Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1385&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=1405&sort=-program_reference_codes", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1386&sort=-program_reference_codes", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=-program_reference_codes" }, "data": [ { "type": "Grant", "id": "11576", "attributes": { "award_id": "5R01AR080089-02", "title": "Leveraging Community-Academic Partnerships and Social Networks to Disseminate Vaccine-Related Information and Increase Vaccine Uptake Among Black Individuals with Rheumatic Diseases", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 22629, "first_name": "Yan Z.", "last_name": "Wang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-10", "end_date": "2027-04-30", "award_amount": 738723, "principal_investigator": { "id": 23848, "first_name": "Candace Hillary", "last_name": "Feldman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 924, "ror": "", "name": "NORTHWESTERN UNIVERSITY AT CHICAGO", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23849, "first_name": "Rosalind", "last_name": "Ramsey-Goldman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 924, "ror": "", "name": "NORTHWESTERN UNIVERSITY AT CHICAGO", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "Individuals with chronic rheumatic diseases including arthritis comprise approximately 25% of the U.S. population. Racial/ethnic and socioeconomic disparities in adverse, often avoidable outcomes occur in nearly all rheumatic diseases particularly among Black and lower socioeconomic status individuals. Despite the importance of vaccinations in patients with rheumatic diseases, and the high rates of serious infections, vaccine uptake is consistently poor. In the U.S., COVID-19 vaccine uptake is lower and vaccine hesitancy higher among Black patients compared with White patients, and this holds true in rheumatic diseases. With the profound disparities uncovered by the COVID-19 pandemic aggravated by proven disparities in rheumatic disease outcomes, and heightened vulnerability to infections, there is an urgent need to address low vaccine uptake and hesitancy among Black individuals with these conditions. In addition, it is critical to also increase vaccine uptake among the social networks of individuals with rheumatic diseases who are immunosuppressed and may have less robust vaccination responses. Our team has forged longstanding community-academic partnerships in the Boston and Chicago areas to understand the needs of Black individuals with lupus, a systemic rheumatic disease, and the role racism plays in health and healthcare access. Framed by the Public Health Critical Race Praxis that recognizes the pervasiveness of racism in our society, we will leverage our community-academic partnerships to implement the CDC's Popular Opinion Leader (POL) model whereby trusted community leaders are trained to disseminate information regarding COVID-19 vaccination through their social networks in predominately Black communities to increase vaccine uptake and reduce hesitancy. In response to the NOSI NOT-MD-21-008: Research to Address Vaccine Hesitancy, Uptake and Implementation among Populations that Experience Disparities, we propose the following aims: Aim 1. To leverage community- academic partnerships across two U.S. cities to develop training and evaluation materials for POLs. Aim 2a. To establish the efficacy of a community-based intervention with and without a racial justice framework to increase COVID-19 vaccine uptake and reduce hesitancy among social networks of Black individuals with rheumatic conditions. We will conduct a cluster randomized controlled trial to test whether POLs trained with racial justice framing embedded in information on vaccine safety and efficacy will result in greater COVID-19 vaccine uptake among their social network members compared to safety and efficacy training alone. Aim 2b. To determine the structure and composition of the outreach social networks of POLs. We will enhance the existing POL model by adding a validated mixed methods approach to compare the social networks reached by POLs in each arm. We hypothesize that incorporating a racial justice lens will empower POLs to disseminate information more broadly and more persuasively and increase vaccine uptake by reducing fear and mistrust.", "keywords": [ "Address", "Advocacy", "Area", "Arthritis", "Assessment tool", "Black Populations", "Black race", "Boston", "COVID-19 pandemic", "COVID-19 stress", "COVID-19 vaccination", "COVID-19 vaccine", "Caring", "Characteristics", "Chicago", "Chronic", "Cities", "Clinical Trials", "Communicable Diseases", "Communities", "Critical Race Theory", "Disease Outcome", "Disease susceptibility", "Education", "Educational Curriculum", "Educational Intervention", "Enrollment", "Evaluation", "Exhibits", "Fright", "General Population", "Goals", "Health", "Immunocompromised Host", "Individual", "Infection", "Information Dissemination", "Intervention", "Interview", "Justice", "Knowledge", "Lupus", "Maps", "Methods", "Modeling", "Outcome", "Patients", "Persons", "Pharmaceutical Preparations", "Physicians", "Play", "Population", "Positioning Attribute", "Process", "Public Health", "Race", "Randomized", "Randomized Controlled Trials", "Recommendation", "Regimen", "Research", "Rheumatism", "Rheumatoid Arthritis", "Rheumatology", "Risk", "Role", "SARS-CoV-2 infection", "Safety", "Social Network", "Societies", "Structural Racism", "Structure", "Systemic Lupus Erythematosus", "Testing", "Training", "Training Activity", "Trust", "Underrepresented Minority", "Vaccinated", "Vaccination", "Vaccines", "Work", "acute care", "adverse outcome", "arm", "black patient", "comorbidity", "density", "design", "empowerment", "ethnic disparity", "evidence base", "experience", "forging", "health care availability", "health care disparity", "high risk", "immunosuppressed", "improved", "lens", "long-standing disparities", "low socioeconomic status", "member", "mortality", "outreach", "people of color", "physically handicapped", "racial disparity", "racism", "recruit", "response", "severe COVID-19", "social health determinants", "socioeconomic disparity", "standard of care", "transmission process", "treatment arm", "uptake", "vaccine acceptance", "vaccine efficacy", "vaccine hesitancy", "vaccine response", "vaccine safety", "virtual" ], "approved": true } }, { "type": "Grant", "id": "11577", "attributes": { "award_id": "5R01AI159290-02", "title": "The role of TRIM2 and SIRPA in New World Arenavirus entry", "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": 7012, "first_name": "LESLEY CONRAD", "last_name": "Dupuy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-23", "end_date": "2027-04-30", "award_amount": 493835, "principal_investigator": { "id": 23850, "first_name": "SUSAN R", "last_name": "ROSS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 163, "ror": "https://ror.org/02mpq6x41", "name": "University of Illinois at Chicago", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 163, "ror": "https://ror.org/02mpq6x41", "name": "University of Illinois at Chicago", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "New world hemorrhagic fever arenaviruses (NWAs), such as Junín virus, are rodent-transmitted viruses that cause ~30% mortality when they zoonose into humans. The mechanism by the NWAs induce disease is still not certain, although it likely includes induction of high levels of cytokines by infected sentinel cells of the immune system, leading to endothelia and thrombocyte dysfunction and neurological disease. Survivors of Junín infection develop strong humoral immune responses, suggesting that controlling infection at early times post-infection is critical for virus clearance. Although an effective Junín virus vaccine has decreased disease incidence, sporadic cases of this as well as the other known and novel NWAs for which there are no vaccines or effective therapeutics still occur. It is well-established that the clade B pathogenic NWAs bind to transferrin receptor 1 and other receptors on the cell surface, but the steps leading to their entry from an acidic cellular compartment are not well-determined. We recently performed a siRNA screen with pseudotyped viruses bearing a pathogenic Junín glycoprotein with the goal of finding host genes involved in entry that could serve as therapeutic targets. We found that TRIM2, a member of the tripartite motif family that includes well-known members of the host's intrinsic defense against viral infections, limits NWA endocytosis into cells. By probing the TRIM2 interactome for other host proteins that block NWA infection, we discovered that SIRPA, a cell surface protein that inhibits macrophage phagocytosis of tumor and dead cells and erythrocytes, also decreases infection. Importantly, SIRPA, unlike TRIM2, inhibits infection by various human pathogenic viruses that require trafficking to an acidic compartment, including VSV, Zika virus, LCMV and Ebola and SARS-Cov-2 pseudoviruses. Our data suggest that TRIM2 and SIRPA act at the viral entry/internalization step. These finding suggests that there are common mechanisms that regulate virus endocytosis and phagocytosis. We propose here to further investigate the overlap between virus-mediated endocytosis and phagocytosis in vitro, ex vivo and in vivo in three aims that will 1) investigate the overlap in the NWA entry and phagocytosis pathways; 2) determine where TRIM2/SIRPA inhibition of infection occurs; and 3) use TRIM2, SIRPA and other relevant knockout mice to probe the roles of these proteins in cell-type specific and in vivo infection by replication-competent NWAs. In addition to providing mechanistic insight into the entry of NWAs into cells, these studies have the potential of increasing our understanding as to how host factors limit infection and could lead to new approaches to therapeutic intervention.", "keywords": [ "2019-nCoV", "Actins", "Aerosols", "Amino Acid Motifs", "Antiviral Response", "Antiviral Therapy", "Apoptosis", "Arenavirus", "Arenavirus Infections", "Argentina", "Binding", "Biological Process", "Blood Platelets", "C-terminal", "Cell Culture Techniques", "Cell Extracts", "Cell Proliferation", "Cell Surface Proteins", "Cell surface", "Cells", "Complex", "Cultured Cells", "Cytoskeleton", "Data", "Disease", "Ebola", "Endocytosis", "Endothelium", "Erythrocytes", "Family", "Functional disorder", "Genes", "Glycoproteins", "Goals", "Human", "Human Pathology", "Image", "Immune response", "Immune system", "In Vitro", "Incidence", "Infection", "Infection Control", "Integration Host Factors", "Junin virus", "Knockout Mice", "Link", "Lymphocytic choriomeningitis virus", "Mediating", "Modeling", "Mus", "Mutation", "Old World Arenaviruses", "PTPN6 gene", "PTPNS1 gene", "Pathogenicity", "Pathway interactions", "Patients", "Phagocytosis", "Phagocytosis Inhibition", "Phosphoric Monoester Hydrolases", "Phosphorylation", "Primates", "Process", "Protein Family", "Proteins", "RNA Viruses", "RNA interference screen", "Rodent", "Role", "Sentinel", "Signal Transduction", "Signal Transduction Pathway", "Small Interfering RNA", "Specificity", "Survivors", "TFRC gene", "TRIM Motif", "Tacaribe Complex Viruses", "Tacaribe virus", "Testing", "Therapeutic Intervention", "Tissue Extracts", "Ubiquitination", "Vaccines", "Vesicular stomatitis Indiana virus", "Viral", "Viral Hemorrhagic Fevers", "Virus", "Virus Diseases", "Visualization", "Work", "Zika Virus", "Zoonoses", "cell type", "cellular targeting", "cytokine", "experimental study", "in vivo", "insight", "knock-down", "macrophage", "member", "mortality", "neoplastic cell", "nervous system disorder", "novel", "novel strategies", "novel therapeutic intervention", "pathogenic virus", "prevent", "receptor", "therapeutic target", "therapeutically effective", "trafficking", "transmission process", "tumor", "ubiquitin ligase", "viral transmission" ], "approved": true } }, { "type": "Grant", "id": "11578", "attributes": { "award_id": "5R21AI160950-02", "title": "Elucidating the role of SERINC5 in SARS-CoV-2 infection", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 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": "2022-05-18", "end_date": "2024-04-30", "award_amount": 199375, "principal_investigator": { "id": 7522, "first_name": "Spyridon", "last_name": "Stavrou", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 856, "ror": "", "name": "STATE UNIVERSITY OF NEW YORK AT BUFFALO", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 856, "ror": "", "name": "STATE UNIVERSITY OF NEW YORK AT BUFFALO", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "A viral pathogen associated with severe pneumonia was recently identified as the cause of a global pandemic that has resulted in the death of over two million people. This viral pathogen was later classified as a coronavirus that was subsequently named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Currently, there is a paucity of information regarding SARS-CoV-2 infection and the cellular factors associated with it. The identification of host factors that target SARS-CoV-2 infection and the elucidation of their mechanism of action is critical for the development of SARS-CoV-2 therapeutics. It was recently shown that the Serine Incorporator (SERINC) protein family, which is comprised by 5 multipass transmembrane proteins (SERINC1-5) plays a critical role in retroviral entry, yet the role of SERINC factors on other viral infections including SARS-CoV-2 infection is currently unknown. This proposal investigates the effect of SERINC5 on SARS-CoV-2 infection. The goal of this proposal is to provide mechanistic evidence on the effect of SERINC5 on SARS-CoV-2 entry, as many times, host factors use different mechanisms to restrict viruses that belong to different viral families. Previous research has shown that human immunodeficiency virus (HIV) is potently restricted by SERINC5 in a mechanism that has not been fully elucidated. However, HIV encodes an accessory protein, Nef, which counteracts the deleterious effect of SERINC5. Similar viral proteins have been identified in other retroviruses, which demonstrates the importance of SERINC5 in retrovirus infection. Hence another aspect of this proposal is to determine a SARS-CoV-2 encoded factor that targets SERINC5 and the mechanism it utilizes to counteract SERINC5. This study will provide much needed insight into the role of a novel host factor that targets SARS- CoV-2, which is of great importance as there is not a lot of mechanistic understanding of host factors that target SARS-CoV-2. Moreover, little is known about the role of SARS-CoV-2 proteins and how they modulate the host cell; hence, the findings of this proposal will provide valuable information regarding the function of SARS-CoV-2 encoded factors. Finally, the discovery of host factors that restrict SARS-CoV-2 infection may expand the gamut of potential drug targets for the development of SARS-CoV-2 antivirals.", "keywords": [ "2019-nCoV", "ACE2", "Acute Respiratory Distress Syndrome", "Adult", "Affect", "Binding", "Biogenesis", "Biological Assay", "COVID-19 therapeutics", "Cell fusion", "Cells", "Cessation of life", "Classification", "Complex", "Coronavirus", "Coughing", "Data", "Development", "Drug Targeting", "Event", "Family", "Fever", "Genome", "Goals", "HIV", "HIV-1", "Human", "Infection", "Integral Membrane Protein", "Integration Host Factors", "Malaise", "Mediating", "Molecular Biology", "Multiple Organ Failure", "Mutate", "Mutation", "Names", "Parvovirus", "Persons", "Phosphatidylserines", "Play", "Pneumonia", "Protein Family", "Proteins", "Research", "Resources", "Respiratory Failure", "Retroviridae", "Retroviridae Infections", "Reverse Transcription", "Role", "SARS coronavirus", "SARS-CoV-2 antiviral", "SARS-CoV-2 infection", "SARS-CoV-2 inhibitor", "Series", "Serine", "Shortness of Breath", "Sphingolipids", "Surface", "Viral", "Viral Genome", "Viral Proteins", "Virus", "Virus Diseases", "Virus Replication", "antiviral drug development", "common symptom", "current pandemic", "domain mapping", "insight", "member", "mutant", "novel", "pandemic disease", "pathogenic virus", "receptor", "receptor binding", "targeted treatment", "therapeutic development", "therapeutic target", "viral entry inhibitor" ], "approved": true } }, { "type": "Grant", "id": "11579", "attributes": { "award_id": "5U01CK000643-02", "title": "RFA-CK-22-003, Emerging Infections Sentinel Networks (EISN) Research - 2022", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2022-05-01", "end_date": "2027-04-30", "award_amount": 250000, "principal_investigator": { "id": 23853, "first_name": "DAVID ANDREW", "last_name": "TALAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 818, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 818, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "In 1995, following the Institute of Medicine’s report, “Emerging Infections,” and in response to the CDC’s strategic plan to enhance surveillance, EMERGEncy ID NET was established. EMERGEncy ID NET's goal was to address the threat of emerging infectious diseases by assessing disease prevalence, risk factors, and management practices for acute presentations from the community among a diverse and underserved population of patients presenting to US emergency departments (EDs). A CDC cooperative grant has funded the network for the last 25 years. Due to the ability to prospectively collect clinical data and specimens for on-site laboratory analysis 24/7 from acutely ill patients from the community, EMERGEncy ID NET has been able to produce translational research that has impacted physician practices and informed public health policy. The research network demonstrated its capability to successfully address an urgent public health threat during the COVID-19 pandemic by rapidly implementing 20-site and 16-site public health surveillance projects of ED patient care-related infection risk and vaccine effectiveness among frontline health care personnel. Numerous peer-reviewed publications have resulted from EMERGEncy ID NET research, including in high-impact journals such as The New England Journal of Medicine, the Journal of the American Medical Association, Clinical Infectious Diseases, Emerging Infectious Diseases, and Annals of Emergency Medicine. Aims of EMERGEncy ID NET for the next 5 years are to: 1) identify emerging infections and risk factors for these conditions affecting US ED patients, including among underserved groups; 2) leverage EMERGEncy ID NET’s findings to create new collaborations to develop and improve diagnostic tests, treatments, and vaccines; and 3) disseminate results at national medical conferences, in high-impact journals, and on infectious diseases, public health, and emergency medicine social media outlets to inform treatment and public health policy, and educate the public. Support of EMERGEncy ID NET for the next 5 years will ensure that the network can continue to answer new questions about emerging infections and related areas of high public health priority.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "11580", "attributes": { "award_id": "5R21MH127284-02", "title": "The cognitive and neural mechanisms supporting naturalistic dyadic social interactions", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 22777, "first_name": "Andrew Lee", "last_name": "Breeden", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-09", "end_date": "2024-04-30", "award_amount": 202500, "principal_investigator": { "id": 23854, "first_name": "Diana", "last_name": "Tamir", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 191, "ror": "https://ror.org/00hx57361", "name": "Princeton University", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 191, "ror": "https://ror.org/00hx57361", "name": "Princeton University", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true }, "abstract": "/ Abstract Social interactions are key to well-being. When successful, interactions engender social bonds that reduce stress, loneliness, and depression, and that support longevity. This proposal aims to identify the mechanisms by which social interactions produce social connection. Two studies use state-of-the-art tools in computer vision, natural language processing, and fMRI hyperscanning–where two people are scanned at the same time–to peer into the minds of people as they interact in real time. This project focuses on naturalistic interactions. To date, neuroscience research into social interaction has relied primarily on paradigms that do not actually allow people to interact. The current proposal offers a shift from these conventional paradigms. We will leverage rich data from real-time conversations to investigate two conversation features—social content and positive affect—that may effectively support social connection. We test the direct relation between these conversation features and social connection in Aim 1. Aim 2 will then test the hypothesis that these features promote connection by helping conversation partners to get ‘on the same page’—to align their thoughts and feelings. We will measure alignment using fMRI hyperscanning. Study 1 will use a unique virtual video conversation platform that connects two remote communicators. Dyads will freely converse while we record real-time acoustic, visual, and language data, from which our analysis tools can automatically extract both conversation features. Participants will also complete a post-conversation survey to assess the primary outcome: social connection. We will use factor analysis and cross-validation to optimally cluster our multimodal features and to optimize our model of how conversation features induce alignment, which, in turn, supports social connection. Study 2 aims to replicate this behavioral model, and further, to identify the underlying mechanism that links conversation features to social connection using neuroimaging. If conversation brings about social connection because it induces alignment, then we should see that socially connected dyads experience neural alignment within networks associated with both content and affect: the default and limbic networks, respectively. Our unique research site, with two MRI scanners in adjacent rooms, allows us to use fMRI hyperscanning and high-resolution imaging of cortical and subcortical neural networks, a resolution far beyond what is possible with methods typically employed for studying naturalistic interactions. The proposed investigation into the real-time dynamics of interactions will assess how communication syncs minds, and how this alignment supports social connection. This work will reveal the basic ingredients of successful interactions. In doing so, it offers promising future directions for alleviating the devastating effects of social disconnection, as felt by healthy populations during moments of stress or social distancing during the Covid-19 pandemic and by vulnerable populations with depression, social anxiety, or autism.", "keywords": [ "Acoustics", "Affect", "Behavioral Model", "COVID-19 pandemic", "Cognitive", "Communication", "Computer Vision Systems", "Data", "Electroencephalography", "Empathy", "Facial Expression", "Factor Analysis", "Feeling", "Free Will", "Functional Magnetic Resonance Imaging", "Future", "Heart Diseases", "Individual", "Intervention", "Investigation", "Knowledge", "Language", "Linguistics", "Link", "Loneliness", "Longevity", "Magnetic Resonance Imaging", "Malignant Neoplasms", "Measures", "Mediating", "Mental Depression", "Methods", "Mind", "Modeling", "Motivation", "Natural Language Processing", "Neurosciences Research", "Participant", "Personal Satisfaction", "Persons", "Population", "Populations at Risk", "Process", "Research", "Research Personnel", "Resolution", "Route", "Scanning", "Self Disclosure", "Site", "Sleep", "Social Distance", "Social Interaction", "Social outcome", "Social support", "Stimulus", "Stress", "Surveys", "Testing", "Thinking", "Time", "Validation", "Visual", "Vulnerable Populations", "Work", "autism spectrum disorder", "experience", "functional near infrared spectroscopy", "high resolution imaging", "mortality", "multimodality", "neural", "neural network", "neuroimaging", "neuromechanism", "peer", "primary outcome", "psychologic", "social", "social anxiety", "social attachment", "social communication", "stress reduction", "tool", "virtual" ], "approved": true } }, { "type": "Grant", "id": "11581", "attributes": { "award_id": "5R01AI170514-02", "title": "How infectious SARS-CoV-2 exploits two ER membrane proteins to promote 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": 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": "2022-05-17", "end_date": "2027-04-30", "award_amount": 381807, "principal_investigator": { "id": 7649, "first_name": "Billy", "last_name": "Tsai", "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": "SARS-CoV-2 exploits the function of the endoplasmic reticulum (ER) to promote its infection life cycle. Despite its strong reliance on the ER, the molecular basis by which SARS-CoV-2 hijacks ER factors to promote defined steps of this life cycle remains unclear. Using infectious SARS-CoV-2, we recently identified two ER membrane proteins – RTN3 and SigmaR1 – as critical host factors that support virus infection. Our findings further reveal that RTN3 plays a role in viral replication, while SigmaR1 exerts a function in viral secretion. However, how SARS-CoV-2 exploits the activities of RTN3 and SigmaR1 to accomplish these two distinct tasks, in mechanistic terms, is completely unknown. Accordingly, the objective of this application is to elucidate the molecular basis by which these two ER membrane factors promote replication and secretion of SARS- CoV-2. We believe these insights will not only illuminate the basic infection mechanism of SARS-CoV-2, but given the continuing global COVID-19 pandemic, may lead to the development of effective anti-virals to blunt the devastating impact of SARS-CoV-2.", "keywords": [ "2019-nCoV", "Antiviral Agents", "Biology", "COVID-19", "COVID-19 pandemic", "Cells", "Complex", "Cytosol", "Data", "Development", "Disease Progression", "Drug Modulation", "Endoplasmic Reticulum", "Endosomes", "FDA approved", "Genetic Transcription", "Genome", "Golgi Apparatus", "Impairment", "Infection", "Integration Host Factors", "Life Cycle Stages", "Link", "Membrane", "Membrane Fusion", "Membrane Proteins", "Methods", "Molecular", "Nature", "Nonstructural Protein", "Organelles", "Pathway interactions", "Process", "Protein S", "Proteins", "RNA", "Role", "SARS-CoV-2 infection", "Shapes", "Site", "Structural Protein", "Structure", "Testing", "Translating", "Translations", "Vesicle", "Viral", "Viral Genome", "Viral Proteins", "Viral Structural Proteins", "Virus", "Virus Assembly", "Virus Diseases", "Virus Replication", "endosome membrane", "experimental study", "genomic RNA", "insight", "loss of function", "multiple myeloma M Protein", "particle", "polypeptide", "receptor mediated endocytosis", "recruit", "viral genomics" ], "approved": true } }, { "type": "Grant", "id": "11582", "attributes": { "award_id": "5R21AI161400-02", "title": "Targeting SARS-CoV-2 induced lung immunopathology using novel genetic mouse models", "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": "2022-05-09", "end_date": "2024-04-30", "award_amount": 190161, "principal_investigator": { "id": 7653, "first_name": "Ekaterina", "last_name": "Koroleva", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 748, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7654, "first_name": "Alexei V", "last_name": "Tumanov", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 7655, "first_name": "YAN", "last_name": "XIANG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 748, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 748, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Lung immunopathology is a major cause of the morbidity and mortality associated with the SARS-CoV-2 infection. Accumulating evidence suggests that SARS-CoV-2-associated lung damage is caused not only by the virus, but also by excessive production of proinflammatory cytokines, known as cytokine storm. Although available vaccines and antiviral drugs protect against infection, these strategies do not specifically target immune-mediated pathology. Therefore, uncoupling anti-viral host defense mechanisms from the immunopathology induced by these mechanisms, represents a novel therapeutic strategy for COVID-19 treatment. However, to develop such strategies, a better understanding of the fundamental mechanisms that regulate SARS-CoV-2-induced immunopathology using animal models of COVID-19 disease is critical. The critical gap is limited therapeutic approaches that specifically target immune-mediated pathology and availability of animal models that recapitulate human lung disease. Experiments with mouse models expressing SARS-CoV-2 receptor, human ACE2 (hACE2) demonstrated virus invasion to the brain and multiple organ pathology with limited lung pathology, which does not fully recapitulate acute respiratory distress syndrome in patients with severe COVID-19 disease. Our ongoing results demonstrate that lymphotoxin beta receptor (LTR)-deficient mice are protected from SARS-CoV-2-induced immunopathology. We also found that LTβR promotes cytokine storm and lung damage in another model of respiratory disease, influenza infection. The objective of this proposal is to develop novel mouse models that mimic lung disease of COVID-19 patients and to test the efficacy of LTR inhibitor to block SARS-CoV- 2-induced lung damage. Our central hypothesis is that expression of hACE2 in type II alveolar epithelial cells is required for SARS-CoV-2 induced lung disease and that LTR antagonist inhibits SARS- CoV-2 induced lung immunopathology. To test this hypothesis, we propose two specific aims. In Aim 1, we will generate mice with regulated hACE2 expression in type II alveolar epithelial cells using CRISPR- Cas9 system. We will infect these mice intranasally with SARS-CoV-2 and evaluate lung immunopathology and cytokine expression. In Aim 2, we will test the effectiveness of LTR antagonist to block SARS-CoV- 2-induced immunopathology. We will optimize dose and timing of LTR inhibitors and evaluate lung immunopathology, viral replication, cytokine production, and protective immunity. This proposal is innovative and significant, as it will generate novel animal models to study SARS-CoV-2 pathogenesis, provide deeper understanding of the mechanisms regulating virus-induced immunopathology and test the feasibility of targeting novel immune regulator, LTR, to inhibit SARS-CoV-2 induced immunopathology without limiting protective immunity.", "keywords": [ "2019-nCoV", "ACE2", "Acute Respiratory Distress Syndrome", "Age", "Animal Model", "Antibody Response", "Antiviral Agents", "Biochemical", "Biological Response Modifiers", "Body Weight Changes", "Brain", "CCL2 gene", "CCL20 gene", "CCL3 gene", "COVID-19", "COVID-19 patient", "COVID-19 treatment", "CRISPR/Cas technology", "CXCL1 gene", "CXCL2 gene", "Cells", "Complex", "Consensus", "Cytokine Receptors", "Data", "Development", "Disease", "Disease model", "Dose", "Enterobacteria phage P1 Cre recombinase", "Epithelial Cells", "Equilibrium", "Flow Cytometry", "Gene Expression Profiling", "Generations", "Genetic", "Goals", "Histology", "Host Defense Mechanism", "Human", "Immune", "Immune Targeting", "Immune response", "Immunity", "Immunohistochemistry", "Infection", "Inflammation", "Inflammatory", "Influenza A Virus H1N1 Subtype", "Interleukin-6", "Invaded", "Knock-in Mouse", "Lung", "Lung diseases", "Mediating", "Modeling", "Morbidity - disease rate", "Mouse Strains", "Mus", "Organ", "Pathologic", "Pathology", "Pathway interactions", "Patients", "Production", "Proteins", "Protocols documentation", "Public Health", "Publishing", "Pulmonary Pathology", "Receptor Signaling", "Reproducibility", "Research", "Respiratory Disease", "Role", "SARS-CoV-2 infection", "SARS-CoV-2 inhibitor", "SARS-CoV-2 pathogenesis", "Severe Acute Respiratory Syndrome", "System", "Testing", "Therapeutic", "Therapeutic Uses", "Transgenic Mice", "Tumor Necrosis Factor Receptor", "Viral", "Virus", "Virus Replication", "alveolar epithelium", "antagonist", "biosafety level 3 facility", "chemokine", "cytokine", "cytokine release syndrome", "design", "effective therapy", "effectiveness testing", "efficacy testing", "experimental study", "feasibility testing", "human tissue", "immune activation", "immunopathology", "in vivo", "influenza infection", "influenzavirus", "inhibitor", "innovation", "lung development", "lung injury", "lymphotoxin beta receptor", "member", "mortality", "mouse model", "novel", "novel therapeutic intervention", "post SARS-CoV-2 infection", "prevent", "promoter", "receptor", "severe COVID-19", "sex", "therapeutic target", "transcriptome sequencing", "vaccine access" ], "approved": true } }, { "type": "Grant", "id": "11583", "attributes": { "award_id": "5R03AI169063-02", "title": "Mechanistic Insights of TIMP-1 in Influenza Virus 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": "2022-05-01", "end_date": "2024-04-30", "award_amount": 75500, "principal_investigator": { "id": 23855, "first_name": "Xiaoyun", "last_name": "Wang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 888, "ror": "https://ror.org/00te3t702", "name": "University of Georgia", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 888, "ror": "https://ror.org/00te3t702", "name": "University of Georgia", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY/ ABSTRACT Influenza A virus (IAV) epidemics are associated with high morbidity and mortality. Complications such as the development of secondary bacterial pneumonia and cytokine storm leading to multi-organ failure increase morbidity and mortality. Although vaccines are developed annually for emerging IAV strains, not all subjects are vaccinated or able to mount robust protective immune responses to the vaccines. Anti-viral drugs such as oseltamivir are not fully effective at preventing mortality associated with severe IAV infections. Thus, there is an urgent need to identify new therapeutic targets to facilitate the development of more effective antiviral agents to limit the high global healthcare burden associated with IAV infections. TIMP-1 (tissue inhibitor of metalloproteinases 1) controls the enzymatic activity of matrix metalloproteinases (MMPs) and is well-known for regulating extracellular matrix (ECM) turnover, but its contributions to the pathogenesis of IAV disease have not been deeply explored. Our novel preliminary data showed that plasma TIMP-1 levels are significantly upregulated in patients diagnosed with pandemic H1N1 and seasonal IAV infections, and levels correlate inversely with the PaO2/FiO2 ratio. Furthermore, our data using immunofluorescence staining suggested TIMP- 1 is dramatically induced in lipofibroblasts. Compared with WT mice, Timp-1-/- mice have reduced H1N1 IAV- induced body weight loss; mortality; lung injury; increased adaptive immune responses and T cell and B cell activation, and attenuated capillary leak. Based on our data, TIMP-1 might serve as a novel therapeutic target during serious IAV infection. The experiments proposed in this application aim to 1) identify the regulation and function of TIMP-1 during the IAV infection; 2) provide novel insights into the mechanism by which Timp-1 deficiency provides better outcomes during IAV infection. Successful completion of these studies will pave the way for future investigational new drug (IND)-enabling studies to test the safety and efficacy of a “first in class” therapeutic targeting the host response to reduce the morbidity and mortality associated with serious IAV infection.", "keywords": [ "18 year old", "Activated Lymphocyte", "Acute Lung Injury", "Antiviral Agents", "Apoptotic", "Attenuated", "B-Cell Activation", "B-Lymphocytes", "Bacterial Pneumonia", "Biological Response Modifiers", "Blood Vessels", "Blood capillaries", "Body Weight decreased", "Capillary Permeability", "Cell Proliferation", "Cells", "Cessation of life", "Data", "Development", "Diagnosis", "Extracellular Matrix", "Extracellular Matrix Degradation", "Future", "Goals", "Hospitalization", "Immune response", "Immunofluorescence Immunologic", "Impairment", "In Vitro", "Individual", "Inflammatory Response", "Influenza", "Influenza A Virus H1N1 Subtype", "Influenza A virus", "Investigational Drugs", "Knowledge", "Link", "Lung", "Matrix Metalloproteinase Inhibitor", "Matrix Metalloproteinases", "Measures", "Mediating", "Morbidity - disease rate", "Multiple Organ Failure", "Mus", "Myofibroblast", "Oseltamivir", "Outcome", "Oxygen", "Pathogenesis", "Patients", "Peptide Hydrolases", "Plasma", "Proteins", "Pulmonary Inflammation", "Regulation", "Role", "Seasons", "Severities", "Stains", "Structure of parenchyma of lung", "T-Lymphocyte", "Testing", "Tissue Inhibitor of Metalloproteinase-1", "Vaccinated", "Vaccinee", "Vaccines", "Viral Proteins", "Virus", "Virus Diseases", "Virus Replication", "Wild Type Mouse", "adaptive immune response", "care burden", "cell type", "cytokine release syndrome", "effective therapy", "epidemic virus", "experimental study", "flu", "global health", "human subject", "influenza infection", "insight", "lung injury", "mortality", "new therapeutic target", "novel", "pandemic disease", "prevent", "protective effect", "recruit", "safety testing", "seasonal influenza", "therapeutic target", "transdifferentiation", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "11584", "attributes": { "award_id": "5R21AI169392-02", "title": "Spatiotemporal transcriptomics at the maternal-fetal interface in COVID placenta", "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": "2022-05-06", "end_date": "2024-04-30", "award_amount": 219000, "principal_investigator": { "id": 7729, "first_name": "YUPING", "last_name": "WANG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 835, "ror": "", "name": "LOUISIANA STATE UNIV HSC SHREVEPORT", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 835, "ror": "", "name": "LOUISIANA STATE UNIV HSC SHREVEPORT", "address": "", "city": "", "state": "LA", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as the greatest threat to global health and significantly impact pregnant women worldwide. COVID-19 infection during pregnancy is associated with substantial risk of increases in maternal morbidity and mortality and neonatal complications, compared with their non-infected pregnant counterparts. However, vertical transmission of the virus is uncommon, which suggest that innate immune system must function at the maternal-fetal interface to shield the developing fetus from infection. Despite fast-tracked intensive research on many aspects of SARS- CoV-2, the impact of the viral infection in the placenta and the placental defense mechanism(s) are poorly explored. Placenta is the structural and immunological barrier of pathogen transmission. To explore the innate antiviral defense mechanism(s), in our preliminary study we specifically determined expression of interferon pathway-related molecules in placental tissues. Strikingly, we found distinct patterns of stimulator of interferon genes (STING), interferon regulator factor 3 (IRF3), and Type I IFN (such as IFNb) expression at the maternal- fetal interface of the placentas from women infected with COVID-19. STING is a sensor for viral infection. STING-IRF3 pathway signaling regulates Type I IFN production, and Type I IFNs are potent antiviral cytokines. We also noticed that Toll-like receptor 7 (TLR7) is upregulated in both syncytiotrophoblasts ( STs) and extravillous trophoblasts (EVTs) in placentas from patients with COVID-19 compared to those are not. TLR7, located on the X chromosome, is a sensor for single strand RNA (ssRNA) viruses. These findings are intriguing and indicate that an innate antiviral immune system is activated at the maternal-fetal interface in patients with COVID-19 during pregnancy. The objective of the study is to identify spatiotemporal transcriptomic signatures and networks of the innate antiviral immune system at the maternal-fetal interface. We will test the hypothesis an effective and robust innate antiviral immune system is activated at the maternal-fetal interface to prevent viral transmission and shield the fetus from infection, which will be tested in two specific aims. Aim 1 will identify spatiotemporal innate immunity gene profiles and networks in villous tissue that respond to maternal SARS-CoV-2 infection. Aim 2 will identify spatiotemporal innate immunity gene profiles and networks in fetal membrane and decidual tissue that respond to maternal SARS-CoV-2 infection. A state-of-the-art novel technique of 10x Genomics Visium Gene Expression assay in placental formalin-fixed paraffin embedded (FFPE) tissues combined with RNA-seq will be employed . Placentas from women with active COVID infection, recovered from COVID infection, and received COVID vaccination, etc. will be studied. This novel ideal approach will allow us to map the whole transcriptome with morphological context in placental FFPE tissue and discover the cellular and molecular profiles and networks in different cell types and gene activity at the maternal-fetal interface without disruption of the tissue integrity. Results of the study will provide novel insights into how SARS-CoV-2 infection impacts the innate immune system at the mater-fetal interface, and how the innate immune system at the maternal-fetal interface responds to COVID vaccination during pregnancy, which may help to identify new strategies to prevent COVID-19 infection and reduce maternal and fetal complications in women with COVID-19 infection in the future.", "keywords": [ "2019-nCoV", "Brain", "COVID-19", "COVID-19 patient", "COVID-19 prevention", "COVID-19 vaccination", "Cells", "Cerebrum", "Clinical Management", "Decidual Cell", "Defense Mechanisms", "Embryo", "Epithelial Cells", "Fetal Development", "Fetal Membranes", "Fetus", "Formalin", "Future", "Gene Expression Profiling", "Genes", "Genomics", "Gestational Diabetes", "Homeostasis", "Immune", "Immune system", "Immunologics", "Infection", "Innate Immune System", "Institution", "Interferon-beta", "Interferons", "International", "Low Birth Weight Infant", "Maps", "Maternal Mortality", "Maternal-Fetal Exchange", "Mesenchymal", "Molecular", "Molecular Profiling", "Morphology", "Natural Immunity", "Neonatal", "Nucleic Acids", "Nucleocapsid Proteins", "Organ", "Organoids", "Outcome", "Paraffin Embedding", "Pathway interactions", "Pattern", "Placenta", "Pre-Eclampsia", "Pregnancy", "Pregnant Women", "Premature Birth", "Prevent viral transmission", "Production", "Proteins", "RNA Viruses", "Research", "Risk", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Signal Pathway", "Signal Transduction Pathway", "Stimulator of Interferon Genes", "Stromal Cells", "Symptoms", "Syncytiotrophoblast", "System", "TLR7 gene", "Techniques", "Testing", "Tissue Embedding", "Tissues", "Vaccination", "Vertical Transmission", "Villous", "Viral", "Virus Diseases", "Woman", "Women&apos", "s Group", "X Chromosome", "adverse pregnancy outcome", "cell type", "coronavirus disease", "cytokine", "cytotrophoblast", "epidemiology study", "fetal", "gene network", "global health", "insight", "maternal morbidity", "novel", "pandemic disease", "pathogen", "post SARS-CoV-2 infection", "pregnant", "response", "sensor", "spatiotemporal", "stillbirth", "transcriptome", "transcriptome sequencing", "transcriptomics", "transmission process", "trophoblast", "viral transmission" ], "approved": true } }, { "type": "Grant", "id": "11585", "attributes": { "award_id": "5R01AI164266-02", "title": "AI-based platform for predicting emerging vaccine-escape variants and designing mutation-proof antibodies", "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": "2022-05-06", "end_date": "2027-04-30", "award_amount": 541935, "principal_investigator": { "id": 7733, "first_name": "Guowei", "last_name": "Wei", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 521, "ror": "https://ror.org/05hs6h993", "name": "Michigan State University", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7734, "first_name": "YONG-HUI", "last_name": "ZHENG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 521, "ror": "https://ror.org/05hs6h993", "name": "Michigan State University", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Due to massive vaccination, coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been partially under control. However, emerging contagious variants such as Delta are still fueling new waves of infections around the world. Vaccine-escape (or vaccine-breakthrough) variants pose renewed threats to our battle against COVID-19. Understanding viral mutagenesis and evolution is of preeminent importance. By integrating genomic analysis, artificial intelligence (AI), computational biophysics, advanced mathematics, and experimental data, the PIs have built a comprehensive program with the experimental level of accuracy and population-level of reliability for predicting SARS-CoV-2 variant infectivity and antibody disruption. It remains challenging to forecast future emerging vaccine-escape variants, to develop the next-generation of vaccines, and to design mutation- proof antibody therapeutics. These challenges are tackled in the proposed project. New mathematical tools and AI algorithms will be developed to further improve the current state-of- the-art in predicting mutation-induced viral infectivity changes, vaccine breakthroughs, and antibody disruptions. Vital mutations in future emerging variants will be forecasted based on molecular mechanisms, natural selection, and evolutionary effects. New mutation-proof antibody drugs will be designed and tested based on those antibodies that had gone through earlier clinical trials. The predictive models will be implemented into a user-friendly platform with online servers for researchers to design mutation-proof new vaccines and antibody therapies. The proposed methods will be applied to forecast emerging variants in the flu and improve the efficacy of seasonal flu vaccines.", "keywords": [ "2019-nCoV", "ACE2", "Affinity", "Antibodies", "Antibody Therapy", "Antigens", "Artificial Intelligence", "Artificial Intelligence platform", "Binding", "Biophysical Process", "Biophysics", "COVID-19", "COVID-19 patient", "COVID-19 vaccination", "Categories", "Cells", "Cessation of life", "Clinical Trials", "Computer Assisted", "Country", "Data", "Databases", "Deposition", "Development", "Elements", "Emergency Situation", "Evolution", "Future", "Generations", "Genes", "Genome", "Genomics", "Genotype", "Goals", "Graph", "Induced Mutation", "Infection", "Libraries", "Life", "Literature", "Mathematics", "Methodology", "Methods", "Modeling", "Molecular", "Mutagenesis", "Mutate", "Mutation", "Natural Selections", "Patients", "Pattern", "Pharmaceutical Preparations", "Phase", "Play", "Population", "Prevention Measures", "Probability", "Property", "Proteins", "Race", "Research Personnel", "SARS-CoV-2 antibody", "SARS-CoV-2 genome", "SARS-CoV-2 spike protein", "SARS-CoV-2 variant", "Series", "Structure", "Testing", "Therapeutic antibodies", "Training", "Vaccine Therapy", "Vaccines", "Validation", "Variant", "Viral", "Viral Vaccines", "Virus", "Work", "algebraic topology", "antibody libraries", "artificial intelligence algorithm", "base", "design", "differential geometry", "drug discovery", "early phase clinical trial", "efficacy validation", "experimental study", "flu", "future pandemic", "improved", "influenza virus vaccine", "innovation", "next generation", "novel vaccines", "pandemic disease", "predictive modeling", "programs", "receptor", "receptor binding", "seasonal influenza", "software development", "success", "theories", "tool", "user friendly software", "user-friendly" ], "approved": true } } ], "meta": { "pagination": { "page": 1385, "pages": 1405, "count": 14046 } } }