Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1384&sort=-start_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-start_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=-start_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1385&sort=-start_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1383&sort=-start_date" }, "data": [ { "type": "Grant", "id": "6512", "attributes": { "award_id": "3T15LM007092-29S1", "title": "BIC TRAIN - Biomedical Informatics COVID-19 Training", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Library of Medicine (NLM)" ], "program_reference_codes": [], "program_officials": [ { "id": 21833, "first_name": "YANLI", "last_name": "WANG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "1992-07-01", "end_date": "2022-06-30", "award_amount": 174995, "principal_investigator": { "id": 21834, "first_name": "Nils", "last_name": "Gehlenborg", "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": "For Parent Grant: Harvard Biomedical Informatics and Data Science Research Training (BIRT) program, April 2016. This proposal for the Harvard Biomedical Informatics and Data Science Research Training (BIRT) program recognizes that the field of biomedical informatics is an increasingly relevant, if not essential, field for medicine and research in the health sciences. The practice of clinical care and biomedical investigation each constitute complex enterprises that are dependent on the mastery of enormous data streams. There is a crucial need for trained individuals who are able to integrate, interpret, and act upon the large-scale, high-throughput, and complex data that are generated in the course of biomedical research and the practice of medicine. The primary aim of this proposal is to contribute to the cadre of highly trained independent and successful researchers in the field of biomedical informatics. This proposal builds on the strengths of our many years of National Library of Medicine (NLM) fellowship training. The current proposed program will be overseen and administered by the Department of Biomedical Informatics at Harvard Medical School (HMS) and will involve collaboration with faculty at HMS and its affiliated hospitals, including Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, Dana Farber Cancer Institute, and Massachusetts General Hospital. In addition, the program will work closely with other Harvard University Schools in the university-wide data science initiative, and, in particular, with its Data Science Education Working Group, of which the proposed PI is a member. We meet all requirements of the current NLM RFA, which focuses on those informatics areas that directly pertain to health-related application domains. The breadth and depth of our research laboratories, real-world clinical systems, research activities, academic programs, and experienced faculty provide an outstanding environment to mentor and instruct trainees in all four of the NLM-identified focus areas – healthcare informatics, translational bioinformatics, clinical research informatics, and public health informatics. We request support for a total of fifteen trainees per year: ten at the postdoctoral level and five at the predoctoral level. In addition, we propose to train four short-term trainees each summer. BIRT trainees work with internationally recognized faculty on high-profile grants and research projects. The program has a formal, required academic component, which includes the Master’s degree for all postdoctoral trainees, and the PhD degree for all predoctoral students. Trainees’ overall progression throughout the training period is closely monitored. Trainees are regularly evaluated through their course work and through progress on their research projects.", "keywords": [ "Area", "Bioinformatics", "Biomedical Research", "Boston", "COVID-19", "Clinical", "Clinical Research", "Collaborations", "Complex", "Dana-Farber Cancer Institute", "Data Science", "Doctor of Philosophy", "Environment", "Faculty", "Fellowship", "General Hospitals", "Grant", "Health", "Health Sciences", "Healthcare", "Hospitals", "Individual", "Informatics", "International", "Investigation", "Israel", "Laboratory Research", "Massachusetts", "Master&apos", "s Degree", "Medical center", "Medicine", "Mentors", "Monitor", "Pediatric Hospitals", "Public Health Informatics", "Research", "Research Activity", "Research Personnel", "Research Project Grants", "Research Training", "Schools", "Students", "Training", "Training Programs", "United States National Library of Medicine", "Universities", "Woman", "Work", "academic program", "biomedical informatics", "clinical care", "clinical practice", "complex data", "data streams", "experience", "medical schools", "member", "parent grant", "pre-doctoral", "programs", "science education", "systems research", "working group" ], "approved": true } }, { "type": "Grant", "id": "5386", "attributes": { "award_id": "3U01AG009740-33S1", "title": "Health and Retirement Study: Years 29-34", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 18863, "first_name": "John", "last_name": "Phillips", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "1990-09-25", "end_date": "2023-12-31", "award_amount": 990154, "principal_investigator": { "id": 18864, "first_name": "DAVID R.", "last_name": "WEIR", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "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": "This competing continuation proposal for Years 29-34 of the Health and Retirement Study (HRS) cooperative agreement is in response to NIA RFA #AG-18-005. The primary aim of the HRS is to design, collect and distribute longitudinal multi-disciplinary data to support research on aging and the health and well- being of the older population. This proposal seeks to collect three additional waves of panel data, continue collection of venous blood specimens, implement the next scheduled refreshment by adding the first Gen-X cohort in 2022, continue to conduct off-year mail surveys, and implement cost-saving innovations, including an internet mode for Core data collection. It will continue the same expanded minority oversample design for the Gen-X cohort as was implemented in 2010 and 2016 for the baby boom cohorts in which half the sample consists of traditionally underrepresented minorities. The new Gen-X cohort will be fully integrated into the HRS design, including collection of biomarkers, DNA, and linkage consents to Social Security and other records as appropriate. This parent project will provide sample, data, and coordinate fully with the separate proposal to repeat the Harmonized Cognitive Assessment Protocol dementia study. HRS provides a uniquely rich, nationally representative longitudinal dataset for the community of scientific and policy researchers who study the health and demography of aging. It provides a research data base that can simultaneously support cross-sectional descriptions of the U.S. population age 50+, longitudinal studies of a given cohort over a substantial period of time and research on cross-cohort trends. The HRS project creates a data system extending beyond the core survey data. One component of this extended data system consists of linkages to administrative data, including Social Security earnings and benefit records, Medicare utilization and diagnostic records, including Minimum Data Set and Medicaid records, employer pension records, Veterans Health Administration data and the National Death Index. We plan to expand access to these secure data through secure enclaves. Another component is genome-wide genotyping data from consenting respondents distributed through dbGaP and a new repository of blood samples including cryopreserved cells. HRS provides public use data designed to allow the full power and creativity of America's scientific community to address the challenges of an aging population. HRS is making a significant impact on research on aging through investigator-initiated research which uses the HRS as an input without charge to researchers or granting agencies. Over 2,000 peer-reviewed journal publications have appeared, nearly 1,000 in the past six years. HRS also supports training of new scientists as over 400 doctoral dissertations have used HRS data.", "keywords": [ "Address", "Age", "Aging", "Americas", "Baby Booms", "Bibliography", "Biological Assay", "Biological Markers", "Biological Specimen Banks", "Blood", "Blood specimen", "Brazil", "Cessation of life", "Charge", "China", "Collaborations", "Collection", "Communities", "Complex", "Consent", "Consumption", "Cost Savings", "Country", "Creativeness", "Cryopreserved Cell", "DNA", "Data", "Data Collection", "Data Set", "Databases", "Decision Making", "Dementia", "Development", "Devices", "Diagnostic", "Documentation", "Elements", "England", "Enrollment", "Europe", "Exhibits", "Future", "Genetic", "Genotype", "Geography", "Grant", "Health", "Health and Retirement Study", "Income", "India", "Indonesia", "Information Systems", "International", "Internet", "Interview", "Investigator-Initiated Research", "Japan", "Journals", "Life Experience", "Longitudinal Studies", "Measurement", "Measures", "Medicaid", "Medicare", "Methods", "Mexico", "Minority", "Older Population", "Online Systems", "Peer Review", "Pensions", "Personal Satisfaction", "Persons", "Physical activity", "Policies", "Population", "Population Study", "Prevalence Study", "Protocols documentation", "Public Health", "Publications", "Records", "Research", "Research Design", "Research Personnel", "Research Support", "Respondent", "Rotation", "Sampling", "Schedule", "Scientist", "Secure", "Security", "Services", "Social Security", "Source", "South Africa", "Structure", "Surveys", "Time", "Training Support", "U-Series Cooperative Agreements", "Underrepresented Minority", "Update", "Venous", "Veterans Health Administration", "aging demography", "aging population", "cognitive ability", "cognitive function", "cognitive testing", "cohort", "cost", "cost effective", "data access", "data quality", "data resource", "database of Genotypes and Phenotypes", "design", "distributed data", "genome-wide", "improved", "indexing", "innovation", "longitudinal dataset", "member", "multidisciplinary", "neuroimaging", "parent project", "prospective", "psychosocial", "recruit", "repository", "research and development", "response", "screening", "sustained attention", "symposium", "trend", "web site" ], "approved": true } }, { "type": "Grant", "id": "6179", "attributes": { "award_id": "3U01AG009740-32S1", "title": "HRS Yrs 29-34: Covid Antibody Revision", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 20968, "first_name": "John", "last_name": "Phillips", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "1990-09-25", "end_date": "2023-12-31", "award_amount": 1538248, "principal_investigator": { "id": 20969, "first_name": "DAVID R.", "last_name": "WEIR", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "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": "This revision to Years 29-34 of the Health and Retirement Study (HRS) cooperative agreement seeks to collect and analyze saliva samples from up to 17,639 HRS participants for the presence of antibodies to SARS-CoV-2. The effect of the virus on cognitive function and the development of Alzheimer’s Disease and Alzheimer’s Related Dementias (AD/ADRD) is a major concern for the future public health of the older population. While severe cases of COVID-19 requiring hospitalization will be well-documented for future study, many less severe cases go completely undiagnosed, making it difficult to accurately study outcomes of all types of exposure. To be useful, antibody testing must be done before vaccines are available, which means the risk of infection from the collection of samples in person is a serious concern. We therefore propose to use a self-administered saliva test, with innovative shipping technology to maintain samples at 4 degrees Celsius during return shipping to the analytic lab. The University of Minnesota’s Advanced Research Diagnostics Lab, a CLIA-certified facility and one of 4 national reference laboratories selected by the National Cancer Institute for SARS-CoV-2 antibody testing, will conduct the assays. Participants will receive a report of positive or negative antibody status, while more detailed continuous measures of antibody titers will be available for research from the positive cases. Data will be made available to the research community for use with the wealth of HRS data on genetics, immune function, and social interactions.", "keywords": [ "Acute", "Address", "Aging", "Alzheimer&apos", "s Disease", "Alzheimer&apos", "s disease related dementia", "Antibodies", "Antibody titer measurement", "Biological Assay", "Biosocial", "Blood Vessels", "Blood coagulation", "Brain", "CLIA certified", "COVID-19", "Caring", "Chronic", "Cognition", "Communities", "Data", "Data Linkages", "Dementia", "Development", "Diagnostics Research", "Disease Outcome", "Exposure to", "Family", "Flow Cytometry", "Future", "Genetic", "Genomics", "Health and Retirement Study", "Hispanics", "Hospitalization", "Household", "Immunologics", "Impaired cognition", "Infection", "Inflammation", "Laboratories", "Laboratory Research", "Liquid substance", "Location", "Longitudinal Studies", "Measures", "Mechanical ventilation", "Medicare", "Methods", "Minnesota", "National Cancer Institute", "Occupations", "Older Population", "Oral", "Outcome", "Outcome Study", "Participant", "Persons", "Pharmaceutical Preparations", "Public Health", "Publishing", "Records", "Reporting", "Research", "Research Personnel", "Risk", "SARS-CoV-2 antibody", "SARS-CoV-2 exposure", "SARS-CoV-2 infection", "Sampling", "Self Administration", "Severities", "Shipping", "Social Interaction", "Source", "Stroke", "Structure", "Subgroup", "Technology", "Testing", "Time", "Tissues", "U-Series Cooperative Agreements", "Universities", "Virus", "antibody test", "cognitive change", "cognitive function", "coronavirus disease", "data dissemination", "genomic data", "immune function", "infection risk", "innovation", "pandemic disease", "population based", "racial disparity", "saliva sample", "salivary assay", "sample collection", "study population", "trend", "vaccine acceptance", "vaccine access" ], "approved": true } }, { "type": "Grant", "id": "7406", "attributes": { "award_id": "3R01DC000566-31S2", "title": "Complex Odor Recognition of the Main Olfactory Bulb", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Deafness and Other Communication Disorders (NIDCD)" ], "program_reference_codes": [], "program_officials": [ { "id": 6520, "first_name": "SUSAN L.", "last_name": "SULLIVAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "1988-12-12", "end_date": "2023-04-30", "award_amount": 194375, "principal_investigator": { "id": 23206, "first_name": "Diego", "last_name": "Restrepo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 784, "ror": "https://ror.org/02hh7en24", "name": "University of Colorado Denver", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 784, "ror": "https://ror.org/02hh7en24", "name": "University of Colorado Denver", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19 is a devastating disease caused by the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV2) that has resulted in 100,442 deaths in the U.S. (May 28th, 2020). Smell loss is a major symptom for COVID-19 (1-4). In a recent publication we identified TRPM5-expressing cells (microvillous cells (MVCs) and olfactory sensory neurons (OSNs)) as viral-responding cells in the olfactory epithelium (OE)(5). MVCs are part of a family of TRPM5-expressing cells found in the airways and the intestine that respond to virus, bacteria and irritants with a type 2 immune response through IL-25 and release of acetylcholine (6, 7). In preliminary studies we find that intranasal herpes simplex virus type 1 (HSV-1) infection in mice elicits a dramatic shift in TRPM5 expression from MVCs to the basal epithelium consistent with activation of stem cells (SCs) for immune defense, as proposed for chronic inflammation of the OE (8-10) expression However, inflammation It is unclear whether this increased and altered location of TRPM5 is an aberrant response, contributing to persistent inflammation. influenza infection increases TRPM5 expressing cells in the lung, leading to damaging persistent (11) Here . . we hypothesize that SARS-CoV-2 infection of OE upregulates TRPM5 expression, leading to proinflammatory cytokine release, decrease in OSN numbers and activity, persistent inflammation yet ineffective viral clearance leading to worse COVID-19; whereas addition of TRPM5 blockers will attenuate cytokine release and viral loads. We epithelial flufenamic will test this hypothesis with studies of changes in inflammation and olfactory function in human olfactory cell cultures infected with by inhibition of TRPM5 using the FDA approved drug acid in two specific aims: SARS-CoV2 Aim 1. Determine if activation of the TRPM5 transduction cascade in MVCs mediates the inflammatory response to SARS-CoV-2 viral infection leading to loss of olfactory function. Aim 2. Determine if TRPM5 expression in the OE promotes SARS-CoV-2 neurotropism, facilitating nervous system disease.", "keywords": [ "2019-nCoV", "Acetylcholine", "Acids", "Adult Respiratory Distress Syndrome", "Afferent Neurons", "Anosmia", "Anti-Inflammatory Agents", "Antiviral Agents", "Apoptosis", "Attenuated", "Bacteria", "Bioinformatics", "Biological Assay", "Biology", "Biopsy", "Brain Stem", "COVID-19", "Cell Culture Techniques", "Cells", "Cessation of life", "Characteristics", "Chronic", "Clinical", "Complex", "Data", "Disease", "Effectiveness", "Ensure", "Enzyme-Linked Immunosorbent Assay", "Epithelial", "Epithelium", "FDA approved", "Family", "Flufenamic Acid", "Gene Expression", "Generations", "Gland", "Herpesvirus 1", "Human", "Human Resources", "Immune", "Immune response", "Immunofluorescence Immunologic", "Infection", "Inflammation", "Inflammatory", "Inflammatory Response", "Influenza", "Intestines", "Irritants", "Location", "Lung", "Mediating", "Microfluidics", "Mus", "Neurites", "Neurologic", "Neurotropism", "Nose", "Odors", "Olfactory Epithelial Cell", "Olfactory Epithelium", "Pathway interactions", "Pharmaceutical Preparations", "Phenotype", "Pneumonia", "Process", "Proteins", "Publications", "Recovery", "Respiratory Failure", "Respiratory System", "Route", "SARS coronavirus", "Sensory", "Serine Protease", "Severe Acute Respiratory Syndrome", "Severity of illness", "Site", "Smell Perception", "Surveys", "Symptoms", "TMPRSS2 gene", "TRPM5 gene", "Testing", "Transcript", "Travel", "Trigeminal System", "Viral", "Viral Load result", "Viral load measurement", "Virus", "Virus Diseases", "biosafety level 3 facility", "cytokine", "cytokine release syndrome", "experience", "experimental study", "human coronavirus", "immunocytochemistry", "inhibitor/antagonist", "nervous system disorder", "novel", "olfactory bulb", "olfactory sensory neurons", "prevent", "receptor", "response", "stem cells", "therapeutic target", "transcriptome", "transcriptome sequencing", "virology" ], "approved": true } }, { "type": "Grant", "id": "5038", "attributes": { "award_id": "3P60AA006282-40S1", "title": "Environmental Approaches to Prevention", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [ { "id": 18038, "first_name": "Gregory", "last_name": "Bloss", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "1983-09-29", "end_date": "2022-11-30", "award_amount": 154923, "principal_investigator": { "id": 18039, "first_name": "PAUL J", "last_name": "GRUENEWALD", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 807, "ror": "", "name": "PACIFIC INSTITUTE FOR RES AND EVALUATION", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "The Prevention Research Center (PRC), a division of Pacific Institute for Research and Evaluation (PIRE), was formed in October 1983 around the \"Environmental Approaches to Prevention\" Research Center grant, selected by peer review as the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) national Center for prevention research. The goals of the Center are: (1) to undertake innovative basic research that contributes to the development of cost-effective environmental prevention programs and policies at the local, state, and national levels; (2) to undertake research of applied and practical importance to inform policies and programs to prevent alcohol-related problems, especially in the area of environmental factors; (3) to summarize and synthesize new and existing knowledge about prevention theories, policies, and programs, and to disseminate this information to professional, academic, and community audiences; and (4) to provide multidisciplinary training and research opportunities for post-doctoral fellows and other early investigators. We take a multidisciplinary approach to prevention research that emphasizes integration across theories from the biological to the behavioral and social sciences to enhance our understanding of the causal impacts of drinking environments on drinking patterns and problems. Research we are proposing for the renewal of the Center continues this approach, building upon extensive work conducted among cities in California in the previous rounds, and continuing to focus on the micro- and macro-ecological contexts of alcohol use. We will consider the social and situational conditions that affect early initiation of underage alcohol use, intoxication, and progression to heavier drinking and related problems (Component #3). Identification of these conditions will improve our understanding of how micro-environments affect early developmental trajectories and guide us toward effective preventive interventions to reduce underage alcohol use. We will examine young adult drinking patterns and problems in large Hispanic/Latino communities situated along the California-Mexico border and some distance away in order to assess how macro- and micro-ecological differences in access to alcohol affect drinking and problems in this subpopulation (Component #4). This study will illuminate sources of alcohol-related health disparities that arise among Hispanic/Latino drinkers and help us identify those unique drinking contexts and situations for which effective preventive interventions should be designed. We will investigate the dynamic inter-relationships of alcohol use, problems, and AUD symptomatology among heavy drinkers in order to establish how micro-ecological contexts of heavy drinking might be manipulated to reduce the large number of problems that arise in communities in association with AUDs (Component #5). For the first time in any environmental research program we will integrate theoretical models and empirical data from these studies into an agent-based modeling framework that allows us to test a select set of scenarios that involve altering social ecological mechanisms that could ameliorate alcohol- related problems in communities (the Framework for Reconstructing Epidemiological Dynamics, FRED; Component #6). Finally, we will continue our focus on providing information and dissemination of community-based preventive intervention research, expanding our utilization of social media (Component #2).", "keywords": [ "Affect", "Alcohol abuse", "Alcohol consumption", "Alcoholic beverage heavy drinker", "Alcohols", "Applied Research", "Area", "Basic Science", "Behavioral", "Behavioral Sciences", "Biological", "California", "Cities", "Communities", "Data", "Development", "Developmental Process", "Economic Conditions", "Economics", "Environment", "Environmental Risk Factor", "Epidemiology", "Etiology", "Evaluation", "Geographic Locations", "Goals", "Grant", "Heavy Drinking", "Hispanics", "Individual", "Information Dissemination", "Intervention", "Intervention Studies", "Intoxication", "Knowledge", "Latino", "Mexico", "Mission", "Modeling", "National Institute on Alcohol Abuse and Alcoholism", "Pattern", "Peer Review", "Persons", "Policies", "Population", "Postdoctoral Fellow", "Prevention", "Prevention Research", "Prevention approach", "Prevention program", "Process", "Research", "Research Activity", "Research Institute", "Research Personnel", "Risk", "Safety", "Social Conditions", "Social Sciences", "Socioeconomic Factors", "Source", "Testing", "Theoretical model", "Time", "Training", "Work", "alcohol availability", "alcohol misuse prevention", "alcohol prevention", "alcohol related problem", "alcohol use disorder", "base", "behavioral/social science", "community setting", "cost", "cost effective", "design", "differences in access", "drinking", "effectiveness testing", "efficacy study", "field study", "health disparity", "high risk", "improved", "innovation", "interdisciplinary approach", "interest", "multidisciplinary", "preventive intervention", "programs", "psychologic", "public policy on alcohol", "social", "social media", "social situation", "symptomatology", "theories", "underage drinking", "young adult" ], "approved": true } }, { "type": "Grant", "id": "5719", "attributes": { "award_id": "3P60AA006282-39S1", "title": "Environmental Approaches to Prevention", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [ { "id": 19726, "first_name": "Gregory", "last_name": "Bloss", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "1983-09-29", "end_date": "2022-11-30", "award_amount": 154923, "principal_investigator": { "id": 19727, "first_name": "PAUL J", "last_name": "GRUENEWALD", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 807, "ror": "", "name": "PACIFIC INSTITUTE FOR RES AND EVALUATION", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "The Prevention Research Center (PRC), a division of Pacific Institute for Research and Evaluation (PIRE), was formed in October 1983 around the \"Environmental Approaches to Prevention\" Research Center grant, selected by peer review as the National Institute on Alcohol Abuse and Alcoholism's (NIAAA's) national Center for prevention research. The goals of the Center are: (1) to undertake innovative basic research that contributes to the development of cost-effective environmental prevention programs and policies at the local, state, and national levels; (2) to undertake research of applied and practical importance to inform policies and programs to prevent alcohol-related problems, especially in the area of environmental factors; (3) to summarize and synthesize new and existing knowledge about prevention theories, policies, and programs, and to disseminate this information to professional, academic, and community audiences; and (4) to provide multidisciplinary training and research opportunities for post-doctoral fellows and other early investigators. We take a multidisciplinary approach to prevention research that emphasizes integration across theories from the biological to the behavioral and social sciences to enhance our understanding of the causal impacts of drinking environments on drinking patterns and problems. Research we are proposing for the renewal of the Center continues this approach, building upon extensive work conducted among cities in California in the previous rounds, and continuing to focus on the micro- and macro-ecological contexts of alcohol use. We will consider the social and situational conditions that affect early initiation of underage alcohol use, intoxication, and progression to heavier drinking and related problems (Component #3). Identification of these conditions will improve our understanding of how micro-environments affect early developmental trajectories and guide us toward effective preventive interventions to reduce underage alcohol use. We will examine young adult drinking patterns and problems in large Hispanic/Latino communities situated along the California-Mexico border and some distance away in order to assess how macro- and micro-ecological differences in access to alcohol affect drinking and problems in this subpopulation (Component #4). This study will illuminate sources of alcohol-related health disparities that arise among Hispanic/Latino drinkers and help us identify those unique drinking contexts and situations for which effective preventive interventions should be designed. We will investigate the dynamic inter-relationships of alcohol use, problems, and AUD symptomatology among heavy drinkers in order to establish how micro-ecological contexts of heavy drinking might be manipulated to reduce the large number of problems that arise in communities in association with AUDs (Component #5). For the first time in any environmental research program we will integrate theoretical models and empirical data from these studies into an agent-based modeling framework that allows us to test a select set of scenarios that involve altering social ecological mechanisms that could ameliorate alcohol- related problems in communities (the Framework for Reconstructing Epidemiological Dynamics, FRED; Component #6). Finally, we will continue our focus on providing information and dissemination of community-based preventive intervention research, expanding our utilization of social media (Component #2).", "keywords": [ "Affect", "Alcohol abuse", "Alcohol consumption", "Alcoholic beverage heavy drinker", "Alcohols", "Applied Research", "Area", "Basic Science", "Behavioral", "Behavioral Sciences", "Biological", "California", "Cities", "Communities", "Data", "Development", "Developmental Process", "Economic Conditions", "Economics", "Environment", "Environmental Risk Factor", "Epidemiology", "Etiology", "Evaluation", "Geographic Locations", "Goals", "Grant", "Heavy Drinking", "Hispanics", "Individual", "Information Dissemination", "Intervention", "Intervention Studies", "Intoxication", "Knowledge", "Latino", "Mexico", "Mission", "Modeling", "National Institute on Alcohol Abuse and Alcoholism", "Pattern", "Peer Review", "Policies", "Population", "Postdoctoral Fellow", "Prevention", "Prevention Research", "Prevention approach", "Prevention program", "Process", "Research", "Research Activity", "Research Institute", "Research Personnel", "Risk", "Safety", "Social Conditions", "Social Sciences", "Socioeconomic Factors", "Source", "Testing", "Theoretical model", "Time", "Training", "Work", "alcohol availability", "alcohol misuse prevention", "alcohol prevention", "alcohol related problem", "alcohol use disorder", "base", "behavioral/social science", "community setting", "cost", "cost effective", "design", "differences in access", "drinking", "effectiveness testing", "efficacy study", "field study", "health disparity", "high risk", "improved", "innovation", "interdisciplinary approach", "interest", "multidisciplinary", "preventive intervention", "programs", "psychologic", "public policy on alcohol", "social", "social media", "social situation", "symptomatology", "theories", "underage drinking", "young adult" ], "approved": true } }, { "type": "Grant", "id": "6112", "attributes": { "award_id": "3R01DA003371-32A1S1", "title": "Substance Use Among American Indian Youth: Epidemiology & Etiology", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)" ], "program_reference_codes": [], "program_officials": [ { "id": 20786, "first_name": "Kathleen", "last_name": "ETZ", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "1983-09-01", "end_date": "2025-07-31", "award_amount": 150852, "principal_investigator": { "id": 20787, "first_name": "Mark A", "last_name": "Prince", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 323, "ror": "https://ror.org/03k1gpj17", "name": "Colorado State University", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 20788, "first_name": "RANDALL C", "last_name": "SWAIM", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 20789, "first_name": "Linda Rae", "last_name": "Stanley", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 323, "ror": "https://ror.org/03k1gpj17", "name": "Colorado State University", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19 has had disproportionate negative impacts on American Indian (AI) communities for a variety of reasons, including inadequate healthcare, lack of or broken infrastructure, high rates of comorbidity, devastation of economies (e.g., gaming and tourism), and inadequate and disjointed efforts to ameliorate the effects of the virus (Doshi, Jordan, Kelly and Solomon, 2020). AI adolescents have some of the highest substance use rates in the U.S. and findings from other research indicate that the COVID-19 pandemic may be changing substance use rates and patterns. This study would examine COVID-related changes in substance use and relationships between substance use and psychosocial and other variables that may be affected by the pandemic among American Indian adolescents who live on or near reservations. One aim of this project is to provide nationally representative rates and mean levels of COVID-related variables by grade, sex, and ethnicity (AI and non-AI) for COVID-related substance use behavior measures; COVID morbidity and mortality experienced by these adolescents; COVID-specific attitudes and behaviors (e.g., perceived risks of infection); COVID-related protective factors for substance use; and COVID-related risk factors for substance use. In addition, the study will examine models of COVID-19 related risk and protective factors that might influence AI adolescent substance use. These models will be focused on resilience to identify the strengths that result in positive outcomes for these adolescents. School principals will also be surveyed to gather information about their COVID-related responses and resources available to help students cope with the effects from the pandemic. This data will be incorporated into multilevel models. The findings from this research will be published in scientific peer-reviewed journals and will be disseminated widely to Native, public health, school, and policy officials.", "keywords": [ "Adolescent", "Affect", "American Indians", "Anxiety", "Attitude", "Behavior", "COVID-19", "COVID-19 morbidity", "COVID-19 pandemic", "Categories", "Communities", "Data", "Ecosystem", "Epidemiology", "Ethnic Origin", "Etiology", "Family", "Future", "Health", "Healthcare", "Infrastructure", "Jordan", "Journals", "Measures", "Mental Health", "Modeling", "Monitor", "Outcome", "Pattern", "Peer Review", "Policies", "Public Health Schools", "Publishing", "Research", "Reservations", "Resources", "Risk", "Risk Factors", "Schools", "Social isolation", "Stress and Coping", "Students", "Substance Use Disorder", "Surveys", "Testing", "Virus", "Work", "Youth", "addiction", "adolescent substance use", "behavioral economics", "comorbidity", "coronavirus disease", "epidemiologic data", "experience", "food insecurity", "infection risk", "member", "mortality", "multilevel analysis", "neurodevelopment", "pandemic disease", "parent grant", "peer influence", "protective factors", "psychosocial", "resilience", "response", "sex", "substance use" ], "approved": true } }, { "type": "Grant", "id": "7475", "attributes": { "award_id": "3R01DE006014-37S1", "title": "Bacteria and Lymphocyte Suppression in Periodontitis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Dental and Craniofacial Research (NIDCR)" ], "program_reference_codes": [], "program_officials": [ { "id": 21363, "first_name": "Tamara L", "last_name": "McNealy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "1982-08-01", "end_date": "2022-03-31", "award_amount": 243125, "principal_investigator": { "id": 23273, "first_name": "BRUCE J", "last_name": "SHENKER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 232, "ror": "https://ror.org/00b30xv10", "name": "University of Pennsylvania", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 232, "ror": "https://ror.org/00b30xv10", "name": "University of Pennsylvania", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "We are requesting a one year administrative supplement to our RO1 grant DE006014 entitled Bacteria and lymphocyte suppression in periodontitis. The purpose of this request is to expand the scope of the grant to take advantage of recent observations made on the cytolethal distending toxin (Cdt) and apply them to advancing our knowledge of and identifying novel therapeutic pathways for preventing SARS-CoV-2 infection. Specifically, we have identified a novel role for a host cell protein, cellugyrin (synaptogyrin-2; discussed below), which plays a requisite role in the internalization and endososmal trafficking of the active subunit of Cdt, CdtB; these events are critical to toxicity. Like the internalization process utilized by exotoxins, viruses must gain entry into host cells; this process involves the interaction between viral glycoprotein, such as SARS-CoV-2 spike protein. This protein, like other viral spike proteins, provides a receptor binding domain that confers host cell specificity (e.g, ACE2) and also fusogenic function critical to merging the virus envelope with host endosomal membrane during viral entry. Recent studies have indicated that oral epithelial cells express ACE2 and may be a target for SARS- CoV-2 infection. Therefore, this study will focus on human oral-pulmonary epithelial cells lines. We propose that cellugyrin is a major component of a universal endocytic process utilized by both virus and exotoxins to achieve entry into host cells. This study will focus on the requirement for cellugyrin for SARS-CoV-2 entry into host cells. In order to contain SARS-CoV-2 infection, it is important to identify early molecular mechanism(s) that contribute to its high infectivity as these likely also represent attractive targets for therapeutic intervention. This proof-of-principle study is aimed at demonstrating a key role for cellugyrin in the pathogenesis of SARS-CoV-2 infection of cells within the oral-respiratory tract. The potential for high impact of these studies is to provide the underpinnings for developing a novel, alternative and potentially transformative therapeutic approach to mitigate SARS-CoV-2 infection. It is in this context that this study directly addresses the spirit and focus of the Notice of Special Interest (NOSI) (NOT-DE-20-022): Urgent Competitive Revisions and Administrative Supplements for Coronavirus Disease 2019 (COVID-19) as it is not only of potential high impact, but also addresses acquisition of a more robust understanding of SARS-CoV-2 pathogenesis. Moreover, the proposal addresses one of the bulleted targets of this funding announcement: examination of the role of oral/nasal microbiota and ACE2 receptor on SARS-CoV-2 infectivity and carriage in oral fluids and nasal secretions, as gateways to the spread of infection into the respiratory tract via proof of principle studies.", "keywords": [ "1-Phosphatidylinositol 3-Kinase", "2019-nCoV", "Accounting", "Actinobacillus actinomycetemcomitans", "Address", "Administrative Supplement", "Amino Acids", "Apoptosis", "Bacteria", "Binding", "Binding Sites", "CDC2 gene", "COVID-19", "Campylobacter", "Cell Communication", "Cell Cycle Arrest", "Cell Cycle Proteins", "Cell Death", "Cell Line", "Cell surface", "Cells", "Chancroids", "Cholesterol", "Chromosomes", "Cyclin-Dependent Kinases", "DNA Damage", "DNA Repair", "Deoxyribonucleases", "Disease", "Dose", "Epithelial", "Epithelial Cells", "Epithelium", "Escherichia coli", "Event", "Exotoxins", "Exposure to", "Family", "Funding", "Genital system", "Glycoproteins", "Goals", "Grant", "Hela Cells", "Helicobacter", "Hemophilus ducreyi", "Homologous Gene", "Host Defense", "Human", "Immune response", "Impairment", "Infection", "Inflammation", "Inositol", "Knowledge", "Lead", "Link", "Liquid substance", "Lung", "Lymphocyte", "Lymphocyte Suppression", "Lymphoid Cell", "Mediating", "Membrane", "Molecular", "Nose", "Nuclear", "Oral", "PTEN gene", "Pathogenesis", "Pathway interactions", "Peptides", "Periodontitis", "Phosphatidylinositols", "Phosphoric Monoester Hydrolases", "Play", "Process", "Progress Reports", "Proteins", "Proteobacteria", "Respiratory System", "Role", "Salmonella enterica", "Sexual Transmission", "Shigella", "Ships", "Signal Transduction", "Specificity", "Stomach", "Structure", "Synaptic Vesicles", "Testing", "Therapeutic", "Therapeutic Intervention", "Toxic effect", "Toxin", "Tumor Suppressor Proteins", "Viral", "Virulence Factors", "Virus", "Work", "Yersinia enterocolitica", "acquired immunity", "base", "carcinogenicity", "cell growth", "cell type", "cellugyrin", "cytokine", "cytolethal distending toxin", "human pathogen", "immune clearance", "immunogenic", "inhibitor/antagonist", "insight", "interest", "keratinocyte", "macrophage", "nasal microbiota", "neutralizing antibody", "novel", "novel therapeutics", "oncoprotein p21", "oral cavity epithelium", "oral pathogen", "paralogous gene", "pathogen", "prevent", "protein expression", "receptor", "receptor binding", "response", "retrograde transport", "synaptogyrin", "targeted treatment", "tensin", "trafficking", "tripolyphosphate", "vesicle transport", "virus envelope" ], "approved": true } }, { "type": "Grant", "id": "7128", "attributes": { "award_id": "3P50AA005595-40S1", "title": "Epidemiology of Alcohol Problems: Alcohol-related Disparities", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [ { "id": 6554, "first_name": "Gregory", "last_name": "Bloss", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "1981-07-01", "end_date": "2021-02-28", "award_amount": 287615, "principal_investigator": { "id": 22926, "first_name": "William C", "last_name": "Kerr", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1188, "ror": "https://ror.org/019621n74", "name": "Public Health Institute", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1188, "ror": "https://ror.org/019621n74", "name": "Public Health Institute", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 (C-19) pandemic has drastically changed life in the US, starting in March 2020 with stay-at-home orders for much of the population and mass closures of businesses, including on-premise alcohol outlets. To date, off-premise alcohol sales have been maintained in most states, and delivery and to-go options temporarily expanded. Alcohol sales in March 2020 were substantially higher than expected, indicating consumers increased home alcohol stocks, and potentially consumption. By June 2020, bars and restaurants have re-opened in many states with varying distancing restrictions, prompting concerns of virus spread through congregation. The focus of this Center Project was originally on analyses of selected major causes of illness, injury, disability and death where significant racial/ethnic and socioeconomic disparities are evident in the US and which are substantially alcohol-related. The proposed revision Aims will focus on changes in drinking patterns, substance use and mental health measures from before to during the COVID-19 restriction period, associations between drinking patterns and COVID-19 risk behaviors and behavioral health care need, access and utilization with attention to racial/ethnic and socioeconomic disparities. The 2019-2020 National Alcohol Survey (N14) completed fielding on April 20, 2020 with 80% of cases collected before March 2020 and included web survey respondents recruited through address-based sampling (ABS; n=5,176) and telephone respondents recruited through random digit dialing (RDD; n=1,323). We propose to re-survey 1,500 N14 ABS and RDD respondents with a follow-up instrument, N14C, focused on drinking, substance use, and COVID-19 risk behaviors and attitudes in the COVID-19 period. This longitudinal design allows us to build on the rich lifecourse data and pre-COVID-19 measures collected in N14, integrating new questions on recent substance use behaviors and problems, physical and mental health, and COVID-19-related risk behaviors, attitudes and impacts, including job loss and financial insecurity. N14C questions on alcohol and drug use and related problems will reference appropriate C-19 period timeframes, including during stay-at-home orders (closed period) and during phased reopening (open period). Changes in alcohol and drug use, co-use and problems will be assessed through comparisons with N14 responses. N14C questions will include drinking motives and alcohol purchasing, as well as COVID-19 risk behaviors such as mask wearing, hand washing and congregating in groups of non-household members. Updated geocoding information of area characteristics and policies, such as bar closures and expanded delivery, will be utilized, allowing policy analyses utilizing within-person, pre-post comparisons to assess impacts on alcohol use and problems. Measures of an individual's pre-existing health conditions, including diabetes, hypertension and heart disease, will facilitate analyses of factors expected to raise the risk of COVID-19 impacts and measures of depression and anxiety symptoms and discrimination will be utilized for important and timely analyses focused on mental health, stress, and discrimination experiences related to COVID-19 impacts.", "keywords": [ "Address", "Alcohol abuse", "Alcohol consumption", "Alcohol or Other Drugs use", "Alcohols", "Area", "Attention", "Attitude", "Behavior", "Behavioral", "Businesses", "COVID-19", "COVID-19 pandemic", "Caring", "Cessation of life", "Characteristics", "Chronic", "Climacteric", "Consumption", "County", "Data", "Diabetes Mellitus", "Digit structure", "Discrimination", "Drug usage", "Education", "Employment Status", "Ethnic Origin", "Factor Analysis", "Family", "Family health status", "Frequencies", "Handwashing", "Health", "Health Policy", "Healthcare", "Heart Diseases", "Home environment", "Hypertension", "Individual", "Injury", "Insurance", "Internet", "Interview", "Lifestyle-related condition", "Link", "Location", "Marital Status", "Masks", "Measures", "Medicaid", "Mental Health", "Neighborhoods", "Occupations", "Outcome", "Pattern", "Persons", "Pharmaceutical Preparations", "Phase", "Police", "Policies", "Policy Analysis", "Population", "Provider", "Race", "Research", "Research Project Grants", "Respondent", "Restaurants", "Risk", "Risk Behaviors", "Risk Factors", "Risk Reduction", "Risk Reduction Behavior", "Sales", "Sampling", "Services", "Severities", "Social Distance", "Source", "Stress", "Surveys", "Telephone", "Time", "Unemployment", "Update", "Virus", "alcohol consequences", "alcohol epidemiology", "alcohol misuse", "alcohol related problem", "alcohol risk", "alcohol use disorder", "anxiety symptoms", "base", "behavioral health", "demographics", "depressive symptoms", "disability", "drinking", "economic impact", "ethnic discrimination", "experience", "follow-up", "health care disparity", "health disparity", "health economics", "high risk", "instrument", "longitudinal design", "member", "pandemic disease", "physical conditioning", "public health relevance", "racial and ethnic", "racial and ethnic disparities", "recruit", "response", "socioeconomic disparity", "socioeconomics", "telehealth" ], "approved": true } }, { "type": "Grant", "id": "6760", "attributes": { "award_id": "2R01HL019278-46A1", "title": "Platelet Integrin AlphaIIbBeta3 Structure, Activation, and Ligand Binding: Fibrinogen, Fibrin, D-dimer, and von Willebrand Factor", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 22561, "first_name": "Andrei L.", "last_name": "Kindzelski", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "1976-09-01", "end_date": "2026-01-31", "award_amount": 776645, "principal_investigator": { "id": 22562, "first_name": "Barry", "last_name": "Coller", "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": "Platelets play a key role in both hemostasis and thrombosis and contribute to COVID-19 pathology. Platelet αIIbβ3 is the paradigmatic integrin receptor and a validated drug target, with abciximab, developed under this grant, the first FDA-approved αIIbβ3 antagonist. In the current grant period, we rationally designed and synthesized novel αIIbβ3 and αVβ3 antagonists that lock the receptor in the inactive conformation, which may confer therapeutic benefits. The αIIbβ3 antagonist (RUC-4; zalunfiban) is now in Phase 2 human studies for pre- hospital therapy of heart attacks and the αVβ3 antagonists are being developed for pre-clinical testing. We also began studying key gaps in our understanding of how αIIbβ3: 1. Binds its medically important ligands, including fibrinogen, polymerizing fibrin, von Willebrand factor (vWf), and cross-linked fibrin. 2. Initiates clot retraction to confer resistance to thrombolysis. 3. Transitions from its inactive to its active state. Thus, we studied the interaction of αIIbβ3 with fragment D-dimer and used a novel functional assay to dissect the interaction of αIIbβ3 with polymerizing fibrin. In addition, we obtained high-resolution cryo-electron microscopy (EM) structures of αIIbβ3 in complex with abciximab and with the activating monoclonal antibody (mAb) PT25-2, providing data on each antibody’s mechanism of activation. We also initiated hydrogen-deuterium exchange-mass spectroscopy (HDX) studies of αIIbβ3 to provide peptide-level dynamic structural information on ligand binding and receptor activation to complement cryo-EM data. The new Specific Aims build on the PI’s long-standing collaborations with Dr. Marta Filizola, an expert in computational methods, and Dr. Thomas Walz, an expert in cryo-EM. Specific Aim 1. A. To determine high-resolution cryo-EM structures of D-dimer and of αIIbβ3 in complex with: 1) fibrinogen fragment D100 and fibrinogen γ-module; 2) vWf C4 domain; 3) D-dimer. B. To obtain peptide- level solvent-exposed area data by HDX on αIIbβ3 alone and in complex with the ligands. C. To obtain complementary structural and dynamics information from computer simulations to guide mutational analysis and mAb production to validate the proposed mechanisms of binding, as well as to develop novel ligand-specific small-molecule antagonists. Specific Aim 2. To utilize currently available and future cryo-EM data sets in concert with computational and HDX data to define intermediate structures of the integrin leg domains along the αIIbβ3 activation pathway. Specific Aim 3. To utilize our novel functional polymerizing fibrin assays using platelets and HEK293 cells expressing native and mutant forms of αIIbβ3, in concert with mAbs and small-molecule αIIbβ3 antagonists, to define the unique αIIbβ3 ligand-specific binding mechanisms and develop ligand-specific inhibitors. A. To produce mAbs to D-dimer that inhibit platelet-fibrin, but not platelet-fibrinogen interactions. B. To identify mutations that selectively impair fibrinogen, fibrin, or vWf binding, and examine their impact on clot retraction. C. To test predictions derived from the structural and computational studies with mAb and small- molecule ligand-specific inhibitors as a prelude to animal and ultimately human studies.", "keywords": [ "Address", "Affinity", "Animals", "Antibodies", "Antiplatelet Drugs", "Area", "Binding", "Binding Sites", "Biological Assay", "Biology", "Blood Platelets", "COVID-19", "Cells", "Chimeric Proteins", "Clot retraction", "Coagulation Process", "Collaborations", "Complement", "Complex", "Computer Simulation", "Computing Methodologies", "Cryoelectron Microscopy", "Data", "Data Set", "Deuterium", "Development", "Disease", "Docking", "Drug Targeting", "Electron Microscopy", "FDA approved", "Fab Immunoglobulins", "Family", "Fibrin", "Fibrin fragment D", "Fibrinogen", "Fibrinolysis", "Future", "Goals", "Grant", "Hemostatic function", "Hospitals", "Human", "Hydrogen", "Impairment", "Individual", "Inflammation", "Integrins", "Leg", "Length", "Ligand Binding", "Ligands", "Mass Spectrum Analysis", "Medical", "Methods", "Molecular", "Molecular Conformation", "Monitor", "Monoclonal Antibodies", "Mutation", "Mutation Analysis", "Myocardial Infarction", "Natural Immunity", "Nature", "Neoplasm Metastasis", "Pathologic", "Pathology", "Pathway interactions", "Patients", "Peptides", "Pharmaceutical Chemistry", "Pharmaceutical Preparations", "Phase", "Platelet Glycoprotein GPIIb-IIIa Complex", "Platelet aggregation", "Plavix", "Play", "Polymers", "Pre-Clinical Model", "Preclinical Testing", "Process", "Proteins", "RGD (sequence)", "Receptor Activation", "Resistance", "Resolution", "Review Literature", "Role", "Solvents", "Stroke", "Structure", "Testing", "Therapeutic", "Thrombosis", "Thrombus", "Time", "VWF gene", "X-Ray Crystallography", "abciximab", "clopidogrel", "computer studies", "crosslink", "design", "high throughput screening", "inhibitor/antagonist", "maltose-binding protein", "monoclonal antibody production", "mutant", "nanodisk", "novel", "novel therapeutics", "pre-clinical", "protein structure", "receptor", "reconstitution", "small molecule", "thrombolysis", "vascular injury", "von Willebrand Factor", "wound healing" ], "approved": true } } ], "meta": { "pagination": { "page": 1384, "pages": 1392, "count": 13920 } } }