Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=3&sort=-id
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-id", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=-id", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=-id", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=-id" }, "data": [ { "type": "Grant", "id": "15975", "attributes": { "award_id": "1R01AI195779-01", "title": "Regulatory T cell memory in human tissues", "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": 44428, "first_name": "CHAO", "last_name": "JIANG", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-06", "end_date": "2030-01-31", "award_amount": 3144408, "principal_investigator": { "id": 7597, "first_name": "Donna L.", "last_name": "Farber", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 745, "ror": "", "name": "SCRIPPS RESEARCH INSTITUTE, THE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 44429, "first_name": "Peter Alan", "last_name": "Sims", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 781, "ror": "", "name": "COLUMBIA UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "T cell memory is stored across heterogeneous subsets with diverse functions in both tissues and circulation. While most studies have focused on the pro-inflammatory and cytotoxic functions of memory T cells, regulatory T cells (Tregs) serve an equally important immunomodulatory role in memory responses, particularly in tissues. While specific roles for Tregs in establishing tolerance and promoting tissue homeostasis have been elucidated in mouse models, the role of human Tregs in healthy immune responses and protective immunity in vivo has been difficult to assess. Moreover, the identity and function of human Tregs in diverse tissues remains unknown. We have established an organ donor tissue resource for human immunology that has allowed us to profile antigen-specific T cells across human tissues. Through these efforts, we found that antigen-specific Tregs are substantially enriched among memory T cells that respond to antigens from multiple viruses, including SARS-CoV-2, influenza, and EBV, and are particularly enriched in lymph nodes, spleen and lungs compared to blood, bone marrow and other sites. In addition, we found that memory Tregs induce an activation program that is distinct from effector memory T cells (TEM) involving CCL17 as a novel Treg-derived cytokine not produced by TEM cells or any other T cell subset. Moreover, tissue memory Tregs exhibit clonal overlap with TEM cells within and between sites. These findings raise the possibility that memory Tregs are generated along with TEM during priming and that they share a common pre-cursor with TEM. In the proposed studies, we will pursue three aims: 1) Determine the role of antigen and tissue in memory Treg induction; 2) Define the clonal and migratory relationships (i.e. tissue distributions) between memory Treg and other memory subsets; 3) Elucidate the functional and spatial interactions of tissue Tregs with immune and structural cells in the lymph node. We will combine state-of-the-art technologies for single-cell and spatial profiling with our unique human tissue resource to elucidate mechanisms for the generation, function, and maintenance of memory Tregs in human tissues. The results from this study will be important for designing strategies to promote immunoregulation and tissue repair for protective immunity and can inform Treg-directed therapies for autoimmunity and transplantation.", "keywords": [ "2019-nCoV", "Adult", "Affect", "Age", "Allergens", "Antigens", "Autoantigens", "Autocrine Communication", "Autoimmunity", "Blocking Antibodies", "Blood", "Bone Marrow", "CCL17 gene", "CCR8 gene", "COVID-19", "Cell Communication", "Cells", "Cellular Indexing of Transcriptomes and Epitopes by Sequencing", "Chemotaxis", "Circulation", "Cytoprotection", "Drug or chemical Tissue Distribution", "Environment", "Exhibits", "FOXP3 gene", "Fatty acid glycerol esters", "Frequencies", "Gene Expression", "Gene Expression Profile", "Generations", "Homeostasis", "Homing", "Human", "Human Herpesvirus 4", "Human Resources", "IL2RA gene", "Immune", "Immune response", "Immune system", "Immunity", "Immunization", "Immunology", "In Situ", "Individual", "Infection", "Inflammation", "Inflammatory", "Influenza", "Life", "Lung", "Lymphoid Tissue", "Maintenance", "Mediating", "Memory", "Mucous Membrane", "Mus", "Muscle", "Organ Donor", "Pathway interactions", "Phenotype", "Play", "Population", "Proteins", "RNA vaccine", "Regulation", "Regulatory T-Lymphocyte", "Research", "Role", "SARS-CoV-2 infection", "Signal Transduction", "Site", "Slice", "Spleen", "Stromal Cells", "T cell differentiation", "T cell therapy", "T memory cell", "T-Cell Activation", "T-Lymphocyte", "T-Lymphocyte Subsets", "Technology", "Thymus Gland", "Tissues", "Transplantation", "Vaccines", "Virus", "Virus Diseases", "age related changes", "antigen-specific T cells", "cell motility", "chemokine", "cytokine", "cytotoxic", "design", "human tissue", "immunoregulation", "in vivo", "lymph nodes", "lymphoid organ", "memory CD4 T lymphocyte", "mouse model", "multimodality", "novel", "pathogen", "programs", "receptor", "recruit", "response", "single cell technology", "tissue repair", "tissue resident memory T cell", "tissue resource", "transcription factor", "tumor" ], "approved": true } }, { "type": "Grant", "id": "15974", "attributes": { "award_id": "1R01AI191417-01A1", "title": "MARVELOUS: Maternal RSV Vaccination- Evaluating Optimal Immune Responses", "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": 44292, "first_name": "MERCY R", "last_name": "PRABHUDAS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-06", "end_date": "2030-01-31", "award_amount": 3859259, "principal_investigator": { "id": 21683, "first_name": "Andrea Goldberg", "last_name": "Edlow", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 736, "ror": "https://ror.org/002pd6e78", "name": "Massachusetts General Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22942, "first_name": "SABRA L.", "last_name": "KLEIN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, { "id": 44427, "first_name": "Liza", "last_name": "Konnikova", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3427, "ror": "", "name": "MASSACHUSETTS GENERAL HOSPITAL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The recent approval of the Respiratory Syncytial Virus (RSV) vaccine for administration in pregnancy presents a novel opportunity to define immune responses of the maternal-fetal dyad, and how that response crosses the placenta and mammary tissue. Recent work indicates that timing of maternal RSV vaccination alters placental antibody transfer to the fetus. To maximize infant protection after maternal RSV vaccination, key gaps in knowledge include: 1. The extent to which maternal vaccination elicits direct fetal antigen-agnostic and antigen- specific cellular responses to augment infant protection from RSV and other infections. 2. How gestational age at vaccination alters maternal antibody response, subsequent placental and breastmilk antibody transfer, and persistence of immunity in the infant. The proposed studies will test the central hypothesis that timing of maternal vaccination, antibody Fc-receptor binding properties, glycosylation profiles, neutralizing antibody levels and non-neutralizing antibody functions are all key determinants of placental and breastmilk antibody transfer to the neonate. These antibody features will work in concert with fetal innate and adaptive immune responses to maternal vaccination, driving protection of the infant through 6 months of age. In a cohort of 400 pregnant women and their infants, this study will examine fetal cellular responses to maternal RSV vaccination, both RSV-agnostic and RSV-specific, by evaluating fetal immune cells isolated from placental villi and cord blood (Aim 1). It will comprehensively profile placentally- and breastmilk-transferred antibodies after RSV vaccination in pregnancy, evaluating IgG subclass, Fc-receptor binding, glycosylation profile, and neutralizing capacity of antibodies using in vivo and in vitro assays (Aim 2). It will then evaluate how antibody properties and timing of maternal vaccination impact the durability of antibody-mediated and cellular immunity in infant blood and breastmilk, through 6 months of age (Aim 3). Machine learning approaches will be used to estimate the magnitude and specific features of protective immune responses induced by maternal vaccination, not only for RSV, but also for influenza, Tdap, and COVID-19. These methods will generate a comprehensive model of durable infant protection from maternal vaccination spanning multiple pathogens. Defining these immune principles across the maternal-fetal dyad will generate key biological insights necessary to optimize neonatal and infant protection.", "keywords": [ "3-Dimensional", "Address", "Age Months", "Antibodies", "Antibody Response", "Antibody-mediated protection", "Antigens", "Automobile Driving", "Biological", "Biological Assay", "Blood", "Breast", "Breast Epithelial Cells", "COVID-19", "COVID-19 vaccination", "COVID-19 vaccine", "Cell Separation", "Cells", "Cellular Immunity", "Characteristics", "Chorionic villi", "Clinical Trials", "Clonal Expansion", "Colostrum", "Data", "Disease", "Ensure", "Fc Receptor", "Fetus", "Future", "Gene Expression Profile", "Gestational Age", "Human Milk", "Immune", "Immune response", "Immune system", "Immunity", "Immunoglobulin G", "In Vitro", "Infant", "Infection", "Influenza", "Innate Immune Response", "Knowledge", "Life", "Longevity", "Machine Learning", "Maternal antibody", "Measures", "Mediating", "Memory", "Methods", "Milk", "Modeling", "Mononuclear", "Mothers", "Nature", "Neonatal", "Peptides", "Pertussis", "Phase III Clinical Trials", "Phenotype", "Placenta", "Plasma", "Polysaccharides", "Pregnancy", "Pregnant Women", "Premature Birth", "Property", "Prospective cohort", "Recommendation", "Respiratory Syncytial Virus Vaccines", "Respiratory syncytial virus", "Serology", "System", "T cell response", "T memory cell", "T-Lymphocyte", "Testing", "Time", "Tissues", "Training", "Umbilical Cord Blood", "Vaccinated", "Vaccination", "Vaccine Design", "Vaccines", "Work", "adaptive immune response", "anti-influenza", "antibody test", "antibody transfer", "cohort", "embryo/fetus antigen", "emerging pathogen", "experimental study", "fetal", "fetal immunity", "glycosylation", "immune function", "in vitro Assay", "in vivo", "infant morbidity", "infant morbidity/mortality", "insight", "large datasets", "machine learning method", "machine learning model", "mammary", "maternal vaccination", "neonatal immunity", "neonate", "neutralizing antibody", "novel", "pathogen", "placental transfer", "predictive modeling", "prenatal exposure", "receptor binding", "respiratory pathogen", "response", "sex", "transcytosis", "unvaccinated", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "15973", "attributes": { "award_id": "1R21AI190550-01A1", "title": "Discovery and evolution of mammalian Serpins as host-encoded viral protease inhibitors", "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": 32808, "first_name": "MINDY I", "last_name": "DAVIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-04", "end_date": "2028-01-31", "award_amount": 439250, "principal_investigator": { "id": 25173, "first_name": "Matthew", "last_name": "Daugherty", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 760, "ror": "https://ror.org/0168r3w48", "name": "University of California, San Diego", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3426, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN DIEGO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Viral proteases are essential for the replication of many RNA and DNA viruses. Through sequence specific recognition of cleavage sites, these proteases process viral polyproteins into their functional components, while also cleaving host proteins to facilitate viral replication. Interestingly, organisms from every domain of life encode proteins known as SERPINs (SERine Protease INhibitors) that serve as natural inhibitors of serine and cysteine proteases, the types of proteases encoded by many viruses. SERPINs contain a conserved structural core and a disordered reactive center loop (RCL) that ‘baits’ a protease into cleaving it by mimicking the sequence specificity of the protease to be inhibited. Following protease-mediated cleavage of the RCL, the SERPIN undergoes a large conformation change that covalently traps and inactivates the protease, thus connecting sequence-specific recognition of the SERPIN RCL to protease inhibition. While SERPINs have been largely characterized as inhibitors of a wide range of cellular proteases, we hypothesize in this grant that SERPINs have also evolved, in a species-specific manner, to directly inhibit viral protease activity and thereby inhibit viral replication. Supporting this hypothesis, we have found that several mammalian SERPINs contain RCLs that are rapidly evolving under positive selection, consistent with SERPINs being engaged in evolutionary arms races with pathogen-encoded proteases. Moreover, we have identified primate SERPINs that have independently evolved sequences that mimic the cleavage site preferences of proteases from picornaviruses and coronaviruses, and find that these SERPINs can inhibit viral protease activity during infection. These data lead us to propose a model in which SERPINs, with their protease baiting RCLs, represent a modular platform for evolution of host-specific antiviral activity through viral protease inhibition. Based on this model, we now propose to use evolutionary biology, protease biochemistry, and virology to discover and characterize the natural variation, evolvability, protease specificity, and antiviral activity of viral protease inhibitors among mammalian SERPINs. In Aim 1, we will test the antiviral potency and specificity of primate SERPIN-mediated viral protease inhibition, while also computationally and functionally searching for additional mammalian SERPINs that can inhibit proteases from a wide range of RNA viruses. In Aim 2, we will probe the modularity and evolvability of SERPINs to determine the degree to which the SERPIN ‘core’ and RCL sequence impact function, and how sequence evolution of each can mediate selective viral protease inhibition. By identifying SERPINs as novel, rapidly evolving, host-encoded viral protease inhibitors, our work will reveal the impact of SERPIN and viral protease evolution on this new host-virus evolutionary conflict and on species-specific barriers to virus replication, and unveil the evolutionary potential of SERPINs to inhibit a wide range of viral proteases.", "keywords": [ "2019-nCoV", "Adjustment Disorders", "Alpha Virus", "Aotus trivirgatus", "Architecture", "Attenuated", "Binding", "Biochemical", "Biochemistry", "Biological Assay", "Biology", "Caspase", "Cells", "Conflict (Psychology)", "Coronavirus", "DNA Viruses", "Data", "Dengue Virus", "Enterovirus", "Evolution", "Family", "Family Picornaviridae", "Flavivirus", "Grant", "HIV-1", "Hepatitis C virus", "Homologous Gene", "Human", "Infection", "Life", "Macaca mulatta", "Mammals", "Mediating", "Modeling", "Molecular", "Molecular Conformation", "Organism", "Peptide Hydrolases", "Polyproteins", "Primates", "Process", "Protease Inhibitor", "Protein Region", "Proteins", "RNA Viruses", "Rhinovirus", "Serine Proteinase Inhibitors", "Serpins", "Site", "Specificity", "Substrate Specificity", "Testing", "Variant", "Viral", "Viral Physiology", "Virus", "Virus Diseases", "Virus Inhibitors", "Virus Replication", "Work", "arms race", "expectation", "field study", "guided inquiry", "human coronavirus", "human pathogen", "inhibitor", "insight", "mutant", "novel", "pathogen", "preference", "success", "virology", "virus testing" ], "approved": true } }, { "type": "Grant", "id": "15972", "attributes": { "award_id": "1R01AI195981-01", "title": "Understanding programmed ribosomal frameshifting in coronaviruses", "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": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-19", "end_date": "2031-01-31", "award_amount": 414029, "principal_investigator": { "id": 44426, "first_name": "Victoria Manuel", "last_name": "D'Souza", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3425, "ror": "", "name": "HARVARD UNIVERSITY", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Coronaviruses (CoV) are associated with severe diseases as demonstrated by the 2003 severe acute respiratory syndrome (SARS)-CoV1 epidemic and the SARS-CoV2 pandemic. One of the critical steps of infection involves viral mRNA mediated recoding of gene expression; a -1 frameshifting event that occurs during translation. It is this elegant mechanism that allows the ribosome to bypass a stop codon and synthesize viral enzymatic proteins. Furthermore, the frequency by which this event occurs is important for efficient viral infectivity and is regulated by domains in the translating mRNA (in the case of the SARS-CoV, this domain is a pseudoknot). Although structural studies of frameshifting have received considerable aOention and various structures have been proposed and solved, information on exactly which structure causes the frameshifting is lacking. Our preliminary studies indicate that CoV gene expression is regulated by a dynamic, proton-driven equilibrium between an active, and two inactive pseudoknot conformations that allows for strict control over the protein ratios. This proposal aims to gain a complete structural and mechanistic understanding of the frameshifting frequency in CoV by combining structural studies with biochemical and in vivo experiments. Our aims will be: (#1) to understand the basis for how the frameshifting frequency is maintained by engineering structure-guided mutants to test our equilibrium model, (#2) to determine the structures of the pseudoknot signal in both configurations: permissive and nonpermissive for frameshifting, and (#3) to determine the structure of ribosomes as they encounter the permissive conformation of the pseudoknot.", "keywords": [ "2019-nCoV", "Anti-viral Agents", "Biochemical", "Bypass", "COVID-19 pandemic", "Cell Line", "Characteristics", "Chemicals", "Code", "Complex", "Coronavirus", "Cryoelectron Microscopy", "Data", "Development", "Disease", "Engineering", "Equilibrium", "Event", "Frequencies", "Gene Expression", "Genetic", "In Vitro", "Infection", "Mediating", "Messenger RNA", "Molecular Conformation", "Mutation", "Nuclear Magnetic Resonance", "Nucleotides", "Outcome", "Population", "Preparation", "Process", "Proteins", "Protocols documentation", "Protons", "RNA", "Reading Frames", "Respiratory Disease", "Ribosomal Frameshifting", "Ribosomes", "SARS coronavirus", "Sampling", "Signal Transduction", "Structure", "Terminator Codon", "Testing", "Translating", "Translations", "Viral", "Virus", "Virus Replication", "conformer", "drug discovery", "equilibrium model", "experimental study", "in vivo", "insight", "live cell imaging", "mutant", "pandemic disease", "permissiveness", "protonation", "ribosome profiling", "sensor", "translation assay" ], "approved": true } }, { "type": "Grant", "id": "15971", "attributes": { "award_id": "1R35GM162359-01", "title": "The multifaceted pathways of astrovirus entry and egress", "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": [ { "id": 22244, "first_name": "MICHAEL", "last_name": "SAKALIAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-24", "end_date": "2030-12-31", "award_amount": 422677, "principal_investigator": { "id": 44425, "first_name": "Valerie", "last_name": "Cortez", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3424, "ror": "", "name": "UNIVERSITY OF CALIFORNIA SANTA CRUZ", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Astroviruses are a major cause of pediatric diarrhea worldwide. Despite causing one of the most common early childhood infections, astroviruses are one of the least studied enteric RNA viruses. We previously discovered that the virus infects small intestinal goblet cells, specialized epithelial cells that secrete mucus. Few studies have investigated viral infection in goblet cells due to the lack of cell-specific models. Because the mechanisms by which viruses replicate inside of goblet cells are completely unknown, my lab is interested in addressing 1) how do astroviruses enter cells with highly dynamic apical membranes? and 2) what role does mucus secretion play in viral egress? We have established new in vitro models and tools to address these questions and have built a strong and collaborative investigative team with complementary expertise that will ensure the success of these projects. To evaluate receptor-mediated and fluid-phase endocytosis entry pathways into goblet cells, we will use a combination of CRISPR-Cas9 engineering, biochemical analysis, and high-resolution microscopy. We will use a similar suite of techniques as well as cryo-electron microscopy to define the egress pathway of astrovirus from goblet cells via mucus secretion. In addition to murine and human astroviruses, other respiratory and enteric viruses have also been shown to target goblet cells for infection. Thus, our work aims to initially provide foundational knowledge on the basic biology of astroviruses before shedding light on key host pathways in goblet cells that are co-opted by viruses from other families, including influenza and SARS-CoV2. Completion of these studies will provide the first major insights into the virus-host interactions at the apical membrane surface of intestinal goblet cells, which will pave the way for the future development of targeted drug treatments for the numerous viruses that target this unique cell population.", "keywords": [ "2019-nCoV", "Address", "Astrovirus", "Biochemical", "Biology", "CRISPR/Cas technology", "Cell model", "Cells", "Childhood", "Cryoelectron Microscopy", "Development", "Diarrhea", "Endocytosis", "Engineering", "Ensure", "Enteral", "Family", "Foundations", "Future", "Goblet Cells", "Human", "Infection", "Influenza", "Intestines", "Knowledge", "Light", "Liquid substance", "Mediating", "Microscopy", "Modeling", "Mucous body substance", "Mucus-Secreting Cell", "Mus", "Pathway interactions", "Phase", "Play", "Population", "Prevention strategy", "RNA Viruses", "Resolution", "Role", "Small Intestinal Goblet Cell", "Specialized Epithelial Cell", "Surface", "Techniques", "Viral", "Virus", "Virus Diseases", "Virus Replication", "Work", "apical membrane", "early childhood", "enteric virus infection", "in vitro Model", "insight", "interest", "novel", "receptor", "respiratory", "success", "targeted treatment", "tool", "treatment strategy", "virus host interaction" ], "approved": true } }, { "type": "Grant", "id": "15970", "attributes": { "award_id": "1R01DK145476-01", "title": "Mechanisms of non-HIV Collapsing Glomerulopathy in Hispanic Patients", "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": 44424, "first_name": "KEVIN E", "last_name": "CHAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-15", "end_date": "2030-11-30", "award_amount": 783899, "principal_investigator": { "id": 22546, "first_name": "Sumant Singh", "last_name": "Chugh", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 804, "ror": "https://ror.org/01j7c0b24", "name": "Rush University Medical Center", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3423, "ror": "", "name": "RUSH UNIVERSITY MEDICAL CENTER", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "Non-HIV collapsing glomerulopathy (CG) is a severe form of glomerular disease seen in all parts of the world. Major etiological factors include circulating proteins that cause recurrent CG, infections like SARS-CoV-2 and Parvovirus B19, drugs like pamidronate, and background genomic changes potentially present in any of the preceding categories. Whereas variants of the APOL1 gene have been implicated in select populations with West African heritage, a genomic basis in other patient populations has not been elucidated. Using data from two decades of investigations into CG centered around Hispanic patients from Mexico City and more recent genomic data from Peruvian Hispanic patients, several novel mechanistic rat and mouse models of CG were developed. Critical components of the CG upstream pathways are the podocyte expressed transcriptional factor ZHX2 and glomerular integrins, including α3β1 in the podocyte, αvβ5 in the glomerular endothelium, and αvβ3 at both locations. Finally, recombinant mutated human Angiopoietin-like 4 protein 8520 is known to have an integrin stabilizing effect specific to Integrins β1 and β5, and could be potentially used to treat CG in the future. The overall premise of this application is that high podocyte ZHX2 expression and low glomerular endothelial Integrin β5 expression predispose to the development of CG. In Aim 1, changes in glomeruli with high podocyte ZHX2 expression will be investigated using transgenic rat models. Disease mechanism during the development of CG and just prior to the collapse of capillary loops will be elucidated. In Aim 2, changes in glomeruli with low endothelial Integrin β5 expression will be investigated using knockout mouse models. Disease mechanism during the development of CG and just prior to the collapse of capillary loops will be elucidated. In Aim 3, rat and mouse models of CG will be treated with protein 8520 to test for prevention or improvement in CG, and to potentially halt the disease process before the development of collapse.", "keywords": [ "10 year old", "2019-nCoV", "8 year old", "ANGPTL4 gene", "APOL1 gene", "Admixture", "Adriamycin PFS", "Affect", "African American", "Albuminuria", "Apoptosis", "Binding", "Binding Proteins", "Blood capillaries", "COVID-19 pandemic", "CRISPR/Cas technology", "Categories", "Cell Membrane Proteins", "Cell Nucleus", "Cell membrane", "Cells", "Cities", "Cytoplasmic Tail", "Data", "Development", "Disease", "Down-Regulation", "Endothelium", "Environment", "Ephrin-B1", "Etiology", "Event", "Feedback", "Focal and Segmental Glomerulosclerosis", "Foot Process", "Future", "Genetic", "Genomics", "Glomerular Capillary", "High Prevalence", "Hispanic", "Hispanic Populations", "Homeobox", "Homeodomain Proteins", "Human", "Human Parvovirus B19", "ITGB3 gene", "Incubated", "Infection", "Integrins", "Investigation", "Kidney Diseases", "Knockout Mice", "Location", "Membrane", "Mexico", "Modeling", "Mus", "Mutate", "Nuclear", "Pathogenesis", "Pathway interactions", "Patients", "Pattern", "Peruvian", "Pharmaceutical Preparations", "Phase", "Population", "Prevention", "Process", "Proliferating", "Proteins", "Proteinuria", "Publishing", "Rat Transgene", "Rattus", "Recombinants", "Recurrence", "Renal glomerular disease", "Rodent", "Role", "Series", "Serum", "Signal Transduction", "Site", "Sprague-Dawley Rats", "Testing", "Therapeutic Agents", "Therapeutic Effect", "Upregulation", "Variant", "Virus Diseases", "WT1 gene", "West African", "Zinc Fingers", "cytokine release syndrome", "diabetic", "exome", "genetic variant", "genomic data", "genotyped patients", "glomerular endothelium", "glomerular function", "glutamyl aminopeptidase", "improved", "in vivo", "induced pluripotent stem cell", "insertion/deletion mutation", "migration", "mouse model", "nephrotoxicity", "novel", "overexpression", "pamidronate", "pathogen", "patient population", "podocyte", "post SARS-CoV-2 infection", "prevent", "rat parvovirus", "slit diaphragm", "therapeutic evaluation", "transcription factor", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "15969", "attributes": { "award_id": "1UG3NS141843-01A1", "title": "Low-dose naltrexone (LDN) for the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 44422, "first_name": "LINA FERNANDA", "last_name": "GARCIA", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-03-06", "end_date": "2028-02-28", "award_amount": 556686, "principal_investigator": { "id": 44423, "first_name": "Jarred W.", "last_name": "Younger", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3422, "ror": "", "name": "UNIVERSITY OF ALABAMA AT BIRMINGHAM", "address": "", "city": "", "state": "AL", "zip": "", "country": "United States", "approved": true }, "abstract": "In this UG3/UH3 Exploratory Clinical Trial, we will test low-dose naltrexone (LDN) as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). ME/CFS affects approximately 1 million people in the United States, with incidence rates increasing with the SARS-CoV-2 pandemic. ME/CFS is characterized by profound fatigue, cognitive issues, pain sensitivity, and post-exertional malaise (PEM). Several studies support the hypothesis that ME/CFS involves chronic inflammatory activity in the central nervous system (CNS) that is driven by hyperactive microglia. More than 35 years since recognizing ME/CFS as a distinct medical condition, there is still no FDA-approved medications and no consensus on optimal treatment of the disorder. There is an urgent need to identify treatments that are safe and effective in reducing the severity of ME/CFS. Low dose naltrexone (LDN) involves daily doses of naltrexone in the 0.5mg to 6.0mg range. LDN crosses the blood-brain barrier, pushes microglia from an inflammatory to a resting state, and reduces the production of pro-inflammatory chemicals in the brain. LDN reduces fatigue severity in conditions such as ME/CFS, fibromyalgia, and Long-COVID. LDN is an ideal first treatment for ME/CFS because it is generically available, inexpensive, safe, and well-tolerated. LDN also has no abuse potential. In this Phase II trial, several questions will be answered to optimize a future Phase III efficacy trial of LDN for ME/CFS. This trial uses a remote design where individuals can enroll from anywhere in the United States and can complete all study tasks from their home. This approach allows individuals who are homebound or bedbound to participate in the clinical trial. Study 1 is a dose-finding study where 75 ME/CFS participants will receive LDN at 1.5mg/day, 3.0mg/day, 4.5mg/day, and 6.0mg/day for 2 months each, in blinded order. This study will be used to determine the best dose of LDN to be used in future trials. Study 2 is a randomized controlled trial (RCT) in 150 individuals with ME/CFS. Participants will be randomized to receive LDN or placebo. This study will be used to test safety and tolerability, determine the likely side-effects, determine the best measure to use as a primary outcome, identify predictors of a positive LDN response, and preliminarily measure the strength of the LDN effect. A subgroup of participants (25 LDN and 25 placebo) will be recruited close to the University of Alabama at Birmingham (UAB) to complete advanced neuroimaging and blood tests of neuroinflammation, neurodegeneration, and oxidate stress. These tests may yield biomarkers of LDN response for predicting who is a good LDN candidate, or for tracking improvement with the treatment. Neuroimaging will focus on brain lactate and temperature, two measures of brain inflammation. Study 3 is an extended-duration study where participants may be switched between placebo and LDN, in order to collect additional safety, tolerability, efficacy, and durability information. Ultimately, we hope this study will lead to the first widely accepted pharmaceutical treatment for ME/CFS.", "keywords": [ "Affect", "Alabama", "Anti-Inflammatory Agents", "Autoimmune", "Behavior", "Biological Markers", "Blinded", "Blood", "Blood Tests", "Blood specimen", "Brain", "COVID-19 pandemic", "Cells", "Central Nervous System", "Chemicals", "Choline", "Chronic", "Chronic Fatigue Syndrome", "Clinical", "Clinical Research", "Clinical Trials", "Cognition", "Cognitive", "Consensus", "Crohn's disease", "Data", "Disease", "Dose", "Eligibility Determination", "Encephalitis", "Enrollment", "Ensure", "Esthesia", "Exertion", "FDA-approved drug", "Fatigue", "Fibromyalgia", "Future", "Generic Drugs", "Home", "Hyperactivity", "Immune", "Impaired cognition", "Incidence", "Individual", "Inflammatory", "Infrastructure", "Long COVID", "Malaise", "Measures", "Medical", "Methods", "Microglia", "N-acetylaspartate", "Naltrexone", "Nerve Degeneration", "Outcome", "Oxygen", "Pain", "Participant", "Pathologic", "Perfusion", "Persons", "Pharmacologic Substance", "Phase", "Placebos", "Production", "Protocols documentation", "Random Allocation", "Randomized", "Randomized Controlled Trials", "Recording of previous events", "Reporting", "Research", "Research Personnel", "Rest", "Safety", "Severities", "Stress", "Subgroup", "Symptoms", "TLR4 gene", "Temperature", "Testing", "United States", "Universities", "Visit", "Woman", "abuse liability", "active method", "blood-based biomarker", "blood-brain barrier crossing", "capsule", "clinical effect", "clinical predictors", "conventional dosing", "cytokine", "design", "efficacy trial", "improved", "information gathering", "magnetic resonance spectroscopic imaging", "meetings", "myoinositol", "neuroimaging", "neuroinflammation", "optimal treatments", "oxidation", "pain sensitivity", "phase II trial", "predicting response", "primary outcome", "recruit", "response", "safety testing", "side effect", "tool" ], "approved": true } }, { "type": "Grant", "id": "15968", "attributes": { "award_id": "1R01AG092489-01A1", "title": "Effect of paid family care (vs aides) on Medicaid waiver participants w/ IDD across the lifespan", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 44276, "first_name": "PRISCILLA JOY", "last_name": "NOVAK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-03-01", "end_date": "2031-02-28", "award_amount": 678231, "principal_investigator": { "id": 44421, "first_name": "Courtney Harold", "last_name": "Van Houtven", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2652, "ror": "", "name": "DUKE UNIVERSITY", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Home and community-based services are the most common support for people with Intellectual and/or Developmental Disability (I/DD) who otherwise would require facility-level care. Many state Medicaid waivers allow participants to choose to hire family as direct support personnel to meet their care needs at home and in the community rather than a professional aide. Ability to hire family increased during the Covid-19 pandemic through state policy changes, and yet we do not know how involving paid family affects the ability for people with I/DD to remain at home. The objectives of this study are to use North Carolina (NC) as a case to elucidate the experiences of waiver participants with I/DD (Innovations Waiver participants). With no national data fields systematically identifying self-direction status or who is paid for personal care, foundational state-level work is required to understand people with I/DD’s experiences with self-direction. First, we will describe prevalence and dynamics of paid family care using Medicaid administrative data over the past 9+ years, including patterns by self-direction or not, by individual and geographic factors and by era (pre-post Covid-19 (Aim 1). Second, qualitative approaches will center the voices of people with I/DD and their families to obtain their perspectives on what is gained and what is lost from self-directed care including paid family care (Aim 2). Specifically, photo elicitation, case study, and focus group interviews will examine the lived experience of accessing and receiving care through the Innovations Waiver according to 1) individuals with I/DD, 2) their parent/partner/guardian/unpaid family caregiver, 3) their paid family caregivers, 4) their paid aide, and 5) Innovations Waiver experts. Third, we will estimate the comparative effectiveness of paid family care versus paid aide care only on person-centered outcomes (e.g., home time, preventive care) and on potential harms (potentially harmful medications, injurious falls, mistreatment) (Aim 3). We hypothesize that waiver participants with paid family care will have better person-centered outcomes and no increase in harms compared to those with paid aides alone. Effects of self- direction will also be explored. By using a convergent parallel mixed-methods process we will integrate results to paint a full picture of the comparative effectiveness of paid family care and self-direction from childhood to older adulthood, including identification of any harms. The results of this 5-year R01 study will be immediately applicable to state Medicaid office benefit design and inform strategies to optimize quality of care and life for people living with I/DD from childhood throughout the lifespan. Results from the North Carolina case will also position us to pursue a national study, given knowledge gained along with emerging efforts to identify “self- direction” in national CMS data sets. Examining paid family care and self-direction’s effects across the lifespan aligns with NIA’s strategic goal to improve the health, well-being, and independence of adults as they age.", "keywords": [ "Accident and Emergency department", "Acute", "Address", "Adult", "Affect", "Age", "Antipsychotic Agents", "COVID-19 pandemic", "Caring", "Case Study", "Characteristics", "Child", "Childhood", "Communities", "Control Groups", "Data", "Data Set", "Developmental Disabilities", "Disabilities experience", "Effectiveness", "Eligibility Determination", "Emergency Care", "Emergency department visit", "Ethnic Origin", "Exercise", "Family", "Family Caregiver", "Family member", "Focus Groups", "Geographic Factor", "Goals", "Group Interviews", "Health", "Health Care Facility", "Home", "Hospitalization", "Human Resources", "Incidence", "Individual", "Inpatients", "Intellectual functioning disability", "Intermediate Care Facilities", "Knowledge", "Life", "Lived experience", "Medicaid", "Methods", "North Carolina", "Outcome", "Paint", "Parents", "Participant", "Patient Preferences", "Pattern", "Perception", "Personal Satisfaction", "Persons", "Pharmaceutical Preparations", "Policies", "Policy Research", "Population", "Positioning Attribute", "Prevalence", "Preventive care", "Process", "Qualifying", "Qualitative Methods", "Quality of Care", "Quality of life", "Quasi-experiment", "Race", "Risk", "Self Care", "Self Direction", "Services", "Supported Employment", "Time", "Voice", "Work", "acute care", "beneficiary", "community based service", "comparative effectiveness", "cost", "design", "disabled", "experience", "fall injury", "flexibility", "health care quality", "improved", "innovation", "life span", "maltreatment", "older adult", "payment", "person centered", "post-COVID-19", "preference", "programs", "rurality", "treatment effect", "waiver" ], "approved": true } }, { "type": "Grant", "id": "15967", "attributes": { "award_id": "1R21DA062030-01A1", "title": "Understanding trajectories of cannabis use frequency across the lifespan based on routine screening in a large outpatient population", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)" ], "program_reference_codes": [], "program_officials": [ { "id": 44419, "first_name": "KEVA WONTORIA", "last_name": "COLLIER KIDEMU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-03-15", "end_date": "2028-02-29", "award_amount": 470979, "principal_investigator": { "id": 44420, "first_name": "Gwen", "last_name": "Lapham", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3421, "ror": "", "name": "KAISER FOUNDATION RESEARCH INSTITUTE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Cannabis use is prevalent and increasing in the US, with growth in older adult use outpacing increases in all other age groups. Cannabis use increases risk of cannabis use disorder (CUD) and other adverse health outcomes, with up to 33% of people who use cannabis having a CUD. In the context of legalized, more frequent and higher potency cannabis use, longitudinal studies examining the long-term risks of cannabis use are critically needed. Latent class trajectory modeling is an established approach to modeling cannabis use patterns among adolescent and young adult research participants. Few studies have included middle-aged or older adults, for whom cannabis morbidity may be most concerning due to risks of drug interactions, diminished health, falls and injuries, and impaired cognition. The proposed study responds to NIDA’s call for research on the health effects of cannabis, particularly among older adults, and trajectories of substance use and adverse health outcomes. This study will use 10 years of electronic health record data from a large health system that screens patients annually with a valid practical, single-item cannabis screen. The sample includes more than 331,000 adult patients (≥ 18 years)—including large samples of middle aged and older adults—who have completed the cannabis screen on 3 or more occasions as part of routine clinical care (2016 – 2025). The screen asks about the frequency of cannabis use (none to daily), with frequency of use being the most important predictor of CUD and adverse health conditions, even when accounting for heterogeneity of cannabis products. Specific aims are to conduct developmental research to inform a future R01 that will assess the extent to which different longitudinal cannabis use patterns predict subsequent adverse health outcomes. Aim 1 is to conduct preliminary analyses to understand sample biases, cohort effects (e.g., COVID- 19) and data missing. Aim 2 is to apply multistep trajectory modeling to identify groups of patients, separately for 4 age groups (18-34, 35-49, 50-64, ≥ 65), who follow similar trajectories of cannabis use and characterize patients in each trajectory group by demographics, health conditions, medication use, health care utilization and diagnosed CUD. Aim 3 is to describe, for each age-based trajectory group, the year-by-year prevalence of concurrent adverse health outcomes associate with cannabis use (i.e., depression, psychotic disorder, chronic pain, polysubstance use, cognitive impairment, diagnosed CUD) over the study period. Secondarily, by age group, we will repeat Aims 2 and 3 separately in women and men and in 4 subgroups defined by race and ethnicity: Black, Hispanic, Asian and White. Public Health Impact: More than 59 million US adults use cannabis, yet little is known about the long-term patterns of cannabis use and associated adverse health outcomes, particularly for middle-aged and older adults. Results will have direct clinical implications for care of patients whose cannabis use is associated with adverse outcomes and build the foundation for future research to predict subsequent adverse health outcomes by trajectory group.", "keywords": [ "Accounting", "Adolescent and Young Adult", "Adult", "Age", "Anxiety", "Anxiety Disorders", "Asian", "Black race", "COVID-19", "Cannabis", "Cessation of life", "Characteristics", "Chronic", "Clinical", "Cohort Effect", "Cohort Studies", "Data", "Data Sources", "Development", "Diagnosis", "Drug Interactions", "Electronic Health Record", "Epidemiology", "Ethnic Origin", "Foundations", "Frequencies", "Future", "Growth", "Health", "Health Insurance", "Health system", "Heterogeneity", "Hispanic", "Impaired cognition", "Individual", "Injury", "Legal", "Link", "Longitudinal Studies", "Medical", "Mental Depression", "Modeling", "Mood Disorders", "Morbidity", "National Institute of Drug Abuse", "Outcome", "Outpatients", "Pain", "Participant", "Patient Care", "Patients", "Pattern", "Perception", "Persons", "Pharmaceutical Preparations", "Population", "Prevalence", "Psychoses", "Psychotic Disorders", "Public Health", "Race", "Recreation", "Reporting", "Research", "Risk", "Risk Factors", "Route", "Sampling", "Sampling Biases", "Sleep", "Subgroup", "Substance Use Disorder", "Suicide attempt", "Surveys", "Testing", "Warfarin", "Washington", "Woman", "acute care", "adverse outcome", "age group", "alcohol risk", "automobile accident", "cannabis use behavior", "care utilization", "chronic pain", "clinical care", "cohort", "demographics", "falls", "health care service utilization", "human old age (65+)", "insurance claims", "life span", "marijuana legalization", "marijuana use", "marijuana use disorder", "men", "middle age", "mortality", "older adult", "patient screening", "polysubstance use", "primary care patient", "risk perception", "routine care", "routine screening", "screening", "sex", "substance use", "young adult" ], "approved": true } }, { "type": "Grant", "id": "15966", "attributes": { "award_id": "1R35GM161764-01", "title": "Elucidating kinetics and thermodynamics of RNA-ligand interactions using single molecule approaches", "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": [ { "id": 22244, "first_name": "MICHAEL", "last_name": "SAKALIAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-03-01", "end_date": "2031-02-28", "award_amount": 425100, "principal_investigator": { "id": 44418, "first_name": "Maria", "last_name": "Kamenetska", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3420, "ror": "", "name": "BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Project summary/abstract: Current understanding of and predictive models for folded RNA structures lag far behind our advances in protein folding. Yet recent work reveals the central role of RNA folds in diseases like viral infection, cancer and neurodegeneration. The potential to develop drugs against RNA targets causing illness is impeded by critical knowledge gaps in our understanding of the sequence-structure-function relationships of RNA polymers. Beyond structure, the role of fast fluctuations between the various conformations of RNA is being recognized as playing a bigger role in RNA than in amino acid function. Quantifying both shape and kinetics of RNA requires single molecule tools that can achieve millisecond time and nanometer distance resolution. Through this Maximizing Investigator Research Award (MIRA), the Kamenetska Lab will be supported in their continued efforts to develop such single molecule biophysical tools combined with machine learning approaches in order to expand our knowledge and understanding of the structural and kinetic properties of RNA. These optical tweezer force spectroscopy tools are uniquely suited to quantifying the full energy landscape profile of RNA structures that governs the dynamics of these molecules. Here I propose to use these methods, based on published results from my laboratory, to fill three critical knowledge gaps. First, I will investigate the effects on RNA mechanics and dynamics of non-specific interactions between nucleic acids, including RNA, with small molecules and ions present in mammalian cells. Second, I will build on our work on synthetic and modified RNA structures to systematically quantify the relationship between structure and folding energetics, generating data for training predictive models of RNA folding not currently available. Finally, I will build analytic methods and pursue structural and kinetic characterization of complex RNA tertiary structures with multiple conformations. My targets include SARS-CoV-2 viral genomic RNA implicated in viral gene regulation, telomeric and 5’ untranslated regions (5’ UTR) structures associated with cancer phenotypes.", "keywords": [ "2019-nCoV", "5' Untranslated Regions", "Amino Acids", "Award", "Biological Process", "Biophysics", "Complex", "Disease", "Gene Expression Regulation", "Ions", "Kinetics", "Knowledge", "Laboratories", "Ligands", "Machine Learning", "Malignant Neoplasms", "Mammalian Cell", "Measurement", "Mechanics", "Methods", "Molecular Conformation", "Nerve Degeneration", "Nucleic Acids", "Pharmaceutical Preparations", "Phenotype", "Play", "Polymers", "Process", "Property", "Publishing", "RNA", "RNA Conformation", "RNA Folding", "Research", "Research Personnel", "Resolution", "Role", "Shapes", "Spectrum Analysis", "Structure", "Structure-Activity Relationship", "Therapeutic Intervention", "Thermodynamics", "Time", "Viral Genes", "Virus Diseases", "Virus Replication", "Work", "analytical method", "biophysical tools", "drug development", "genomic RNA", "millisecond", "nanometer", "optic tweezer", "optical traps", "predictive modeling", "protein folding", "single molecule", "small molecule", "telomere", "therapy development", "tool", "training data", "viral genomics" ], "approved": true } } ], "meta": { "pagination": { "page": 3, "pages": 1424, "count": 14236 } } }