Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1404&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=1424&sort=title", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=title", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1403&sort=title" }, "data": [ { "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 } }, { "type": "Grant", "id": "6004", "attributes": { "award_id": "3U19AI095227-11S2", "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": 20521, "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": "2020-12-14", "end_date": "2022-07-31", "award_amount": 164815, "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 infection", "infant morbidity", "innovation", "microbial", "microbial host", "mouse model", "population based", "precision medicine", "programs", "respiratory morbidity", "response", "reverse genetics", "therapeutic target" ], "approved": true } }, { "type": "Grant", "id": "15392", "attributes": { "award_id": "1R01AI177498-01A1", "title": "Viral and Host Dynamics during Pediatric COVID-19 and Respiratory Virus Co-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": 6243, "first_name": "BROOKE ALLISON", "last_name": "Bozick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-22", "end_date": "2029-05-31", "award_amount": 804976, "principal_investigator": { "id": 10830, "first_name": "Judd F", "last_name": "Hultquist", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 924, "ror": "", "name": "NORTHWESTERN UNIVERSITY AT CHICAGO", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 31993, "first_name": "LARRY K", "last_name": "KOCIOLEK", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 924, "ror": "", "name": "NORTHWESTERN UNIVERSITY AT CHICAGO", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "Children infected with SARS-CoV-2 are frequently reported to have co-infection with other respiratory viruses, including respiratory syncytial virus, human rhinovirus/enterovirus, and parainfluenza virus. Respiratory virus co- infection may lead to more severe COVID-19 and worse clinical outcomes, but this is complicated by ascertainment biases in clinical testing algorithms that make co-detection of multiple respiratory pathogens more likely in the most at-risk and severely ill children. Severe COVID-19 outcomes have been previously linked to immune dysregulation following infection, but it is unknown how the host response to SARS-CoV-2 may be influenced by co-infection with another respiratory virus. Likewise, it is unclear what impact co-infection may have on intra-host viral dynamics, including viral load, time to clearance, and viral diversification, all of which may contribute to the evolution of new variants with enhanced immune evasion or antiviral resistance. We hypothesize that children with SARS-CoV-2 experience frequent respiratory virus co-infection, and that this co- infection is associated with more severe disease, increased inflammation and mucosal injury in the upper respiratory tract, and enhanced viral diversity due to increased persistence and viral load. We propose to test this hypothesis in three aims designed to: 1) assess the prevalence of SARS-CoV-2 and respiratory virus co- infection and its association with clinical outcome; 2) characterize the mucosal immune response to SARS-CoV- 2 and how it differs in response to viral co-infection; and 3) determine the influence of co-infection on viral intra- host dynamics and evolution. To achieve this goal, we will leverage our retrospective biobank of residual COVID- 19 diagnostic specimens from Lurie Children’s Hospital (n>6000 specimens collected since March 2020) as well as prospectively collected specimens spanning a total of 6 years. In Aim 1, we will use a combination of multiplex PCR and hybrid-capture sequencing to establish respiratory virus co-infection prevalence over time. Electronic medical record data will be used to examine associations between co-infection, clinical outcomes, and disease severity, adjusting for relevant demographic and clinical cofactors, including treatment, vaccination, and prior infection. In Aim 2, bulk transcriptomic sequencing, cytokine profiling, immune cell profiling, and single-cell RNA sequencing will be used to assess the mucosal immune response in co-infected individuals and controls. Host response data will be modeled in the context of the extracted demographic and clinical metadata to determine association with disease severity and outcomes. In Aim 3, viral whole genome sequencing and quantitative PCR will be used to assess viral load, intra-host quasispecies composition, and genetic diversity. Phylogenetic and phylodynamic models will be used to determine evolutionary rate and selection. Mutations in antiviral drug targets will be assessed for resistance potential. Taken together, these data will clarify the prevalence, clinical impact, and virus-host dynamics underlying SARS-CoV-2 and respiratory virus co-infection in children towards the development of evidence-based guidance to optimize diagnosis/treatment and minimize morbidity.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "6166", "attributes": { "award_id": "5R01AI153087-02", "title": "Viral and immune kinetics in rhinovirus infection following hematopoietic cell transplantation", "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": 20932, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-04", "end_date": "2024-05-31", "award_amount": 672657, "principal_investigator": { "id": 20933, "first_name": "Alpana Amalkant", "last_name": "Waghmare", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 732, "ror": "https://ror.org/01njes783", "name": "Seattle Children's Hospital", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Human rhinovirus (HRV) is the most common respiratory virus detected in the upper and lower respiratory tract in hematopoietic cell transplant (HCT) recipients; mortality rates following HRV lower respiratory tract infection are similar to those seen with known pulmonary viral pathogens including respiratory syncytial virus, influenza, and parainfluenza virus. Despite the high burden of disease and the observed complications of HRV infection in HCT recipients, the development of HRV therapeutics is hindered by the lack of a comprehensive understanding of the relationship between viral detection, symptoms and host immune responses and the impact of these factors on disease severity. We have demonstrated that clinical risk factors, including cytopenias and steroid use, are associated with progression from upper respiratory tract infection (URTI) to LRTI. However, up to 70% of patients with profound immunosuppression at the time of virus acquisition clear their infections without treatment. Our preliminary data show that gene expression signatures at the time of URTI may be predictive of progression to LRTI. We aim to characterize the interplay between viral detection, cytokine levels and cellular immune responses early during HRV infection in HCT recipients in a prospective surveillance cohort. We will also perform in depth gene expression analyses at a single cell level to identify specific cellular populations that are associated with severe disease in both peripheral blood and in proximal bronchoalveolar lavage fluid. The central hypothesis of this proposal is that viral and host immune kinetics, including both global and cell specific gene expression profiles in specific tissue compartments, impact disease severity in HCT recipients with HRV infection. Results from these experiments will characterize the optimal timing and most predictive viral and host immune markers that can be used to design rational clinical trials for novel therapeutics. Our deep interrogation of compartment and cell specific immune responses will further our understanding of virus-host interactions and of potential targets for intervention.", "keywords": [ "Acute", "Age", "Allogenic", "Antiviral Agents", "Biological Markers", "Blood", "Blood specimen", "Bronchoalveolar Lavage Fluid", "Cells", "Cessation of life", "Clinical", "Clinical Trials", "Collection", "Complex", "Containment", "Cytotoxic T-Lymphocytes", "Data", "Detection", "Development", "Disease", "Enrollment", "Equilibrium", "Evaluation", "Future", "Gene Expression", "Gene Expression Profile", "Gene Expression Profiling", "Genes", "Genetic Transcription", "Home", "Human", "Immune", "Immune response", "Immunologic Markers", "Immunologics", "Immunophenotyping", "Immunosuppression", "Infection", "Infection Control", "Inflammatory", "Intervention", "Kinetics", "Lower Respiratory Tract Infection", "Lower respiratory tract structure", "Lung", "Modeling", "Nose", "Outcome", "Pathway interactions", "Patients", "Pattern", "Peripheral Blood Mononuclear Cell", "Play", "Population", "Prevention strategy", "Prognostic Marker", "Progressive Disease", "Prospective Studies", "Prospective cohort", "Respiratory Signs and Symptoms", "Respiratory syncytial virus", "Rhinovirus", "Rhinovirus infection", "Risk", "Risk Factors", "Role", "Sampling", "Severity of illness", "Specimen", "Steroids", "Surveys", "Symptoms", "T-Lymphocyte", "Therapeutic", "Therapeutic Clinical Trial", "Time", "Tissues", "Transplant Recipients", "Upper Respiratory Infections", "Upper respiratory tract", "Viral", "Viral Load result", "Virus", "Whole Blood", "acute infection", "base", "burden of illness", "clinical risk", "cohort", "cytokine", "cytopenia", "design", "disorder control", "early detection biomarkers", "experimental study", "handheld mobile device", "hematopoietic cell transplantation", "improved", "influenzavirus", "innovation", "mathematical model", "mortality", "nasal swab", "novel therapeutics", "overexpression", "parainfluenza virus", "pathogenic virus", "patient stratification", "peripheral blood", "prospective", "respiratory", "respiratory virus", "risk stratification", "self testing", "single cell analysis", "single-cell RNA sequencing", "temporal measurement", "transcriptome", "transcriptome sequencing", "transcriptomics", "viral detection", "virus host interaction" ], "approved": true } }, { "type": "Grant", "id": "5360", "attributes": { "award_id": "5R01AI153087-03", "title": "Viral and immune kinetics in rhinovirus infection following hematopoietic cell transplantation", "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": 18790, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-04", "end_date": "2024-05-31", "award_amount": 781685, "principal_investigator": { "id": 18791, "first_name": "Alpana Amalkant", "last_name": "Waghmare", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 732, "ror": "https://ror.org/01njes783", "name": "Seattle Children's Hospital", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Human rhinovirus (HRV) is the most common respiratory virus detected in the upper and lower respiratory tract in hematopoietic cell transplant (HCT) recipients; mortality rates following HRV lower respiratory tract infection are similar to those seen with known pulmonary viral pathogens including respiratory syncytial virus, influenza, and parainfluenza virus. Despite the high burden of disease and the observed complications of HRV infection in HCT recipients, the development of HRV therapeutics is hindered by the lack of a comprehensive understanding of the relationship between viral detection, symptoms and host immune responses and the impact of these factors on disease severity. We have demonstrated that clinical risk factors, including cytopenias and steroid use, are associated with progression from upper respiratory tract infection (URTI) to LRTI. However, up to 70% of patients with profound immunosuppression at the time of virus acquisition clear their infections without treatment. Our preliminary data show that gene expression signatures at the time of URTI may be predictive of progression to LRTI. We aim to characterize the interplay between viral detection, cytokine levels and cellular immune responses early during HRV infection in HCT recipients in a prospective surveillance cohort. We will also perform in depth gene expression analyses at a single cell level to identify specific cellular populations that are associated with severe disease in both peripheral blood and in proximal bronchoalveolar lavage fluid. The central hypothesis of this proposal is that viral and host immune kinetics, including both global and cell specific gene expression profiles in specific tissue compartments, impact disease severity in HCT recipients with HRV infection. Results from these experiments will characterize the optimal timing and most predictive viral and host immune markers that can be used to design rational clinical trials for novel therapeutics. Our deep interrogation of compartment and cell specific immune responses will further our understanding of virus-host interactions and of potential targets for intervention.", "keywords": [ "Acute", "Age", "Allogenic", "Antiviral Agents", "Biological Markers", "Blood", "Blood specimen", "Bronchoalveolar Lavage Fluid", "Cells", "Cessation of life", "Clinical", "Clinical Trials", "Collection", "Complex", "Containment", "Cytotoxic T-Lymphocytes", "Data", "Detection", "Development", "Disease", "Enrollment", "Equilibrium", "Evaluation", "Future", "Gene Expression", "Gene Expression Profile", "Gene Expression Profiling", "Genes", "Genetic Transcription", "Home", "Human", "Immune", "Immune response", "Immunologic Markers", "Immunologics", "Immunophenotyping", "Immunosuppression", "Infection", "Infection Control", "Inflammatory", "Intervention", "Kinetics", "Lower Respiratory Tract Infection", "Lower respiratory tract structure", "Lung", "Modeling", "Nose", "Outcome", "Pathway interactions", "Patients", "Pattern", "Peripheral Blood Mononuclear Cell", "Play", "Population", "Prevention strategy", "Prognostic Marker", "Progressive Disease", "Prospective Studies", "Prospective cohort", "Respiratory Signs and Symptoms", "Respiratory syncytial virus", "Rhinovirus", "Rhinovirus infection", "Risk", "Risk Factors", "Role", "Sampling", "Severity of illness", "Specimen", "Steroids", "Surveys", "Symptoms", "T-Lymphocyte", "Therapeutic", "Therapeutic Clinical Trial", "Time", "Tissues", "Transplant Recipients", "Upper Respiratory Infections", "Upper respiratory tract", "Viral", "Viral Load result", "Virus", "Whole Blood", "acute infection", "base", "burden of illness", "clinical risk", "cohort", "cytokine", "cytopenia", "design", "disorder control", "early detection biomarkers", "experimental study", "handheld mobile device", "hematopoietic cell transplantation", "improved", "influenzavirus", "innovation", "mathematical model", "mortality", "nasal swab", "novel therapeutics", "overexpression", "parainfluenza virus", "pathogenic virus", "patient stratification", "peripheral blood", "prospective", "respiratory", "respiratory virus", "risk stratification", "self testing", "single cell analysis", "single-cell RNA sequencing", "temporal measurement", "transcriptome", "transcriptome sequencing", "transcriptomics", "viral detection", "virus host interaction" ], "approved": true } } ], "meta": { "pagination": { "page": 1404, "pages": 1424, "count": 14236 } } }