Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1385&sort=title
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=title", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=title", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1386&sort=title", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=title" }, "data": [ { "type": "Grant", "id": "8887", "attributes": { "award_id": "5R01MD016465-02", "title": "Video-based Intervention to Reduce Treatment and OUtcome Disparities in Adults Living with Stroke or Transient Ischemic Attack (VIRTUAL)", "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": 6437, "first_name": "Rada K", "last_name": "Dagher", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-09-18", "end_date": "2026-05-31", "award_amount": 657170, "principal_investigator": { "id": 24707, "first_name": "Anjail Z", "last_name": "Sharrief", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 788, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 788, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary: Hypertension is the most important risk factor for ischemic and hemorrhagic stroke, and reduction in blood pressure (BP) after stroke is associated with reduced risk of stroke recurrence1-4. However, for the majority of stroke survivors (SS), hypertension remains poorly controlled early after an incident stroke.5-7 In the United States, Black and Hispanic SS are more likely to have poorly controlled risk factors after stroke compared to White SS, and Black and Hispanic SS have higher rates of stroke recurrence compared to White SS.5-11 Prior efforts to reduce racial disparities in BP control among SS have been uniformly unsuccessful.12 Multicomponent care models that include multidisciplinary approaches show promise for improving risk factor control after stroke.13, 14 Social determinants of health (SDOH) help to explain racial disparities in BP control and stroke recurrence, therefore multidisciplinary post-stroke care models that target SDOH may be key to decreasing disparities in BP control.5, 7, 15 Limited access to post-stroke outpatient care contributes to challenges in developing system-level interventions for post-stroke BP control. Telemedicine and telemonitoring may be ideal approaches for improving access to care in SS. The COVID-19 pandemic has led to rapid expansion of telemedicine for post-acute care in stroke survivors; however, its effectiveness is unproven. Based on preliminary data at our center, we propose a randomized trial testing an integrated multidisciplinary telehealth intervention, the Video-based Intervention to Reduce Treatment and OUtcome Disparities in Adults Living with Stroke or Transient Ischemic Attack (VIRTUAL), in SS recently discharged home after inpatient hospitalization for ischemic stroke, hemorrhagic stroke, or transient ischemic attack. The intervention will include post-discharge telehealth visits by a multidisciplinary team, social risk assessments to facilitate social risk-targeted and social risk-informed care, and home BP telemonitoring and management. The care team includes neurology providers (physician and nurse practitioner), a pharmacist, and a social worker. Standard care will include follow-up with a neurologist and primary care provider and pharmacist-assisted BP adjustment. We aim to assess 1) the impact of the intervention on BP control 6 months following stroke assessed with ambulatory BP monitoring; 2) the impact of the intervention on recurrent vascular events 1 year after stroke; 3) the impact of the intervention on health services access and utilization following stroke; 4) moderating effects of race / ethnicity on the impact of the intervention on BP control, vascular events, and health services utilization; 5) the relationship between additional measured SDOH and primary and secondary outcomes.", "keywords": [ "Accident and Emergency department", "Acute", "Address", "Adult", "Ambulatory Blood Pressure Monitoring", "Ambulatory Care", "Area", "Behavior", "Black race", "Blood Pressure", "Blood Pressure Monitors", "Blood Vessels", "Brain hemorrhage", "COVID-19 pandemic", "Caring", "Cessation of life", "Cities", "Clinical", "Communities", "Coronary", "Data", "Discrimination", "Effectiveness", "Enrollment", "Environment", "Ethnic Origin", "Event", "Health Services Accessibility", "Healthcare", "Heart failure", "Heterogeneity", "Hispanics", "Home", "Hospitalization", "Hospitals", "Hour", "Hypertension", "Improve Access", "Inpatients", "Insurance", "Insurance Coverage", "Intervention", "Ischemic Stroke", "Language", "Link", "Measures", "Medicaid", "Medical", "Modeling", "Myocardial Infarction", "Neighborhoods", "Neurologist", "Neurology", "Nurse Practitioners", "Outcome", "Outpatients", "Patients", "Pharmacists", "Physicians", "Provider", "Race", "Randomized", "Recurrence", "Research", "Resources", "Risk", "Risk Assessment", "Risk Factors", "Services", "Social Workers", "Social support", "Socioeconomic Status", "Stroke", "System", "Technology", "Telemedicine", "Testing", "Transient Ischemic Attack", "Treatment outcome", "Uninsured", "United States", "Visit", "acute care", "base", "blood pressure reduction", "blood pressure regulation", "care delivery", "care providers", "care systems", "cohort", "comparative effectiveness trial", "ethnic diversity", "evidence based guidelines", "experience", "follow-up", "food insecurity", "health care service utilization", "health service use", "hospital readmission", "improved", "indexing", "individual patient", "interdisciplinary approach", "intervention effect", "metropolitan", "mortality", "multi-component intervention", "multidisciplinary", "post intervention", "post stroke", "predictive modeling", "primary outcome", "programs", "racial and ethnic disparities", "racial disparity", "racial diversity", "racism", "randomized trial", "recruit", "secondary outcome", "segregation", "social", "social health determinants", "social vulnerability", "standard care", "stroke risk", "stroke survivor", "telehealth", "telemonitoring", "trial comparing", "urgent care", "video visit", "virtual intervention", "virtual model" ], "approved": true } }, { "type": "Grant", "id": "8888", "attributes": { "award_id": "1R01MD016465-01", "title": "Video-based Intervention to Reduce Treatment and OUtcome Disparities in Adults Living with Stroke or Transient Ischemic Attack (VIRTUAL)", "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": 6437, "first_name": "Rada K", "last_name": "Dagher", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-09-18", "end_date": "2026-05-31", "award_amount": 652525, "principal_investigator": { "id": 24707, "first_name": "Anjail Z", "last_name": "Sharrief", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 788, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 788, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary: Hypertension is the most important risk factor for ischemic and hemorrhagic stroke, and reduction in blood pressure (BP) after stroke is associated with reduced risk of stroke recurrence1-4. However, for the majority of stroke survivors (SS), hypertension remains poorly controlled early after an incident stroke.5-7 In the United States, Black and Hispanic SS are more likely to have poorly controlled risk factors after stroke compared to White SS, and Black and Hispanic SS have higher rates of stroke recurrence compared to White SS.5-11 Prior efforts to reduce racial disparities in BP control among SS have been uniformly unsuccessful.12 Multicomponent care models that include multidisciplinary approaches show promise for improving risk factor control after stroke.13, 14 Social determinants of health (SDOH) help to explain racial disparities in BP control and stroke recurrence, therefore multidisciplinary post-stroke care models that target SDOH may be key to decreasing disparities in BP control.5, 7, 15 Limited access to post-stroke outpatient care contributes to challenges in developing system-level interventions for post-stroke BP control. Telemedicine and telemonitoring may be ideal approaches for improving access to care in SS. The COVID-19 pandemic has led to rapid expansion of telemedicine for post-acute care in stroke survivors; however, its effectiveness is unproven. Based on preliminary data at our center, we propose a randomized trial testing an integrated multidisciplinary telehealth intervention, the Video-based Intervention to Reduce Treatment and OUtcome Disparities in Adults Living with Stroke or Transient Ischemic Attack (VIRTUAL), in SS recently discharged home after inpatient hospitalization for ischemic stroke, hemorrhagic stroke, or transient ischemic attack. The intervention will include post-discharge telehealth visits by a multidisciplinary team, social risk assessments to facilitate social risk-targeted and social risk-informed care, and home BP telemonitoring and management. The care team includes neurology providers (physician and nurse practitioner), a pharmacist, and a social worker. Standard care will include follow-up with a neurologist and primary care provider and pharmacist-assisted BP adjustment. We aim to assess 1) the impact of the intervention on BP control 6 months following stroke assessed with ambulatory BP monitoring; 2) the impact of the intervention on recurrent vascular events 1 year after stroke; 3) the impact of the intervention on health services access and utilization following stroke; 4) moderating effects of race / ethnicity on the impact of the intervention on BP control, vascular events, and health services utilization; 5) the relationship between additional measured SDOH and primary and secondary outcomes.", "keywords": [ "Accident and Emergency department", "Acute", "Address", "Adult", "Ambulatory Blood Pressure Monitoring", "Ambulatory Care", "Area", "Behavior", "Black race", "Blood Pressure", "Blood Pressure Monitors", "Blood Vessels", "Brain hemorrhage", "COVID-19 pandemic", "Caring", "Cessation of life", "Cities", "Clinical", "Communities", "Coronary", "Data", "Discrimination", "Effectiveness", "Enrollment", "Environment", "Ethnic Origin", "Event", "Health Services Accessibility", "Healthcare", "Heart failure", "Heterogeneity", "Hispanics", "Home", "Hospitalization", "Hospitals", "Hour", "Hypertension", "Improve Access", "Inpatients", "Insurance", "Insurance Coverage", "Intervention", "Ischemic Stroke", "Language", "Link", "Measures", "Medicaid", "Medical", "Modeling", "Myocardial Infarction", "Neighborhoods", "Neurologist", "Neurology", "Nurse Practitioners", "Outcome", "Outpatients", "Patients", "Pharmacists", "Physicians", "Provider", "Race", "Randomized", "Recurrence", "Research", "Resources", "Risk", "Risk Assessment", "Risk Factors", "Services", "Social Workers", "Social support", "Socioeconomic Status", "Stroke", "System", "Technology", "Telemedicine", "Testing", "Transient Ischemic Attack", "Treatment outcome", "Uninsured", "United States", "Visit", "acute care", "base", "blood pressure reduction", "blood pressure regulation", "care delivery", "care providers", "care systems", "cohort", "comparative effectiveness trial", "ethnic diversity", "evidence based guidelines", "experience", "follow-up", "food insecurity", "health care service utilization", "health service use", "hospital readmission", "improved", "indexing", "individual patient", "interdisciplinary approach", "intervention effect", "metropolitan", "mortality", "multi-component intervention", "multidisciplinary", "post intervention", "post stroke", "predictive modeling", "primary outcome", "programs", "racial and ethnic disparities", "racial disparity", "racial diversity", "racism", "randomized trial", "recruit", "secondary outcome", "segregation", "social", "social health determinants", "social vulnerability", "standard care", "stroke risk", "stroke survivor", "telehealth", "telemonitoring", "trial comparing", "urgent care", "video visit", "virtual intervention", "virtual model" ], "approved": true } }, { "type": "Grant", "id": "15199", "attributes": { "award_id": "1UG1EY036346-01", "title": "Village-Integrated Eye Worker Trial II (VIEW II) Extension", "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": 31781, "first_name": "DONALD F", "last_name": "EVERETT", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-01", "end_date": "2029-08-31", "award_amount": 1448874, "principal_investigator": { "id": 31782, "first_name": "Jeremy David", "last_name": "Keenan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The World Health Organization estimates that 80% of blindness worldwide is avoidable. However, in resource-limited settings progressive eye diseases such as glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD) often go undiagnosed until it is too late. New approaches that detect progressive eye diseases before they cause irreversible vision loss could help reduce visual impairment of communities. One such approach is community-based eye disease screening. The Village Integrated Eye Workers Trial II (VIEW II) is an ongoing cluster-randomized trial in which communities in Nepal receive visual acuity screening and are subsequently randomized to receive either a community-based eye disease screening intervention consisting of optical coherence tomography (OCT) and intraocular pressure (IOP) assessment, or to no intervention. The goal of the screening intervention is to detect cases of glaucoma, diabetic retinopathy, and age-related macular degeneration—all of which are progressive and cause irreversible vision loss if left untreated—and refer these cases to the local eye hospital for management. A door-to-door census is performed four years after starting the screening intervention to determine the effectiveness of screening for reducing vision impairment relative to communities not receiving the screening intervention. This is a proposal for the extension of the VIEW II trial, maintaining the original randomization and continuing the same screening intervention in the study clusters except that fundus photography is also included in the screening intervention and that the targeted age group is expanded to those ≥50 years. The specific aims of the proposal are (1) to determine if the screening intervention is effective for preventing vision loss at the community level over 7 years, (2) to compare text messages versus community volunteers for improving linkage to care, and (3) to determine the natural history of OCT measurements over time in a population-based study. Glaucoma, DR, and AMD are slowly progressive diseases, and given interruptions to study activities caused by the COVID-19 pandemic, the originally planned 4-year endpoint in the original VIEW II trial may not be long enough to observe the full effect of the screening intervention. Extending the trial will provide a more accurate assessment of any benefit of screening. Extending the trial also allows for repeated OCTs in a population-based sample, providing much needed data on the natural history of OCT parameters to help clinicians better determine what constitutes progression. This research is significant because it will provide the strongest type of evidence to guide national eye health programs – results from a randomized controlled trial. Ultimately, this trial will benefit blindness prevention programs worldwide in deciding how to allocate limited resources to optimally detect eye disease.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "10262", "attributes": { "award_id": "1U24AI171008-01", "title": "VIOLIN 2.0: Vaccine Information and Ontology LInked kNowledgebase", "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": 12912, "first_name": "Misrak", "last_name": "Gezmu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-19", "end_date": "2027-05-31", "award_amount": 753786, "principal_investigator": { "id": 26210, "first_name": "Yongqun", "last_name": "He", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 22889, "first_name": "Cui", "last_name": "Tao", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 26211, "first_name": "Junguk", "last_name": "Hur", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary: Vaccination is one of the most successful innovations in the fight against infectious disease. However, we still lack effective and safe vaccines against many major infectious diseases (e.g., HIV, tuberculosis, and malaria). We also lack a comprehensive and interoperable vaccine knowledgebase to accelerate vaccine development and better understand vaccine safety. Based on the preliminary version of our current VIOLIN vaccine knowledgebase, we propose to develop VIOLIN 2.0, a new generation Vaccine Information and Ontology LInked kNowledgebase. Strong preliminary data were generated: Originally funded by an NIH-NIAID R01, our VIOLIN has grown to include information on >4,000 vaccines for >200 pathogens. In addition, we have led the development of the community-based Vaccine Ontology (VO) and Ontology of Adverse Events (OAE) for vaccine and adverse event representation. We have also developed the widely used Vaxign and Vaxign-ML vaccine design programs and applied them to predict vaccines for many diseases including COVID-19. Many ontology- and bioinformatics-based methods and tools, including natural language processing (NLP) tools, have also been developed to analyze vaccine information and identify new scientific insights. However, the existing VIOLIN also faces new challenges in areas such as knowledge integration, interoperability, and analysis. In this proposal, we aim to systematically develop VIOLIN 2.0, which will be a community-based comprehensive vaccine knowledgebase (KB) with data FAIRness. Basic science, clinical, and public health (safety, epidemiology, vaccine coverage) knowledge will be included with robust linkage and analysis. Four specific aims are proposed: Aim 1: Implement a pipeline for automatic knowledge harvest, standardization, and integration using advanced ontology and natural language processing technologies. Aim 2: Expand the vaccine KB and management. Three specific knowledge aspects will be included: (i) vaccine formulation and development, (ii) protective responses, and (iii) vaccine safety. Aim 3: Provide VIOLIN 2.0 knowledge browser, query, and showcases. For showcase demonstration, three use cases will be built up, including pattern detection of vaccine components (including protective antigens and vaccine adjuvants), vaccine-induced host immune signatures, and vaccine adverse events. The patterns identified will be utilized with statistical and machine learning methods to support rational vaccine design and immune signature prediction. Aim 4: Community engagement and outreach. Many events such as hackathons and workshops will be held to support the development and applications of community-based ontologies, standards, and tools. VIOLIN 2.0 will significantly enhance the VIOLIN with breadth and depth of vaccine information, include knowledge not available in the current VIOLIN (e.g., vaccine adverse events), and develop new methods for efficient and scalable knowledge extraction and analysis. Our study will advance the understanding of vaccine mechanisms, and support rational vaccine design against COVID-19 and other infectious diseases.", "keywords": [ "Acquired Immunodeficiency Syndrome", "Address", "Adjuvant", "Adverse event", "Antigens", "Applications Grants", "Area", "Basic Science", "Bioinformatics", "COVID-19", "COVID-19 pandemic", "Cessation of life", "Clinical", "Clinical Trials", "Communicable Diseases", "Communities", "Community Developments", "Community Outreach", "Consensus", "Data", "Databases", "Detection", "Development", "Dimensions", "Disease", "Educational workshop", "Ensure", "Epidemiology", "Evaluation", "Event", "FAIR principles", "Face", "Funding", "Generations", "Grant", "HIV/TB", "Harvest", "Immune", "Immune response", "Immunologic Factors", "Informatics", "Information Retrieval", "Knowledge", "Knowledge Discovery", "Knowledge Extraction", "Life Cycle Stages", "Link", "Literature", "Machine Learning", "Malaria", "Manuals", "Methods", "Modern Medicine", "Molecular", "Monitor", "National Institute of Allergy and Infectious Disease", "Natural Language Processing", "Ontology", "Pattern", "Public Health", "Reproducibility", "Research", "Resources", "Safety", "Semantics", "Source", "Standardization", "System", "Systems Analysis", "Technology", "United States National Institutes of Health", "Vaccination", "Vaccine Adjuvant", "Vaccine Antigen", "Vaccine Design", "Vaccines", "Visualization", "Work", "base", "community engagement", "data access", "data integration", "disability", "experience", "fight against", "gene expression database", "genetic linkage analysis", "hackathon", "informatics tool", "innovation", "insight", "interoperability", "invention", "knowledge graph", "knowledge integration", "knowledgebase", "machine learning method", "meetings", "method development", "outreach", "pathogen", "programs", "research and development", "response", "statistical and machine learning", "text searching", "tool", "vaccine adverse event", "vaccine development", "vaccine formulation", "vaccine safety", "vector", "web interface", "web site" ], "approved": true } }, { "type": "Grant", "id": "11485", "attributes": { "award_id": "5U24AI171008-02", "title": "VIOLIN 2.0: Vaccine Information and Ontology LInked kNowledgebase", "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": 12912, "first_name": "Misrak", "last_name": "Gezmu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-19", "end_date": "2027-05-31", "award_amount": 743543, "principal_investigator": { "id": 26210, "first_name": "Yongqun", "last_name": "He", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 22889, "first_name": "Cui", "last_name": "Tao", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 26211, "first_name": "Junguk", "last_name": "Hur", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary: Vaccination is one of the most successful innovations in the fight against infectious disease. However, we still lack effective and safe vaccines against many major infectious diseases (e.g., HIV, tuberculosis, and malaria). We also lack a comprehensive and interoperable vaccine knowledgebase to accelerate vaccine development and better understand vaccine safety. Based on the preliminary version of our current VIOLIN vaccine knowledgebase, we propose to develop VIOLIN 2.0, a new generation Vaccine Information and Ontology LInked kNowledgebase. Strong preliminary data were generated: Originally funded by an NIH-NIAID R01, our VIOLIN has grown to include information on >4,000 vaccines for >200 pathogens. In addition, we have led the development of the community-based Vaccine Ontology (VO) and Ontology of Adverse Events (OAE) for vaccine and adverse event representation. We have also developed the widely used Vaxign and Vaxign-ML vaccine design programs and applied them to predict vaccines for many diseases including COVID-19. Many ontology- and bioinformatics-based methods and tools, including natural language processing (NLP) tools, have also been developed to analyze vaccine information and identify new scientific insights. However, the existing VIOLIN also faces new challenges in areas such as knowledge integration, interoperability, and analysis. In this proposal, we aim to systematically develop VIOLIN 2.0, which will be a community-based comprehensive vaccine knowledgebase (KB) with data FAIRness. Basic science, clinical, and public health (safety, epidemiology, vaccine coverage) knowledge will be included with robust linkage and analysis. Four specific aims are proposed: Aim 1: Implement a pipeline for automatic knowledge harvest, standardization, and integration using advanced ontology and natural language processing technologies. Aim 2: Expand the vaccine KB and management. Three specific knowledge aspects will be included: (i) vaccine formulation and development, (ii) protective responses, and (iii) vaccine safety. Aim 3: Provide VIOLIN 2.0 knowledge browser, query, and showcases. For showcase demonstration, three use cases will be built up, including pattern detection of vaccine components (including protective antigens and vaccine adjuvants), vaccine-induced host immune signatures, and vaccine adverse events. The patterns identified will be utilized with statistical and machine learning methods to support rational vaccine design and immune signature prediction. Aim 4: Community engagement and outreach. Many events such as hackathons and workshops will be held to support the development and applications of community-based ontologies, standards, and tools. VIOLIN 2.0 will significantly enhance the VIOLIN with breadth and depth of vaccine information, include knowledge not available in the current VIOLIN (e.g., vaccine adverse events), and develop new methods for efficient and scalable knowledge extraction and analysis. Our study will advance the understanding of vaccine mechanisms, and support rational vaccine design against COVID-19 and other infectious diseases.", "keywords": [ "Acceleration", "Acquired Immunodeficiency Syndrome", "Address", "Adjuvant", "Adverse event", "Antigens", "Applications Grants", "Area", "Basic Science", "Bioinformatics", "COVID-19", "COVID-19 pandemic", "Cessation of life", "Clinical", "Clinical Trials", "Collaborations", "Communicable Diseases", "Communities", "Community Developments", "Community Outreach", "Consensus", "Data", "Databases", "Detection", "Development", "Dimensions", "Disease", "Educational workshop", "Ensure", "Epidemiology", "Evaluation", "Event", "FAIR principles", "Face", "Funding", "Generations", "Grant", "HIV", "Harvest", "Immune", "Immune response", "Immunologic Factors", "Informatics", "Information Retrieval", "Knowledge", "Knowledge Discovery", "Knowledge Extraction", "Licensing", "Life Cycle Stages", "Link", "Literature", "Machine Learning", "Malaria", "Manuals", "Methods", "Modern Medicine", "Molecular", "Monitor", "National Institute of Allergy and Infectious Disease", "Natural Language Processing", "Ontology", "Pattern", "Public Health", "Reproducibility", "Research", "Resources", "Safety", "Semantics", "Source", "Standardization", "System", "Systems Analysis", "Technology", "Tuberculosis", "United States National Institutes of Health", "Vaccination", "Vaccine Adjuvant", "Vaccine Antigen", "Vaccine Design", "Vaccines", "Visualization", "Work", "community engagement", "data access", "data integration", "disability", "experience", "fighting", "gene expression database", "hackathon", "improved", "informatics tool", "innovation", "insight", "interoperability", "invention", "knowledge graph", "knowledge integration", "knowledgebase", "machine learning method", "meetings", "method development", "outreach", "pathogen", "predictive signature", "programs", "research and development", "response", "statistical and machine learning", "text searching", "tool", "vaccine adverse event", "vaccine development", "vaccine formulation", "vaccine safety", "vector", "web interface", "web site" ], "approved": true } }, { "type": "Grant", "id": "11809", "attributes": { "award_id": "2325840", "title": "Viral afterlife: Pandemic viruses as rich reservoirs of immunomimetic peptide fragments capable of re-assembly into pro-inflammatory supramolecular complexes", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Mathematical and Physical Sciences (MPS)", "BIOMATERIALS PROGRAM" ], "program_reference_codes": [], "program_officials": [ { "id": 2299, "first_name": "Abraham", "last_name": "Joy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-10-01", "end_date": "2026-09-30", "award_amount": 402000, "principal_investigator": { "id": 5385, "first_name": "Gerard", "last_name": "Wong", "orcid": null, "emails": "[email protected]", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 151, "ror": "", "name": "University of California-Los Angeles", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 151, "ror": "", "name": "University of California-Los Angeles", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Non-technical Abstract:\nThe knowledge of what makes a coronavirus a pandemic coronavirus capable of causing a profoundly dangerous immune response is inadequate. This knowledge gap remains a threat to multiple national interests, such as health and economic prosperity. The central hypothesis in this work is that a pandemic coronavirus is one that harbors peptide fragments that strongly amplify immune responses, fragments that can be liberated even after the virus is destroyed by the immune system. In preliminary data, artificial intelligence methods are used to find fragments in 3 proteins in the SARS-CoV-2 virus (the COVID-19 virus) that can mimic peptides from the host that amplify immune activation. These preliminary studies found that these biomimetic viral peptides capable of amplifying immune responses are strongly enriched in SARS-CoV-2 relative to ‘common cold’ coronaviruses. Moreover, these peptides from SARS-CoV-2 but not corresponding analogs from ‘common cold’ coronaviruses can organize into crystalline complexes capable of such amplified immune activation. Such complexes amplify immune responses in diverse human cell types. The induced gene expression pattern from an examination of ~30,000 genes matches well with the COVID-19 gene expression pattern from the curated database in Kyoto. The goals of this present proposal are: 1) to analyze all proteins of the coronavirus using x-ray and immune activation experiments, and 2) to examine why the Omicron variant is less toxic to hosts, based on first principles. The research topics here are conducive to training for academic and industrial employment. Research internships will be provided through underrepresented undergraduate and veteran outreach programs. Results from this will be incorporated into the PI’s advanced undergraduate/graduate classes. \n\nTechnical Abstract:\nThe knowledge of what makes a coronavirus a pandemic coronavirus capable of causing a profoundly dangerous immune response is at present inadequate. This knowledge gap remains a threat to multiple national interests, such as health and economic prosperity. The central hypothesis in this work is that a pandemic coronavirus is one that harbors peptide fragments that strongly amplify immune responses, fragments that can be liberated even after the virus is proteolytically destroyed by the immune system. Artificial intelligence methods were used to find fragments in 3 prototypical proteins (S, M, a non-structural protein) in the SARS-CoV-2 virus that can mimic antimicrobial peptides (AMPs) from the host that amplify immune activation. These preliminary studies found that these biomimetic viral peptides (‘xenoAMPs’) capable of amplifying immune responses are strongly enriched in SARS-CoV-2 relative to ‘common cold’ coronaviruses. Moreover, these peptides from SARS-CoV-2 but not corresponding homologs from ‘common cold’ coronaviruses can organize dsRNA commonly found in viral infections into nanocrystalline complexes capable of amplified immune activation. Such complexes amplify immune responses in diverse human cell types relevant to COVID-19. The transcriptome from uninfected endothelial cells exposed to these complexes matches well with the COVID-19 gene expression pattern from the curated KEGG database in Kyoto. The goals of this present proposal are: 1) to analyze all proteins of the coronavirus using x-ray and immune activation experiments, and 2) to examine why the Omicron variant is less toxic to hosts, based on first principles of electrostatic self assembly. The research topics here are conducive to training for academic and industrial employment. Research internships will be provided through underrepresented undergraduate and veteran outreach programs. Results from this will be incorporated into the PI’s advanced undergraduate/graduate classes.\n\nThis award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "5695", "attributes": { "award_id": "3U19AI104317-09S1", "title": "Viral and Environmental Determinants of Rhinovirus Illness Severity", "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": 19659, "first_name": "Gang", "last_name": "Dong", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-07-21", "end_date": "2023-01-31", "award_amount": 403465, "principal_investigator": { "id": 19660, "first_name": "James E.", "last_name": "Gern", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 799, "ror": "", "name": "UNIVERSITY OF WISCONSIN-MADISON", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "Rhinovirus (RV) infections frequently cause colds, and yet these viruses also contribute to lower respiratory infections in young children and the elderly, and to 50-90% of asthma exacerbations. Moreover, RV associated wheezing illnesses in preschoolers are strong risk factors for developing asthma. The lack of specific treatments for more severe RV illnesses and exacerbations of asthma is a major unmet medical need. What determines the severity of illness caused by RV infections? This is a key question, since it is the severe colds that cause exacerbations in patients with asthma and increase the risk of recurrent wheeze and asthma in preschoolers. We propose that factors related to the virus (RV species), host (RV receptor genetics, innate immune response), and environment (the farm microbiome) strongly influence the severity of illness associated with RV infection. Our highly interactive program consisting of 2 projects and 2 cores will define mechanisms of susceptibility vs. resistance to severe viral respiratory illnesses (VRI). The clinical centerpiece of the program is the Wisconsin Infant Study Cohort (WISC) (Project I), a unique dairy farm birth cohort designed to investigate links between farm exposures, immune maturation, and infectious and allergic respiratory disease. The cohort is now fully enrolled, and our preliminary data suggest that farm exposures reduce both VRI and atopic dermatitis, two important risk factors for asthma. We now hypothesize that farming microbial exposures and unique patterns of microbial colonization in early life alter of innate and T regulatory development, which lead to protection from VRI and allergic diseases. To test this hypothesis, we will follow current WISC participants to age 4-8 years, and recruit additional farm and non-farm newborns (50/group) who will be monitored with new technologies to better define early life microbial exposures and immune development. We have established relationships with the Wisconsin Amish community, who have very low rates of allergic diseases, and will include 50 Amish newborns in the new recruits. Project II will focus on interactions between the RV C species (RV-C) and cadherin related protein-3 (CDHR3) on host airway epithelial cells. RV-C are linked to more severe illnesses and severe exacerbations of asthma, but little is known about RV-C pathogenesis. Our recent work has greatly advanced this cause by developing novel molecular tools, culture and production techniques, identifying the first cell surface receptor, and determining the 3D molecular structure for RV-C. In the current proposal for Project II, we will conduct experiments to further define RV-C structure, the biochemistry of interactions with CDHR3, and genetic and biochemical mechanisms regulating the subcellular expression and function of CDHR3. Understanding the virus capsid and interactions with CDHR3 would provide two new targets for small molecule RV-C antivirals. Ultimately, this information will lead to new strategies for the treatment of prevention of VRI and respiratory allergies in children.", "keywords": [ "3-Dimensional", "Address", "Adult", "Affect", "Age", "Allergic", "Allergic Disease", "Allergic inflammation", "Amish", "Antiviral Agents", "Antiviral Response", "Asthma", "Atopic Dermatitis", "Bacteria", "Biochemical", "Birth", "C cadherin", "Cadherins", "Capsid", "Cell Surface Receptors", "Cell physiology", "Cells", "Child", "Childhood", "Chronic", "Chronic Obstructive Airway Disease", "Clinical", "Cohort Studies", "Common Cold", "Communities", "Cystic Fibrosis", "Data", "Detection", "Development", "Disease", "Elderly", "Enrollment", "Environment", "Epithelial", "Epithelial Cells", "Exposure to", "Farming environment", "Genetic", "Goals", "Growth", "Hospitalization", "Hypersensitivity", "Immune", "Immune response", "Infant", "Infection", "Inflammatory", "Innate Immune Response", "Interferons", "Knowledge", "Lead", "Life", "Link", "Lower Respiratory Tract Infection", "Lung diseases", "Medical", "Microbe", "Molecular", "Molecular Structure", "Molecular Virology", "Monitor", "Mononuclear", "Morbidity - disease rate", "Natural Immunity", "Newborn Infant", "Participant", "Pathogenesis", "Patients", "Pattern", "Population", "Predisposition", "Prevention", "Production", "Program Research Project Grants", "Proteins", "Recurrence", "Regulatory T-Lymphocyte", "Resistance", "Rhinovirus", "Rhinovirus infection", "Risk", "Risk Factors", "Services", "Severities", "Severity of illness", "Shapes", "Societies", "Structural Biochemistry", "Symptoms", "Techniques", "Testing", "Viral", "Virulence", "Virus", "Virus Diseases", "Virus Replication", "Wheezing", "Wisconsin", "Work", "airway epithelium", "airway obstruction", "asthma exacerbation", "burden of illness", "chemokine", "cofactor", "cohort", "commensal bacteria", "community acquired pneumonia", "cost", "design", "early life exposure", "experimental study", "follow-up", "improved", "infancy", "microbial", "microbial colonization", "microbiome", "neonate", "neutrophil", "new technology", "novel", "novel therapeutic intervention", "pathogen", "pathogenic bacteria", "pediatric patients", "programs", "receptor", "recruit", "respiratory", "respiratory microbiome", "respiratory morbidity", "respiratory virus", "response", "small molecule", "tool", "treatment strategy" ], "approved": true } }, { "type": "Grant", "id": "5026", "attributes": { "award_id": "3U19AI104317-10S1", "title": "Viral and Environmental Determinants of Rhinovirus Illness Severity", "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": 17990, "first_name": "Gang", "last_name": "Dong", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-07-21", "end_date": "2023-01-31", "award_amount": 122066, "principal_investigator": { "id": 17991, "first_name": "James E.", "last_name": "Gern", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 17992, "first_name": "CHRISTINE Marie", "last_name": "SEROOGY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 799, "ror": "", "name": "UNIVERSITY OF WISCONSIN-MADISON", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "Rhinovirus (RV) infections frequently cause colds, and yet these viruses also contribute to lower respiratory infections in young children and the elderly, and to 50-90% of asthma exacerbations. Moreover, RV associated wheezing illnesses in preschoolers are strong risk factors for developing asthma. The lack of specific treatments for more severe RV illnesses and exacerbations of asthma is a major unmet medical need. What determines the severity of illness caused by RV infections? This is a key question, since it is the severe colds that cause exacerbations in patients with asthma and increase the risk of recurrent wheeze and asthma in preschoolers. We propose that factors related to the virus (RV species), host (RV receptor genetics, innate immune response), and environment (the farm microbiome) strongly influence the severity of illness associated with RV infection. Our highly interactive program consisting of 2 projects and 2 cores will define mechanisms of susceptibility vs. resistance to severe viral respiratory illnesses (VRI). The clinical centerpiece of the program is the Wisconsin Infant Study Cohort (WISC) (Project I), a unique dairy farm birth cohort designed to investigate links between farm exposures, immune maturation, and infectious and allergic respiratory disease. The cohort is now fully enrolled, and our preliminary data suggest that farm exposures reduce both VRI and atopic dermatitis, two important risk factors for asthma. We now hypothesize that farming microbial exposures and unique patterns of microbial colonization in early life alter of innate and T regulatory development, which lead to protection from VRI and allergic diseases. To test this hypothesis, we will follow current WISC participants to age 4-8 years, and recruit additional farm and non-farm newborns (50/group) who will be monitored with new technologies to better define early life microbial exposures and immune development. We have established relationships with the Wisconsin Amish community, who have very low rates of allergic diseases, and will include 50 Amish newborns in the new recruits. Project II will focus on interactions between the RV C species (RV-C) and cadherin related protein-3 (CDHR3) on host airway epithelial cells. RV-C are linked to more severe illnesses and severe exacerbations of asthma, but little is known about RV-C pathogenesis. Our recent work has greatly advanced this cause by developing novel molecular tools, culture and production techniques, identifying the first cell surface receptor, and determining the 3D molecular structure for RV-C. In the current proposal for Project II, we will conduct experiments to further define RV-C structure, the biochemistry of interactions with CDHR3, and genetic and biochemical mechanisms regulating the subcellular expression and function of CDHR3. Understanding the virus capsid and interactions with CDHR3 would provide two new targets for small molecule RV-C antivirals. Ultimately, this information will lead to new strategies for the treatment of prevention of VRI and respiratory allergies in children.", "keywords": [ "3-Dimensional", "Address", "Adult", "Affect", "Age", "Allergic", "Allergic Disease", "Allergic inflammation", "Amish", "Antiviral Agents", "Antiviral Response", "Asthma", "Atopic Dermatitis", "Bacteria", "Biochemical", "Biochemistry", "Birth", "C cadherin", "Cadherins", "Capsid", "Cell Surface Receptors", "Cell physiology", "Cells", "Child", "Childhood", "Chronic Obstructive Pulmonary Disease", "Clinical", "Cohort Studies", "Common Cold", "Communities", "Data", "Detection", "Development", "Disease", "Elderly", "Enrollment", "Environment", "Epithelial", "Epithelial Cells", "Exposure to", "Farming environment", "Genetic", "Goals", "Growth", "Hospitalization", "Hypersensitivity", "Immune", "Immune response", "Infant", "Infection", "Inflammatory", "Innate Immune Response", "Interferons", "Knowledge", "Lead", "Life", "Link", "Lower Respiratory Tract Infection", "Medical", "Microbe", "Molecular", "Molecular Structure", "Molecular Virology", "Monitor", "Mononuclear", "Morbidity - disease rate", "Natural Immunity", "Newborn Infant", "Participant", "Pathogenesis", "Patients", "Pattern", "Population", "Predisposition", "Prevention", "Production", "Program Research Project Grants", "Proteins", "Recurrence", "Regulatory T-Lymphocyte", "Resistance", "Respiratory Disease", "Rhinovirus", "Rhinovirus infection", "Risk", "Risk Factors", "Services", "Severities", "Severity of illness", "Shapes", "Societies", "Structure", "Symptoms", "Techniques", "Testing", "Viral", "Virulence", "Virus", "Virus Diseases", "Virus Replication", "Wheezing", "Wisconsin", "Work", "airway epithelium", "airway obstruction", "asthma exacerbation", "burden of illness", "chemokine", "chronic respiratory disease", "cofactor", "cohort", "commensal bacteria", "community acquired pneumonia", "cost", "design", "early life exposure", "experimental study", "follow-up", "improved", "infancy", "microbial", "microbial colonization", "microbiome", "neonate", "neutrophil", "new technology", "novel", "novel therapeutic intervention", "pathogen", "pathogenic bacteria", "pediatric patients", "programs", "receptor", "recruit", "respiratory", "respiratory microbiome", "respiratory morbidity", "respiratory virus", "response", "small molecule", "tool", "treatment strategy" ], "approved": true } }, { "type": "Grant", "id": "7350", "attributes": { "award_id": "3U19AI095227-10S1", "title": "Viral and Host Determinants of Infant and Childhood Allergy and Asthma", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 7248, "first_name": "Wendy F.", "last_name": "Davidson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-04-23", "end_date": "2021-07-31", "award_amount": 1505841, "principal_investigator": { "id": 20522, "first_name": "Ray Stokes", "last_name": "Peebles", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 456, "ror": "https://ror.org/05dq2gs74", "name": "Vanderbilt University Medical Center", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 456, "ror": "https://ror.org/05dq2gs74", "name": "Vanderbilt University Medical Center", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true }, "abstract": "The long term objective of this application is to define the relationship between infant respiratory syncytial virus (RSV) infection and the host response that enables asthma inception. There is abundant evidence that children who experience severe RSV bronchiolitis during infancy are at greater risk for developing asthma later in childhood; however the viral and host determinants that lead to asthma development are not known. In Project 1, we propose to extend longitudinal follow-up of the INSPIRE (Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure) population based birth cohort of over 1,900 middle Tennessee infants who will be age 4 years at the end of the first U19 funding period. This will enable us to confirm if the RSV strains that we have identified to cause more severe infant morbidity and early wheezing outcomes are also associated with asthma, and the pathways through which these RSV strains cause asthma. We propose the following: (1) Identify RSV strains associated with asthma inception at ages 6 to 8 years; (2) Determine how RSV strains impact the host microbial environment during primary RSV infection; (3) Assess primary airway epithelial cell (AEC) response to asthma-causing RSV strains; (4) Determine RSV induced immune responses associated with asthma inception in the INSPIRE cohort. In the first funding cycle we have been the first group to ever sequence and identify RSV strains associated with significantly increased risk of recurrent wheezing outcomes, as well as differential immune response and airway microbial patterns. We found that infants infected with RSV strains that contained a mutation in the attachment (G) gene end sequence (2stop-A4G mutation) had statistically significantly increased bronchiolitis severity scores compared to infants infected with the RSV WT genotype. Infection with 2stop-A4G mutation strains is becoming increasingly more common in human infants and studies from our group reveal that strains containing the 2stop-A4G mutation cause Th2 innate immune responses in mice and humans. In Project 2, we propose the following in the mouse model of RSV infection: (1) determine the contribution of infection with RSV 2stop-A4G to Th2 immunity in primary bronchiolitis, and (2) determine the contribution of 2stop-A4G to enhanced adaptive immune responses to inhaled aeroallergen. Defining the contribution of specific RSV strains to infant bronchiolitis and asthma pathogenesis highlights the clinical significance of our studies and may provide a therapeutic target for vaccines and precision medicine approaches that focus on RSV mutations.", "keywords": [ "4 year old", "Acute", "Age", "Allergens", "Asthma", "Birth", "Bronchiolitis", "Child", "Childhood", "Childhood Asthma", "Clinical", "Data", "Development", "ENG gene", "Enrollment", "Environment", "Epithelial Cells", "Funding", "Genes", "Genetic", "Genetic Transcription", "Genotype", "Glycoproteins", "Goals", "Hospitalization", "Human", "Hypersensitivity", "Immune", "Immune response", "Immunity", "In Vitro", "Incidence", "Individual", "Infant", "Infection", "Inhalation", "Innate Immune Response", "Lead", "Life", "Lung infections", "Mediating", "Mus", "Mutation", "Nucleotides", "Outcome", "Pathogenesis", "Pathway interactions", "Pattern", "Peripheral Blood Mononuclear Cell", "Phenotype", "Physiological", "Positioning Attribute", "Predisposition", "Publishing", "Recurrence", "Research", "Resources", "Respiration", "Respiratory Syncytial Virus Infections", "Respiratory System", "Respiratory syncytial virus", "Risk", "Risk Factors", "Services", "Severities", "Subgroup", "T memory cell", "Tennessee", "Terminator Codon", "Testing", "Time", "United States", "Vaccines", "Viral", "Virus", "Wheezing", "Work", "acute infection", "adaptive immune response", "airborne allergen", "airway epithelium", "airway inflammation", "allergic airway inflammation", "clinically significant", "cohort", "cytokine", "data management", "defined contribution", "design", "experience", "experimental study", "follow-up", "genetic approach", "infancy", "infant morbidity", "innovation", "microbial", "microbial host", "mouse model", "neonatal infection", "population based", "precision medicine", "programs", "respiratory morbidity", "response", "reverse genetics", "therapeutic target" ], "approved": true } }, { "type": "Grant", "id": "7351", "attributes": { "award_id": "3U19AI095227-11S1", "title": "Viral and Host Determinants of Infant and Childhood Allergy and Asthma", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 7248, "first_name": "Wendy F.", "last_name": "Davidson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-04-23", "end_date": "2022-07-31", "award_amount": 1550210, "principal_investigator": { "id": 20522, "first_name": "Ray Stokes", "last_name": "Peebles", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 456, "ror": "https://ror.org/05dq2gs74", "name": "Vanderbilt University Medical Center", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 456, "ror": "https://ror.org/05dq2gs74", "name": "Vanderbilt University Medical Center", "address": "", "city": "", "state": "TN", "zip": "", "country": "United States", "approved": true }, "abstract": "The long term objective of this application is to define the relationship between infant respiratory syncytial virus (RSV) infection and the host response that enables asthma inception. There is abundant evidence that children who experience severe RSV bronchiolitis during infancy are at greater risk for developing asthma later in childhood; however the viral and host determinants that lead to asthma development are not known. In Project 1, we propose to extend longitudinal follow-up of the INSPIRE (Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure) population based birth cohort of over 1,900 middle Tennessee infants who will be age 4 years at the end of the first U19 funding period. This will enable us to confirm if the RSV strains that we have identified to cause more severe infant morbidity and early wheezing outcomes are also associated with asthma, and the pathways through which these RSV strains cause asthma. We propose the following: (1) Identify RSV strains associated with asthma inception at ages 6 to 8 years; (2) Determine how RSV strains impact the host microbial environment during primary RSV infection; (3) Assess primary airway epithelial cell (AEC) response to asthma-causing RSV strains; (4) Determine RSV induced immune responses associated with asthma inception in the INSPIRE cohort. In the first funding cycle we have been the first group to ever sequence and identify RSV strains associated with significantly increased risk of recurrent wheezing outcomes, as well as differential immune response and airway microbial patterns. We found that infants infected with RSV strains that contained a mutation in the attachment (G) gene end sequence (2stop-A4G mutation) had statistically significantly increased bronchiolitis severity scores compared to infants infected with the RSV WT genotype. Infection with 2stop-A4G mutation strains is becoming increasingly more common in human infants and studies from our group reveal that strains containing the 2stop-A4G mutation cause Th2 innate immune responses in mice and humans. In Project 2, we propose the following in the mouse model of RSV infection: (1) determine the contribution of infection with RSV 2stop-A4G to Th2 immunity in primary bronchiolitis, and (2) determine the contribution of 2stop-A4G to enhanced adaptive immune responses to inhaled aeroallergen. Defining the contribution of specific RSV strains to infant bronchiolitis and asthma pathogenesis highlights the clinical significance of our studies and may provide a therapeutic target for vaccines and precision medicine approaches that focus on RSV mutations.", "keywords": [ "4 year old", "Acute", "Age", "Allergens", "Asthma", "Birth", "Bronchiolitis", "Child", "Childhood", "Childhood Asthma", "Clinical", "Data", "Development", "ENG gene", "Enrollment", "Environment", "Epithelial Cells", "Funding", "Genes", "Genetic", "Genetic Transcription", "Genotype", "Glycoproteins", "Goals", "Hospitalization", "Human", "Hypersensitivity", "Immune", "Immune response", "Immunity", "In Vitro", "Incidence", "Individual", "Infant", "Infection", "Inhalation", "Innate Immune Response", "Lead", "Life", "Lung infections", "Mediating", "Mus", "Mutation", "Nucleotides", "Outcome", "Pathogenesis", "Pathway interactions", "Pattern", "Peripheral Blood Mononuclear Cell", "Phenotype", "Physiological", "Positioning Attribute", "Predisposition", "Publishing", "Recurrence", "Research", "Resources", "Respiration", "Respiratory Syncytial Virus Infections", "Respiratory System", "Respiratory syncytial virus", "Risk", "Risk Factors", "Services", "Severities", "Subgroup", "T memory cell", "Tennessee", "Terminator Codon", "Testing", "Time", "United States", "Vaccines", "Viral", "Virus", "Wheezing", "Work", "acute infection", "adaptive immune response", "airborne allergen", "airway epithelium", "airway inflammation", "allergic airway inflammation", "clinically significant", "cohort", "cytokine", "data management", "defined contribution", "design", "experience", "experimental study", "follow-up", "genetic approach", "infancy", "infant morbidity", "innovation", "microbial", "microbial host", "mouse model", "neonatal infection", "population based", "precision medicine", "programs", "respiratory morbidity", "response", "reverse genetics", "therapeutic target" ], "approved": true } } ], "meta": { "pagination": { "page": 1385, "pages": 1405, "count": 14046 } } }