Grant List
Represents Grant table in the DB
GET /v1/grants?sort=-program_officials
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-program_officials", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=-program_officials", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=-program_officials", "prev": null }, "data": [ { "type": "Grant", "id": "15805", "attributes": { "award_id": "1K01DA062904-01", "title": "Clinician cannabis use-related preconceptions perpetuating low quality of prenatal care for women who use cannabis during pregnancy", "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": 32896, "first_name": "SARAH", "last_name": "VIDAL", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-15", "end_date": "2030-06-30", "award_amount": 196236, "principal_investigator": { "id": 32897, "first_name": "Rachel Carmen", "last_name": "Ceasar", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2622, "ror": "", "name": "UNIVERSITY OF SOUTHERN CALIFORNIA", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Cannabis is the most used illicit substance during pregnancy. Rates of self-medicating with cannabis escalated during the COVID-19 pandemic. The scientific objective of this proposal is to investigate the mechanisms contributing to preconceptions about those who use cannabis, especially during pregnancy. The central hypothesis is that preconceptions about those who use cannabis result in negative interactions between patients and clinicians that reduce the quality of healthcare and result in poor outcomes. This innovative project will be the first to: (a) leverage natural language processing/artificial intelligence (NLP/AI) techniques to investigate preconceptions about cannabis use in clinical notes, and (b) investigate associations between cannabis use and prenatal care quality. Research aims will: (Aim 1) Investigate preconceptions about those who use cannabis during pregnancy using a mixed methods approach that integrates NLP/AI and qualitative interviews; (Aim 2) Investigate associations between cannabis use and prenatal care quality among different population groups, such as differences in socioeconomic status and education levels; and (Aim 3) Develop, adapt, and test the feasibility and usability of a clinician training on quality health care practices for those who use cannabis during pregnancy using a multistage modified Delphi process, survey, and qualitative focus groups. This research is complemented by a training plan that builds upon Dr. Rachel Carmen Ceasar’s background in mixed qualitative-quantitative methods and substance use research. The training plan includes using NLP/AI approaches, advanced survey methods in reproductive epidemiology, and implementation science. Together, this research and training will prepare Dr. Ceasar to advance as an independent investigator conducting research on health and substance use among those who are pregnant across the lifespan. The proposed project will improve clinicians’ care of those who use cannabis during pregnancy, providing evidence to inform the development of interventions designed to reduce cannabis-use-related notions in prenatal care.", "keywords": [ "Adverse effects", "American College of Obstetricians and Gynecologists", "Artificial Intelligence", "Belief", "COVID-19 pandemic", "California", "Cannabis", "Caring", "Child Welfare", "Clinical", "Clinical Treatment", "Consensus", "Cross-Sectional Studies", "Data", "Detection", "Education", "Educational Status", "Family", "Focus Groups", "Fright", "Future", "Goals", "Guidelines", "Gynecologic", "Health", "Health Benefit", "Health Care", "Income", "Infant", "Interview", "Knowledge", "Language", "Legal", "Link", "Los Angeles", "Medical", "Medical center", "Mentored Research Scientist Development Award", "Mentors", "Methods", "Modeling", "Moods", "Mothers", "Natural Language Processing", "Nausea", "Outcome", "Output", "Pain", "Patient Outcomes Assessments", "Patients", "Persons", "Policies", "Policy Maker", "Population", "Population Group", "Pregnancy", "Pregnancy Outcome", "Pregnant Women", "Prenatal care", "Prevalence", "Process", "Quality of Care", "Questionnaires", "Recommendation", "Reporting", "Research", "Research Personnel", "Rice", "Risk", "Socioeconomic Status", "Supervision", "Survey Methodology", "Surveys", "Techniques", "Testing", "Time", "Training", "Woman", "authority", "cannabis cessation", "comparative", "efficacy evaluation", "evidence base", "experience", "feasibility testing", "follow-up", "health care delivery", "health care quality", "implementation science", "improved", "indexing", "innovation", "large language model", "life span", "low socioeconomic status", "marijuana use", "marijuana use in pregnancy", "neurodevelopment", "open source", "preconception", "prenatal", "provider behavior", "reproductive epidemiology", "substance use", "therapy design", "therapy development", "usability" ], "approved": true } }, { "type": "Grant", "id": "15801", "attributes": { "award_id": "1R21AI190246-01", "title": "Interrogating stress and viral shedding in a migratory bat model", "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": "2025-07-21", "end_date": "2027-06-30", "award_amount": 376932, "principal_investigator": { "id": 25386, "first_name": "Daniel", "last_name": "Becker", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2659, "ror": "", "name": "UNIVERSITY OF OKLAHOMA", "address": "", "city": "", "state": "OK", "zip": "", "country": "United States", "approved": true }, "abstract": "Bats harbor many zoonotic viruses, including both genera of coronaviruses (CoVs) pathogenic in humans (α- and β- CoVs). Limited evidence to-date suggests that periods of active infection in bats—and thus opportunities to transmit zoonotic viruses to humans—are driven by energetically demanding periods that modulate immune tolerance of infection and facilitate viral replication and shedding. However, such work has largely ignored immune mechanisms and has focused primarily on reproductive and nutritional stress. This project will combine field studies and in vitro analyses to test long-distance migration in bats as a driver of CoV infection and shedding. We will focus on Mexican free-tailed bats (Tadarida brasiliensis), a common and widespread migratory bat species in North America for which we and others have detected CoVs similar to HCoV-229E and that are susceptible to SARS-CoV-2. In Aim 1, we will sample T. brasiliensis at monthly intervals at our established study site in western Oklahoma, capturing energetically demanding periods of spring migration from Mexico, birth and lactation, and fall migration back to Mexico. We will characterize CoV diversity and infection status in saliva and fecal samples using RT-PCR followed by Sanger sequencing and will attempt to isolate naturally occuring bat CoVs. We will also quantify stress physiology through fecal cortisol and ratios of neutrophils to lymphocytes in blood, followed by generalized additive models to assess seasonality in physiological metrics and viral infection as well as to test how bat physiology relates to viral shedding. In Aim 2, we will collect lung and intestine from male and female T. brasiliensis bats and use our established protocols to develop new primary and immortalized cell lines, expanding the limited in vitro resources currently available for this bat species from an existing lung epithelial cell line. We will then test virus susceptibility and permissivity by infecting these new cell lines with HCoV 229E, SARS-CoV-2, and MERS-CoV; if isolation of natural bat CoVs is successful, we will also include infections with these viruses. Viral replication will be assessed by qRT-PCR, immunofluorescence microscopy, and TCID50 assays. In Aim 3, we will use our novel T. brasiliensis cell lines to run factorial viral and cortisol challenge experiments to mimic the stressors observed in the field and their impacts on virus replication (i.e., HCoV 229E, SARS-CoV-2, and MERS-CoV as well as any CoVs we isolate here). Viral and cortisol challenges will be followed by global gene expression analyses via RNA-Seq to discover the response of bat cells to field-relevant cortisol concentrations in the face of CoV infection. This project will thus characterize relationships between the physiological demands of migration and CoV infection in wild bats and in vitro systems, establishing a pipeline for studying how stressors affect bat-borne zoonoses.", "keywords": [ "2019-nCoV", "Affect", "Back", "Biological Assay", "Birth", "Blood", "COVID-19 detection", "COVID-19 susceptibility", "Cell Line", "Cell Physiology", "Cells", "Chiroptera", "Coronavirus", "Coronavirus Infections", "Couples", "Coupling", "Data", "Dideoxy Chain Termination DNA Sequencing", "Digestion", "Disease", "Enzyme-Linked Immunosorbent Assay", "Epithelial Cells", "Feces", "Female", "Gene Expression Profiling", "Genes", "Glucocorticoids", "Goals", "Hour", "Human", "Hydrocortisone", "Immune", "Immune Tolerance", "Immunocompetent", "Immunofluorescence Microscopy", "Immunosuppression", "In Vitro", "Indiana", "Infection", "Innate Immune System", "Intestines", "Lactation", "Lung", "Lymphocyte", "Mammals", "Measures", "Mediating", "Methods", "Mexican", "Mexico", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "North America", "Nutritional", "Oklahoma", "Pathogenicity", "Peptide Hydrolases", "Physiological", "Physiological Processes", "Physiology", "Pilot Projects", "Predisposition", "Protocols documentation", "Quantitative Reverse Transcriptase PCR", "RNA", "Resources", "Reverse Transcriptase Polymerase Chain Reaction", "Running", "Saliva", "Sampling", "Seasonal Variations", "Seasons", "Site", "Stress", "System", "Tail", "Techniques", "Testing", "Time", "Trypsin", "Universities", "Vertebrates", "Viral", "Viral Genes", "Virulent", "Virus", "Virus Diseases", "Virus Replication", "Virus Shedding", "Washington", "Work", "Zoonoses", "bat-borne", "betacoronavirus", "cell immortalization", "cost", "experimental study", "falls", "field study", "gene network", "human coronavirus", "immunoregulation", "in vitro Model", "in vivo", "male", "medical schools", "migration", "neutrophil", "novel", "permissiveness", "reproductive", "response", "saliva sample", "sex", "stool sample", "stressor", "transcriptome", "transcriptome sequencing", "transmission process", "viral transmission", "virus testing" ], "approved": true } }, { "type": "Grant", "id": "15802", "attributes": { "award_id": "1R21AI183054-01A1", "title": "Formation of a Novel SARS-CoV-2 Nucleocapsid Dimer: Impacts on Viral and Cellular Processes", "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": "2025-07-08", "end_date": "2027-06-30", "award_amount": 438983, "principal_investigator": { "id": 23536, "first_name": "Emily A.", "last_name": "Bruce", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1131, "ror": "", "name": "UNIVERSITY OF VERMONT & ST AGRIC COLLEGE", "address": "", "city": "", "state": "VT", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1131, "ror": "", "name": "UNIVERSITY OF VERMONT & ST AGRIC COLLEGE", "address": "", "city": "", "state": "VT", "zip": "", "country": "United States", "approved": true }, "abstract": "While most SARS-CoV-2 research to date has focused on the biological consequences of mutations seen in the Spike (S) protein, the nucleocapsid protein (N) is also under selective pressure and an array of mutations within this protein have been documented in different Variants of Concern (VOCs). In this study, we identified three SARS-CoV-2 variants (Beta, Iota, and Delta) that encode different cysteine mutations, all introduced into the linker region of N. These mutations facilitate a highly stable N-N dimer mediated by the introduction of a cysteine and the formation of a di-sulfide bond. Beta, Iota, and Delta variants isolated and grown at BSL-3 all contained a novel cysteine residue in the linker region of N, which appear to be unique introductions amongst pandemic- causing Betacoronaviruses. Nucleoproteins encoding these cysteine mutations and transiently expressed in HEK-293T cells also form a dimer in the absence of other viral machinery. Removal of these cysteine mutations in the linker abolishes dimer formation. Notably, our biochemical studies also revealed this dimer is highly stable and can be visualized on standard non-reducing SDS-PAGE gels. Our proposal focuses on the G215C mutation, which quickly rose to dominance within the Delta lineages and mutations back to wildtype within transmission chains were quickly followed by a reversion to a cysteine at this position. Using reverse genetics, Drs Johnson and Menachery will construct a SARS-CoV-2 Delta virus that reverts the nucleocapsid cysteine back to the ancestral sequence to specifically evaluate N dimer impact on infection. This proposal aims to study the biological impact of stable N dimer formation during infection by characterizing viral growth kinetics (in vitro and in vivo) as well as the effect on viral fitness and transmission in the hamster model. Notably, a related virus (G215C in the WA1 background) showed substantially increased growth both in vitro and in vivo, suggesting that stable N dimer formation is important for viral replication. The stably dimerized form of N is highly enriched in virions (vs. the cellular environment) and we hypothesize it is increasing the efficiency of encapsidation and thus the stability of the viral RNA during transmission. As the cysteines we observe in the nucleocapsid linker lie near/on the N/NSP3 binding interface we will use proteomics to determine how the cellular and viral binding partners of the nucleoprotein change with/without this disulfide bond. Overall, the observation that mutations introducing a cysteine in the N linker have arisen multiple independent times and been maintained during human transmission, as well as our preliminary viral growth kinetics suggest that stable N dimer formation may drive positive selection and convey a growth advantage during SARS-CoV-2 infection and/or a selective benefit during animal-to-animal transmission.", "keywords": [ "2019-nCoV", "Affect", "Animals", "Back", "Binding", "Biochemical", "Biological", "Biological Assay", "Biology", "COVID-19 pandemic", "Cell Physiology", "Cells", "Code", "Collaborations", "Coronavirus", "Cysteine", "Data", "Dimerization", "Elements", "Environment", "Epithelial Cells", "Excision", "Gel", "Genome", "Genomics", "Growth", "Hamsters", "Human", "Immune Evasion", "Immune response", "In Vitro", "Individual", "Infection", "Inflammation", "Interferons", "Kinetics", "Mass Spectrum Analysis", "Mediating", "Middle East Respiratory Syndrome", "Modeling", "Molecular Weight", "Mutation", "Nucleocapsid", "Nucleocapsid Proteins", "Nucleoproteins", "Organoids", "Pathogenesis", "Play", "Population", "Positioning Attribute", "Process", "Production", "Proteins", "Proteomics", "Public Health", "RNA", "RNA Binding", "RNA Stability", "RNA-Directed RNA Polymerase", "Research", "Role", "SARS-CoV-2 B.1.617.2", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "SH2D3C gene", "Severe Acute Respiratory Syndrome", "Shapes", "Site", "System", "Testing", "Vaccines", "Variant", "Viral", "Viral Genome", "Viral Pathogenesis", "Viral Proteins", "Virion", "Virus", "Virus Replication", "Visualization", "airway epithelium", "betacoronavirus", "clinical predictors", "dimer", "disulfide bond", "fitness", "flexibility", "genomic RNA", "improved", "in vivo", "insight", "loss of function", "migration", "monomer", "mutant", "novel", "novel coronavirus", "pandemic disease", "pressure", "reverse genetics", "structural biology", "transmission process", "variants of concern", "viral RNA", "viral fitness", "viral transmission", "virology", "virus host interaction" ], "approved": true } }, { "type": "Grant", "id": "15800", "attributes": { "award_id": "1F31AI191669-01", "title": "Uncovering the mechanisms and implications of BST2 antagonism by SARS-CoV-2", "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": "2025-07-01", "end_date": "2028-06-30", "award_amount": 49538, "principal_investigator": { "id": 32892, "first_name": "Haley", "last_name": "Aull", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2634, "ror": "", "name": "UNIVERSITY OF ROCHESTER", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "BST2/Tetherin is a key factor of the cellular intrinsic immune response that broadly restricts enveloped viruses. BST2 tethers nascent virions to the cell surface by embedding itself into cellular and viral membranes. Tethering not only limits viral release, but also facilitates adaptive immune recognition of the infecting virus. Tethered virions are opsonized by antibodies, which can be recognized by Fc receptors on both natural killer cells and macrophages, activating their ability to kill or phagocytose the infected cell. We have recently reported that SARS-CoV-2 is susceptible to BST2 restriction. However, the virus has evolved to use its Spike to downregulate BST2. Downregulation is achieved by an interaction between Spike and the extracellular domains of BST2, routing BST2 for lysosomal degradation in a Clathrin- and Ubiquitin-dependent manner. Remarkably, newly emerged variants of concern (VOC) have enhanced their ability to counteract BST2, suggesting that BST2 antagonism is a contributing factor to the host adaptation of SARS-CoV-2. Therefore, my long-term goal is to block the ability of SARS-CoV-2 to evade BST2 restriction. My overall objective is to understand the mechanism and implications of BST2 evasion by SARS-CoV-2. My central hypothesis is that mutations accumulated in the Spike of SARS-CoV-2 allow for more efficient counteraction of BST2, increasing virion release and reducing the susceptibility of SARS-CoV-2 to BST2-dependent antibody-mediated cellular responses. I will achieve my overall objective by exploring these two specific aims: (1) elucidate the mechanism of enhancement of BST2 antagonism across VOC, and (2) identify the driving pressures of BST2 antagonism. This work is significant as it will (1) fill the critical gap in knowledge of how SARS-CoV-2 evades BST2 restriction, and how VOC enhance this activity; (2) define the extent to which evasion of BST2 allows for evasion of antibody-mediated responses, and how this translates to vaccine efficacy; and (3) provide proof-of-concept for the design of antivirals to disable SARS-CoV- 2 antagonism of BST2 with the goal of both blocking viral replication and enhancing clearance of infected cells. The support provided by this F31 award will enhance my education by (1) facilitating my training in Surface Plasmon Resonance by Dr. Jermaine Jenkins and the URMC Structural Biology Core Facility (see letter of support), (2) allowing me to travel to the University of Wisconsin-Madison to gain hands-on training from my co- sponsor, Dr. David Evans (see co-sponsor statement), who developed assays to measure Fc receptor-mediated killing of infected cells, which we are proposing to use here, and (3) expanding my experience in scientific writing and communication as I publish my findings and present at both national and international conferences.", "keywords": [ "2019-nCoV", "Affinity", "Anti-viral Agents", "Antibodies", "Antibody-Dependent Enhancement", "Automobile Driving", "Award", "Binding", "Biological Assay", "COVID-19 susceptibility", "COVID-19 vaccine", "Cell surface", "Cells", "Clathrin", "Collaborations", "Communication", "Core Facility", "Coronavirus", "Defect", "Down-Regulation", "Education", "Extracellular Domain", "Fc Receptor", "Future", "Goals", "Immune", "Immune response", "Immunoprecipitation", "International", "Knowledge", "Letters", "Macrophage", "Maps", "Measures", "Mediating", "Membrane", "Mutation", "Natural Killer Cells", "Predisposition", "Process", "Proteins", "Publications", "Publishing", "Reporting", "Resistance", "Role", "Route", "SARS-CoV-2 B.1.1.529", "SARS-CoV-2 antibody", "Surface Plasmon Resonance", "Susceptibility Gene", "Testing", "Training", "Translating", "Travel", "Ubiquitin", "Universities", "Vaccine Design", "Viral", "Virion", "Virus", "Virus Replication", "Wisconsin", "Work", "Writing", "antagonist", "antibody-dependent cell cytotoxicity", "antibody-dependent cellular phagocytosis", "base", "design", "experience", "improved", "pressure", "response", "skills", "structural biology", "symposium", "vaccine efficacy", "variants of concern" ], "approved": true } }, { "type": "Grant", "id": "15799", "attributes": { "award_id": "1R43CA298267-01A1", "title": "Ultra-precision diagnostics for ALK+ non-small cell lung cancer", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [ { "id": 32888, "first_name": "SWAMY KRISHNA", "last_name": "TRIPURANI", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-09", "end_date": "2026-06-30", "award_amount": 399153, "principal_investigator": { "id": 32889, "first_name": "David Randall", "last_name": "Armant", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32890, "first_name": "Rodrigo C", "last_name": "Fernandez-Valdivia", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2658, "ror": "", "name": "ALELOPHARMA INC.", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Background & Significance: Identifying ALK-positive lesions, which are highly responsive to treatment with Crizotinib or Alectinib, is a high-priority for managing patients with ALK+ Non-Small Cell Lung Cancer (NSCLC). A blood-based companion diagnostic (liquid biopsy) could monitor NSCLC patients post-treatment for tumor recurrence without tissue re-biopsy, and also identify non-symptomatic ALK+ individuals for earlier, more effective treatment with ALK kinase inhibitors. Expansion of this approach to other major oncogenic mutations has potential as a non-invasive cancer screening tool that would be transformative for healthcare. Objective & Innovation: AleloPharma Inc. is achieving solutions for personalized precision medicine using AleloMAX, an innnovative high-dimensional molecular detection system that allows ultra-specific detection of target nucleic acids with an impressive 1-absolute copy per reacting assay limit-of-detection (LOD) that effectively eliminates both false positives and false negatives. We aim to offer clinicians a cutting-edge diagnostic capable of accurately detecting ALK translocations among cell-free RNA in the blood plasma of affected patients. Approach: A proof-of-principle study, supported by preliminary LOD data obtained with synthetic ALK constructs, is proposed to develop a liquid biopsy test to detect ALK translocation variants in a kit for use in clinical labs. • Specific Aim 1: Develop an ultra-specific and ultra-sensitive molecular detection platform for EML4-ALK gene fusion translocations in ALK+ NSCLC. We will probe EML4-ALK fusion RNAs using synthetic, in vitro-transcribed mRNAs encompassing the distinct EML4-ALK oncogenic variants. • Specific Aim 2: Demonstrate AleloMAX-ALK’s superior resolution power in ultra-specific molecular probing and limit-of-detection (LOD) analysis in a clinical proof-of-principle study. The EML4-ALK diagnostic platform will be tested using plasma- and/or blood-derived nucleic acid samples obtained from ALK+ NSCLC patients, ALK- NSCLC patients, and healthy control volunteers. Team & Commercialization: Led by a distinguished team with a track record of groundbreaking research in molecular pharmacology, oncology and cellular biology, we are uniquely positioned to tackle this challenge. Our clear roadmap includes patenting all IP and aspires to launch a diagnostic that will have significant clinical utility. Feasibility & Impact: The assay is expected to detect low levels of EML4-ALK mutations in blood of individuals with ALK+ NSCLC. AleloMAX demonstrated diagnostic superiority in prior studies of the NSCLC biomarker POGLUT-1, SARS-CoV-2 and RSV with impressive results. Assay parameters established in this project will be developed as a kit for use in a Phase II study to establish its clinical utility as a companion diagnostic for NSCLC. Successful development of an ALK+ cancer diagnostic will be expanded to include assays for RET, ROS1 and other onco-mutations with additional AleloMAX liquid biopsy assays to monitor a broader panel of cancers. Conclusion: Combining innovation and tangible clinical benefit, our initiative represents a transformative shift in early detection and management of cancer that will positively impact patient survival.", "keywords": [ "2019-nCoV", "ALK gene", "Acceleration", "Address", "Affect", "Aftercare", "Algorithms", "Archives", "Award", "Biological Assay", "Biopsy", "Blood", "Businesses", "COVID-19 diagnosis", "Cancer Detection", "Cancer Diagnostics", "Cancer Patient", "Cells", "Cellular biology", "Chemistry", "Chromosomal translocation", "Clinical", "DNA Sequence Alteration", "Data", "Detection", "Development", "Diagnosis", "Diagnostic", "Diagnostic tests", "Disease", "Early Diagnosis", "Evaluation", "Event", "Fluorescent in Situ Hybridization", "Future", "Gene Amplification", "Gene Fusion", "Genetic Transcription", "Health Care", "Image", "In Vitro", "Individual", "Industry", "Legal patent", "Lesion", "Malignant Neoplasms", "Malignant neoplasm of lung", "Marketing", "Methods", "Molecular", "Molecular Genetics", "Molecular Probes", "Monitor", "Mutation", "Neoplasms", "Non-Small-Cell Lung Carcinoma", "Nucleic Acids", "Oncogenes", "Oncogenic", "Oncology", "Patient Monitoring", "Patients", "Performance", "Pharmacology", "Phase", "Plasma", "Positioning Attribute", "Probability", "Procedures", "Process", "Prognosis", "Protein Tyrosine Kinase", "RNA", "ROS1 gene", "Reaction", "Recurrent tumor", "Research", "Resolution", "Sampling", "Screening for cancer", "Screening procedure", "Sensitivity and Specificity", "Series", "Signal Transduction", "Specificity", "Techniques", "Technology", "Testing", "Therapeutic", "Therapeutic Intervention", "Time", "Tissues", "Transcript", "Tube", "Tyrosine Kinase Inhibitor", "Variant", "Vision", "Work", "biobank", "cancer biomarkers", "cancer diagnosis", "chromosome fusion", "cohort", "commercialization", "companion diagnostics", "comparative", "crizotinib", "detection assay", "detection limit", "detection platform", "diagnostic platform", "diagnostic technologies", "diagnostic tool", "diagnostic value", "early screening", "effective intervention", "effective therapy", "genetic diagnostics", "high dimensionality", "improved", "inhibitor", "innovation", "kinase inhibitor", "liquid biopsy", "molecular diagnostics", "next generation", "next generation sequencing", "novel", "overexpression", "patient screening", "personalized diagnostics", "phase 2 study", "precision medicine", "screening", "sensor technology", "success", "tumor", "validation studies", "volunteer" ], "approved": true } }, { "type": "Grant", "id": "15796", "attributes": { "award_id": "1R44NS145848-01", "title": "Development of Tissue Engineered Tregs as a Treatment for Acute Ischemic Stroke", "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": 32884, "first_name": "FLOY ANNETTE", "last_name": "GILCHRIST", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": "2027-07-31", "award_amount": 1150417, "principal_investigator": { "id": 32885, "first_name": "Payam", "last_name": "Zarin", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2656, "ror": "", "name": "GENTIBIO, INC.", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "In the U.S., nearly 800,000 individuals experience a stroke each year, predominantly ischemic strokes. The economic burden of stroke is staggering, with projected stroke-related medical costs in the U.S. expected to surpass $94 billion by 2035. This underscores the urgent need for effective therapies to address this significant public health challenge. While the potential of regulatory T cells (Tregs) in promoting stroke recovery has been recognized, translating this promise into clinical success has been hampered by several obstacles. Traditional Treg therapies face challenges in manufacturing, phenotypic instability, and a lack of tissue specificity. This proposal focuses on the development of allogeneic engineered tissue Tregs (EngTregs) as a novel off-the-shelf therapeutic approach for stroke. Overexpression of ST2, the receptor for the alarmin IL-33, enhances the ability of EngTregs to: (i) sense and respond to tissue damage (ST2-expressing EngTregs efficiently migrate to sites of inflammation and injury); (ii) suppress excessive inflammation (EngTregs exert potent anti-inflammatory effects through multiple mechanisms, including direct suppression of immune cells and modulation of the inflammatory environment); and (iii) actively participate in tissue repair (EngTregs produce growth factors and interact with other cells to promote tissue regeneration). Overexpression of FOXP3 ensures a stable and suppressive Treg phenotype, crucial for long-term therapeutic efficacy. A chemically induced signaling complex (CISC) enables tunable IL-2 signaling, promoting Treg survival and function while facilitating scalable manufacturing. These innovations culminate in a first-in-class allogeneic tissue EngTreg product with advantages in manufacturing scalability, cost-effectiveness, and therapeutic potential compared to conventional Treg therapies. Preliminary studies demonstrate the ability of allogeneic EngTregs to accumulate in the injured brain and improve motor skills, sensory function, learning, and memory following ischemic injury induced in the transient middle cerebral artery occlusion (tMCAO) mouse model of stroke. This proposal outlines three aims to further advance the preclinical development of EngTregs for stroke: Aim 1: Evaluate the therapeutic efficacy of EngTregs in two preclinical stroke models (permanent middle cerebral artery occlusion and photothrombosis) in both adult and aged mice, assessing a comprehensive range of functional and histological outcomes. Aim 2: Characterize the mechanism of action and define a comprehensive in vitro profile of the human EngTreg drug product, including assessment of cytokine sequestration, T cell suppression, macrophage polarization, and transcriptomic analysis. Aim 3: Assess the immunotoxicity and immunogenicity of human EngTregs to ensure clinical safety, including evaluation of cytokine release syndrome and allo-immunogenicity. Successful completion of these aims will provide critical preclinical data supporting the clinical translation of EngTregs as a novel and promising therapeutic strategy for stroke, addressing a significant unmet medical need.", "keywords": [ "AREG gene", "Acute", "Address", "Adhesives", "Adult", "Age", "Allogenic", "Antiinflammatory Effect", "Area", "Autologous", "Biological Assay", "Blood flow", "Brain Injuries", "C57BL/6 Mouse", "CCR5 gene", "CCR8 gene", "Cell Physiology", "Cell Survival", "Cell Therapy", "Cells", "Cessation of life", "Characteristics", "Chemicals", "Clinical", "Clinical Data", "Cognitive", "Complex", "Development", "Economic Burden", "Engraftment", "Ensure", "Evaluation", "FOXP3 gene", "Face", "Female", "Flow Cytometry", "Growth Factor", "Guidelines", "Health Care Systems", "High Prevalence", "Histologic", "Homing", "Human Engineering", "IL2RA gene", "Immune Cell Suppression", "In Vitro", "Individual", "Infarction", "Inflammation", "Inflammatory", "Injury", "Interleukin-13", "Interleukin-2", "Ischemic Stroke", "Learning", "Macrophage", "Mediating", "Medical", "Medical Care Costs", "Memory", "Middle Cerebral Artery Occlusion", "Mixed Lymphocyte Culture Test", "Modeling", "Motor Skills", "Mus", "Outcome", "Outcome Measure", "Patient-Focused Outcomes", "Patients", "Performance", "Persons", "Pharmaceutical Preparations", "Phase", "Phenotype", "Preclinical data", "Process", "Public Health", "Receptors Tumor Necrosis Factor Type II", "Recovery of Function", "Regulatory T-Lymphocyte", "Reperfusion Therapy", "Research", "Risk", "Safety", "Sensory", "Signal Induction", "Signal Transduction", "Sirolimus", "Site", "Specificity", "Stroke", "T cell therapy", "T-Lymphocyte", "TNFRSF1B gene", "Testing", "Therapeutic", "Tissue Engineering", "Tissues", "Toxic effect", "Translating", "Treatment Efficacy", "Upregulation", "Work", "aged", "angiogenesis", "axon injury", "blood-brain barrier permeabilization", "brain repair", "clinical translation", "cost", "cost effectiveness", "cytokine", "cytokine release syndrome", "disability", "disease heterogeneity", "effective therapy", "experience", "foot", "human tissue", "immunogenicity", "immunotoxicity", "improved", "inflammatory milieu", "inflammatory modulation", "innovation", "ischemic injury", "male", "manufacture", "manufacturing process", "migration", "morris water maze", "mortality", "mouse model", "neurogenesis", "novel", "object recognition", "old mice", "osteopontin", "overexpression", "patient subsets", "post stroke", "pre-clinical", "preclinical development", "preclinical evaluation", "programs", "public health relevance", "receptor", "repaired", "stroke model", "stroke recovery", "stro" ], "approved": true } }, { "type": "Grant", "id": "15795", "attributes": { "award_id": "1R21EB037846-01", "title": "Design principles for engineering therapeutic macrophages", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Biomedical Imaging and Bioengineering (NIBIB)" ], "program_reference_codes": [], "program_officials": [ { "id": 32882, "first_name": "TUBA HALISE", "last_name": "FEHR", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2028-07-31", "award_amount": 621158, "principal_investigator": { "id": 32883, "first_name": "Jason Hung-Ying", "last_name": "Yang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2655, "ror": "", "name": "RUTGERS BIOMEDICAL AND HEALTH SCIENCES", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true }, "abstract": "Genetically engineered immune cells are an exciting and promising frontier for treating a wide range of complex diseases. However, hyperinflammatory toxicities such as cytokine release syndrome plague clinical trials, stymieing their widespread clinical adoption. Macrophages are innate immune cells that fulfill many roles in tissue repair, regeneration, and homeostasis and are important regulators of inflammation. However, they are significantly under-utilized as engineered immune cell therapies because significant knowledge gaps exist in understanding how to engineer synthetic gene circuits that work robustly in human macrophages. Tools do not yet exist for determining how macrophages should be biologically manipulated to activate desired effector functions (biological design principles). Tools also do not exist for determining what gene circuit architectures are needed to robustly induce desired gene circuit behaviors (gene circuit design principles). The overall goal for this proposal is to create a human macrophage design toolkit for engineering therapeutic macrophages. Our published and preliminary data demonstrate that we have developed tools that enable us to discover cell signaling interventions that can control macrophage effector functions (biological design principles) and gene circuit architectures that can exert robust behaviors in human macrophages (gene circuit design principles). Here we will apply both these approaches to elucidate biological and gene circuit design principles that can be used to engineer therapeutic macrophages that can suppress inflammatory cytokine secretion or induce anti- inflammatory cytokine secretion in inflamed tissues. We will elucidate biological design principles using an interpretable machine learning approach that we previous developed. This approach combines biochemical screening with predictive network modeling and machine learning to discover network mechanisms causally regulating cell phenotypes. We will elucidate gene circuit design principles using a recently developed ultra-high- throughput genetic screening approach (CLASSIC). This approach synthesizes and screens large, barcoded gene circuit libraries to associate gene circuit architectures with gene circuit behaviors. With these design principles we will engineer gene circuits for controlling IL-1β or IL-10 secretion in inflamed tissue contexts and validate these synthetic gene circuits in human monocyte-derived macrophages and THP-1 cells. In its entirety, this Trailblazer R21 project is a first step towards addressing the unmet need for design principles for engineering therapeutic macrophages. We envision that insights gained by this project will help establish engineered macrophages as a platform technology for treating a wide range of complex human diseases.", "keywords": [ "Address", "Adoption", "Anti-Inflammatory Agents", "Architecture", "Bar Codes", "Behavior", "Biochemical", "Biological", "Cells", "Cellular immunotherapy", "Clinical", "Clinical Trials", "Complex", "Data", "Disease", "Engineered Gene", "Engineering", "Environment", "Future", "Genes", "Genetic", "Genetic Engineering", "Genetic Screening", "Goals", "Homeostasis", "Human", "Immune", "Inflammation", "Inflammatory", "Interleukin-1 beta", "Interleukin-10", "Intervention", "Knowledge", "Libraries", "Machine Learning", "Macrophage", "Natural regeneration", "Phenotype", "Plague", "Process", "Publishing", "Role", "Signal Transduction", "Synthetic Genes", "Therapeutic", "Tissues", "Toxic effect", "Work", "cytokine", "cytokine release syndrome", "design", "explainable machine learning", "frontier", "gene discovery", "human disease", "immunoengineering", "insight", "monocyte", "network models", "prototype", "screening", "simulation", "synthetic biology", "technology platform", "tissue repair", "tool" ], "approved": true } }, { "type": "Grant", "id": "15794", "attributes": { "award_id": "1R21EB037897-01", "title": "Programmable RNA-Based Sensors for In Situ Cell Type Detection and Response", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Biomedical Imaging and Bioengineering (NIBIB)" ], "program_reference_codes": [], "program_officials": [ { "id": 32881, "first_name": "SHAWN PATRICK", "last_name": "MULVANEY", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2028-07-31", "award_amount": 673600, "principal_investigator": { "id": 30867, "first_name": "Lei", "last_name": "Wang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2654, "ror": "", "name": "NORTHEASTERN UNIVERSITY", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "There is a technology gap in currently developed tools that simultaneously monitor, compute, and respond to both coding and non-coding RNA in real-time within living cells or patients. The continued existence of this gap represents an urgent unmet need because, until it is filled, the accuracy of RNA-based therapeutics remains limited in complex and evolving biological systems like differentiation or cancer. The long-term goal of this proposal is to develop safe, universal, and programmable synthetic biology tools that using both coding and non- coding RNAs as disease marker inputs and program outputs to trigger therapeutic responses in patients. The objective of this particular application is to develop an RNA-based sensor (using mRNA as the delivery modality) that detects integrated changes in both mRNA and miRNA for in situ therapeutic responses within living cells and mouse models, given the crucial role of ncRNAs, especially microRNAs (miRNAs), as key regulators of post- transcriptional gene regulation, which allow only the correct set of genes to be active in each cell type. The central hypothesis is that an RNA-based sensor integrating both mRNA and miRNA inputs, using Boolean logic gate computation, can improve the specificity of cell type identification in complex biological systems. This proposed work builds on our and other’s recent works on sensing individual RNA species like mRNA in live cells. The rationale for the proposed research is that a deeper understanding of disease progression, derived from the vast RNA sequencing resources now available in user-friendly databases, creates a timely and unique opportunity for synthetic biologists to develop tools that can precisely identify diseased cells based on their RNA species and levels in living cells or even in patients. This allows for the development of treatments that specifically target diseased cells while minimizing off-target effects on healthy cells. Additionally, the success of COVID-19 mRNA vaccines using lipid nanoparticle delivery systems highlights the potential to translate RNA-based genetic circuits into practical medical applications. Given these advances, we plan to develop two independent and complementary aims for in situ cell state sensing using endogenous mRNA and miRNA as inputs: AND logic gates (requiring both inputs for an output) in Aim 1 and NOR logic gates (requiring neither input for an output) in Aim 2. This platform has broad biomedical potentials. As a proof of concept, we will demonstrate its ability to distinguish breast cancer cells from normal breast epithelial cells, evaluating its translational potential using a syngeneic mouse model of triple-negative breast cancer, which lacks key cell surface targets in current therapies. The proposed platform is innovative because it develops new platform by integration of existing miRNA sensing and RNA detecting approaches in a previously unproven combinatorial logic computation format to address a significant unmet need for accurate cell type identification for basic and translational applications. The proposed research is significant, because in situ monitoring and intervening based on endogenous RNAs will be key to addressing this unmet need, transforming disease detection and treatment.", "keywords": [ "4T1", "Address", "Animal Model", "Award", "Biological", "Biomedical Engineering", "Breast Cancer Cell", "Breast Cancer therapy", "Breast Epithelial Cells", "COVID-19", "Cell Line", "Cell Physiology", "Cell model", "Cell surface", "Cells", "Clinical", "Code", "Complex", "Data", "Databases", "Detection", "Disease", "Disease Marker", "Disease Progression", "Double-Stranded RNA", "Elements", "Engineering", "Ensure", "Gene Expression", "Genes", "Genetic", "Goals", "Human", "Immune System Diseases", "In Situ", "Individual", "Logic", "MCF10A cells", "MDA MB 231", "Malignant Neoplasms", "Medical", "Messenger RNA", "MicroRNAs", "Mission", "Modality", "Modeling", "Monitor", "National Institute of Biomedical Imaging and Bioengineering", "Nature", "Nerve Degeneration", "Output", "Patients", "Performance", "Play", "Post-Transcriptional Regulation", "Proteins", "Publishing", "RNA", "RNA vaccine", "Regulation", "Regulator Genes", "Repression", "Research", "Resources", "Role", "Sampling", "Specificity", "Survival Rate", "System", "Technology", "Testing", "Time", "Tissues", "Translating", "United States National Institutes of Health", "Untranslated RNA", "Work", "biological systems", "cell type", "combinatorial", "complex biological systems", "design", "design and construction", "differential expression", "improved", "in vitro Model", "innovation", "lipid nanoparticle", "mRNA delivery", "mammary", "model design", "model organism", "molecular sequence database", "mouse model", "nanoparticle delivery", "novel", "novel strategies", "programs", "prototype", "response", "risk mitigation", "scaffold", "sensor", "single-cell RNA sequencing", "success", "synthetic biology", "targeted treatment", "therapeutic RNA", "therapy development", "tool", "transcriptome sequencing", "transcriptomics", "translational applications", "translational potential", "treatment response", "triple-negative invasive breast carcinoma", "user-friendly" ], "approved": true } }, { "type": "Grant", "id": "15792", "attributes": { "award_id": "1R21AI193885-01", "title": "UTS-1401 as a Medical Countermeasure to H-ARS Consequent to a Radiation Mass Casualty", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 32879, "first_name": "LANYN P", "last_name": "TALIAFERRO", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-18", "end_date": "2027-07-31", "award_amount": 157000, "principal_investigator": { "id": 32877, "first_name": "Stephen L", "last_name": "Brown", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32878, "first_name": "FREDERICK Augustus", "last_name": "VALERIOTE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2633, "ror": "", "name": "HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Abstract: Our long term objective is to develop a new class of radiation mitigating agents with attractive chemical, physical and biological characteristics required to be an effective drug that can be distributed widely. We have identified a small molecule, UTS-1401 [5-(methylthiomethyl) isoxazole-3-carboxylic acid] which demonstrates mitigation of hematopoietic stem cell death when administered at either 24h or 48h following whole body irradiation (WBI). Using the endogenous spleen colony assay, we demonstrated a mitigating effect in that the colony number with and without UTS-1401 was 3.5 ± 0.4 for a 24h interval and 2.3 ± 0.5 for a 48h interval. We have recently demonstrated a significant radioprotection for both mouse survival and hematopoietic stem cells for this compound when administered up to 72h before irradiation (Valeriote et al, Radiation Research, 202:16- 25, 2024). In this application, we propose to further examine solely the mitigating effect on the hematopoietic acute radiation syndrome (H-ARS) using survival as the endpoint in specific aim 1. Groups of Swiss mice will receive a series of graded doses of WBI (in 0.5 Gy increments) around the LD50 for this syndrome (approximately 7.5 Gy in females and 8.5 Gy in males) with and without the administration of 150 mg/kg UTS-1401. The single dose of UTS-1401 being used in all studies is the highest dose administrable due to its aqueous solubility (in tartrate buffered saline). The radiation mitigation factors will be calculated as the ratio of the LD50 for radiation plus UTS-1401 versus that for radiation alone. The degree of mitigation will be examined at 24, 48 and 72 h following WBI to determine the radiation mitigation fraction as a function of time after radiation exposure. Three routes of drug delivery, intravenous (iv), oral, and subcutaneous (sc), will be examined and compared. Radiation will be delivered by 16 MeV electrons from a Linac. In specific aim 2, we will examine the pharmacokinetics (PK) for 150 mg/kg UTS-1401 comparing the iv, oral, and sc routes to obtain a determination of both the drug kinetics and bioavailability. The AUC values will be correlated with the extent of mitigation. For both specific aims, both male and female mice will be separately studied. The results from these studies are expected to demonstrate an effective first-in-class compound, UTS-1401, which has a small molecular weight, is chemically stable, nontoxic, aqueous soluble and inexpensive with H-ARS radiation mitigating properties which extend for a number of days following WBI. The mechanism studies (not proposed here) are expected to demonstrate UTS- 1401 as a new class of agents for mitigating the cytokine storm consequent to the irradiation.", "keywords": [ "Accidents", "Acute", "Address", "Animal Model", "Animals", "Biologic Characteristic", "Biological", "Biological Assay", "Biological Availability", "Biotechnology", "Blood", "Bone Marrow", "Buffers", "Carboxylic Acids", "Cell Death", "Cells", "Chemicals", "Chernobyl Nuclear Accident", "China", "Clinical", "Conflict (Psychology)", "Cyclic GMP", "Data", "Development", "Dose", "Drug Delivery Systems", "Drug Kinetics", "Drug Stability", "Electromagnetics", "Electrons", "Employee", "Equipment and supply inventories", "Exposure to", "FDA approved", "Federal Government", "Female", "Fibrosis", "Follow-Up Studies", "Formulation", "Fukushima", "Geographic Distribution", "Goals", "Growth Factor", "Hematopoietic", "Hematopoietic System", "Hematopoietic stem cells", "Hospitals", "Individual", "Industry", "Inflammation", "Inflammatory", "Injury", "International", "Intervention", "Intravenous", "Ionizing radiation", "Iran", "Isoxazoles", "Israel", "Korea", "Lethal Dose 50", "Location", "Molecular Weight", "Mus", "North Korea", "Nuclear", "Nuclear Accidents", "Nuclear Weapon", "Oral", "Oral Administration", "Organ", "Pharmaceutical Preparations", "Pharmacologic Substance", "Pharmacology and Toxicology", "Phase", "Phase I Clinical Trials", "Physiologic pulse", "Procedures", "Process", "Property", "Radiation", "Radiation Accidents", "Radiation Protection", "Radiation Toxicity", "Radiation exposure", "Refrigeration", "Research", "Rotation", "Route", "Russia", "Saline", "Schedule", "Series", "Solubility", "South Korea", "Spleen", "Swiss Mice", "Syndrome", "System", "Taiwan", "Tartrates", "Temperature", "Terrorism", "Time", "Tissues", "Ukraine", "United States National Aeronautics and Space Administration", "Vomiting", "War", "Whole-Body Irradiation", "Work", "aqueous", "chemical stability", "cost effective", "cytokine", "cytokine release syndrome", "design", "drug development", "efficacy study", "expiration", "irradiation", "male", "manufacture", "mass casualty", "medical countermeasure", "novel", "product development", "radiation countermeasure", "radiation mitigation", "radiation response", "radioprotected", "research study", "safety study", "scale up", "small molecule", "subcutaneous", "success" ], "approved": true } }, { "type": "Grant", "id": "15791", "attributes": { "award_id": "1R21AI186055-01A1", "title": "UTS-1401: A Novel Mitigator of Radiation Injury", "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": 32876, "first_name": "ANDREA L", "last_name": "DICARLO-COHEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2027-07-31", "award_amount": 431750, "principal_investigator": { "id": 32877, "first_name": "Stephen L", "last_name": "Brown", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32878, "first_name": "FREDERICK Augustus", "last_name": "VALERIOTE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2633, "ror": "", "name": "HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Abstract: Our long term objective is to develop a new class of radiation mitigating agents with attractive chemical, physical and biological characteristics required to be an effective drug that can be distributed widely. We have identified a small molecule, UTS-1401 [5-(methylthiomethyl) isoxazole-3-carboxylic acid] which demonstrates mitigation of hematopoietic stem cell death when administered at either 24h or 48h following whole body irradiation (WBI). Using the endogenous spleen colony assay we demonstrated a significant mitigating effect (ratio of colony number with and without UTS-1401) when drug was given 24h or 48h after radiation. We have also recently demonstrated a significant radioprotection for both mouse survival and hematopoietic stem cells for this compound for up to 72h before irradiation (Valeriote et al, Radiation Research, 202:16-25, 2024). In this application, we propose to examine solely the mitigating effect to both the hematopoietic acute radiation syndrome (H-ARS) in specific aim 1 and the gastrointestinal acute radiation syndrome (GI-ARS) in specific aim 2 following WBI (with 5% bone marrow protection for specific aim 2). Swiss mice will receive a series of graded doses of WBI around the LD50 for both syndromes with and without the administration of 150 mg/kg UTS- 1401. The single dose of UTS-1401 being used in all studies is the highest dose administrable due to its aqueous solubility (in tartrate buffered saline). The radiation mitigation factors will be calculated as the ratio of the LD50 for radiation plus UTS-1401 versus radiation alone. The degree of mitigation will be examined at 24, 48 and 72 h following WBI to determine the timeframe of mitigation after radiation exposure. Three routes of drug delivery, intravenous (iv), oral, and subcutaneous (sc), will be examined and compared. For all specific aims, both male and female mice will be separately studied. Radiation will be delivered by electrons from a Linac. In specific aim 3, we will examine the pharmacokinetics (PK) for 150 mg/kg UTS-1401 comparing the iv, oral, and sc routes to obtain a determination of both the drug kinetics and bioavailability. The AUC values will be correlated with the extent of mitigation. Finally, in specific aim 4, we will address the mechanism of action with studies focused on the role of specific cytokines induced by radiation in the so-called “cytokine storm”. We will assess the time course changes of TNF-α, IL-1β, IL-6, CSF and TGF-β in blood as well as bone marrow and intestinal mucosa over 20 days following: UTS-1401 alone, 10 Gy irradiation, and the combination of UTS-1401 and radiation at a 24h interval. The results from these studies are expected to demonstrate an effective first-in-class compound, UTS-1401, which has a small molecular weight, is chemically stable, nontoxic, aqueous soluble and inexpensive with radiation mitigating properties which extend for a number of days following irradiation. 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