Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1385&sort=keywords
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=keywords", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1397&sort=keywords", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1386&sort=keywords", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=keywords" }, "data": [ { "type": "Grant", "id": "7603", "attributes": { "award_id": "3R44HD074319-04S1", "title": "An Evidence-based Approach for Bullying Prevention", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 11889, "first_name": "Karen", "last_name": "Lee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-09-09", "end_date": "2021-08-31", "award_amount": 99142, "principal_investigator": { "id": 23397, "first_name": "Christopher", "last_name": "Williams", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1594, "ror": "https://ror.org/04dzpzw79", "name": "National Health Promotion Associates", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1594, "ror": "https://ror.org/04dzpzw79", "name": "National Health Promotion Associates", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "An Evidence-Based Serious Game Approach for Bullying Prevention Administrative Supplement Bullying, in its most familiar form, is a serious public health concern. This is especially true during the middle-school years, a transition period when bullying increases. Cyberbullying, an electronic evolution of face-to-face bullying, is willful and repeated harm inflicted through computers, cell phones and other electronic devices to threaten, harass, embarrass, or socially exclude another. Both victims and offenders of bullying and cyberbullying are more likely to have low self-esteem, suicidal ideation, depression, substance use, and lower academic achievement. In this project, National Health Promotion Associates (NHPA) developed a bullying and cyberbullying prevention intervention for middle school students, including interactive classroom sessions and corresponding serious games, based on the evidence-based substance abuse prevention approach called Life Skills Training (LST). The LST prevention model teaches youth personal self-management skills, social skills, drug refusal skills, and other life skills needed to successfully navigate developmental tasks, increase resilience, and facilitate healthy psychosocial development. The LST program has been extensively tested and found to effectively prevent substance use in a series of randomized controlled trials (RCT) with behavioral effects reported in over 30 peer-reviewed publications. In the present study, we have developed the intervention materials and are now conducting a rigorous randomized controlled trial with 24 middle/junior high schools that have been assigned to either the LST prevention program alone or LST with the newly developed bullying/cyberbullying materials. The outcome evaluation assesses changes in behaviors, norms, attitudes, and knowledge for bullying/cyberbullying and concurrent alcohol, tobacco, and other drug (ATOD) abuse between the two experimental conditions. To examine the impact of the intervention, survey data are being collected immediately before and after its implementation and at 12- and 24-month follow-up assessments. We are also conducting a process evaluation to document dosage, fidelity implementation, and school/community events. In March of 2020, the Covid-19 pandemic spread across the United States and had a disruptive impact on this research, especially the activities conducted in schools. Schools throughout the country, including those participating in our randomized controlled trial, were closed by state and/or local officials. These abrupt closures had a severe impact on the trial fieldwork. All field activities, including intervention implementation and data collection, had to be halted. In addition, NHPA’s office (located in White Plains, New York) and all businesses not designated as “essential” were closed by an executive order of the NYS governor. Where possible, employees were instructed to establish at-home workstations and work from home. The proposed administrative supplement is requested to address the significant and adverse disruption to the trial based on the Covid-19 school closures that abruptly stopped: 1) intervention implementation; 2) survey data collection; and 3) process data collection.", "keywords": [ "ATOD", "Academic achievement", "Address", "Administrative Supplement", "Administrator", "Adverse effects", "Alcohol or Other Drugs use", "Attitude", "Behavior", "Behavioral", "Businesses", "COVID-19", "COVID-19 pandemic", "Cellular Phone", "Communities", "Computers", "Country", "Data", "Data Collection", "Development", "Distance Learning", "Drug abuse", "Electronics", "Employee", "Evaluation", "Event", "Evolution", "Feeling suicidal", "Future", "Health Promotion", "Home environment", "Intervention", "Knowledge", "Life", "Mental Depression", "Middle School Student", "Modeling", "Monitor", "Needs Assessment", "New York", "Outcome", "Peer Review", "Persons", "Pharmaceutical Preparations", "Prevention", "Prevention approach", "Prevention program", "Preventive Intervention", "Process", "Provider", "Public Health", "Publications", "Randomized Controlled Trials", "Reporting", "Research", "Schools", "Self Management", "Series", "Surveys", "Testing", "Training", "Training Activity", "Training Programs", "United States", "Work", "Youth", "base", "bullying", "bullying prevention", "commercialization", "cyberbullying", "dosage", "educational atmosphere", "evidence base", "flexibility", "follow up assessment", "junior high school", "learning materials", "offender", "psychosocial development", "resilience", "self esteem", "skills", "skills training", "social", "social skills", "substance abuse prevention", "substance use prevention", "teacher" ], "approved": true } }, { "type": "Grant", "id": "7520", "attributes": { "award_id": "3P50AI150464-14S1", "title": "Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH Center)", "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": 7146, "first_name": "DAVID JOSEPH", "last_name": "McDonald", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-08-01", "end_date": "2021-07-31", "award_amount": 449404, "principal_investigator": { "id": 23332, "first_name": "WESLEY I.", "last_name": "SUNDQUIST", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 202, "ror": "https://ror.org/03r0ha626", "name": "University of Utah", "address": "", "city": "", "state": "UT", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 202, "ror": "https://ror.org/03r0ha626", "name": "University of Utah", "address": "", "city": "", "state": "UT", "zip": "", "country": "United States", "approved": true }, "abstract": "Our Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH) studies HIV-Host interactions involved in viral replication, trafficking and transmission. Our studies focus on four key aspects of HIV-1 biology: 1) HIV assembly and host budding restrictions, 2) HIV transmission in whole animals and in vitro models, 3) Intracellular trafficking, transformations and restriction of the viral core, and 4) New directions in viral latency and immune receptors. In each case, we aim to understand: 1) The relevant molecular machines, 2) The mechanisms by which host pathways are recruited and utilized, and 3) The structures of underlying tissues, cellular assemblies, and viral components. Two other overarching themes of the Center are: 1) Studies of dynamic processes, ranging from key molecular transformations in the viral life cycle to studies of virus transmission and dissemination in whole animals, and 2) Developing and applying complementary approaches for studying viral and cellular structures across a range of resolutions, spatial and temporal dimensions, and biological contexts. In parallel, we are developing and applying tools that will advance important frontiers in structural biology and HIV molecular virology, including: 1) New approaches for transforming cryo-EM reconstructions, 2) Correlated light and electron cryotomography (CLEM-ECT) approaches for visualizing viral complexes inside cells, 3) Imaging HIV transmission in humanized mice and primate tissues, and 4) Designing new proteins that can mimic viral assembly, release, and entry. All of these efforts are supported by state-of-the-art Cores for: 1) Producing biological reagents, 2) Performing structural biology, 3) Spectroscopy and imaging, 4) Computation and data science, and 5) Biological models. The efforts of our Center are also extended through: 1) Extensive collaborations with other researchers and P50 Centers, 2) A Collaborative Development Awards program that will fund promising young investigators who will enhance and benefit from interactions with our Center, and 3) Educational programs for Center trainees. Our overall goals are to continue to develop HIV into an unparalleled model system for studying how a human virus interacts with its host, and to lay the groundwork for the development of new antiviral therapies.", "keywords": [ "ATP phosphohydrolase", "Anatomy", "Animals", "Antibodies", "Antiviral Therapy", "Award", "Biological", "Biological Assay", "Biological Models", "Biology", "Biophysics", "Capsid", "Cells", "Cellular Structures", "Cellular biology", "Collaborations", "Complex", "Computational Science", "Cryoelectron Microscopy", "Data Science", "Development", "Dimensions", "Electrons", "Elements", "Enzymes", "Face", "Family", "Filament", "Funding", "Genes", "Genetic", "Goals", "HIV", "HIV Budding", "HIV-1", "Human", "Image", "Imaging technology", "Immune response", "Immunologic Receptors", "Immunology", "Individual", "Innate Immune Response", "Integration Host Factors", "Laboratories", "Learning", "Life Cycle Stages", "Light", "Lysine-Specific tRNA", "Maintenance", "Mediating", "Membrane", "Membrane Fusion", "Methods", "Micro Electron Diffraction", "Microscopy", "Modeling", "Molecular", "Molecular Conformation", "Molecular Machines", "Molecular Virology", "Mus", "Natural Immunity", "Neck", "Pathway interactions", "Peptides", "Primates", "Process", "Protein Engineering", "Proteins", "RNA", "RNA-Directed DNA Polymerase", "Reagent", "Replication Initiation", "Research Personnel", "Resolution", "Resources", "Reverse Transcription", "Spectrum Analysis", "Structure", "System", "T-Lymphocyte", "Therapeutic Intervention", "Tissues", "Toxic effect", "Viral", "Virion", "Virus", "Virus Assembly", "Virus Latency", "Virus Replication", "animation", "cellular imaging", "cellular transduction", "design", "env Gene Products", "env Glycoproteins", "experimental study", "frontier", "humanized mouse", "in vitro Model", "interdisciplinary approach", "macromolecule", "mouse model", "nonhuman primate", "novel strategies", "outreach", "particle", "programs", "reactivation from latency", "receptor", "reconstitution", "reconstruction", "recruit", "screening", "simulation", "structural biology", "targeted treatment", "three dimensional structure", "tool", "tool development", "trafficking", "transmission process", "viral RNA", "viral transmission", "virology", "virus host interaction" ], "approved": true } }, { "type": "Grant", "id": "12206", "attributes": { "award_id": "1UC7AI180309-01", "title": "UofL RBL Operations, Workforce Development and Pandemic Preparedness Research", "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": 27982, "first_name": "FAYNA C", "last_name": "Diaz San Segundo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-18", "end_date": "2028-07-31", "award_amount": 2935664, "principal_investigator": { "id": 28078, "first_name": "KENNETH E", "last_name": "PALMER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 795, "ror": "https://ror.org/01ckdn478", "name": "University of Louisville", "address": "", "city": "", "state": "KY", "zip": "", "country": "United States", "approved": true }, "abstract": "(OVERALL): The University of Louisville Regional Biocontainment Laboratory (RBL) is operated by the University Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases (CPM). The RBL is a regional resource that facilitates translational research to develop diagnostics, prognostics, therapeutics and vaccines to mitigate biodefense and emerging infectious disease threats. Our Center operates the only BSL-3 and ABSL-3 facilities currently operating in the Commonwealth of Kentucky. The CPM mandate is to prepare for and respond to public health emergencies, such as the COVID-19 pandemic. The broad, long-range objectives and goals of the University of Louisville (UofL) CPM RBL are: 1. To offer state-of-the-art research services to the regional and national biomedical research community to learn from past pandemics and biological warfare experiences and effectively predict and mitigate future emerging infectious disease threats. 2. To manage, maintain and operate the UofL RBL to serve the national and regional need for biocontainment facilities suitable for research on Risk Group 3 pathogens and other biothreats. 3. To follow a philosophy of continuous improvement in BSL-3 and ABSL-3 work practices and to ensure that all personnel who need to access BSL-3 and ABSL-3 containment laboratories are appropriately trained and prepared to serve the national and regional need for biocontainment research professionals. To achieve these aims we propose to establish three collaborative Cores. The Facilities Management Maintenance and Operations Core (FMMO Core) is responsible for ensuring that the facility is always available to meet the research and emergency preparedness mission of the RBL. The BSL-3 Practices and Workforce Development Core (BSL-3PWD Core) formalizes our mentor-mentee training plan to ensure our laboratory is staffed with BSL-3 research professionals who are proficient at biocontainment research professionals. This core responds to the reality that response to rapidly emerging public health emergencies like COVID-19 is limited by the number of available BSL-3 trained and experienced research professionals. Our Pandemic Preparedness and Response Integrated Research Core (PaPR Core) responds to the substantially increased requests for our BSL-3 research services by organizing an integrated full-service BSL-3 research support function to support investigator needs. These cores will work in unison to achieve the CPM mission: to prepare for and respond to public health emergencies like the COVID-19 pandemic.", "keywords": [ "Attention", "Biological Warfare", "Biomedical Research", "Biotechnology", "COVID-19", "COVID-19 pandemic", "COVID-19 patient", "China", "Clinical Trials", "Communities", "Containment", "Creativeness", "Crowns", "Dedications", "Diagnostic", "Disease Outbreaks", "Economics", "Emerging Communicable Diseases", "Ensure", "Federal Government", "Funding Opportunities", "Future", "Goals", "Health Services Research", "Health care facility", "Hospitals", "Hour", "Human Resources", "Industry", "Infection", "Institution", "International", "Investigational New Drug Application", "Kentucky", "Laboratories", "Leadership", "Learning", "Maintenance", "Managed Care", "Medicine", "Mentors", "Mission", "Modeling", "National Center for Advancing Translational Sciences", "National Institute of Diabetes and Digestive and Kidney Diseases", "Nose", "Patients", "Philosophy", "Play", "Public Health", "Research", "Research Personnel", "Research Support", "Resources", "Rest", "Reverse Transcriptase Polymerase Chain Reaction", "Risk", "Role", "Scientist", "Serology test", "Services", "System", "Talents", "Techniques", "Testing", "Therapeutic", "Training", "Translational Research", "United States National Institutes of Health", "Universities", "University resources", "Vaccines", "Work", "Workforce Development", "biocontainment facility", "biodefense", "biothreat", "cohort", "experience", "improved", "laboratory experience", "medical countermeasure", "metropolitan", "novel", "novel coronavirus", "operation", "pandemic disease", "pandemic preparedness", "pandemic response", "pathogen", "previous pandemic", "prognostic", "prophylactic", "public health emergency", "recruit", "response", "service organization", "skills", "wastewater surveillance" ], "approved": true } }, { "type": "Grant", "id": "7272", "attributes": { "award_id": "1R01AI153602-01", "title": "Identifying host and viral correlates for coronavirus pathogenesis", "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": 6011, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-15", "end_date": "2024-05-31", "award_amount": 497886, "principal_investigator": { "id": 7025, "first_name": "VINEET D", "last_name": "MENACHERY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 851, "ror": "", "name": "UNIVERSITY OF TEXAS MED BR GALVESTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 851, "ror": "", "name": "UNIVERSITY OF TEXAS MED BR GALVESTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "The coronavirus (CoV) spike protein is a key viral determinant responsible for receptor binding and fusion/entry. The spike protein has also been predicted to be the major factor driving cross-species transmission, allowing the emergence of epidemic strains like SARS- and MERS-CoV. In the first decade after SARS-CoV emergence, changes to the epidemic spike that allowed binding to a new host receptor were thought to underlie this zoonotic emergence. However, our work has shown that bat species already harbor SARS-like CoVs with spike proteins capable of infecting human cells. These results argue that for a subset of bat CoVs, receptor binding and infection of human cells is not the major barrier for emergence. We found that despite equivalent replication in vitro, chimeric viruses containing bat CoV spikes have reduced virulence in vivo. Mice infected with a chimeric SARS-CoV expressing the bat derived SHC014-CoV spike had reduced weight loss and lethality compared to SARS-CoV controls. Importantly, this attenuation occurs despite equivalent replication to SARS-CoV in the lung. The results indicate that virulence is dictated by more than just the ability to infect host cells in vitro. Notably, we also found that the SHC014 spike chimera has reduced infection of the large airways of the lung. These preliminary data shaped our central hypothesis that SARS- CoV virulence is predicated on both host interactions with and viral motifs in the CoV spike protein. Understanding the host and viral mechanisms that drive reduced airway infection may predict in vivo pathogenesis and have critical implications for zoonotic emergence. In this proposal, we explore the host factors and CoV spike changes that attenuate the zoonotic SHC014 spike in vivo. In part one, we examine tropism changes finding that the zoonotic SHC014 spike has impaired upper airway infection. We predict that this incompatibility relates to differences in host protease activity. We subsequently define the specific host proteases that mediate this attenuation using both in vitro and in vivo approaches. In part two, we use mouse-adaptation and structural analysis to predict spike changes responsible for attenuation of the SHC014 spike. We subsequently generate mutant viruses and restore the SHC014 spike or attenuate the SARS spike in vivo. Finally, we evaluate the mechanism of attenuation focusing on spike interactions with host proteases. Together, the proposal identifies host proteases and spike interactions that alter airway infection and dictate virulence following coronavirus infection. These findings provide critical insights for understanding virulence as well as have important implications for emergence and transmission of coronaviruses.", "keywords": [ "Attenuated", "Automobile Driving", "Binding", "Body Weight decreased", "Cells", "Chimera organism", "Chiroptera", "Clustered Regularly Interspaced Short Palindromic Repeats", "Coronavirus", "Coronavirus Infections", "Coronavirus spike protein", "Data", "Disease", "Drug usage", "Epidemic", "Family", "Goals", "Human", "Immune response", "Impairment", "In Vitro", "Infection", "Integration Host Factors", "Lung", "Mediating", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Monitor", "Mus", "Mutation", "Pathogenesis", "Peptide Hydrolases", "Pharmacotherapy", "Proteins", "SARS coronavirus", "Serine Protease", "Severe Acute Respiratory Syndrome", "Structural Models", "Structure", "System", "Testing", "Tropism", "Viral", "Virulence", "Virus", "Work", "Zoonoses", "attenuation", "base", "coronavirus receptor", "cross-species transmission", "experimental study", "in vivo", "insight", "knockout gene", "mutant", "novel", "novel coronavirus", "receptor", "receptor binding", "restoration", "reverse genetics", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "5931", "attributes": { "award_id": "5R01AI153602-02", "title": "Identifying host and viral correlates for coronavirus pathogenesis", "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": 20254, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-15", "end_date": "2024-05-31", "award_amount": 497886, "principal_investigator": { "id": 20255, "first_name": "VINEET D", "last_name": "MENACHERY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 851, "ror": "", "name": "UNIVERSITY OF TEXAS MED BR GALVESTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "The coronavirus (CoV) spike protein is a key viral determinant responsible for receptor binding and fusion/entry. The spike protein has also been predicted to be the major factor driving cross-species transmission, allowing the emergence of epidemic strains like SARS- and MERS-CoV. In the first decade after SARS-CoV emergence, changes to the epidemic spike that allowed binding to a new host receptor were thought to underlie this zoonotic emergence. However, our work has shown that bat species already harbor SARS-like CoVs with spike proteins capable of infecting human cells. These results argue that for a subset of bat CoVs, receptor binding and infection of human cells is not the major barrier for emergence. We found that despite equivalent replication in vitro, chimeric viruses containing bat CoV spikes have reduced virulence in vivo. Mice infected with a chimeric SARS-CoV expressing the bat derived SHC014-CoV spike had reduced weight loss and lethality compared to SARS-CoV controls. Importantly, this attenuation occurs despite equivalent replication to SARS-CoV in the lung. The results indicate that virulence is dictated by more than just the ability to infect host cells in vitro. Notably, we also found that the SHC014 spike chimera has reduced infection of the large airways of the lung. These preliminary data shaped our central hypothesis that SARS- CoV virulence is predicated on both host interactions with and viral motifs in the CoV spike protein. Understanding the host and viral mechanisms that drive reduced airway infection may predict in vivo pathogenesis and have critical implications for zoonotic emergence. In this proposal, we explore the host factors and CoV spike changes that attenuate the zoonotic SHC014 spike in vivo. In part one, we examine tropism changes finding that the zoonotic SHC014 spike has impaired upper airway infection. We predict that this incompatibility relates to differences in host protease activity. We subsequently define the specific host proteases that mediate this attenuation using both in vitro and in vivo approaches. In part two, we use mouse-adaptation and structural analysis to predict spike changes responsible for attenuation of the SHC014 spike. We subsequently generate mutant viruses and restore the SHC014 spike or attenuate the SARS spike in vivo. Finally, we evaluate the mechanism of attenuation focusing on spike interactions with host proteases. Together, the proposal identifies host proteases and spike interactions that alter airway infection and dictate virulence following coronavirus infection. These findings provide critical insights for understanding virulence as well as have important implications for emergence and transmission of coronaviruses.", "keywords": [ "Attenuated", "Automobile Driving", "Binding", "Body Weight decreased", "Cells", "Chimera organism", "Chiroptera", "Clustered Regularly Interspaced Short Palindromic Repeats", "Coronavirus", "Coronavirus Infections", "Coronavirus spike protein", "Data", "Disease", "Drug usage", "Epidemic", "Family", "Goals", "Human", "Immune response", "Impairment", "In Vitro", "Infection", "Integration Host Factors", "Lung", "Mediating", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Monitor", "Mus", "Mutation", "Pathogenesis", "Peptide Hydrolases", "Pharmacotherapy", "Proteins", "SARS coronavirus", "Serine Protease", "Severe Acute Respiratory Syndrome", "Structural Models", "Structure", "System", "Testing", "Tropism", "Viral", "Virulence", "Virus", "Work", "Zoonoses", "attenuation", "base", "coronavirus receptor", "cross-species transmission", "experimental study", "in vivo", "insight", "knockout gene", "mutant", "novel", "novel coronavirus", "receptor", "receptor binding", "restoration", "reverse genetics", "transmission process", "zoonotic coronavirus" ], "approved": true } }, { "type": "Grant", "id": "5114", "attributes": { "award_id": "5R01AI153602-03", "title": "Identifying host and viral correlates for coronavirus pathogenesis", "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": 18222, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-15", "end_date": "2024-05-31", "award_amount": 497886, "principal_investigator": { "id": 18224, "first_name": "VINEET D", "last_name": "MENACHERY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 851, "ror": "", "name": "UNIVERSITY OF TEXAS MED BR GALVESTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "The coronavirus (CoV) spike protein is a key viral determinant responsible for receptor binding and fusion/entry. The spike protein has also been predicted to be the major factor driving cross-species transmission, allowing the emergence of epidemic strains like SARS- and MERS-CoV. In the first decade after SARS-CoV emergence, changes to the epidemic spike that allowed binding to a new host receptor were thought to underlie this zoonotic emergence. However, our work has shown that bat species already harbor SARS-like CoVs with spike proteins capable of infecting human cells. These results argue that for a subset of bat CoVs, receptor binding and infection of human cells is not the major barrier for emergence. We found that despite equivalent replication in vitro, chimeric viruses containing bat CoV spikes have reduced virulence in vivo. Mice infected with a chimeric SARS-CoV expressing the bat derived SHC014-CoV spike had reduced weight loss and lethality compared to SARS-CoV controls. Importantly, this attenuation occurs despite equivalent replication to SARS-CoV in the lung. The results indicate that virulence is dictated by more than just the ability to infect host cells in vitro. Notably, we also found that the SHC014 spike chimera has reduced infection of the large airways of the lung. These preliminary data shaped our central hypothesis that SARS- CoV virulence is predicated on both host interactions with and viral motifs in the CoV spike protein. Understanding the host and viral mechanisms that drive reduced airway infection may predict in vivo pathogenesis and have critical implications for zoonotic emergence. In this proposal, we explore the host factors and CoV spike changes that attenuate the zoonotic SHC014 spike in vivo. In part one, we examine tropism changes finding that the zoonotic SHC014 spike has impaired upper airway infection. We predict that this incompatibility relates to differences in host protease activity. We subsequently define the specific host proteases that mediate this attenuation using both in vitro and in vivo approaches. In part two, we use mouse-adaptation and structural analysis to predict spike changes responsible for attenuation of the SHC014 spike. We subsequently generate mutant viruses and restore the SHC014 spike or attenuate the SARS spike in vivo. Finally, we evaluate the mechanism of attenuation focusing on spike interactions with host proteases. Together, the proposal identifies host proteases and spike interactions that alter airway infection and dictate virulence following coronavirus infection. These findings provide critical insights for understanding virulence as well as have important implications for emergence and transmission of coronaviruses.", "keywords": [ "Attenuated", "Automobile Driving", "Binding", "Body Weight decreased", "CRISPR/Cas technology", "Cells", "Chimera organism", "Chiroptera", "Coronavirus", "Coronavirus Infections", "Coronavirus spike protein", "Data", "Disease", "Drug usage", "Epidemic", "Family", "Goals", "Human", "Immune response", "Impairment", "In Vitro", "Infection", "Integration Host Factors", "Lung", "Mediating", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Monitor", "Mus", "Mutation", "Pathogenesis", "Peptide Hydrolases", "Pharmacotherapy", "Proteins", "Respiratory Tract Infections", "SARS coronavirus", "Serine Protease", "Severe Acute Respiratory Syndrome", "Structural Models", "System", "Testing", "Tropism", "Viral", "Virulence", "Virus", "Work", "Zoonoses", "attenuation", "base", "coronavirus receptor", "cross-species transmission", "experimental study", "in vivo", "insight", "knockout gene", "mutant", "novel", "novel coronavirus", "receptor", "receptor binding", "restoration", "reverse genetics", "transmission process", "zoonotic coronavirus" ], "approved": true } }, { "type": "Grant", "id": "6464", "attributes": { "award_id": "3UL1TR002369-04S2", "title": "Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Advancing Translational Sciences (NCATS)" ], "program_reference_codes": [], "program_officials": [ { "id": 21695, "first_name": "Christopher", "last_name": "Hartshorn", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2017-09-02", "end_date": "2022-06-30", "award_amount": 100000, "principal_investigator": { "id": 21696, "first_name": "David H", "last_name": "Ellison", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 765, "ror": "https://ror.org/009avj582", "name": "Oregon Health & Science University", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 21697, "first_name": "Cynthia D", "last_name": "Morris", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 765, "ror": "https://ror.org/009avj582", "name": "Oregon Health & Science University", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "The Oregon Clinical and Translational Research Institute (OCTRI) has been accelerating research at Oregon Health & Science University since 2006. Its many highly functional programs assist investigators and trainees by providing diverse services. Here, we propose that OCTRI will transition to retain our strengths, but also become a key hub in the national network, by focusing on five crosscutting aims. These align closely with the goals of the Funding Opportunity Announcement, and the goals outlined by NCATS for the CTSA program in an ideal state. OCTRI's overall aims are to: Overall Aim 1: Catalyze Clinical and Translational Research. Overall Aim 2: Enhance Partnerships with Communities. Overall Aim 3: Foster and Support Scientific Collaboration. Overall Aim 4: Expand the Translational Workforce for the 21st Century. Overall Aim 5: Cultivate Innovation in Research. We have organized a highly functional leadership structure to enable us to meet these goals, and will seek the guidance of several advisory groups. We will catalyze research by developing and supporting new informatics approaches that both integrate the clinical care enterprise with the research enterprise and facilitate the recruitment of patients into clinical trials, locally and across the CTSA network. We will engage diverse stakeholders in the translational research process, by partnering with OHSU investigators, community coalitions, and business enterprises. We will foster team science through local awards to trainees and to emerging investigators. We will partner with regional institutions to foster community-engaged research, to enhance the diversity of trainees, and to provide opportunities in biomedical research not available at other institutions. We will train clinical and translational scientists and research staff for the next generation, by focusing on the skills and attitudes necessary for research in the future. At all steps, we will measure outcomes and, when necessary, “turn the curve.”", "keywords": [ "Attitude", "Award", "Biomedical Research", "Businesses", "COVID-19", "Center for Translational Science Activities", "Clinical", "Clinical Data", "Clinical Research", "Clinical Trials", "Collaborations", "Communities", "Coronavirus", "Data", "Data Mart", "Data Set", "Disease", "Electronic Health Record", "Fostering", "Funding Opportunities", "Future", "Goals", "Health", "Health Sciences", "Healthcare", "Informatics", "Infrastructure", "Institutes", "Institution", "Institutional Review Boards", "Leadership", "Location", "Oregon", "Outcome Measure", "Patient Recruitments", "Process", "Research", "Research Institute", "Research Personnel", "Resources", "Science", "Secure", "Services", "Strategic Planning", "Stream", "Structure", "Time", "Training", "Translational Research", "United States", "Universities", "Work", "base", "clinical care", "cohort", "collaborative approach", "coronavirus disease", "data enclave", "data exchange", "data modeling", "data quality", "data sharing", "data warehouse", "improved", "innovation", "interoperability", "next generation", "novel strategies", "pandemic disease", "programs", "skills", "translational scientist" ], "approved": true } }, { "type": "Grant", "id": "7472", "attributes": { "award_id": "3U19AI133524-04S1", "title": "Defining regulators of immunity to acute infection using CRISPR screens", "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": 6173, "first_name": "QIAN", "last_name": "Liu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-08-21", "end_date": "2022-06-30", "award_amount": 109850, "principal_investigator": { "id": 20729, "first_name": "Arlene H.", "last_name": "Sharpe", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 855, "ror": "", "name": "HARVARD MEDICAL SCHOOL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 855, "ror": "", "name": "HARVARD MEDICAL SCHOOL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The overarching goal of this U19 Program is to use forward genetic screens in mice to advance our understanding of immune responses to pathogens. This U19 Program is driven by our recent development of a genetic screening platform that uses pooled, in vivo CRISPR-mediated loss-of- function genetic screens to identify genes that positively or negatively regulate the fate and function of immune cells. We will couple this novel approach with single-cell gene profiling and systems-level computational modeling of innate and adaptive cells during acute infection to nominate candidates to perturb functionally in genetic screens. We will then test thousands of potential regulators in pooled CRISPR-Cas9 based forward genetic screens in mice, and validate novel candidate regulators in mouse infection models and human cells. Our proposed U19 Program consists of 2 highly interactive Projects, supported by 4 Cores. Project 1 (Haining/Kuchroo/Sharpe) will conduct forward genetic screens to identify genes that regulate the fate and function of CD8+ and CD4+ T cells responding to acute infection. Project 2 (Hacohen/Kagan) will conduct screens to identify genes that control DC activation in response to pathogens, pathogen components and T cells. Administrative Core A (Sharpe/Haining) will provide administrative and scientific coordination, and implement our Pilot Project program. Data Management and Bioinformatics Core B (Regev) will develop, apply and disseminate cutting-edge methods and tools for single cell RNA-seq analysis of immune cell responses and for selecting and ranking candidate genes for genetic manipulation in CRISPR screens. Core B will also establish and maintain a public portal and software pipelines for sharing data, analyses and methods. CRISPR Library Core C (Doench) will design and generate custom single guide RNA (sgRNA) libraries needed to conduct forward genetic screens and to validate candidate regulators. Core C will also analyze genomic DNA from cells obtained pooled screens, performing sequencing and sequence deconvolution to identify sgRNAs that caused the phenotype of interest. Mouse Perturbation Core D (Sharpe/Haining) will provide a uniform platform to execute CRISPR-Cas9 screens and validation experiments in mouse infection models. The use of standardized experimental methods and computational tools by the cores will make it possible to compare and integrate results in different settings and disease models. We expect that our in vivo forward genetic screens and systems level single-cell genomic analyses will identify the central molecules, pathways and mechanism that guide innate and adaptive immune responses to infection. These findings will lay the foundation for new vaccination strategies for infectious diseases and therapies for allergy and autoimmunity.", "keywords": [ "Autoimmunity", "Bioinformatics", "Boston", "CD4 Positive T Lymphocytes", "CD8B1 gene", "CRISPR library", "CRISPR screen", "CRISPR/Cas technology", "Candidate Disease Gene", "Cell physiology", "Cells", "Clustered Regularly Interspaced Short Palindromic Repeats", "Collaborations", "Communicable Diseases", "Complement", "Computer Models", "Computer software", "Custom", "Dana-Farber Cancer Institute", "Data Analyses", "Dendritic Cells", "Development", "Disease", "Disease model", "Expression Profiling", "Foundations", "Gene Expression", "General Hospitals", "Genes", "Genetic Screening", "Genomic DNA", "Genomics", "Goals", "Guide RNA", "Hematopoietic", "Hospitals", "Human", "Hypersensitivity", "Immune", "Immune response", "Immune system", "Immunity", "Immunotherapy", "Infection", "Institutes", "Massachusetts", "Mediating", "Methods", "Modeling", "Mus", "Pathway interactions", "Pediatric Hospitals", "Phenotype", "Pilot Projects", "RNA library", "Regimen", "Research Personnel", "Research Project Grants", "Standardization", "System", "T-Lymphocyte", "Testing", "Translations", "Vaccine Adjuvant", "Vaccines", "Validation", "Woman", "acute infection", "adaptive immune response", "base", "computerized tools", "data management", "data sharing", "design", "experimental study", "genetic manipulation", "immune function", "immunoregulation", "in vivo", "innovation", "insight", "interest", "loss of function", "medical schools", "novel", "novel strategies", "pathogen", "programs", "response", "single cell analysis", "single-cell RNA sequencing", "tool", "vaccination strategy", "validation studies" ], "approved": true } }, { "type": "Grant", "id": "6088", "attributes": { "award_id": "3U19AI133524-05S1", "title": "Defining regulators of immunity to acute infection using CRISPR screens", "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": 20728, "first_name": "QIAN", "last_name": "Liu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2017-07-05", "end_date": "2022-06-30", "award_amount": 109850, "principal_investigator": { "id": 20729, "first_name": "Arlene H.", "last_name": "Sharpe", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 855, "ror": "", "name": "HARVARD MEDICAL SCHOOL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 855, "ror": "", "name": "HARVARD MEDICAL SCHOOL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The overarching goal of this U19 Program is to use forward genetic screens in mice to advance our understanding of immune responses to pathogens. This U19 Program is driven by our recent development of a genetic screening platform that uses pooled, in vivo CRISPR-mediated loss-of- function genetic screens to identify genes that positively or negatively regulate the fate and function of immune cells. We will couple this novel approach with single-cell gene profiling and systems-level computational modeling of innate and adaptive cells during acute infection to nominate candidates to perturb functionally in genetic screens. We will then test thousands of potential regulators in pooled CRISPR-Cas9 based forward genetic screens in mice, and validate novel candidate regulators in mouse infection models and human cells. Our proposed U19 Program consists of 2 highly interactive Projects, supported by 4 Cores. Project 1 (Haining/Kuchroo/Sharpe) will conduct forward genetic screens to identify genes that regulate the fate and function of CD8+ and CD4+ T cells responding to acute infection. Project 2 (Hacohen/Kagan) will conduct screens to identify genes that control DC activation in response to pathogens, pathogen components and T cells. Administrative Core A (Sharpe/Haining) will provide administrative and scientific coordination, and implement our Pilot Project program. Data Management and Bioinformatics Core B (Regev) will develop, apply and disseminate cutting-edge methods and tools for single cell RNA-seq analysis of immune cell responses and for selecting and ranking candidate genes for genetic manipulation in CRISPR screens. Core B will also establish and maintain a public portal and software pipelines for sharing data, analyses and methods. CRISPR Library Core C (Doench) will design and generate custom single guide RNA (sgRNA) libraries needed to conduct forward genetic screens and to validate candidate regulators. Core C will also analyze genomic DNA from cells obtained pooled screens, performing sequencing and sequence deconvolution to identify sgRNAs that caused the phenotype of interest. Mouse Perturbation Core D (Sharpe/Haining) will provide a uniform platform to execute CRISPR-Cas9 screens and validation experiments in mouse infection models. The use of standardized experimental methods and computational tools by the cores will make it possible to compare and integrate results in different settings and disease models. We expect that our in vivo forward genetic screens and systems level single-cell genomic analyses will identify the central molecules, pathways and mechanism that guide innate and adaptive immune responses to infection. These findings will lay the foundation for new vaccination strategies for infectious diseases and therapies for allergy and autoimmunity.", "keywords": [ "Autoimmunity", "Bioinformatics", "Boston", "CD4 Positive T Lymphocytes", "CD8B1 gene", "CRISPR library", "CRISPR screen", "CRISPR/Cas technology", "Candidate Disease Gene", "Cell physiology", "Cells", "Clustered Regularly Interspaced Short Palindromic Repeats", "Collaborations", "Communicable Diseases", "Complement", "Computer Models", "Computer software", "Custom", "Dana-Farber Cancer Institute", "Data Analyses", "Dendritic Cells", "Development", "Disease", "Disease model", "Foundations", "Gene Expression", "General Hospitals", "Genes", "Genetic Screening", "Genomic DNA", "Genomics", "Goals", "Guide RNA", "Hematopoietic", "Hospitals", "Human", "Hypersensitivity", "Immune", "Immune response", "Immune system", "Immunity", "Immunotherapy", "Infection", "Institutes", "Massachusetts", "Mediating", "Methods", "Modeling", "Mus", "Pathway interactions", "Pediatric Hospitals", "Phenotype", "Pilot Projects", "RNA library", "Regimen", "Research Personnel", "Research Project Grants", "Standardization", "System", "T-Lymphocyte", "Testing", "Translations", "Vaccine Adjuvant", "Vaccines", "Validation", "Woman", "acute infection", "adaptive immune response", "base", "computerized tools", "data management", "data sharing", "design", "experimental study", "genetic manipulation", "immune function", "immunoregulation", "in vivo", "innovation", "insight", "interest", "loss of function", "medical schools", "novel", "novel strategies", "pathogen", "programs", "response", "single cell analysis", "single-cell RNA sequencing", "tool", "vaccination strategy", "validation studies" ], "approved": true } }, { "type": "Grant", "id": "8748", "attributes": { "award_id": "1R35GM142677-01", "title": "Ancient viral threats through the lens of adaptation in human genomes", "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": 24539, "first_name": "Ronald", "last_name": "Adkins", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-09-17", "end_date": "2026-07-30", "award_amount": 377363, "principal_investigator": { "id": 24540, "first_name": "David", "last_name": "Enard", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 438, "ror": "https://ror.org/03m2x1q45", "name": "University of Arizona", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 438, "ror": "https://ror.org/03m2x1q45", "name": "University of Arizona", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true }, "abstract": "The current SARS-COV2 pandemic has brought to light that more efforts are needed to evaluate the pandemic potential of viruses that can spill over in human populations. To assess the pandemic potential of specific viruses, over the next five years my lab will ask if similar viruses caused epidemics not only during the recent documented past, but during the much longer time scale of human evolution. Viruses that caused epidemics in the past are indeed the most likely to cause epidemics again in the future, and hundreds of viral epidemics likely plagued human populations during their evolution. This work will fill gaps in knowledge on epidemics in ancestral human populations, and by doing so, will enable a better assessment of the viruses that represent a future pandemic threat. To study ancient epidemics, my lab will exploit host genomic adaptation driven by ancient viruses. Arms races with viruses have shaped the host immune system by driving a large number of adaptations. I recently showed that viruses left abundant signals of adaptation not only in immune genes, but across the entire human genome. The lab will examine signals of adaptation left by specific viruses in human genomes, to detect, date, and functionally characterize ancient epidemics. To this aim, we will develop new statistical tools based on recent advances in machine learning and in the reconstruction of Ancestral Recombination Graphs (ARGs). These new approaches with increased power to detect and date genomic adaptation will allow us to ask the following questions: 1) Which viruses drove ancient epidemics in human evolution? My lab will create deep learning tests with high power to detect complex genomic adaptation within the past ~200,000 years of human evolution. 2) When did specific viruses drive ancient epidemics? We will use ARGs and Approximate Bayesian Computation to date ancient epidemics, by dating the host adaptive events driven by specific viruses. 3) Which functional host genetic changes were selected during ancient epidemics, in which genes, and how do they influence genetic susceptibility to present viruses? We will investigate regulatory adaptation to viruses and the overall impact of virus-driven host adaptation on the genetic susceptibility of different human populations to specific present viruses, thereby providing virologists with strong candidate host genes for further inquiry. My lab is uniquely suited to decipher ancient epidemics by linking host-pathogen interactions together with the latest developments in the population genomics of adaptation.", "keywords": [ "Automobile Driving", "Bayesian Analysis", "COVID-19 pandemic", "Complex", "Development", "Epidemic", "Event", "Evolution", "Future", "Genes", "Genetic Predisposition to Disease", "Genetic Recombination", "Genomics", "Graph", "Human", "Human Genome", "Immune", "Immune system", "Knowledge", "Left", "Link", "Machine Learning", "Mutation", "Population", "Race", "Signal Transduction", "Testing", "Time", "Viral", "Virus", "Work", "arm", "base", "deep learning", "lens", "novel strategies", "pandemic disease", "pathogen", "reconstruction", "tool" ], "approved": true } } ], "meta": { "pagination": { "page": 1385, "pages": 1397, "count": 13961 } } }