name": "Abigail Rose", "last_name": "Vanderheiden", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "Millions of individuals in the United States suffer from post-acute symptoms of COVID-19 (PASC), many of which are neurological in origin. Although SARS-CoV-2 does not cause widespread infection of the central nervous system (CNS), significant neuroinflammation, decreased adult neurogenesis, alterations in synaptic proteins, decreased total brain volume, and poor performance on tests of learning and memory have all been observed in COVID-19 patients. However, the mechanisms by which a respiratory virus is causing persistent neurological dysfunction are not well understood. Studies of PASC patients identified ongoing dysregulation of T cell responses in the serum and imaging studies confirmed that PASC patients have activated T cells in the CNS. Homeostatic T cells in the meninges are known to influence learning, memory, and anxiety-like behavior through the secretion of cytokines, however the impact of T cells on neurological symptoms after COVID-19 is unknown. Thus, I hypothesize that systemic inflammation promotes recruitment of antigen-specific T cells to the CNS after SARS-CoV-2 infection, and these cells contribute to persistent deficits in learning and memory via secretion of cytokines and other pro-inflammatory mediators. To investigate this, I will utilize my recently developed mouse model of neurological dysfunction after COVID-19, in which intranasal infection of wild-type mice with SARS-CoV-2 causes robust infection of the respiratory tract, but not the CNS, post-acute memory deficits, loss of hippocampal neurogenesis, and increased pro-inflammatory cytokines in the CNS. Preliminary data found that CD4+ T cells are recruited to the meningeal dura after infection and promote post-acute memory deficits as determined via the Novel Object recognition test. In the K99 phase of this proposal, (Aim 1) I will investigate the phenotype of CD4+ T cells in the CNS after SARS-CoV-2 infection and determine how cytokines secreted by CD4+ T cells may contribute to memory deficits using a behavioral test battery and investigation of neurogenesis and tri-synaptic circuit function. In Aim 2, I will test if T cell priming and differentiation impact pathogenicity in the CNS after COVID-19 by first, determining if antigen specificity is required for recruitment to and effector functions in the CNS and second, investigating which CD4+ T cell effector subset is driving post-acute memory deficits. In the R00 phase, I will utilize a previously established murine model of breakthrough vaccination to investigate how priming of CD4+ T cells in the periphery influences differentiation into a pathogenic CD4+ effector subset. In Aim 3, I will explore how severe, systemic inflammation may be driving recruitment of these pathogenic T cells to the CNS and which chemokine: receptor pairs are critical for this process. Combined, this project will determine the mechanisms by which pathogenic CD4+ T cells are recruited to the CNS after COVID-19 and how they promote post-acute learning and memory deficits. These data could identify fundamental mechanisms by which immunity to viral infections controls neurological function and potential druggable targets for treatment of PASC.", "keywords": [ "2019-nCoV", "Acute", "Address", "Antigens", "Attentional deficit", "Automobile Driving", "Autopsy", "Brain", "CD4 Positive T Lymphocytes", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "COVID-19", "COVID-19 patient", "COVID-19 therapeutics", "CXCL10 gene", "Cells", "Central Nervous System", "Central Nervous System Infections", "Cerebrospinal Fluid", "Clonal Expansion", "Cognitive deficits", "Data", "Development", "Disease", "Dura Mater", "Flow Cytometry", "Genetic", "Gliosis", "Hippocampus", "Immune", "Immune response", "Immunity", "Impairment", "Incidence", "Individual", "Infection", "Infection Control", "Inflammation", "Inflammation Mediators", "Inflammatory", "Investigation", "Knockout Mice", "Learning", "Location", "Long COVID", "Measures", "Mediating", "Memory", "Memory impairment", "Meningeal", "Meninges", "Mental Depression", "Microscopy", "Modeling", "Mus", "Myeloid Cell Activation", "Myeloid Cells", "Nervous System Physiology", "Neurodegenerative Disorders", "Neurologic", "Neurologic Dysfunctions", "Neurologic Symptoms", "Organ", "Pathogenicity", "Patients", "Performance", "Peripheral", "Phase", "Phenotype", "Population", "Process", "Proteins", "Recovery", "Respiratory Tract Infections", "Risk", "Risk Reduction", "Role", "SARS-CoV-2 B.1.351", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "Serum", "Severity of illness", "Sorting", "Specificity", "Symptoms", "Synapses", "System", "T cell response", "T-Cell Activation", "T-Cell Depletion", "T-Cell Immunologic Specificity", "T-Lymphocyte", "T-Lymphocyte Subsets", "T-cell receptor repertoire", "Testing", "United States", "Vaccinated", "Vaccination", "Viral Respiratory Tract Infection", "Virus", "Virus Diseases", "Wild Type Mouse", "acute COVID-19", "acute symptom", "adult neurogenesis", "antigen-specific T cells", "anxiety-like behavior", "behavior test", "brain volume", "candidate identification", "chemokine", "comparison control", "conditional knockout", "congenic", "cytokine", "druggable target", "effector T cell", "experience", "experimental study", "imaging study", "improved", "insight", "microscopic imaging", "mouse model", "neural circuit", "neural correlate", "neurogenesis", "neuroinflammation", "neuropsychiatric disorder", "novel", "object recognition", "performance tests", "post SARS-CoV-2 infection", "prevent", "receptor", "recruit", "respiratory virus", "single-cell RNA sequencing", "systemic inflammatory r" ], "approved": true } }, { "type": "Grant", "id": "15930", "attributes": { "award_id": "1R24AI192250-01", "title": "Repository of Monoclonal Antibodies (RoMA) against Hamster and Guinea Pig Proteins", "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": 32843, "first_name": "JOSEPH J", "last_name": "BREEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-24", "end_date": "2030-06-30", "award_amount": 835137, "principal_investigator": { "id": 44375, "first_name": "JAMES A", "last_name": "DUTY", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44376, "first_name": "Domenico", "last_name": "Tortorella", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3386, "ror": "", "name": "ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Small animal models are ideal to study diverse infectious and inflammatory diseases with mice being a widely used model system due to the well-characterized immune response and availability of reagents. Yet, the drawbacks of the mouse animal model are that it does not mimic many diseases due to the lack of clinical symptoms, differences in immune activation, and non-susceptible to infection of many pathogens. In fact, ferrets, Guinea pigs, and hamsters are a more suited animal model for numerous infectious pathogens including bat coronaviruses (SARS-CoV and SARS-CoV-2), influenza virus, and respiratory syncytial virus, respectively; yet, the lack of reagents that define the immune and inflammatory responses in ferrets, Guinea pigs, and hamsters prevent their utilization to comprehensively understand disease pathology and effectiveness of therapeutics and vaccines. Thus, there is a severe reagent gap for monoclonal antibodies against immune and inflammatory markers of ferrets, Guinea pigs, and hamsters to use these animal models in infectious disease studies. The main objective of the R24 application is to create a Repository of Monoclonal Antibodies (RoMA) for use in small animal models for evaluating infectious and inflammatory disorders fulfilling a major reagent gap in the scientific community. We hypothesize that reagents that monitor the immune response in hamster and Guinea pig model systems will be widely used in infectious disease model systems to predict disease progression and effectiveness of vaccines and therapeutics in human disease. A panel of monoclonal antibodies will be generated upon completion of the following aims: Aim 1: Develop antibodies targeting hamster and guinea pig surface markers on the respective immune cells. The hamster has become an excellent model for respiratory pathogens including SARS-corona viruses, Rift Valley fever, and Clostridium difficile; while the Guinea pig animal model provides insight into numerous infection and transmission models such as influenza virus and herpesviruses. Aim 2: Identify and generate monoclonal antibodies to hamster and guinea pig immune cell activation markers. We plan to identify and generate monoclonal antibodies to activated immune cell immune markers of hamster and Guinea pigs. These activated biomarkers will consist of previously characterized human and mouse orthologs that likely function in immune regulation. We expect to generate a total of 50 monoclonal antibodies (25 anti-hamster and 25 anti-Guinea pig proteins) over the 5-year grant period that will be available to the scientific community. These antibodies will be essential for evaluating the immune and inflammatory responses in the hamster and Guinea pig animal models.", "keywords": [ "2019-nCoV", "Animal Model", "Animals", "Antibodies", "B-Lymphocytes", "Bacterial Infections", "Biological Markers", "Biological Models", "Blood", "Cavia", "Cell surface", "Cells", "Chiroptera", "Clinical", "Clinical Pathology", "Clostridium difficile", "Communicable Diseases", "Communities", "Coronavirus", "Dendritic Cells", "Disease", "Disease Progression", "Evaluation", "Ferrets", "Grant", "Hamsters", "Herpesviridae", "Human", "Immune", "Immune System Diseases", "Immune response", "Immunologic Factors", "Immunologic Markers", "Immunologic Monitoring", "Immunologic Stimulation", "Infection", "Infectious Agent", "Inflammatory", "Inflammatory Response", "Laboratories", "Lymphoid", "Lymphoid Cell", "Macrophage", "Modeling", "Monoclonal Antibodies", "Mouse Protein", "Mus", "Myelogenous", "Myeloid Cells", "Natural Killer Cells", "Orthologous Gene", "Oryctolagus cuniculus", "Pathology", "Phenotype", "Physiology", "Prevention", "Proteins", "R24", "Rattus", "Reagent", "Research", "Respiratory syncytial virus", "Rift Valley Fever", "SARS coronavirus", "Scientific Advances and Accomplishments", "Spleen", "Surface", "Symptoms", "T-Lymphocyte", "Therapeutic", "Transgenic Animals", "Treatment Efficacy", "United States National Institutes of Health", "Vaccines", "Virus Diseases", "Zebrafish", "animal model selection", "cost", "cross reactivity", "design", "diagnostic tool", "guinea pig model", "human disease", "immune activation", "immunological status", "immunoregulation", "infectious disease model", "inflammatory marker", "influenzavirus", "insight", "monocyte", "neutrophil", "next generation sequencing", "nonhuman primate", "pathogen", "preclinical study", "prevent", "programs", "repository", "respiratory pathogen", "response", "therapeutic effectiveness", "transmission process", "vaccine effectiveness", "vaccine efficacy" ], "approved": true } }, { "type": "Grant", "id": "15929", "attributes": { "award_id": "1R21AI188112-01", "title": "The role of the mRNA-based or Newcastle disease virus (NDV)-based vaccine platform in mucosal B cell priming and recirculation", "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": 44341, "first_name": "MORIAH JOVITA", "last_name": "CASTLEMAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-23", "end_date": "2027-06-30", "award_amount": 464750, "principal_investigator": { "id": 44374, "first_name": "Weina", "last_name": "Sun", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3386, "ror": "", "name": "ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The experiences and lessons learned from the COVID-19 pandemic geared our interests towards investigating the mechanism of action of different vaccine platforms and vaccination strategies that aim to induce long-lasting protective systemic and mucosal immune responses to prevent disease and transmission via the mucosal route. Dr. Weina Sun co-developed a Newcastle disease virus vector (NDV)-based COVID-19 vaccine that can be used either as an injectable inactivated whole virion vaccine or a live intranasal vaccine, the latter of which can elicit mucosal immune responses as a “stand-alone” vaccine platform. In naïve mice, a 2-dose regimen of intranasal NDV-based vaccine induced a high level of mucosal IgA antibodies. In mice that were pre- vaccinated with mRNA-LNP COVID-19 vaccines via the intramuscular route, a third intranasal NDV booster also substantially enhanced nasal wash antigen-specific IgA. By closely examining samples obtained from different anatomical mucosal sites in mRNA-LNP vaccinated mice without the NDV booster, spike-specific IgA were detected in nasal wash, intestinal lavage as well as vaginal lavage, among which Intestinal lavage contained the highest levels of IgA. Dr. Jennifer Gommerman is an immunologist with special interests studying mucosal B lymphocytes. In humans, she developed methods to detect salivary antibodies. While SARS-CoV-2 infection induces high levels of spike-specific salivary IgG and IgA, salivary IgG are also abundantly found after intramuscular 2-dose mRNA vaccinations. Intriguingly, some of the mRNA-vacccinated individuals developed and maintained modest salivary secretory-IgA that were resistence to decay after a 2-dose mRNA vaccine. Given that both in mice and humans, mucosal antigen-specific IgA were detected after mRNA-LNP vaccination, we hypothesize that mRNA-LNP vaccines can prime de novo mucosal B cells that are close to the administration sites, which are able to recirculate to other mucosal surfaces. Consequently, a further mucosal booster vaccine, such as the intranasal live NDVvaccine, would be able to recall pre-exisiting memory B cell responses. We will follow two specific aims to test our hypothesis, utilizing mRNA-LNP vaccine and NDV vaccine encoding the spike of Beta variant as a proof of concept: (Aim 1) To examine temporal and spatial dynamics of antigen-specific IgA and IgG secreting B cells in the mucosa-associated lymphoid tissues after mRNA and NDV vaccination in mice. (Aim 2) To track circulation of antigen-specific mucosal B cells in photoconvertible Kikume mice after mRNA prime followed by NDV vaccination or infection by flowcytometry. The proposed work entails innovative approaches and mouse models to test our hypothesis. We believe the outcomes of the study can inform the mechanism of action of not only mRNA-based and NDV-based SARS-CoV-2 vaccines, but also the same types of vaccines against other respiratory or enteric viral pathogens, in which mucosal antibody responses plays a critical role to mitigate virus infection and transmission.", "keywords": [ "Anatomy", "Animals", "Antibodies", "Antibody Response", "Antigens", "B-Cell Development", "B-Lymphocytes", "Biological Assay", "C57BL/6 Mouse", "COVID-19 pandemic", "COVID-19 vaccine", "Cells", "Cessation of life", "Circulation", "Conceptions", "Disease", "Dose", "Enteral", "Flow Cytometry", "Future", "Genetic", "Human", "Immunize", "Immunoglobulin A", "Immunoglobulin G", "Immunoglobulin M", "Immunologist", "Individual", "Infection", "Inguinal lymph node group", "Injectable", "Intestines", "Intramuscular", "Lavage", "Left", "Lymphoid", "Measures", "Memory B-Lymphocyte", "Messenger RNA", "Methods", "Mucosal Immune Responses", "Mucous Membrane", "Mus", "Nasal Lavage Fluid", "Newcastle disease virus", "Oncolytic", "Outcome Study", "Phase I Clinical Trials", "Plasma", "Plasma Cells", "Play", "RNA vaccination", "RNA vaccine", "Regimen", "Research", "Resistance", "Respiratory System", "Role", "Route", "SARS-CoV-2 B.1.351", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Safety", "Salivary", "Sampling", "Secondary Immunization", "Secretory Immunoglobulin A", "Shapes", "Site", "Spleen", "Surface", "Testing", "Transgenic Organisms", "Upper respiratory tract", "Vaccinated", "Vaccination", "Vaccines", "Vagina", "Vaginal Douching", "Variant", "Viral Vector", "Virion", "Virus Diseases", "Wild Type Mouse", "Work", "animal data", "antigen binding", "booster vaccine", "breakthrough infection", "enzyme linked immunospot assay", "experience", "human data", "innovation", "interest", "mRNA lipid nano particle vaccine", "mouse model", "mucosa-associated lymphoid tissue", "mucosal site", "mucosal vaccine", "pathogenic virus", "pre-clinical", "prevent", "receptor", "research clinical testing", "respiratory", "response", "spatiotemporal", "success", "tool", "transmission process", "urogenital tract", "vaccination strategy", "vaccine development", "vaccine platform", "vector", "vector vaccine", "vector-based vaccine", "viral transmission" ], "approved": true } }, { "type": "Grant", "id": "15928", "attributes": { "award_id": "1R03DA062573-01A1", "title": "Vitamin C protect against nicotine induced lung ailment", "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": 44372, "first_name": "GUIFANG", "last_name": "LAO", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-15", "end_date": "2027-06-30", "award_amount": 78500, "principal_investigator": { "id": 44373, "first_name": "VEEDAMALI S", "last_name": "SUBRAMANIAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 971, "ror": "", "name": "UNIVERSITY OF CALIFORNIA-IRVINE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Smoking has been demonstrated to induce oxidative stress, which is compounded with significantly reduced antioxidant availability, increased production of inflammatory cytokines as well as neutrophilic infiltration that are implicated in pathogenic processes in the lungs. Additionally, studies involving mice exposed to cigarette smoke reveal impaired pulmonary anti-bacterial and anti-viral defenses in response to infections. Other research has found that smokers also exhibit increased susceptibility to infections including influenza and SARS-CoV2. Investigations concerning the harmful effects that tobacco use exerts to lower bodily defenses are undeniably urgent, particularly those that address strategies for amelioration of smoking-induced health risks. Nicotine is the main component among the thousands of chemicals in all tobacco products including e-cigarettes. Nicotine binds to a family of nicotinic acetylcholine receptors (nAChRs) like acetylcholine (ACh). nAChRs are highly expressed in the lung fibroblasts and epithelial cells. Nicotine functions as an immunomodulator and has been reported to impair the immune response of smokers to infections. Vitamin C (vitC; ascorbic acid: AA) is an essential water- soluble vitamin with known respiratory health enhancing properties. Humans cannot synthesize vitC endogenously and thus obtain it from dietary sources via intestinal absorption. Dietary vitC is absorbed from the intestine via carrier-mediated sodium-dependent vitC transporters (SVCT1 and SVCT2, the products of the SLC23A1 and SLC23A2 genes, respectively). Low plasma levels of vitC have been found in patients with viral infections and other critical illnesses. Many previous studies have highlighted the role of vitC in protection against lung infections. Administration of vitC to patients with pneumonia, for example, can reduce the severity and duration of the disease. Pneumonia and influenza infections and related pathologies are also more severe in Gulo KO mice (a mouse model that cannot synthesize vitC endogenously, similar to humans). Both smokers and passive smokers have lower plasma and leukocyte vitC levels than non-smokers. Mean serum concentrations of vitC in adults who smoke have been found to be one-third lower than those of non-smokers. Our preliminary studies showed that nicotine reduces the functional expression of vitC transporters in the intestine and lung epithelial cells. We therefore hypothesize that nicotine induced vitC deficiency/insufficiency is a major factor in increasing the risk of respiratory viral infections in smokers. To test this hypothesis we propose two specific aims: Aim 1: To determine the mechanisms underlying nicotine-mediated impaired uptake of vitC by intestinal and lung epithelial cells using in vitro and in vivo models. Aim 2: To determine whether vitC supplementation is able to overcome the increased susceptibility to viral infections induced by nicotine. The expected outcomes of this project will advance our knowledge regarding the changes in uptake of vitC in the intestine and in the lungs, which is essential to develop novel therapeutics to improve vitC deficiency and insufficiency while also addressing ensuing lung viral infections and injury found in smoking population.", "keywords": [ "2019-nCoV", "Acetylcholine", "Acute", "Address", "Adult", "Affect", "Anti-Bacterial Agents", "Antioxidants", "Applications Grants", "Ascorbic Acid", "Ascorbic Acid Deficiency", "Binding", "Cells", "Cessation of life", "Chemicals", "Complex Mixtures", "Critical Illness", "Data", "Dendritic Cells", "Disease", "Distress", "Electronic cigarette", "Epithelial Cells", "Epithelium", "Evolution", "Exhibits", "Family", "Fibroblasts", "Genes", "Glutathione", "Gulo", "Hazardous Substances", "Health", "Human", "Immune response", "Immunity", "Immunomodulators", "Immunosuppression", "Impairment", "In Vitro", "Infection", "Inflammatory", "Influenza", "Injury", "Intestinal Absorption", "Intestines", "Investigation", "Joints", "Knockout Mice", "Knowledge", "Leukocytes", "Lung", "Lung infections", "Macrophage", "Mediating", "Micronutrients", "Modeling", "Molecular", "Mus", "Neutrophil Infiltration", "Nicotine", "Nicotinic Receptors", "Outcome", "Oxidative Stress Induction", "Pathogenicity", "Pathology", "Patients", "Pilot Projects", "Plasma", "Pneumonia", "Population", "Positioning Attribute", "Predisposition", "Process", "Production", "Property", "Pulmonary Inflammation", "Reporting", "Research", "Risk", "Role", "Serum", "Severities", "Site", "Smoke", "Smoker", "Smoking", "Sodium", "Source", "Supplementation", "Testing", "Tobacco smoke", "Tobacco use", "United States", "Viral", "Viral Genes", "Viral Respiratory Tract Infection", "Virus Diseases", "Vitamins", "Water-Soluble Vitamin", "absorption", "cigarette smoking", "cytokine", "dietary", "disability", "exposure to cigarette smoke", "fitness", "illness length", "immune modulating agents", "immune system function", "improved", "in vivo", "in vivo Model", "influenza infection", "lung injury", "mouse model", "new therapeutic target", "nicotine exposure", "non-smoker", "novel therapeutics", "prevent", "pulmonary", "respiratory health", "response", "sodium DEPENDENDENT vitamin C transporter 1", "sodium-dependent vitamin C transporter 2", "tobacco products", "uptake" ], "approved": true } }, { "type": "Grant", "id": "15927", "attributes": { "award_id": "1U01DA063078-01", "title": "A binational cohort of the intersection between substance use, HIV, and associated comorbidities among people who inject drugs in San Diego, CA", "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": 44370, "first_name": "SHEBA KING", "last_name": "DUNSTON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-15", "end_date": "2030-05-31", "award_amount": 2437310, "principal_investigator": { "id": 23320, "first_name": "STEFFANIE A.", "last_name": "STRATHDEE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 760, "ror": "https://ror.org/0168r3w48", "name": "University of California, San Diego", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 44371, "first_name": "Britt", "last_name": "Skaathun", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2637, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN DIEGO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "We will prospectively study the intersection between substance use, HIV and related co-morbidities in a cohort of people who use drugs (PWUD) in San Diego County (SD). For >25 years, Strathdee has studied the epidemiology of HIV and related co-infections among PWUD across North America, with N=500-1000 and annual retention ≥90%. Since 2020, our La Frontera I cohort situated on the U.S.-Mexico border has documented the highest HIV and HCV incidence among people who inject drugs in North America. Currently, HIV prevalence among former injectors in SD is 16% compared to 10% among current injectors. Consistent with other U.S. cities, we observed a dramatic shift from injection to non-injection of opiates in recent years, leading us to propose cohort expansion to non-injectors. Due to our location on a major drug trafficking corridor, we observe a wide range of substances (e.g., heroin, fentanyl, methamphetamine, xylazine, benzodiazepines). We previously leveraged La Frontera I to evaluate initiatives to improve uptake of PrEP, COVID-19 testing and vaccination. We propose: 1) To characterize trends and predictors of use of established and emerging drugs, drug use transitions (e.g., shifts from IDU to non-IDU & vice versa) and their impact on HIV incidence and utilization of HIV prevention and treatment. 2) To study prevalence and incidence of the following co-morbidities and their relationship to HIV incidence and utilization of HIV prevention and treatment: i) HCV; ii) STIs (i.e., syphilis, gonorrhea, Chlamydia, MPox), iii) neurobehavioral disturbances. 3) To evaluate the influence of structural interventions on HIV-related risk behaviors and utilization of HIV prevention and treatment including: i) new homelessness policies; ii) drug checking services; iii) vending machines. 4) To contribute to a shared database and biorepositories that serve as a platform for collaborations with end users and community partners. To meet these aims, we will continue to follow PWUD from La Frontera I who are actively using illicit substances, replenishing to arrive at 500 PWID and 500 PWUD (non-injectors) for a total sample of 1000. This will include subgroups vulnerable to HIV in SD (e.g., sex workers, people experiencing homelessness) among whom we expect 52 HIV seroconversions after 5 years of follow-up. Our cohort will include at least 50 PWUD living with HIV who will provide samples for viral load, sequencing and biobanking. All participants will undergo semi-annual interviews and specimen collection. SD is designated as a high priority jurisdiction for the Ending the HIV Epidemic Initiative (EHE) and a high intensity drug trafficking area by the DEA. La Frontera II leverages NIH-funded T32s, the California NeuroHIV Tissue Network, Last Gift Study brain/tissue repositories and the PREPARE Institute which tracks emerging and re-emerging infectious disease threats. Our work is aligned with priorities identified by RFA-DA-25-003, the NIH Office of AIDS Research and the EHE.", "keywords": [ "AIDS prevention", "Area", "Benzodiazepines", "Biological", "Border Crossings", "Brain", "COVID-19", "COVID-19 testing", "COVID-19 vaccination", "California", "Chlamydia", "Cities", "Collaborations", "County", "Coupled", "Drug usage", "Drug user", "Emerging Communicable Diseases", "Environmental Exposure", "Epidemic", "Epidemiology", "Fentanyl", "Functional disorder", "Funding", "Gifts", "Goals", "Gonorrhea", "HIV", "HIV Seropositivity", "HIV risk", "HIV/HCV", "Harm Reduction", "Health", "Hepatitis C Incidence", "Hepatitis C virus", "Heroin", "Homelessness", "Incidence", "Infectious disease threat", "Injecting drug user", "Injections", "Intervention", "Interview", "Lived experience", "Location", "Meta-Analysis", "Methamphetamine", "Mexico", "Modeling", "Molecular Epidemiology", "Monkeypox", "Mood Disorders", "NIH Office of AIDS Research", "National Institute of Drug Abuse", "Needle Sharing", "Neurocognitive", "North America", "Opioid", "Participant", "Pattern", "Persons", "Pharmaceutical Preparations", "Policies", "Positioning Attribute", "Postdoctoral Fellow", "Prevalence", "Prevalence Study", "Prospective Studies", "Prospective cohort", "Prospective cohort study", "Research", "Research Priority", "Risk Behaviors", "Sample Size", "Sampling", "Services", "Statutes and Laws", "Subgroup", "Syphilis", "Testing", "Tissue Banks", "Tissues", "Travel", "United States National Institutes of Health", "Viral Load result", "Visit", "Work", "Xylazine", "biobank", "co-infection", "cohort", "community partners", "comorbidity", "data sharing", "end of life", "epidemiology study", "experience", "fentanyl use", "follow-up", "housing instability", "improved", "member", "neuroAIDS", "neurobehavioral", "novel", "pre-doctoral", "pre-exposure prophylaxis", "prevention service", "recruit", "repository", "response", "retention rate", "sample collection", "seroconversion", "severe mental illness", "sex", "shared database", "sociodemographics", "substance use", "syndemic", "synthetic drug", "systematic review", "trafficking", "transmission process", "treatment services", "trend", "uptake" ], "approved": true } }, { "type": "Grant", "id": "15926", "attributes": { "award_id": "1R13CA301730-01", "title": "CSHL 2025 Conference on Eukaryotic mRNA Processing", "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": 44262, "first_name": "RUIBAI", "last_name": "LUO", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-01", "end_date": "2026-06-30", "award_amount": 15000, "principal_investigator": { "id": 23978, "first_name": "DAVID J.", "last_name": "STEWART", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [ { "id": 992, "ror": "https://ror.org/02qz8b764", "name": "Cold Spring Harbor Laboratory", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3401, "ror": "", "name": "COLD SPRING HARBOR LABORATORY", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The proposed conference on “Eukaryotic mRNA Processing” will convene scientists studying various aspects of mRNA processing, transport, turnover and their roles in human diseases. Major advances have recently been made in all these areas, and the proposed conference will be a timely event for discussing the latest unpublished results and exchanging ideas, thereby fostering new developments in this rapidly moving field. The proposed conference will be the fifteenth meeting in the series that is held every other year at Cold Spring Harbor Laboratory. The most recent meeting was held in August 2023 and attracted 435 scientists internationally, who are actively investigating various aspects of messenger RNA maturation in eukaryotic cells using genetic, biochemical, molecular, cell biological, and computational approaches. The 2025 meeting will be held in person with a virtual audience for broadening access and for those that cannot attend in person. As in the previous meetings, a major focus of the 2025 meeting will be on nuclear events in mRNA maturation, including mRNA splicing and polyadenylation, the connections between transcription and mRNA maturation steps, the roles of mRNA processing events in the biology of viruses, the application of informatics and genome-wide approaches to the analysis of RNA processing, as well as the relevance of mRNA processing to the etiology of cancer and other diseases. We also expect relevant and timely contributions on topics related to the new coronavirus variant SARS-CoV-2, in particular on the experimental vaccines based on messenger RNA. The meeting will include two keynote lectures, eight plenary oral sessions and two poster sessions. Oral sessions will include ten or five 12-minute talks, respectively, with additional time for discussion. In response to major developments in the fields of RNA modification and the roles of RNA structure in processing, we have expanded the sessions devoted to these topics; this adaptability to the major movements in the field helps keep this meeting at the cutting edge and ensures that we will draw participants from traditional as well as emerging areas of RNA research. This subdivision, successfully piloted at the 2019 meeting, allows a broader representation of scientific fields. As always, except for the two keynote lectures, all speakers will be selected on the basis of the submitted abstracts, which encourages active participation by junior scientists. We will particularly encourage presentation of unpublished work by the students and postdoctoral fellows who are leading these projects, as has traditionally been a hallmark and a unique strength of the Cold Spring Harbor meetings.", "keywords": [ "Acceleration", "Architecture", "Area", "Back", "Binding", "Biochemical", "Biological", "Biology", "Cancer Etiology", "Cancer Model", "Cell Physiology", "Cells", "Communities", "Complement", "DNA Sequence", "Data", "Defect", "Development", "Disease", "Emerging Technologies", "Ensure", "Environment", "Eukaryota", "Eukaryotic Cell", "Event", "Faculty", "Fostering", "Future", "Gene Expression Regulation", "Genes", "Genetic", "Genetic Transcription", "Goals", "Human", "Individual", "Industrialization", "Informatics", "Inherited", "International", "Interruption", "Introns", "Knowledge", "Laboratories", "Location", "Malignant Neoplasms", "Messenger RNA", "Methodology", "Modification", "Molecular", "Movement", "Nervous System Disorder", "Nuclear", "Nuclear Accidents", "Oncogenic", "Oral", "Organism", "Participant", "Persons", "Physiological", "Play", "Polyadenylation", "Postdoctoral Fellow", "Process", "Property", "Proteins", "RNA", "RNA Processing", "RNA Splicing", "RNA analysis", "Reaction", "Regulation", "Regulatory Pathway", "Request for Applications", "Research", "Research Institute", "Research Personnel", "Role", "SARS-CoV-2 variant", "Scientist", "Seasons", "Series", "Shapes", "Structure", "Students", "Syndrome", "Therapeutic", "Time", "Untranslated RNA", "Vaccines", "Virus", "Yeasts", "cell growth", "computing resources", "disease-causing mutation", "genetic approach", "genome editing", "genome resource", "genome-wide", "graduate student", "human disease", "insight", "interest", "lectures", "mRNA Precursor", "man", "meetings", "member", "mouse model", "new technology", "next generation", "novel coronavirus", "posters", "response", "skills", "success", "symposium", "synergism", "therapeutic RNA", "tool", "unpublished works", "virtual" ], "approved": true } }, { "type": "Grant", "id": "15925", "attributes": { "award_id": "1R21AI187845-01A1", "title": "Determining the role of 90K on SARS-CoV-2", "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": "2025-07-14", "end_date": "2027-06-30", "award_amount": 437895, "principal_investigator": { "id": 7522, "first_name": "Spyridon", "last_name": "Stavrou", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 856, "ror": "", "name": "STATE UNIVERSITY OF NEW YORK AT BUFFALO", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 856, "ror": "", "name": "STATE UNIVERSITY OF NEW YORK AT BUFFALO", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a newly discovered coronavirus that is responsible for the current pandemic that is plaguing the world and has resulted in millions of dead. Due to the recent emergence of this viral pathogen, there is a dearth of information regarding SARS-CoV-2 infection and the role of cellular host factors associated with it. A better understanding of SARS-CoV-2 infection and the host factors involved with it is necessary for the development of SARS-CoV-2-directed therapeutics. A factor that has been associated with antiviral activity, yet its antiviral mechanism is not elucidated is galectin-3-binding-protein (LGALS3BP/90K). 90K is a secreted glycoprotein that is upregulated during viral infections and is an interferon stimulated gene. Despite the fact that 90K is an interferon stimulated gene, very little is known about its contribution to the antiviral defense of the cell. It is suggested that 90K affects human immunodeficiency virus (HIV) virion biogenesis in a process that is not yet elucidated. Moreover, the antiviral role of 90K has never been studied in other virus families outside of retroviruses. This proposal investigates the role of 90K on SARS-CoV- 2 infection. The goal of this proposal is to provide mechanistic evidence on the effect of 90K during SARS-CoV- 2 infection. Furthermore, many host genes that target viral infections are antagonized by virally encoded genes. There are currently no viral genes known to counteract 90K. SARS-CoV-2 encodes a number of viral accessory proteins, whose function is largely unknown. Therefore, another aspect of this proposal is to identify the mechanism by which SARS-CoV-2 accessory proteins counteract 90K. This study will elucidate the role of 90K during SARS-CoV-2 infections, as a better understanding of host cellular factors that target SARS-CoV-2 is needed and will provide novel valuable information regarding the role of SARS-CoV-2 encoded genes. In conclusion, the identification of host genes that target SARS-CoV-2 infection and their viral antagonists provide possible new targets for the development of SARS-CoV-2 pharmaceutical treatments.", "keywords": [ "2019-nCoV", "Acute Respiratory Distress Syndrome", "Affect", "Ageusia", "Binding", "Binding Proteins", "Biogenesis", "COVID-19 pandemic", "COVID-19 therapeutics", "Cell Physiology", "Cell Surface Receptors", "Cell membrane", "Cells", "Cessation of life", "Coronavirus", "Coughing", "Data", "Development", "Elderly", "Excision", "Family", "Fever", "Galectin 3", "Gene Targeting", "Genes", "Glycoproteins", "Goals", "HIV", "Impairment", "Infection", "Integration Host Factors", "Interferons", "LGALS3BP gene", "Learning", "Malaise", "Malignant Neoplasms", "Mediating", "Membrane", "Multiple Organ Failure", "Mutation", "Names", "Persons", "Pharmaceutical Preparations", "Pharmacologic Substance", "Plasma Cells", "Process", "Prognosis", "Proteins", "RNA Viruses", "Retroviridae", "Role", "SARS-CoV-2 infection", "SARS-CoV-2 inhibitor", "SARS-CoV-2 spike protein", "Shortness of Breath", "Smell Perception", "Therapeutic", "Viral", "Viral Genes", "Viral Physiology", "Viral Proteins", "Virion", "Virus", "Virus Assembly", "Virus Diseases", "antagonist", "common symptom", "current pandemic", "domain mapping", "emerging virus", "env Gene Products", "exosome", "experimental study", "in vitro Assay", "member", "novel", "pathogenic virus", "respiratory", "targeted treatment", "therapeutic development" ], "approved": true } }, { "type": "Grant", "id": "15924", "attributes": { "award_id": "1R21AI190938-01", "title": "Identification and enrichment of signature regions of antimicrobial resistant pathogen genomes for wastewater disease surveillance", "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": 32875, "first_name": "INKA I", "last_name": "SASTALLA", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-24", "end_date": "2027-06-30", "award_amount": 421673, "principal_investigator": { "id": 44369, "first_name": "Lauren", "last_name": "Stadler", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3400, "ror": "", "name": "RICE UNIVERSITY", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Antimicrobial resistance is recognized as a global public health threat that makes infections more difficult to treat and increases the risk of other medical procedures. Global and local surveillance of antimicrobial resistance is critical to understanding transmission of resistant pathogens, detecting the emergence of resistance mechanisms, and mitigating the spread of resistant pathogens. Wastewater surveillance represents a powerful, resource-efficient, and comprehensive approach for population-level surveillance of infectious diseases. It has been widely applied to track COVID-19 and other respiratory virus levels in communities, as well as identify circulating variants. However, wastewater surveillance of antimicrobial resistant pathogens has not been widely implemented because of specific challenges that limit its actionability (i.e., the direct use of the surveillance data to inform public health action). This is because antimicrobial resistance is ubiquitous in the environment and even clinically-important antibiotic resistance genes (ARGs) are abundant and widespread in wastewater. Thus, previous approaches that quantified ARGs generated information that was not specific to antimicrobial resistant pathogens. This proposal focuses on the development of foundational computational tools and laboratory methods necessary to identify and detect signature regions of antimicrobial resistant pathogens for wastewater surveillance. Signature regions are defined as genomic regions that are conserved in a pathogen strain but not found in neighboring strains or other genomes. We propose to develop a genomic language model approach to identify signature regions of target antimicrobial resistant pathogens. This will be integrated with a fully automated design pipeline for quantitative assay design. On the wet lab side, we will use microdroplet encapsulation of wastewater microbes to do high-throughput enrichment and isolation of antimicrobial resistant bacteria. This approach will enable sensitive and specific detection of antimicrobial resistant pathogens by encapsulating individual cells and assaying them for signature regions using digital droplet PCR. The proposed computational and laboratory tools will result in software and wet lab methodologies that can be used by public health laboratories and wastewater surveillance programs for specific and sensitive antimicrobial resistance monitoring. Software, assays, and protocols will be made publicly available and can also be applied for other pathogen targets. Advancing the actionability of antimicrobial resistance wastewater monitoring has the potential to enable the prediction of outbreaks, forecast hospitalizations, guide treatment decisions, understand transmission, and evaluate mitigation strategies for antimicrobial resistant infections.", "keywords": [ "2019-nCoV", "Adoption", "Antibiotic Resistance", "Antimicrobial Resistance", "Behavior", "Biological Assay", "COVID-19", "Cells", "Circulation", "Cities", "Classification", "Clinical", "Communicable Diseases", "Communities", "Complement", "Complex", "Computer software", "Computing Methodologies", "Death Rate", "Decision Making", "Detection", "Development", "Disease Surveillance", "Emulsions", "Encapsulated", "Environment", "Extended spectrum Beta lactamase producing Escherichia coli", "Extended-spectrum β-lactamase", "Genes", "Genome", "Genomic Segment", "Genomics", "Goals", "Health", "Health Care Costs", "Health Care Facility", "Health Care Systems", "Hospitalization", "Hospitals", "Individual", "Infection", "Influenza", "Intervention", "Klebsiella pneumoniae", "Knowledge", "Laboratories", "Language", "Length of Stay", "Literature", "Medical", "Methodology", "Methods", "Microbe", "Microfluidics", "Mobile Genetic Elements", "Modeling", "Monitor", "Outcome", "Pathogenicity", "Patient Care", "Persons", "Plasmids", "Population", "Prevalence", "Procedures", "Protocols documentation", "Pseudomonas aeruginosa", "Public Health", "Reporting", "Research", "Resistance", "Resources", "Respiratory syncytial virus", "Risk", "Sampling", "Sensitivity and Specificity", "Side", "Surveillance Program", "Technology", "Vancomycin Resistance", "Vancomycin resistant enterococcus", "Vancomycin-resistant S. aureus", "Variant", "Virus", "antimicrobial resistant infection", "antimicrobial resistant pathogen", "bacterial resistance", "carbapenem resistance", "carbapenemase", "clinical care", "clinical risk", "community transmission", "computational pipelines", "computerized tools", "design", "detection limit", "droplet digital PCR", "genomic signature", "improved", "metagenomic sequencing", "methicillin resistant Staphylococcus aureus", "microbial community", "microbial host", "outbreak prediction", "pathogen", "pathogen genome", "public health intervention", "resistance gene", "resistance mechanism", "resistant strain", "respiratory virus", "surveillance data", "tool", "transmission process", "wastewater monitoring", "wastewater samples", "wastewater surveillance" ], "approved": true } } ], "meta": { "pagination": { "page": 2, "pages": 1419, "count": 14184 } } }