Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1405&sort=-program_reference_codes
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-program_reference_codes", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=-program_reference_codes", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1406&sort=-program_reference_codes", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1404&sort=-program_reference_codes" }, "data": [ { "type": "Grant", "id": "11586", "attributes": { "award_id": "5R21AI163720-02", "title": "Immunoproteasome-Mediated Inflammation in Coronavirus Respiratory Infection", "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": 7248, "first_name": "Wendy F.", "last_name": "Davidson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-16", "end_date": "2024-04-30", "award_amount": 195000, "principal_investigator": { "id": 7743, "first_name": "Jason Brice", "last_name": "Weinberg", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that has caused the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 is associated with severe, frequently life-threatening respiratory illness in a substantial proportion of affected people. Severe COVID-19 is characterized by an exuberant systemic inflammatory response to SARS-CoV-2 infection. That response aids in control of viral replication during acute infection, but it also drives virus-induced pathology and disease manifestations. For reasons that remain incompletely understood, that deleterious inflammatory response is less likely to develop in children infected with SARS-CoV-2, and children are more likely than adults to have asymptomatic infection or mild disease. The immunoproteasome (IP), an inducible component of the ubiquitin- proteasome system, is more efficient than the constitutive proteasome in generating MHC class I epitopes for recognition by CD8 T cells. IP activity also exerts intrinsic effects on T cell, B cell, macrophage, and DC functions and contributes to inflammatory responses via mechanisms that include degradation of IκB and subsequent activation of NF-κB-mediated inflammatory pathways. No studies have addressed contributions of the IP to the pathogenesis of human or animal coronaviruses. Our published and preliminary data suggest that IP subunit activity is developmentally regulated in the lungs and other organs, increasing with age. IP subunit expression increases in mice during acute infection with a murine coronavirus, and IP inhibition suppresses virus-induced expression of pro-inflammatory cytokines but enhances weight loss and mortality. In this proposal, we will test the hypothesis that increased IP activity during coronavirus infection drives immunopathology in an age-dependent manner. We will use a tractable animal model with an animal coronavirus, murine hepatitis virus type 1 (MHV-1), to define the role of the IP in coronavirus pathogenesis and identify effects of IP inhibition on virus-induced inflammation and disease during acute infection. In Aim 1, we will define age-based differences in IP response, inflammation, and disease induced by acute MHV-1 respiratory infection. In Aim 2, we will use pharmacologic inhibition of IP subunit activity to define effects of IP activity on key immune cells and determine the extent to which the IP contributes to virus-induced inflammation and disease. There is a clear and pressing need to development effective preventative and therapeutic measures for COVID-19. Modulation of an inducible host factor, such as the IP, that is predominantly active during an inflammatory state such as infection would be an appealing strategy if it could facilitate reduction of detrimental inflammatory responses with minimal impact on essential constitutively active host processes.", "keywords": [ "2019-nCoV", "Acute", "Address", "Adrenal Cortex Hormones", "Adult", "Affect", "Age", "Alveolar Macrophages", "Animal Model", "Anti-Inflammatory Agents", "B-Lymphocytes", "Body Weight decreased", "CD8-Positive T-Lymphocytes", "COVID-19", "Cells", "Child", "Classification", "Clinical", "Coronavirus", "Coronavirus Infections", "Data", "Development", "Disease", "Epitopes", "Goals", "Immune", "Immune response", "Immunomodulators", "In Vitro", "Infection", "Inflammation", "Inflammation Mediators", "Inflammatory", "Inflammatory Response", "Innate Immune Response", "Integration Host Factors", "Interferon Type II", "Knowledge", "Life", "Link", "Literature", "Lung", "MHC Class I Genes", "Measures", "Mediating", "Mediator", "Morbidity - disease rate", "Mouse Strains", "Murine hepatitis virus", "Mus", "Organ", "Outcome", "Pathogenesis", "Pathology", "Pathway interactions", "Patient Selection", "Persons", "Play", "Population", "Predisposition", "Process", "Production", "Publishing", "Pulmonary Pathology", "Regulation", "Research", "Respiratory Tract Infections", "Role", "SARS-CoV-2 infection", "SARS-CoV-2 pathogenesis", "Signal Transduction", "Structure of parenchyma of lung", "System", "T cell response", "T-Lymphocyte", "Testing", "Therapeutic", "Ubiquitin", "Virus", "Virus Diseases", "Virus Replication", "Work", "World Health Organization", "acute infection", "age related", "animal coronavirus", "chemokine", "coronavirus disease", "cytokine", "cytokine release syndrome", "defined contribution", "human coronavirus", "immune function", "immunopathology", "improved", "improved outcome", "in vivo", "macrophage", "mortality", "mouse model", "multicatalytic endopeptidase complex", "multiorgan damage", "neutrophil", "novel", "pandemic disease", "patient population", "pharmacologic", "respiratory", "response", "severe COVID-19", "systemic inflammatory response" ], "approved": true } }, { "type": "Grant", "id": "11587", "attributes": { "award_id": "5R21AI166575-02", "title": "Animal models of SARS-CoV-2 bacterial Coinfection", "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": 26420, "first_name": "MARY KATHERINE", "last_name": "Bradford", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-16", "end_date": "2024-04-30", "award_amount": 193750, "principal_investigator": { "id": 7655, "first_name": "YAN", "last_name": "XIANG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 748, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 748, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic has infected over 26 million and killed at least 450,000 Americans as of 4 February 2021. Early reports show coinfections are possibly the greatest predictor of disease severity. Mixed viral/bacterial pneumonias are notoriously difficult to treat. The most extensively researched respiratory coinfection is influenza and Streptococcus pneumoniae, which contribute significant morbidity and mortality during normal respiratory infection seasons. Despite nearly two decades of vaccination with the highly effective pneumococcal conjugate vaccine (PCV), S. pneumoniae (Spn or the pneumococcus) remains a significant cause of community acquired pneumonia, sepsis, and meningitis. Much pneumococcal morbidity and mortality occurs during seasonal and pandemic flus. The physiological reasons for this are incompletely understood despite extensive investigation into this critical aspect of pneumococcal pathogenesis. Anti-viral immunological shifts, “activation” signals, proinflammatory upregulation of adhesins, and sialic acid availability have all been implicated. The general host responses observed during flu (fever, strong inflammatory cytokine profile, and release of DAMPS) are recapitulated during COVID-19. Spn is a normal colonizer of the human nasopharynx and a febrile state has been shown to lead to invasive pneumococcal disease by “activating” pneumococci. This also occurs with respiratory viruses other than flu and is likely to occur during COVID-19-associated fever, promoting the development of secondary bacterial pneumonia. A recent single-site study found S. pneumoniae to be the most common coinfection in SARS-CoV-2 infected individuals and a significant source of mortality in the aged. Although much work has been conducted with influenza/Spn coinfections, essentially nothing is known about SARS-CoV-2/Spn coinfections. As the world braces for multiple waves of SARS-CoV-2, it is of paramount importance to understand how these pathogens interact to promote severe disease. The long-term goal of this research program is to understand the interaction between SARS-CoV-2 and the pneumococcus; the objective here is to investigate the mechanisms of SARS-CoV-2 + pneumococcal disease pathogenesis during mixed infections and to model disease in appropriate animal models. The overarching hypothesis is that the host response to SARS-CoV-2 promotes invasive pneumococcal disease (IPD), ultimately resulting in increased disease severity including mixed pneumonia. More specifically, we hypothesize the inflammatory milieu created by SARS-CoV-2 infection upregulates pIGr, PafR, LamininR, and K-10, adhesins utilized by Spn to facilitate IPD. We further hypothesize that common COVID-19 treatments could impact the severity of coinfection.", "keywords": [ "2019-nCoV", "American", "Animal Model", "Antibiotics", "Bacterial Adhesins", "Bacterial Pneumonia", "Binding", "COVID-19", "COVID-19 pandemic", "COVID-19 treatment", "Cell surface", "Clinical", "Development", "Disease", "Disease model", "Epithelial Cells", "Exposure to", "Fever", "Goals", "Hamsters", "Human", "Immune response", "Immunologics", "Individual", "Infection", "Inflammation", "Inflammatory", "Inflammatory Response", "Influenza", "Investigation", "Lung", "Meningitis", "Microbial Biofilms", "Morbidity - disease rate", "Nasopharynx", "Pathogenesis", "Physiological", "Pneumococcal Infections", "Pneumococcal conjugate vaccine", "Pneumonia", "Reporting", "Research", "Respiratory Tract Infections", "SARS-CoV-2 infection", "SARS-CoV-2 pathogenesis", "Seasons", "Sepsis", "Severities", "Severity of illness", "Sialic Acids", "Signal Transduction", "Site", "Source", "Steroids", "Streptococcus pneumoniae", "Streptococcus pneumoniae plY protein", "Testing", "Up-Regulation", "Vaccination", "Viral", "Virion", "Work", "aged", "co-infection", "community acquired pneumonia", "cytokine", "flu", "in vivo", "inflammatory milieu", "influenza pneumonia", "mortality", "pandemic disease", "pandemic influenza", "pathogen", "programs", "respiratory", "respiratory virus", "seasonal influenza" ], "approved": true } }, { "type": "Grant", "id": "11588", "attributes": { "award_id": "7R21AI168808-02", "title": "Development of a rapid multiplex CRISPR-based testing pathway for tuberculosis and COVID-19", "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": 7856, "first_name": "Karen A.", "last_name": "Lacourciere", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-12", "end_date": "2024-04-30", "award_amount": 193004, "principal_investigator": { "id": 7857, "first_name": "Padmapriya", "last_name": "Banada", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 925, "ror": "", "name": "RBHS-NEW JERSEY MEDICAL SCHOOL", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7858, "first_name": "Cameron Amadeus", "last_name": "Myhrvold", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 7859, "first_name": "Yingda Linda", "last_name": "Xie", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1856, "ror": "", "name": "RUTGERS BIOMEDICAL AND HEALTH SCIENCES", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true }, "abstract": "Tuberculosis (TB) and COVID-19 (COVID) are currently the deadliest pathogens worldwide, with 1.4 million TB and 2.5 million COVID deaths annually, both perpetuated by potential transmission from undiagnosed, asymptomatic infection. In the many TB-COVID co-endemic populations in Asia, sub-Saharan Africa, South America, and Eastern Europe, there is a critical need for widespread, active, symptom-agnostic screening of TB and COVID to control transmission and reduce morbidity and mortality. However, the simultaneous burden of COVID and TB poses enormous stress on these health care systems with severely limited bandwidth and resources for active case finding and surveillance. Consequently, around 400 thousand more TB deaths are estimated in the next 5 years compared to prior years as a direct consequence of COVID. Beyond their global co-prevalence and potential for asymptomatic transmission, TB and COVID’s overlapping clinical signs and symptoms, risk factors, and shared respiratory transmission pathways allow for a combined rapid screening approach that can detect both infections using one sample and testing pathway. This would enable i) more wide-spread screening, ii) at higher efficiency – fewer individuals need to be screened to detect one TB or COVID infected individual. We propose to leverage our existing TB and COVID non-invasive samples (eg. sputum, concentrated saliva, oral swabs), common processing methods and a novel point-of-care compatible CRISPR-Cas 13 COVID diagnostic system (SHINE) to pilot a streamlined approach to simultaneously screen for TB and COVID. Specifically, to develop this combined screening strategy, we will pursue the following aims: 1) transition a point-of-care CRISPR platform for multiplex screening of TB and COVID, and 2) optimize co-extraction methods from TB and COVID sputum and sputum specimens. These complementary aims will contribute independent value to enable streamlined testing and control of both COVID and TB, and are adaptable towards rapid, multiplex screening and surveillance of future pandemics.", "keywords": [ "2019-nCoV", "Africa South of the Sahara", "Asia", "Biological Assay", "COVID diagnostic", "COVID-19", "COVID-19 assay", "COVID-19 patient", "Cause of Death", "Cessation of life", "Chemicals", "Clinical", "Clustered Regularly Interspaced Short Palindromic Repeats", "Communicable Diseases", "DNA", "Detection", "Development", "Diagnostic", "Eastern Europe", "Evaluation", "Health Resources", "Healthcare Systems", "Individual", "Infection", "Methods", "Morbidity - disease rate", "Mycobacterium tuberculosis", "Nucleic Acids", "Oral", "Pathway interactions", "Patients", "Performance", "Phase", "Population", "Prevalence", "Property", "Protocols documentation", "Public Health", "RNA", "Rapid screening", "Research Personnel", "Resource-limited setting", "Resources", "Risk Factors", "Saliva", "Sampling", "Signs and Symptoms", "South America", "Specimen", "Sputum", "Stress", "Swab", "Symptoms", "Technical Expertise", "Technology", "Testing", "Tuberculosis", "Validation", "Work", "case finding", "coronavirus disease", "cost", "detection limit", "diagnostic platform", "future pandemic", "mortality", "novel", "pandemic pathogen", "pathogen", "point of care", "prototype", "rapid technique", "respiratory", "respiratory pathogen", "saliva sample", "screening", "transmission process", "tuberculosis diagnostics" ], "approved": true } }, { "type": "Grant", "id": "11589", "attributes": { "award_id": "5R21AI169430-02", "title": "Roles of CCR10 in regulation of IgA responses to SARS-CoV-2 infection", "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": 26918, "first_name": "Michelle Marie", "last_name": "Arnold", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-16", "end_date": "2024-04-30", "award_amount": 193750, "principal_investigator": { "id": 7655, "first_name": "YAN", "last_name": "XIANG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 748, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7866, "first_name": "NA", "last_name": "XIONG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 748, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "The novel coronavirus SARS-CoV-2 causes the COVID-19 pandemic. The virus infects through the respiratory tracts. While most COVID-19 patients display no or mild clinical symptoms, a small percentage develop severe immune-mediated pathological complications, which could lead to injury and failure of the lung and various important organs and account for the majority of COVID-19 deaths. Understanding how different components of the immune system are involved in the viral control and pathological development is crucial for our understanding of pathogenesis of the disease and developing preventative and therapeutic strategies. In this grant application, we propose to dissect involvement of CCR10-regulated mucosal IgA antibody responses in SARS-CoV-2 infection clearance versus immune-pathological development using mouse models in two specific aims. In the Aim 1, we will determine the role of CCR10-regulated primary mucosal IgA responses in SARS-CoV-2-infection clearance and immunopathological development. In the Aim 2, we will determine the role of CCR10- regulated memory mucosal IgA responses in SARS-CoV-2 infection and immune-pathological development. The findings of our proposed study will not only help our understanding of involvement of mucosal IgA responses in clearance of the viral infection and pathogenesis of COVID-19 but also provide a guide on future development of vaccination strategies to induce proper IgA response for the disease prevention.", "keywords": [ "2019-nCoV", "Antibodies", "Antibody Response", "Antibody titer measurement", "Applications Grants", "B-Lymphocytes", "COVID-19 mortality", "COVID-19 pandemic", "COVID-19 pathogenesis", "COVID-19 patient", "COVID-19 vaccine", "Cells", "Cessation of life", "Clinical", "Code", "Development", "Developmental Process", "Disease", "Future", "GPR2 gene", "Homing", "Immune", "Immune response", "Immune system", "Immunize", "Immunoglobulin A", "Immunoglobulin-Secreting Cells", "Infection", "Infection Control", "Infection prevention", "Injury", "Invaded", "Knock-in Mouse", "Knock-out", "Knockout Mice", "Maintenance", "Mediating", "Memory", "Memory B-Lymphocyte", "Modified Vaccinia Virus Ankara", "Mucous Membrane", "Mus", "Nucleocapsid", "Nucleocapsid Proteins", "Organ", "Pathogenesis", "Pathologic", "Patients", "Proteins", "Recombinants", "Regulation", "Respiratory System", "Role", "Route", "SARS-CoV-2 infection", "SARS-CoV-2 pathogenesis", "SARS-CoV-2 spike protein", "Severities", "Site", "Symptoms", "Therapeutic", "Tissues", "Viral", "Viral Pathogenesis", "Virus", "Virus Diseases", "chemokine receptor", "disorder prevention", "enhanced green fluorescent protein", "immunopathology", "lung failure", "migration", "mouse model", "mucosa-associated lymphoid tissue", "mucosal site", "novel coronavirus", "pathogen", "response", "vaccination strategy" ], "approved": true } }, { "type": "Grant", "id": "11590", "attributes": { "award_id": "5R21AI166521-02", "title": "Development of PROTACs Targeting Papain-like Protease as Broad-Spectrum Anti-Coronavirus Therapeutics", "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": 6115, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-26", "end_date": "2024-04-30", "award_amount": 183651, "principal_investigator": { "id": 7872, "first_name": "Shiqing", "last_name": "Xu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 342, "ror": "https://ror.org/01f5ytq51", "name": "Texas A&M University", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1996, "ror": "", "name": "TEXAS A&M UNIVERSITY", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "The current COVID-19 pandemic caused by SARS-CoV-2 has paralyzed much of the world. Encouragingly, a few COVID-19 vaccines have been developed and approved for human immunization. However, existing COVID-19 vaccines target the highly mutable membrane Spike protein of SARS-CoV-2. New viral strains with critical mutations in Spike have emerged such as alpha, beta, delta, and gamma variants that could make current vaccines less effective. To truly overcome the threat posed by SARS-CoV-2 and its emerging variants of concern, it is paramount to develop antiviral drugs that can combat COVID-19 and also be potentially repurposed to combat novel coronaviruses (CoVs) in the future. To address this urgent need, this proposal aims to interface papain-like protease (PLpro) inhibitors/binders and the emerging proteolysis targeting chimera (PROTAC) technology for the development of broad-spectrum anti-CoV PROTACs. PLpro, one of two essential SARS-CoV- 2 proteases, plays a dual role in promoting viral transcription and replication, and antagonizing host innate immune responses. PLpro is encoded by nonstructural protein 3 (nsp3) which is relatively conserved across various CoVs. Thus, PLpro is an attractive target for the development of broad-spectrum anti-CoV drugs. The proposed small-molecule PROTACs are bifunctional small molecules containing two active ligands connected via a chemical linker. One ligand binds specifically to a viral protein target PLpro while the other ligand selectively engages an E3 ubiquitin ligase. The recruitment of the E3 ligase to PLpro facilitates the formation of a ternary complex, leading to ubiquitination and ultimate degradation of PLpro by the ubiquitination-proteasome pathway. As PROTACs regulate protein function by degrading target proteins instead of inhibiting them, they offer many advantages over traditional occupancy-based inhibitors, including (i) sub-stoichiometric activity, (ii) high barrier to resistance, (iii) improved target selectivity, and (iv) that weak binders (no inhibition required) can become potent degraders. On this basis, the overall goal of this application is to validate the degradation of PLpro as a new strategy for the development of broad-spectrum antiviral therapeutics to combat CoVs. In Aim 1, to chemically optimize non-covalent, reversible covalent, and multiple binding-mode PROTACs by linking VHL E3 ligands and PLpro inhibitors/binders, and to evaluate their degradation potency of PLpro in cell-based assays. In Aim 2, to determine the anti-SARS-CoV-2 activity of developed PROTAC molecules. Potent PROTACs (EC50 < 500 nM) will be further tested for their antiviral activities against other CoVs. In vitro DMPK and cytotoxicity studies of potent PROTACs will be conducted. The successful completion of the proposed study will lead to potent anti-CoV PROTACs against COVID-19 that the mechanism of action is fundamentally different from existing antivirals. The developed PROTAC molecules will also have the potential to be repurposed to contain future coronavirus outbreaks.", "keywords": [ "2019-nCoV", "Active Sites", "Address", "Antiviral Agents", "Authorization documentation", "Binding", "Binding Sites", "Biological Assay", "COVID-19", "COVID-19 pandemic", "COVID-19 therapeutics", "COVID-19 vaccine", "Cells", "Cessation of life", "Chemicals", "Complex", "Coronavirus", "Development", "Disadvantaged", "Disease", "Disease Outbreaks", "Drug Targeting", "Event", "Fingers", "Future", "Genetic Transcription", "Goals", "Health Promotion", "Human", "Immunization", "In Vitro", "Infection", "Innate Immune Response", "Knowledge", "Lead", "Length", "Ligand Binding", "Ligands", "Link", "Mass Spectrum Analysis", "Membrane", "Mission", "Mutation", "Nature", "Nonstructural Protein", "Papain", "Paralysed", "Pathway interactions", "Peptide Hydrolases", "Pharmaceutical Preparations", "Play", "Property", "Protac", "Protease Inhibitor", "Proteins", "Public Health", "RNA Viruses", "Research", "Resistance", "Role", "SARS-CoV-2 B.1.617.2", "SARS-CoV-2 P.1", "SARS-CoV-2 protease", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Site", "System", "Technology", "Testing", "Thumb structure", "Ubiquitination", "United States", "United States National Institutes of Health", "Vaccines", "Variant", "Viral", "Viral Physiology", "Viral Proteins", "Virus Replication", "antiviral drug development", "authority", "combat", "coronavirus therapeutics", "cytotoxicity", "drug development", "drug discovery", "global health emergency", "human coronavirus", "improved", "inhibitor", "insight", "multicatalytic endopeptidase complex", "new technology", "novel coronavirus", "pathogen", "protein function", "protein protein interaction", "recruit", "small molecule", "targeted treatment", "technology development", "tool", "ubiquitin isopeptidase", "ubiquitin-protein ligase", "vaccine development", "variants of concern" ], "approved": true } }, { "type": "Grant", "id": "11591", "attributes": { "award_id": "5R01AI168209-02", "title": "A risk-varying and perturbed self-controlled case series design for assessing the safety of COVID-19 vaccines in a large health care system", "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": 26420, "first_name": "MARY KATHERINE", "last_name": "Bradford", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-17", "end_date": "2026-04-30", "award_amount": 664451, "principal_investigator": { "id": 7877, "first_name": "Stanley", "last_name": "Xu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 769, "ror": "", "name": "KAISER FOUNDATION RESEARCH INSTITUTE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 769, "ror": "", "name": "KAISER FOUNDATION RESEARCH INSTITUTE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Despite the success of the unprecedented COVID-19 vaccine rollout in the U.S., vaccine hesitancy is evident, partly due to safety concerns about severe adverse events (SAEs) surrounding the novel technology of mRNA COVID-19 vaccines and reports of blood clots following receipt of the Janssen COVID-19 vaccine. While rigorous safety monitoring may help support COVID-19 vaccination, it is methodologically challenging to thoroughly evaluate the safety of the two-dose mRNA COVID-19 vaccines and the one-dose Janssen COVID- 19 vaccine. Existing approaches can produce false positive and false negative signals when 1) risk windows after vaccination are incorrectly specified, 2) a constant risk of SAEs during the risk window is wrongly assumed, 3) factors that may influence receipt of the second dose of mRNA COVID-19 vaccines are not accounted for, and 4) the nature of the risk of SAEs during potential overlapping risk windows of the first and second doses of mRNA COVID-19 vaccines is not assessed. In response to the FOA, PA-18-873, this proposal addresses the specific objective: “creation/evaluation of statistical methodologies for analyzing data on vaccine safety, including data available from existing data sources such as passive reporting systems or healthcare databases.” We propose to develop novel statistical models to properly measure the risk of new COVID-19 vaccines by allowing the risk level to vary during unknown risk windows and using a data-driven approach to define these risk windows. We will also create a new metric for measuring the risk of SAEs considering both the risk level and the length of the risk window, address the potential overlap of risk windows of two doses, and employ a propensity score model approach to account for factors that may influence receipt of the second dose of mRNA COVID-19 vaccines. We will establish these novel approaches to evaluate COVID-19 vaccine safety and will apply them to existing data from members of Kaiser Permanente Southern California, a large, racially, and socio-economically diverse population. Through this research, we will detect SAEs of concern, better inform the public and policymakers about the safety of COVID-19 vaccines, and generate vaccine safety information that may be helpful for clinicians to deliver appropriate care to those at risk.", "keywords": [ "Address", "American", "Area Under Curve", "Blood coagulation", "COVID-19 vaccination", "COVID-19 vaccine", "COVID-19 vaccine evaluation", "California", "Caring", "Case Series", "Characteristics", "Clinical", "Clinical Trials", "Data", "Data Sources", "Databases", "Detection", "Dose", "Epidemiologist", "Evaluation", "Family", "Foundations", "Healthcare", "Healthcare Systems", "Incidence", "Individual", "Length", "Measures", "Messenger RNA", "Methodology", "Methods", "Modeling", "Monitor", "Nature", "Patients", "Pattern", "Persons", "Policy Maker", "Population", "Population Heterogeneity", "Race", "Recommendation", "Reporting", "Research", "Risk", "Safety", "Schedule", "Serious Adverse Event", "Signal Transduction", "Specific qualifier value", "Statistical Models", "System", "Time", "United States", "Vaccinated", "Vaccination", "Vaccinee", "Vaccines", "adverse event risk", "combat", "design", "experience", "fighting", "health care service organization", "member", "new technology", "novel", "novel strategies", "pandemic disease", "response", "safety assessment", "safety study", "socioeconomics", "success", "tool", "vaccine acceptance", "vaccine distribution", "vaccine evaluation", "vaccine hesitancy", "vaccine safety" ], "approved": true } }, { "type": "Grant", "id": "11592", "attributes": { "award_id": "5R03AI159286-02", "title": "Integrative and interactive analyses of host transcriptional response to COVID-19 and other respiratory viral infections", "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": 26420, "first_name": "MARY KATHERINE", "last_name": "Bradford", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-05", "end_date": "2024-04-30", "award_amount": 77742, "principal_investigator": { "id": 27539, "first_name": "Ka Yee", "last_name": "Yeung-Rhee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "The current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to global public health concerns. This novel coronavirus disease (COVID-19) shares similar clinical symptoms with diseases caused by other viruses in the coronavirus family and other common respiratory viruses. When an infectious agent replicates within a host organism, the host interacts with, and responds to the virus with various mechanisms. Given the varying severity across patients and emergence of new SARS-CoV-2 variants, there is an urgent need to understand how the host responds to COVID-19 and its variants. RNA sequencing (RNA-seq) data that profile transcriptional response to SARS-CoV-2 and other respiratory viral infections are available from public databases. Comparing the gene signatures across respiratory viruses will identify similarities and differences of how the host responds to these infections. In particular, compendium analyses in which multiple datasets are integrated bring great opportunities for generating novel biological hypotheses. However, compendium analysis of RNA-seq data generated across different laboratories is an onerous task given the different protocols, parameters, software and software versions used at the time of analyses. This proposal focuses on the development of software tools to facilitate re-analyses of existing host-response RNA-seq data to create a compendium of gene signatures using the same set of analytical tools and input parameters. Our deliverables will include workflows with saved input files and parameters, fixed software versions and dependencies that will facilitate reproducibility and collaboration. We will provide an accessible graphical user interface that allows users to create custom signature sets by querying the data and if desired, re-analyzing the data using one of our provided workflows or a workflow of their own choosing. Users will be able to filter biological variables, perform cross species analysis, compare gene signatures to other gene set repositories. In addition, we will create an accessible dashboard that will support the query, download, visualization and reproducible analysis of gene expression data from SARS-CoV-2 and other common respiratory viruses. Tools will be provided to allow the user to interactively visualize the data and inform the choice of appropriate gene signatures. Not only will our software tools and dashboard provide an accessible front end, we will also develop an easy-to-use, scalable and cloud-enabled backend that enables efficient alignment of sequencing data. Our proposed project will empower biomedical scientists to experiment with different computational methods, input parameters (including the alignment step) across multiple datasets and respiratory viral infections. Thus, facilitating integrated and interactive analyses using datasets generated by multiple laboratories to advance our understanding of host transcriptional response to COVID-19.", "keywords": [ "2019-nCoV", "Bioinformatics", "Biological", "COVID-19", "COVID-19 pandemic", "Clinical", "Code", "Collaborations", "Communities", "Computer software", "Computing Methodologies", "Coronavirus", "Custom", "Data", "Data Set", "Databases", "Dependence", "Disease", "Family", "Gene Expression", "Gene Expression Profile", "Gene Expression Profiling", "Gene set enrichment analysis", "Generations", "Genes", "Genetic Transcription", "Human", "Image", "Immune response", "Infection", "Infectious Agent", "Influenza", "Intuition", "Laboratories", "Learning Module", "Machine Learning", "Manuals", "Methodology", "Methods", "Middle East Respiratory Syndrome Coronavirus", "Organism", "Patients", "Performance", "Process", "Protocols documentation", "Public Health", "RNA Processing", "RNA analysis", "Race", "Reproducibility", "Respiratory Tract Infections", "Rhinovirus", "SARS coronavirus", "SARS-CoV-2 variant", "Selection Criteria", "Sequence Alignment", "Severities", "Software Tools", "Specific qualifier value", "Symptoms", "Technology", "Time", "Traction", "Transcript", "Update", "Variant", "Viral Respiratory Tract Infection", "Virus", "Virus Diseases", "Visualization", "analytical tool", "biomedical scientist", "coronavirus disease", "current pandemic", "dashboard", "data integration", "data visualization", "diagnostic strategy", "differential expression", "empowerment", "experimental study", "genetic signature", "genomic data", "graphical user interface", "knowledge base", "large scale data", "multiple datasets", "novel", "novel coronavirus", "pandemic disease", "portability", "prototype", "public database", "public repository", "repository", "respiratory virus", "response", "sex", "software development", "tool", "transcriptome sequencing", "treatment strategy", "usability", "user-friendly", "vaccine development", "vaccine strategy" ], "approved": true } }, { "type": "Grant", "id": "11593", "attributes": { "award_id": "5R21AI160576-02", "title": "Single gene inborn errors of immunity underlying SARS-CoV-2-related multisystem inflammatory syndrome in children: a new approach to tackle a seemingly old puzzle", "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": 26918, "first_name": "Michelle Marie", "last_name": "Arnold", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-20", "end_date": "2024-04-30", "award_amount": 211875, "principal_investigator": { "id": 6183, "first_name": "Shen-Ying", "last_name": "Zhang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 763, "ror": "https://ror.org/0420db125", "name": "Rockefeller University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 763, "ror": "https://ror.org/0420db125", "name": "Rockefeller University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been quickly spreading around the world since December 2019 and causing coronavirus disease 2019 (COVID-19) in populations naive to this new pathogen. Since early May 2020, a rare and life-threatening SARS-CoV-2-related Kawasaki-like disease, designated by the CDC as Multisystem Inflammatory Syndrome in Children (MIS-C), emerged in communities with high rates of COVID-19. Clinical and laboratory characteristics of patients have revealed multiple similarities between MIS-C and Kawasaki disease (KD), a well-known but poorly understood pediatric inflammatory condition. The past ~50 years of studies on KD suggest that infectious agents, including a variety of viruses in particular, can trigger an inflammatory cascade that drives the clinical manifestations in genetically vulnerable children. However, the genetic etiologies and immunological mechanisms of KD remain largely unknown. The emergence of MIS-C during the COVID-19 epidemic provides compelling evidence of a viral trigger, at least for this specific form of Kawasaki-like disease. We and others have previously identified a number of monogenic inborn errors of immunity (IEIs) underlying a variety of severe viral diseases. We now aim to dissect the immunopathogenesis of MIS-C by testing a monogenic hypothesis. We will recruit a cohort of at least 1,000 MIS-C patients, by utilizing the COVID Human Genetic Effort (www.covidhge.com), our global network of pediatricians, and the New York State Department of Health (NYSDOH). We will perform whole exome sequencing (WES) and whole genome sequencing (WGS) sequentially for all enrolled patients. We will search for rare single gene IEIs underlying MIS-C via an unbiased genome-wide approach, by analyzing the WES and WGS data at the cohort population (genetic homogeneity) and individual patient levels (genetic heterogeneity), also testing models of immunological homogeneity and heterogeneity. For all candidate MIS-C- causing genes, we will perform in-depth characterization at the molecular and cellular levels, to connect the candidate genotype to molecular mechanism(s) and cellular phenotype(s) relevant to the MIS-C pathogenesis. We will use patient-specific leukocytes, dermal fibroblasts, and human pluripotent stem cell (hPSC)-derived MIS- C disease-relevant cell types, such as cardiovascular endothelial cells or cardiomyocytes. Our preliminary data are encouraging, as we have already enrolled 812 patients and performed WES on 620 of them. For comparison, we have also enrolled 158 patients with classic KD and have sequenced all of them. This project focuses on a timely and devastating problem, tests a bold but plausible hypothesis, and takes advantage of cutting-edge genetic and mechanistic approaches. It will enable us to gain insight into the molecular and cellular basis of the immunopathology of SARS-CoV-2-related MIS-C in previously healthy children and adolescents. The results of this project will also permit genetic diagnosis and counseling, while facilitating the development of novel preventive and therapeutic strategies in both genetic and non-genetic cases.", "keywords": [ "2019-nCoV", "Accounting", "Adolescent", "Affect", "Attenuated", "BIRC4 gene", "Brain Stem", "COVID-19", "COVID-19 pandemic", "COVID-19 pneumonia", "Cardiac Myocytes", "Cells", "Characteristics", "Child", "Childhood", "Clinical", "Collaborations", "Communities", "Cytomegalovirus", "Data", "Defect", "Dermal", "Development", "Disease", "Encephalitis", "Endothelial Cells", "Enrollment", "Epidermodysplasia Verruciformis", "Family member", "Fibroblasts", "Gene Frequency", "Genes", "Genetic", "Genetic Counseling", "Genetic Heterogeneity", "Genetic Models", "Genetic Predisposition to Disease", "Genotype", "Health", "Hepatitis", "Hepatitis A Virus", "Hereditary Disease", "Herpesvirus 1", "Herpesvirus Type 3", "Heterogeneity", "Human", "Human Genetics", "Human Herpesvirus 4", "Human Papillomavirus", "IFNAR1 gene", "IFNAR2 gene", "IRF3 gene", "Immunity", "Immunological Models", "Immunologics", "Impairment", "Individual", "Infection", "Infectious Agent", "Inflammation", "Inflammatory", "Influenza A virus", "Intervention", "Investigation", "Laboratories", "Leukocytes", "Life", "Measles", "Minor", "Molecular", "Mucocutaneous Lymph Node Syndrome", "Multisystem Inflammatory Syndrome in Children", "Mutate", "Mutation", "NOS2A gene", "New York", "Pathogenesis", "Patient Recruitments", "Patients", "Phenotype", "Population", "Predisposition", "Preventive", "Prosencephalon", "Pulmonary Inflammation", "Recurrent respiratory papillomatosis", "Reporting", "Rhinovirus", "SH2D1A gene", "STAT2 gene", "Single-Gene Defect", "TBK1 gene", "TLR3 gene", "TNF receptor-associated factor 3", "Testing", "Therapeutic", "Therapeutic Intervention", "Variant", "Viral", "Viral Encephalitis", "Virus", "Virus Diseases", "Yellow Fever Vaccine", "autosome", "cardiovascular endothelium", "cell type", "cohort", "coronavirus disease", "design", "emerging pathogen", "exome", "exome sequencing", "gene product", "genetic disorder diagnosis", "genome sequencing", "genome-wide", "human pluripotent stem cell", "immunopathology", "individual patient", "innovation", "insight", "non-genetic", "novel", "novel coronavirus", "novel strategies", "participant enrollment", "pediatric patients", "pediatrician", "preventive intervention", "proband", "recruit", "severe COVID-19", "whole genome", "young adult" ], "approved": true } }, { "type": "Grant", "id": "11594", "attributes": { "award_id": "5R21AI163425-02", "title": "Modifying Remdesivir Prodrug Design to Enhance the Active Metabolite Accumulation in the Lung (Resubmission)", "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": 6115, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-13", "end_date": "2024-04-30", "award_amount": 195000, "principal_investigator": { "id": 7948, "first_name": "Haojie", "last_name": "Zhu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Although remdesivir is among few medications approved by the FDA for treating patients with COVID-19, a significant portion of patients did not respond adequately to the treatment. Remdesivir is formed as a 2- ethylbutyl ester prodrug of the nucleoside analog GS-441524 to overcome the poor cell permeability of nucleosides and bypass the rate-limiting mono-phosphorylation metabolism required for GS-441524 activation. Remdesivir is extensively hydrolyzed in human plasma, raising the concerns that only a small portion of remdesivir can reach the lung in its intact prodrug form. Thus, the benefits associated with the prodrug design may be unattainable for the treatment of COVID-19. Another limitation is that remdesivir is only available in an intravenous injection dosage form due to its intensive first-pass effect. Because of those limitations, some investigators advocate for using the parent compound GS-441524 as an alternative to remdesivir to treat COVID-19 patients. However, it remains unknown how GS-441524's poor cell permeability affects intracellular drug accumulation and the extent to which the required rate-limiting mono-phosphorylation step could affect GS-441524 activation. During remdesivir development, several GS-441524 ester prodrugs were synthesized and evaluated for their plasma stability and in vitro antiviral activity. Remdesivir was chosen as the drug candidate for further development because of its superior anti-Ebola activity relative to other prodrugs in several non-lung cell lines. Among those, the isopropyl ester prodrug of GS-441524 showed lower antiviral potency but much greater plasma stability than remdesivir. Given that all the prodrugs have the same active metabolite, the antiviral activity differences among the tested prodrugs are likely attributed to their differences in intracellular accumulation and activation. Existing evidence suggests that carboxylesterase 1 (CES1) and cathepsin A (CatA) are involved in the activation of ester nucleoside prodrugs, and both CES1 and CatA are highly expressed in the human lung. Thus, isopropyl-GS-441524 could be efficiently activated in the lung and consequently exert its anti-SARS-CoV-2 effect. Moreover, the excellent stability of isopropyl-GS-441524 in plasma, liver, and intestine could improve the intracellular drug accumulation in the lung and allow the compound to be developed into an oral dosage form. In this project, we will conduct a pharmacokinetics (PK) study in mice to compare the activation and disposition between isopropyl-GS-441524, remdesivir, and GS- 441524 in various tissues. We will also determine the activation rates of the three compounds in the human lung and other PK-related organs and identify and characterize the hydrolases responsible for the prodrug activation. Furthermore, we will evaluate the anti-SARS-CoV-2 activity of the three compounds using an in vitro model. The project will provide evidence supporting that isopropyl-GS-441524 is advantageous over remdesivir and GS-441524 for treating COVID-19. Moreover, studying tissue-specific ester prodrug-activating hydrolases will shed light on the future development of more effective nucleoside prodrugs.", "keywords": [ "2019-nCoV", "Advocate", "Affect", "Authorization documentation", "Bypass", "COVID-19", "COVID-19 patient", "COVID-19 treatment", "Carboxylesterase 1", "Cell Line", "Cell membrane", "Cells", "Clinical", "Data", "Development", "Dosage Forms", "Dose", "Drug Kinetics", "Ebola", "Ebola virus", "Enzymes", "Epithelial Cells", "Esters", "Exclusion", "Exhibits", "FDA approved", "Foundations", "Future", "GS-441524", "Hela Cells", "Human", "Hydrolase", "In Vitro", "Incubated", "Intestines", "Kinetics", "Liver", "Lung", "Metabolism", "Mus", "Nucleosides", "Nucleotides", "Oral", "Organ", "Outpatients", "Parents", "Patients", "Permeability", "Pharmaceutical Preparations", "Phosphorylation", "Plasma", "Prodrugs", "Property", "Proteomics", "Research Personnel", "Tenofovir", "Testing", "Tissues", "Viral", "Viral Physiology", "activity-based protein profiling", "alveolar epithelium", "authority", "carboxypeptidase C", "design", "drug candidate", "improved", "improved outcome", "in vitro Model", "in vivo", "intravenous injection", "macrophage", "novel", "nucleoside analog", "nucleoside triphosphate", "phosphoramidate", "remdesivir", "severe COVID-19" ], "approved": true } }, { "type": "Grant", "id": "11595", "attributes": { "award_id": "5T34GM145513-02", "title": "U-RISE at Howard University", "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": 27540, "first_name": "MARIE DEBORAHGAYNELLE", "last_name": "Harton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-01", "end_date": "2027-03-31", "award_amount": 271543, "principal_investigator": { "id": 22220, "first_name": "Shawn Maurice", "last_name": "Abernathy", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [ { "id": 288, "ror": "https://ror.org/05gt1vc06", "name": "Howard University", "address": "", "city": "", "state": "DC", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 15527, "first_name": "Clarence M", "last_name": "Lee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 22221, "first_name": "DINARI A", "last_name": "HARRIS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 288, "ror": "https://ror.org/05gt1vc06", "name": "Howard University", "address": "", "city": "", "state": "DC", "zip": "", "country": "United States", "approved": true }, "abstract": "Summary/Abstract The United States (US) biomedical science (BMS) enterprise critically lacks diversity at the Ph.D. level. This problem is due to the lack of underrepresented minority (URM) students at the undergraduate level majoring in STEM (science technology engineering and mathematics) disciplines. Diversifying our BMS workforce would improve health equity by eradicating health disparities. This is of the utmost importance since the COVID-19 pandemic is disproportionately affecting underrepresented populations in the US. Given the proper academic and research training along with encouragement, a substantial number of academically talented URM students would seek research career in the BMS workforce. The Undergraduate Research Training Initiative for Student Enhancement (U-RISE) at Howard University Program will tap into this reservoir of students that would contribute to the diversification of our BMS workforce. Hence, the U-RISE at HU Program leadership mission is to recruit talented and passionate undergraduate students who envision themselves as innovative BMS scientists and global leaders in their fields. Our program mission is to engage them in an enhanced academic curriculum and hands-on research activities during the junior and senior years. This will produce a cadre highly educated, motivated, and well-trained URM students. To implement and sustain U-RISE at HU Program, the objective of the project needs to be integrated into our science community and culture. Our specific aims are the following: 1) To recruit academically talented and highly motivated URMs students to participate as trainees who aspire to a career as a Ph.D. level scientist in BMS discipline. 2) To provide our trainees with an enhanced and structured research training through an interdisciplinary hands-on intramural research experience, extramural summer research experience (SRE) as well as a classroom based didactic research. 3) To have at least 75% our program trainees accepted into a research intensive (R1) university Ph.D. programs in a BMS discipline within two years of graduation from Howard University, and 4) To design, implement, and institutionalize a STEM professional development course to stimulate our trainees’ interest. Finally, we envision our program will create a strong foundation for Howard University in the recruitment, enrollment, retention, and advancement of enthusiastic undergraduate students majoring in the BMS disciplines.", "keywords": [ "Academic Training", "Affect", "COVID-19 pandemic", "Communities", "Discipline", "Doctor of Philosophy", "Educational Curriculum", "Enrollment", "Extramural Activities", "Foundations", "Institutionalization", "Intramural Research", "Leadership", "Mission", "Research", "Research Activity", "Research Training", "STEM field", "Science", "Science Technology Engineering and Mathematics", "Scientist", "Structure", "Students", "Talents", "Training", "Underrepresented Minority", "Underrepresented Populations", "United States", "Universities", "career", "course development", "design", "experience", "hands on research", "health disparity", "health equity", "improved", "innovation", "interest", "programs", "recruit", "summer research", "undergraduate research", "undergraduate student", "underrepresented minority student" ], "approved": true } } ], "meta": { "pagination": { "page": 1405, "pages": 1424, "count": 14236 } } }