Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=2&sort=-principal_investigator
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-principal_investigator", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=-principal_investigator", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-principal_investigator", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-principal_investigator" }, "data": [ { "type": "Grant", "id": "15979", "attributes": { "award_id": "1R21AI188074-01A1", "title": "Identification of RNAi-independent antiviral genes through biased genetic screen in C. elegans", "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": 32860, "first_name": "KENTNER L", "last_name": "SINGLETON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-02", "end_date": "2028-01-31", "award_amount": 412500, "principal_investigator": { "id": 44434, "first_name": "Rui", "last_name": "Lu", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3430, "ror": "", "name": "LOUISIANA STATE UNIV A&M COL BATON ROUGE", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Viruses, especially RNA viruses, are formidable pathogens to cellular hosts. Owing to the error-prone nature of their replicases, RNA viruses rapidly accumulate large numbers of genetic mutations in their genome, enabling them to evade immune detection. Some RNA viruses, such as influenza viruses and coronaviruses, can also generate genome variants through genome reassortment or genome recombination mechanisms. It is thus important to study antiviral mechanisms intrinsically resistant to genetic mutations in viral genome, which may lead to the development of novel antiviral strategies. In plants, insects and vertebrates, there are antiviral mechanisms triggered by non-dsRNA products of invading viruses. These antiviral mechanisms provide another layer of protection in case viral dsRNA-triggered immunity is compromised by the invading viruses. In supporting this hypothesis, many plant and animal viruses have been found to produce diverse types of dsRNA binding proteins that are able to bind and sequester viral dsRNA to block immune detection. So far, RNAi is known as the most important antiviral defense mechanism in Caenorhabditis elegans. However, some recent studies on worm antiviral defense suggest that viral infection in C. elegans triggers transcriptional programs that in return provide protection against invading viruses in an RNAi-independent manner. Therefore, very much like what has been demonstrated in plants and insects, RNAi-independent antiviral defense (RiAD) may provide worms another layer of protection against virus in case antiviral RNAi is compromised. To fill the knowledge gap in our understanding of worm RiAD and as proof of principle, the PI’s lab has recently carried out a biased genetic screen of limited scale, aiming to identify genes specifically contributing to worm RiAD. This genetic screen identified 8 candidate genes that confer RiAD targeting a flock house virus (FHV) replicon. 5 of these candidate genes also mediate RiAD against Orsay virus, which naturally infects C. elegans (21). In this application, we propose to continue the biased genetic screen and finish it on a much greater scale to ensure double coverage on all genes involved in RiAD. We will then map and identify the candidate genes through whole genome sequencing combined with feeding RNAi and function rescue assay. Since approximately 70% of C. elegans genes have human homologs, function and mechanism study of the identified genes may not only lead to the identification of novel conserved mechanisms of antiviral innate immunity across kingdoms but also inform the development of novel antiviral strategies.", "keywords": [ "Alleles", "Animals", "Anti-viral Agents", "Anti-viral Response", "Binding", "Binding Proteins", "Biological Assay", "Caenorhabditis elegans", "Candidate Disease Gene", "Complement", "Coronavirus", "Defense Mechanisms", "Detection", "Development", "Double-Stranded RNA", "Ensure", "Genes", "Genetic", "Genetic Recombination", "Genetic Screening", "Genetic Transcription", "Genome", "Homologous Gene", "Human", "Immune", "Immune Evasion", "Immunity", "Insecta", "Interferons", "Invaded", "Knowledge", "Lead", "Mammals", "Maps", "Mediating", "Mutation", "Natural Immunity", "Nature", "Nematoda", "Organism", "Pathway interactions", "Plants", "RNA Interference", "RNA Viruses", "Replicon", "Research", "Resistance", "Variant", "Vertebrates", "Viral", "Viral Genes", "Viral Genome", "Virus", "Virus Diseases", "Work", "antiviral immunity", "candidate identification", "design", "feeding", "gene function", "genome sequencing", "genome-wide", "influenzavirus", "novel", "pathogen", "pathogenic virus", "programs", "protective pathway", "replicase", "response", "whole genome" ], "approved": true } }, { "type": "Grant", "id": "15978", "attributes": { "award_id": "1R01AI196176-01", "title": "Inhibiting Chikungunya Virus Protease using MTase-like Domain Interactions for Novel Antiviral Therapies.", "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": "2026-02-23", "end_date": "2031-01-31", "award_amount": 632994, "principal_investigator": { "id": 44433, "first_name": "Jeanne Ann", "last_name": "Hardy", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3429, "ror": "", "name": "UNIVERSITY OF MASSACHUSETTS AMHERST", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Chikungunya (CHIKV) is an RNA alphavirus that infects 3 million people in 45 countries including the US annually. Acute infection is flu-like, but in 40% of infections, debilitating joint pain emerges that can last for years. Infection during pregnancy also results in severe encephalopathy in newborns or aborted fetuses. Viral proteases are effective antiviral drug targets and are the standard of care for viral diseases (e.g HIV, hepatitis C, SARS-CoV- 2). The activity of the nsP2 protease from CHIKV (CHIKVP) is vital for infection. Inhibition of CHIKVP blocks processing of the viral polyprotein, prevents viral replication, lowers viral titers and stops disease progression. Thus, CHIKVP is an excellent antiviral drug target. To date, no effective antivirals of CHIKVP have been approved for acute or chronic infection. Our ultimate goal is to use insights into CHIKVP structure and dynamics to develop an inhibitor to oppose CHIKV infection, the resulting chronic pain and prevent pediatric neurological syndromes. CHIKVP is composed of a protease domain and a methyltransferase-like domain (MTL). To date, no functions of the MTL have been identified. In a search for novel CHIKVP binders, we identified ligands that bind to the MTL at an elongated cavity and allosterically inactivate the protease. The site shares structural homology with S-adenosyl methionine (SAM) cofactor binding sites, but does not bind SAM. The allosteric site binds to GTP, which suggests that a function such as RNA binding may be conserved in the MTL. Here we propose a research strategy for the development and direct comparison of CHIKVP active-site and allosteric inhibitors. We will build compounds derived from a large compound screen and also build from MTL-binding fragments we have already identified. We have developed NMR approaches that allow us to readily distinguish active-site from allosteric inhibitors. Importantly, we have developed approaches that allow us to monitor activity, binding and dynamics in solution without having to rely on freezing samples which is required for other structural techniques, to inform our inhibitor design. Recent data have suggested that RNA plays a critical role in CHIKVP function, enhancing protease activity. We have identified a site that we hypothesize binds RNA and describe a series of studies to understand the mechanism by which RNA impacts protease function. We will bring all these structural insights into our inhibitor development approach. At each step of development, we will closely monitor efficacy against viral infection for CHIKV and other related alphaviruses to determine whether pan-alphaviral inhibition is achievable with a given class of compounds. Critically, we will also implement a directed evolution approach across both domains of CHIKVP to predict the susceptibility of our inhibitors to resistance mutations. This will enable us to develop enduring antivirals and will also address longstanding unanswered questions about the favorability of allosteric inhibition in antiviral drug development.", "keywords": [ "2019-nCoV", "Aborted Fetus", "Active Sites", "Address", "Adult", "Allosteric Site", "Alpha Virus", "Anti-viral Agents", "Anti-viral Therapy", "Arthralgia", "Back", "Binding", "Binding Sites", "Characteristics", "Chikungunya virus", "Child", "Childhood", "Clinical", "Country", "Data", "Development", "Directed Molecular Evolution", "Disease", "Disease Progression", "Drug Targeting", "Drug resistance", "Encephalopathies", "FDA approved", "Family", "Fluorogenic Substrate", "Freezing", "Future", "Goals", "Guanosine Triphosphate", "HIV", "HIV Care", "Hepatitis C", "Hepatitis C virus", "Infection", "Inflammation", "Intervention", "Late pregnancy", "Ligand Binding", "Light", "Mediating", "Methyltransferase", "Molecular", "Monitor", "Motion", "Myalgia", "Nervous System Disorder", "Neurologic", "Newborn Infant", "Peptide Hydrolases", "Persons", "Pharmaceutical Chemistry", "Play", "Polyproteins", "Predisposition", "Pregnancy", "Pregnant Women", "Property", "Protease Domain", "Protease Inhibitor", "RNA", "RNA Binding", "Reporting", "Research", "Role", "S-Adenosylhomocysteine", "S-Adenosylmethionine", "SARS-CoV-2 infection", "Sampling", "Series", "Site", "Structure", "Syndrome", "Techniques", "Testing", "Time", "Vaccination", "Vaccines", "Viral", "Virus Diseases", "Virus Inhibitors", "Virus Replication", "acute infection", "antiviral drug development", "chikungunya infection", "chronic infection", "chronic pain", "cofactor", "design", "drug resistance development", "emerging pathogen", "enzyme mechanism", "flu", "high throughput screening", "inhibitor", "insight", "mosquito-borne", "novel", "pain symptom", "pandemic potential", "pandemic virus", "pharmacologic", "prevent", "resistance mutation", "screening", "small molecule", "standard of care", "unborn child" ], "approved": true } }, { "type": "Grant", "id": "15976", "attributes": { "award_id": "1R21AI190571-01A1", "title": "Statistical Methods for Assessing Immune Correlates of Risk and Protection Using Flexible Two-Phase Sampling Designs that Enrich Longitudinal Samples", "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": 32873, "first_name": "MISRAK", "last_name": "GEZMU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-09", "end_date": "2028-01-31", "award_amount": 220000, "principal_investigator": { "id": 44430, "first_name": "Youyi", "last_name": "Fong", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44431, "first_name": "Ying", "last_name": "Huang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2062, "ror": "", "name": "FRED HUTCHINSON CANCER CENTER", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Immune correlates of protection (CoP) are biomarkers that predict vaccine-induced protection against dis- eases and play a crucial role in the design and development of effective vaccines. The U.S. government (USG)-led initiative to identify CoPs for COVID vaccines highlighted the importance of neutralizing antibody titers as surrogate endpoints, significantly impacting vaccine recommendations and approvals. To effec- tively measure these immune biomarkers, researchers utilize two-phase designs, such as case-cohort or case-control studies, to boost statistical power and enhance representation. This proposal aims to develop novel two-phase sampling designs that allow enrichment of longitudinal immune response marker mea- surements in immune correlates studies. The proposal also aims to develop advanced statistical methods for datasets collected under sampling designs that would introduce bias if analyzed using conventional in- verse probability-weighted methods. Aim 1 focuses on the analysis of the immune response biomarkers measured at the peak immunogenicity time point, while Aim 2 delves into the study of the decaying im- mune response biomarkers. The final product will feature a user-friendly software implementation of the proposed methods, along with its application to analyze COVID correlates datasets from past and ongoing USG-sponsored vaccine efficacy trials.", "keywords": [ "Acceleration", "Adult", "Advisory Committees", "Antibodies", "Antibody titer measurement", "Authorization documentation", "COVID-19", "COVID-19 vaccine", "Case/Control Studies", "Child", "Clinical Data", "Communicable Diseases", "Correlation Studies", "Cost Measures", "Data Correlations", "Data Set", "Development", "Disease", "Future", "Government", "Immune", "Immune System Diseases", "Immune response", "Immunologic Markers", "Infection", "Institution", "Length", "Longitudinal Studies", "Measurement", "Measures", "Methodology", "Methods", "Onset of illness", "Participant", "Phase", "Placebos", "Play", "Probability", "RNA vaccine", "Randomized", "Recommendation", "Research", "Research Personnel", "Resources", "Risk", "Role", "Sampling", "Sampling Biases", "Sampling Studies", "Security", "Series", "Statistical Methods", "Structure", "Surrogate Endpoint", "Techniques", "Time", "Vaccination", "Vaccines", "Visit", "Work", "booster vaccine", "case control", "cohort", "design", "disorder prevention", "disorder risk", "efficacy trial", "flexibility", "global health", "immunogenicity", "immunological status", "improved", "innovation", "interest", "meetings", "neutralizing antibody", "novel", "novel vaccines", "participant enrollment", "predictive marker", "programs", "rational design", "response biomarker", "software development", "time to event", "trial enrollment", "user friendly software", "user-friendly", "vaccine development", "vaccine efficacy", "vaccine platform", "vaccine-induced immunity", "vaccinology" ], "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": "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 } }, { "type": "Grant", "id": "15965", "attributes": { "award_id": "1P50DC022549-01A1", "title": "Sensory and molecular studies of human taste dysfunction", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Deafness and Other Communication Disorders (NIDCD)" ], "program_reference_codes": [], "program_officials": [], "start_date": "2026-03-01", "end_date": "2031-02-28", "award_amount": 786679, "principal_investigator": { "id": 44417, "first_name": "PeiHua", "last_name": "Jiang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3419, "ror": "", "name": "MONELL CHEMICAL SENSES CENTER", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Project 3. Sensory and molecular studies of human taste dysfunction Taste dysfunction is a cardinal feature of COVID. Project 3 of this P50 Clinical Research Center (CRC) proposal focuses on (1) molecular description of taste tissue from people with sustained COVID-19-associated taste dysfunction, compared to people with no current taste problems (regardless of infection history) (Aim 3.1), and (2) mechanistic interrogation of COVID-associated taste dysfunction using taste organoids (Aim 3.2). We will test the hypothesis that people with COVID taste dysfunction have fewer taste receptor cells, reduced expression of taste-relevant genes, and immune cell infiltration due to sustained inflammation. In Aim 3.1, we will sample taste tissue from people with and without sustained COVID-19-associated taste dysfunction to measure taste receptor cell number and gene expression of inflammatory (e.g., cytokines and chemokines) and other molecules with single-cell RNA sequencing (scRNA-seq) methods. In Aim 3.2, we will use taste organoids derived from wild-type mice, humanized-ACE2 mice, and humans to examine SARS-CoV-2 tropism in taste tissue to determine if taste tissue homeostasis is altered by (a) SARS-CoV-2 infection or (b) inflammatory molecules identified in Aim 3.1 and/or known to be elevated in COVID. Project 3 of this CRC proposal is supported by Project 1 and the Chemosensory Clinical Services Core, which will perform and support remote and in-house sensory screening of all participants in this research program. The investigators here are experts in their fields, particularly in single-cell biology, genetics, and stem cell biology of taste tissue. We have engaged consultants who are inflammation, infection, and immunology experts. Several types of pilot data support this application, including scRNA-seq data from human fungiform tissue and taste organoid data after treatment with inflammatory molecules. Institutional support for this project is outlined in a Letter of Support from administrative officials, and the Monell Chemical Senses Center is well suited to complete this project because of its cross-disciplinary focus on chemosensory biology and its connection with an experienced coronavirus expert at the nearby University of Pennsylvania. This project is part of a larger program to understand and treat people with communication disorders of taste and smell dysfunction due to COVID. We anticipate our data will answer key unsolved questions regarding taste dysfunction and point to potential avenues of treatment for this debilitating condition.", "keywords": [ "2019-nCoV", "3-Dimensional", "ACE2", "Acute", "Address", "Affect", "Aftercare", "Age", "Ageusia", "Biological Models", "Biology", "COVID-19", "COVID-19 patient", "COVID-19 susceptibility", "Cell Count", "Cell Physiology", "Cell secretion", "Cells", "Cellular Structures", "Cellular biology", "Chemicals", "Clinical Research", "Clinical Services", "Communication impairment", "Coronavirus", "Data", "Desire for food", "Functional disorder", "Fungiform Papilla", "Gene Expression", "Gene Expression Profile", "Genes", "Genetic", "Health", "Homeostasis", "Human", "Immune", "Immunology", "Individual", "Infection", "Inflammation", "Inflammatory", "Institution", "Knock-in", "Knowledge", "Letters", "Long COVID", "Measures", "Methods", "Modeling", "Molecular", "Mucous body substance", "Mus", "Nose", "Organoids", "Participant", "Patients", "Pennsylvania", "Persons", "Phase", "Predisposition", "Psychophysics", "Race", "Receptor Cell", "Recording of previous events", "Research", "Research Personnel", "Resources", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "Saliva", "Salivary", "Sampling", "Sensory", "Signal Transduction", "Smell Perception", "Symptoms", "System", "Taste Buds", "Taste Disorders", "Taste Perception", "Testing", "Tissues", "Tropism", "United States National Institutes of Health", "Universities", "Viral", "Virus", "Virus Diseases", "Wild Type Mouse", "acute COVID-19", "biobank", "cell regeneration", "cell type", "chemokine", "cytokine", "experience", "human RNA sequencing", "human data", "humanized mouse", "immune cell infiltrate", "immunocytochemistry", "inflammatory marker", "novel therapeutic intervention", "programs", "response", "screening", "sex", "single-cell RNA sequencing", "stem cell biology", "stem cells", "synergism", "tongue papilla", "tool" ], "approved": true } } ], "meta": { "pagination": { "page": 2, "pages": 1424, "count": 14236 } } }