Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=5&sort=-principal_investigator
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-principal_investigator", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=-principal_investigator", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=6&sort=-principal_investigator", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=-principal_investigator" }, "data": [ { "type": "Grant", "id": "16086", "attributes": { "award_id": "1F31AA033272-01", "title": "Modeling Peer Network Dynamics and Alcohol Use Throughout High School", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [ { "id": 44563, "first_name": "BEVERLY", "last_name": "RUFFIN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-01", "end_date": "2028-12-01", "award_amount": 50114, "principal_investigator": { "id": 44564, "first_name": "Kristina", "last_name": "Miljkovic", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3495, "ror": "", "name": "UNIVERSITY OF SOUTHERN CALIFORNIA", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Statement/Abstract. Adolescent alcohol use remains a major public health concern in the United States, with early initiation linked to long-term mental and physical health risks. Although overall prevalence has been declining in recent years, adolescents today engage in riskier patterns of alcohol consumption than before, including binge drinking and alcohol-induced blackouts. Peer relationships are a key influence on adolescent alcohol use. Adolescents both select peers with similar behaviors (peer selection) and are also influenced by their peers’ behaviors (peer influence). Social network analysis offers a powerful framework for examining these peer processes, but conceptual and methodological gaps remain in understanding how, when, and for whom they matter. Most existing studies rely on data collected in the 1990s and early 2000s, which do not account for the increasingly digital age and COVID-19 pandemic, both of which have shifted socialization. In addition, studies often assume that the effect of peer influence is constant across adolescence and overlook individual differences in network position or demographic characteristics like sex. This project will address those limitations using data from an NIH-funded, recently collected (2020-2024) longitudinal cohort study of high school students in Southern California. More than 3,000 students were surveyed once per semester throughout all of high school, resulting in eight waves of data on friendship nominations, alcohol use, and demographic characteristics. Retention exceeded 80% across all eight waves. These data provide a unique opportunity to model peer dynamics throughout high school as they relate to alcohol use. The project has three aims: 1) assess whether the association between peer alcohol exposure and individual use is moderated by an adolescent’s position in the network (i.e., centrality), 2) examine how alcohol use similarity contributes to the formation and dissolution of adolescent friendships and whether this differs by sex, and 3) determine when peer influence is most impactful during high school. This study will use lagged logistic regression models, temporal exponential random graph models, and time-varying effect modeling to test these three aims. This research will address key gaps in adolescent alcohol research by identifying who is most vulnerable to peer influence, how peer selection operates, and when prevention efforts may be most impactful. Findings will inform the development of network-based, developmentally timed prevention strategies and advance understanding of the social and developmental etiology of alcohol use. This project also offers a rigorous training platform in longitudinal network analysis and adolescent alcohol use, supporting the applicant’s development as an NIH-funded prevention scientist.", "keywords": [ "Adolescence", "Adolescent", "Adolescent Risk Behavior", "Adult", "Age", "Alcohol consumption", "Alcohols", "Behavior", "Beverages", "COVID-19 pandemic", "California", "Characteristics", "Consumption", "Data", "Development", "Distance Learning", "Etiology", "Exhibits", "Exposure to", "Friends", "Friendships", "Funding", "Future", "Graph", "Health", "Health behavior", "High School Student", "Home", "Individual", "Individual Differences", "Industry", "Influentials", "Intervention", "Link", "Logistic Regressions", "Longitudinal", "Longitudinal cohort study", "Maintenance", "Mental Depression", "Mental Health", "Methodology", "Modeling", "Network-based", "Pathway Analysis", "Pattern", "Peer Pressure", "Positioning Attribute", "Predisposition", "Prevalence", "Prevention", "Prevention strategy", "Process", "Public Health", "Reporting", "Research", "Risk", "Role", "Scientist", "Shapes", "Social Network", "Socialization", "Structure", "Students", "Surgeon", "Surveys", "System", "Techniques", "Testing", "Theoretical model", "Time", "Training", "United States", "United States National Institutes of Health", "Youth", "adolescent health", "adolescent substance use", "alcohol exposure", "alcohol measurement", "alcohol research", "alcohol use disorder", "binge drinking", "boys", "cohort", "community-level factor", "digital", "drinking", "girls", "high intensity drinking", "high school", "innovation", "insight", "later life", "liver injury", "novel", "peer", "peer influence", "peer networks", "physical conditioning", "post-pandemic", "sex", "sex variable", "social", "social factors", "social norm", "twelfth grade", "underage drinking" ], "approved": true } }, { "type": "Grant", "id": "16084", "attributes": { "award_id": "1U44TR004958-01A1", "title": "Industrial production of milk extracellular vesicles for dual-use as a systemic radiotherapeutic medical countermeasure and cancer adjuvant therapy", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Advancing Translational Sciences (NCATS)" ], "program_reference_codes": [], "program_officials": [ { "id": 44561, "first_name": "CHRISTINE MARIE", "last_name": "HAPPEL", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-01", "end_date": "2028-06-30", "award_amount": 985974, "principal_investigator": { "id": 44562, "first_name": "Spencer Reid", "last_name": "Marsh", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3494, "ror": "", "name": "TINY CARGO COMPANY, THE", "address": "", "city": "", "state": "VA", "zip": "", "country": "United States", "approved": true }, "abstract": "The Tiny Cargo Company has developed a novel therapeutic called XoLactatm comprised of milk-derived extracellular vesicles (mEVs) loaded with a drug that promotes regenerative healing of the gastrointestinal (GI) tract and bone marrow when given following exposure to high dose ionizing radiation (IR). Tiny Cargo is actively meeting with the FDA (PIND#167551) to gain regulatory approval under the Animal Rule for XoLacta to meet the dire unmet needs of: A) Radiotherapeutic Medical Countermeasure, and; B) Dual-Use Radiotherapeutic Adjuvant treatment during Radiation Therapy. Aided by our selection by BARDA to participate in the BlueKnight program, our initial customer will be the US Strategic National Stockpile – a potential multi-billion dollar order. Our patent portfolio includes an exclusive license from Virginia Tech on pending patents with confirmed FTO for: 1) Methods for industrial purification of mEVs from milk; 2) Compositions and methods for mEV loading necessary for preparation of XoLacta; 3) Methods for non-cold chain storage of XoLacta; 4) Methods for enhancing mEV targeting and uptake in diseased tissues; and 5) Methods for use of XoLacta as an orally available radiotherapeutic. Importantly, beyond XoLacta, Tiny Cargo’s innovative mEV isolation method and ester-based drug loading approach provide a true platform for oral systemic delivery of other therapeutic and nutraceutical molecules by mEVs. Our drug is a novel esterified composition called αCT11-4Ome based on the CT-most 9 amino acids of gap junctional Cx43, a therapeutic of proven clinical efficacy when applied topically to radiation burns, which is currently in late-stage clinical testing. Importantly, Tiny Cargo has completed successful studies wherein orally administered XoLacta increased survival of C57BL/6 mice by >40% following lethal IR (14 Gy) — accompanied by regenerative healing of the GI tract and bone marrow in treated animals. These landmark results have led to more than $4m in funding to support toxicology testing, Phase I clinical testing in humans and pivotal studies in a large animal model under the FDA Animal Rule. In this application we propose to advance XoLacta storage properties, breaking reliance on cold-chain, as exemplified by COVID vaccines. Our preliminary data indicates that mEVs lyophilized in our proprietary formulation retain >95 % structure and bioactivity after 6 months storage at 20°C. Building on these results, Tiny Cargo seeks to: 1) Optimize lyophilization of XoLacta at industrial scale, potentially enabling storage of our product at 20°C for up to 12 months; and 2) Establish GMP production of XoLacta. Under guidance by the FDA, Tiny Cargo plans to clinically test XoLacta, which will require pharmaceutical-grade therapeutic produced at scale to GMP standards. This will be done by Tiny Cargo at the worlds’ first industrial milk extracellular vesicle production plant. GMP levels established at our industrial facility will guarantee consistent manufacture of active product under exacting environmental monitoring programs, including strict adherence to cleanroom standards. Pertinent to this objective, we have an active contract with Jeff Yuen & Associates to ensure adherence to GMP guidelines during construction and operation of our plant. The GMP mEVs will be used to both formulate XoLacta and also provide GMP dairy ingredients to industrial giant Fonterra, who wishes to sell our mEVs as a novel dairy ingredient. Successful completion of the industrialization work of our two aims will facilitate entry into clinical testing and enable ongoing FDA review of orally administered XoLacta as a systemic treatment for high-dose radiation, as well as potential revenue through sale of mEVs to customers such as Fonterra. Beyond development of XoLacta as an RT MCM as detailed herein, Tiny Cargo is planning clinical programs that will enable dual-use regulatory approval of XoLacta for treating side-effects of radiation therapy in cancer patients.", "keywords": [ "Adherence", "Adjuvant Therapy", "Amino Acids", "Animal Model", "Animals", "Biochemistry", "Biological Assay", "Bone Marrow", "Bone Marrow Stem Cell", "Businesses", "C57BL/6 Mouse", "COVID-19 vaccine", "Cancer Patient", "Classification", "Clinical", "Clinical Research", "Cold Chains", "Communication", "Complex", "Connexin 43", "Consultations", "Contracts", "Dairying", "Data", "Development", "Disease", "Documentation", "Dose", "Drug Kinetics", "Electron Microscopy", "Ensure", "Environmental Monitoring", "Esterification", "Esters", "Exposure to", "Fluorescence", "Food", "Formulation", "Freeze Drying", "Funding", "Gap Junctions", "Gastrointestinal tract structure", "Grant", "Guidelines", "Human", "Human Resources", "In Vitro", "Industrialization", "Investments", "Ionizing radiation", "Kilogram", "Legal patent", "Licensing", "Malignant Neoplasms", "Measures", "Mediation", "Methods", "Milk", "Modeling", "Monitor", "National Center for Advancing Translational Sciences", "Nutraceutical", "Oral", "Oral Administration", "Organ", "Patients", "Peptides", "Pharmaceutical Preparations", "Pharmacologic Substance", "Phase", "Phase I Clinical Trials", "Plants", "Powder dose form", "Preparation", "Procedures", "Process", "Production", "Property", "Protocols documentation", "Quality Control", "Radiation Dose Unit", "Radiation Injuries", "Radiation exposure", "Radiation therapy", "Regulation", "Regulatory approval", "Reproducibility", "Safety", "Sales", "Secure", "Sorting", "Source", "Structure", "System", "Temperature", "Testing", "Therapeutic", "Tissues", "Topical application", "Toxicology", "Training Programs", "Validation", "Vesicle", "Virginia", "Western Blotting", "Whole-Body Irradiation", "Work", "animal rule", "calcein AM", "clinical efficacy", "cost", "efficacy study", "extracellular vesicles", "gastrointestinal", "in vivo", "industrial production", "innovation", "manufacture", "manufacturing facility", "manufacturing process", "medical countermeasure", "meetings", "milk production", "novel", "novel therapeutics", "operation", "preservation", "programs", "radiation burn", "radiation mitigation", "regenerative healing", "regenerative therapy", "research clinical testing", "safety study", "safety testing", "side effect", "small molecule", "uptake", "zeta potential" ], "approved": true } }, { "type": "Grant", "id": "16079", "attributes": { "award_id": "1F31AI200156-01", "title": "Dissection of functional 5' UTR elements that repress SARS-CoV-2 Nsp1 activity", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-01", "end_date": "2029-06-30", "award_amount": 43869, "principal_investigator": { "id": 44558, "first_name": "Jacob Stephen", "last_name": "Horn", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "SARS-CoV-2 protein nonstructural protein 1 (Nsp1) induces a global translation shutdown in host cells upon infection. Irrespective of mechanism, the Nsp1 imparted translation shutdown is required for efficient viral replication and to suppress the host immune response. Thus, fully understanding this protein involves understanding how it interacts with viral components and host machinery. The viral genome can escape the translational shutdown via secondary structure in its 5’ untranslated region (UTR). The first hairpin structure, stem-loop 1 (SL1), has been identified as necessary and sufficient to evade Nsp1-mediated translation shutdown. Previous reports show that host genes are suppressed differently by Nsp1. For example, translation- related genes, especially those with terminal oligopyrimidine (TOP) motifs, are translated more efficiently in the presence of Nsp1, while immune response genes are suppressed. Despite proven significant impacts of the 5’ UTR of SARS-CoV-2 and host genes, other elements remain understudied in this interaction with Nsp1. Therefore, this work examines if the 5’ UTR has other functional regions that might influence translational control and evasion of the translational shutdown. This research utilizes a recently developed method called direct analysis of ribosome targeting (DART), a high throughput method that tests the ribosome recruitment ability of thousands of 5’ UTRs. To analyze RNA features of SARS-CoV-2 and host genes that impact ribosome recruitment, a diverse pool of viral and host sequences was generated to allow thorough examination of each region of the 5’ UTR and its role in translation and evasion of host shutdown. The pool includes all known natural mutations reported in the NCBI virus sequence repository, along with systematic scanning, structural disrupting and compensatory mutations. Completing DART with and without Nsp1 will elucidate what elements facilitate translation and the evasion of Nsp1-mediated translational shutdown. The translation shutdown mechanism is thought to function through a two-pronged approach where the C-terminal domain binds the ribosome at the mRNA entry channel and sterically blocks RNAs from loading onto the ribosome, and the N-terminal domain (NTD) cleaves RNAs while bound to the ribosome, both activities preventing RNAs from being translated. However, it is unclear whether channel exclusion and cleavage are linked activities of Nsp1, or if different RNA features can mediate mRNA channel entry or escape of RNA cleavage. To address this, a high throughput cleavage experiment will be completed on pools of diverse RNAs to examine what host or viral features mediate resistance or susceptibility to cleavage, in ribosome-containing or depleted lysate. These cleavage experiments will be completed using the previously described RNA pool containing SARS-CoV-2 and immune related genes, along with another RNA pool of 24,000 sequences comprised of human genes, including translation-related sequences. This work will be instrumental for understanding the role of Nsp1 in coronavirus pathogenesis and to inform the design of future therapeutics.", "keywords": [ "2019-nCoV", "5' Untranslated Regions", "Address", "Affect", "Antisense Oligonucleotides", "Binding", "Biochemistry", "C-terminal", "COVID-19 pandemic", "Cells", "Chemicals", "Coronavirus", "Data", "Dissection", "Elements", "Exclusion", "Exonuclease", "Experimental Designs", "Future", "Genes", "Goals", "Human", "Immune", "Immune Response Genes", "Immune response", "Infection", "Integration Host Factors", "Left", "Link", "Measures", "Mediating", "Messenger RNA", "Methods", "Mutation", "N-terminal", "Nonstructural Protein", "Output", "Pathogenesis", "Predisposition", "Process", "Protein Binding Domain", "Proteins", "RNA", "RNA Viruses", "Regulatory Element", "Reporting", "Repression", "Research", "Resistance", "Ribosomal Interaction", "Ribosomes", "Role", "Scanning", "Structure", "Testing", "Therapeutic", "Transcript", "Translating", "Translation Initiation", "Translational Repression", "Translations", "Untranslated Regions", "Variant", "Viral", "Viral Genome", "Viral Physiology", "Virus", "Virus Replication", "Work", "betacoronavirus", "design", "experimental study", "future pandemic", "in vitro Assay", "mutant", "novel", "prevent", "recruit", "repository", "ribosome profiling", "stem", "targeted treatment", "therapeutic development", "therapeutic target", "translational impact", "viral RNA" ], "approved": true } }, { "type": "Grant", "id": "16078", "attributes": { "award_id": "1R01AI201635-01", "title": "Using albumin-hitchhiking intranasal vaccines to enhance immune protection against infectious disease", "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": 44528, "first_name": "AARON MICHAEL", "last_name": "JOFFE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-23", "end_date": "2031-06-30", "award_amount": 687661, "principal_investigator": { "id": 44557, "first_name": "Brittany L", "last_name": "Hartwell", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3492, "ror": "", "name": "UNIVERSITY OF MINNESOTA", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true }, "abstract": "To combat the global HIV epidemic as well as persisting threats such as SARS-CoV-2, immunization strategies are needed that elicit protection at mucosal portals of pathogen entry. However, traditional parenteral vaccines that are injected typically elicit poor mucosal immunity. While vaccination at mucosal surfaces is known to be an effective strategy to activate protective mucosal immunity, delivery of vaccine components across mucosal barriers has been a major challenge for mucosal vaccine development. Development of technologies to overcome barriers to mucosal delivery while meeting safety and efficacy requirements of prophylactic vaccines remains an urgent unmet need. While mucosal barriers are very good at keeping most vaccine components ‘out’, the endogenous protein albumin is known to be very good at getting ‘in’. Albumin, a major blood protein also present in mucosal fluids, is constitutively transcytosed across mucosal epithelium through interactions with the neonatal Fc receptor (FcRn) while functioning in vivo as a fatty acid transporter. Exploiting this biology, we recently developed a novel immunoengineering strategy of ‘albumin hitchhiking’ to promote mucosal immunity using an intranasal vaccine consisting of protein immunogens conjugated to an albumin-binding polymer-lipid tail, forming ‘amph-proteins’. Amph-proteins exhibit enhanced FcRn-dependent uptake into nasal mucosal tissue, leading to enhanced local immune responses in the nasal-associated lymphoid tissue (NALT) and robust long-lasting systemic and mucosal humoral responses in tandem. These results suggest that employing amph- vaccines to deliver antigen (Ag) and adjuvant across mucosal epithelium is a promising strategy to promote mucosal immunity against infectious diseases. Motivated by these findings, here we propose to further develop the amph-vaccine platform for mucosal delivery of a range of immune cargo (antigens and adjuvants) while identifying molecular and cellular mechanisms of action, immune correlates of protection, and the role of vaccine dosing and kinetics in mucosal associated lymphoid tissue (MALT) for promoting functional protective immunity in translational mouse models through the following aims. Aim 1: Identify molecular properties and kinetic mechanisms of intranasal amphiphile-antigen vaccines that drive mucosal humoral immune activation. Aim 2: Evaluate immunogenicity, adjuvanticity, and toxicity of intranasal amphiphile-antigen/adjuvant vaccines in a ‘dirty’ mouse model. Aim 3: Define mucosal vaccine kinetics that drive functional immune protection by evaluating efficacy of intranasal amph-vaccines in challenge models of SARS-CoV-2. Our central hypothesis is that i.n. amph-vaccines that exhibit enhanced mucosal uptake and persistence in NALT will better prime functional protective immunity against respiratory pathogens (demonstrated across multiple mouse models) by activating robust GC responses in NALT, generating a mucosal antibody response of greater magnitude, affinity, and breadth than soluble or parenteral controls.", "keywords": [ "2019-nCoV", "Adjuvant", "Adjuvanticity", "Affinity", "Albumins", "Antibody Response", "Antibody titer measurement", "Antigens", "Behavior", "Binding", "Biological Models", "Biology", "Blood Proteins", "Communicable Diseases", "Dose", "Drug Delivery Systems", "Epithelium", "Exhibits", "Fatty Acids", "Fc Receptor", "Future", "Genitourinary system", "Goals", "HIV", "HIV epidemic", "Immune", "Immune response", "Immune system", "Immunity", "Immunization", "Immunoglobulin A", "Immunoglobulin G", "Influenza", "K-18 conjugate", "Kinetics", "Licensure", "Lipids", "Liquid substance", "Lymphoid Tissue", "Modeling", "Molecular", "Molecular Conformation", "Mucosal Immunity", "Mucous Membrane", "Mus", "Nose", "Paper", "Polymers", "Preventive vaccine", "Property", "Proteins", "Respiratory System", "Role", "SARS-CoV-2 transmission", "Safety", "Serum", "Serum Proteins", "Site", "Structure of germinal center of lymph node", "Structure of mucous membrane of nose", "Subunit Vaccines", "Surface", "Tail", "Tissues", "Topical application", "Toxic effect", "Translational Research", "Translations", "Vaccination", "Vaccine Antigen", "Vaccines", "Variant", "Viral", "Wild Type Mouse", "amphiphilicity", "clinically relevant", "combat", "design", "efficacy evaluation", "germ free condition", "immune activation", "immunoengineering", "immunogen", "immunogenicity", "improved", "in vivo", "innovation", "insight", "meetings", "microbial", "mouse model", "mucosa-associated lymphoid tissue", "mucosal uptake", "mucosal vaccination", "mucosal vaccine", "neonatal Fc receptor", "nonhuman primate", "novel", "pathogen", "respiratory", "respiratory pathogen", "response", "spatiotemporal", "technology development", "tool", "trafficking", "translational medicine", "transmission process", "uptake", "vaccination strategy", "vaccine acceptance", "vaccine delivery", "vaccine development", "vaccine platform" ], "approved": true } }, { "type": "Grant", "id": "16077", "attributes": { "award_id": "1R01MH141161-01A1", "title": "Social experience guides BMA mediated social development", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 44555, "first_name": "ANDREW LEE", "last_name": "BREEDEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-25", "end_date": "2031-04-30", "award_amount": 465301, "principal_investigator": { "id": 44556, "first_name": "Nicole Christine", "last_name": "Ferrara", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3491, "ror": "", "name": "ROSALIND FRANKLIN UNIV OF MEDICINE & SCI", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "Social experiences are indispensable for mental health, and this is particularly important in younger populations where there is a developmental need for peer-peer social interactions. Atypical social experiences in the form of social isolation or deprivation became common during the COVID19 pandemic and have been particularly harmful for adolescent mental health. This can be seen with impaired age-specific social behaviors, like play in adolescent rats and investigation in adult rats. The poor social opportunity that arises from social deprivation alters brain function that contributes to adolescent vulnerabilities to social perturbations. The amygdala is a candidate brain region to investigate the impact of social deprivation on social development, as it is important for regulating social behavior and is sensitive to atypical social experiences. Adolescent amygdala maturation is epitomized by increases in inhibitory parvalbumin (PV) GABAergic tone and in activity evoked by the infralimbic region of the medial prefrontal cortex (IL). The adult basomedial amygdala (BMA) in particular receives dense inputs from the IL and is regulated by GABAergic neurons. Further, the adult BMA dynamically responds to social stimuli and is unique in that its activity directly correlates to the degree of social interaction. Our preliminary data show that BMA principal neuron activity regulates adolescent and adult social engagement. Within the BMA, we have identified IL inputs as a source of BMA principal neuron activation. This IL-evoked principal neuron activation is greater adolescents relative to adults, and the age-dependent reduction in IL-driven excitation is regulated by inhibitory GABAergic neurons in adults. However, it is unclear how social deprivation compromises unique developmental features of the BMA to subsequently impair social development. Our goal is to understand the initial effects of adolescent and adult social deprivation on BMA-driven changes in social behavior, as these initial changes will identify the adolescent-specific vulnerabilities when contrasted with adults. Our aims address a novel central hypothesis that social deprivation shapes BMA activity through reductions in principal neuron activity driven by the IL at both ages and reduction of PV activity in adults. This social deprivation-driven change to BMA activity impairs social interaction across ages. Our central hypothesis will be tested in three specific aims quantifying the contribution of excitation (Aim 1), PV activity (Aim 2), and the ILBMA pathway (Aim 3) to adult and adolescent social behavior and how this is neural circuitry is impacted by social deprivation. Each aim will use a combination of in vitro electrophysiology to mechanistically quantify BMA maturation, fiber photometry for functional changes in BMA activity time-locked to social investigation, and chemogenetics to understand the BMA regulation of adolescent and adult social behavior. The results from the proposed project are expected to create a novel framework through which social deprivation shapes BMA activation underlying adolescent and adult social dysfunction. This will identify distinguishing factors between ages that may contribute to age-specific mechanisms of social abnormalities and adolescent vulnerability to social perturbations.", "keywords": [ "Address", "Adolescence", "Adolescent", "Adult", "Age", "Amygdaloid structure", "Automobile Driving", "Behavior", "Brain", "Brain region", "COVID-19 pandemic", "Characteristics", "Complex", "Data", "Development", "Electrophysiology (science)", "Fiber", "Fluorescence", "Genetic", "Goals", "Impairment", "In Vitro", "Incidence", "Individual", "Interneurons", "Investigation", "Measures", "Medial", "Mediating", "Mental Health", "National Institute of Mental Health", "Neurons", "Parvalbumins", "Pathway interactions", "Photometry", "Play", "Population", "Prefrontal Cortex", "Rattus", "Regulation", "Role", "Shapes", "Social Behavior", "Social Development", "Social Interaction", "Social isolation", "Source", "Stimulus", "Testing", "Time", "Work", "adolescent mental health", "age group", "age related", "cognitive system", "deprivation", "ex vivo", "experience", "neural circuit", "neuromechanism", "neuropsychiatric disorder", "novel", "pandemic disease", "peer", "postsynaptic", "response", "social", "social contact", "social deficits", "social deprivation", "social engagement", "treatment strategy", "vulnerable adolescent" ], "approved": true } }, { "type": "Grant", "id": "16076", "attributes": { "award_id": "1R44TR006096-01", "title": "Enhanced nucleic acid therapeutics: synthetic sequence elements for boosting protein expression in genetic medicines", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Advancing Translational Sciences (NCATS)" ], "program_reference_codes": [], "program_officials": [ { "id": 44553, "first_name": "TYLER", "last_name": "BECK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-08", "end_date": "2028-05-31", "award_amount": 951630, "principal_investigator": { "id": 44554, "first_name": "Patrik", "last_name": "Engstrom", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3490, "ror": "", "name": "PRIMROSE BIO, INC.", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Nucleic acid-based medicines have demonstrated remarkable potential in preventing and treating a wide range of diseases, as exemplified by their crucial role in the COVID-19 pandemic response. However, several challenges remain, including inherent instability, manufacturing complexities, and the need for efficient delivery mechanisms. The development of new nucleic acidbased medicines offers potential solutions to these issues by reducing dosage requirements, lowering manufacturing costs, and improving efficacy. Noncoding sequence elements such as 5' untranslated regions and internal ribosome entry sites required for protein expression from these medicines offer promising targets to improve efficacy, lower manufacturing costs, and pave the way for the next generation of genetic medicines. In collaboration with an established mRNA medicines company, Primrose Bio has created a novel ultra-high-throughput platform for non-coding sequence element discovery and evolution. This platform has higher throughput and flexibility than other non-coding sequence discovery systems described to date and has unlimited potential to discover highly efficient synthetic non-coding sequence elements that stimulate protein expression. In this project, Primrose Bio will utilize this platform to create a panel of optimized synthetic 5' noncoding sequence elements for enhancing protein expression that can be seamlessly integrated into nucleic acid therapeutics. These sequences elements will be tested in partnership with SoCal Biosciences. The sequence elements developed in this program will find direct commercial outlets through existing and new partners developing disruptive therapies, such as cancer therapeutics.", "keywords": [ "5' Untranslated Regions", "Benchmarking", "Biological Sciences", "COVID-19 pandemic", "Cell Extracts", "Cell Line", "Cells", "Client", "Clinic", "Clinical", "Collaborations", "Collection", "DNA", "DNA Sequence", "Development", "Disease", "Elements", "Emulsions", "Evolution", "Genes", "Genetic Carriers", "Genetic Medicine", "Genetic Transcription", "Human", "Human Cell Line", "In Vitro", "Internal Ribosome Entry Site", "Libraries", "Malignant Neoplasms", "Medicine", "Messenger RNA", "Modification", "Nature", "Nucleic Acids", "Nucleotides", "Pharmacologic Substance", "Phase", "Primula", "Process", "RNA", "RNA Instability", "RNA Sequences", "Randomized", "Role", "Small Business Innovation Research Grant", "Support Contracts", "System", "Testing", "Therapeutic", "Translations", "Untranslated RNA", "Uridine", "Vaccines", "Validation", "artificial intelligence based", "commercialization", "commercialization readiness", "design", "disorder prevention", "dosage", "flexibility", "gene therapy", "genetic information", "high throughput screening", "human tissue", "improved", "innovation", "large scale production", "mRNA Expression", "manufacture", "manufacturing cost", "next generation", "novel", "nucleic acid-based therapeutics", "pandemic response", "prevent", "programs", "protein expression", "research and development", "screening", "service providers", "side effect", "targeted treatment" ], "approved": true } }, { "type": "Grant", "id": "16075", "attributes": { "award_id": "1K99HL179247-01A1", "title": "Mechanisms of Cardiovascular Complications in Respiratory Viral Infections", "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": 44551, "first_name": "KAZUYO", "last_name": "KEGAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-16", "end_date": "2028-06-30", "award_amount": 179496, "principal_investigator": { "id": 44552, "first_name": "Natalia", "last_name": "Eberhardt", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3489, "ror": "", "name": "NEW YORK UNIVERSITY SCHOOL OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Cardiovascular diseases (CVD) are the leading cause of death, accounting for an estimate of 19.05 million deaths in 2020, representing 32% of global deaths. The coronavirus outbreak highlighted impact of respiratory viral infections on atherosclerotic cardiovascular (CV) disease. Viral infections not only heighten the risk of CVD but also render individuals with pre-existing CVD and/or risk factors more susceptible to severe viral illnesses. However, the extent to which immune-mediated anti-viral response, viral tropism and cytotoxic mechanisms contribute to the increased CV risk remains poorly understood. Defining the mechanisms of viral CV tropism and resulting inflammation is key to understanding and preventing post-acute sequelae (PASC). Our previous work demonstrated that SARS-CoV-2 preferentially infects atherosclerotic plaques, correlating with macrophage infiltration in coronary lesions from patients with acute coronavirus disease. Foam cells, a hallmark of atherosclerosis, showed higher viral burden, delayed clearance, impaired interferon anti-viral responses, and increased secretion of pro-atherogenic cytokines, indicating a link between viral infection, lipid metabolism and inflammation in the context of CVD. Preliminary evidence shows that SARS-CoV-2 directly targets vascular immune cells, particularly macrophages altering their metabolism and inflammatory programs that contribute to atherosclerosis and post-viral CV sequelae. Building on our previous findings and promising preliminary data, this project aims to define how viral infection drives macrophage metabolic and inflammatory reprogramming that accelerates atherosclerosis progression and establishes long-lasting vascular inflammation. Aim 1 will define how SARS-CoV-2 infection reprograms macrophages toward a pro-atherogenic state, promoting foam-cell formation, defective efferocytosis, and plaque inflammation, and whether this accelerates atherosclerosis progression. Aim 2 will determine how viral infection induces long-lived myeloid reprogramming that sustains vascular inflammation and promotes post-viral inflammation and CVD and the role of early inflammatory monocyte recruitment and infection in initiating these persistent immune changes and inflammation. Together, these studies will provide the mechanistic foundation for developing targeted interventions to mitigate CV complications triggered by viral agents.", "keywords": [ "2019-nCoV", "ATAC-seq", "Acceleration", "Accounting", "Acute", "Anti-viral Response", "Aorta", "Apoptotic", "Arterial Fatty Streak", "Arteries", "Atherogenicity", "Atherosclerosis", "BODIPY", "Biological Assay", "Blood", "Blood Vessels", "Bone Marrow", "CD36 gene", "COVID-19 outbreak", "COVID-19 patient", "Cardiovascular Diseases", "Cardiovascular system", "Cause of Death", "Cells", "Cessation of life", "Cholesterol", "Clinical", "Convalescence", "Coronary", "Data", "Data Set", "Disease", "Disease Progression", "Epigenetic Process", "Equus caballus", "Exhibits", "Flow Cytometry", "Foam Cells", "Foundations", "Gene Expression Profile", "Genetic Transcription", "Growth", "Hamsters", "Harvest", "Histopathology", "Human", "Image Cytometry", "Immune", "Immunity", "Impairment", "In Vitro", "Individual", "Infection", "Infiltration", "Inflammation", "Inflammatory", "Injections", "Interferon Type I", "Interferons", "Intervention", "Knowledge", "LDLR gene", "Label", "Laboratories", "Lesion", "Link", "Lipids", "Lipoproteins", "Macrophage", "Macrophage Activation", "Mediating", "Mesocricetus auratus", "Metabolic", "Metabolism", "Modeling", "Myelogenous", "Myeloid Cells", "Myocardial Infarction", "Output", "PKH 26", "Patients", "Phase", "Phenocopy", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Predisposition", "Proliferating", "Proteins", "Regulation", "Research", "Rest", "Role", "SARS-CoV-2 infection", "Stroke", "Testing", "Time", "Tissues", "Tracer", "Training", "Tropism", "Viral", "Viral Load result", "Viral Respiratory Tract Infection", "Virus", "Virus Diseases", "Virus Replication", "Work", "acute infection", "atherogenesis", "cardiovascular disorder risk", "cardiovascular risk factor", "coronary lesion", "coronavirus disease", "coronavirus outbreak", "cytokine", "cytotoxic", "design", "differential expression", "imprint", "lipid metabolism", "monocyte", "multiple omics", "novel", "novel therapeutic intervention", "prevent", "programs", "receptor", "recruit", "response", "single-cell RNA sequencing", "spatial transcriptomics", "transcriptome sequencing", "uptake", "vascular inflammation", "viral RNA", "virology" ], "approved": true } }, { "type": "Grant", "id": "16074", "attributes": { "award_id": "1R21AI202391-01", "title": "A Bioinorganic Approach to Coordinate Covalent Protease Inhibitors", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32536, "first_name": "DIPANWITA", "last_name": "BASU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-01", "end_date": "2028-06-30", "award_amount": 196250, "principal_investigator": { "id": 44550, "first_name": "SETH M", "last_name": "COHEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3488, "ror": "", "name": "UNIVERSITY OF CALIFORNIA-IRVINE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The primary objective of this proposal is to explore the ability of coordination complexes to serve as coordinate covalent inhibitors of cysteine proteases. We propose a hit-to-lead, systematic, proof-of-concept to syntheisize, characterize, and demonstrate the ability of Re(I) transition metal complexes to inhibit the SARS-CoV-2 main protease (3CLpro). To identify inhibitors of 3CLpro, this proposal will complete two specific aims. In Specific Aim 1, we will employ a library of bidentate ligands to generate ~150 distinct [Re(CO)3(L)(X)] complexes where ‘L’ represents different bidentate ligands and ‘X’ represents a leaving group (e.g., H2O). These complexes will be evaluated for their stability in buffer, reactivity with amino acids, and activity against 3CLpro. Specific Aim 1 will provide the initial hits to feed into Specific Aim 2. In Specific Aim 2, the most active hits identified in Specific Aim 1 will be further elaborated to establish a structure-activity relationship (SAR) and drive hit-to-lead development against 3CLpro. A typical design- synthesize-test iterative cycle will be used to develop the SAR and obtain increasingly better inhibitors. Upon completion of Specific Aim 2, we will complete the hit-to-lead effort, with the goal of obtaining at least one lead compound with an IC50 value of <50 nM against the SARS-CoV-2 3CLpro and good selectivity (IC50 >100 µM against non-target enzymes). This project will test the central hypothesis of whether metal-based compounds can provide a new class of covalent inhibitors against a relevant model target enzyme. Although not a drug discovery effort per se, our preliminary findings strongly suggest Re(I) complexes have the potential to generate potent and selective covalent inhibitors. In the long term, inhibitors derived from Re(I) complexes will demonstrate attractive features that are not readily achieved with conventional, organic inhibitors. For example, Re(I) compounds can be transformed into ‘theranostics’ simply by changing the choice of metal in (e.g., 99Tc). This proposal will provide a conceptual framework for exploring and exploiting the unique advantages afforded by metal-based therapeutics.", "keywords": [ "2019-nCoV", "Amino Acids", "Bioinorganic Chemistry", "Biological Assay", "Buffers", "Caspase", "Chymase", "Complex", "Computer Models", "Crystallography", "Cysteine", "Cysteine Proteinase Inhibitors", "Data", "Development", "Enzyme Inhibitor Drugs", "Enzymes", "Goals", "Kinetics", "Lead", "Libraries", "Ligands", "Metals", "Modeling", "Modification", "Peptide Hydrolases", "Pharmaceutical Chemistry", "Protease Inhibitor", "Reaction", "Research", "Rhenium", "SARS-CoV-2 inhibitor", "SARS-CoV-2 protease", "Structure-Activity Relationship", "Testing", "Therapeutic", "Transition Elements", "adduct", "design", "drug discovery", "high throughput screening", "improved", "inhibitor", "innovation", "metal complex", "meter", "novel", "programs", "scaffold", "screening", "small molecule inhibitor", "theranostics", "therapeutic target" ], "approved": true } }, { "type": "Grant", "id": "16073", "attributes": { "award_id": "1R13AI200365-01", "title": "FASEB Virus Structure and Assembly Conference", "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": 44546, "first_name": "BARBARA L", "last_name": "MULACH", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-16", "end_date": "2027-06-30", "award_amount": 23500, "principal_investigator": { "id": 44547, "first_name": "Kyung H", "last_name": "Choi", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 44548, "first_name": "Sarah M", "last_name": "Doore", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 44549, "first_name": "Joseph Che-Yen", "last_name": "Wang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3487, "ror": "", "name": "TRUSTEES OF INDIANA UNIVERSITY", "address": "", "city": "", "state": "IN", "zip": "", "country": "United States", "approved": true }, "abstract": "Support is requested for partial funding of the 2026 FASEB Science Research Conference on Virus Structure and Assembly, to be held July 20 - 23, 2026, in Niagara Falls, New York. This biennial conference serves as the premier international forum for scientists investigating the molecular architecture, assembly, and dynamic behavior of viruses infecting hosts across all domains of life. As global viral threats continue to emerge, the ability to understand virus biology at the structural and mechanistic levels is essential for the development of vaccines, antiviral therapeutics, and surveillance tools to combat infectious diseases. The 2026 program will highlight three timely and scientifically impactful themes: (1) pandemic-causing viruses such as HIV-1, SARS-CoV-2, and Influenza, with a focus on viral entry, immune evasion, and intracellular trafficking; (2) emerging antiviral strategies, including vaccine design, small-molecule inhibitors, and bacteriophage therapy as an approach to address antimicrobial resistance; and (3) transformational technologies that are revolutionizing virus research, including cryo-electron tomography (cryo-ET), native mass spectrometry, and integrative structural biology methods capable of resolving virus-host interactions in situ. Together, these topics will shed light on the fundamental principles of virus biology while advancing translational efforts. The four- day scientific program will include ten thematic sessions, three keynote lectures, short talks selected from abstracts, two poster sessions, and structured activities designed to promote mentoring and collaboration. Approximately 150 participants are expected, representing a wide spectrum of career stages, institutions, and geographic regions. More than 30% of attendees are anticipated to be graduate students and postdoctoral researchers, who will be supported through travel scholarships and featured in short talks and flash presentations. Several professional development opportunities, such as “Career Development and Enhancement,” “Meet the Experts,” and “Meet the Sponsors” sessions, will facilitate interactions among early-career scientists, established investigators, technology developers, and industrial partners. The conference fosters a collaborative and intellectually vibrant environment that advances structural virology and supports the scientific workforce needed to address current and future infectious disease threats.", "keywords": [ "2019-nCoV", "Academia", "Acceleration", "Address", "Anti-viral Agents", "Antimicrobial Resistance", "Architecture", "Bacteriophages", "Behavior", "Biology", "Biophysics", "Biotechnology", "Collaborations", "Communicable Diseases", "Complex", "Computer Models", "Country", "Cryo-electron tomography", "Cryoelectron Microscopy", "Development", "Discipline", "Environment", "Fostering", "Foundations", "Funding", "Future", "Geographic Locations", "Goals", "Government", "HIV-1", "Immune Evasion", "In Situ", "Industrialization", "Industry", "Infectious Diseases Research", "Infectious disease threat", "Influenza", "Institution", "International", "Knowledge", "Life", "Mass Spectrum Analysis", "Mentors", "Methodology", "Methods", "Mission", "Molecular", "Molecular Virology", "National Institute of Allergy and Infectious Disease", "New York", "Oral", "Outcome", "Participant", "Postdoctoral Fellow", "Problem Solving", "Public Health", "Readiness", "Research", "Research Personnel", "Scholarship", "Science", "Scientist", "Structure", "Technology", "Therapeutic", "Training", "Training Support", "Translational Research", "Travel", "Vaccine Design", "Vaccines", "Viral", "Virus", "Virus Diseases", "antimicrobial", "antiviral drug development", "career", "career development", "career networking", "combat", "design", "falls", "graduate student", "high-resolution", "innovation", "lectures", "meetings", "novel", "novel strategies", "pandemic disease", "pathogen", "posters", "prevent", "programs", "response", "skills", "small molecule inhibitor", "structural biology", "symposium", "therapeutic target", "tool", "trafficking", "transforming virus", "translational applications", "unpublished works", "vaccine development", "vaccine strategy", "virology", "virus host interaction", "workforce needs" ], "approved": true } }, { "type": "Grant", "id": "16072", "attributes": { "award_id": "1R01HL179266-01A1", "title": "Elucidating an immune epithelial niche underlying post viral lung fibrosis", "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": 44544, "first_name": "CHRISTIAN RENE", "last_name": "GOMEZ", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-07-01", "end_date": "2029-03-31", "award_amount": 717680, "principal_investigator": { "id": 44545, "first_name": "PETER", "last_name": "CHEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 20818, "first_name": "Jie", "last_name": "Sun", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1426, "ror": "", "name": "MAYO CLINIC ROCHESTER", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 3486, "ror": "", "name": "CEDARS-SINAI MEDICAL CENTER", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Respiratory viruses can acutely lead to high mortality from respiratory failure. However, respiratory viral infections also cause permanent morbidity long after recovery from the acute infection. Such chronic debilitation was best exemplified during the COVID-19 pandemic that left many patients with post-acute sequelae of SARS-CoV-2 (PASC; aka long COVID). One unfortunate consequence after a severe COVID-19 infection is the development of persistent pulmonary fibrosis (PASC-PF). However, this fibrotic remodeling of the lungs is not unique to infections by SARS-CoV-2 and has also been found with other viral infections such as influenza, MERS-CoV, SARS-CoV-1. Investigations into PASC-PF have revealed common features when compared to idiopathic pulmonary fibrosis (IPF), the archetype of progressive lung fibrosis. A fundamental feature in PASC-PF, IPF, and other types of lung fibrosis is the maladaptive repair of the lung epithelium that is an upstream driver of fibroproliferation. In particular, the type 2 alveolar epithelial cell (AT2) cells, which are the facultative epithelial stem cells of the alveoli, are exhausted and fail to properly repair the lungs after injury. Accordingly, damaged alveoli have a repair deficiency with a failure of AT2 differentiation into alveolar type 1 (AT1) cells that are necessary for lining the alveoli to facilitate gas exchange in the lungs. To that end, recent studies have found IFN-γ to be a key signaling node that is enriched in PASC-PF and IPF. Moreover, studies by our group and others have demonstrated IFN-γ blockade to reduce fibrosis and augment epithelial repair in a viral-induced lung fibrosis model. Accordingly, we have developed a central hypothesis that anti-viral immunity by CD8+ T cells directly (via IFN-γ) and indirectly (via MDM secretion of IL-1β) stalls alveolar regeneration thereby shifting the injury response toward maladaptive repair thereby activating fibroproliferative pathways. We will test the hypothesis in three aims: Aim 1. Evaluate viral-mediated maladaptive reprogramming of AT2 cell. Aim 2. Uncover the cellular and molecular mechanisms that mediate the abnormal immune-epithelial interactions contributing to chronic lung fibrosis following viral infection. Aim 3. Identify abnormal immune-epithelial interactions in human post-viral lung fibrosis . The successful completion of this study promises to elucidate the cellular and molecular etiology of lung fibrosis and have a broad impact on understanding fibroproliferative mechanisms in PASC-PF, IPF, and other forms of lung fibrosis.", "keywords": [ "Acute", "Alveolar", "Alveolus", "Biological Response Modifiers", "Bleomycin", "CD8-Positive T-Lymphocytes", "COVID-19 pandemic", "COVID-19 patient", "COVID-19 survivors", "Cell Differentiation process", "Cells", "Chronic", "Coenzyme A", "Development", "Disease", "Epithelial Cells", "Epithelium", "Etiology", "Failure", "Fibrosis", "Gases", "Gene Deletion", "Gene Modified", "Human", "Immune", "Immune signaling", "Impairment", "Infection", "Influenza", "Injury", "Interferon Type II", "Interferons", "Interleukin-1", "Interleukin-1 beta", "Investigation", "Lead", "Left", "Literature", "Long COVID", "Lung", "Lung Transplantation", "Macrophage", "Mediating", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Molecular", "Morbidity", "Mus", "Natural regeneration", "Organoids", "Oxygen", "Pathogenicity", "Pathologic", "Pathway interactions", "Patients", "Persons", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Production", "Proliferating", "Pulmonary Fibrosis", "Pulmonary Pathology", "Recovery", "Regulation", "Research", "Respiratory Failure", "SARS coronavirus", "SARS-CoV-2 infection", "Signal Transduction", "Slice", "Supplementation", "Syndrome", "T cell response", "T-Lymphocyte", "Testing", "Tissues", "Transitional Cell", "Transitional Epithelium", "Viral", "Viral Respiratory Tract Infection", "Virus", "Virus Diseases", "Work", "acute infection", "aged", "alveolar epithelium", "alveolar stem cell", "antiviral immunity", "attenuation", "biobank", "cell motility", "epithelial repair", "epithelial stem cell", "exhaust", "fibrogenesis", "fibrotic lung", "idiopathic pulmonary fibrosis", "immune activation", "in vivo Model", "influenza infection", "insight", "lung injury", "lung repair", "monocyte", "mortality", "novel", "novel therapeutics", "old mice", "pharmacologic", "post SARS-CoV-2 infection", "prevent", "repaired", "respiratory virus", "response", "response to injury", "severe COVID-19", "spatiotemporal" ], "approved": true } } ], "meta": { "pagination": { "page": 5, "pages": 1442, "count": 14420 } } }