Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=3&sort=-start_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-start_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=-start_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=-start_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=-start_date" }, "data": [ { "type": "Grant", "id": "15601", "attributes": { "award_id": "1R13NS141592-01", "title": "2025 Patrica Levy Zusman International Workshop on Neuroregeneration", "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": 24007, "first_name": "LINDA LOUISE", "last_name": "Bambrick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-03-01", "end_date": "2026-02-28", "award_amount": 14000, "principal_investigator": { "id": 26852, "first_name": "Philip J", "last_name": "Horner", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1455, "ror": "", "name": "METHODIST HOSPITAL RESEARCH INSTITUTE", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "This R13 resulted from discussions between investigators in the fields of neurostimulation and neuroplasticity at the Houston Methodist Research Institute (HMRI). In 2017, we held an R13-funded pilot workshop that combined research in neural stimulation with new insight into the molecular understanding of neural plasticity and regeneration. The workshop received a strong, positive response by participants and interest in further catalysts for working collaboration. Thus, in 2019, we fostered relationship development and crossover opportunities among attendees via a blitz session wherein newly formed (i.e., established at the 2019 Workshop) collaborative teams competed for two $5K mini grants that supported travel to and from each other’s institutions. In 2021, we went 100% virtual due to COVID-19, however, this did not diminish the R13-funded Workshop’s impact. In 2023, our R13-funded workshop returned to an in-person event, bringing with it many of the successful virtual tools from 2021. On March 4th – 6th, 2025, we will host the 5th Patricia Levy Zusman International Workshop on Neuroregeneration (Zusman Workshop), which will focus on the intersection of electrical activity, brain connectomics, and molecular neural plasticity. Our specific aims are to: 1) formulate new ideas to fill the gap between physiology and functional-based brain stimulation technologies and the molecular and cellular understanding of innate neuronal plasticity; 2) provide promising trainees with various avenues to present their work; and 3) ensure trainees participate in substantial discussions and interactions with faculty members. The 2025 Workshop will be held at HMRI, which is part of the Texas Medical Center (TMC; a one-of-a-kind medical and research hub that fosters cross-institutional collaboration, creativity, and innovation) and is in Houston, Texas (one of the United States’ most diverse cities). A key aspect of the Zusman Workshop is the active inclusion and participation of trainees, particularly women and under-represented minorities. We will encourage their participation via travel scholarships and active promotion and recruitment throughout the TMC. The Workshop promotes the voices of graduate and postdoctoral trainees by including a trainee poster session as well as a session dedicated to trainee oral presentations (given by travel awardees). Further, goal-oriented breakout sessions, led by senior/early-stage investigators and selected trainees, will foster discussion and promote cross-training and collaboration among participants. Overall, this workshop distinguishes itself from established physiology conferences and dedicated neural regeneration conferences by being 1) highly focused on the gap between molecular regeneration and electrophysiology/stimulation, 2) concept driven by clinicians and experimentalists currently problem solving in human therapy, and 3) focused on the establishment of cross training and expertise development in graduate, post-graduate, and clinical fellows. The 2025 Zusman Workshop will ignite nascent collaborations and spur novel multidisciplinary teams to develop innovative, transdisciplinary methods, technologies, and treatments to modulate performance in the damaged nervous system.", "keywords": [ "Acceleration", "Address", "Adjuvant Therapy", "Award", "Back", "Basic Science", "Brain", "COVID-19", "Cells", "Central Nervous System", "Cities", "Clinical", "Collaborations", "Creativeness", "Dedications", "Development", "Devices", "Discipline", "Disease", "Educational workshop", "Electrodes", "Electrophysiology (science)", "Elements", "Ensure", "Event", "Faculty", "Feedback", "Fostering", "Frequencies", "Funding", "Funding Opportunities", "Goals", "Grant", "Health Sciences", "Human", "Institution", "International", "Laboratories", "Machine Learning", "Medical", "Medical center", "Medicine", "Mental Depression", "Mentors", "Methodist Church", "Methods", "Molecular", "Movement Disorders", "Natural regeneration", "Nerve Regeneration", "Nervous System Trauma", "Neuronal Plasticity", "Neuropsychology", "Oral", "Paralysed", "Participant", "Performance", "Persons", "Physical Rehabilitation", "Physicians", "Physiologic pulse", "Physiology", "Postdoctoral Fellow", "Problem Solving", "Productivity", "Research", "Research Institute", "Research Personnel", "Rice", "Schedule", "Scholarship", "Science", "Scientist", "Speed", "Stroke", "Study Section", "System", "Technology", "Texas", "Training", "Travel", "Underrepresented Minority", "United States", "United States National Institutes of Health", "Universities", "Virtual Tool", "Voice", "Woman", "Work", "brain based", "brain computer interface", "catalyst", "clinical application", "college", "combinatorial", "exoskeleton", "graduate student", "gulf coast", "improved", "innovation", "insight", "interdisciplinary collaboration", "interest", "lectures", "meetings", "member", "multidisciplinary", "neural", "neural stimulation", "neuromechanism", "neurophysiology", "neuroregulation", "novel", "post-doctoral training", "posters", "recruit", "regenerative therapy", "repaired", "response", "success", "symposium", "training opportunity", "translational approach", "virtual", "working group" ], "approved": true } }, { "type": "Grant", "id": "15649", "attributes": { "award_id": "2451399", "title": "SBIR Phase I: Novel Peptide Immunomodulators for Treatment of Autoimmune and Inflammatory Disorders", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Technology, Innovation and Partnerships (TIP)", "SBIR Phase I" ], "program_reference_codes": [], "program_officials": [ { "id": 936, "first_name": "Henry", "last_name": "Ahn", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-03-01", "end_date": null, "award_amount": 305000, "principal_investigator": { "id": 32152, "first_name": "Masha", "last_name": "Fridkis-Hareli", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2552, "ror": "", "name": "PALENA THERAPEUTICS, INC.", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is in developing a novel class of compounds capable of treating autoimmune and inflammatory conditions safely and effectively. With the constant threat of new COVID variants, influenza, and RSV, there is an unmet medical need for therapeutics that can effectively treat autoimmune diseases especially in pediatric patients without compromising the immune system to respond to infections. This problem has been overcome with the discovery of novel compositions that demonstrate efficacy equal or superior to many of the first line therapies used to treat immune diseases. The improved safety, efficacy and lower cost of these therapeutics should provide a significant benefit to patients by overall contributing to their quality of life as compared to current medications, as well as marketing and partnering advantage in its commercialization efforts, which will focus on rare diseases, such as juvenile idiopathic arthritis-associated uveitis and pediatric Crohn’s disease among others. In the era of socio-economic disparities, these affordable drugs will become available to the historically neglected low-income communities. If executed successfully, this proposal would validate the platform technology and demonstrate the feasibility of identifying candidates for further development into life-changing treatments. This Small Business Innovation Research (SBIR) Phase I project will demonstrate the unique design of novel compounds to augment and re-program the immune responses from pro- to anti-inflammatory, based on the binding to MHC class II molecules that leads to immunomodulation. The technical complexities of understanding the effects of peptide sequences on the outcomes of cellular interactions present challenges related to selecting the appropriate amino acids both for the random and specific components of these compositions. These hurdles will be addressed by design of several candidate compounds for each target condition, juvenile idiopathic arthritis-associated uveitis and pediatric Crohn’s disease, that will take into account the structure of autoantigenic peptides known to interact with both the MHC class II and T cell receptor (TCR). These candidate compounds will be initially tested in vitro in human macrophages to assess their potential to inhibit secretion of pro-inflammatory cytokines. Of these compounds, the most efficient ones will be tested for activity in relevant animal models. This approach will allow identifying and selecting the best drug candidates for further development into therapies for pediatric conditions as outlined above. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15605", "attributes": { "award_id": "1R33CA286947-01A1", "title": "Sequence optimization for mRNA cancer therapy", "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": 21123, "first_name": "Jerry", "last_name": "Li", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-03-01", "end_date": "2028-02-29", "award_amount": 380337, "principal_investigator": { "id": 32101, "first_name": "Georg", "last_name": "Seelig", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "mRNA technology is in the public spotlight thanks to its role in fighting the COVID-19 pandemic, and it is also rapidly transforming cancer therapeutics development through application areas such as immunotherapy. This wave of mRNA therapeutics is the result of decades of work on many fronts including improved delivery using lipid nanoparticles and inclusion of modified nucleosides for modulating immunogenicity. However, optimization of primary sequences still remains a difficult yet coveted challenge due to its untapped potential in controlling protein expression or encoding complex pharmacokinetics. Currently, mRNA therapy design typically involves adding UTRs from highly expressed native genes such as globin genes to codon-optimized (choosing most frequent synonymous codons) or GC content-enriched coding sequences. However, there is growing evidence that these strategies may be conceptually questionable and empirically suboptimal. At present, there exists no systematically validated model for mRNA therapeutics that can accurately predict and/or generate an optimal sequence to express a given target gene at desired levels. There is a significant need for such an in silico platform to accelerate therapy development timelines. Finally, mRNA sequences are largely chosen to have high expression but future therapies will impose additional design specifications for controllable expression. For example, it might be desirable to target protein expression to specific locations such as the site of a tumor. Improved design algorithms are necessary to satisfy constraints such as cell type or tissue specificity. Here, we propose to combine machine learning with massively parallel reporter assays (MPRAs) to build predictive models that relate mRNA sequence to stability and translation. We will then combine these models with innovative design algorithms to generate synthetic UTR and CDS sequences that result in (1) high protein expression across cell types or (2) highly cell type-specific protein expression. We will take an iterative approach to sequence design wherein we will synthesize designed UTRs, experimentally test them in a panel of cell types and then use the data to retrain the predictors until we meet the design objective. We will validate our approach by engineering improved mRNAs for cancer immunotherapy. In Specific Aim 1, we will develop MPRAs that interrogate 5’UTRs and coding sequences as well as 3’UTRs. In Specific Aim 2, we will develop machine learning approaches that enable us to integrate results from multiple measurements and generalize predictive rules learned from such assays. In Specific Aim 3, we will validate models by engineering regulatory elements that target protein expression to specific cell types of interest or that result in a specific level of protein expression.", "keywords": [ "3&apos", "Untranslated Regions", "5&apos", "Untranslated Regions", "Acceleration", "Algorithm Design", "Area", "Biological Assay", "COVID-19 pandemic", "Cell Line", "Chemicals", "Code", "Codon Nucleotides", "Communicable Diseases", "Complex", "Data", "Drug Kinetics", "Engineering", "Future", "Genes", "Globin", "Guanine + Cytosine Composition", "Immunotherapy", "Learning", "Length", "Location", "Machine Learning", "Malignant Neoplasms", "Measurement", "Measures", "Messenger RNA", "MicroRNAs", "Modeling", "Modification", "Nucleosides", "Production", "Proteins", "RNA-Binding Proteins", "Regulation", "Regulatory Element", "Reporter", "Research", "Ribosomes", "Role", "Site", "Specific qualifier value", "Specificity", "Technology", "Testing", "Therapeutic", "Tissues", "Training", "Transcript", "Translations", "Untranslated Regions", "Vaccines", "Variant", "Work", "cancer immunotherapy", "cancer therapy", "cell type", "clinical application", "design", "fighting", "fitness", "generative adversarial network", "immunogenicity", "improved", "in silico", "innovation", "interest", "lipid nanoparticle", "mRNA Stability", "mRNA Translation", "multitask", "predictive modeling", "protein expression", "recurrent neural network", "therapeutic development", "therapy design", "therapy development", "timeline", "training data", "tumor" ], "approved": true } }, { "type": "Grant", "id": "15602", "attributes": { "award_id": "4R42HL166050-02", "title": "Aerosolized Chemically Modified Tetracycline Nanoformulation for the Treatment of Acute Respiratory Distress Syndrome", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 26329, "first_name": "SIDDHARTH KAUP", "last_name": "Shenoy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-03-01", "end_date": "2027-02-28", "award_amount": 887354, "principal_investigator": { "id": 26768, "first_name": "Michaela Christina", "last_name": "Kollisch-Singule", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 26769, "first_name": "Juntao", "last_name": "Luo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1682, "ror": "", "name": "CMTX BIOTECH, INC.", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "CMTx Biotech is a drug development company working to rescue, develop and commercialize a proprietary clinical-stage drug candidate, incyclinide (CMT-3 / COL-3), for the treatment of sepsis patients at risk of acute respiratory distress syndrome (ARDS). According to the U.S. Centers for Disease Control (CDC), at least 1.7 million American adults develop sepsis annually, resulting in nearly 270,000 deaths. Sepsis accounts for more than 50% of hospital deaths, and mortality increases dramatically with greater disease severity: 10–20% for sepsis, 20–40% for severe sepsis, and 40–80% for septic shock. Sepsis is a medical emergency characterized by severe immune dysregulation with a very complex immunopathogenesis. ARDS is a devastating complication of severe sepsis, both with similar underlying mechanisms characterized by inflammation and endothelial dysfunction. Sepsis is the leading cause of ARDS and accounts for 32% of the etiology of the condition. Approximately 6-7% of sepsis patients rapidly progress to ARDS, which is associated with a significantly increased risk of in-hospital mortality. There is currently no specific treatment for sepsis-induced ARDS. Moreover, researchers have not yet elucidated the multifactorial mechanisms by which sepsis induces ARDS, or why the inflammatory cytokine storm eventually induces diffuse alveolar damage and severe hypoxia. Though advances in treatment modalities have improved the outcome over recent decades, including lung protective ventilation, prone positioning, use of neuromuscular blockade, and extracorporeal membrane oxygenation, the mortality rate still remains high. There remains a critical unmet need for the development of safe and efficacious therapeutics to prevent the onset of sepsis-induced ARDS, protect against lung injury and improve survival. CMTx Biotech is working to develop and commercialize a novel and proprietary nanoformulation of incyclinide (nCMT-3) that can be aerosolized, and which can be delivered to specifically target the lung and treat sepsis- induced ARDS while limiting systemic toxicity. Incyclinide is a clinical-stage, non-antibiotic, chemically-modified tetracycline that belongs to a class of pleiotropic matrix metalloproteinase (MMP) modulators which inhibit pathologically-excessive collagenolysis and resolve systemic inflammation. Importantly, the safety of incyclinide has already been demonstrated in Investigational New Drug (IND)-enabling studies, and incyclinide has been evaluated in a number of human clinical trials for the treatment of diseases as disparate as AIDS-related Kaposi’s sarcoma, recurrent high-grade gliomas, refractory metastatic cancer, acne, rosacea and periodontitis. Published pre-clinical efficacy studies have shown that systemic administration of incyclinide prevents the development of ARDS and septic shock, and improves survival in several chronic insidious onset animal models of ARDS across several species, including mice, rats, pigs, and sheep. Our long-term goal is to obtain regulatory approval from the FDA and comparable international regulatory authorities to market aerosolized nCMT-3 for the treatment and prevention of sepsis-induced ARDS. We strongly anticipate that nCMT-3 will inhibit disease progression, mitigate acute lung injury and respiratory distress, reduce the need for intensive care and intubation, and improve clinical outcomes for sepsis patients, including overall survival. Our specific aims are (a) to determine the pharmacokinetics, biodistribution, and safety of aerosolized nCMT-3 in mechanically ventilated pigs with healthy lungs, (b) to demonstrate the efficacy of aerosolized nCMT-3 in reducing the incidence and mortality of sepsis- mediated ARDS in a high-fidelity, clinically applicable porcine sepsis-induced ARDS model, and (c) to demonstrate the efficacy of aerosolized nCMT-3 at reducing local and systemic inflammation. Successful completion of these studies will allow CMTx Biotech to advance nCMT-3 towards human clinical trials for the treatment of ARDS patients.", "keywords": [ "AIDS with Kaposi&apos", "s sarcoma", "Accounting", "Acne", "Acute Lung Injury", "Acute Respiratory Distress Syndrome", "Adult", "Agreement", "Alveolar", "American", "Animal Model", "Animals", "Area", "Biodistribution", "Biotechnology", "Centers for Disease Control and Prevention (U.S.)", "Cessation of life", "Chemicals", "Chronic", "Clinical", "Clinical Research", "Clinical Treatment", "Clinical Trials", "Complex", "Complication", "Data", "Death Rate", "Dermatology", "Development", "Diffuse", "Disease", "Disease Progression", "Disparate", "Disseminated Malignant Neoplasm", "Dose", "Drug Kinetics", "Etiology", "Extracorporeal Membrane Oxygenation", "FDA approved", "Family suidae", "Formulation", "Glioma", "Goals", "Hospital Mortality", "Hospitals", "Human", "Hydrophobicity", "Hypoxia", "Immune", "Incidence", "Induction of neuromuscular blockade", "Inflammation", "Inflammatory", "Intensive Care", "International", "Intubation", "Investigational Drugs", "Knowledge", "Licensing", "Lung", "Marketing", "Matrix Metalloproteinases", "Mechanical ventilation", "Mediating", "Medical", "Medical emergency", "Methods", "Modality", "Modeling", "Morbidity - disease rate", "Mus", "Oncology", "Oral", "Outcome", "Pathologic", "Pathway interactions", "Patients", "Periodontitis", "Periostat", "Pharmaceutical Preparations", "Pharmacologic Substance", "Pharmacotherapy", "Phase", "Prevention", "Prone Position", "Public Health", "Publishing", "Rattus", "Recurrence", "Refractory", "Research", "Research Personnel", "Respiratory distress", "Risk", "Rosacea", "Safety", "Schedule", "Sepsis", "Septic Shock", "Severity of illness", "Sheep", "Small Business Technology Transfer Research", "Supportive care", "Tetracyclines", "Therapeutic", "Therapeutic Intervention", "Therapy trial", "Tissues", "Toxic effect", "Work", "aerosolized", "authority", "clinical application", "clinical development", "commercial application", "commercialization", "cytokine release syndrome", "design", "drug candidate", "drug development", "efficacy evaluation", "efficacy study", "endothelial dysfunction", "experimental study", "forging", "improved", "improved outcome", "lung injury", "mortality", "nanoformulation", "novel", "pharmacokinetics and pharmacodynamics", "pre-Investigational New Drug meeting", "preclinical development", "preclinical efficacy", "prevent", "repository", "safety study", "sepsis induced ARDS", "septic patients" ], "approved": true } }, { "type": "Grant", "id": "15599", "attributes": { "award_id": "1R01CA301643-01", "title": "Role of respiratory viral infections and inflammation in promoting metastatic outgrowth in the lung", "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": 21648, "first_name": "Elizabeth Lee", "last_name": "Read-Connole", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-03-01", "end_date": "2030-02-28", "award_amount": 672011, "principal_investigator": { "id": 32096, "first_name": "James V", "last_name": "Degregori", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32097, "first_name": "Mercedes", "last_name": "Rincon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 784, "ror": "https://ror.org/02hh7en24", "name": "University of Colorado Denver", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "The leading cause of breast cancer deaths is metastasis. Metastatic relapse can occur months to years after the initial diagnosis and treatment of the primary tumor. Cancer cells can disseminate from the primary tumor into different tissues including lungs and remain in a dormant state for years to decades. Awakening of these dormant disseminated cancer cells (DCC) leads to metastasis. Finding factors that trigger the awakening of dormant DCC and developing strategies to reduce the risk of awakening is therefore an unmet need. While it is known that inflammation is a key contributing factor to the awakening of dormant DCC, no studies have investigated whether inflammation triggered by viral respiratory infections (a very common infection worldwide) in the lung can promote the expansion of DCC and lead to the development of metastases. Our recent studies using a mouse model of breast cancer DCC dormancy in the lung have revealed a dramatic increase in DCC awakening and expansion in the lungs following influenza virus infection. Our data support the hypothesis that respiratory viral infections can promote DCC awakening and expansion through two phases: first, through IL-6 dependent DCC awakening and expansion, and second, CD4 T-cell mediated protection from elimination (in part by CD8 cells). We further show that infection with a mouse-adapted SARS-CoV-2 promotes a similar awakening and expansion of DCC in mice. Finally, epidemiological studies reveal how prior infection with SARS-CoV-2 infection increases metastatic progression in lungs and cancer- related deaths for cancer survivors. We propose to determine mechanisms by which acute respiratory viral infections induce the awakening of dormant DCC leading to metastatic disease, whether and how such infections can prime DCC for activation by subsequent exposures, and how CD4 and CD8 cells differentially control the persistence of expanded DCC during influenza virus infection. Impact: Proposed studies to understand how different pulmonary viral infections alter DCC dormancy and host immune responses, to determine the consequences for progression to metastatic disease, and to explore underlying mechanisms, should yield valuable and actionable insight into the key cell types and molecular mediators, informing early detection and prevention strategies for at-risk individuals.", "keywords": [ "2019-nCoV", "Acute", "Affect", "B-Lymphocytes", "Biological Markers", "Breast", "Breast Cancer Model", "Bronchus-Associated Lymphoid Tissue", "CD4 Positive T Lymphocytes", "CD8-Positive T-Lymphocytes", "COVID-19", "COVID-19 pandemic", "Cancer Patient", "Cancer Survivor", "Cells", "Cessation of life", "Data", "Development", "Diagnosis", "Disease", "Early Diagnosis", "Epidemic", "Epithelial Cells", "Genetic Transcription", "IL6 gene", "Immune", "Immune response", "Individual", "Infection", "Inflammation", "Inflammatory", "Influenza", "Interleukin-6", "Intervention", "Link", "Lung", "Lung infections", "Lymphocytic choriomeningitis virus", "Lymphoid Tissue", "Maintenance", "Malignant Breast Neoplasm", "Malignant Neoplasms", "Malignant neoplasm of lung", "Mediating", "Mediator", "Mesenchymal", "Metastatic Neoplasm to the Lung", "Metastatic/Recurrent", "Modeling", "Molecular", "Mus", "Neoplasm Metastasis", "Pathway interactions", "Persons", "Phase", "Phenotype", "Prevalence", "Prevention strategy", "Primary Neoplasm", "Proliferating", "Relapse", "Research", "Respiratory Tract Infections", "Risk", "Risk Reduction", "Role", "SARS-CoV-2 infection", "Seasons", "Signal Pathway", "Signal Transduction", "Source", "Testing", "Tissues", "Upregulation", "Viral", "Viral Respiratory Tract Infection", "Virus", "Virus Diseases", "cancer cell", "cell type", "cigarette smoking", "cytokine", "epidemiology study", "experience", "influenza infection", "influenzavirus", "insight", "mouse model", "pandemic disease", "prevent", "programs", "progression risk", "respiratory", "response", "risk mitigation", "seasonal influenza" ], "approved": true } }, { "type": "Grant", "id": "15600", "attributes": { "award_id": "1K23AI187708-01", "title": "Active and passive humoral immunity to enteric adenovirus infection in Bangladeshi children", "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": 7031, "first_name": "RUTH HUAB", "last_name": "Florese", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-03-01", "end_date": "2030-02-28", "award_amount": 192260, "principal_investigator": { "id": 32098, "first_name": "Jennifer Marie", "last_name": "Hendrick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 908, "ror": "https://ror.org/0153tk833", "name": "University of Virginia", "address": "", "city": "", "state": "VA", "zip": "", "country": "United States", "approved": true }, "abstract": "Candidate: I am an Assistant Professor at the University of Virginia (UVA) in the Division of Infectious Disease and International Health and a KL2- Funded Scholar in the Integrated Translational Health Research Institute of Virginia (iTHRIV) Scholars Program. I have pursued research in host pathogen immune interactions with Dr. William Petri for the past 6 years. Beginning initially with enteric pathogens and shifting to SARS-CoV-2 during the pandemic, I will now return to my work in diarrheal disease utilizing my background in viral immunology through study of adenovirus (AdV) 40/41 infection, a major cause of childhood diarrheal illness in low- and middle- income countries (LMIC). Career Development Plan/Career Goals & Objectives: My goal is to become an independent translational investigator. I will do so by furthering my knowledge base in the design of clinical trials, host pathogen immune interactions, viral immunology and data analysis. I will utilize my advisory committee who are not only successfully funded researchers but have a proven track record for mentoring young physician scientists. Research Plan: Characterize the systemic and mucosal immune response to AdV 40/41 infection in children in Bangladesh and determine the efficacy breast milk antibodies in providing passive immunity. Aim 1 (PASSIVE IMMUNITY): (1A) Describe the antibody repertoire to AdV 40/41 in the breast milk of mothers of Bangladeshi children using a novel protein microarray and (1B) determine their association with infection in the first 2 years of life. Plan: Determine maternal breast milk antibody breadth and magnitude, and test for its association to infant infection. Aim 2 (ACTIVE IMMUNITY): Characterize the antibody responses to AdV 40/41 infection in Bangladeshi children and test for their association with subsequent infection utilizing longitudinal (2A) serum and (2B) stool samples. Plan: Describe mucosal and systemic antibody scope and magnitude and test for association with protection from subsequent infection. Mentor/Co-Mentor(s), and Collaborator(s): The primary mentor of this K23, Dr. Petri, has a 30-year record of NIH Funding and has mentored 10 prior K awardees, 6 of whom have already made the K to R transition. My mentors include experts in immunology, virology, childhood diarrheal disease and statistics. Environment and Institutional Commitment to the Candidate: The intellectual environment at UVA is robust. I have a strong commitment from my Department and Division assuring 90% protected research time regardless of the outcome of this K23 proposal, and support of my continued mentorship under Dr. Petri at UVA.", "keywords": [ "2 year old", "2019-nCoV", "5 year old", "Active immunity", "Address", "Adenovirus Protein", "Adenoviruses", "Advisory Committees", "Affect", "Antibodies", "Antibody Repertoire", "Antibody Response", "Antigens", "Bangladesh", "Bangladeshi", "Biometry", "Birth", "Cause of Death", "Child", "Childhood", "Clinical Trials Design", "Cohort Studies", "Communicable Diseases", "Data", "Data Analyses", "Development", "Development Plans", "Diarrhea", "Disease", "Enteral", "Environment", "Faculty", "Feces", "Fellowship", "Filtration", "Funding", "Goals", "Growth", "Health", "Human Milk", "Humoral Immunities", "Immune", "Immune Targeting", "Immune response", "Immunity", "Immunology", "Infant", "Infection", "Institution", "Internal Medicine", "International", "Intervention", "Knowledge", "Life", "Longitudinal cohort", "Maternal antibody", "Measures", "Mentors", "Mentorship", "Morbidity - disease rate", "Mothers", "Mucosal Immune Responses", "Mucous Membrane", "Outcome", "Passive Immunity", "Passive Transfer of Immunity", "Physicians", "Plasma", "Polymerase Chain Reaction", "Population", "Population Attributable Risks", "Protein Microchips", "Publishing", "Recurrent disease", "Reproducibility", "Research", "Research Institute", "Research Personnel", "Residencies", "Sampling", "Scholars Program", "Scientist", "Serum", "Testing", "Time", "Translational Research", "United States National Institutes of Health", "Universities", "Vaccination", "Viral", "Virginia", "Virus", "Work", "biobank", "career", "career development", "cohort", "cost effective", "design", "diarrheal disease", "efficacy evaluation", "enteric adenovirus infection", "enteric infection", "enteric pathogen", "infant infection", "innovation", "insight", "knowledge base", "low and middle-income countries", "low income country", "maternal vaccination", "member", "molecular diagnostics", "mortality", "neurodevelopment", "novel", "pandemic disease", "pathogen", "prevent", "professor", "recurrent infection", "response", "statistics", "stool sample", "translational health science", "translational scientist", "vaccination strategy", "vaccine development", "virology" ], "approved": true } }, { "type": "Grant", "id": "15617", "attributes": { "award_id": "1R01AI189657-01", "title": "Synergistic Nanobodies for Pandemic Preparedness", "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": 6115, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-02-24", "end_date": "2030-01-31", "award_amount": 867563, "principal_investigator": { "id": 32114, "first_name": "JOHN D.", "last_name": "AITCHISON", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32115, "first_name": "MICHAEL P", "last_name": "ROUT", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 763, "ror": "https://ror.org/0420db125", "name": "Rockefeller University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Betacoronaviruses (beta-CoVs), including SARS-CoV-1, MERS-CoV, and SARS-CoV-2, have reshaped our understanding of pandemic preparedness. These viruses demonstrate a remarkable ability to mutate and evade defenses, continuing to infect populations worldwide despite extensive vaccination efforts and antiviral therapies. The chameleon-like nature of SARS-CoV-2, particularly its modifications to the Spike protein, consistently outpaces existing countermeasures, necessitating new strategies. This proposal introduces a pioneering class of nanobodies (Nbs), engineered from the immune system of llamas, designed to provide comprehensive protection against all beta-CoVs. These biologics not only advance treatment but also signify a pivotal step in pandemic preparedness, equipping us to outpace the relentless evolution of beta-CoVs. Our innovation lies in developing multivalent, synergistic combinations of broad-spectrum, high-efficacy Nbs. By harnessing these combinations, we amplify their efficacy and scope, concurrently increasing their resistance to viral mutations. Administered intranasally or directly to the lungs, these Nbs serve as both prophylactics and therapeutic agents. Our first Aim is to strategically expand upon our proven repertoires to identify, isolate, and characterize a much larger and more diverse repertoire of Nbs that collectively are strongly neutralizing across the beta-CoVs. We will use cutting-edge methods to produce diverse Nbs from llamas exposed to spike proteins of various beta- CoVs, selecting those with high affinity, specificity, and stability. We aim to discover synergistic, escape-resistant Nb pairs through combination testing and structural analysis. In our second Aim, we will optimize critical parameters important for developing broadly neutralizing Nb combinations and derivatives for human use. We will evaluate the in vivo synergistic potential of Nbs targeting major threats like MERS-CoV and SARS-CoV-2, and engineer Nbs to optimize their properties and efficacy in preparation for clinical trials. Deploying these pre- programmed Nbs at an outbreak's onset will protect first responders and medical personnel, reduce hospital surges, limit transmission, and buy time for new vaccine development and rollout. They will also provide crucial support to immunocompromised individuals, safeguarding the most vulnerable from the start. We hypothesize that our synergistic Nb combinations will introduce new beta-CoV neutralization methods, effectively prevent and treat infections, and maintain efficacy against emerging beta-CoV threats.", "keywords": [ "2019-nCoV", "Acceleration", "Affinity", "Anti-viral Therapy", "Antibodies", "Binding", "Biological Products", "Cells", "Clinical Trials", "Collaborations", "Development", "Disease Outbreaks", "Ensure", "Evolution", "Exhibits", "Exposure to", "Future", "Health Personnel", "Hospitals", "Human", "Immunocompromised Host", "Individual", "Infection", "Inhalators", "Intranasal Administration", "Llama", "Lung", "Membrane Glycoproteins", "Methods", "Middle East Respiratory Syndrome Coronavirus", "Modification", "Monoclonal Antibodies", "Mutate", "Mutation", "Nature", "Outcome", "Population", "Preparation", "Prevention", "Property", "Proteins", "Readiness", "Resistance", "SARS coronavirus", "SARS-CoV-2 variant", "Shapes", "Specificity", "Sum", "System", "Testing", "Therapeutic Agents", "Time", "Vaccination", "Variant", "Viral", "Virus", "betacoronavirus", "biophysical properties", "design", "first responder", "global health", "immunoengineering", "immunogenicity", "in vivo", "innovation", "insight", "nanobodies", "nanoengineering", "novel vaccines", "pandemic disease", "pandemic preparedness", "prevent", "prophylactic", "respiratory virus", "stem", "synergism", "transmission process", "vaccine development", "vaccine distribution" ], "approved": true } }, { "type": "Grant", "id": "15651", "attributes": { "award_id": "2501232", "title": "Advantaging the National Artificial Intelligence Research Resource (NAIRR) Pilot: Leveraging the COVID-19 HPC Consortium Experience", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Unknown", "NAIRR-Nat AI Research Resource" ], "program_reference_codes": [], "program_officials": [ { "id": 32154, "first_name": "Sharon", "last_name": "Geva", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-02-15", "end_date": null, "award_amount": 896755, "principal_investigator": { "id": 32155, "first_name": "John", "last_name": "Towns", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 15575, "first_name": "Christine R", "last_name": "Kirkpatrick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 281, "ror": "", "name": "University of Illinois at Urbana-Champaign", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "This project supports the broader efforts of the National Artificial Intelligence Research Resource (NAIRR) Pilot to address how powerful Artificial Intelligence (AI) resources can be used to accelerate scientific understanding and discovery and further the capabilities of AI models. It also develops efficient processes for providing these resources to researchers. This project builds on the successful model of, and lessons learned from, the COVID-19 HPC Consortium (C19HPCC), which demonstrated the power of public-private partnerships in addressing global challenges. By applying these lessons to the NAIRR Pilot, the project creates a robust framework for future government-academia-industry collaborations. This not only enhances the NAIRR Pilot but also paves the way for the full NAIRR program, ultimately supporting a broader range of research efforts and fostering innovation in artificial intelligence. The project leverages lessons learned from the C19HPCC to enhance the National Artificial Intelligence (NAIRR) Pilot. The C19HPCC was a collaborative effort that brought together high-performance computing (HPC) resources from government, academia, and industry to accelerate research and discovery in the fight against COVID-19. The primary goals are to develop efficient processes for allocating AI resources, improve proposal review mechanisms, establish effective reporting methods, foster partnerships across government, academia, and industry, and establish and evolve governance structures and coordination mechanisms to manage the diverse set of resources and stakeholders involved. The scope includes leveraging prior policies, procedures, and tools from the C19HPCC to support the NAIRR Pilot and ultimately the full NAIRR program. By applying these methods, the project aims to create a robust framework for future AI research and innovation. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15613", "attributes": { "award_id": "1K99ES036168-01A1", "title": "Environmental mixtures, immune function, and vaccine antibody response in children", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Environmental Health Sciences (NIEHS)" ], "program_reference_codes": [], "program_officials": [ { "id": 32109, "first_name": "Ashlinn Ko", "last_name": "Quinn", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-02-04", "end_date": "2027-01-31", "award_amount": 126985, "principal_investigator": { "id": 32110, "first_name": "Mike Zhongyu", "last_name": "He", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "I am an environmental epidemiologist and exposure scientist by training with a primary research interest in the impact of environmental exposures on immune function and vaccine response – a critical public health issue highlighted by COVID-19. The goal of this proposal is to obtain training and acquire the skills necessary to become an independent investigator at the air pollution-immunology-infectious disease nexus. I have assembled a world-class mentoring team with interdisciplinary expertise in immunology, toxicology, biostatistics, data science, exposure science, exposomics, and epidemiology. The proposed training plan includes formal coursework, field work, clinical observations, laboratory rotations, academic meetings and conferences, and a variety of activities designed for leadership and professional development. I am confident that by the end of the K99 phase of this proposal, my existing expertise combined with the training proposed in this project will allow me to establish myself as an independent investigator in a tenure-track faculty position, with the skillset to build my future independent research program integrating exposure science, epidemiology, and infectious diseases. For this proposal, I will leverage the Programming Research in Growth, Environment and Social Stress (PROGRESS) cohort, an ongoing longitudinal pregnancy/birth cohort based in Mexico City to investigate the impact of ambient environmental pollutants on the antibody response to routine vaccinations. Specifically, I will: 1) build a daily ozone model for Mexico City, which will be integrated with our existing models for fine particulate matter, nitrogen dioxide, and temperature that already exists for the area; 2) assess the association between these ambient environmental pollutants with vaccine antibody levels to routine vaccinations; 3) assess the association between the same pollutants and levels of several specific cell types involved in vaccine response; and 4) explore whether the associations between ambient environmental pollutants and vaccine antibody levels are partially or fully mediated through the immune cell population subsets assessed in #3). This research proposal has several innovations, including the generation of new exposure data (the first of its kind in Mexico City), the use of cutting-edge statistical approaches, and its leverage of both extant data and new measurements that addresses a unique research question while maximizing cost effectiveness. If successful, this work will be able to significantly foster interdisciplinary research and advance our understanding of a critical and urgent public health issue.", "keywords": [ "Address", "Adult", "Affect", "Age", "Air Pollution", "Antibodies", "Antibody Repertoire", "Antibody Response", "Applied Skills", "Area", "Attenuated", "Attenuated Vaccines", "Biological", "Biometry", "Birth", "COVID-19", "COVID-19 pandemic", "Cells", "Child", "Child Development", "Childhood", "Cities", "Climate", "Clinical", "Collaborations", "Communicable Diseases", "Complement", "Data", "Data Science", "Development", "Developmental Process", "Disease", "Environment", "Environmental Exposure", "Environmental Impact", "Environmental Pollutants", "Environmental Risk Factor", "Epidemiologist", "Epidemiology", "Epigenetic Process", "Exposure to", "Faculty", "Flow Cytometry", "Fostering", "Future", "Gases", "Generations", "Goals", "Growth", "Health", "Immune", "Immune system", "Immunity", "Immunologics", "Immunology", "Immunophenotyping", "Individual", "Innate Immune Response", "Innate Immune System", "Interdisciplinary Study", "Joints", "Laboratories", "Leadership", "Leukocytes", "Life", "Life Cycle Stages", "Link", "Literature", "Long-Term Effects", "Measurement", "Mediating", "Mentors", "Metabolic", "Mexico", "Modeling", "Modification", "Nitrogen Dioxide", "Ozone", "Participant", "Pathway interactions", "Perinatal", "Peripheral Blood Mononuclear Cell", "Phase", "Population", "Positioning Attribute", "Predictive Factor", "Pregnancy", "Public Health", "Research", "Research Personnel", "Research Proposals", "Resolution", "Risk Factors", "Role", "Rotation", "Sampling", "Science", "Scientist", "Statistical Methods", "Systems Development", "T-Lymphocyte Subsets", "Temperature", "Tissue Differentiation", "Toxicology", "Training", "Vaccination", "Vaccines", "Work", "adaptive immune response", "ambient air pollution", "career", "cell type", "cohort", "cost effectiveness", "design", "early childhood", "exposomics", "fine particles", "future pandemic", "immune function", "in utero", "infancy", "innovation", "insight", "interest", "late life", "meetings", "methylomics", "nanoparticle", "pandemic disease", "peripheral blood", "pollutant", "prenatal", "preservation", "prevent", "programs", "response", "skill acquisition", "skills", "social stress", "symposium", "tenure track", "vaccine failure", "vaccine response", "vaccine-induced antibodies" ], "approved": true } }, { "type": "Grant", "id": "15616", "attributes": { "award_id": "1R01AI185617-01A1", "title": "RNA epigenetic modifications in 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": 27781, "first_name": "Mary Katherine Bradford", "last_name": "Plimack", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-02-01", "end_date": "2030-01-31", "award_amount": 582618, "principal_investigator": { "id": 26224, "first_name": "Jianrong", "last_name": "Li", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32113, "first_name": "Mark E.", "last_name": "Peeples", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 778, "ror": "", "name": "OHIO STATE UNIVERSITY", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Post-transcriptional RNA modifications are widespread and regulates numerous biological processes including RNA metabolism, protein translation, gene expression, and disease. Among the more than 180 types of RNA modifications, N6-methyladenosine (m6A) and pseudouridine (Ψ) are the two most prevalent. The m6A modification is catalyzed by the host RNA methyltransferase complex of METTL3 and METTL14. The Ψ modification is converted from the nucleoside uridine (U) by the host pseudouridine synthases (PUSs). Despite being discovered in the 1950s, the biological functions of the m6A and Ψ modifications in the context of virus infection remain poorly understood. This project is built upon our recent development of high throughput sequencing techniques that have enabled mapping of m6A and ψ sites at a single base resolution. Using these techniques, we discovered that SARS-CoV-2 RNA isolated from well-differentiated primary human bronchial epithelial (HBE) cultures that include their in vivo target cells is heavily modified with m6A and ψ. In addition, we have found that depletion of several m6A and ψ writer proteins decreases SARS-CoV-2 replication in HBE culture. These findings led to our hypothesis that SARS-CoV-2 acquires m6A and Ψ modifications in its RNA to maximize virus replication. Thus, the goal of this project is to determine the mechanisms by which RNA m6A and ψ modifications modulate SARS-CoV-2 replication, gene expression, innate and adaptive immunity, and pathogenesis. In Aim 1, we will use a CRISP-Cas 9 technique to knock out host RNA m6A methyltransferases and PUSs in HBE cultures to determine the role(s) of m6A and Ψ modifications in the SARS-CoV-2 life cycle. We will also use knockout mice to examine the role(s) of m6A and Ψ modification in SARS-CoV-2 replication in vivo. We will also identify the specific PUS enzyme(s) that catalyze pseudouridylation on SARS-CoV-2 RNA. In Aim 2, we will mutate the m6A and/or ψ sites in the SARS-CoV-2 genomic RNA and use the reverse genetics system to generate recombinant SARS-CoV-2 lacking m6A and/or ψ modification sites and use them to determine the roles of m6A and ψ modifications on viral RNA metabolism, encapsidation, RNA replication, viral protein translation, and innate immunity. In Aim 3, we will determine whether m6A and ψ modifications modulate mucosal and adaptive immune responses of SARS-CoV-2 live attenuated vaccines (LAVs) and determine whether LAVs lacking m6A and/or ψ are more immunogenic in golden Syrian hamsters. Upon completion of this project, we expect to have unravelled the mechanisms by which m6A and Ψ modifications modulate the SARS- CoV-2 replication cycle, leading to the development of novel and improved LAVs and therapies for COVID-19 that target these RNA modifications.", "keywords": [ "2019-nCoV", "Adenosine", "Anti-viral Agents", "Anti-viral Therapy", "Antibodies", "Attenuated", "Attenuated Vaccines", "B-Lymphocytes", "Biological Process", "COVID-19", "COVID-19 treatment", "COVID-19 vaccine", "Carbon", "Cells", "Cessation of life", "Collaborations", "Complementary DNA", "Complex", "Development", "Disease", "Effectiveness", "Enzymes", "Epigenetic Process", "Exposure to", "Gene Expression", "Genetic Recombination", "Genetic Transcription", "Goals", "Hamsters", "High-Throughput Nucleotide Sequencing", "High-Throughput RNA Sequencing", "Human", "Immune response", "Infection", "Innate Immune Response", "Intramuscular", "Isomerism", "Knock-out", "Knockout Mice", "Life Cycle Stages", "Maps", "Mediating", "Mesocricetus auratus", "Methylation", "Methyltransferase", "Modeling", "Modification", "Mucosal Immune Responses", "Mucous Membrane", "Mutate", "Natural Immunity", "Nucleosides", "Nucleotides", "Pathogenesis", "Pharmaceutical Preparations", "Positioning Attribute", "Post-Transcriptional RNA Processing", "Process", "Proteins", "Pseudouridine", "Public Health", "RNA", "RNA Stability", "RNA metabolism", "RNA purification", "RNA replication", "Reader", "Recombinants", "Resolution", "Role", "Rotation", "SARS-CoV-2 immunity", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "Signal Transduction", "Site", "Small Interfering RNA", "Societies", "System", "T-Lymphocyte", "Techniques", "Therapeutic Agents", "Translations", "Uridine", "Vaccines", "Viral Pathogenesis", "Viral Proteins", "Virus Diseases", "Virus Replication", "adaptive immune response", "adaptive immunity", "attenuation", "base", "bronchial epithelium", "genomic RNA", "immunogenic", "improved", "in vivo", "knock-down", "mRNA Translation", "novel", "novel therapeutics", "novel vaccines", "obligate intracellular parasite", "prevent", "public health relevance", "reverse genetics", "small hairpin RNA", "targeted treatment", "transmission process", "vaccine delivery", "variants of concern", "viral RNA" ], "approved": true } } ], "meta": { "pagination": { "page": 3, "pages": 1392, "count": 13920 } } }