Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=5&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=1442&sort=-start_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=6&sort=-start_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=-start_date" }, "data": [ { "type": "Grant", "id": "16039", "attributes": { "award_id": "1R01HD118970-01A1", "title": "Examining Impacts of Technology and Digital Media on Cognitive and Socioemotional Skills and Underlying Neural Mechanisms from Age 3 to 6 Years Old", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 44486, "first_name": "VIRGINIA CHARLOTTE", "last_name": "SALO", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-08-10", "end_date": "2031-07-31", "award_amount": 683107, "principal_investigator": { "id": 44506, "first_name": "Tzipi", "last_name": "Horowitz-Kraus", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3455, "ror": "", "name": "HUGO W. MOSER RES INST KENNEDY KRIEGER", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Technology and digital media (TDM) increasingly influence how young children learn and form relationships, amplified since the COVID pandemic. The American Academy of Pediatrics (AAP) recommends limits on TDM use, citing risks for adverse cognitive, socioemotional (SE), school and health outcomes. However, evidence is conflicting and limited in scope, ranging from clear negatives, to benefits in certain contexts, to no discernible effect. This has been termed “differential susceptibility,” a theme of this research project, though predisposing and protective factors are uncertain. Early childhood is a dynamic span of brain growth, where core functional networks are shaped (e.g., language), and also integrated (e.g., for reading and math). The overarching goal of this project is to address major research gaps and opportunities to better understand how TDM use during early childhood influences trajectories of cognitive, socioemotional and brain development driving long-term academic and health outcomes. It builds on unique, cross-sectional preliminary data from MRI-based studies published by the applicant team, involving language and literacy skills at this age. A total of 150 parents and their 3-year-old children will be recruited, with a goal of at least 40% from underserved backgrounds (racial minority, poverty). Baseline assessment will be at age 3-years, with annual follow-up visits at ages 4, 5 and 6, reflecting early preschool through kindergarten. Measures of language, emergent literacy, numeracy, executive function and SE skills will be given at each visit by research staff. Visits at age 4 & 6 will include structural and functional MRI, using established, play-based protocols. TDM use will be measured with a validated parent report survey and child usage data captured using a validated mobile sensing app installed in a device used by the child, and a time use diary completed by the child’s parent. Both reported and measured TDM use will be used as predictors of cognitive and SE skills at each visit and changes between-visits (Aim 1). These will also be used in MRI analyses as predictors of brain structure (cortical and white matter morphology) and function (activation, connectivity) at age 4 & 6 and changes between ages (Aim 2). Both analyses will account for the influence of sex, income and select TDM usage and family factors. The Aim 1 hypotheses are that higher TDM use will predict lower skills, yet impacts will be moderated by TDM and family factors (e.g., content, parental use, reading). Aim 2 hypotheses are that higher TDM use will predict differences in brain structure and function supporting respective skills, moderated by the same factors. This project is highly significant as it addresses major evidence gaps regarding impacts of TDM on vital skills during early childhood, a dynamic span of brain development shaped by experiences. It is highly innovative as it captures reported and objective TDM use, combines a range of cognitive and MRI measures in a longitudinal design to elucidate brain-behavior relationships, and accounts for potentially moderating factors. It is timely on a societal level, addresses NICHD aspirational and priorities, and has potential to inform AAP guidelines, interventions and additional research.", "keywords": [ "2 year old", "3 year old", "4 year old", "6 year old", "Academy", "Address", "Age", "American", "Area", "Automobile Driving", "Behavior", "Black race", "Brain", "COVID-19 pandemic", "Child", "Cognition", "Cognitive", "Data", "Development", "Devices", "Early Intervention", "Education", "Emotional", "Family", "Family Policy", "Functional Magnetic Resonance Imaging", "Goals", "Growth", "Guidelines", "Health", "Hippocampus", "Home", "Hour", "Human", "Income", "Inferior", "Intervention", "Language", "Learning", "Learning Skill", "Left", "Link", "Magnetic Resonance Imaging", "Mathematics", "Measures", "Methods", "Morphology", "National Institute of Child Health and Human Development", "Neurobiology", "Neuronal Plasticity", "Nursery Schools", "Outcome", "Parent-Child Relations", "Parents", "Parietal", "Pediatrics", "Play", "Poverty", "Predisposing Factor", "Predisposition", "Prefrontal Cortex", "Process", "Protocols documentation", "Public Policy", "Publishing", "Reading", "Recommendation", "Reporting", "Research", "Research Project Grants", "Risk", "Risk Factors", "Sampling", "School-Age Population", "Schools", "Shapes", "Stream", "Structure", "Surveys", "Tablets", "Technology", "Time", "Trajectory", "Visit", "Vocation", "Work", "analog", "brain behavior", "cognitive skill", "cohort", "cost", "design", "diaries", "digital media", "disadvantaged background", "early childhood", "executive function", "experience", "follow-up", "gray matter", "handheld mobile device", "high risk", "innovation", "kindergarten", "literacy", "longitudinal design", "mathematical ability", "media use", "mobile sensing", "multisensory", "neural growth", "neural stimulation", "neuromechanism", "poor sleep", "protective factors", "racial minority", "recruit", "sex", "skills", "social", "socioeconomic disadvantage", "success", "support network", "time use", "white matter", "younger age" ], "approved": true } }, { "type": "Grant", "id": "16044", "attributes": { "award_id": "1R41AI197273-01", "title": "Development of NPC1-targeting nanobodies against filovirus infections", "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": 32845, "first_name": "JULIE", "last_name": "DYALL", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-08-10", "end_date": "2028-07-31", "award_amount": 300000, "principal_investigator": { "id": 8318, "first_name": "Fang", "last_name": "Li", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3460, "ror": "", "name": "NANOLI THERAPEUTICS LLC", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true }, "abstract": "Development of NPC1-targeting nanobodies against filovirus infections Summary Filoviruses, including Ebola (EBOV), Sudan (SUDV), and Marburg (MARV) viruses, are highly lethal pathogens with fatality rates ranging from 44% to 73%. With known or potential animal reservoirs, these viruses are likely to persist in human populations long term. While one vaccine and two antibody treatments exist for EBOV, their effectiveness, accessibility, and antiviral spectrum remain limited. Currently, no approved vaccines or treatments are available for SUDV or MARV, highlighting the urgent need for new therapeutics. Our research focuses on developing nanobody-based antiviral treatments for filoviruses. Nanobodies are small, single-domain antibodies derived from camelids. They are highly effective, broadly neutralizing, and easy to produce, store, and transport. They can also be administered intranasally and are safe for human use. Our team has previously developed nanobodies targeting SARS-CoV-2 and filoviruses and pioneered a rapid, structure-guided adaptation method to optimize nanobodies against emerging viral variants. Filoviruses infect human cells by using their glycoprotein (GP) to bind NPC1 (hNPC1), a receptor inside endosomes. Our current nanobodies block GP to prevent viral entry. In this project, we aim to develop nanobodies that target NPC1 itself. Since NPC1 is intracellular and plays a role in cholesterol metabolism, we will design bispecific nanobodies that target both GP and NPC1. This dual-targeting approach ensures specificity for virus-infected cells while minimizing effects on uninfected cells. Our research has three key objectives: (i) Develop and optimize hNPC1-targeting nanobodies. We will generate and screen nanobodies from alpacas, selecting those that most effectively block filovirus GP from binding to hNPC1. (ii) Adapt NPC1-targeting nanobodies for animal models. Before human trials, treatments must be tested in animals. Using our recently developed structure- guided in vitro evolution approach, we will engineer nanobodies to recognize NPC1 from mice, guinea pigs, and non-human primates for preclinical studies. (iii) Create bispecific nanobodies targeting both GP and NPC1. By combining NPC1-targeting nanobodies with GP-targeting nanobodies, we aim to enhance selectivity and potency. These bispecific nanobodies will be tested against filovirus pseudoviruses to evaluate their ability to neutralize filovirus GP-mediated viral entry. Beyond this project, the most promising nanobody candidates will be tested against authentic filoviruses and evaluated for safety and efficacy in animal models. In sum, guided by structural biology and leveraging the unique properties of nanobodies, this project aims to develop potent, broad-spectrum, safe, cost-effective, and accessible treatments for filoviruses. In addition to addressing a critical gap in global health and national security, this research will advance nanobody technology and potentially lead to new therapies for other viruses and human diseases.", "keywords": [ "2019-nCoV", "Address", "Affinity", "Alpaca", "Animal Model", "Animal Structures", "Animals", "Anti-viral Agents", "Antibody Therapy", "Binding", "Cavia", "Cells", "Cholesterol Homeostasis", "Clinical Trials", "Complex", "Development", "Drug Kinetics", "Ebola", "Ebola virus", "Effectiveness", "Endocytosis", "Endosomes", "Engineering", "Ensure", "Epitopes", "Evolution", "Fatality rate", "Fc domain", "Filoviridae Infections", "Filovirus", "Future", "GP2 gene", "GTPBP1 gene", "Glycoproteins", "Human", "Human body", "Immunize", "In Vitro", "Infection", "Intranasal Administration", "Marburgvirus", "Measures", "Mediating", "Membrane Fusion", "Methods", "Mus", "NPC1 gene", "Names", "National Security", "Outcome", "Pathway interactions", "Penetration", "Population", "Positioning Attribute", "Preclinical Testing", "Preventive", "Property", "Research", "Retroviridae", "Safety", "Series", "Specificity", "Structure", "Sudan", "Sudan Ebola virus", "Technology", "Testing", "Therapeutic", "Tissues", "Toxic effect", "Vaccines", "Variant", "Vesicular stomatitis Indiana virus", "Viral", "Virus", "Virus Diseases", "cost effective", "cytotoxicity", "design", "global health", "human disease", "in vivo", "nanobodies", "nanoengineering", "nonhuman primate", "novel", "novel therapeutics", "pathogen", "preclinical study", "prevent", "receptor", "structural biology", "viral entry inhibitor" ], "approved": true } }, { "type": "Grant", "id": "16036", "attributes": { "award_id": "1R01AI195925-01", "title": "Structure and function of distinct conformational states of coronavirus spike in membrane", "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": "2026-08-10", "end_date": "2031-07-31", "award_amount": 864475, "principal_investigator": { "id": 8930, "first_name": "Bing", "last_name": "Chen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 798, "ror": "https://ror.org/00dvg7y05", "name": "Boston Children's Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3454, "ror": "", "name": "BOSTON CHILDREN'S HOSPITAL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising alarms about all pathogenic coronaviruses with pandemic potential. The first critical step for coronaviruses to enter host cells is viral membrane fusion mediated by their spike (S) proteins. Among them, the best-studied spike protein is the SARS-CoV-2 spike, which is a heavily glycosylated type I membrane protein anchored in the viral membrane. It is first produced as a precursor that trimerizes and then cleaved by a furin-like protease into two fragments: the receptor-binding fragment S1 and the fusion fragment S2. Binding of the receptor-binding domain (RBD) in S1 to the host cell receptor ACE2 and further proteolytic cleavage at a second site in S2 (S2’ site) are believed to trigger dissociation of S1 and irreversible refolding of S2 into a postfusion conformation. These large structural rearrangements bring together the viral and cellular membranes, ultimately leading to fusion of the two bilayers. Previous studies have revealed both pre- and post-fusion conformations of the soluble fragments of many spike proteins, but less is known for structures of their transmembrane and membrane- proximal regions in the context of lipid bilayers. There is strong evidence for functional roles of these membrane- interacting regions in viral fusion, and yet mechanistic studies on how they exert their functions remain scarce. We hypothesize that high-resolution structural studies of distinct conformational states of the membrane-bound coronavirus spike proteins in membrane will reveal novel structure features that are critical for our understanding of viral entry. We have determined a structure of the SARS-CoV-2 postfusion spike containing all the membrane-interacting regions reconstituted in a lipid bilayer. Our structure has revealed some unexpected findings that the internal fusion peptide forms a hairpin-like wedge spanning almost the entire lipid bilayer and the transmembrane segment wraps around the fusion peptide at the last stage of membrane fusion, demonstrating the importance of membrane in studying these viral fusion proteins. In this project, we plan to determine structures of the distinct conformational states of the coronavirus S proteins reconstituted in lipid nanodiscs. We will also define roles of critical structural elements of the S proteins in membrane fusion and determine impact of other viral structural proteins by mutagenesis and functional studies. Our goal is to visualize novel structural features of the spike proteins in the context of membrane and elucidate their functions to inform development of intervention strategies. We will pursue the following specific aims: 1) we will determine structure of the S2’ fragment in the postfusion conformation in membrane; 2) we will determine structure of the full-length prefusion S proteins in membrane; 3) we will elucidate roles of novel structural features of the full-length S proteins in their stability, function and antigenicity, and impact of other viral components.", "keywords": [ "2019-nCoV", "ACE2", "Adopted", "Binding", "Biogenesis", "Biological Assay", "COVID-19 pandemic", "Caspase", "Cathepsins", "Cells", "Cellular Membrane", "Classification", "Coronavirus", "Coronavirus spike protein", "Cryoelectron Microscopy", "Detergents", "Disease", "Dissociation", "Elements", "Endosomes", "Goals", "Infection", "Intervention Strategies", "Laboratories", "Length", "Lipid Bilayers", "Lipids", "Location", "Mediating", "Membrane", "Membrane Fusion", "Membrane Proteins", "Molecular Conformation", "Mutagenesis", "Pathogenicity", "Peptide Hydrolases", "Process", "Property", "Proteins", "Protocols documentation", "Publishing", "RNA Viruses", "Receptor Cell", "Resolution", "Role", "SARS-CoV-2 spike protein", "Serine Protease", "Site", "Source", "Structure", "TMPRSS2 gene", "Technology", "Testing", "Vaccines", "Viral", "Viral Fusion Proteins", "Viral Structural Proteins", "Visualization", "alphacoronavirus", "betacoronavirus", "fascinate", "fusion peptide", "glycosylation", "high-resolution", "insight", "nanodisc technology", "nanodisk", "novel", "pandemic coronavirus", "protein folding", "protein reconstitution", "receptor binding", "reconstitution", "theories", "therapeutic development", "therapeutic target", "therapy development", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "16065", "attributes": { "award_id": "1R21AI193667-01A1", "title": "Determining the role of the cytokine interleukin-22 (IL-22) in SARS-CoV-2 infection", "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": "2026-08-10", "end_date": "2028-07-31", "award_amount": 178750, "principal_investigator": { "id": 44536, "first_name": "Lauren A", "last_name": "Zenewicz", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3479, "ror": "", "name": "UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR", "address": "", "city": "", "state": "OK", "zip": "", "country": "United States", "approved": true }, "abstract": "SARS-CoV-2 infection often has lasting, long-term effects on people’s health. Post-acute sequelae SARS-CoV- 2 infection (PASC), informally called “Long COVID”, is a clinically heterogenous disease with different patients having different affected tissues. In addition to the lungs, the site of primary infection, PASC patients also report issues with other tissues, including the gastrointestinal (GI) tract. Although we still do not understand the mechanisms for PASC, there is an urgent need to identify therapeutics to prevent and/or treat PASC patients. Early in the pandemic, COVID-19 patients were described as having a cytokine storm that is likely one of the major complications leading to PASC. Although many of these cytokines contribute to tissue damage and destruction, interleukin-22 (IL-22) is well-described to be protective to inflamed tissues in diseases such as airway inflammation and inflammatory bowel disease. IL-22 stimulation alters the transcriptional profile of epithelial cells within the target tissues to increase cellular proliferation and decrease sensitivity to apoptosis. IL- 22 can also aid in wound repair and recombinant IL-22-Fc is in clinical trials for the treatment of flares in ulcerative colitis patients and tissue repair in patients with acute graft versus host disease. There is a gap in our knowledge of how individual cytokines may affect patient outcomes and if they can be used for preventing or repairing tissue damage. Our hypothesis is that IL-22 is a protective cytokine to tissues during SARS-CoV-2 infection. In this proposal we will examine the role of IL-22 in vitro in respiratory and GI cells and in an in vivo mouse model of SARS-CoV-2 infection. Our overall objective is to determine if IL-22 is a protective cytokine in this disease and can be beneficial to the lung and GI tissues during infection. Upon completion of these aims, the expected outcome is a new understanding of the critical role of the cytokine IL-22 in SARS-CoV-2 infection. This breakthrough will have a positive impact on our understanding of immune responses to SARS-CoV-2 infection as they may provide strong evidence-based rationale for further development of IL-22 biology targeted therapies in the prevention and/or treatment of PASC.", "keywords": [ "2019-nCoV", "Acute Graft Versus Host Disease", "Affect", "Anti-viral Response", "Apoptosis", "Biology", "COVID-19 patient", "COVID-19 susceptibility", "Cell Line", "Cell Proliferation", "Cells", "Clinical", "Clinical Treatment", "Clinical Trials", "Colon", "Data", "Development", "Disease", "Disease Progression", "Down-Regulation", "Epithelial Cells", "Flare", "Gastrointestinal tract structure", "Gene Expression Profile", "Genes", "Genetic Transcription", "Goals", "Health", "Human", "Immune response", "Immunology", "In Vitro", "Individual", "Infection", "Inflammation", "Inflammatory Bowel Diseases", "Inhibition of Apoptosis", "Knowledge", "Laboratories", "Long COVID", "Long-Term Effects", "Lung", "Mission", "Monitor", "Morbidity", "Mus", "Organoids", "Outcome", "Pathology", "Patient-Focused Outcomes", "Patients", "Persons", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Predisposition", "Prevention", "Primary Infection", "Proliferating", "Public Health", "Recombinant Interleukins", "Reporting", "Research", "Role", "SARS-CoV-2 infection", "STAT3 gene", "Series", "Serum", "Signal Transduction", "Site", "Technology", "Therapeutic", "Tissues", "Transcriptional Regulation", "Ulcerative Colitis", "United States", "United States National Institutes of Health", "Upregulation", "Viral", "Viral Load result", "Virus", "Virus Diseases", "Wild Type Mouse", "airway inflammation", "chemokine", "cytokine", "cytokine release syndrome", "evidence base", "experimental study", "gastrointestinal", "human disease", "in vivo", "in vivo Model", "insight", "interleukin-22", "mouse model", "nanostring", "pandemic disease", "pathogen", "prevent", "receptor", "respiratory", "targeted treatment", "tissue repair", "wound healing" ], "approved": true } }, { "type": "Grant", "id": "16046", "attributes": { "award_id": "1F31AI194952-01A1", "title": "Effect of wildfire smoke exposure on the development of tuberculosis and mortality due to COVID-19", "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": 44508, "first_name": "SUSANA", "last_name": "MENDEZ", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-08-10", "end_date": "2029-08-09", "award_amount": 53114, "principal_investigator": { "id": 44515, "first_name": "Lauren", "last_name": "Linde", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3462, "ror": "", "name": "BOSTON UNIVERSITY MEDICAL CAMPUS", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Wildfires are currently growing in size, frequency, and severity in many places globally. Consequently, increasingly large populations are being exposed to high concentrations of air pollution from wildfire smoke. Wildfire smoke exposure has been linked to numerous adverse health outcomes, particularly non-communicable pulmonary conditions. There is growing evidence that pollutants present in wildfire smoke are also associated with human immune cell changes that increase susceptibility to infection with both viral and bacterial respiratory pathogens. However, relatively few studies have directly examined the relationship between wildfire smoke exposure and infectious respiratory diseases. Given the enormous, overlapping populations affected by both wildfire smoke and infectious respiratory diseases, better understanding the relationship between these phenomena may have important health consequences. The aim of the proposed research is to use large, individual-level data sources to establish robust evidence on the impact of wildfire smoke exposure for two leading infectious respiratory diseases that each impact millions of people globally each year, tuberculosis (TB) and COVID-19. Aim 1 uses a surveillance dataset of every case of and death due to COVID-19 in six western US States over a two-year period to assess whether exposure to wildfire smoke close in time to infection with COVID-19 is associated with increased mortality risk. Aims 2 and 3 investigate the relationship between wildfire smoke exposure and TB. Aim 2 uses a detailed dataset of close contacts to individuals with TB in Los Angeles County over a nine-year period to assess whether wildfire smoke exposure that occurs close in time to exposure to TB is associated with increased risk of Mycobacterium tuberculosis infection and subsequent development of TB. Aim 3 uses a national surveillance dataset of TB cases in Brazil over a five-year period to assess whether wildfire smoke exposure is temporally associated with increased TB diagnoses using a case-crossover design. Results from these studies will contribute among the first individual-level data regarding the risks of wildfire smoke exposure for TB and COVID-19 outcomes. The proposed research will improve understanding of how trends in wildfires may exacerbate the burden of infectious respiratory diseases. This mentored Ruth L. Kirschstein National Research Service Award proposes to provide the trainee, a doctoral student in epidemiology at Boston University, with rigorous interdisciplinary training in both environmental and infectious disease epidemiology that is supplemental to the standard PhD curriculum. Guided by a team of senior mentors with diverse backgrounds in both fields, the trainee will gain the necessary skills and expertise to launch an academic career as an independent researcher generating novel evidence at the nexus of environmental health and infectious diseases. A detailed training plan, in conjunction with the proposed mentored research, provides dedicated time for the trainee to obtain supplemental training in relevant epidemiologic methods and sources of environmental data, and hands-on experience building interdisciplinary, multi-institutional research partnerships.", "keywords": [ "Address", "Affect", "Air Pollutants", "Air Pollution", "Boston", "Brazil", "COVID-19", "COVID-19 diagnosis", "COVID-19 mortality", "California", "Cells", "Centers for Disease Control and Prevention (U.S.)", "Cessation of life", "Communicable Diseases", "County", "Crossover Design", "Data", "Data Set", "Data Sources", "Databases", "Dedications", "Development", "Disease", "Doctor of Philosophy", "Educational Curriculum", "Environmental Exposure", "Environmental Health", "Epidemiologic Methods", "Epidemiology", "Exposure to", "Fire - disasters", "Foundations", "Frequencies", "Goals", "Health", "Human", "Immune", "Immune response", "Immunity", "Impairment", "Incidence", "Individual", "Infection", "Infectious Disease Epidemiology", "Institution", "Link", "Literature", "Los Angeles", "Mentors", "Methods", "Mycobacterium tuberculosis", "National Research Service Awards", "Outcome", "Persons", "Population", "Predisposition", "Publishing", "Registries", "Research", "Research Personnel", "Research Training", "Respiratory Disease", "Risk", "Risk Factors", "Severities", "Smoke", "Source", "Time", "Training", "Tuberculosis", "Tuberculosis diagnosis", "US State", "United States", "Universities", "Vaccines", "Viral", "Wildfire", "air monitoring", "burden of illness", "career", "cohort", "doctoral student", "experience", "exposure mixture", "geospatial analysis", "improved", "infection risk", "insight", "mortality", "mortality risk", "national surveillance", "novel", "pandemic disease", "pollutant", "programs", "pulmonary", "respiratory pathogen", "skills", "sociodemographics", "surveillance data", "training project", "transmission process", "trend" ], "approved": true } }, { "type": "Grant", "id": "16064", "attributes": { "award_id": "1R21AI202433-01", "title": "Novel In-Clinic Molecular Adjuvant Enhances Antiviral Humoral Immunity of Vaccines Across Sexes", "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": "2026-08-07", "end_date": "2028-07-31", "award_amount": 234370, "principal_investigator": { "id": 44535, "first_name": "ZHAOYANG", "last_name": "YOU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3478, "ror": "", "name": "UNIVERSITY OF PITTSBURGH AT PITTSBURGH", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Novel In-Clinic Molecular Adjuvant Enhances Antiviral Humoral Immunity of Vaccines Across Sexes Abstract Females typically generate more effective humoral immunity of vaccines (e.g., influenza vaccine) than males. Discovering safe and effective adjuvants, which are crucial for vaccinations, to enhance immunogenicity of viral antigens across sexes is an urgent need. We have found the in-clinic small molecule latanoprost that promotes intradermally co-delivered influenza H1N1 Hemagglutinin (HA) or SARS-CoV-2 Spike (S) protein vaccine for inducing HA-specific IgG1 or S-specific neutralizing antibody (NAb) across sexes in C57BL/6 mice. HA or S protein vaccine alone induces a remarkable difference of IgG1 or NAb responses in females vs. males; interestingly, latanoprost preferentially promotes IgG1 or NAb responses to HA or S protein vaccine in males, resulting in a reduced difference to a comparable level of IgG1 or NAb in males vs. females. Conventional type 1 DC (cDC1) are tied to long-lasting NAb responses following latanoprost-adjuvanted vaccinations. There are more migratory cDC1 in the skin of females than males; intriguingly, latanoprost increases skin migratory cDC1 across sexes, with a greater effectiveness in males, leading to a similar level of migratory cDC1 in the skin of females vs. males. Combined data from both females and males demonstrate that latanoprost-adjuvanted vaccines are superior to non-adjuvanted vaccines in eliciting humoral responses to viral antigens. We hypothesize that latanoprost increases migratory cDC1 and eliminates their differences between females and males in the skin to enhance antiviral humoral immunity of vaccines across sexes. We will 1) explore the mechanisms by which latanoprost enhances humoral responses to viral antigens in males and females, and 2) develop latanoprost-adjuvanted vaccines across sexes. If successful, we will discover latanoprost as a novel in-clinic molecular adjuvant to enhance humoral responses to viral antigens in males and females and develop clinically translatable latanoprost-adjuvanted influenza and SARS-CoV-2 vaccines across sexes which differ from past reports for female-biased humoral responses to conventional vaccines.", "keywords": [ "Adjuvant", "Adjuvanticity", "Agonist", "Androgens", "Antibody Response", "Antigens", "B-Lymphocytes", "Blood", "C57BL/6 Mouse", "COVID-19 vaccine", "Chronic", "Clinic", "Data", "Disproportionately impacts women", "Effectiveness", "FLT3 ligand", "Female", "Flow Cytometry", "Formulation", "Gene Expression Profile", "Helper-Inducer T-Lymphocyte", "Hemagglutinin", "Hormonal", "Hormones", "Humoral Immunities", "IgG1", "Immunoglobulin G", "Inbred BALB C Mice", "Inbreeding", "Inflammatory Response", "Influenza", "Influenza A Virus H1N1 Subtype", "Latanoprost", "Link", "Mediating", "Molecular", "Mus", "PGF receptor", "Pfizer-BioNTech COVID-19 vaccine", "Pharmaceutical Preparations", "Prostaglandins", "Protein Analysis", "Proteins", "Reporting", "Role", "SARS-CoV-2 spike protein", "Sex Bias", "Skin", "Structure of germinal center of lymph node", "Swiss Mice", "TLR7 gene", "Testing", "Vaccination", "Vaccines", "Viral", "Viral Antigens", "Virus", "XCR1 gene", "antagonist", "antiviral immunity", "clinical translation", "cytokine", "cytokine release syndrome", "draining lymph node", "immunogenicity", "improved", "influenza virus vaccine", "influenzavirus", "irritation", "male", "migration", "neutralizing antibody", "novel", "old age", "preclinical development", "protein expression", "receptor", "response", "sex", "single-cell RNA sequencing", "small molecule", "vaccine development", "vaccine immunogenicity", "women versus men" ], "approved": true } }, { "type": "Grant", "id": "16054", "attributes": { "award_id": "1R21AI193680-01A1", "title": "Mechanistic characterization and rational design of Lassa virus entry inhibitors", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32808, "first_name": "MINDY I", "last_name": "DAVIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-08-07", "end_date": "2028-07-31", "award_amount": 282250, "principal_investigator": { "id": 44523, "first_name": "Huihui", "last_name": "Mu", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3469, "ror": "", "name": "BOSTON CHILDREN'S HOSPITAL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Lassa virus (LASV), a BSL-4 pathogen and the causative agent of Lassa fever, poses a significant public health threat due to its epidemic potential both within and outside endemic regions and the lack of FDA-approved treatments or vaccines. The LASV glycoprotein complex (GPC), the sole envelope-anchored viral protein, and the entry process it mediates are key targets for developing intervention strategies. Despite extensive efforts, progress on vaccines and immunotherapies has been impeded by glycosylation of GPC, the genetic diversity of LASV, and the cost and time required for these strategies. Small-molecule arenavirus inhibitors have shown promise, but further development has been limited by poor target specificity and a lack of mechanistic insight. These challenges raise a critical question: how can we accelerate the development of effective, accessible LASV therapeutics suitable for broad use, particularly in resource-limited endemic regions? To address this unmet need, we conducted two parallel screens of a 665,000-compound library, controlled by SARS-CoV-2 and Machupo virus, respectively, and identified a family of small-molecule entry inhibitors that are non-toxic, potent, and specific for LASV entry, with pan-lineage activity. To the best of our knowledge, these compounds are the first to inhibit LASV entry without targeting other arenaviruses. Preliminary mechanistic studies suggest their direct interactions with the membrane-proximal region of LASV GPC, indicating a potential mechanism for disrupting conformational changes required for secondary receptor engagement or subsequent membrane fusion. Additionally, these inhibitors exhibit encouraging drug-like properties in both in vitro and in vivo drug metabolism and pharmacokinetics (DMPK) studies. Our initial structure-activity relationship (SAR) analyses support their potential for further optimization towards clinical development. In this proposal, we will develop these LASV-specific entry inhibitors through two independent and synergistic approaches. In Aim 1, we will investigate how these compounds interact with LASV GPC and inhibit viral entry. This effort will reveal the antiviral mechanisms of our lead compounds and inform targets for future LASV-specific antiviral design. In Aim 2, we will further optimize their antiviral efficacy and drug-likeness through detailed SAR and DMPK studies. Together, these studies will advance first-in-class LASV-specific small-molecule therapeutics and establish a robust platform for antiviral discovery against high-priority emerging pathogens.", "keywords": [ "2019-nCoV", "Acceleration", "Address", "Affect", "Africa", "Anti-viral Agents", "Arenavirus", "Binding", "Biological Assay", "Biological Availability", "Bolivian Hemorrhagic Fever Virus", "Cell Surface Receptors", "Cessation of life", "Chemicals", "Clinical", "Combined Modality Therapy", "Complex", "Cryoelectron Microscopy", "Data", "Development", "Drug Kinetics", "Endosomes", "Exhibits", "FDA approved", "Face", "Family", "Flow Cytometry", "Future", "Genetic Variation", "Giant Cells", "Glycoproteins", "Goals", "Hemorrhage", "Human", "Immunotherapy", "In Vitro", "Infection", "International", "Intervention Strategies", "Lassa Fever", "Lassa virus", "Lead", "Libraries", "Mastomys", "Mediating", "Membrane", "Membrane Fusion", "Membrane Proteins", "Metabolic", "Molecular", "Molecular Conformation", "Oral", "Outcome", "Pathogenicity", "Pharmaceutical Chemistry", "Pharmaceutical Preparations", "Population", "Process", "Prodrugs", "Property", "Proteins", "Public Health", "Reagent", "Research Personnel", "Resource-limited setting", "Resources", "Rodent", "Series", "Specificity", "Structure-Activity Relationship", "Sulfonamides", "Testing", "Therapeutic", "Time", "Travel", "Vaccines", "Viral", "Viral Genome", "Viral Proteins", "Virus", "Work", "analog", "anti-viral efficacy", "career", "clinical development", "cost", "cost effective", "cytotoxicity", "design", "drug discovery", "drug metabolism", "emerging pathogen", "epidemic potential", "experience", "glycosylation", "health care settings", "high throughput screening", "improved", "in vivo", "inhibitor", "insight", "neutralizing antibody", "novel", "pathogen", "pharmacologic", "preclinical development", "rational design", "receptor", "scaffold", "small molecule", "small molecule inhibitor", "small molecule therapeutics", "structural biology", "synergism", "therapeutic development", "tool", "translational therapeutics", "transmission process", "vaccine-induced antibodies", "viral entry inhibitor", "virology", "α-Dystroglycan" ], "approved": true } }, { "type": "Grant", "id": "16059", "attributes": { "award_id": "1R01AI201438-01", "title": "Development of broadly protective merbecovirus and sarbecovirus countermeasures", "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": 32831, "first_name": "JENNIFER L", "last_name": "GORDON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-08-04", "end_date": "2031-07-31", "award_amount": 756936, "principal_investigator": { "id": 44402, "first_name": "KEVIN O", "last_name": "SAUNDERS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3473, "ror": "", "name": "DUKE UNIVERSITY", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "There are two subgenera of βCoVs, Merbecovirus and Sarbecovirus, that cause severe disease in humans, for which broadly protective medical countermeasures are needed. While conserved sites of vulnerability on the virus Spike, called the receptor binding domain (RBD) and stem helix (SH), have been noted for merbecoviruses (MERBs) and sarbecoviruses (SARBs), antibodies to these epitopes tend to be infrequently elicited during infection or with current treatments. Our scientific premise is that nanoparticle (NP) S fragment immunogens elicit high titers of broadly neutralizing antibodies by focusing the immune response on subdominant epitopes. We proposed here to employ our innovative NP design technology to elicit broadly protective immunity against both subgenera of viruses. In rigorous preliminary studies, our RBD NP elicited neutralizing antibodies and protected mice against MERB MERS-CoV and four different SARBs. Also, our RBD NPs elicited neutralizing antibodies against 11 different SARBs, 5 different MERBs, and protected monkeys against SARB and MERB infection. Our central hypothesis is that neutralizing antibody breadth can be increased to cover many viruses within a βCoV subgenera by simultaneously eliciting a polyclonal, high-affinity antibody response to RBD and SH on CoV S. To determine the extent that polyclonal responses are needed, Specific Aim 1 will determine the antibody clonality and immunogenetics features that afford broad MERB and SARB neutralization. No known antibodies that bind to RBD and neutralize both MERBs and SARBs have been identified to date. The work in this aim will define the antibodies that mediate neutralization of each subgenus of viruses in order to understand the structural and genetic basis for how the neutralization breadth of these antibodies is limited within or across subgenera. In Specific Aim 2, we will further optimize our NP immunogens to increase the breadth of antibody response they elicit. Guided by the information about what viral sequences are resistant to the current induced antibodies, new immunogens will be designed using computational structural and bioinformatic approaches. These new immunogens will be tested for the ability to elicit broader neutralizing antibodies in mice than a commercial drug and our earlier immunogen designs. In Specific Aim 3, we will define the Ab responses that correlate with protection against SARBs and MERBs. Successful immunogens will be examined for their ability to elicit protective immunity against both Merbecoviruses and Sarbecoviruses in innovative mouse challenge models uniquely available to this team. Upon completion of this study, its impact will be the elucidation of new design approaches to target and protect against large subgenera of viruses rather than a single virus. Also, the final immunogen designed here, can be manufactured in the future to provide a countermeasure against deadly viruses for which there is no current treatment.", "keywords": [ "Amino Acids", "Antibodies", "Antibody Affinity", "Antibody Formation", "Antibody Response", "Antibody-mediated protection", "Antigens", "B-Lymphocytes", "Binding", "Bioinformatics", "Clonality", "Collection", "Coronavirus", "Coronavirus Infections", "Coronavirus spike protein", "Death Rate", "Development", "Disease", "Engineering", "Epitopes", "Future", "Genetic", "Glean", "Goals", "Human", "Immune response", "Immunity", "Immunize", "Immunogenetics", "Infection", "Infection prevention", "Infusion procedures", "Intervention", "Lung", "Macaca", "Machine Learning", "Mediating", "Merbecovirus", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Monkeys", "Mus", "Nucleotides", "Pathogenicity", "Performance", "Pharmaceutical Preparations", "Preventive", "Proteins", "Resistance", "SARS coronavirus", "Sarbecovirus", "Serum", "Site", "Surface", "Technology", "Testing", "Upper respiratory tract", "Viral", "Virus", "Work", "betacoronavirus", "cross reactivity", "design", "humanized mouse", "immunogen", "immunogenicity", "improved", "innovation", "manufacture", "medical countermeasure", "nanoparticle", "neutralizing antibody", "polyclonal antibody", "programs", "receptor binding", "response", "self assembly", "stem", "structural mutation", "structure-guided design" ], "approved": true } }, { "type": "Grant", "id": "16043", "attributes": { "award_id": "1K23AI197092-01A1", "title": "Defining the Scope and Consequences of Gut Microbiome Dysbiosis in Hospitalized Patients", "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": 44511, "first_name": "RYAN", "last_name": "RANALLO", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-08-03", "end_date": "2031-07-31", "award_amount": 185760, "principal_investigator": { "id": 44512, "first_name": "Christopher", "last_name": "Lehmann", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3459, "ror": "", "name": "UNIVERSITY OF CHICAGO", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "This K23 proposal outlines a 5-year research and training plan that will accelerate Dr. Christopher Lehmann’s career as an independent physician-scientist with expertise in the gut microbiome and AR infections. Dr. Lehmann is a practicing infectious disease physician whose translational research is focused on identifying associations between the gut microbiome and clinical outcomes. He has demonstrated that antibiotics kill beneficial members of the gut microbiome, lower the production of beneficial metabolites, and permit the expansion of AR pathogens that, in turn, cause invasive infection. His collaborative work has demonstrated that dysbiosis is associated with disease progression and death in COVID-19, cirrhosis, and heart transplant Other groups have shown similar results in additional defined populations. Despite these strong links, the populations studied are select and account for only a fraction of patients at risk for gut microbial dysbiosis and AR infection. In this proposal, Dr. Lehmann will test the hypothesis that dysbiosis occurs broadly in hospitalized patients and is associated with AR infections and other morbidities. In Aim 1, he will (1) enroll 500 patients admitted to a general acute care hospital floor, (2) serially collect and sequence the stool microbiomes of those patients, and (3) determine the microbiome composition of hospitalized patients. In Aim 2, he will interrogate the microbiome’s function by determining the prevalence and degree of beneficial metabolite depletion. Finally, in Aim 3, he will identify the consequences of dysbiosis on patients by comparing the microbiome and metabolome to post discharge outcomes and AR infection. To accomplish these goals, Dr. Lehmann has designed a training plan that builds on his clinical skills and research background with focused training in bioinformatics, biostatistics, and epidemiology. Dr. Lehmann’s research will be overseen by dedicated mentors from University of Chicago with expertise in translational research, microbial genomics, microbial metabolomics, bioinformatics, biostatistics, and hospital epidemiology. Additionally, this project will leverage extensive data and sample collection supported by the Duchossois Family Institute and led by Dr. Lehmann’s primary mentors Dr. Eric Pamer and Dr. Erika Claud. This integrated training and mentorship plan will support him in his discovery of the interactions between the microbiome and infectious disease. Facilitated by this award, Dr. Lehmann will develop into an independent physician-scientist poised to advance understanding in the field of the microbiome, antimicrobial resistance, and human health.", "keywords": [ "Acceleration", "Accounting", "Advisory Committees", "Antibiotics", "Antimicrobial Resistance", "Award", "Bacteroidaceae", "Bile Acids", "Bioinformatics", "Biometry", "Bypass", "COVID-19 mortality", "Cessation of life", "Chicago", "Cirrhosis", "Clinical", "Clinical Data", "Clinical Investigator", "Clinical Research", "Clinical Skills", "Clostridium difficile", "Communicable Diseases", "Complex", "Coupled", "Data Collection", "Dedications", "Disease Progression", "Enrollment", "Epidemiology", "Family", "Feces", "Floor", "Fostering", "Frequencies", "Genes", "Goals", "Health", "Heart Transplantation", "Hospitalization", "Hospitals", "Human", "Impairment", "Infection", "Injury", "Inpatients", "K-Series Research Career Programs", "Knowledge", "Link", "Liver diseases", "Malignant Neoplasms", "Measurement", "Measures", "Mentors", "Mentorship", "Metabolic Pathway", "Morbidity", "Outcome", "Patient Admission", "Patient Care", "Patient-Focused Outcomes", "Patients", "Pattern", "Physicians", "Population", "Population Study", "Populations at Risk", "Prevalence", "Production", "Research", "Risk", "Scientist", "Taxonomy", "Testing", "Training", "Translational Research", "Tryptophan", "Universities", "Vancomycin resistant enterococcus", "Volatile Fatty Acids", "Work", "acute care", "antimicrobial resistant infection", "antimicrobial resistant pathogen", "carbapenem resistant Enterobacterales", "career", "career development", "clinically actionable", "combat", "design", "dysbiosis", "experience", "fecal microbiome", "gut microbiome", "hospital care", "hospital patient care", "hospital readmission", "immune function", "improved", "improved outcome", "individual patient", "insight", "knowledge base", "member", "metabolome", "metabolomics", "metagenomic sequencing", "microbial", "microbial genomics", "microbiome", "microbiome composition", "microbiome therapeutics", "mortality", "participant enrollment", "pathogen", "preservation", "prospective", "restoration", "sample collection", "skills" ], "approved": true } }, { "type": "Grant", "id": "16042", "attributes": { "award_id": "1DP2AI201031-01", "title": "Next-Generation Interferons: Mapping and Engineering Antiviral Function", "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": 32556, "first_name": "TIMOTHY A", "last_name": "GONDRE-LEWIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-08-03", "end_date": "2031-07-31", "award_amount": 456000, "principal_investigator": { "id": 44510, "first_name": "Jeremie", "last_name": "Le Pen", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3458, "ror": "", "name": "HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Modern medicine has learned to harness adaptive immunity through vaccines, monoclonal antibodies, and engineered T cells. In contrast, the innate immune system—our first and most universal line of defense—remains largely untapped as a therapeutic frontier. Interferons (IFNs) sit at the core of this system, yet we lack a predictive framework linking IFN sequence, timing, and cross-family signaling to biological function. The human genome encodes 22 distinct IFNs with multiple alleles and polymorphisms, but their functional “grammar”—the rules that govern antiviral potency, duration, and inflammatory cost—remains unreadable. The stakes are high. In collaboration with Jean-Laurent Casanova (HHMI, Rockefeller University), we found that autoantibodies neutralizing type I IFNs account for ~15% of critical COVID-19 pneumonia and ~20% of related deaths, while recessive inborn errors of IFN immunity explain ~10% of pediatric COVID-19 hospitalizations and cause severe reactions to live-attenuated vaccines. Defective IFN function—whether due to genetics or autoantibodies—is therefore one of the strongest known risk factors for life-threatening viral disease. Yet we still cannot interpret patient IFN variants or design new IFN therapies that resist antibody blockade while avoiding inflammation. To close this gap, I propose SuperScan, a synthetic-DNA–enabled, arrayed screening platform to decode the IFN sequence–function grammar. Unlike pooled approaches, which lose genotype–phenotype linkage once secreted proteins diffuse, SuperScan preserves spatial separation, enabling precise, time-resolved measurements of antiviral activity, inflammatory signaling, cell viability, and autoantibody susceptibility. Aim 1 will build the first systematic functional atlas of human IFNs and their natural variants. Aim 2 will engineer next-generation IFN-λ3 variants with optimized potency and safety. Aim 3 will map the combinatorial logic of type I and type III IFNs—defining how these cytokines cooperate or antagonize each other to balance protection and inflammation. I am uniquely positioned to lead this effort. During my postdoctoral training with Charles M. Rice (2020 Nobel Laureate, Rockefeller University), I developed genome-scale, arrayed infection assays under authentic viral challenge—the technical and conceptual foundation for SuperScan. This high-risk, high-reward project will deliver the first predictive framework linking IFN sequence and timing to biological function. By redefining type I and III IFNs not as redundant antiviral signals but as parameters of a molecular code that programs the strength, duration, and inflammatory cost of innate immunity, this work establishes a foundation for programmable cytokine engineering. Beyond interferons, SuperScan provides a versatile blueprint for decoding and designing other immune mediators, directly advancing the NIAID mission to prevent and treat infectious and immune-mediated diseases.", "keywords": [ "Address", "Affect", "Alleles", "Amino Acid Substitution", "Anti-viral Agents", "Antibodies", "Atlases", "Attenuated Vaccines", "Autoantibodies", "Biological", "Biological Assay", "Biological Process", "Biological Response Modifiers", "COVID-19", "COVID-19 pneumonia", "Cell Survival", "Cells", "Cessation of life", "Childhood", "Code", "Collaborations", "Cytoprotection", "Diffuse", "Disease", "Engineering", "Epithelial Cells", "Equilibrium", "Family", "Feedback", "Foundations", "Gene Expression Profiling", "Genes", "Genetic", "Genetic Polymorphism", "Genotype", "Goals", "Hereditary Disease", "Hospitalization", "Human", "Human Genome", "Immune", "Immunity", "Infection", "Inflammation", "Inflammatory", "Influenza", "Innate Immune System", "Interferon Type I", "Interferons", "Lead", "Learning", "Libraries", "Life", "Link", "Logic", "Maps", "Measurement", "Mediating", "Middle East Respiratory Syndrome", "Mission", "Modeling", "Modern Medicine", "Molecular", "Monoclonal Antibodies", "Mutation", "National Institute of Allergy and Infectious Disease", "Natural Immunity", "Outcome", "Pathology", "Pathway interactions", "Patients", "Persons", "Phenotype", "Positioning Attribute", "Postdoctoral Fellow", "Predisposition", "Protein Secretion", "Reaction", "Recombinant Interferon", "Regulation", "Resistance", "Rice", "Risk Factors", "Safety", "Shapes", "Signal Transduction", "Structural Models", "System", "Testing", "Therapeutic", "Tick-Borne Encephalitis", "Time", "Training", "Trajectory", "Universities", "Vaccines", "Variant", "Viral", "Viral Physiology", "Virus", "Virus Diseases", "West Nile Encephalitis", "Work", "Yellow Fever", "adaptive immunity", "anti-viral efficacy", "career", "combinatorial", "cost", "cytokine", "cytokine therapy", "desensitization", "design", "engineered T cells", "experience", "frontier", "functional genomics", "genome-wide", "high reward", "high risk", "improved", "innovation", "interferon therapy", "neutralizing antibody", "next generation", "post-doctoral training", "preservation", "prevent", "programs", "receptor binding", "response", "screening", "severe COVID-19", "synergism", "synthetic construct", "transcriptome sequencing" ], "approved": true } } ], "meta": { "pagination": { "page": 5, "pages": 1442, "count": 14420 } } }