Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1382&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=1424&sort=-start_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1383&sort=-start_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1381&sort=-start_date" }, "data": [ { "type": "Grant", "id": "5639", "attributes": { "award_id": "3R01CA149105-10S1", "title": "Urban Revitalization and Long-Term Effects on Diet, Economic, and Health Outcomes", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 19509, "first_name": "Jill", "last_name": "Reedy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2010-05-14", "end_date": "2023-05-31", "award_amount": 196619, "principal_investigator": { "id": 19510, "first_name": "Tamara", "last_name": "Dubowitz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 515, "ror": "https://ror.org/00f2z7n96", "name": "RAND Corporation", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Food insecurity—a lack of consistent access to enough food for an active, healthy life—is a fundamental social determinant of health linked to poor nutrition, obesity, and chronic disease. During the initial months of the COVID-19 pandemic, existing racial inequities in food insecurity were exacerbated. Compared to an estimated increase of 60% in the U.S. general population, food insecurity increased nearly 80% among residents of two low-income African American food desert neighborhoods in Pittsburgh, Pennsylvania. Other data from our cohort as well as other studies suggests there were also substantial upticks in financial instability and mental health challenges as the pandemic and policy responses to it unfolded. We propose these three factors may be part of a syndemic (synergy of epidemics), i.e., that food insecurity, financial instability and mental distress may share similar causal roots, that they also influence one another, and that this process is exacerbated by disadvantage. Few scientific studies have longitudinal data with which to examine these factors. Our longitudinal cohort of low-income African Americans allows an opportunity to examine the health and economic impact of the pandemic. We propose analyses of our Pittsburgh Research on Neighborhood Change and Health (PHRESH) cohort data collected during three periods, including before and during the COVID-19 pandemic, to test these ideas. Specifically, our aims are to: (1) Examine the effects of the COVID-19 containment and mitigation efforts (shut downs, stay at home orders, school closings) on food security, financial stability, and mental health from pre-pandemic (2018) to its early months (Spring 2020), to more than one year following the U.S. outbreak (through mid-year 2021), testing for trends in these outcomes and how these trends are associated with one another. In addition, we will (2) test the extent to which pre-existing (2018) individual-level perceived (e.g., self-reported discrimination, low social status) and structural (neighborhood investments, improved socioeconomic conditions, walkability) inequities moderated pandemic impacts, buffering or exacerbating its influence on residents’ food security, financial stability and mental health.", "keywords": [ "Address", "Affect", "African American", "Buffers", "COVID-19", "COVID-19 pandemic", "Chronic Disease", "Communities", "Containment", "Data", "Development", "Diet", "Disadvantaged", "Discrimination", "Disease Outbreaks", "Distress", "Documentation", "Economics", "Epidemic", "Food", "Funding", "General Population", "Grant", "Health", "Health Policy", "Home", "Individual", "Intervention", "Investments", "Life", "Link", "Long-Term Effects", "Longitudinal Studies", "Longitudinal cohort", "Low income", "Mental Health", "Natural experiment", "Neighborhoods", "Nutritional", "Obesity", "Outcome", "Parents", "Patient Self-Report", "Pennsylvania", "Personal Satisfaction", "Plant Roots", "Policies", "Privatization", "Process", "Psyche structure", "Public Housing", "Research", "Risk", "Role", "Schools", "Series", "Services", "Social Distance", "Social status", "Structure", "Supermarket", "Testing", "Work", "base", "behavioral economics", "cohort", "economic impact", "epidemiology study", "experience", "food desert", "food insecurity", "food security", "health economics", "health inequalities", "improved", "marginalized population", "nutrition", "pandemic disease", "parent grant", "psychological distress", "resilience", "response", "social", "social health determinants", "socioeconomics", "synergism", "trend", "walkability" ], "approved": true } }, { "type": "Grant", "id": "5010", "attributes": { "award_id": "1007615", "title": "Student Travel Support for the Infocom 2010 Conference; San Diego, CA", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Unknown", "Networking Technology and Syst" ], "program_reference_codes": [], "program_officials": [], "start_date": "2010-05-01", "end_date": "2011-04-30", "award_amount": 25000, "principal_investigator": { "id": 17962, "first_name": "Athina", "last_name": "Markopoulou", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 177, "ror": "", "name": "University of California-Irvine", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The 2010 IEEE INFOCOM Conference on Computer Communications will be held in San Diego, CA from March 15 to March 19, 2010. This flagship technical conference is a premier venue in the area of computer communications, and is widely attended by researchers and practitioners in the field. This project provides funds to support approximately twenty-one graduate and post-graduate students in the United States to attend INFOCOM 2010 and to present their work. Participating students will also have the opportunity to attend several technical activities, including paper presentations, workshops, tutorials and panel/keynote sessions.\n\nThe intellectual merit of the proposal resides in encouraging and supporting student attendance to INFOCOM 2010. This continues the tradition of previous INFOCOM conferences as a premier venue for bringing together academia, industry, and government to share newest developments. Its rich program exposes participants to new ideas and cutting-edge research and allows for interaction between researchers from all over the world.\n\nIn terms of broader Impact, the project integrates research and education through exposure of students to one of the premier conferences in computer communications. Students have the opportunity to attend high-quality presentations and interact with senior researchers as well as peers in the field. This experience is expected to have a positive impact on the students? development as well as in shaping the future of the field. The project also promotes diversity by encouraging and enabling the participation of women, graduate students from under-represented minorities and institutions, and, for the first time, postdoctoral students as well.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "5875", "attributes": { "award_id": "3UG1EY020522-13S1", "title": "Comparative Effectiveness Research & Cochrane Eyes and Vision (CEV)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Eye Institute (NEI)" ], "program_reference_codes": [], "program_officials": [ { "id": 20118, "first_name": "Sangeeta", "last_name": "Bhargava", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2010-05-01", "end_date": "2022-06-30", "award_amount": 249361, "principal_investigator": { "id": 20119, "first_name": "Tianjing", "last_name": "Li", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "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": "As in related eyes throughout problem disproportionally society adapts to the constantly evolving COVID-19 pandemic, the evidence supporting face mask wearing public and in healthcare settings is strong. Yet, regular and prolonged mask use may increase dry eye- symptoms, even in individuals without a history of dry eye. The upward air flow from the mask into the likely accelerates the evaporation of the tear film, which, when masks are worn continuously for hours the work week, may result in ocular surface irritation and/or inflammation. Dry eye is global health associated with multiple underlying diagnoses that has a considerable impact on quality of life, affects the elderly and women, and is expensive to treat. a This symptoms mask understand prevalence eye-related administrative supplement will measure the ocular surface, cular environment, and dry eye-related mong a sample of healthcare workers across the job spectrum exposed to regular and prolonged use ( Aim 1 ); elucidate the potential role of masks in exacerbating dry eye-related symptoms and coping behaviors among hospital workers who participated in Aim 1 ( Aim 2 ); and assess the of barriers and facilitators of the use of environmental and behavioral modifications to reduce dry symptoms ( Aim 3 ). o a To achieve these aims, we will utilize innovative technology to measure relative humidity in front of the eyes. We will integrate qualitative and quantitative approaches and data. We will focus on underserved population and those of lower socioeconomic positions, and purposely sample from these groups. Findings from the proposed study will drive innovative and affordable healthcare solutions, promoting self-management of dry eye. The collaborations (Grant proposed work will leverage key research findings, the theoretica l basis, resources, expertise, and supported by grant Comparative Effectiveness Research & Cochrane Eyes and Vision #: UG1 EY020522).", "keywords": [ "Administrative Supplement", "Affect", "Air", "Air Movements", "Behavior", "Behavior Therapy", "Behavioral", "Biological", "COVID-19", "COVID-19 pandemic", "Clinical Services", "Collaborations", "Comparative Effectiveness Research", "Coping Behavior", "Cornea", "Country", "Data", "Diagnosis", "Disease", "Dryness", "Economics", "Effectiveness", "Elderly woman", "Environment", "Exposure to", "Eye", "Eyeglasses", "Face", "Film", "Fluorescein", "Foundations", "Grant", "Health", "Health Personnel", "Healthcare", "Homelessness", "Hospitals", "Hour", "Humidifier", "Humidity", "Indigent", "Individual", "Inflammation", "Interferometry", "Intervention", "Interview", "Lead", "Masks", "Measurement", "Measures", "Medicaid", "Methods", "Modification", "Occupations", "Patient Self-Report", "Patients", "Perception", "Population", "Prevalence", "Quality of life", "Questionnaires", "Recording of previous events", "Refugees", "Reporting", "Research", "Research Personnel", "Resources", "Respondent", "Role", "Sampling", "Self Management", "Severities", "Societies", "Stains", "Structure", "Surface", "Surveys", "Symptoms", "Telephone", "Testing", "Time", "Touch sensation", "Underserved Population", "Uninsured", "Vent", "Vision", "Vulnerable Populations", "Work", "authority", "comparative", "coping", "coronavirus disease", "cost", "design", "effectiveness research", "evaporation", "eye dryness", "face mask", "global health", "health care settings", "indexing", "innovation", "innovative technologies", "instrument", "intervention cost", "irritation", "low socioeconomic status", "ocular surface", "pandemic disease", "parent grant", "population health", "prevent", "psychosocial", "recruit", "response", "safety net", "socioeconomics", "tv watching", "viral transmission" ], "approved": true } }, { "type": "Grant", "id": "6344", "attributes": { "award_id": "3U54MD004811-09S1", "title": "Transdisciplinary Research, Equity and Engagement Center for Advancing Behavioral Health", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Minority Health and Health Disparities (NIMHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 21389, "first_name": "DOROTHY M", "last_name": "CASTILLE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2010-05-01", "end_date": "2022-06-30", "award_amount": 189376, "principal_investigator": { "id": 21390, "first_name": "Maria Yellow Horse", "last_name": "Brave Heart", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 761, "ror": "", "name": "UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR", "address": "", "city": "", "state": "NM", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 21391, "first_name": "Lisa Marie", "last_name": "Cacari Stone", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 21392, "first_name": "Gabriel Ramon", "last_name": "Sanchez", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 21393, "first_name": "Steven P.", "last_name": "Verney", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 761, "ror": "", "name": "UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR", "address": "", "city": "", "state": "NM", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT We propose an innovative Transdisciplinary Research, Equity and Engagement Center for Advancing Behavioral Health (TREE Center). We propose to expand on and leverage the knowledge, research capacities and cross-sectoral collaborations established by the former NM CARES Health Disparities Center (P20 MD004811, R. Williams, PI). We will use these strengths to specifically target improvement of behavioral health disparities for socioeconomically disadvantaged and underserved rural populations with a southwest regional focus on American Indian/Alaska Natives (AI/ANs) and Latinos in New Mexico. Our goal is to highlight the social determinants of behavioral health, including Adverse Childhood Experiences, historical trauma, and intersectional effects of poverty and discrimination to improve conditions and outcomes related to youth suicide, alcohol and drug misuse, depression, and access to behavioral health services. The four aims of the TREE Center are to: 1. Implement a co-leadership model in order to promote transdisciplinary, multi-level intervention research that will advance the knowledge and science to improve behavioral health outcomes; 2. Operationalize collaborative integration of theories, study design, and analysis into multi-level interventions that improve behavioral health outcomes due to an the interplay of biological, behavioral, physical environment, health care system, economic, and political forces in our representative rural, AI/AN, Latino and other partner communities; 3. Expand the development of a diverse scientific workforce by training new and early stage under-represented minority investigators in a transdisciplinary context, to conduct community engaged, multi- level intervention behavioral health research; and 4. Cultivate equitable collaborations with community and tribal stakeholders regionally and nationally in order to translate and co-disseminate transdisciplinary research evidence into practice and policy. The combined human, intellectual and relational resources and institutional commitments of Tree Center office space, travel funding for engaging with the Community Scientific Advisory Committee and dedicated mentoring of senior faculty will strengthen our impact in training the next generation of under-represented minorities and advancing the behavioral health of diverse populations in the southwest.", "keywords": [ "Address", "Advisory Committees", "Advocacy", "Affect", "Age", "Alaska Native", "American Indians", "Area", "Behavioral", "Biological", "Collaborations", "Communities", "Complex", "Data", "Development", "Disadvantaged", "Discrimination", "Economics", "Elements", "Ethics", "Foundations", "Funding", "Geography", "Goals", "Health", "Health Promotion", "Health Services", "Health Status", "Health system", "Healthcare Systems", "Human", "Human Rights", "Individual", "Infrastructure", "Internet", "Intervention", "Intervention Studies", "Knowledge", "Latino", "Leadership", "Mental Depression", "Mentors", "Minority", "Modeling", "New Mexico", "Outcome", "Physical environment", "Plant Roots", "Policies", "Politics", "Population", "Population Heterogeneity", "Poverty", "Research", "Research Design", "Research Personnel", "Research Project Grants", "Resources", "Role", "Rural", "Rural Population", "Science", "Suicide", "System", "Testing", "Training", "Translating", "Translations", "Trauma", "Trees", "Underrepresented Minority", "Work", "Youth", "adverse childhood events", "alcohol misuse", "base", "behavioral health", "behavioral health intervention", "community based participatory research", "dissemination research", "drug misuse", "ethnic minority population", "frontier", "health care disparity", "health disparity", "health equity", "improved", "innovation", "intersectionality", "minority health", "minority investigator", "next generation", "novel strategies", "racial and ethnic", "rural Americans", "rural underserved", "senior faculty", "social", "social determinants", "social health determinants", "socioeconomic disadvantage", "socioeconomic disparity", "space travel", "success", "theories", "therapy design" ], "approved": true } }, { "type": "Grant", "id": "4950", "attributes": { "award_id": "3R01AI088364-13S1", "title": "Inborn errors of immunity in children with herpes simplex encephalitis", "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": 17812, "first_name": "Deborah", "last_name": "Hodge", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2010-04-06", "end_date": "2023-03-31", "award_amount": 74534, "principal_investigator": { "id": 17813, "first_name": "Jean-Laurent", "last_name": "Casanova", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 17814, "first_name": "Shen-Ying", "last_name": "Zhang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 763, "ror": "https://ror.org/0420db125", "name": "Rockefeller University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Childhood herpes simplex encephalitis (HSE) is a life-threatening complication of primary infection with herpes simplex virus 1 (HSV-1), which is typically innocuous. Acyclovir-treated survivors often suffer from severe neurological sequelae. Most infections affect the forebrain, with only a minority affecting the brainstem. HSE is the most common sporadic viral encephalitis in Western countries. Its pathogenesis remained unclear until we showed that it results, in some children, from single-gene inborn errors of immunity to HSV-1 in the central nervous system (CNS). Using a candidate gene approach, we and others discovered the first six genetic etiologies of forebrain HSE: mutations of TLR3, UNC93B1, TRIF, TRAF3, TBK1, and IRF3. These disorders impair TLR3-dependent, IFN-α/β- and IFN-l-mediated, cell-intrinsic immunity in iPSC-derived cortical neurons. With NIH R01AI088364 funding, we initiated a genome-wide approach to search for novel HSE-causing genes by a combination of genome-wide linkage (GWL) analysis and whole-exome sequencing (WES). This led to the discovery of 1) a novel genetic etiology of forebrain HSE, SNORA31 mutations, and 2) the first genetic etiology of brainstem HSE, DBR1 mutations. Both disorders impair cell-intrinsic immunity to HSV-1 by novel mechanisms, independent of TLR3. No genetic etiology has yet been identified for 258 of the 280 HSE patients studied. We now hypothesize that 1) other single-gene inborn errors of CNS-intrinsic immunity to HSV-1 can underlie HSE, and 2) mutations affecting different pathways are responsible for forebrain and brainstem HSE. In the work proposed in this renewal application, we will use next-generation sequencing (NGS), including WES, whole- genome sequencing (WGS), and RNA-seq, to search for novel genetic etiologies of HSE. We will analyze the NGS data at both the population and patient levels, following both a candidate gene approach and an unbiased hypothesis-generating approach. We will consider models based on both genetic homogeneity and genetic heterogeneity, while also testing both physiological homogeneity (HSE-causing genes being physiologically related) and heterogeneity (different pathways involved), making use of novel computational approaches. We will analyze the function of mutant alleles of candidate genes. We will also use the patients’ fibroblasts to investigate the impact of the candidate genotypes on anti-HSV-1 immunity. This application is innovative but supported by exciting preliminary data. We have established a unique international cohort of 450 HSE children and intend to enroll at least 600 patients. From the WES data for the first 280 patients, we have already identified biallelic mutations of MEX3B and IFNAR1 (in the TLR3-IFN-a/b circuit), RIPK1 and RIPK3 (in the TLR3- necroptosis pathway), and TMEFF1 (defining a novel pathway). Our research will decipher the pathogenesis of a devastating pediatric illness, paving the way for new therapeutic approaches. The genetic analysis of HSE will also provide proof-of-principle that sporadic, life-threatening infectious diseases striking an isolated organ in otherwise healthy children can result from single-gene inborn errors of non-hematopoietic cell-intrinsic immunity.", "keywords": [ "Acyclovir", "Affect", "Alleles", "Architecture", "Biochemical", "Brain Stem", "Candidate Disease Gene", "Cells", "Child", "Childhood", "Clinical", "Collection", "Communicable Diseases", "Complication", "Country", "Data", "Disease", "Encephalitis", "Enrollment", "Family", "Fibroblasts", "Funding", "Genes", "Genetic", "Genetic Counseling", "Genetic Heterogeneity", "Genetic Predisposition to Disease", "Genetic study", "Genotype", "Hereditary Disease", "Herpes encephalitis", "Herpesvirus 1", "Heterogeneity", "Human Genetics", "IFNAR1 gene", "IRF3 gene", "Immunity", "Immunologics", "Impairment", "Individual", "Infection", "Interferon-alpha", "Interferons", "International", "Laboratories", "Lesion", "Leukocytes", "Life", "Mediating", "Mendelian disorder", "Minority", "Modeling", "Molecular", "Molecular Diagnosis", "Molecular Genetics", "Mutation", "Neuraxis", "Neurologic", "Neurons", "Olfactory Nerve", "Organ", "Parents", "Pathogenesis", "Pathway interactions", "Patients", "Penetrance", "Phenotype", "Physiological", "Population", "Primary Infection", "Privatization", "Prosencephalon", "RIPK1 gene", "RIPK3 gene", "Research", "Resistance", "Solid", "Survivors", "TBK1 gene", "TLR3 gene", "TNF receptor-associated factor 3", "Techniques", "Testing", "Trigeminal nerve structure", "United States National Institutes of Health", "Validation", "Variant", "Viral Encephalitis", "Work", "base", "candidate selection", "clinical care", "cohort", "congenital immunodeficiency", "design", "exome sequencing", "genetic analysis", "genetic linkage analysis", "genome sequencing", "genome-wide", "genome-wide linkage", "induced pluripotent stem cell", "innovation", "kindred", "mutant", "next generation sequencing", "novel", "novel therapeutic intervention", "recruit", "response", "trait", "transcriptome sequencing", "whole genome" ], "approved": true } }, { "type": "Grant", "id": "5573", "attributes": { "award_id": "3R01AI088364-12S1", "title": "Monogenic basis of resistance to SARS-CoV2 and predisposition to severe COVID-19", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 19329, "first_name": "Deborah", "last_name": "Hodge", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2010-04-06", "end_date": "2023-03-31", "award_amount": 446039, "principal_investigator": { "id": 19330, "first_name": "Jean-Laurent", "last_name": "Casanova", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 19331, "first_name": "Shen-Ying", "last_name": "Zhang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 763, "ror": "https://ror.org/0420db125", "name": "Rockefeller University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "In December 2019, a novel coronavirus (SARS-CoV-2) emerged in the city of Wuhan, China, and quickly spread worldwide, with an increasing number of cases and deaths. In populations naive to this new pathogen, there has been immense inter-individual clinical variability among infected individuals, ranging from asymptomatic infection to lethal coronavirus infectious disease-19 (COVID-19), which is typically due to pneumonitis and rarely to encephalitis. The infection to severe/life-threatening ratio is estimated to be < 1/1,000 in people <20 years, around 5/1,000 in people 20-50 years, >1/100 over 50 years, and > 1/10 over 80 years. Underlying medical conditions also greatly increase the risk of severe COVID-19. On the other hand, rare cases of apparent resistance to the infection itself have also been identified (viral PCR-negative and seronegative individuals despite repeated and confirmed exposure). In this context, we hypothesize that monogenic inborn errors of immunity (IEI) may underlie life-threatening COVID-19 infections in previously healthy, young individuals (<50 years), whereas monogenic inborn variations of resistance (IVR) may protect other individuals from SARS-CoV- 2 infection. Both hypotheses are based on 25 years of studies of a wide range of other viral infections, for which IEI (e.g. influenza virus pneumonitis) and IVR (e.g. resistance to human immunodeficiency virus) have been identified. We will recruit both IEI and IVR cohorts not only in the USA but also, importantly, at the international level; search for candidate disease-causing variants using a cutting-edge strategy developed in our laboratory to analyze whole-exome sequencing (WES) data; and perform in-depth functional studies to characterize the products of candidate genotypes biochemically, and to analyze the corresponding patients’ cells immunologically. Our program aims to discover the human genetic and immunological basis of both severe “idiopathic” COVID- 19 and natural resistance to SARS-CoV-2. Our preliminary results are exciting. In less than 2 months, we and Helen Su (NIAID) have organized the global and growing “COVID Human Genetic Effort” (CHGE), with over 400 collaborators and 40 sequencing hubs in 50 countries (www.covidhge.com). In the last month, our own hub sequenced over 100 patients in the IEI cohort and enrolled 2 individuals in the IVR cohort. We have already selected 5 promising candidate genes (IKFZ1, POLR3C,TLR7, IRF7, IL22), which are all involved in anti-viral interferon immunity. Our program focuses on a timely problem (severe COVID in previously healthy young patients and individuals naturally resistant to infection), tests a bold but plausible hypothesis (monogenic basis for both groups of outliers), and uses cutting-edge genetic and mechanistic studies (including the study of leukocyte subsets and induced pluripotent stem cells (iPSC)-derived pulmonary epithelial cells). Our project will permit genetic diagnosis and counseling, while facilitating the development of novel preventive and therapeutic strategies including anti-viral drugs (e.g. aimed at restoring a deficient immunity or blocking viral entry) and vaccines (e.g. aimed at boosting certain immunological pathways) in both genetic and non-genetic cases.", "keywords": [ "Acyclovir", "Affect", "Alleles", "Architecture", "Biochemical", "Brain Stem", "Candidate Disease Gene", "Cells", "Child", "Childhood", "Clinical", "Collection", "Communicable Diseases", "Complication", "Country", "Data", "Disease", "Encephalitis", "Enrollment", "Family", "Fibroblasts", "Funding", "Genes", "Genetic", "Genetic Counseling", "Genetic Heterogeneity", "Genetic Predisposition to Disease", "Genetic study", "Genotype", "Hereditary Disease", "Herpes encephalitis", "Herpesvirus 1", "Heterogeneity", "Human Genetics", "IFNAR1 gene", "IRF3 gene", "Immunity", "Immunologics", "Impairment", "Individual", "Infection", "Interferon-alpha", "Interferons", "International", "Laboratories", "Lesion", "Leukocytes", "Life", "Mediating", "Mendelian disorder", "Minority", "Modeling", "Molecular", "Molecular Diagnosis", "Molecular Genetics", "Mutation", "Neuraxis", "Neurologic", "Neurons", "Olfactory Nerve", "Organ", "Parents", "Pathogenesis", "Pathway interactions", "Patients", "Penetrance", "Phenotype", "Physiological", "Population", "Primary Infection", "Privatization", "Prosencephalon", "RIPK1 gene", "RIPK3 gene", "Research", "Resistance", "Solid", "Survivors", "TBK1 gene", "TLR3 gene", "TNF receptor-associated factor 3", "Techniques", "Testing", "Trigeminal nerve structure", "United States National Institutes of Health", "Validation", "Variant", "Viral Encephalitis", "Work", "base", "candidate selection", "clinical care", "cohort", "congenital immunodeficiency", "design", "exome sequencing", "genetic analysis", "genetic linkage analysis", "genome sequencing", "genome-wide", "genome-wide linkage", "induced pluripotent stem cell", "innovation", "kindred", "mutant", "next generation sequencing", "novel", "novel therapeutic intervention", "recruit", "response", "trait", "transcriptome sequencing", "whole genome" ], "approved": true } }, { "type": "Grant", "id": "5685", "attributes": { "award_id": "2R37AI087846-12", "title": "Regulation of Host Innate Immunity Against Viral Infection", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 19633, "first_name": "Mary Chelsea", "last_name": "Lane", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2010-04-01", "end_date": "2026-05-31", "award_amount": 452960, "principal_investigator": { "id": 19634, "first_name": "Michaela Ulrike", "last_name": "Gack", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1013, "ror": "", "name": "CLEVELAND CLINIC LERNER COM-CWRU", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "RIG-I and MDA5 are key cytosolic receptors for sensing various RNA viruses, including coronaviruses, influenza virus, and flaviviruses. Upon binding of viral RNA, RIG-I-like receptors initiate signal transduction pathways that result in type-I interferon (IFN) induction to suppress viral replication and the spread of infection. For their efficient replication, however, viruses have evolved elegant strategies to evade the IFN-mediated host immune response. Work from many laboratories has identified the precise mechanisms that lead to activation of RIG-I, which include RNA binding, K63-linked ubiquitination, oligomerization, and the re-distribution of RIG-I from the cytoplasm to mitochondria. In striking contrast, our knowledge about the mechanisms that govern activation of the related sensor MDA5 remains elusive. The proposed study builds on a recent discovery by the Gack laboratory that covalent modification of MDA5 by ISG15 activates MDA5 signaling by promoting its CARD-dependent oligomerization and cytosol-to-mitochondria translocation. Molecular and cell biological studies in ISG15-deficient human and mouse cells, including primary immune cells, demonstrated that ISG15 is required for an effective antiviral IFN response mediated by MDA5 (but not RIG-I). Our data also showed that MDA5 ISGylation is required for restricting the infection of SARS-CoV-2, Zika, dengue and picornaviruses. Furthermore, our most recent work revealed that SARS-CoV- 2 uses its papain-like protease (PLpro) to antagonize MDA5 by actively removing its ISGylation. Molecular, biochemical, and cell biological approaches combined with gene-targeting screens will focus on defining in precise detail how ISGylation regulates MDA5-mediated innate immunity, and also identify the E3 ligase that mediates MDA5 ISGylation and thereby its activation. We will also determine the relevance of MDA5 ISGylation for effective virus restriction using MDA5 gene-edited cells using CRISPR-Cas9 technology, and a novel mutant MDA5 knock-in mouse model. This study will also give detailed insight into the mechanisms by which SARS-CoV-2 and other coronaviruses counteract MDA5 ISGylation and determine the physiological role of this novel immune escape strategy in IFN antagonism, virus replication and pathogenesis. Our studies will provide a molecular understanding of the mechanisms that lead to activation of antiviral innate immunity, and also define a novel immune evasion strategy of coronaviruses, which may provide the foundation for new therapeutic approaches or help design better vaccines.", "keywords": [ "2019-nCoV", "Adaptor Signaling Protein", "Antiviral Agents", "Antiviral Response", "Architecture", "Attenuated", "Binding", "Biochemical", "Biological", "COVID-19 pandemic", "CRISPR/Cas technology", "Caspase", "Cell Culture System", "Cells", "Complex", "Coronavirus", "Coronavirus Infections", "Cytoplasm", "Cytosol", "Data", "Defense Mechanisms", "Dengue", "Dengue Virus", "Disease", "Family", "Family Picornaviridae", "Flavivirus", "Foundations", "Gene Targeting", "Genes", "HIV", "Human", "ISG15 gene", "Immune", "Immune Evasion", "Immune response", "Immune system", "Immunity", "In Vitro", "Infection", "Innate Immune Response", "Interferon Type I", "Interferons", "Knock-in Mouse", "Knowledge", "Laboratories", "Lead", "Link", "Mediating", "Mitochondria", "Modification", "Molecular", "Mus", "N-terminal", "Natural Immunity", "Outcome", "Papain", "Pathogenesis", "Peptide Hydrolases", "Physiological", "Proteins", "RNA", "RNA Binding", "RNA Virus Infections", "RNA Viruses", "Recombinants", "Regulation", "Role", "SARS-CoV-2 infection", "Series", "Severity of illness", "Signal Transduction", "Signal Transduction Pathway", "Ubiquitination", "Vaccines", "Viral Pathogenesis", "Virus", "Virus Diseases", "Virus Replication", "Work", "ZIKA", "Zika Virus", "adaptive immunity", "antiviral immunity", "cytosolic receptor", "design", "global health", "in vivo", "influenzavirus", "insight", "mouse model", "mutant", "novel", "novel therapeutic intervention", "pathogenic virus", "receptor", "recruit", "response", "sensor", "ubiquitin-protein ligase", "vaccine development", "viral RNA", "virtual" ], "approved": true } }, { "type": "Grant", "id": "6850", "attributes": { "award_id": "5R37AI087846-13", "title": "Regulation of Host Innate Immunity Against Viral Infection", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6050, "first_name": "Mary Chelsea", "last_name": "Lane", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2010-04-01", "end_date": "2026-05-31", "award_amount": 437723, "principal_investigator": { "id": 9999, "first_name": "Michaela Ulrike", "last_name": "Gack", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1013, "ror": "", "name": "CLEVELAND CLINIC LERNER COM-CWRU", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1013, "ror": "", "name": "CLEVELAND CLINIC LERNER COM-CWRU", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "RIG-I and MDA5 are key cytosolic receptors for sensing various RNA viruses, including coronaviruses, influenza virus, and flaviviruses. Upon binding of viral RNA, RIG-I-like receptors initiate signal transduction pathways that result in type-I interferon (IFN) induction to suppress viral replication and the spread of infection. For their efficient replication, however, viruses have evolved elegant strategies to evade the IFN-mediated host immune response. Work from many laboratories has identified the precise mechanisms that lead to activation of RIG-I, which include RNA binding, K63-linked ubiquitination, oligomerization, and the re-distribution of RIG-I from the cytoplasm to mitochondria. In striking contrast, our knowledge about the mechanisms that govern activation of the related sensor MDA5 remains elusive. The proposed study builds on a recent discovery by the Gack laboratory that covalent modification of MDA5 by ISG15 activates MDA5 signaling by promoting its CARD-dependent oligomerization and cytosol-to-mitochondria translocation. Molecular and cell biological studies in ISG15-deficient human and mouse cells, including primary immune cells, demonstrated that ISG15 is required for an effective antiviral IFN response mediated by MDA5 (but not RIG-I). Our data also showed that MDA5 ISGylation is required for restricting the infection of SARS-CoV-2, Zika, dengue and picornaviruses. Furthermore, our most recent work revealed that SARS-CoV- 2 uses its papain-like protease (PLpro) to antagonize MDA5 by actively removing its ISGylation. Molecular, biochemical, and cell biological approaches combined with gene-targeting screens will focus on defining in precise detail how ISGylation regulates MDA5-mediated innate immunity, and also identify the E3 ligase that mediates MDA5 ISGylation and thereby its activation. We will also determine the relevance of MDA5 ISGylation for effective virus restriction using MDA5 gene-edited cells using CRISPR-Cas9 technology, and a novel mutant MDA5 knock-in mouse model. This study will also give detailed insight into the mechanisms by which SARS-CoV-2 and other coronaviruses counteract MDA5 ISGylation and determine the physiological role of this novel immune escape strategy in IFN antagonism, virus replication and pathogenesis. Our studies will provide a molecular understanding of the mechanisms that lead to activation of antiviral innate immunity, and also define a novel immune evasion strategy of coronaviruses, which may provide the foundation for new therapeutic approaches or help design better vaccines.", "keywords": [ "2019-nCoV", "Adaptor Signaling Protein", "Antiviral Agents", "Antiviral Response", "Architecture", "Attenuated", "Binding", "Biochemical", "Biological", "COVID-19 pandemic", "CRISPR/Cas technology", "Caspase", "Cell Culture System", "Cells", "Complex", "Coronavirus", "Coronavirus Infections", "Cytoplasm", "Cytosol", "Data", "Defense Mechanisms", "Dengue", "Dengue Virus", "Disease", "Family", "Family Picornaviridae", "Flavivirus", "Foundations", "Gene Targeting", "Genes", "HIV", "Human", "ISG15 gene", "Immune", "Immune Evasion", "Immune response", "Immune system", "Immunity", "In Vitro", "Infection", "Innate Immune Response", "Interferon Type I", "Interferons", "Knock-in Mouse", "Knowledge", "Laboratories", "Lead", "Link", "Mediating", "Mitochondria", "Modification", "Molecular", "Mus", "N-terminal", "Natural Immunity", "Outcome", "Papain", "Pathogenesis", "Peptide Hydrolases", "Physiological", "Proteins", "RNA", "RNA Binding", "RNA Virus Infections", "RNA Viruses", "Recombinants", "Regulation", "Role", "SARS-CoV-2 infection", "Series", "Severity of illness", "Signal Transduction", "Signal Transduction Pathway", "Ubiquitination", "Vaccines", "Viral Pathogenesis", "Virus", "Virus Diseases", "Virus Replication", "Work", "ZIKA", "Zika Virus", "adaptive immunity", "antiviral immunity", "cytosolic receptor", "design", "global health", "in vivo", "influenzavirus", "insight", "mouse model", "mutant", "novel", "novel therapeutic intervention", "pathogenic virus", "receptor", "recruit", "response", "sensor", "ubiquitin-protein ligase", "vaccine development", "viral RNA", "virtual" ], "approved": true } }, { "type": "Grant", "id": "5006", "attributes": { "award_id": "NNX10AK05G", "title": "We request support from NASA for the overlapping open science meetings/conferences of the Global Land Project (GLP) and the Urbanization and Global Environment Change (UGEC) project to be held October 15-19, 20 I 0, on the campus of Arizona State Universi", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2010-03-04", "end_date": "2012-02-17", "award_amount": 0, "principal_investigator": { "id": 17954, "first_name": "BILLIE", "last_name": "TURNER", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [] }, "other_investigators": [], "awardee_organization": null, "abstract": "We request support from NASA for the overlapping open science meetings/conferences of the Global Land Project (GLP) and the Urbanization and Global Environment Change (UGEC) project to be held October 15-19, 20 I 0, on the campus of Arizona State Universi", "keywords": [], "approved": true } }, { "type": "Grant", "id": "4988", "attributes": { "award_id": "0908151", "title": "Innulluartaarneq (Having the Good Life Study)", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Unknown", "ASSP-Arctic Social Science" ], "program_reference_codes": [], "program_officials": [], "start_date": "2010-01-15", "end_date": "2013-12-31", "award_amount": 954530, "principal_investigator": { "id": 17914, "first_name": "Elizabeth", "last_name": "Rink", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 259, "ror": "https://ror.org/02w0trx84", "name": "Montana State University", "address": "", "city": "", "state": "MT", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 17913, "first_name": "Dionne C Gesink", "last_name": "Law", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 259, "ror": "https://ror.org/02w0trx84", "name": "Montana State University", "address": "", "city": "", "state": "MT", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT ABSTRACT\nThe purpose of Innuluataarneq research project is to develop, implement, evaluate, and disseminate a public health intervention in Greenland that focuses on Greenlandic ways of understanding and knowing about healthy behavior and sexually transmitted infections (STI). The target population for Innuluataarneq is 15 to 19 year old adolescents and their parents. Innuluataarneq will be conducted as an interdisciplinary international, collaborative community based participatory research (CBPR) study involving researchers and students from the United States, Canada, Denmark and Greenland. Innuluataarneq will be implemented in three communities in Greenland: Nuuk, Sisimut, and Tasiilaq. There are two components to Innulataarneq: 1) Component 1 will build capacity within Greenland to conduct CBPR projects that enhance community ownership in reducing STIs and empower communities in Greenland to partner with academic institutions to conduct research that resonates with Greenlandic knowledge and social and cultural practices; and 2) Component 2 will provide a socially and culturally relevant health education intervention to adolescents 15 to 19 years old and their parents in order to enhance awareness of STIs and their long term consequences \n\nThere are several elements to the intellectual merit of Innulataarneq. First, little is known about how cultural practices affect the transmission of STIs in the Arctic. Innulataarneq builds on our current STI research in Greenland, The Greenland Sexual Health Study, which is gathering information on the individual behaviors, social determinants, and cultural, historical, and political factors influencing the country?s high STI rates. Second, CBPR has not been practiced in Greenland to address any social science or health question. Innulataarneq?s CBPR approach advances our knowledge and understanding of the practical application of CBPR methodologies in a socially and culturally diverse Arctic community such as Greenland. Third, the reproductive future of Greenland is in jeopardy due to the countries high STI rates and low birth rates. Innulataarneq will explore Greenlandic ways of promoting educational efforts to prevent STI?s in order to secure Greenland?s reproductive future. \n\nThe relevance and importance of Innulataarneq to broader impacts in the field of social sciences and health related fields include the following: 1) Provide experience and training for students from indigenous populations in the United States, Canada and Greenland in the skills, techniques and knowledge needed to carry out community based participatory research on sexual health in Arctic communities; 2) Create a dialogue and build connections between institutions in the United States, Canada, and Greenland to foster a greater understanding of the importance of this health research in the Arctic; 3) Raise awareness about CBPR methods in Greenland, STIs, and culturally relevant ways of addressing this problem in an Arctic country; 4) Promote social science research that addresses health issues in Arctic communities; and 5) Documents and shares Greenlandic traditional knowledge and how it influences sexual behavior in an Arctic community.", "keywords": [], "approved": true } } ], "meta": { "pagination": { "page": 1382, "pages": 1424, "count": 14236 } } }