Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1424&sort=-program_reference_codes
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-program_reference_codes", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=-program_reference_codes", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1425&sort=-program_reference_codes", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1423&sort=-program_reference_codes" }, "data": [ { "type": "Grant", "id": "11592", "attributes": { "award_id": "5R03AI159286-02", "title": "Integrative and interactive analyses of host transcriptional response to COVID-19 and other respiratory viral 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": 26420, "first_name": "MARY KATHERINE", "last_name": "Bradford", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-05", "end_date": "2024-04-30", "award_amount": 77742, "principal_investigator": { "id": 27539, "first_name": "Ka Yee", "last_name": "Yeung-Rhee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "The current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to global public health concerns. This novel coronavirus disease (COVID-19) shares similar clinical symptoms with diseases caused by other viruses in the coronavirus family and other common respiratory viruses. When an infectious agent replicates within a host organism, the host interacts with, and responds to the virus with various mechanisms. Given the varying severity across patients and emergence of new SARS-CoV-2 variants, there is an urgent need to understand how the host responds to COVID-19 and its variants. RNA sequencing (RNA-seq) data that profile transcriptional response to SARS-CoV-2 and other respiratory viral infections are available from public databases. Comparing the gene signatures across respiratory viruses will identify similarities and differences of how the host responds to these infections. In particular, compendium analyses in which multiple datasets are integrated bring great opportunities for generating novel biological hypotheses. However, compendium analysis of RNA-seq data generated across different laboratories is an onerous task given the different protocols, parameters, software and software versions used at the time of analyses. This proposal focuses on the development of software tools to facilitate re-analyses of existing host-response RNA-seq data to create a compendium of gene signatures using the same set of analytical tools and input parameters. Our deliverables will include workflows with saved input files and parameters, fixed software versions and dependencies that will facilitate reproducibility and collaboration. We will provide an accessible graphical user interface that allows users to create custom signature sets by querying the data and if desired, re-analyzing the data using one of our provided workflows or a workflow of their own choosing. Users will be able to filter biological variables, perform cross species analysis, compare gene signatures to other gene set repositories. In addition, we will create an accessible dashboard that will support the query, download, visualization and reproducible analysis of gene expression data from SARS-CoV-2 and other common respiratory viruses. Tools will be provided to allow the user to interactively visualize the data and inform the choice of appropriate gene signatures. Not only will our software tools and dashboard provide an accessible front end, we will also develop an easy-to-use, scalable and cloud-enabled backend that enables efficient alignment of sequencing data. Our proposed project will empower biomedical scientists to experiment with different computational methods, input parameters (including the alignment step) across multiple datasets and respiratory viral infections. Thus, facilitating integrated and interactive analyses using datasets generated by multiple laboratories to advance our understanding of host transcriptional response to COVID-19.", "keywords": [ "2019-nCoV", "Bioinformatics", "Biological", "COVID-19", "COVID-19 pandemic", "Clinical", "Code", "Collaborations", "Communities", "Computer software", "Computing Methodologies", "Coronavirus", "Custom", "Data", "Data Set", "Databases", "Dependence", "Disease", "Family", "Gene Expression", "Gene Expression Profile", "Gene Expression Profiling", "Gene set enrichment analysis", "Generations", "Genes", "Genetic Transcription", "Human", "Image", "Immune response", "Infection", "Infectious Agent", "Influenza", "Intuition", "Laboratories", "Learning Module", "Machine Learning", "Manuals", "Methodology", "Methods", "Middle East Respiratory Syndrome Coronavirus", "Organism", "Patients", "Performance", "Process", "Protocols documentation", "Public Health", "RNA Processing", "RNA analysis", "Race", "Reproducibility", "Respiratory Tract Infections", "Rhinovirus", "SARS coronavirus", "SARS-CoV-2 variant", "Selection Criteria", "Sequence Alignment", "Severities", "Software Tools", "Specific qualifier value", "Symptoms", "Technology", "Time", "Traction", "Transcript", "Update", "Variant", "Viral Respiratory Tract Infection", "Virus", "Virus Diseases", "Visualization", "analytical tool", "biomedical scientist", "coronavirus disease", "current pandemic", "dashboard", "data integration", "data visualization", "diagnostic strategy", "differential expression", "empowerment", "experimental study", "genetic signature", "genomic data", "graphical user interface", "knowledge base", "large scale data", "multiple datasets", "novel", "novel coronavirus", "pandemic disease", "portability", "prototype", "public database", "public repository", "repository", "respiratory virus", "response", "sex", "software development", "tool", "transcriptome sequencing", "treatment strategy", "usability", "user-friendly", "vaccine development", "vaccine strategy" ], "approved": true } }, { "type": "Grant", "id": "11593", "attributes": { "award_id": "5R21AI160576-02", "title": "Single gene inborn errors of immunity underlying SARS-CoV-2-related multisystem inflammatory syndrome in children: a new approach to tackle a seemingly old puzzle", "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": 26918, "first_name": "Michelle Marie", "last_name": "Arnold", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-20", "end_date": "2024-04-30", "award_amount": 211875, "principal_investigator": { "id": 6183, "first_name": "Shen-Ying", "last_name": "Zhang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 763, "ror": "https://ror.org/0420db125", "name": "Rockefeller University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 763, "ror": "https://ror.org/0420db125", "name": "Rockefeller University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been quickly spreading around the world since December 2019 and causing coronavirus disease 2019 (COVID-19) in populations naive to this new pathogen. Since early May 2020, a rare and life-threatening SARS-CoV-2-related Kawasaki-like disease, designated by the CDC as Multisystem Inflammatory Syndrome in Children (MIS-C), emerged in communities with high rates of COVID-19. Clinical and laboratory characteristics of patients have revealed multiple similarities between MIS-C and Kawasaki disease (KD), a well-known but poorly understood pediatric inflammatory condition. The past ~50 years of studies on KD suggest that infectious agents, including a variety of viruses in particular, can trigger an inflammatory cascade that drives the clinical manifestations in genetically vulnerable children. However, the genetic etiologies and immunological mechanisms of KD remain largely unknown. The emergence of MIS-C during the COVID-19 epidemic provides compelling evidence of a viral trigger, at least for this specific form of Kawasaki-like disease. We and others have previously identified a number of monogenic inborn errors of immunity (IEIs) underlying a variety of severe viral diseases. We now aim to dissect the immunopathogenesis of MIS-C by testing a monogenic hypothesis. We will recruit a cohort of at least 1,000 MIS-C patients, by utilizing the COVID Human Genetic Effort (www.covidhge.com), our global network of pediatricians, and the New York State Department of Health (NYSDOH). We will perform whole exome sequencing (WES) and whole genome sequencing (WGS) sequentially for all enrolled patients. We will search for rare single gene IEIs underlying MIS-C via an unbiased genome-wide approach, by analyzing the WES and WGS data at the cohort population (genetic homogeneity) and individual patient levels (genetic heterogeneity), also testing models of immunological homogeneity and heterogeneity. For all candidate MIS-C- causing genes, we will perform in-depth characterization at the molecular and cellular levels, to connect the candidate genotype to molecular mechanism(s) and cellular phenotype(s) relevant to the MIS-C pathogenesis. We will use patient-specific leukocytes, dermal fibroblasts, and human pluripotent stem cell (hPSC)-derived MIS- C disease-relevant cell types, such as cardiovascular endothelial cells or cardiomyocytes. Our preliminary data are encouraging, as we have already enrolled 812 patients and performed WES on 620 of them. For comparison, we have also enrolled 158 patients with classic KD and have sequenced all of them. This project focuses on a timely and devastating problem, tests a bold but plausible hypothesis, and takes advantage of cutting-edge genetic and mechanistic approaches. It will enable us to gain insight into the molecular and cellular basis of the immunopathology of SARS-CoV-2-related MIS-C in previously healthy children and adolescents. The results of this project will also permit genetic diagnosis and counseling, while facilitating the development of novel preventive and therapeutic strategies in both genetic and non-genetic cases.", "keywords": [ "2019-nCoV", "Accounting", "Adolescent", "Affect", "Attenuated", "BIRC4 gene", "Brain Stem", "COVID-19", "COVID-19 pandemic", "COVID-19 pneumonia", "Cardiac Myocytes", "Cells", "Characteristics", "Child", "Childhood", "Clinical", "Collaborations", "Communities", "Cytomegalovirus", "Data", "Defect", "Dermal", "Development", "Disease", "Encephalitis", "Endothelial Cells", "Enrollment", "Epidermodysplasia Verruciformis", "Family member", "Fibroblasts", "Gene Frequency", "Genes", "Genetic", "Genetic Counseling", "Genetic Heterogeneity", "Genetic Models", "Genetic Predisposition to Disease", "Genotype", "Health", "Hepatitis", "Hepatitis A Virus", "Hereditary Disease", "Herpesvirus 1", "Herpesvirus Type 3", "Heterogeneity", "Human", "Human Genetics", "Human Herpesvirus 4", "Human Papillomavirus", "IFNAR1 gene", "IFNAR2 gene", "IRF3 gene", "Immunity", "Immunological Models", "Immunologics", "Impairment", "Individual", "Infection", "Infectious Agent", "Inflammation", "Inflammatory", "Influenza A virus", "Intervention", "Investigation", "Laboratories", "Leukocytes", "Life", "Measles", "Minor", "Molecular", "Mucocutaneous Lymph Node Syndrome", "Multisystem Inflammatory Syndrome in Children", "Mutate", "Mutation", "NOS2A gene", "New York", "Pathogenesis", "Patient Recruitments", "Patients", "Phenotype", "Population", "Predisposition", "Preventive", "Prosencephalon", "Pulmonary Inflammation", "Recurrent respiratory papillomatosis", "Reporting", "Rhinovirus", "SH2D1A gene", "STAT2 gene", "Single-Gene Defect", "TBK1 gene", "TLR3 gene", "TNF receptor-associated factor 3", "Testing", "Therapeutic", "Therapeutic Intervention", "Variant", "Viral", "Viral Encephalitis", "Virus", "Virus Diseases", "Yellow Fever Vaccine", "autosome", "cardiovascular endothelium", "cell type", "cohort", "coronavirus disease", "design", "emerging pathogen", "exome", "exome sequencing", "gene product", "genetic disorder diagnosis", "genome sequencing", "genome-wide", "human pluripotent stem cell", "immunopathology", "individual patient", "innovation", "insight", "non-genetic", "novel", "novel coronavirus", "novel strategies", "participant enrollment", "pediatric patients", "pediatrician", "preventive intervention", "proband", "recruit", "severe COVID-19", "whole genome", "young adult" ], "approved": true } }, { "type": "Grant", "id": "11594", "attributes": { "award_id": "5R21AI163425-02", "title": "Modifying Remdesivir Prodrug Design to Enhance the Active Metabolite Accumulation in the Lung (Resubmission)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6115, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-13", "end_date": "2024-04-30", "award_amount": 195000, "principal_investigator": { "id": 7948, "first_name": "Haojie", "last_name": "Zhu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Although remdesivir is among few medications approved by the FDA for treating patients with COVID-19, a significant portion of patients did not respond adequately to the treatment. Remdesivir is formed as a 2- ethylbutyl ester prodrug of the nucleoside analog GS-441524 to overcome the poor cell permeability of nucleosides and bypass the rate-limiting mono-phosphorylation metabolism required for GS-441524 activation. Remdesivir is extensively hydrolyzed in human plasma, raising the concerns that only a small portion of remdesivir can reach the lung in its intact prodrug form. Thus, the benefits associated with the prodrug design may be unattainable for the treatment of COVID-19. Another limitation is that remdesivir is only available in an intravenous injection dosage form due to its intensive first-pass effect. Because of those limitations, some investigators advocate for using the parent compound GS-441524 as an alternative to remdesivir to treat COVID-19 patients. However, it remains unknown how GS-441524's poor cell permeability affects intracellular drug accumulation and the extent to which the required rate-limiting mono-phosphorylation step could affect GS-441524 activation. During remdesivir development, several GS-441524 ester prodrugs were synthesized and evaluated for their plasma stability and in vitro antiviral activity. Remdesivir was chosen as the drug candidate for further development because of its superior anti-Ebola activity relative to other prodrugs in several non-lung cell lines. Among those, the isopropyl ester prodrug of GS-441524 showed lower antiviral potency but much greater plasma stability than remdesivir. Given that all the prodrugs have the same active metabolite, the antiviral activity differences among the tested prodrugs are likely attributed to their differences in intracellular accumulation and activation. Existing evidence suggests that carboxylesterase 1 (CES1) and cathepsin A (CatA) are involved in the activation of ester nucleoside prodrugs, and both CES1 and CatA are highly expressed in the human lung. Thus, isopropyl-GS-441524 could be efficiently activated in the lung and consequently exert its anti-SARS-CoV-2 effect. Moreover, the excellent stability of isopropyl-GS-441524 in plasma, liver, and intestine could improve the intracellular drug accumulation in the lung and allow the compound to be developed into an oral dosage form. In this project, we will conduct a pharmacokinetics (PK) study in mice to compare the activation and disposition between isopropyl-GS-441524, remdesivir, and GS- 441524 in various tissues. We will also determine the activation rates of the three compounds in the human lung and other PK-related organs and identify and characterize the hydrolases responsible for the prodrug activation. Furthermore, we will evaluate the anti-SARS-CoV-2 activity of the three compounds using an in vitro model. The project will provide evidence supporting that isopropyl-GS-441524 is advantageous over remdesivir and GS-441524 for treating COVID-19. Moreover, studying tissue-specific ester prodrug-activating hydrolases will shed light on the future development of more effective nucleoside prodrugs.", "keywords": [ "2019-nCoV", "Advocate", "Affect", "Authorization documentation", "Bypass", "COVID-19", "COVID-19 patient", "COVID-19 treatment", "Carboxylesterase 1", "Cell Line", "Cell membrane", "Cells", "Clinical", "Data", "Development", "Dosage Forms", "Dose", "Drug Kinetics", "Ebola", "Ebola virus", "Enzymes", "Epithelial Cells", "Esters", "Exclusion", "Exhibits", "FDA approved", "Foundations", "Future", "GS-441524", "Hela Cells", "Human", "Hydrolase", "In Vitro", "Incubated", "Intestines", "Kinetics", "Liver", "Lung", "Metabolism", "Mus", "Nucleosides", "Nucleotides", "Oral", "Organ", "Outpatients", "Parents", "Patients", "Permeability", "Pharmaceutical Preparations", "Phosphorylation", "Plasma", "Prodrugs", "Property", "Proteomics", "Research Personnel", "Tenofovir", "Testing", "Tissues", "Viral", "Viral Physiology", "activity-based protein profiling", "alveolar epithelium", "authority", "carboxypeptidase C", "design", "drug candidate", "improved", "improved outcome", "in vitro Model", "in vivo", "intravenous injection", "macrophage", "novel", "nucleoside analog", "nucleoside triphosphate", "phosphoramidate", "remdesivir", "severe COVID-19" ], "approved": true } }, { "type": "Grant", "id": "11595", "attributes": { "award_id": "5T34GM145513-02", "title": "U-RISE at Howard University", "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": 27540, "first_name": "MARIE DEBORAHGAYNELLE", "last_name": "Harton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-01", "end_date": "2027-03-31", "award_amount": 271543, "principal_investigator": { "id": 22220, "first_name": "Shawn Maurice", "last_name": "Abernathy", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [ { "id": 288, "ror": "https://ror.org/05gt1vc06", "name": "Howard University", "address": "", "city": "", "state": "DC", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 15527, "first_name": "Clarence M", "last_name": "Lee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 22221, "first_name": "DINARI A", "last_name": "HARRIS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 288, "ror": "https://ror.org/05gt1vc06", "name": "Howard University", "address": "", "city": "", "state": "DC", "zip": "", "country": "United States", "approved": true }, "abstract": "Summary/Abstract The United States (US) biomedical science (BMS) enterprise critically lacks diversity at the Ph.D. level. This problem is due to the lack of underrepresented minority (URM) students at the undergraduate level majoring in STEM (science technology engineering and mathematics) disciplines. Diversifying our BMS workforce would improve health equity by eradicating health disparities. This is of the utmost importance since the COVID-19 pandemic is disproportionately affecting underrepresented populations in the US. Given the proper academic and research training along with encouragement, a substantial number of academically talented URM students would seek research career in the BMS workforce. The Undergraduate Research Training Initiative for Student Enhancement (U-RISE) at Howard University Program will tap into this reservoir of students that would contribute to the diversification of our BMS workforce. Hence, the U-RISE at HU Program leadership mission is to recruit talented and passionate undergraduate students who envision themselves as innovative BMS scientists and global leaders in their fields. Our program mission is to engage them in an enhanced academic curriculum and hands-on research activities during the junior and senior years. This will produce a cadre highly educated, motivated, and well-trained URM students. To implement and sustain U-RISE at HU Program, the objective of the project needs to be integrated into our science community and culture. Our specific aims are the following: 1) To recruit academically talented and highly motivated URMs students to participate as trainees who aspire to a career as a Ph.D. level scientist in BMS discipline. 2) To provide our trainees with an enhanced and structured research training through an interdisciplinary hands-on intramural research experience, extramural summer research experience (SRE) as well as a classroom based didactic research. 3) To have at least 75% our program trainees accepted into a research intensive (R1) university Ph.D. programs in a BMS discipline within two years of graduation from Howard University, and 4) To design, implement, and institutionalize a STEM professional development course to stimulate our trainees’ interest. Finally, we envision our program will create a strong foundation for Howard University in the recruitment, enrollment, retention, and advancement of enthusiastic undergraduate students majoring in the BMS disciplines.", "keywords": [ "Academic Training", "Affect", "COVID-19 pandemic", "Communities", "Discipline", "Doctor of Philosophy", "Educational Curriculum", "Enrollment", "Extramural Activities", "Foundations", "Institutionalization", "Intramural Research", "Leadership", "Mission", "Research", "Research Activity", "Research Training", "STEM field", "Science", "Science Technology Engineering and Mathematics", "Scientist", "Structure", "Students", "Talents", "Training", "Underrepresented Minority", "Underrepresented Populations", "United States", "Universities", "career", "course development", "design", "experience", "hands on research", "health disparity", "health equity", "improved", "innovation", "interest", "programs", "recruit", "summer research", "undergraduate research", "undergraduate student", "underrepresented minority student" ], "approved": true } }, { "type": "Grant", "id": "11596", "attributes": { "award_id": "5R21AI164006-02", "title": "Sex-Dependent Regulation of Host Factors Influencing SARS-CoV-2 Infection and COVID-19 Disease", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 26918, "first_name": "Michelle Marie", "last_name": "Arnold", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-15", "end_date": "2024-03-31", "award_amount": 201063, "principal_investigator": { "id": 6051, "first_name": "Montserrat C", "last_name": "Anguera", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 232, "ror": "https://ror.org/00b30xv10", "name": "University of Pennsylvania", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 232, "ror": "https://ror.org/00b30xv10", "name": "University of Pennsylvania", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19, the disease caused by the SARS-CoV-2 virus, commonly presents as pneumonia, with those most severely affected progressing to Acute Respiratory Distress Syndrome (ARDS). Notably, males seem to be at significantly higher risk for severe or fatal outcomes from COVID-19, and male-specific skewing was also observed with related coronaviruses SARS-CoV and MERS. The X chromosome is enriched for immunity-related genes, and females (XX) mount stronger immune responses than do males (XY). X-chromosome Inactivation (XCI) normalizes the gene dosage effect between the sexes and we have previously found that immune cells have novel and dynamic XCI mechanisms that allow for gene-specific transcriptional activation from the inactive X (Xi) in a cell-type specific manner. Notably, our preliminary data suggest the regulation of XCI in lung alveolar type 2 (AT2) cells, the predominant target of SARS-CoV-2 in the lung and a cell type critically involved in lung repair following viral injury, phenocopies that seen in immune cells. As such, we will test the novel hypothesis that X-linked genes, including immune genes and ACE2, escape XCI in a lineage-specific fashion and contribute to the relative resistance of females to COVID-19 (Aim 1). We will test the hypothesis that our novel humanized ACE2 mice, which are susceptible to SARS-CoV-2 infection, will exhibit sex differences with resulting lung pathologies in aged mice (Aim 2). Together, these studies will further our understanding of the mechanisms that predispose males to COVID-19 disease and will reveal novel strategies to reduce disease severity.", "keywords": [ "2019-nCoV", "ACE2", "Acute Respiratory Distress Syndrome", "Affect", "Age", "Alveolar", "Angiotensin II", "CD4 Positive T Lymphocytes", "COVID-19", "COVID-19 morbidity", "COVID-19 mortality", "COVID-19 severity", "COVID-19 susceptibility", "COVID-19 treatment", "Cells", "Code", "Coronavirus", "Coronavirus Infections", "Data", "Development", "Disease", "Disease Outbreaks", "Disease Outcome", "Disease Progression", "Disease model", "Elements", "Endothelial Cells", "Epigenetic Process", "Estrogen Therapy", "Estrogens", "Exhibits", "Fatal Outcome", "Female", "Future", "Gene Dosage", "Genes", "Genetic", "Gonadal Steroid Hormones", "Hormonal", "Hormone Responsive", "Hormones", "Human", "Hybrids", "Immune", "Immune response", "Immunity", "Infection", "Inflammation", "Inflammatory", "Inflammatory Response", "Injury", "Integration Host Factors", "Link", "Lung", "Middle East Respiratory Syndrome", "Morbidity - disease rate", "Mus", "Outcome", "Pathology", "Pathway interactions", "Pattern", "Peripheral", "Phenocopy", "Pneumonia", "Population", "Predisposition", "Production", "Publications", "Pulmonary Pathology", "Regulation", "Regulatory Element", "Resistance", "SARS coronavirus", "SARS-CoV-2 infection", "Severity of illness", "Sex Bias", "Sex Differences", "Signal Transduction", "Supplementation", "System", "Testing", "Transcript", "Transcriptional Activation", "Transgenic Mice", "Type 2 Angiotensin II Receptor", "Vascular Diseases", "Viral", "Virus", "Virus Diseases", "Wild Type Mouse", "Woman", "X Chromosome", "X Inactivation", "age related", "aged", "burden of illness", "cell type", "coronavirus disease", "cytokine", "high risk", "insight", "lung repair", "macrophage", "male", "men", "mortality", "mouse model", "novel", "novel coronavirus", "novel strategies", "post SARS-CoV-2 infection", "preservation", "prevent", "promoter", "receptor", "respiratory", "response", "severe COVID-19", "sex", "transcriptome sequencing" ], "approved": true } }, { "type": "Grant", "id": "11597", "attributes": { "award_id": "5R01NS126260-02", "title": "Biomarkers and risk factors for prodromal Parkinson's disease and its progression", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 22292, "first_name": "Christine R", "last_name": "Swanson-Fischer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-01", "end_date": "2027-03-31", "award_amount": 477028, "principal_investigator": { "id": 22293, "first_name": "ALBERTO", "last_name": "ASCHERIO", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 961, "ror": "", "name": "HARVARD SCHOOL OF PUBLIC HEALTH", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 961, "ror": "", "name": "HARVARD SCHOOL OF PUBLIC HEALTH", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The highest priority recommended by NINDS for clinical Parkinson’s research is to define “the features and natural history of prodromal Parkinson disease (PPD), including the events that underlie phenoconversion to clinically manifest PD, and biomarkers or other determinants of prodromal subtypes with the goal of providing sufficient rationale to initiate proof-of-concept prevention trials....” We are in a privileged position to address this priority by leveraging 25 years of research on PD in the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), large cohorts of women and men recruited in mid-adult life and followed prospectively for over 30 years. In 2012, we screened the active participants in these cohorts for probable REM sleep behavior disorder (pRBD) and constipation, and selected a sub-cohort enriched for these features for further investigation (the ProPD cohort). This sub-cohort included 20,455 individuals who have so far completed two olfactory tests and two comprehensive mailed surveys of non-motor and early motor features of PPD, and have been actively followed until 2018. We are now proposing to extend the longitudinal follow-up of this unique cohort and its source population to monitor the progression of prodromal features and phenoconversion to clinically manifest PD (“phenoconversion”, for brevity), thus providing important insights on the course of PPD and fill the gap between current knowledge and what we need to know for implementing prevention trials. Further, as part of the proposed project, we will examine the impact of covid-19 on PPD and its progression and collect new biological samples to evaluate the sebum volatilome and metabolome, novel promising and non-invasive biomarkers that could play an important role in the early identification of PPD. The Aims of the study include: i) to obtain an in-depth descriptive characterization of PPD and its heterogeneity; ii) to identify risk factors for PPD progression and phenoconversion; iii) to assess the impact of SARS-Cov2/covid-19 on features of prodromal PD and phenoconversion; and iv) to evaluate the relationship between the sebum volatilome and metabolome with prodromal features and manifest PD (sebum samples will be collected from individuals with high probability of PPD, manifest PD, and matched controls). A unique and virtually irreproducible strength of the proposed study are the data prospectively collected since mid-adult life (men were 40 to 65 at recruitment, women 30 to 55) on lifestyle and medical history, including risk factors for PD and several features associated with PPD. If funded, the proposed study stands to lead to groundbreaking discoveries and create an invaluable resource that will offer numerous opportunities for further in-depth investigations on PPD and its determinants. Most importantly, the information generated by the proposed investigation will be pivotal to assess the feasibility of prevention trials and inform their design.", "keywords": [ "2019-nCoV", "Address", "Adrenergic beta-Antagonists", "Adult", "Agonist", "Antigens", "Appearance", "Biological", "Biological Markers", "Brain", "COVID-19", "COVID-19 impact", "Caffeine", "Carnitine", "Clinical", "Complement", "Constipation", "Data", "Diagnosis", "Dietary Practices", "Disease Progression", "Early Intervention", "Early identification", "Event", "Flavonoids", "Follow-Up Studies", "Food", "Funding", "Future", "Goals", "Health Professional", "Heterogeneity", "Individual", "Intervention", "Investigation", "Knowledge", "Life", "Life Style", "Lipids", "Machine Learning", "Medical History", "Metabolism", "Monitor", "Motor", "Movement Disorders", "National Institute of Neurological Disorders and Stroke", "Natural History", "Nerve Degeneration", "Nurses&apos", "Health Study", "Nutrient", "Parkinson Disease", "Parkinsonian Disorders", "Participant", "Patients", "Pharmaceutical Preparations", "Phase", "Physical activity", "Play", "Population", "Positioning Attribute", "Prevention trial", "Probability", "REM Sleep Behavior Disorder", "Recommendation", "Research", "Resources", "Risk Factors", "Role", "Sampling", "Sebum", "Smoking", "Societies", "Source", "Sphingolipids", "Subgroup", "Surveys", "Testing", "Time", "Training", "Volatilization", "Woman", "algorithm training", "case control", "cohort", "design", "dietary", "disability", "disorder risk", "experience", "follow-up", "hyposmia", "insight", "men", "metabolome", "modifiable risk", "novel", "novel marker", "prediction algorithm", "prevent", "prospective", "recruit", "screening", "sex", "virtual" ], "approved": true } }, { "type": "Grant", "id": "11598", "attributes": { "award_id": "5R01AG075507-02", "title": "The Use of Telemedicine in the Care of Nursing Home Residents with Alzheimer's Disease and Related Dementias During and After the COVID-19 Pandemic", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 27518, "first_name": "THERESA YOUNGJOO", "last_name": "Kim", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-01", "end_date": "2026-01-31", "award_amount": 536943, "principal_investigator": { "id": 8343, "first_name": "Michael Lawrence", "last_name": "Barnett", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 961, "ror": "", "name": "HARVARD SCHOOL OF PUBLIC HEALTH", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 961, "ror": "", "name": "HARVARD SCHOOL OF PUBLIC HEALTH", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The Use of Telemedicine in the Care of Nursing Home Residents with Alzheimer's Disease and Related Dementias During and After the COVID-19 Pandemic PROJECT SUMMARY The novel coronavirus disease 2019 (COVID-19) pandemic has devastated nursing home residents in the US, nearly half of whom are diagnosed with Alzheimer's and other related dementias (ADRD). To limit resident exposure and expand safe access to desperately-needed care from physicians and advanced practice providers, Medicare dropped previously tight restrictions and temporarily allowed SNFs to broadly use telemedicine to obtain care for residents. Dropping these restrictions helped facilitate a rapid adoption of telemedicine in SNFs, from <1% of SNFs billing for any telemedicine services in Oct-Dec 2019 to 55% in Apr- May 2020. Telemedicine has long been regarded as a promising, but underused, delivery innovation for SNFs addressing two major gaps in care. First, SNF clinicians are not always onsite, so medical issues that present during off-hours are often addressed by transferring patients, often unnecessarily, to the emergency department. Second, due to both financial and logistic reasons it is very difficult for SNF residents to obtain specialty care, including specialties critical those with ADRD like neurology or psychiatry. A limited literature suggests that telemedicine can bridge both of these care gaps, but more rigorous evidence is needed. In 2021, understanding the adoption and clinical impact of SNF telemedicine for the vulnerable population of older adults with ADRD has new urgency. We propose to use Medicare claims, the Minimum Data Set and a national survey on SNF telemedicine implementation to answer the following specific aims: 1) Evaluate the patient-level association of SNF adoption of telemedicine in 2020 with health care use and clinical outcomes (COVID-19 and non-COVID-19) for SNF residents with and without ADRD. 2) Use group-based trajectory models to characterize 2020-2021 SNF-level patterns of telemedicine use (e.g., sustaining vs. de-adopting) and SNF characteristics associated with different trajectories. 3) Survey a national sample of SNFs, stratified by their trajectories measured in Aim 2, to assess facility leadership perceptions of telemedicine use and telemedicine implementation strategies. Understanding how SNFs have used telemedicine and its association with clinical outcomes is essential to inform how Medicare and state Medicaid programs should regulate and promote telemedicine use in SNFs. Our findings will also help guide clinicians who care for SNF residents with ADRD on the clinical impact associated with telemedicine use and how it is being used nationally.", "keywords": [ "Accident and Emergency department", "Address", "Administrator", "Adopted", "Adoption", "Agreement", "Alzheimer&apos", "s Disease", "Alzheimer&apos", "s disease related dementia", "American", "Area", "COVID-19", "COVID-19 pandemic", "Caring", "Cessation of life", "Characteristics", "Clinical", "Data", "Data Set", "Dementia", "Diagnosis", "Drops", "Elderly", "Emergency department visit", "Geriatric Psychiatry", "Goals", "Health", "Healthcare", "Home Nursing Care", "Hospitalization", "Hour", "Individual", "Institutionalization", "Knowledge", "Leadership", "Literature", "Logistics", "Measures", "Medicaid", "Medical", "Medicare", "Medicare claim", "Mission", "Modeling", "Neurology", "Nursing Homes", "Outcome", "Patient Transfer", "Patients", "Pattern", "Perception", "Personal Satisfaction", "Persons", "Physician Executives", "Physicians", "Policies", "Population", "Provider", "Psychiatry", "Reporting", "Rural", "Sampling", "Services", "Site", "Skilled Nursing Facilities", "Surveys", "Telemedicine", "Vaccines", "Visit", "Vulnerable Populations", "coronavirus disease", "cost", "disadvantaged population", "hospitalization rates", "implementation barriers", "implementation strategy", "improved", "improved outcome", "innovation", "medical specialties", "novel coronavirus", "pandemic disease", "programs" ], "approved": true } }, { "type": "Grant", "id": "11599", "attributes": { "award_id": "5K01OD032309-02", "title": "The impact of vaping aerosol exposure on innate pulmonary defense mechanisms in nonhuman primates", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 20741, "first_name": "MIGUEL A.", "last_name": "CONTRERAS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-01", "end_date": "2025-03-31", "award_amount": 198597, "principal_investigator": { "id": 22423, "first_name": "Robert", "last_name": "Blair", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 811, "ror": "", "name": "TULANE UNIVERSITY OF LOUISIANA", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 811, "ror": "", "name": "TULANE UNIVERSITY OF LOUISIANA", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "Vaping is a serious public health concern that was associated with outbreaks of hospitalizations and deaths in 2019. These outbreaks of electronic vaping associated lung injury (EVALI) coincided with increased use of electronic vaping devices by adolescents and young adults. The rapid disease onset of EVALI and the role of macrophages in its progression, support a role for the innate immune system in the pathogenesis of EVALI. Despite its rising use little is currently known about the effect of vaping on pulmonary immunology and physiology highlighting the need for animal models to better understand its effects. Small animal models have shown pathologic changes following exposure to vaping aerosols; however, they do not recapitulate the pathologic manifestations of EVALI reported in humans necessitating a more translatable animal model to investigate the pathogenesis of EVALI. Nonhuman primates (NHPs) are ideally suited for studying respiratory diseases in humans due to their similarity in both pulmonary anatomy and immunology which provide advantages over other animal models. Here, we aim to utilize a NHP model to investigate the impact of vaping aerosol exposure on innate pulmonary defense mechanisms. We will longitudinally assess pulmonary and innate immune function (immune cell infiltrates, alveolar macrophage phagocytosis, and secretion of cytokines, chemokines, and defense molecules) over a four-week period of daily vaping aerosol exposure. At the end of the study, correlation with pathologic changes will occur through rigorous postmortem examination and sampling of the upper and lower respiratory tract. The data generated from this study will inform on mechanisms by which vaping aerosols effect innate pulmonary defenses, an important area of investigation in this time of highly infectious respiratory diseases. Furthermore, this study will provide preliminary data for future investigations evaluating the contribution of individual constituents within the vaping liquid (nicotine, tetrahydrocannabinol, and vitamin E acetate); and vaping in the context of comorbid conditions (SARS-CoV-2 and HIV/SIV), areas of special interest supported by several funding agencies (NIDA, NHLBI, NIAID). This proposed study and Mentored Career Development Plan will be conducted at the Tulane National Primate Research Center under the guidance of Drs. Ronald Veazey and Chad Roy. The TNPRC has been a national resource and center of excellence for biomedical research using nonhuman primates for over 50 years. The TNPRC has a strong commitment to training and mentorship and provides support (financial and effort-based) to create a rich and diverse training environment for early-stage investigators. The TNPRC fully supports Dr. Blair in his career goal to develop into an independently funded private investigator working with NHP models to study diseases of major public health importance. The dedicated time and additional mentorship provided by this K01 will help Dr. Blair refine his grant writing and project management skills to ensure the success of his future R01 proposals.", "keywords": [ "2019-nCoV", "Acceleration", "Acute", "Adolescent", "Adolescent and Young Adult", "Adoption", "Aerosols", "Affect", "Alveolar", "Alveolar Macrophages", "Anatomy", "Animal Model", "Area", "Autopsy", "Biological Assay", "Bronchiolitis", "Bronchoalveolar Lavage Fluid", "Cell Separation", "Cells", "Centers of Research Excellence", "Cessation of life", "Chad", "Clinical", "Data", "Dedications", "Defense Mechanisms", "Defensins", "Development Plans", "Devices", "Diffuse", "Disease", "Disease Outbreaks", "Disease model", "Dyspnea", "Educational workshop", "Ensure", "Environment", "Enzyme-Linked Immunosorbent Assay", "Exposure to", "Flow Cytometry", "Foundations", "Functional disorder", "Funding", "Funding Agency", "Future", "Goals", "Grant", "HIV", "Hospitalization", "Human", "Immune", "Immunohistochemistry", "Immunology", "Individual", "Inflammation", "Inflammatory", "Innate Immune Response", "Innate Immune System", "Investigation", "Lipids", "Liquid substance", "Lower respiratory tract structure", "Lung", "Lung immune response", "Macaca mulatta", "Mentors", "Mentorship", "Microscopic", "Modeling", "National Heart Lung and Blood Institute", "National Institute of Allergy and Infectious Disease", "National Institute of Drug Abuse", "Nicotine", "Onset of illness", "Pathogenesis", "Pathogenicity", "Pathologic", "Patients", "Phagocytes", "Phagocytosis", "Phenotype", "Physiology", "Play", "Pneumonia", "Policies", "Positioning Attribute", "Primates", "Privatization", "Public Health", "Pulmonary Inflammation", "Pulmonary Pathology", "Pulmonary function tests", "Reporting", "Research", "Research Personnel", "Resources", "Respiratory Disease", "Rodent Model", "Role", "SIV", "Saline", "Sampling", "Study models", "System", "Terminal Bronchiole", "Testing", "Tetrahydrocannabinol", "Time", "Tissues", "Toll-like receptors", "Training", "Trees", "Tumor-infiltrating immune cells", "United States National Institutes of Health", "Upper respiratory tract", "Vitamin E Acetate", "Writing", "aerosolized", "airway inflammation", "career", "career development", "chemokine", "comorbidity", "cytokine", "electronic vape", "improved", "innate immune function", "innate immune mechanisms", "interest", "macrophage", "nonhuman primate", "novel", "pulmonary function", "radiological imaging", "receptor expression", "response", "skills", "success", "surfactant", "targeted treatment", "vaping", "vaping associated lung i" ], "approved": true } }, { "type": "Grant", "id": "11600", "attributes": { "award_id": "5R21AI161061-02", "title": "Covalent inhibitors of host cell entry by SARS-CoV-2 for treatment of 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": 6115, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-20", "end_date": "2024-03-31", "award_amount": 236100, "principal_investigator": { "id": 6116, "first_name": "Matthew", "last_name": "Bogyo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 266, "ror": "https://ror.org/00f54p054", "name": "Stanford University", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 266, "ror": "https://ror.org/00f54p054", "name": "Stanford University", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Current strategies to overcome virus outbreaks are focused on development of effective vaccines as well as novel treatments that can either block infection or prevent mortality from the resulting disease. One of the strategies that has shown promise is the use of serum from patients who have recovered from infection. This strategy relies on the presence of high titers of neutralizing antibodies that bind to antigens on the virus and block uptake into host cells. For the SARS-CoV-2 virus this requires antibodies that bind to regions on the receptor binding domain (RBD) of the viral ‘spike’ (S) protein and block its interaction with the host receptor, angiotensin converting enzyme 2 (ACE2). Significant efforts over the past 15 years of studies on related coronaviruses has produced a detailed picture of the interactions between these two protein domains. These studies have facilitated strategies to select optimal neutralizing antibodies likely to have the greatest therapeutic value. While antibodies are effective biological therapies, they suffer from limitations that make their widespread use for a global pandemic limited. This includes the high cost of production, poor uptake by oral or localized administration and general incompatibility with long-term storage and stockpiling. Furthermore, interactions with the target viral proteins are reversible and can be rendered ineffective for antibody neutralization through single point mutations in virus variants. In this proposal, we outline plans to develop a phage display screening approach to identify synthetic cyclic peptides that carry a covalent ‘warhead’ to induce specific and permanent binding to the SARS-CoV-2 S protein at highly conserved and functionally important residues. This approach will lead to the identification of fully synthetic molecules that irreversibly block key interactions between the S protein RBD and the host cell receptor, ACE2. Such molecules will possess the selectivity of antibodies but can be synthesized and handled like small molecule drugs. Furthermore, their covalent binding mode will lead to prolonged therapeutic effects and reduced ability to induce resistance causing mutations in the S protein.", "keywords": [ "2019-nCoV", "ACE2", "Animal Model", "Antibodies", "Antigens", "Azoles", "Bacteriophages", "Binding", "Biological Assay", "Biological Response Modifier Therapy", "COVID-19", "COVID-19 therapeutics", "COVID-19 treatment", "Cell model", "Cells", "Chemistry", "China", "Complex", "Coronavirus", "Cyclic Peptides", "Development", "Disease", "Disease Outbreaks", "Enzyme-Linked Immunosorbent Assay", "Fluorides", "Fluorine", "Future", "Goals", "Health", "Human", "Infection", "Knowledge", "Libraries", "Ligand Binding", "Malignant Neoplasms", "Mass Spectrum Analysis", "Methods", "Modification", "Mutation", "Oral", "Patients", "Peptide Hydrolases", "Phage Display", "Pharmaceutical Preparations", "Point Mutation", "Production", "Proteins", "Proteomics", "Reaction", "Receptor Cell", "Resistance", "Resolution", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Serum", "Site", "Structure", "Sulfur", "Surface", "Technology", "Tertiary Protein Structure", "Test Result", "Testing", "Therapeutic", "Therapeutic Effect", "Therapeutic Uses", "Time", "Tyrosine", "Vaccines", "Variant", "Viral", "Viral Proteins", "Virus", "Virus Diseases", "cost", "economic impact", "high reward", "high risk", "in vivo", "inhibitor", "lead optimization", "mortality", "neutralizing antibody", "novel", "novel coronavirus", "pandemic disease", "pathogen", "prevent", "protein protein interaction", "receptor", "receptor binding", "screening", "small molecule", "success", "uptake", "validation studies", "viral outbreak" ], "approved": true } }, { "type": "Grant", "id": "11601", "attributes": { "award_id": "5R21AI161437-02", "title": "Profiling the immune response to convalescent plasma therapy during severe acute respiratory syndrome coronavirus 2 (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": 26918, "first_name": "Michelle Marie", "last_name": "Arnold", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-04-13", "end_date": "2024-03-31", "award_amount": 245625, "principal_investigator": { "id": 6138, "first_name": "Jay H.", "last_name": "Bream", "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 } ] }, "other_investigators": [], "awardee_organization": { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic continues to grow at an exponential pace around the globe threatening health systems and the world economy. In the 9 months since the novel SARS-CoV-2 virus was identified as the cause of the life-threatening disease COVID-19, there have been over 20.6 million confirmed cases and over 750,000 deaths globally. With few options for treatment and no vaccine, the immediate outlook remains grim. Even in less severe cases, illness can be prolonged, recovery slow with long term consequences, such as immunity to re-infection and chronic complications remain largely unknown. Convalescent plasma from recovered individuals is being increasingly used as a stopgap treatment to mitigate disease morbidity and mortality and slow the spread of SARS-CoV-2 infection. Although COVID-19 convalescent plasma appears to be well-tolerated and there is general enthusiasm for the treatment, randomized clinical trials will be required to determine efficacy not to mention optimum delivery. Surprisingly, convalescent plasma therapy (CPT) has been used historically for the treatment and prevention of numerous infectious diseases, but the mechanisms of action are not fully understood. Likewise, the effects of CPT on the host immune response to the specific pathogen are not well defined. The primary goal of this application is to identify cellular and molecular immune signatures that predict COVID-19 outcomes and clinical response to therapy. We propose to leverage samples from ongoing convalescent plasma clinical trials at Johns Hopkins to link CPT-induced immune signatures with clinical outcomes. We will utilize a unique pipeline of advanced flow cytometry, single cell next generation sequencing and antibody profiling to provide a focused map charting the effects of CPT on SARS-CoV-2- specific T cells and antibody. We will determine the COVID-19 antibody profile and neutralization capacity in convalescent donors and define how CPT subsequently shapes the COVID-19 antibody profile at epitope resolution in recipients. 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