Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1391&sort=end_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=end_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=end_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=end_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1390&sort=end_date" }, "data": [ { "type": "Grant", "id": "11437", "attributes": { "award_id": "1U01DK135002-01", "title": "Assessing Diabetes Risk Origins in Teens (ADROIT)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 6382, "first_name": "MIRANDA MARGUERITE", "last_name": "Broadney", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-04-05", "end_date": "2029-01-31", "award_amount": 85216, "principal_investigator": { "id": 27501, "first_name": "LORRAINE E LEVITT", "last_name": "KATZ", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1073, "ror": "", "name": "CHILDREN'S HOSP OF PHILADELPHIA", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "While obesity, ancestry, family history of diabetes, insulin resistance, and puberty are all risk factors for pediatric-onset type 2 diabetes (T2D), identifying the subset of youth at greatest risk of advancing from “prediabetes” to T2D and the mechanisms underlying the deterioration remain elusive. This lack of specificity defies the medical community's ability to 1) direct care to the youth at greatest risk of pediatric onset T2D and 2) develop targeted interventions. The particularly aggressive nature of pediatric T2D and the unique hormonal milieu of the adolescent suggest while the mechanisms underlying adult-onset T2D in adults resonate in pediatric T2D, additional perturbances are operative. Our team proposes to collaborate in a multi-center study, informed by partnerships with family and community members, to define clinically accessible metrics of increased diabetes risk as well as potential mechanisms that compromise the normal adaptations to insulin resistance during adolescence. We propose a longitudinal study leveraging a 3-hour, multi-sample oral glucose tolerance test performed at baseline, 18-months, and 36-months in obese pubertal youth with pre-diabetes to 1) test the utility of the one-hour glucose in predicting T2D and deterioration in insulin secretion, 2) perform extensive phenotyping for testing the relationships of changes in insulin secretion (early phase and second phase), insulin sensitivity, incretin secretion, glucagon suppression, hepatic glucose clearance, and free fatty flux with emergence of T2D. The contributions of genetic variants, in utero environment, visceral adipose accumulation, eating behaviors, mental health issues, social determinants of health, diet, physical activity, sleep and COVID infection to perturbances in insulin secretion and sensitivity will be tested. Home health care workers will provide additional critical insight into the home environment. Glucose-potentiated arginine stimulation tests will be conducted in subsets of participants in whom glucose homeostasis is preserved, worsens, or advances to T2D. This study is anticipated to specify useful indicators of T2D risk and advance our understanding of the underpinnings of progressive defects in insulin secretion and sensitivity to inform individualized programs aimed at interrupting emergence of T2D.", "keywords": [ "Acceleration", "Adipose tissue", "Adolescence", "Adolescent", "Adult", "Algorithms", "Arginine", "Beta Cell", "Biological Markers", "Body Composition", "Caring", "Child", "Childhood", "Childhood diabetes", "Clinical", "Collaborations", "Communication", "Communities", "Community Health Aides", "Community Healthcare", "DNA", "Data", "Data Collection", "Defect", "Deterioration", "Development", "Diabetes Mellitus", "Diet", "Disease", "Eating Behavior", "Eating Disorders", "Education", "Environment", "Evaluation", "Exposure to", "Family", "Family history of", "Fatty acid glycerol esters", "Fetal Growth Retardation", "Fetal Macrosomia", "Future", "Genetic Risk", "Genomics", "Genotype", "Glucagon", "Glucose", "Goals", "Growth", "Health Personnel", "Hepatic", "Home Care Services", "Home environment", "Hormonal", "Hour", "Human", "Infection", "Institution", "Insulin", "Insulin Resistance", "Interruption", "Intervention", "Life Style", "Longitudinal Studies", "Longitudinal cohort", "Medical", "Medical Care Team", "Mental Health", "Metabolic", "Methodology", "Methods", "Mission", "Molecular", "Multicenter Studies", "Nature", "Non-Insulin-Dependent Diabetes Mellitus", "OGTT", "Obesity", "Participant", "Patients", "Pediatric Hospitals", "Phase", "Phenotype", "Philadelphia", "Physical activity", "Physical assessment", "Plasma", "Population", "Prediabetes syndrome", "Prevalence", "Process", "Prospective Studies", "Protocols documentation", "Psychosocial Factor", "Puberty", "RNA", "Reporting", "Research", "Research Design", "Resources", "Risk", "Risk Factors", "Sampling", "Science", "Secretory Cell", "Secretory Rate", "Sleep", "Specific qualifier value", "Specificity", "Standardization", "Teenagers", "Testing", "Viral", "Visceral", "Youth", "actigraphy", "adipokines", "anxiety symptoms", "base", "biobank", "blood glucose regulation", "clinical center", "community based participatory research", "coronavirus disease", "depressive symptoms", "design", "diabetes risk", "digital health", "genetic variant", "healthy weight", "high risk", "in utero", "indexing", "innovation", "insight", "insulin secretion", "insulin sensitivity", "intrauterine environment", "maternal diabetes", "member", "open source", "phenomics", "physical inactivity", "prenatal exposure", "preservation", "prevent", "programs", "recruit", "screening", "sleep health", "social health determinants", "study population", "tool" ], "approved": true } }, { "type": "Grant", "id": "11134", "attributes": { "award_id": "2221224", "title": "Building Resilience and Engaging in Achievement through Collaborative, Holistic Programming in STEM", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Unknown", "S-STEM-Schlr Sci Tech Eng&Math" ], "program_reference_codes": [], "program_officials": [ { "id": 2077, "first_name": "Connie", "last_name": "Della-Piana", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-03-15", "end_date": "2029-02-28", "award_amount": 1018320, "principal_investigator": { "id": 27119, "first_name": "Laura", "last_name": "Strausberg", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 27117, "first_name": "Holly", "last_name": "Boettger-Tong", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 27118, "first_name": "Helen", "last_name": "Carter", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1989, "ror": "https://ror.org/05d7pr418", "name": "Wesleyan College", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "This project aims to answer the national need for well-educated scientists, mathematicians, engineers, and technicians by supporting the retention and graduation of high-achieving, low-income students with demonstrated financial need. Over its six-year duration, this project will fund scholarships to 21 unique full-time students who are pursuing bachelor’s degrees in biology, neuroscience, and applied mathematical science. First-year students, particularly students who attend rural high schools in the region, will receive scholarships for four years. Scholarships will begin at $6,500 in Year 1 and incrementally increase to $8,000 in Year 4 based on financial need. Additionally, students will receive summer scholarships of $2,000 during Years 2-4 for those scholars who opt to take six credits of summer courses for academic advancement or recovery. Informed by the research literature, institutional data, and student survey data, the curricular and co-curricular supports include implementation of mathematics support in early gateway STEM courses through co-requisite pre-calculus courses; a summer bridge program; development and support of mindfulness practices by scholars that include self-visualization; robust faculty mentoring; peer tutoring; micro-credentials; networking; undergraduate research experiences and internships; and placement into student cohorts. Recognizing the importance of financial support and a robust system of academic and co-curricular support and cohorts, the design of project activities and strategies respond to the impact of COVID-19 on secondary and post-secondary education. \n\nThe overall goal of this project is to increase STEM degree completion of low-income, high-achieving undergraduates with demonstrated financial need at Wesleyan College, a small liberal arts college for women. Four objectives provide a framework for the project to achieve its goal. First is the recruitment and enrollment of 21 low-income academically talented female undergraduate scholars in biology, neuroscience, and applied mathematical science. Second is the retention of 71% of the scholars in their STEM majors from their first to second year. Third is meeting a graduation target of 67% of scholars in STEM and ensuring that 79% of the graduating scholars enter into the STEM workforce or graduate studies in STEM. Fourth, and finally, is investigation into the efficacy of the proposed strategies and activities to influence student success and the influence of mindfulness practices in reducing stress overall and specifically in gateway mathematics courses. To support and inform project implementation and contribute to a deep understanding of psychosocial factors influencing student success, a mixed methods evaluation and research study will be conducted using quantitative and qualitative research methods for project improvement (formative evaluation), accountability (summative evaluation), and knowledge generation. Findings resulting from this project will be disseminated throughout the Wesleyan College community; statewide conferences for mathematics teachers; local, regional, state, and national conferences focused on curricular and co-curricular innovation (e.g., First Year Experience, undergraduate research experiences, education of women students); and research conferences on education. This project is funded by NSF’s Scholarships in Science, Technology, Engineering, and Mathematics program, which seeks to increase the number of low-income academically talented students with demonstrated financial need who earn degrees in STEM fields. It also aims to improve the education of future STEM workers, and to generate knowledge about academic success, retention, transfer, graduation, and academic/career pathways of low-income students.\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": "14590", "attributes": { "award_id": "1R01MH136218-01", "title": "Phenotypic and genetic architecture of OCD in African Americans", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 26484, "first_name": "Miri", "last_name": "Gitik", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-05-10", "end_date": "2029-02-28", "award_amount": 859577, "principal_investigator": { "id": 31255, "first_name": "DOROTHY E", "last_name": "GRICE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31256, "first_name": "SIDNEY H", "last_name": "HANKERSON", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Obsessive-compulsive disorder (OCD) is a life-long, serious psychiatric disorder that affects 2-3% of the population and is associated with high personal and societal costs. Genetic factors are undoubtedly important in the etiology in OCD, and associated loci and genes are just beginning to be discovered. Studies by us and by others have shown that rare and ultra-rare variation, the latter including recent variation, plays an important role in risk for OCD. In ongoing sequencing studies, we are identifying genes impacted by such variation, using samples collected by the investigators in this application. In this proposal, we take an important new direction to address a critical gap in OCD research by recruiting subjects of self-reported African ancestry (African-American; AA), a group poorly represented in OCD research and not previously represented in OCD genetic research. In fact, AA individuals with OCD are vastly underrepresented, or altogether absent, from treatment centers and research studies, in spite of the evidence for 1) disparities in access to treatment, 2) persistent OCD due to lack of treatment, and, 3) differences in OCD subtypes in AA populations, as well as, 4) Covid-19 pandemic amplified mental-health disparities (including OCD and anxiety disorders). In this proposal, we will systematically investigate the phenotypes of OCD in AA populations, and use high-throughput sequencing to identify rare single nucleotide variation (SNV), insertions/deletions (indels), and structural variation (SV) contributing to OCD susceptibility in this population. To further our understanding of OCD in AA populations we propose the following Specific Aims: 1) To recruit at least 1,250 African American OCD participants and compare phenotypic findings and genetic architecture across ancestries; and, 2) to carry out genetic association studies for ultra-rare variants in the African American cohort and across ancestries. With this new research we will accelerate our overall objective, which is the identification of OCD genes across diverse populations, thereby facilitating our long-term goal of building the foundation from which therapeutic targets for OCD emerge. Our rationale is that the identification of genes conferring significant risk to OCD and associated disorders can form the basis of studies to understand pathogenesis, as well as the basis for novel therapies. Our central hypothesis – formulated based on recent results – is that rare genetic variation contributes significantly to risk of OCD, with certain rare variants conferring substantial risk. The research proposed is innovative, in our opinion, because it uses groundbreaking and novel statistical methods for identifying risk variants for OCD in AA populations, involving a systematic effort to investigate OCD genetic architecture across populations. The research will increase the number of known OCD genes, expand our knowledge of networks and pathways that are disrupted in subjects with OCD, and determine whether recent deleterious variation differs across ancestry. These outcomes are expected to have important positive impact, leading to a molecular understanding of OCD, identifying targets for novel therapeutics, and aiding in gene and locus discovery across ancestries.", "keywords": [ "Acceleration", "Address", "Affect", "African", "African American", "African American population", "African ancestry", "Age of Onset", "American", "Anxiety Disorders", "Architecture", "Black race", "COVID-19 pandemic", "Caring", "Clinical", "Collection", "Communities", "DNA", "Data", "Development", "Diagnosis", "Disease", "Encapsulated", "Etiology", "European", "Foundations", "Gene Expression", "Genes", "Genetic", "Genetic Research", "Genetic Risk", "Genetic Variation", "Genetic study", "Genotype", "Goals", "Health Services Accessibility", "Heritability", "High-Throughput Nucleotide Sequencing", "Individual", "Knowledge", "Latin American", "Maps", "Mental Health", "Mental disorders", "Methods", "Mission", "Molecular", "Mutation", "Nucleotides", "Obsessive-Compulsive Disorder", "Outcome", "Participant", "Pathogenesis", "Pathway interactions", "Patient Self-Report", "Persons", "Phenotype", "Play", "Population", "Population Heterogeneity", "Predisposition", "Prevention", "Public Health", "Research", "Research Personnel", "Research Subject Recruitments", "Resources", "Risk", "Role", "Sampling", "Severities", "Site", "Statistical Methods", "Subgroup", "Testing", "United States National Institutes of Health", "Variant", "access disparities", "case control", "cell type", "clinical phenotype", "cohort", "comorbidity", "de novo mutation", "disorder risk", "disorder subtype", "focus ultra", "genetic architecture", "genetic association", "genetic variant", "genome wide association study", "health disparity", "improved", "innovation", "insertion/deletion mutation", "new therapeutic target", "non-genetic", "novel", "novel therapeutics", "polygenic risk score", "proband", "rare variant", "recruit", "research study", "risk variant", "sex", "societal costs", "therapeutic target", "therapy resistant", "transmission process", "treatment center", "treatment disparity", "treatment research" ], "approved": true } }, { "type": "Grant", "id": "14622", "attributes": { "award_id": "1R01DK138055-01", "title": "Viral-immune interaction in glomerular kidney disease", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 22545, "first_name": "KEVIN E", "last_name": "Chan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-05-01", "end_date": "2029-02-28", "award_amount": 606134, "principal_investigator": { "id": 31304, "first_name": "David Changli", "last_name": "WEI", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 851, "ror": "", "name": "UNIVERSITY OF TEXAS MED BR GALVESTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Viral infection is a major contributor to the global burden of infectious diseases. Virus-related glomerular diseases are seen in increasing frequency in clinical practice but are still underrecognized, thus miss opportunities for timely treatment. Viral exposure can alter host immunity in subtle ways, leaving an indelible footprint on the immune system. While there have been many studies indicating the association of viral infection with glomerular disease, a direct involvement of virus in kidney barrier dysfunction is unknown in most cases. Among remarkable research obstacles, lacking of a convenient and relevant animal model can be the most alarming one. We have recently established a novel mouse model whereby viral proteins drive glomerular disease in concert with a unique immune molecule, soluble urokinase receptor (suPAR). Intranasal injection of SARS-Cov-2 spike S1 protein (2019-nCov) caused proteinuria and podocyte injury specifically in mice with high levels of suPAR. Treatment with anti-suPAR antibody in mice or anti- v 3 integrin antibody on human podocytes blocked proteinuria and protected the glomerular filtration apparatus respectively. Notably, we found this unique synergy between viral protein and host suPAR in causing glomerular disease applies to other integrin binding viruses as well, including HIV-1 and Epstein-Barr virus (EBV). Clinically, suPAR is associated with kidney function loss in patients with HIV-1 infection, and in those with moderate to severe Covid-19. Based on these intriguing new insights, we hypothesize that viral-host suPAR interplay induces glomerular integrin activation and plays an essential role in some virus-associated glomerular disease. We propose to test this hypothesis by comprehensively evaluating the implication of viral protein-suPAR-integrin triad in both mouse models (Aim 1) and virus-associated human glomerular diseases (Aim 2), utilizing state of the art tools, and unique combinations of top-down and bottom-up approaches. Additionally, we will test therapeutic modalities targeting the vicious viral protein-suPAR-integrin cycle with relevant small molecule inhibitors and antibodies (Aim 3).", "keywords": [ "2019-nCoV", "Affinity", "Animal Model", "Antibodies", "Binding", "COVID-19 pandemic", "COVID-19 patient", "Cell-Matrix Junction", "Cells", "Chronic Kidney Failure", "Clinical", "Communicable Diseases", "Coupled", "Data", "Devices", "Disease", "Epitopes", "Exposure to", "Fc Receptor", "Foot Process", "Frequencies", "Functional disorder", "Glomerular Filtration Rate", "HIV Envelope Protein gp120", "HIV-1", "Hantavirus Infections", "Hospitalization", "Human", "Human Herpesvirus 4", "Immune", "Immune system", "Immunity", "Impairment", "In Vitro", "Infection", "Influenza B Virus", "Injections", "Injury", "Integrin Binding", "Integrin Inhibition", "Integrins", "Interleukin-5", "Kidney", "Kidney Diseases", "Modality", "Modeling", "Molecular", "Monitor", "Mus", "Patients", "Photometry", "Play", "Proteins", "Proteinuria", "Publishing", "Renal function", "Renal glomerular disease", "Research", "Role", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Scanning", "Serology", "Signal Transduction", "Testing", "Therapeutic", "Therapeutic Intervention", "Ultrafiltration", "Urokinase Plasminogen Activator Receptor", "Viral", "Viral Proteins", "Virus", "Virus Diseases", "burden of illness", "clinical practice", "efficacy evaluation", "glomerular filtration", "in vivo", "innovation", "insight", "loss of function", "mouse model", "new therapeutic target", "next generation sequencing", "novel", "novel therapeutics", "overexpression", "podocyte", "renal damage", "severe COVID-19", "single-cell RNA sequencing", "small molecule inhibitor", "synergism", "therapeutic evaluation", "tool" ], "approved": true } }, { "type": "Grant", "id": "14629", "attributes": { "award_id": "1R01HL173059-01", "title": "Defining neutrophil pathobiology in pediatric Long COVID", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 24630, "first_name": "Ronald Q", "last_name": "Warren", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-05-01", "end_date": "2029-02-28", "award_amount": 745411, "principal_investigator": { "id": 31319, "first_name": "Lael", "last_name": "Yonker", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 736, "ror": "https://ror.org/002pd6e78", "name": "Massachusetts General Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Over 15.6 million children in the U.S. alone have been infected by SARS-CoV2. While most recover, roughly 1 million children suffer from Long COVID. Neutrophils have been shown to be hyperactivated in Long COVID, which is concerning because they can be quite inflammatory, causing vascular and tissue damage and contributing to disease. We aim is to define the neutrophil profiles driving Long COVID in order to ultimately offer novel strategies for diagnosing and treating this new disease. To achieve this goal, we will use both single-cell RNA sequencing technology to define neutrophil activation profiles and microfluidics to test neutrophil functionality Long COVID, compared to healthy controls. Our central hypothesis is that neutrophil activation in Long COVID carries a distinct neutrophilic gene expression and functional profile, which contributes to pathogenicity. Importantly, we aim to partner with an existing clinical trial of larazotide for Long COVID (ClinicalTrials.gov Identifier: NCT05747534) to test reversibility of neutrophil activation by targeting sources of Spike antigenemia. Ultimately, mechanisms driving the pathogenesis of this newly emerged post-COVID-19- related illness must be defined to establish diagnostics and effective therapies.", "keywords": [ "2019-nCoV", "Acute", "Adult", "Affect", "Antigen-Antibody Complex", "Antigens", "Automobile Driving", "Biological Assay", "Blood", "Blood Platelets", "Blood Vessels", "COVID-19 patient", "Cells", "Cessation of life", "Chest Pain", "Child", "Childhood", "Circulation", "Clinical Treatment", "Clinical Trials", "Coagulation Process", "Diagnosis", "Diagnostic", "Disease", "Dyspnea", "Employment", "Fatigue", "Funding", "Future", "Gene Cluster", "Gene Expression", "Gene Expression Profile", "Gene set enrichment analysis", "Goals", "Health", "Health Care Costs", "Immune", "Immunoglobulin A", "In Vitro", "Individual", "Infection", "Inflammation", "Inflammatory", "Inflammatory Response", "Injury", "Intervention", "Intestinal permeability", "Link", "Measures", "Microfluidics", "Mucous Membrane", "Multisystem Inflammatory Syndrome in Children", "Neutrophil Activation", "Orthostatic tachycardia", "Outcome", "Pathogenesis", "Pathogenicity", "Pathway interactions", "Peptide Hydrolases", "Performance", "Permeability", "Phagocytosis", "Phenotype", "Plasma", "Play", "Population", "Proteins", "Proteomics", "Reporting", "Role", "SARS-CoV-2 antigen", "SARS-CoV-2 infection", "Sampling", "Schools", "Source", "Stomach", "Subgroup", "Symptoms", "Syndrome", "Technology", "Testing", "Therapeutic", "Tissues", "acute COVID-19", "antagonist", "chemokine", "effective therapy", "gastrointestinal", "improved", "migration", "neutrophil", "novel strategies", "post-COVID-19", "programs", "receptor", "single-cell RNA sequencing", "transcriptome sequencing", "zonulin" ], "approved": true } }, { "type": "Grant", "id": "14667", "attributes": { "award_id": "1P20GM152280-01", "title": "Telemedicine, Caregivers, and Rural Population Health", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [], "start_date": "2024-04-15", "end_date": "2029-02-28", "award_amount": 208594, "principal_investigator": { "id": 31362, "first_name": "Misty", "last_name": "Heggeness", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1496, "ror": "", "name": "UNIVERSITY OF KANSAS LAWRENCE", "address": "", "city": "", "state": "KS", "zip": "", "country": "United States", "approved": true }, "abstract": "This project seeks to harness big data in electronic health records to study the impact of increasing access to telemedicine on the health and wellbeing of rural caregivers. Life in rural communities comes with additional barriers to daily activities. Family members may travel hours to make weekly or monthly purchases from big box super stores. Travel time eats away at time for other activities, both paid work and family related. Farm- related family work is often time- and labor-intensive, budgets are often stretched, and household production activities usually require more time. Rural families have less access to restaurants, food preparation programs, food delivery services, and the like. They are less likely to outsource household production tasks like cooking, cleaning, washing clothes, growing food, childcare, and elder care. The compilation of this reality puts disproportionate stress on caregivers in rural communities. Rural caregivers, predominantly women, are vulnerable to exhaustion, increased health issues related to stress, and missing their own preventative care screenings due to the increased burden of care within their households. This was especially true during COVID-19. Using data from the Northeast and Southern regions of the country, the project develops a proof of concept for a future R01 grant to study the dynamics of increasing telemedicine in rural communities in the Midwest. The focus of this project is to document increased access to telemedicine and other remote healthcare options for caregivers during COVID-19 and its effect on the health and wellbeing of caretakers in rural communities. Technological advancements of the past half century have accelerated the use of big data methods to understand major health, economic, and social trends, and the project harnesses electronic health records from major health systems linked to the 2020 Census and American Community Survey (ACS) to analyze differential changes in health service take up and overall health and wellbeing of caregivers and related family members. The project will evaluate what public health policies that can effectively be implemented to support increased access in rural communities, and which types of telemedicine prove particularly helpful in enhancing and increasing the health and wellbeing of caregivers in rural communities.", "keywords": [ "Acceleration", "Affect", "American", "Area", "Big Data", "Big Data Methods", "Budgets", "COVID-19", "COVID-19 pandemic", "Caregiver well-being", "Caregivers", "Caring", "Censuses", "Cessation of life", "Characteristics", "Child", "Child Care", "Community Surveys", "Consumption", "Country", "Creativeness", "Data", "Data Set", "Demographic Analyses", "Eating", "Economics", "Electronic Health Record", "Emotional", "Equity", "Family", "Family member", "Farm", "Food", "Future", "Geography", "Goals", "Grant", "Health", "Health Personnel", "Health Policy", "Health Services", "Health system", "Hour", "Household", "Infrastructure", "Kansas", "Life", "Link", "Long-Term Care for Elderly", "Medical", "Mentors", "Midwestern United States", "Mothers", "Outsourcing", "Parents", "Personal Satisfaction", "Policies", "Policy Maker", "Population", "Preventive care", "Production", "Provider", "Public Health", "Records", "Research", "Resources", "Restaurants", "Risk", "Rural", "Rural Community", "Rural Population", "Service provision", "Services", "Stress", "Stretching", "Taxes", "Techniques", "Technology", "Telemedicine", "Time", "Travel", "Woman", "Women&apos", "s Health", "Work", "access restrictions", "care burden", "cooking", "data cleaning", "disease diagnosis", "econometrics", "exhaustion", "firewall", "food preparation", "health care availability", "health data", "improved", "innovation", "instrument", "next generation", "pandemic disease", "pandemic impact", "population health", "post-pandemic", "programs", "rate of change", "remote delivery", "remote health care", "rural area", "rural families", "rural patients", "screening", "service delivery", "social", "trend", "virtual", "virtual healthcare" ], "approved": true } }, { "type": "Grant", "id": "14677", "attributes": { "award_id": "1K08DK136924-01A1", "title": "Identification of Host-Specific Determinants of APOL1-associated COVAN", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 7449, "first_name": "TRACY L", "last_name": "RANKIN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-04-01", "end_date": "2029-02-28", "award_amount": 153306, "principal_investigator": { "id": 31371, "first_name": "Sarah", "last_name": "Nystrom", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Coronavirus disease 2019 (COVID-19)-associated nephropathy (COVAN) is a severe form of kidney disease resulting from collapse of the glomerular tuft and manifesting clinically with proteinuria and high rates of kidney failure. More than 90% of COVAN cases are associated with two coding variants in the apolipoprotein L1 (APOL1) gene. These variants are mainly found in persons with Black, African American, or Hispanic ancestry. The objective of this proposal is to identify patient-specific determinants of APOL1-mediated COVAN penetrance. Our published and preliminary data suggest that: 1. APOL1 is robustly expressed in the glomeruli of patients with COVAN but not in healthy controls. 2. COVID-19-induced cytokines upregulate pathogenic APOL1 variants via JAK-STAT signaling in human kidney organoids and, in turn, cause podocyte injury. 3. Cytokine-induced podocyte injury is blocked by inhibition of JAK/STAT/APOL1 axis. 4. Expression of variant APOL1 protein is sufficient to cause dose-dependent cytotoxicity in vitro. Consistent with these discoveries, others found that expression of APOL1 variants caused glomerulosclerosis in transgenic mice. Based on these published and preliminary data, we hypothesize that maladaptive crosstalk between glomerular cells and immune cells drive increased expression of APOL1 and the pathogenesis of COVAN. Moreover, that patients who develop COVAN either express higher levels of pathogenic cytokines (those cytokines known to induce APOL1 expression), or the glomerular cells of these individuals have an enhanced and maladaptive response to the same level of cytokine. To test this hypothesis, we will leverage unique patient-derived kidney organoids and immune cells of persons with biopsy-proven COVAN (collected after patients have recovered from infection). We propose two aims: 1.) Delineate the divergent biological responses of kidney organoids derived from COVAN patients versus controls after (i) infection with SARS-CoV-2 or (ii) treatment with COVID-19 induced cytokines. 2.) Identify differences in cellular response of immune cells of COVAN patients versus controls after (i) infection with SARS-CoV2 or (ii) treatment with COVID-19 induced cytokines. Identifying host- factors that regulate APOL1 and immune-glomerular interactions in COVAN will provide novel biomarkers and therapeutic targets for modulating APOL1 expression to treat COVAN and other forms of APOL1 nephropathy, helping to mitigate disparities in kidney disease. Execution of these scientific aims and completion of the career development activities of this proposal, along with the experienced mentorship and strong institutional support, will prepare me for a career as an independent physician scientist equipped for research into APOL1- mediated, inflammatory-mediated, and viral-mediated nephropathies.", "keywords": [ "2019-nCoV", "Acute Renal Failure with Renal Papillary Necrosis", "African American", "African American population", "African ancestry", "Aftercare", "Apolipoproteins", "Automobile Driving", "Basic Science", "Biological", "Biopsy", "Black race", "COVID-19", "COVID-19 disparity", "COVID-19 impact", "COVID-19 pathogenesis", "COVID-19 patient", "COVID-19 treatment", "Cell Compartmentation", "Cell-Mediated Cytolysis", "Cells", "Chronic", "Clinical", "Code", "Complement", "Data", "Development", "Diagnosis", "Disease", "Dose", "End stage renal failure", "Event", "Feedback", "Focal and Segmental Glomerulosclerosis", "Gene Expression", "Genes", "Genetic", "Genotype", "Goals", "Health", "Hispanic ancestry", "Human", "Immune", "Immune response", "Immunologic Factors", "Immunology", "In Vitro", "Incubated", "Individual", "Infection", "Inflammatory", "Injury", "Institution", "Integration Host Factors", "Interferons", "Kidney", "Kidney Diseases", "Kidney Failure", "Knowledge", "Lead", "Ligands", "Measurement", "Mediating", "Mentors", "Mentorship", "Messenger RNA", "Molecular", "Morbidity - disease rate", "Organoids", "Outcome", "Outcome Measure", "Pathogenesis", "Pathogenicity", "Pathway interactions", "Patients", "Penetrance", "Peripheral Blood Mononuclear Cell", "Persons", "Physicians", "Population", "Proteins", "Proteinuria", "Publishing", "RNA", "Research", "Role", "SARS-CoV-2 exposure", "SARS-CoV-2 infection", "Scientist", "Signal Transduction", "Stem Cell Research", "Testing", "Training", "Transgenic Mice", "Translational Research", "Up-Regulation", "Variant", "Viral", "Virus Diseases", "career", "career development", "cell type", "chemokine", "comparison control", "cytokine", "cytotoxicity", "differential expression", "disparity reduction", "dosage", "experience", "glomerulosclerosis", "high risk", "human induced pluripotent stem cells", "human tissue", "immune cell infiltrate", "improved", "kidney biopsy", "kidney cell", "kidney infection", "mortality", "new therapeutic target", "novel marker", "podocyte", "post SARS-CoV-2 infection", "prevent", "primary outcome", "racial disparity", "receptor", "response", "single-cell RNA sequencing", "skill acquisition", "targeted treatment", "training opportunity", "transcriptome", "transcriptomics", "treatment response", "virology" ], "approved": true } }, { "type": "Grant", "id": "14698", "attributes": { "award_id": "1K01MH135783-01A1", "title": "Preventing disruptions in progress towards ending HIV/AIDS: Lessons from the COVID-19 pandemic", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 24064, "first_name": "Lori", "last_name": "Scott-Sheldon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-03-21", "end_date": "2029-02-28", "award_amount": 177304, "principal_investigator": { "id": 31395, "first_name": "Danielle", "last_name": "Giovenco", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 265, "ror": "https://ror.org/03czfpz43", "name": "Emory University", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "Public health emergencies, including conflict, natural disasters, and local and global epidemics and pandemics, have the potential to disrupt progress towards ending the HIV/AIDS epidemic. Understanding the impact that these disruptive events have on the HIV epidemic over time is essential to mitigating their effects. In the present study, using the COVID-19 pandemic in South Africa as a case example, we will establish applied methods for estimating disruptions in HIV outcomes and identifying modifiable intervention targets. Specifically, the research plan focuses on 1) building a database that harmonizes multiple national surveillance systems across South Africa to enable the generation of robust HIV, mental health, and social determinant of health (SDoH) estimates; 2) conducting an interrupted time series analysis to examine short- and long-term trends in HIV prevention and care outcomes, mental health, and SDoH prior to and during COVID-19 in South Africa; and 3) extending an existing agent-based model (ABM) to identify social factors predictive of HIV outcomes during COVID-19 and simulate the impact of changes on predictive factors to identify targets for hypothetical interventions. This application in response NOSI NOT-AI-21-057 (HIV/AIDS in the Era of COVID-19) is extremely timely as the effects of the COVID-19 pandemic continue to evolve and predictions indicate future emerging epidemics and other disruptive events are imminent. Through this award, I will extend my prior experience in program implementation in South Africa and training in epidemiologic methods to 1) acquire a foundation of knowledge in techniques for harmonizing data across multiple national surveillance systems; 2) develop proficiency in advanced data science methods, including an interrupted time series design analysis and agent-based modeling; 3) cultivate expertise on the impact of disruptive events on the HIV epidemic, including the role of social and contextual factors, and methods for identifying effective, policy-relevant intervention programs; and 4) build the foundation for an academic career in global health research by strengthening international collaborations and grantsmanship, research dissemination, and policy engagement skills. To accomplish these goals, I will complete coursework, workshops, and independent study; participate in mentored training and mentored original research; engage with South African policy makers; attend and present at multiple meetings and conferences annually; and complete numerous manuscripts and grant applications. Completion of this training program will allow me to develop the language, concepts, and principles necessary to work with multidisciplinary teams of modeling and implementation experts, which will be instrumental in securing subsequent funding to develop methods for forecasting disruptions and identifying effective, policy-relevant interventions in real time. Importantly, this award will also allow me to launch a robust, independent academic research career focused on conducting rigorous epidemiological research to prevent future disruptive events from perpetuating health disparities in generalized HIV epidemic settings.", "keywords": [ "AIDS prevention", "Accounting", "Acquired Immunodeficiency Syndrome", "Affect", "Africa South of the Sahara", "African", "Applications Grants", "Asian", "Award", "Back", "COVID-19", "COVID-19 impact", "COVID-19 pandemic", "COVID-19 pandemic effects", "Collaborations", "Communities", "Conflict (Psychology)", "Country", "Data", "Data Science", "Data Sources", "Databases", "Diagnosis", "Drops", "Economics", "Education", "Educational workshop", "Ensure", "Environment", "Epidemic", "Epidemiologic Methods", "Epidemiology", "Event", "Foundations", "Funding", "Future", "Generations", "Goals", "HIV", "HIV Infections", "HIV diagnosis", "HIV risk", "HIV/AIDS", "Health Services", "Health care facility", "Household", "Human immunodeficiency virus test", "Incidence", "Individual", "International", "Interruption", "Intervention", "Knowledge", "Language", "Longitudinal trends", "Manuscripts", "Mental Health", "Mentors", "Methods", "Modeling", "Modification", "Natural Disasters", "Outcome", "Persons", "Policies", "Policy Maker", "Population", "Predictive Factor", "Prevalence", "Psychological Factors", "Public Health", "Reporting", "Research", "Risk Estimate", "Risk Factors", "Role", "Secure", "Series", "South Africa", "South African", "Southern Africa", "Surveys", "Suspensions", "System", "Techniques", "Time", "Time Series Analysis", "Training", "Training Activity", "Training Programs", "Viral", "Work", "antiretroviral therapy", "burden of illness", "care outcomes", "career", "contextual factors", "data harmonization", "design", "epidemiology study", "experience", "global health", "health care quality", "health determinants", "health disparity", "intervention program", "meetings", "mortality", "multidisciplinary", "national surveillance", "new epidemic", "pandemic disease", "population movement", "prevent", "programs", "public health emergency", "research data dissemination", "response", "service utilization", "skills", "social determinants", "social factors", "social health determinants", "symposium", "treatment program" ], "approved": true } }, { "type": "Grant", "id": "14701", "attributes": { "award_id": "1P01AI172501-01A1", "title": "The role of senescent cells in dysregulating immune responses and pathogen control", "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": 6621, "first_name": "Mercy R.", "last_name": "Prabhudas", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-03-11", "end_date": "2029-02-28", "award_amount": 2723166, "principal_investigator": { "id": 22876, "first_name": "STEPHEN C", "last_name": "JAMESON", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 764, "ror": "https://ror.org/017zqws13", "name": "University of Minnesota", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 764, "ror": "https://ror.org/017zqws13", "name": "University of Minnesota", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true }, "abstract": "The association between advanced age and impaired resistance to infections is well known, but poorly understood. The current COVID-19 pandemic is a clear example of the vulnerability of the elderly to SARS- CoV-2 infection as well as many other pathogens. Considerable research efforts have shown that components of both the innate and adaptive immune systems show signs of dysfunction as we age, with signs of both immunodeficiency, including reduced innate response and poor induction of adaptive immune memory, and immunopathology including an exaggerated “cytokine storm”. However, while aspects of age-related changes in immune cells have been explored in depth, the focus has been on defining the nature of dysfunction within cells of the immune system itself, rather than investigating the potential role of other cell populations in dominantly compromising immune homeostasis and immunological response to pathogens. Also, although the increase in immunosenescence with age, defined by cell surface markers for immune cell exhaustion, has been examined, the extent of cellular senescence in immune cell populations with age and pathogen exposure remains undefined. Our recent findings indicate that senescent cells (SnCs), including senescent immune cells, can exert a “bystander” effect on immune cells, provoking immunological dysfunction through secretion of inflammatory factors, including cytokines and chemokines, termed the “senescence-associated secretory phenotype” (SASP). We demonstrated that SASP factor production is increased when SnCs or mice containing SnCs are exposed to pathogens or microbial products that induce innate immune activation. Exposure of old mice to normal microbial experience (NME) housing resulted in 100% mortality compared to no mortality in young mice. However, reducing the senescent cell burden in aged mice before or following pathogen exposure reduced the spread of senescence, the cytokine storm and overall mortality. These results suggests that SnCs, acting at least in part through SASP factors, can increase peripheral senescence and immune dysfunction following pathogen exposure. Moreover, viral infection itself drives senescence, termed virus induced senescence, in mice and humans. Using mouse models in which cellular senescence is induced specifically in immune cells, we also demonstrated that senescent immune cells drive immunological dysfunction and secondary senescence and pathology in non-lymphoid tissues. Thus, our overarching hypothesis is that senescent cells, including senescent immune cell types, dominantly compromise innate and adaptive immune cell homeostasis in both lymphoid and non-lymphoid organs and reactivity to pathogens. Importantly, we also hypothesize that these adverse effects can be reversed by SnC elimination with senolytics, providing a new therapeutic strategy to restoring immune function in the aged. We propose to test these hypotheses in our PPG application entitled “The role of senescent cells in dysregulating immune responses and pathogen control”, consisting of three collaborative projects and three integrated cores.", "keywords": [ "Ablation", "Adaptive Immune System", "Address", "Adverse effects", "Affect", "Age", "Age Distribution", "Alzheimer&apos", "s Disease", "Bioinformatics", "Biology of Aging", "Bystander Effect", "COVID-19 pandemic", "COVID-19 patient", "Cell Aging", "Cell Physiology", "Cell surface", "Cells", "Clinical Trials", "Data", "Defect", "Degenerative polyarthritis", "Elderly", "Exposure to", "Functional disorder", "Generations", "Genetic Models", "Genetically Engineered Mouse", "Homeostasis", "Housing", "Human", "Immune", "Immune System Diseases", "Immune response", "Immune system", "Immunologic Deficiency Syndromes", "Immunologic Memory", "Impairment", "Infection", "Inflammatory", "Innate Immune System", "Interruption", "Lymphoid", "Mediating", "Modeling", "Molecular", "Mus", "National Institute of Allergy and Infectious Disease", "Nature", "Organ", "Organism", "Outcome", "Pathology", "Peripheral", "Pharmaceutical Preparations", "Phenotype", "Population", "Process", "Production", "Reporting", "Research", "Resistance", "Resistance to infection", "Role", "SARS-CoV-2 infection", "Standardization", "Surface Antigens", "Testing", "Tissues", "Translating", "Virus", "Virus Diseases", "Work", "age related", "aged", "cell type", "chemokine", "clinical application", "cytokine", "cytokine release syndrome", "exhaustion", "experience", "fighting", "frailty", "immune activation", "immune clearance", "immune function", "immunopathology", "immunosenescence", "improved", "microbial", "microbial products", "mortality", "mouse model", "novel", "novel therapeutic intervention", "novel therapeutics", "pathogen", "pathogen exposure", "preclinical study", "response", "senescence", "single cell analysis" ], "approved": true } }, { "type": "Grant", "id": "14702", "attributes": { "award_id": "1P01AI172501-01A1", "title": "Effect of senescent cells", "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": [], "start_date": "2024-03-11", "end_date": "2029-02-28", "award_amount": 536216, "principal_investigator": { "id": 22876, "first_name": "STEPHEN C", "last_name": "JAMESON", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 764, "ror": "https://ror.org/017zqws13", "name": "University of Minnesota", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 764, "ror": "https://ror.org/017zqws13", "name": "University of Minnesota", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true }, "abstract": "The induction and maintenance of adaptive immune responses are critical for effective and durable protection against diverse pathogens and the efficacy of vaccines. Yet it is known that both the homeostasis and function of adaptive immune cells declines with age – while there may be multiple causes for this, recent studies (including those from our group) indicate a potentially pivotal role for senescent cells. Diverse cell types (including immune cells) become senescent with age and in various chronic disease states, and this state not only affects the replicative potential of the senescent cells (SnC) themselves, but by their production of a variety of factors (in what is termed the senescence-associated secretory phenotype or SASP), they can affect other cells, in trans. Many of these SASP factors are pro-inflammatory and can provoke immunopathology in vulnerable populations (including the aged, as illustrated in the cytokine storm reported in elderly COVID-19 patients). These “bystander” effects have been demonstrated in experimental mouse models. Most exciting, ablation of SnC (using senotherapeutic compounds) results in marked improvement of immune control of pathogens. However, there is a key knowledge gap in understanding what effect SnCs have on adaptive immune populations, how those effects are mediated and how crosstalk between senescent and immune cells influences the physiological establishment of senescence with age. We address these in three Specific Aims. Aim 1 tests how exposure to SnC – as a single variable – influences adaptive immune cell homeostasis and function in response to defined viral infections, using well defined mouse models to pinpoint the consequences of SnC introduction vs destruction on naïve and memory T and B cell populations. This includes functional and single-cell analysis approaches. In Aim 2, we turn the tables by investigating tantalizing data which indicate certain immune populations (including NK cells) may be capable of SnC destruction during normal physiology – a feedback loop that we suspect is compromised with age, resulting in SnC build up. The function of NK cells and other immune populations in culling SnC will be explored. Aim 3 explores how SnC mediate their inhibitory effects on lymphocytes – by harnessing the power of CRISPR/Cas9 approaches to ablate receptors for SASP factors and explore the functional significance of immunoregulatory molecules induced on “young” T cells in the aged environment, as well as test the ability of SASP factors to provoke these age-related changes, in vitro in both mouse and human cells. The approaches and goals integrate with the single-cell studies, novel mouse model development and refinement of senotherapeutics conducted in Project 1, and with complementary studies on generation, homeostasis and function of adaptive immune cells embedded in non-lymphoid tissues, conducted in Project 3. A consistent source of the key mouse models and pathogens used will be provided by Core B, while all the single-cell analysis from Project 2 and the other Projects will be conducted and integrated by Core C. The Administrative Core (Core A) will oversee coordinated work of Projects and Cores and establish internal and external review.", "keywords": [ "2019-nCoV", "Ablation", "Acute", "Address", "Affect", "Age", "Aging", "Animals", "Architecture", "Attenuated", "Automobile Driving", "B-Lymphocytes", "Biological Assay", "Bystander Effect", "CD8-Positive T-Lymphocytes", "COVID-19 patient", "CRISPR screen", "CRISPR/Cas technology", "Cell Aging", "Cell Cycle", "Cells", "Characteristics", "Chronic Disease", "Data", "Defect", "Diabetes Mellitus", "Elderly", "Environment", "Exposure to", "Feedback", "Functional disorder", "Generations", "Goals", "Homeostasis", "Human", "Immune", "Immune System Diseases", "Immune mediated destruction", "Immune response", "Immune system", "Immunity", "Immunologic Memory", "Immunomodulators", "Impairment", "In Vitro", "Individual", "Infection", "Inflammatory", "Innate Immune Response", "Knowledge", "Ligands", "Link", "Literature", "Lymphocyte", "Lymphoid", "Lymphoid Tissue", "Maintenance", "Mediating", "Memory", "Metabolic Diseases", "Modeling", "Molecular", "Mus", "Natural Killer Cells", "Obesity", "Pathway interactions", "Phenotype", "Physiological", "Physiology", "Play", "Population", "Production", "Publishing", "Regulation", "Reporting", "Resistance", "Resistance to infection", "Risk", "Role", "Source", "Sterility", "Stress", "T memory cell", "T-Lymphocyte", "Testing", "Tissues", "Vaccination", "Virus Diseases", "Vulnerable Populations", "Work", "adaptive immune response", "age related", "aged", "attenuation", "cell type", "chemokine", "cytokine", "cytokine release syndrome", "immune clearance", "immune function", "immunopathology", "immunoregulation", "improved", "insight", "microbial", "microbial products", "model development", "mouse model", "novel", "novel strategies", "pathogen", "receptor", "resilience", "response", "senescence", "single cell analysis", "synergism", "vaccine efficacy" ], "approved": true } } ], "meta": { "pagination": { "page": 1391, "pages": 1424, "count": 14236 } } }