Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=2&sort=-awardee_organization
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-awardee_organization", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=-awardee_organization", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=-awardee_organization", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-awardee_organization" }, "data": [ { "type": "Grant", "id": "15981", "attributes": { "award_id": "1R21AI190798-01A1", "title": "Detection of Shigella Species in Wastewater - A Pilot Study for Community and Building Scale Wastewater-Based Surveillance of Bacterial Pathogens", "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": 44432, "first_name": "JONATHAN A", "last_name": "GLOCK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-03", "end_date": "2028-01-31", "award_amount": 422125, "principal_investigator": { "id": 44436, "first_name": "Anthony T", "last_name": "Maurelli", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3432, "ror": "", "name": "UNIVERSITY OF FLORIDA", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "/ Abstract Bacillary dysentery or shigellosis is caused by bacteria of the Shigella species: S. dysenteriae, S. flexneri, S boydii, and S. sonnei. Infections range from mild or asymptomatic to severe bloody diarrhea, so reported prevalence grossly underestimates actual prevalence. Shigellosis is a global public health concern and antimicrobial resistance has compounded the problem. Moreover, shigellosis is also sexually transmitted in the United States, Europe, and other developed countries. Such outbreaks are driven by the emergence of antibiotic resistant strains of S. flexneri infecting men who have sex with men. The objective of this proof-of-concept study is to demonstrate that wastewater-based epidemiology (WBE) using digital PCR to detect pathogen molecular markers can provide a more accurate picture of community prevalence of bacterial pathogens than traditional case reporting. Wastewater surveillance for viral pathogens has been in use for decades and its use to monitor SARS-CoV-2 is now widely applied globally. Analogous methods for wastewater surveillance of bacterial pathogens by digital PCR has lagged. We will develop and validate methods to detect Shigella, an important bacterial agent of diarrheal disease, in wastewater. We will also field test the methods to assess shigellosis prevalence at community and building scale and link the data to the actual population residing in the wastewater collection area. We will provide actionable data to the local health department which can then develop targeted public health interventions. The independent but complementary aims in demonstrating the proof-of-concept are: 1. Develop and validate sensitive, specific, and reproducible WBE methods for detection of Shigella species in wastewater using digital PCR. Three subaims will: 1.1) optimize methods for extraction and detection of Shigella in wastewater using laboratory-grown strains of Shigella species to “spike” authentic wastewater and laboratory prepared “synthetic” wastewater; 1.2) validate molecular targets for differentiation of S. flexneri from S. sonnei in wastewater; and 1.3) culture of Shigella from wastewater to assess antibiotic resistance genotypes and phenotypes. 2. Assess proof-of-concept of WBE as a public health tool for Shigella at community and building scale with emphasis on high risk congregate populations, i.e., day care centers. Two subaims will: 2.1) measure the prevalence of Shigella species at community scale by sampling at the wastewater treatment plant intake and using wastewater flow rate as a population normalization marker; and 2.2) extend shigellosis surveillance to building scale targeting high risk congregate pediatric populations. Strengths of this proposal are the innovative application of WBE to a bacterial pathogen, our method for population normalization, differentiation of Shigella species, prevalence measurement of Shigella species at community and building scale, and the expertise of our multidisciplinary team.", "keywords": [ "2019-nCoV", "Antibiotic Resistance", "Antimicrobial Resistance", "Area", "Automobile Driving", "Bacteria", "Bacterial Infections", "Behavior", "COVID-19 monitoring", "COVID-19 surveillance", "Case Study", "Centers for Disease Control and Prevention (U.S.)", "Childhood", "Collection", "Communities", "County", "Data", "Day center care", "Detection", "Developed Countries", "Development", "Disease", "Disease Outbreaks", "Dysentery", "Effectiveness", "Europe", "Excretory function", "Feces", "Florida", "Foundations", "Future", "Genetic", "Genotype", "Health", "Health Resources", "Hemorrhagic colitis", "Hot Spot", "Individual", "Infection", "Intake", "Intervention", "Laboratories", "Link", "Measles", "Measurement", "Measures", "Methodology", "Methods", "Molecular", "Molecular Analysis", "Molecular Profiling", "Molecular Target", "Monitor", "Pathogen detection", "Patients", "Phenotype", "Pilot Projects", "Plants", "Poliomyelitis", "Population", "Population Surveillance", "Populations at Risk", "Prevalence", "Public Health", "Reporting", "Reproducibility", "Research Proposals", "Sampling", "Sexual Transmission", "Shigella", "Shigella Infections", "Shigella boydii", "Shigella dysenteriae", "Shigella flexneri", "Shigella sonnei", "System", "Techniques", "Testing", "United States", "Universities", "Variant", "Viral", "Work", "detection method", "diarrheal disease", "digital", "experience", "field study", "global health", "high risk", "innovation", "men who have sex with men", "molecular marker", "multidisciplinary", "novel", "pathogenic bacteria", "pathogenic virus", "public health intervention", "resistant strain", "tool", "wastewater epidemiology", "wastewater monitoring", "wastewater samples", "wastewater sampling", "wastewater surveillance" ], "approved": true } }, { "type": "Grant", "id": "15980", "attributes": { "award_id": "1R01AI189659-01A1", "title": "Durable and broad airway immunity through next-generation intranasal boosters", "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": "2026-02-06", "end_date": "2031-01-31", "award_amount": 662465, "principal_investigator": { "id": 44435, "first_name": "David R.", "last_name": "Martinez", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3431, "ror": "", "name": "YALE UNIVERSITY", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "Intramuscular SARS-CoV-2 mRNA-LNP do not reliably nor durably elicit respiratory mucosal IgA. Moreover, vaccinated individuals who become infected are more durably protected and this is thought to be mediated by respiratory mucosal IgA. Currently, there are no mucosal respiratory vaccines for human use. We identified a mucosal booster vaccine admixed with a mast cell agonist adjuvant, mastoparan-7, and a toll-like receptor 9 agonist adjuvant, CpG, that elicits durable mucosal IgA. Importantly, mice intranasally boosted with a multivalent nanoparticle vaccine adjuvanted with mastoparan-7 and CpG are protected from bat SARS-like virus challenge. We propose to study the mechanism of mast cell and antigen-presenting cell signaling modulated by this novel mucosal adjuvant combination. We will pursue our central objective which is to understand how mucosal IgA is elicited and maintained following respiratory mucosal vaccination with our exciting universal vaccines to ultimately achieve durable and broadly protective immunity against zoonotic coronaviruses. To achieve this objective, we will complete these aims: Aim 1: Test the hypothesis that mast cells and antigen-presenting cells elicit specific cytokines and chemokines that modulate durable IgA. We propose to study the impact of intranasal boost dose and interval on IgA kinetics and durability. We will also define if the mastoparan-7 and CpG adjuvant combination requires mast cell and antigen presenting cells that signal through CpG via the TLR-9 pathway. We will then define gene expression profiles from respiratory tract mast cells and antigen presenting cells that are activated by mastoparan-7 and CpG and modulate durable mucosal IgA responses. Aim 2: Test the hypothesis that M7/CpG nanoparticle vaccine elicits durable IgA secreting cells and IgA memory B cells in the respiratory tract using lineage-tracing, fluorescent reporter mice pre- immune with common-cold CoV. We will determine how intranasal boosting modulates IgA-secreting plasma cells and IgA memory B cells that home back to the respiratory mucosa in SARS-CoV-2 immune mice and in mice immune against common-cold coronaviruses. We will use cre-lox inducible, IgA-secreting cell and IgA memory B cell fluorescent reporter mice to define how intranasal boosting modulates mucosal IgA immunity. We will also test adjuvant and intranasal safety using a human lymph node organoid model from upper- respiratory tract draining lymph tissue from humans. Aim 3: Test the hypothesis that durable mucosal IgA can protect against transmissible SARS-CoV-2 variants in hamster transmission models and protect against SARS-related coronaviruses. We will determine if the mastoparan-7 and CpG adjuvanted nanoparticle intranasal booster reduces transmission of SARS-CoV-2 variants in hamster models. We will also use IgA knockout mice to determine if IgA is required for protection against SARS-like viruses.", "keywords": [ "2019-nCoV", "Adjuvant", "Agonist", "Antigen Targeting", "Antigen-Presenting Cells", "Antigens", "B-Lymphocytes", "Back", "COVID-19 vaccine", "Cell Degranulation", "Cell secretion", "Chiroptera", "Common Cold", "Coronavirus", "Coupled", "Data", "Disease", "Dose", "Ferritin", "Frequencies", "Gene Expression Profile", "Generations", "Genes", "Goals", "Hamsters", "Health", "Home", "Human", "Immune", "Immune response", "Immune signaling", "Immunity", "Immunobiology", "Immunoglobulin A", "Immunologics", "Intramuscular", "Intranasal Administration", "Kinetics", "Knockout Mice", "Knowledge", "Length", "Lineage Tracing", "Lymph", "Mediating", "Memory B-Lymphocyte", "Messenger RNA", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Monitor", "Mucosal Immunity", "Mucous Membrane", "Mus", "Organoids", "Pathogenicity", "Pathway interactions", "Patients", "Peptides", "Plasma Cells", "RNA vaccine", "Receptor Signaling", "Reporter", "Respiration", "Respiratory Mucosa", "Respiratory System", "SARS coronavirus", "SARS-CoV-2 transmission", "SARS-CoV-2 variant", "Safety", "Severe Acute Respiratory Syndrome", "Signal Transduction", "TLR9 gene", "Tamoxifen", "Testing", "Upper respiratory tract", "Vaccinated", "Vaccination", "Vaccine Adjuvant", "Vaccinee", "Vaccines", "Virus", "Work", "Zoonoses", "antiviral immunity", "booster vaccine", "chemokine", "coronavirus vaccine", "cross immunity", "cytokine", "experimental study", "gene panel", "human tissue", "lipid nanoparticle", "lymph nodes", "mast cell", "mastoparan", "mucosal vaccination", "mucosal vaccine", "nanoparticle", "next generation", "novel", "novel coronavirus", "pandemic disease", "preclinical safety", "respiratory", "respiratory virus", "response", "single-cell RNA sequencing", "tool", "transmission process", "universal vaccine", "vaccine evaluation", "zoonotic coronavirus" ], "approved": true } }, { "type": "Grant", "id": "15979", "attributes": { "award_id": "1R21AI188074-01A1", "title": "Identification of RNAi-independent antiviral genes through biased genetic screen in C. elegans", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32860, "first_name": "KENTNER L", "last_name": "SINGLETON", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-02", "end_date": "2028-01-31", "award_amount": 412500, "principal_investigator": { "id": 44434, "first_name": "Rui", "last_name": "Lu", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3430, "ror": "", "name": "LOUISIANA STATE UNIV A&M COL BATON ROUGE", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Viruses, especially RNA viruses, are formidable pathogens to cellular hosts. Owing to the error-prone nature of their replicases, RNA viruses rapidly accumulate large numbers of genetic mutations in their genome, enabling them to evade immune detection. Some RNA viruses, such as influenza viruses and coronaviruses, can also generate genome variants through genome reassortment or genome recombination mechanisms. It is thus important to study antiviral mechanisms intrinsically resistant to genetic mutations in viral genome, which may lead to the development of novel antiviral strategies. In plants, insects and vertebrates, there are antiviral mechanisms triggered by non-dsRNA products of invading viruses. These antiviral mechanisms provide another layer of protection in case viral dsRNA-triggered immunity is compromised by the invading viruses. In supporting this hypothesis, many plant and animal viruses have been found to produce diverse types of dsRNA binding proteins that are able to bind and sequester viral dsRNA to block immune detection. So far, RNAi is known as the most important antiviral defense mechanism in Caenorhabditis elegans. However, some recent studies on worm antiviral defense suggest that viral infection in C. elegans triggers transcriptional programs that in return provide protection against invading viruses in an RNAi-independent manner. Therefore, very much like what has been demonstrated in plants and insects, RNAi-independent antiviral defense (RiAD) may provide worms another layer of protection against virus in case antiviral RNAi is compromised. To fill the knowledge gap in our understanding of worm RiAD and as proof of principle, the PI’s lab has recently carried out a biased genetic screen of limited scale, aiming to identify genes specifically contributing to worm RiAD. This genetic screen identified 8 candidate genes that confer RiAD targeting a flock house virus (FHV) replicon. 5 of these candidate genes also mediate RiAD against Orsay virus, which naturally infects C. elegans (21). In this application, we propose to continue the biased genetic screen and finish it on a much greater scale to ensure double coverage on all genes involved in RiAD. We will then map and identify the candidate genes through whole genome sequencing combined with feeding RNAi and function rescue assay. Since approximately 70% of C. elegans genes have human homologs, function and mechanism study of the identified genes may not only lead to the identification of novel conserved mechanisms of antiviral innate immunity across kingdoms but also inform the development of novel antiviral strategies.", "keywords": [ "Alleles", "Animals", "Anti-viral Agents", "Anti-viral Response", "Binding", "Binding Proteins", "Biological Assay", "Caenorhabditis elegans", "Candidate Disease Gene", "Complement", "Coronavirus", "Defense Mechanisms", "Detection", "Development", "Double-Stranded RNA", "Ensure", "Genes", "Genetic", "Genetic Recombination", "Genetic Screening", "Genetic Transcription", "Genome", "Homologous Gene", "Human", "Immune", "Immune Evasion", "Immunity", "Insecta", "Interferons", "Invaded", "Knowledge", "Lead", "Mammals", "Maps", "Mediating", "Mutation", "Natural Immunity", "Nature", "Nematoda", "Organism", "Pathway interactions", "Plants", "RNA Interference", "RNA Viruses", "Replicon", "Research", "Resistance", "Variant", "Vertebrates", "Viral", "Viral Genes", "Viral Genome", "Virus", "Virus Diseases", "Work", "antiviral immunity", "candidate identification", "design", "feeding", "gene function", "genome sequencing", "genome-wide", "influenzavirus", "novel", "pathogen", "pathogenic virus", "programs", "protective pathway", "replicase", "response", "whole genome" ], "approved": true } }, { "type": "Grant", "id": "15978", "attributes": { "award_id": "1R01AI196176-01", "title": "Inhibiting Chikungunya Virus Protease using MTase-like Domain Interactions for Novel Antiviral Therapies.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32808, "first_name": "MINDY I", "last_name": "DAVIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-23", "end_date": "2031-01-31", "award_amount": 632994, "principal_investigator": { "id": 44433, "first_name": "Jeanne Ann", "last_name": "Hardy", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3429, "ror": "", "name": "UNIVERSITY OF MASSACHUSETTS AMHERST", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Chikungunya (CHIKV) is an RNA alphavirus that infects 3 million people in 45 countries including the US annually. Acute infection is flu-like, but in 40% of infections, debilitating joint pain emerges that can last for years. Infection during pregnancy also results in severe encephalopathy in newborns or aborted fetuses. Viral proteases are effective antiviral drug targets and are the standard of care for viral diseases (e.g HIV, hepatitis C, SARS-CoV- 2). The activity of the nsP2 protease from CHIKV (CHIKVP) is vital for infection. Inhibition of CHIKVP blocks processing of the viral polyprotein, prevents viral replication, lowers viral titers and stops disease progression. Thus, CHIKVP is an excellent antiviral drug target. To date, no effective antivirals of CHIKVP have been approved for acute or chronic infection. Our ultimate goal is to use insights into CHIKVP structure and dynamics to develop an inhibitor to oppose CHIKV infection, the resulting chronic pain and prevent pediatric neurological syndromes. CHIKVP is composed of a protease domain and a methyltransferase-like domain (MTL). To date, no functions of the MTL have been identified. In a search for novel CHIKVP binders, we identified ligands that bind to the MTL at an elongated cavity and allosterically inactivate the protease. The site shares structural homology with S-adenosyl methionine (SAM) cofactor binding sites, but does not bind SAM. The allosteric site binds to GTP, which suggests that a function such as RNA binding may be conserved in the MTL. Here we propose a research strategy for the development and direct comparison of CHIKVP active-site and allosteric inhibitors. We will build compounds derived from a large compound screen and also build from MTL-binding fragments we have already identified. We have developed NMR approaches that allow us to readily distinguish active-site from allosteric inhibitors. Importantly, we have developed approaches that allow us to monitor activity, binding and dynamics in solution without having to rely on freezing samples which is required for other structural techniques, to inform our inhibitor design. Recent data have suggested that RNA plays a critical role in CHIKVP function, enhancing protease activity. We have identified a site that we hypothesize binds RNA and describe a series of studies to understand the mechanism by which RNA impacts protease function. We will bring all these structural insights into our inhibitor development approach. At each step of development, we will closely monitor efficacy against viral infection for CHIKV and other related alphaviruses to determine whether pan-alphaviral inhibition is achievable with a given class of compounds. Critically, we will also implement a directed evolution approach across both domains of CHIKVP to predict the susceptibility of our inhibitors to resistance mutations. This will enable us to develop enduring antivirals and will also address longstanding unanswered questions about the favorability of allosteric inhibition in antiviral drug development.", "keywords": [ "2019-nCoV", "Aborted Fetus", "Active Sites", "Address", "Adult", "Allosteric Site", "Alpha Virus", "Anti-viral Agents", "Anti-viral Therapy", "Arthralgia", "Back", "Binding", "Binding Sites", "Characteristics", "Chikungunya virus", "Child", "Childhood", "Clinical", "Country", "Data", "Development", "Directed Molecular Evolution", "Disease", "Disease Progression", "Drug Targeting", "Drug resistance", "Encephalopathies", "FDA approved", "Family", "Fluorogenic Substrate", "Freezing", "Future", "Goals", "Guanosine Triphosphate", "HIV", "HIV Care", "Hepatitis C", "Hepatitis C virus", "Infection", "Inflammation", "Intervention", "Late pregnancy", "Ligand Binding", "Light", "Mediating", "Methyltransferase", "Molecular", "Monitor", "Motion", "Myalgia", "Nervous System Disorder", "Neurologic", "Newborn Infant", "Peptide Hydrolases", "Persons", "Pharmaceutical Chemistry", "Play", "Polyproteins", "Predisposition", "Pregnancy", "Pregnant Women", "Property", "Protease Domain", "Protease Inhibitor", "RNA", "RNA Binding", "Reporting", "Research", "Role", "S-Adenosylhomocysteine", "S-Adenosylmethionine", "SARS-CoV-2 infection", "Sampling", "Series", "Site", "Structure", "Syndrome", "Techniques", "Testing", "Time", "Vaccination", "Vaccines", "Viral", "Virus Diseases", "Virus Inhibitors", "Virus Replication", "acute infection", "antiviral drug development", "chikungunya infection", "chronic infection", "chronic pain", "cofactor", "design", "drug resistance development", "emerging pathogen", "enzyme mechanism", "flu", "high throughput screening", "inhibitor", "insight", "mosquito-borne", "novel", "pain symptom", "pandemic potential", "pandemic virus", "pharmacologic", "prevent", "resistance mutation", "screening", "small molecule", "standard of care", "unborn child" ], "approved": true } }, { "type": "Grant", "id": "15977", "attributes": { "award_id": "1R21AI196845-01", "title": "Rapid point-of-care diagnosis of symptomatic and asymptomatic herpes 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": 44432, "first_name": "JONATHAN A", "last_name": "GLOCK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-06", "end_date": "2028-01-31", "award_amount": 427625, "principal_investigator": { "id": 4494, "first_name": "Ronit", "last_name": "Fraiman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3428, "ror": "", "name": "UNIV OF NORTH CAROLINA CHAPEL HILL", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Herpes simplex virus (HSV) is highly contagious and can be transmitted via physical contact. HSV can be diagnosed by detecting the presence of the virus in lesions or the antibodies in the blood. Yet, viral shedding can happen from asymptomatic infections, highlighting the need for early and accurate detection of HSV to prevent transmission. The most common ways to detect HSV are nucleic acid testing of an active infection via qPCR or serological testing of antibody levels in patient serum. However, qPCR is only accurate if a person is symptomatic and in asymptomatic people both the FDA and the CDC recommend against serological testing due to issues with sensitivity. Additionally, current testing for CNS complications arising from HSV infections requires highly invasive cerebral spinal fluid (CSF) sampling to diagnose. Thus, rapid, accessible, sensitive, and accurate point- of-care tests are in dire need. In 2021, we published a watershed paper describing how we can leverage cell surface glycans that the SARS- CoV-2 virus uses to bind and infect cells, to capture it onto rapid test strips for sensitive detection of the virus (Kim et al, ACS Central Science). Inspired and motivated by our success with SARS-CoV-2 sensing, we propose a novel lateral flow strip assay (LFSA) device for rapid and reliable point-of-care antigen-based detection capable of differentiating between HSV-1 and HSV-2 infections and sensing of CNS complications through serum. As cell surface proteoglycans such as heparan sulfate play an important role in the binding and cell entry of HSV, we will leverage it as a universal binder and use type specific cell receptors to distinguish between HSV strains (Specific Aim 1). Higher selectivity will be achieved by exploring sensitivity to sulfonation of heparan sulfate and other glycocalyx proteins. Sensor performance will be evaluated in complex fluids such as human genital fluids or saliva, and in genital washings of HSV-infected mice. To enhance our ability to identify and subtype HSV, we will engineer tailored cell membranes to optimize their interactions with viral envelope proteins, and strip and print these cell-derived membranes on paper test strips in Specific Aim 2. In Specific Aim 3, we will develop a blood test for the rapid quantitative screening of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), upregulated biomarkers upon CNS damage. We will incorporate electrochemical signals for quantitative assessment. This Bluetooth device will enable early and fast triage of patients for further screening. Together, these devices will enable us rapid and cost-effective screening of high-risk populations, accurate subtyping, and a swift connection of patients with treatment.", "keywords": [ "2019-nCoV", "Address", "Affinity", "Antibodies", "Binding", "Biological Assay", "Biological Markers", "Biomimetics", "Blood", "Blood Tests", "Bluetooth", "Body System", "COVID-19 diagnostic", "Caring", "Cell Separation", "Cell Surface Proteins", "Cell membrane", "Cell surface", "Cells", "Centers for Disease Control and Prevention (U.S.)", "Central Nervous System", "Central Nervous System Infections", "Cerebrospinal Fluid", "Complex", "Detection", "Devices", "Diagnosis", "Diagnostic", "Diagnostic Equipment", "Disease Outbreaks", "Encephalitis", "Engineering", "Equipment", "Eye", "Genitalia", "Glial Fibrillary Acidic Protein", "Glycocalyx", "Glycoproteins", "Goals", "Heparin", "Heparitin Sulfate", "Herpes Simplex Infections", "Herpesviridae Infections", "Herpesvirus 1", "Human", "Human Herpesvirus 2", "Image Analysis", "Individual", "Infection", "Keratitis", "Lateral", "Lesion", "Light", "Link", "Liquid substance", "Membrane", "Meningitis", "Methods", "Mus", "Nervous System Trauma", "Nucleic Acid Amplification Tests", "Paper", "Patient Triage", "Patient-Focused Outcomes", "Patients", "Performance", "Persons", "Play", "Polysaccharides", "Positioning Attribute", "Printing", "Property", "Proteins", "Proteoglycan", "Publishing", "Rapid diagnostics", "Receptor Cell", "Recommendation", "Recurrence", "Role", "Saliva", "Sampling", "Science", "Serology test", "Serum", "Signal Transduction", "Simplexvirus", "Specificity", "Substance Use Disorder", "Sulfate", "Swab", "Testing", "Time", "Viral Antigens", "Viral Envelope Proteins", "Virulent", "Virus", "Virus Shedding", "World Health Organization", "antigen detection", "antigen test", "cost", "cost effective", "design", "disease transmission", "env Gene Products", "global health", "health care burden", "high risk population", "improved", "infection rate", "innovation", "macromolecule", "nectin", "neurofilament", "novel", "point of care", "point of care testing", "point-of-care detection", "point-of-care diagnosis", "prevent", "quantitative imaging", "rapid test", "screening", "sensor", "success", "test strip", "tool", "transmission process", "viral detection", "viral transmission" ], "approved": true } }, { "type": "Grant", "id": "15974", "attributes": { "award_id": "1R01AI191417-01A1", "title": "MARVELOUS: Maternal RSV Vaccination- Evaluating Optimal Immune Responses", "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": 44292, "first_name": "MERCY R", "last_name": "PRABHUDAS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-06", "end_date": "2030-01-31", "award_amount": 3859259, "principal_investigator": { "id": 21683, "first_name": "Andrea Goldberg", "last_name": "Edlow", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 736, "ror": "https://ror.org/002pd6e78", "name": "Massachusetts General Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22942, "first_name": "SABRA L.", "last_name": "KLEIN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, { "id": 44427, "first_name": "Liza", "last_name": "Konnikova", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 3427, "ror": "", "name": "MASSACHUSETTS GENERAL HOSPITAL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The recent approval of the Respiratory Syncytial Virus (RSV) vaccine for administration in pregnancy presents a novel opportunity to define immune responses of the maternal-fetal dyad, and how that response crosses the placenta and mammary tissue. Recent work indicates that timing of maternal RSV vaccination alters placental antibody transfer to the fetus. To maximize infant protection after maternal RSV vaccination, key gaps in knowledge include: 1. The extent to which maternal vaccination elicits direct fetal antigen-agnostic and antigen- specific cellular responses to augment infant protection from RSV and other infections. 2. How gestational age at vaccination alters maternal antibody response, subsequent placental and breastmilk antibody transfer, and persistence of immunity in the infant. The proposed studies will test the central hypothesis that timing of maternal vaccination, antibody Fc-receptor binding properties, glycosylation profiles, neutralizing antibody levels and non-neutralizing antibody functions are all key determinants of placental and breastmilk antibody transfer to the neonate. These antibody features will work in concert with fetal innate and adaptive immune responses to maternal vaccination, driving protection of the infant through 6 months of age. In a cohort of 400 pregnant women and their infants, this study will examine fetal cellular responses to maternal RSV vaccination, both RSV-agnostic and RSV-specific, by evaluating fetal immune cells isolated from placental villi and cord blood (Aim 1). It will comprehensively profile placentally- and breastmilk-transferred antibodies after RSV vaccination in pregnancy, evaluating IgG subclass, Fc-receptor binding, glycosylation profile, and neutralizing capacity of antibodies using in vivo and in vitro assays (Aim 2). It will then evaluate how antibody properties and timing of maternal vaccination impact the durability of antibody-mediated and cellular immunity in infant blood and breastmilk, through 6 months of age (Aim 3). Machine learning approaches will be used to estimate the magnitude and specific features of protective immune responses induced by maternal vaccination, not only for RSV, but also for influenza, Tdap, and COVID-19. These methods will generate a comprehensive model of durable infant protection from maternal vaccination spanning multiple pathogens. Defining these immune principles across the maternal-fetal dyad will generate key biological insights necessary to optimize neonatal and infant protection.", "keywords": [ "3-Dimensional", "Address", "Age Months", "Antibodies", "Antibody Response", "Antibody-mediated protection", "Antigens", "Automobile Driving", "Biological", "Biological Assay", "Blood", "Breast", "Breast Epithelial Cells", "COVID-19", "COVID-19 vaccination", "COVID-19 vaccine", "Cell Separation", "Cells", "Cellular Immunity", "Characteristics", "Chorionic villi", "Clinical Trials", "Clonal Expansion", "Colostrum", "Data", "Disease", "Ensure", "Fc Receptor", "Fetus", "Future", "Gene Expression Profile", "Gestational Age", "Human Milk", "Immune", "Immune response", "Immune system", "Immunity", "Immunoglobulin G", "In Vitro", "Infant", "Infection", "Influenza", "Innate Immune Response", "Knowledge", "Life", "Longevity", "Machine Learning", "Maternal antibody", "Measures", "Mediating", "Memory", "Methods", "Milk", "Modeling", "Mononuclear", "Mothers", "Nature", "Neonatal", "Peptides", "Pertussis", "Phase III Clinical Trials", "Phenotype", "Placenta", "Plasma", "Polysaccharides", "Pregnancy", "Pregnant Women", "Premature Birth", "Property", "Prospective cohort", "Recommendation", "Respiratory Syncytial Virus Vaccines", "Respiratory syncytial virus", "Serology", "System", "T cell response", "T memory cell", "T-Lymphocyte", "Testing", "Time", "Tissues", "Training", "Umbilical Cord Blood", "Vaccinated", "Vaccination", "Vaccine Design", "Vaccines", "Work", "adaptive immune response", "anti-influenza", "antibody test", "antibody transfer", "cohort", "embryo/fetus antigen", "emerging pathogen", "experimental study", "fetal", "fetal immunity", "glycosylation", "immune function", "in vitro Assay", "in vivo", "infant morbidity", "infant morbidity/mortality", "insight", "large datasets", "machine learning method", "machine learning model", "mammary", "maternal vaccination", "neonatal immunity", "neonate", "neutralizing antibody", "novel", "pathogen", "placental transfer", "predictive modeling", "prenatal exposure", "receptor binding", "respiratory pathogen", "response", "sex", "transcytosis", "unvaccinated", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "15973", "attributes": { "award_id": "1R21AI190550-01A1", "title": "Discovery and evolution of mammalian Serpins as host-encoded viral 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": 32808, "first_name": "MINDY I", "last_name": "DAVIS", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-04", "end_date": "2028-01-31", "award_amount": 439250, "principal_investigator": { "id": 25173, "first_name": "Matthew", "last_name": "Daugherty", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 760, "ror": "https://ror.org/0168r3w48", "name": "University of California, San Diego", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3426, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN DIEGO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Viral proteases are essential for the replication of many RNA and DNA viruses. Through sequence specific recognition of cleavage sites, these proteases process viral polyproteins into their functional components, while also cleaving host proteins to facilitate viral replication. Interestingly, organisms from every domain of life encode proteins known as SERPINs (SERine Protease INhibitors) that serve as natural inhibitors of serine and cysteine proteases, the types of proteases encoded by many viruses. SERPINs contain a conserved structural core and a disordered reactive center loop (RCL) that ‘baits’ a protease into cleaving it by mimicking the sequence specificity of the protease to be inhibited. Following protease-mediated cleavage of the RCL, the SERPIN undergoes a large conformation change that covalently traps and inactivates the protease, thus connecting sequence-specific recognition of the SERPIN RCL to protease inhibition. While SERPINs have been largely characterized as inhibitors of a wide range of cellular proteases, we hypothesize in this grant that SERPINs have also evolved, in a species-specific manner, to directly inhibit viral protease activity and thereby inhibit viral replication. Supporting this hypothesis, we have found that several mammalian SERPINs contain RCLs that are rapidly evolving under positive selection, consistent with SERPINs being engaged in evolutionary arms races with pathogen-encoded proteases. Moreover, we have identified primate SERPINs that have independently evolved sequences that mimic the cleavage site preferences of proteases from picornaviruses and coronaviruses, and find that these SERPINs can inhibit viral protease activity during infection. These data lead us to propose a model in which SERPINs, with their protease baiting RCLs, represent a modular platform for evolution of host-specific antiviral activity through viral protease inhibition. Based on this model, we now propose to use evolutionary biology, protease biochemistry, and virology to discover and characterize the natural variation, evolvability, protease specificity, and antiviral activity of viral protease inhibitors among mammalian SERPINs. In Aim 1, we will test the antiviral potency and specificity of primate SERPIN-mediated viral protease inhibition, while also computationally and functionally searching for additional mammalian SERPINs that can inhibit proteases from a wide range of RNA viruses. In Aim 2, we will probe the modularity and evolvability of SERPINs to determine the degree to which the SERPIN ‘core’ and RCL sequence impact function, and how sequence evolution of each can mediate selective viral protease inhibition. By identifying SERPINs as novel, rapidly evolving, host-encoded viral protease inhibitors, our work will reveal the impact of SERPIN and viral protease evolution on this new host-virus evolutionary conflict and on species-specific barriers to virus replication, and unveil the evolutionary potential of SERPINs to inhibit a wide range of viral proteases.", "keywords": [ "2019-nCoV", "Adjustment Disorders", "Alpha Virus", "Aotus trivirgatus", "Architecture", "Attenuated", "Binding", "Biochemical", "Biochemistry", "Biological Assay", "Biology", "Caspase", "Cells", "Conflict (Psychology)", "Coronavirus", "DNA Viruses", "Data", "Dengue Virus", "Enterovirus", "Evolution", "Family", "Family Picornaviridae", "Flavivirus", "Grant", "HIV-1", "Hepatitis C virus", "Homologous Gene", "Human", "Infection", "Life", "Macaca mulatta", "Mammals", "Mediating", "Modeling", "Molecular", "Molecular Conformation", "Organism", "Peptide Hydrolases", "Polyproteins", "Primates", "Process", "Protease Inhibitor", "Protein Region", "Proteins", "RNA Viruses", "Rhinovirus", "Serine Proteinase Inhibitors", "Serpins", "Site", "Specificity", "Substrate Specificity", "Testing", "Variant", "Viral", "Viral Physiology", "Virus", "Virus Diseases", "Virus Inhibitors", "Virus Replication", "Work", "arms race", "expectation", "field study", "guided inquiry", "human coronavirus", "human pathogen", "inhibitor", "insight", "mutant", "novel", "pathogen", "preference", "success", "virology", "virus testing" ], "approved": true } }, { "type": "Grant", "id": "15972", "attributes": { "award_id": "1R01AI195981-01", "title": "Understanding programmed ribosomal frameshifting in coronaviruses", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-19", "end_date": "2031-01-31", "award_amount": 414029, "principal_investigator": { "id": 44426, "first_name": "Victoria Manuel", "last_name": "D'Souza", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3425, "ror": "", "name": "HARVARD UNIVERSITY", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Coronaviruses (CoV) are associated with severe diseases as demonstrated by the 2003 severe acute respiratory syndrome (SARS)-CoV1 epidemic and the SARS-CoV2 pandemic. One of the critical steps of infection involves viral mRNA mediated recoding of gene expression; a -1 frameshifting event that occurs during translation. It is this elegant mechanism that allows the ribosome to bypass a stop codon and synthesize viral enzymatic proteins. Furthermore, the frequency by which this event occurs is important for efficient viral infectivity and is regulated by domains in the translating mRNA (in the case of the SARS-CoV, this domain is a pseudoknot). Although structural studies of frameshifting have received considerable aOention and various structures have been proposed and solved, information on exactly which structure causes the frameshifting is lacking. Our preliminary studies indicate that CoV gene expression is regulated by a dynamic, proton-driven equilibrium between an active, and two inactive pseudoknot conformations that allows for strict control over the protein ratios. This proposal aims to gain a complete structural and mechanistic understanding of the frameshifting frequency in CoV by combining structural studies with biochemical and in vivo experiments. Our aims will be: (#1) to understand the basis for how the frameshifting frequency is maintained by engineering structure-guided mutants to test our equilibrium model, (#2) to determine the structures of the pseudoknot signal in both configurations: permissive and nonpermissive for frameshifting, and (#3) to determine the structure of ribosomes as they encounter the permissive conformation of the pseudoknot.", "keywords": [ "2019-nCoV", "Anti-viral Agents", "Biochemical", "Bypass", "COVID-19 pandemic", "Cell Line", "Characteristics", "Chemicals", "Code", "Complex", "Coronavirus", "Cryoelectron Microscopy", "Data", "Development", "Disease", "Engineering", "Equilibrium", "Event", "Frequencies", "Gene Expression", "Genetic", "In Vitro", "Infection", "Mediating", "Messenger RNA", "Molecular Conformation", "Mutation", "Nuclear Magnetic Resonance", "Nucleotides", "Outcome", "Population", "Preparation", "Process", "Proteins", "Protocols documentation", "Protons", "RNA", "Reading Frames", "Respiratory Disease", "Ribosomal Frameshifting", "Ribosomes", "SARS coronavirus", "Sampling", "Signal Transduction", "Structure", "Terminator Codon", "Testing", "Translating", "Translations", "Viral", "Virus", "Virus Replication", "conformer", "drug discovery", "equilibrium model", "experimental study", "in vivo", "insight", "live cell imaging", "mutant", "pandemic disease", "permissiveness", "protonation", "ribosome profiling", "sensor", "translation assay" ], "approved": true } }, { "type": "Grant", "id": "15971", "attributes": { "award_id": "1R35GM162359-01", "title": "The multifaceted pathways of astrovirus entry and egress", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 22244, "first_name": "MICHAEL", "last_name": "SAKALIAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-24", "end_date": "2030-12-31", "award_amount": 422677, "principal_investigator": { "id": 44425, "first_name": "Valerie", "last_name": "Cortez", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 3424, "ror": "", "name": "UNIVERSITY OF CALIFORNIA SANTA CRUZ", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Astroviruses are a major cause of pediatric diarrhea worldwide. Despite causing one of the most common early childhood infections, astroviruses are one of the least studied enteric RNA viruses. We previously discovered that the virus infects small intestinal goblet cells, specialized epithelial cells that secrete mucus. Few studies have investigated viral infection in goblet cells due to the lack of cell-specific models. Because the mechanisms by which viruses replicate inside of goblet cells are completely unknown, my lab is interested in addressing 1) how do astroviruses enter cells with highly dynamic apical membranes? and 2) what role does mucus secretion play in viral egress? We have established new in vitro models and tools to address these questions and have built a strong and collaborative investigative team with complementary expertise that will ensure the success of these projects. To evaluate receptor-mediated and fluid-phase endocytosis entry pathways into goblet cells, we will use a combination of CRISPR-Cas9 engineering, biochemical analysis, and high-resolution microscopy. We will use a similar suite of techniques as well as cryo-electron microscopy to define the egress pathway of astrovirus from goblet cells via mucus secretion. In addition to murine and human astroviruses, other respiratory and enteric viruses have also been shown to target goblet cells for infection. Thus, our work aims to initially provide foundational knowledge on the basic biology of astroviruses before shedding light on key host pathways in goblet cells that are co-opted by viruses from other families, including influenza and SARS-CoV2. Completion of these studies will provide the first major insights into the virus-host interactions at the apical membrane surface of intestinal goblet cells, which will pave the way for the future development of targeted drug treatments for the numerous viruses that target this unique cell population.", "keywords": [ "2019-nCoV", "Address", "Astrovirus", "Biochemical", "Biology", "CRISPR/Cas technology", "Cell model", "Cells", "Childhood", "Cryoelectron Microscopy", "Development", "Diarrhea", "Endocytosis", "Engineering", "Ensure", "Enteral", "Family", "Foundations", "Future", "Goblet Cells", "Human", "Infection", "Influenza", "Intestines", "Knowledge", "Light", "Liquid substance", "Mediating", "Microscopy", "Modeling", "Mucous body substance", "Mucus-Secreting Cell", "Mus", "Pathway interactions", "Phase", "Play", "Population", "Prevention strategy", "RNA Viruses", "Resolution", "Role", "Small Intestinal Goblet Cell", "Specialized Epithelial Cell", "Surface", "Techniques", "Viral", "Virus", "Virus Diseases", "Virus Replication", "Work", "apical membrane", "early childhood", "enteric virus infection", "in vitro Model", "insight", "interest", "novel", "receptor", "respiratory", "success", "targeted treatment", "tool", "treatment strategy", "virus host interaction" ], "approved": true } }, { "type": "Grant", "id": "15970", "attributes": { "award_id": "1R01DK145476-01", "title": "Mechanisms of non-HIV Collapsing Glomerulopathy in Hispanic Patients", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 44424, "first_name": "KEVIN E", "last_name": "CHAN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2026-02-15", "end_date": "2030-11-30", "award_amount": 783899, "principal_investigator": { "id": 22546, "first_name": "Sumant Singh", "last_name": "Chugh", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 804, "ror": "https://ror.org/01j7c0b24", "name": "Rush University Medical Center", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3423, "ror": "", "name": "RUSH UNIVERSITY MEDICAL CENTER", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "Non-HIV collapsing glomerulopathy (CG) is a severe form of glomerular disease seen in all parts of the world. Major etiological factors include circulating proteins that cause recurrent CG, infections like SARS-CoV-2 and Parvovirus B19, drugs like pamidronate, and background genomic changes potentially present in any of the preceding categories. Whereas variants of the APOL1 gene have been implicated in select populations with West African heritage, a genomic basis in other patient populations has not been elucidated. Using data from two decades of investigations into CG centered around Hispanic patients from Mexico City and more recent genomic data from Peruvian Hispanic patients, several novel mechanistic rat and mouse models of CG were developed. Critical components of the CG upstream pathways are the podocyte expressed transcriptional factor ZHX2 and glomerular integrins, including α3β1 in the podocyte, αvβ5 in the glomerular endothelium, and αvβ3 at both locations. Finally, recombinant mutated human Angiopoietin-like 4 protein 8520 is known to have an integrin stabilizing effect specific to Integrins β1 and β5, and could be potentially used to treat CG in the future. The overall premise of this application is that high podocyte ZHX2 expression and low glomerular endothelial Integrin β5 expression predispose to the development of CG. In Aim 1, changes in glomeruli with high podocyte ZHX2 expression will be investigated using transgenic rat models. Disease mechanism during the development of CG and just prior to the collapse of capillary loops will be elucidated. In Aim 2, changes in glomeruli with low endothelial Integrin β5 expression will be investigated using knockout mouse models. Disease mechanism during the development of CG and just prior to the collapse of capillary loops will be elucidated. In Aim 3, rat and mouse models of CG will be treated with protein 8520 to test for prevention or improvement in CG, and to potentially halt the disease process before the development of collapse.", "keywords": [ "10 year old", "2019-nCoV", "8 year old", "ANGPTL4 gene", "APOL1 gene", "Admixture", "Adriamycin PFS", "Affect", "African American", "Albuminuria", "Apoptosis", "Binding", "Binding Proteins", "Blood capillaries", "COVID-19 pandemic", "CRISPR/Cas technology", "Categories", "Cell Membrane Proteins", "Cell Nucleus", "Cell membrane", "Cells", "Cities", "Cytoplasmic Tail", "Data", "Development", "Disease", "Down-Regulation", "Endothelium", "Environment", "Ephrin-B1", "Etiology", "Event", "Feedback", "Focal and Segmental Glomerulosclerosis", "Foot Process", "Future", "Genetic", "Genomics", "Glomerular Capillary", "High Prevalence", "Hispanic", "Hispanic Populations", "Homeobox", "Homeodomain Proteins", "Human", "Human Parvovirus B19", "ITGB3 gene", "Incubated", "Infection", "Integrins", "Investigation", "Kidney Diseases", "Knockout Mice", "Location", "Membrane", "Mexico", "Modeling", "Mus", "Mutate", "Nuclear", "Pathogenesis", "Pathway interactions", "Patients", "Pattern", "Peruvian", "Pharmaceutical Preparations", "Phase", "Population", "Prevention", "Process", "Proliferating", "Proteins", "Proteinuria", "Publishing", "Rat Transgene", "Rattus", "Recombinants", "Recurrence", "Renal glomerular disease", "Rodent", "Role", "Series", "Serum", "Signal Transduction", "Site", "Sprague-Dawley Rats", "Testing", "Therapeutic Agents", "Therapeutic Effect", "Upregulation", "Variant", "Virus Diseases", "WT1 gene", "West African", "Zinc Fingers", "cytokine release syndrome", "diabetic", "exome", "genetic variant", "genomic data", "genotyped patients", "glomerular endothelium", "glomerular function", "glutamyl aminopeptidase", "improved", "in vivo", "induced pluripotent stem cell", "insertion/deletion mutation", "migration", "mouse model", "nephrotoxicity", "novel", "overexpression", "pamidronate", "pathogen", "patient population", "podocyte", "post SARS-CoV-2 infection", "prevent", "rat parvovirus", "slit diaphragm", "therapeutic evaluation", "transcription factor", "transmission process" ], "approved": true } } ], "meta": { "pagination": { "page": 2, "pages": 1424, "count": 14236 } } }