Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1405&sort=title
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=title", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=title", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1406&sort=title", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1404&sort=title" }, "data": [ { "type": "Grant", "id": "7564", "attributes": { "award_id": "1R01AI153087-01", "title": "Viral and immune kinetics in rhinovirus infection following hematopoietic cell transplantation", "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": 6011, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-04", "end_date": "2024-05-31", "award_amount": 695614, "principal_investigator": { "id": 7700, "first_name": "Alpana Amalkant", "last_name": "Waghmare", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 732, "ror": "https://ror.org/01njes783", "name": "Seattle Children's Hospital", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 732, "ror": "https://ror.org/01njes783", "name": "Seattle Children's Hospital", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Human rhinovirus (HRV) is the most common respiratory virus detected in the upper and lower respiratory tract in hematopoietic cell transplant (HCT) recipients; mortality rates following HRV lower respiratory tract infection are similar to those seen with known pulmonary viral pathogens including respiratory syncytial virus, influenza, and parainfluenza virus. Despite the high burden of disease and the observed complications of HRV infection in HCT recipients, the development of HRV therapeutics is hindered by the lack of a comprehensive understanding of the relationship between viral detection, symptoms and host immune responses and the impact of these factors on disease severity. We have demonstrated that clinical risk factors, including cytopenias and steroid use, are associated with progression from upper respiratory tract infection (URTI) to LRTI. However, up to 70% of patients with profound immunosuppression at the time of virus acquisition clear their infections without treatment. Our preliminary data show that gene expression signatures at the time of URTI may be predictive of progression to LRTI. We aim to characterize the interplay between viral detection, cytokine levels and cellular immune responses early during HRV infection in HCT recipients in a prospective surveillance cohort. We will also perform in depth gene expression analyses at a single cell level to identify specific cellular populations that are associated with severe disease in both peripheral blood and in proximal bronchoalveolar lavage fluid. The central hypothesis of this proposal is that viral and host immune kinetics, including both global and cell specific gene expression profiles in specific tissue compartments, impact disease severity in HCT recipients with HRV infection. Results from these experiments will characterize the optimal timing and most predictive viral and host immune markers that can be used to design rational clinical trials for novel therapeutics. Our deep interrogation of compartment and cell specific immune responses will further our understanding of virus-host interactions and of potential targets for intervention.", "keywords": [ "Acute", "Age", "Allogenic", "Antiviral Agents", "Biological Markers", "Blood", "Blood specimen", "Bronchoalveolar Lavage Fluid", "Cells", "Cessation of life", "Clinical", "Clinical Trials", "Collection", "Complex", "Containment", "Cytotoxic T-Lymphocytes", "Data", "Detection", "Development", "Disease", "Enrollment", "Equilibrium", "Evaluation", "Expression Profiling", "Future", "Gene Expression", "Gene Expression Profile", "Gene Expression Profiling", "Genes", "Genetic Transcription", "Home environment", "Human", "Immune", "Immune response", "Immunologic Markers", "Immunologics", "Immunophenotyping", "Immunosuppression", "Infection", "Infection Control", "Inflammatory", "Intervention", "Kinetics", "Lower Respiratory Tract Infection", "Lower respiratory tract structure", "Lung", "Modeling", "Nose", "Outcome", "Pathway interactions", "Patients", "Pattern", "Peripheral Blood Mononuclear Cell", "Play", "Population", "Prevention strategy", "Prognostic Marker", "Progressive Disease", "Prospective Studies", "Prospective cohort", "Respiratory Signs and Symptoms", "Respiratory syncytial virus", "Rhinovirus", "Rhinovirus infection", "Risk", "Risk Factors", "Role", "Sampling", "Severity of illness", "Specimen", "Steroids", "Surveys", "Swab", "Symptoms", "T-Lymphocyte", "Testing", "Therapeutic", "Therapeutic Clinical Trial", "Time", "Tissues", "Transplant Recipients", "Upper Respiratory Infections", "Upper respiratory tract", "Viral", "Viral Load result", "Virus", "Whole Blood", "acute infection", "base", "burden of illness", "clinical risk", "cohort", "cytokine", "cytopenia", "design", "disorder control", "early detection biomarkers", "experimental study", "handheld mobile device", "hematopoietic cell transplantation", "improved", "influenzavirus", "innovation", "mathematical model", "mortality", "novel therapeutics", "overexpression", "parainfluenza virus", "pathogenic virus", "patient stratification", "peripheral blood", "prospective", "respiratory", "respiratory virus", "single cell analysis", "single-cell RNA sequencing", "temporal measurement", "transcriptome", "transcriptome sequencing", "transcriptomics", "viral detection", "virus host interaction" ], "approved": true } }, { "type": "Grant", "id": "7071", "attributes": { "award_id": "1R01AI157488-01", "title": "Viral and immune-mediated CNS pathology during 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": 8802, "first_name": "Thomas R.", "last_name": "Esch", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-07-24", "end_date": "2025-06-30", "award_amount": 417822, "principal_investigator": { "id": 10916, "first_name": "Shelli", "last_name": "Farhadian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 452, "ror": "https://ror.org/03v76x132", "name": "Yale University", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 10917, "first_name": "AKIKO", "last_name": "IWASAKI", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 452, "ror": "https://ror.org/03v76x132", "name": "Yale University", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic has rampantly affected the population of the world and created lasting effects on the economy, health and psyche of the global community. Although it shares similarities with SARS-CoV-1, the full extent of the pathophysiology caused by SARS-CoV-2 is unclear. In particular, extrapulmonary manifestations effects of SARS-CoV-2 infection remain poorly understood. Case series from China and Europe suggest that the central nervous system is involved in the disease process in at least a subset of patients, with some reports estimating up to 30% of COVID-19 patients having neurological symptoms, including seizure, intractable headache, and impaired smell and taste. Although there are reports of neurological disease in in COVID-19 patients, it is unclear if SARS-CoV-2 invades the central nervous system (CNS). Studies of other coronaviruses, including SARS-CoV-1, demonstrate clear neurotropism as well as neuroinflammation associated with other members of this family of viruses. These studies raise the possibility that SARS-CoV-2 may cause neurological symptoms either through invasion of the CNS or through an increase in inflammatory cytokines within the CNS. We hypothesize that SARS-CoV-2 infections have neuroinvasive potential and lead to altered and hyperinflammatory immune states within the CNS of infected individuals. We further hypothesize that infection of the CNS exacerbates respiratory dysfunction through direct toxicity of ACE2 expressing neurons that are critical regulators of cardiopulmonary function. Our investigations will combine the power of human studies with those utilizing mouse models in which we can readily administer virus and assess for pathophysiology. Aim 1, we will determine the CNS immune responses in COVID-19 patients with neurological symptoms. Using a combination of single cell RNA-sequencing, cytokine profiling, viral sequencing and antibody validations, we will fully dissect out the inflammatory responses within the CNS compartment compared to the systemic circulation in COVID-19 patients. Using mouse models, in Aim 2, we will investigate the encephalitic potential of SARS-CoV-2. Using several complementary approaches to infect mice with SARS-CoV-2, we will introduce the virus into the central nervous system of mice. Using depletion antibodies and various knockout mice, we will identify which immune cells are required for neuropathology in these mice through survival studies, flow cytometry and immunofluorescent staining. Finally, in Aim 3, we will evaluate the effects of CNS infection on respiratory outcomes. Because of the known expression of ACE2 in the brainstem, and the brainstem’s critical role in regulating cardiopulmonary functions, we suspect that CNS infection with SARS-CoV-2 will exacerbate SARS-CoV-2 respiratory disease. These three aims will help support our hypotheses of how SARS-CoV-2 infections can affect the CNS and respiratory compartments. We expect that our findings will uncover new strategies to treat patients diagnosed with COVID-19 and help gain new insight to understanding the biology of SARS-CoV-2 pathophysiology.", "keywords": [ "2019-nCoV", "Affect", "Antibodies", "Ataxia", "Attenuated", "Autopsy", "Biological Assay", "Biology", "Blood", "Blood Circulation", "Brain", "Brain Stem", "COVID-19", "COVID-19 pandemic", "Cardiopulmonary", "Case Series", "Cells", "Central Nervous System Infections", "Cerebrospinal Fluid", "China", "Communities", "Coronavirus", "Data", "Detection", "Diagnosis", "Disease", "Dose", "Encephalopathies", "Enrollment", "Europe", "Evaluation", "Family member", "Fever", "Flow Cytometry", "Functional disorder", "Genomics", "Goals", "Headache", "Health", "Heart", "Heart Hypertrophy", "Histology", "Histopathology", "Human", "Hypertension", "Hypogeusia", "Hypoxemia", "Immune", "Immune response", "Impairment", "Individual", "Infection", "Inflammatory", "Inflammatory Response", "Institutional Review Boards", "Intractable Headaches", "Invaded", "Investigation", "Knockout Mice", "Lead", "Lung", "Lung diseases", "Lung infections", "Maps", "Measurement", "Mediating", "Modeling", "Monitor", "Mus", "Nervous System Trauma", "Nervous system structure", "Neuraxis", "Neurologic", "Neurologic Effect", "Neurologic Symptoms", "Neurological Models", "Neurons", "Neurotropism", "Outcome", "Pathogenicity", "Pathology", "Pathway interactions", "Patients", "Physiological", "Plaque Assay", "Plasma Cells", "Pneumonia", "Population", "Process", "Production", "Protocols documentation", "Pulmonary Heart Disease", "Pulmonary Pathology", "Reporting", "Respiration Disorders", "Respiratory Failure", "Respiratory Signs and Symptoms", "Respiratory Tract Infections", "Role", "SARS coronavirus", "Sampling", "Secondary to", "Seizures", "Smell Perception", "Spinal Puncture", "Stains", "Structure of parenchyma of lung", "Study models", "Supporting Cell", "Symptoms", "Taste Perception", "Tissues", "Toxic effect", "Tumor-infiltrating immune cells", "Validation", "Viral", "Viral Antigens", "Virus", "Wild Type Mouse", "adeno-associated viral vector", "associated symptom", "biobank", "brain tissue", "central nervous system injury", "common symptom", "coronavirus disease", "cytokine", "human tissue", "immunoreaction", "influenzavirus", "insight", "interest", "monocyte", "mortality", "mouse model", "nervous system disorder", "neuroinflammation", "neuron loss", "neuropathology", "neurotropic", "novel", "overexpression", "patient subsets", "receptor", "respiratory", "response", "single-cell RNA sequencing", "success" ], "approved": true } }, { "type": "Grant", "id": "9126", "attributes": { "award_id": "3R01AI157488-02S1", "title": "Viral and immune-mediated CNS pathology during 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": 8802, "first_name": "Thomas R.", "last_name": "Esch", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-07-21", "end_date": "2023-06-30", "award_amount": 61789, "principal_investigator": { "id": 10916, "first_name": "Shelli", "last_name": "Farhadian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 452, "ror": "https://ror.org/03v76x132", "name": "Yale University", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 10917, "first_name": "AKIKO", "last_name": "IWASAKI", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 452, "ror": "https://ror.org/03v76x132", "name": "Yale University", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic has rampantly affected the population of the world and created lasting effects on the economy, health and psyche of the global community. Although it shares similarities with SARS-CoV-1, the full extent of the pathophysiology caused by SARS-CoV-2 is unclear. In particular, extrapulmonary manifestations effects of SARS-CoV-2 infection remain poorly understood. Case series from China and Europe suggest that the central nervous system is involved in the disease process in at least a subset of patients, with some reports estimating up to 30% of COVID-19 patients having neurological symptoms, including seizure, intractable headache, and impaired smell and taste. Although there are reports of neurological disease in in COVID-19 patients, it is unclear if SARS-CoV-2 invades the central nervous system (CNS). Studies of other coronaviruses, including SARS-CoV-1, demonstrate clear neurotropism as well as neuroinflammation associated with other members of this family of viruses. These studies raise the possibility that SARS-CoV-2 may cause neurological symptoms either through invasion of the CNS or through an increase in inflammatory cytokines within the CNS. We hypothesize that SARS-CoV-2 infections have neuroinvasive potential and lead to altered and hyperinflammatory immune states within the CNS of infected individuals. We further hypothesize that infection of the CNS exacerbates respiratory dysfunction through direct toxicity of ACE2 expressing neurons that are critical regulators of cardiopulmonary function. Our investigations will combine the power of human studies with those utilizing mouse models in which we can readily administer virus and assess for pathophysiology. Aim 1, we will determine the CNS immune responses in COVID-19 patients with neurological symptoms. Using a combination of single cell RNA-sequencing, cytokine profiling, viral sequencing and antibody validations, we will fully dissect out the inflammatory responses within the CNS compartment compared to the systemic circulation in COVID-19 patients. Using mouse models, in Aim 2, we will investigate the encephalitic potential of SARS-CoV-2. Using several complementary approaches to infect mice with SARS-CoV-2, we will introduce the virus into the central nervous system of mice. Using depletion antibodies and various knockout mice, we will identify which immune cells are required for neuropathology in these mice through survival studies, flow cytometry and immunofluorescent staining. Finally, in Aim 3, we will evaluate the effects of CNS infection on respiratory outcomes. Because of the known expression of ACE2 in the brainstem, and the brainstem’s critical role in regulating cardiopulmonary functions, we suspect that CNS infection with SARS-CoV-2 will exacerbate SARS-CoV-2 respiratory disease. These three aims will help support our hypotheses of how SARS-CoV-2 infections can affect the CNS and respiratory compartments. We expect that our findings will uncover new strategies to treat patients diagnosed with COVID-19 and help gain new insight to understanding the biology of SARS-CoV-2 pathophysiology.", "keywords": [ "2019-nCoV", "ACE2", "Affect", "Anosmia", "Antibodies", "Ataxia", "Attenuated", "Autopsy", "Biology", "Blood", "Blood Circulation", "Brain", "Brain Stem", "COVID-19", "COVID-19 diagnosis", "COVID-19 pandemic", "COVID-19 patient", "COVID-19 treatment", "Cardiopulmonary", "Case Series", "Cells", "Central Nervous System Infections", "Cerebrospinal Fluid", "China", "Communities", "Coronavirus", "Data", "Disease", "Dose", "Encephalopathies", "Enrollment", "Europe", "Evaluation", "Family member", "Fever", "Flow Cytometry", "Functional disorder", "Genomics", "Goals", "Headache", "Health", "Heart", "Heart Hypertrophy", "Histology", "Histopathology", "Human", "Hypertension", "Hypogeusia", "Hypoxemia", "Immune", "Immune response", "Impairment", "Individual", "Infection", "Inflammatory", "Inflammatory Response", "Institutional Review Boards", "Intractable Headaches", "Invaded", "Investigation", "Knockout Mice", "Lead", "Lung", "Lung diseases", "Lung infections", "Maps", "Measurement", "Mediating", "Modeling", "Monitor", "Mus", "Nervous System Trauma", "Nervous system structure", "Neuraxis", "Neurologic", "Neurologic Effect", "Neurologic Symptoms", "Neurological Models", "Neurons", "Neurotropism", "Olfactory dysfunction", "Outcome", "Pathogenicity", "Pathology", "Pathway interactions", "Patients", "Physiological", "Plaque Assay", "Plasma Cells", "Pneumonia", "Population", "Process", "Production", "Protocols documentation", "Pulmonary Heart Disease", "Pulmonary Pathology", "Reporting", "Respiration Disorders", "Respiratory Failure", "Respiratory Signs and Symptoms", "Respiratory Tract Infections", "Role", "SARS coronavirus", "SARS-CoV-2 infection", "Sampling", "Secondary to", "Seizures", "Smell Perception", "Spinal Puncture", "Stains", "Structure of parenchyma of lung", "Study models", "Supporting Cell", "Symptoms", "Taste Perception", "Tissues", "Toxic effect", "Tumor-infiltrating immune cells", "Validation", "Viral", "Virus", "Wild Type Mouse", "adeno-associated viral vector", "antigen detection", "associated symptom", "biobank", "brain tissue", "central nervous system injury", "common symptom", "coronavirus disease", "cytokine", "detection assay", "human tissue", "immunoreaction", "influenzavirus", "insight", "interest", "monocyte", "mortality", "mouse model", "nervous system disorder", "neuroinflammation", "neuron loss", "neuropathology", "neurotropic", "novel", "overexpression", "patient subsets", "receptor", "r" ], "approved": true } }, { "type": "Grant", "id": "5775", "attributes": { "award_id": "5R01AI157488-02", "title": "Viral and immune-mediated CNS pathology during 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": 19874, "first_name": "Thomas R.", "last_name": "Esch", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-07-24", "end_date": "2025-06-30", "award_amount": 417822, "principal_investigator": { "id": 19875, "first_name": "Shelli", "last_name": "Farhadian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 19876, "first_name": "AKIKO", "last_name": "IWASAKI", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 452, "ror": "https://ror.org/03v76x132", "name": "Yale University", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic has rampantly affected the population of the world and created lasting effects on the economy, health and psyche of the global community. Although it shares similarities with SARS-CoV-1, the full extent of the pathophysiology caused by SARS-CoV-2 is unclear. In particular, extrapulmonary manifestations effects of SARS-CoV-2 infection remain poorly understood. Case series from China and Europe suggest that the central nervous system is involved in the disease process in at least a subset of patients, with some reports estimating up to 30% of COVID-19 patients having neurological symptoms, including seizure, intractable headache, and impaired smell and taste. Although there are reports of neurological disease in in COVID-19 patients, it is unclear if SARS-CoV-2 invades the central nervous system (CNS). Studies of other coronaviruses, including SARS-CoV-1, demonstrate clear neurotropism as well as neuroinflammation associated with other members of this family of viruses. These studies raise the possibility that SARS-CoV-2 may cause neurological symptoms either through invasion of the CNS or through an increase in inflammatory cytokines within the CNS. We hypothesize that SARS-CoV-2 infections have neuroinvasive potential and lead to altered and hyperinflammatory immune states within the CNS of infected individuals. We further hypothesize that infection of the CNS exacerbates respiratory dysfunction through direct toxicity of ACE2 expressing neurons that are critical regulators of cardiopulmonary function. Our investigations will combine the power of human studies with those utilizing mouse models in which we can readily administer virus and assess for pathophysiology. Aim 1, we will determine the CNS immune responses in COVID-19 patients with neurological symptoms. Using a combination of single cell RNA-sequencing, cytokine profiling, viral sequencing and antibody validations, we will fully dissect out the inflammatory responses within the CNS compartment compared to the systemic circulation in COVID-19 patients. Using mouse models, in Aim 2, we will investigate the encephalitic potential of SARS-CoV-2. Using several complementary approaches to infect mice with SARS-CoV-2, we will introduce the virus into the central nervous system of mice. Using depletion antibodies and various knockout mice, we will identify which immune cells are required for neuropathology in these mice through survival studies, flow cytometry and immunofluorescent staining. Finally, in Aim 3, we will evaluate the effects of CNS infection on respiratory outcomes. Because of the known expression of ACE2 in the brainstem, and the brainstem’s critical role in regulating cardiopulmonary functions, we suspect that CNS infection with SARS-CoV-2 will exacerbate SARS-CoV-2 respiratory disease. These three aims will help support our hypotheses of how SARS-CoV-2 infections can affect the CNS and respiratory compartments. We expect that our findings will uncover new strategies to treat patients diagnosed with COVID-19 and help gain new insight to understanding the biology of SARS-CoV-2 pathophysiology.", "keywords": [ "2019-nCoV", "ACE2", "Affect", "Anosmia", "Antibodies", "Ataxia", "Attenuated", "Autopsy", "Biology", "Blood", "Blood Circulation", "Brain", "Brain Stem", "COVID-19", "COVID-19 diagnosis", "COVID-19 pandemic", "COVID-19 patient", "COVID-19 treatment", "Cardiopulmonary", "Case Series", "Cells", "Central Nervous System Infections", "Cerebrospinal Fluid", "China", "Communities", "Coronavirus", "Data", "Disease", "Dose", "Encephalopathies", "Enrollment", "Europe", "Evaluation", "Family member", "Fever", "Flow Cytometry", "Functional disorder", "Genomics", "Goals", "Headache", "Health", "Heart", "Heart Hypertrophy", "Histology", "Histopathology", "Human", "Hypertension", "Hypogeusia", "Hypoxemia", "Immune", "Immune response", "Impairment", "Individual", "Infection", "Inflammatory", "Inflammatory Response", "Institutional Review Boards", "Intractable Headaches", "Invaded", "Investigation", "Knockout Mice", "Lead", "Lung", "Lung diseases", "Lung infections", "Maps", "Measurement", "Mediating", "Modeling", "Monitor", "Mus", "Nervous System Trauma", "Nervous system structure", "Neuraxis", "Neurologic", "Neurologic Effect", "Neurologic Symptoms", "Neurological Models", "Neurons", "Neurotropism", "Olfactory dysfunction", "Outcome", "Pathogenicity", "Pathology", "Pathway interactions", "Patients", "Physiological", "Plaque Assay", "Plasma Cells", "Pneumonia", "Population", "Process", "Production", "Protocols documentation", "Pulmonary Heart Disease", "Pulmonary Pathology", "Reporting", "Respiration Disorders", "Respiratory Failure", "Respiratory Signs and Symptoms", "Respiratory Tract Infections", "Role", "SARS coronavirus", "SARS-CoV-2 infection", "Sampling", "Secondary to", "Seizures", "Smell Perception", "Spinal Puncture", "Stains", "Structure of parenchyma of lung", "Study models", "Supporting Cell", "Symptoms", "Taste Perception", "Tissues", "Toxic effect", "Tumor-infiltrating immune cells", "Validation", "Viral", "Virus", "Wild Type Mouse", "adeno-associated viral vector", "antigen detection", "associated symptom", "biobank", "brain tissue", "central nervous system injury", "common symptom", "coronavirus disease", "cytokine", "detection assay", "human tissue", "immunoreaction", "influenzavirus", "insight", "interest", "monocyte", "mortality", "mouse model", "nervous system disorder", "neuroinflammation", "neuron loss", "neuropathology", "neurotropic", "novel", "overexpression", "patient subsets", "receptor", "r" ], "approved": true } }, { "type": "Grant", "id": "15741", "attributes": { "award_id": "1R35GM160071-01", "title": "Viral Biosensors of Host Post-Translational Modifications", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 22244, "first_name": "MICHAEL", "last_name": "SAKALIAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2030-07-31", "award_amount": 420984, "principal_investigator": { "id": 26190, "first_name": "Mehdi", "last_name": "Bouhaddou", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2612, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Viruses and their hosts are engaged in a constant, dynamic struggle as part of an ongoing evolutionary arms race. It is well established that viruses continually evolve new offensive strategies, like the production of proteins that disrupt host defenses, while hosts develop countermeasures to detect and neutralize viruses. However, a key question that remains is: how do viruses perceive and respond to host cues in real-time? This ability to sense and adapt to the intracellular environment, akin to real-time \"decision-making,\" which helps them decide when to replicate, assemble, or escape, plays a crucial role in their fitness and ability to spread. To understand how viruses sense and respond to their environment, we will study host-derived post-translational modifications (PTMs) of viral proteins. The overarching hypothesis of this proposal is that viral proteins have evolved as substrates for host enzyme-derived PTMs to equip them with molecular sensors to coordinate viral life cycle transitions. Furthermore, we will study how PTMs enable multifunctionality in viral proteins by creating distinct proteoforms. By understanding the molecular mechanisms of viral biosensors, we expect to pinpoint critical viral dependencies, revealing promising targets for antiviral intervention. PTMs, imposed by the host cell, can dramatically alter the functions of viral proteins, influencing their behavior and ultimately the fate of the virus. Our preliminary mass spectrometry phosphoproteomics analysis of alphavirus infection revealed phosphorylation sites at the capsid-glycoprotein interface, likely regulated by plasma membrane-localized kinases, suggesting a functional switch in glycoproteins at the membrane. We similarly identified phosphorylation sites on herpesvirus latency proteins, which we believe may play a role in allowing the viral genome to replicate alongside the host genome during latency. Lastly, we discovered phosphorylation of a SARS-CoV-2 accessory protein by innate immune kinases, suggesting a feedback mechanism that may modify viral protein function in response to immune activation. Our data have led us to three specific areas of inquiry, each forming a distinct research project being conducted by PhD students, a project scientist, and undergraduate trainees: (1) How do viruses navigate through distinct host subcellular locations during their life cycle? (2) How do viruses coordinate their life cycle with the host cell cycle? (3) How do viruses sense, respond to, and exploit the host innate immune system? The projects and questions outlined in this proposal will serve as the foundation for the primary research in my laboratory over the next five years. Our questions seek to establish a new research area centered on the biochemical mechanisms through which viruses act as biosensors of the host signaling environment, how these biosensors adjust their functionality in response to PTMs, and how targeting these sensors may result in innovative antiviral therapies.", "keywords": [ "2019-nCoV", "Alphavirus Infections", "Anti-viral Therapy", "Area", "Behavior", "Biochemical", "Biosensor", "Capsid", "Cell Cycle", "Cell membrane", "Cells", "Cues", "Data", "Decision Making", "Dependence", "Development", "Disease", "Environment", "Enzymes", "Feedback", "Foundations", "Genome", "Glycoproteins", "Herpesviridae", "Host Defense", "Immune", "Innate Immune System", "Intervention", "Knowledge", "Laboratories", "Life Cycle Stages", "Location", "Mass Spectrum Analysis", "Membrane", "Mission", "Molecular", "Phosphorylation", "Phosphorylation Site", "Phosphotransferases", "Play", "Post-Translational Protein Processing", "Production", "Proteins", "Public Health", "Research", "Research Project Grants", "Role", "Scientist", "Signal Transduction", "Time", "United States National Institutes of Health", "Viral", "Viral Genome", "Viral Physiology", "Viral Proteins", "Virus", "Virus Diseases", "arms race", "doctoral student", "fitness", "immune activation", "innovation", "insight", "novel therapeutic intervention", "phosphoproteomics", "protein function", "response", "sensor", "undergraduate student" ], "approved": true } }, { "type": "Grant", "id": "11924", "attributes": { "award_id": "5K43TW012350-02", "title": "Viral Diversity an Innovative Biomarker for Refining Estimates of HIV Incidence", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Fogarty International Center (FIC)" ], "program_reference_codes": [], "program_officials": [ { "id": 8125, "first_name": "GEETHA PARTHASARATHY", "last_name": "Bansal", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-01", "end_date": "2027-06-30", "award_amount": 136537, "principal_investigator": { "id": 25656, "first_name": "Sikhulile", "last_name": "Moyo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1868, "ror": "", "name": "BOTSWANA-HARVARD AIDS INSTITUTE", "address": "", "city": "", "state": "", "zip": "", "country": "BOTSWANA", "approved": true }, "abstract": "Candidate: Dr Sikhulile Moyo is unwaveringly committed to an overarching career focused on contributing to ending the HIV epidemic and related public health emergencies. He committed to a career focused on finding cost-effective tools for estimating the impact of interventions and towards HIV cure research. He envisions himself as a leader globally, in research aimed towards tracking and eliminating new HIV infections & towards developing an HIV cure, working with researchers, program implementers and policy makers for rapid and cost-effective evaluation of interventions. Dr Moyo’s 5-year career development plan is focused on three key areas: phylogenetics, epidemiology and biostatistics; cross-sectional Incidence and Implementation; and HIV cure & characterization of early founder viruses, and SARS-COV-2 genomics. In order to achieve his short- and medium-term career objectives he seeks to: a) develop advanced methodologic and analytic skills in molecular epidemiology, phylogenetic analysis and bioinformatics; b) expand laboratory expertise in real-time high-throughput next generation sequencing and accurate and reliable quantification of proviral reservoirs for advancing HIV cure studies, and c) strengthen leadership abilities particularly in managing large scientific projects, population-level surveys, and diverse research teams with expertise in different fields, organizational leadership and student research supervision. Training activities will encompass formal training and coursework, practical application through the proposed research project, and direct mentorship from my highly experienced mentorship and advisory team. These activities will draw on the strengths of the mentorship team and leading research institutions with strong collaborative ties and have a record of mentoring young investigators to R01 and independence. Research: The study aims to introduce an innovative approach to estimating HIV incidence, which is very important for national HIV programs / public health, and also for HIV prevention research, but can be expensive and challenging to do. The specific aims are: 1) To assess adjusted viral diversity as a potential biomarker of HIV incidence. 2) To refine results of serological screening in subsets of true- and false-recent cases, and patients with established infection (ART-naïve and on ART), by adjusted viral diversity. We will test whether viral diversity within the most informative regions across the HIV-1C genome adjusted for multiplicity of transmission, recombination, and level of viral replication could be used to refine the results of serological screening and improve specificity and sensitivity. We expect that the adjusted viral diversity within the most informative regions will increase specificity and sensitivity in estimation of HIV incidence within the 4 subsets of individuals targeted in this Aim to ≥95%. Establishing a cost-effective algorithm to estimate incidence is of critical public health importance in low resource settings.", "keywords": [ "2019-nCoV", "AIDS prevention", "Adopted", "Advisory Committees", "African", "Algorithms", "Area", "Bioinformatics", "Biological Assay", "Biological Markers", "Biometry", "Country", "Cross-Sectional Studies", "Data", "Development", "Development Plans", "Epidemic", "Epidemiology", "Evaluation", "Exclusion", "Genetic Recombination", "Genome", "Genomics", "Genotype", "HIV", "HIV Genome", "HIV Infections", "HIV-1", "Incidence", "Individual", "Infection", "Institution", "Intervention", "Laboratories", "Leadership", "Length", "Longitudinal Studies", "Measurement", "Measures", "Mentors", "Mentorship", "Methodology", "Methods", "Modeling", "Molecular", "Molecular Epidemiology", "Monitor", "Outcome", "Patients", "Persons", "Phylogenetic Analysis", "Policy Maker", "Population", "Prevention Research", "Process", "Public Health", "RNA", "Research", "Research Personnel", "Research Project Grants", "Resource-limited setting", "Role", "Sampling", "Sensitivity and Specificity", "Serology", "Specificity", "Specimen", "Students", "Supervision", "Surveys", "Testing", "Time", "Training", "Training Activity", "Uncertainty", "Viral", "Viral Genome", "Virus", "Virus Replication", "antiretroviral therapy", "bioinformatics pipeline", "career", "career development", "cost", "cost effective", "experience", "genome sequencing", "improved", "innovation", "longitudinal analysis", "low income country", "next generation sequencing", "potential biomarker", "practical application", "pre-exposure prophylaxis", "programs", "prospective", "public health emergency", "response", "scale up", "screening", "segregation", "seroconversion", "skills", "tool", "transmission process", "trend" ], "approved": true } }, { "type": "Grant", "id": "9802", "attributes": { "award_id": "1K43TW012350-01", "title": "Viral Diversity an Innovative Biomarker for Refining Estimates of HIV Incidence", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Fogarty International Center (FIC)" ], "program_reference_codes": [], "program_officials": [ { "id": 8125, "first_name": "GEETHA PARTHASARATHY", "last_name": "Bansal", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-01", "end_date": "2027-06-30", "award_amount": 136526, "principal_investigator": { "id": 25656, "first_name": "Sikhulile", "last_name": "Moyo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1868, "ror": "", "name": "BOTSWANA-HARVARD AIDS INSTITUTE", "address": "", "city": "", "state": "", "zip": "", "country": "BOTSWANA", "approved": true }, "abstract": "Candidate: Dr Sikhulile Moyo is unwaveringly committed to an overarching career focused on contributing to ending the HIV epidemic and related public health emergencies. He committed to a career focused on finding cost-effective tools for estimating the impact of interventions and towards HIV cure research. He envisions himself as a leader globally, in research aimed towards tracking and eliminating new HIV infections & towards developing an HIV cure, working with researchers, program implementers and policy makers for rapid and cost-effective evaluation of interventions. Dr Moyo’s 5-year career development plan is focused on three key areas: phylogenetics, epidemiology and biostatistics; cross-sectional Incidence and Implementation; and HIV cure & characterization of early founder viruses, and SARS-COV-2 genomics. In order to achieve his short- and medium-term career objectives he seeks to: a) develop advanced methodologic and analytic skills in molecular epidemiology, phylogenetic analysis and bioinformatics; b) expand laboratory expertise in real-time high-throughput next generation sequencing and accurate and reliable quantification of proviral reservoirs for advancing HIV cure studies, and c) strengthen leadership abilities particularly in managing large scientific projects, population-level surveys, and diverse research teams with expertise in different fields, organizational leadership and student research supervision. Training activities will encompass formal training and coursework, practical application through the proposed research project, and direct mentorship from my highly experienced mentorship and advisory team. These activities will draw on the strengths of the mentorship team and leading research institutions with strong collaborative ties and have a record of mentoring young investigators to R01 and independence. Research: The study aims to introduce an innovative approach to estimating HIV incidence, which is very important for national HIV programs / public health, and also for HIV prevention research, but can be expensive and challenging to do. The specific aims are: 1) To assess adjusted viral diversity as a potential biomarker of HIV incidence. 2) To refine results of serological screening in subsets of true- and false-recent cases, and patients with established infection (ART-naïve and on ART), by adjusted viral diversity. We will test whether viral diversity within the most informative regions across the HIV-1C genome adjusted for multiplicity of transmission, recombination, and level of viral replication could be used to refine the results of serological screening and improve specificity and sensitivity. We expect that the adjusted viral diversity within the most informative regions will increase specificity and sensitivity in estimation of HIV incidence within the 4 subsets of individuals targeted in this Aim to ≥95%. Establishing a cost-effective algorithm to estimate incidence is of critical public health importance in low resource settings.", "keywords": [ "2019-nCoV", "AIDS prevention", "Adopted", "Advisory Committees", "African", "Algorithms", "Area", "Bioinformatics", "Biological Assay", "Biological Markers", "Biometry", "Country", "Cross-Sectional Studies", "Data", "Development", "Development Plans", "Epidemic", "Epidemiology", "Evaluation", "Exclusion", "Genetic Recombination", "Genome", "Genomics", "Genotype", "HIV", "HIV Genome", "HIV Infections", "HIV-1", "Incidence", "Individual", "Infection", "Institution", "Intervention", "Laboratories", "Lead", "Leadership", "Length", "Longitudinal Studies", "Measurement", "Measures", "Mentors", "Mentorship", "Methodology", "Methods", "Modeling", "Molecular", "Molecular Epidemiology", "Monitor", "Outcome", "Patients", "Persons", "Phylogenetic Analysis", "Policy Maker", "Population", "Prevention Research", "Process", "Public Health", "RNA", "Research", "Research Personnel", "Research Project Grants", "Resource-limited setting", "Role", "Sampling", "Sensitivity and Specificity", "Serology", "Specificity", "Specimen", "Students", "Supervision", "Surveys", "Testing", "Time", "Training", "Training Activity", "Uncertainty", "Viral", "Viral Genome", "Virus", "Virus Replication", "antiretroviral therapy", "bioinformatics pipeline", "career", "career development", "cost", "cost effective", "experience", "genome sequencing", "improved", "innovation", "longitudinal analysis", "low income country", "next generation sequencing", "potential biomarker", "practical application", "pre-exposure prophylaxis", "programs", "prospective", "public health emergency", "research study", "response", "scale up", "screening", "seroconversion", "skills", "tool", "transmission process", "trend" ], "approved": true } }, { "type": "Grant", "id": "6837", "attributes": { "award_id": "1U19AI168631-01", "title": "Viral Immunity and VAccination (VIVA) Human Immunology Project Consortium (HIPC)", "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": 8224, "first_name": "Kentner L.", "last_name": "Singleton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-03-22", "end_date": "2027-02-28", "award_amount": 2265730, "principal_investigator": { "id": 21760, "first_name": "Ana", "last_name": "Fernandez-Sesma", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7185, "first_name": "Viviana A", "last_name": "Simon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The Viral Immunity and Vaccination (VIVA) Human Immunology Project Consortium (HIPC) will carry out a comprehensive systems immunology program to assess the dynamic human immune response to SARS-CoV- 2, seasonal influenza viruses and tetravalent and trivalent dengue vaccines and subsequent infections by those pathogens. It will generate comprehensive innate, cellular and adaptive immune signatures that correlate with vaccine outcomes. The VIVA HIPC will leverage recent advances in human immune profiling methods to characterize the diverse states of the human immune system before and after vaccination against these viral pathogens of great public health concern using novel immune phenotyping and genomics strategies that generate data and tools to be used for downstream data analysis and functional investigations. The proposed studies will use longitudinal biospecimens from established human cohorts of respiratory infections and vaccinations in the US and Argentina as well as from vaccine trials in the US (provided by the Clinical Core, Core B). In addition, validation experiments using human tonsils sourced from healthy individuals and exposed ex vivo to the different vaccine types will be conducted. Three complementary, well-integrated projects will produce in-depth human immune profiles and signatures of SARS-CoV-2 vaccinations and infections (Project 1), seasonal influenza vaccinations and infections (Project 2) as well as dengue vaccine and human challenge studies (Project 3). Unique in our approach is the use of longitudinal cohorts for in vivo profiling, supported by ex vivo human tonsillar histoculture (HC) models for infection and vaccination. Our holistic approach will provide cutting- responses to vaccinations and infections by the Immune Phenotyping Core (Core C), genomics/transcriptomics, including scRNAseq, CITEseq and spatial tissue transcriptomics by the Genomics Core (Core D), and experimental vaccinations in primary human tonsillar histocultures (HC) in Projects 1, 2 and 3. Data mining, bioinformatics to identify the network components and infer their interactions and correlations important for vaccine outcomes will be done by the Data management and Analysis Core (Core E). The VIVA HIPC will make the data, analyses and immune profiles generated available to the scientific community by coupling our local data infrastructure to ImmPort (directly or through the HIPC Coordinating Center). This integration will ensure full and timely release of clinical, sample, and experimental metadata in synchrony with genomic data releases to standard data repositories including SRA, GEO, and Genbank (Core E). The VIVA team (Drs. Krammer, Garcia-Sastre, Durbin, Gamarnik, van Bakel and Sebra) led by Dr. Fernandez-Sesma and Dr. Simon includes physicians, physician scientists and scientists with complementary expertise in viral immunology, viral pathogenesis, vaccinology, genomics, data analysis and a proven track record of collaboration and excellence.", "keywords": [ "2019-nCoV", "Area", "Argentina", "Attenuated", "Bioinformatics", "Biological Assay", "Biological Models", "COVID-19 pandemic", "COVID-19 vaccination", "COVID-19 vaccine", "Cells", "Cellular Indexing of Transcriptomes and Epitopes by Sequencing", "Characteristics", "Clinical", "Clinical Trials", "Collaborations", "Communicable Diseases", "Communities", "Coupling", "Cryopreserved Cell", "Data", "Data Analyses", "Data Set", "Dengue", "Dengue Vaccine", "Dengue Virus", "Development", "Differentiation Antigens", "Ensure", "Enzyme-Linked Immunosorbent Assay", "Epidemic", "Flow Cytometry", "Foundations", "Frequencies", "Genbank", "Generations", "Genomic approach", "Genomics", "Goals", "Human", "Immune", "Immune response", "Immune system", "Immunity", "Immunization", "Immunoglobulins", "Immunologic Memory", "Immunologics", "Immunology", "Individual", "Infection", "Influenza A virus", "Influenza B Virus", "Influenza vaccination", "Investigation", "Longitudinal cohort", "Lymphoid Tissue", "Maintenance", "Maps", "Measures", "Mediating", "Metadata", "Methods", "Modeling", "Morbidity - disease rate", "Pathway interactions", "Peripheral Blood Mononuclear Cell", "Persons", "Phenotype", "Physicians", "Physiological", "Plasma", "Population", "Population Characteristics", "Prevention strategy", "Public Health", "Research Personnel", "Respiratory Tract Infections", "SARS coronavirus", "Sampling", "Scientist", "Serology", "Serotyping", "Source", "Standardization", "System", "Techniques", "Technology", "Testing", "Time", "Tissues", "Tonsil", "Vaccinated", "Vaccination", "Vaccines", "Validation", "Viral", "Viral Antigens", "Viral Pathogenesis", "Virus", "Virus Diseases", "World Health", "adaptive immune response", "adaptive immunity", "breakthrough infection", "cell type", "cohort", "data infrastructure", "data management", "data mining", "data repository", "data standards", "data tools", "experimental study", "gene network", "genomic data", "holistic approach", "human disease", "immunological status", "in vivo", "influenza infection", "influenza virus vaccine", "influenzavirus", "mortality", "mosquito-borne", "network models", "next generation", "novel", "pathogen", "pathogenic virus", "phenotypic data", "predictive modeling", "programs", "response", "seasonal influenza", "sequencing platform", "tool", "transcriptomics", "vaccination outcome", "vaccine candidate", "vaccine immunogenicity", "vaccine re" ], "approved": true } }, { "type": "Grant", "id": "11667", "attributes": { "award_id": "5U19AI168631-02", "title": "Viral Immunity and VAccination (VIVA) Human Immunology Project Consortium (HIPC)", "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": 8224, "first_name": "Kentner L.", "last_name": "Singleton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-03-22", "end_date": "2027-02-28", "award_amount": 2265730, "principal_investigator": { "id": 21760, "first_name": "Ana", "last_name": "Fernandez-Sesma", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7185, "first_name": "Viviana A", "last_name": "Simon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The Viral Immunity and Vaccination (VIVA) Human Immunology Project Consortium (HIPC) will carry out a comprehensive systems immunology program to assess the dynamic human immune response to SARS-CoV- 2, seasonal influenza viruses and tetravalent and trivalent dengue vaccines and subsequent infections by those pathogens. It will generate comprehensive innate, cellular and adaptive immune signatures that correlate with vaccine outcomes. The VIVA HIPC will leverage recent advances in human immune profiling methods to characterize the diverse states of the human immune system before and after vaccination against these viral pathogens of great public health concern using novel immune phenotyping and genomics strategies that generate data and tools to be used for downstream data analysis and functional investigations. The proposed studies will use longitudinal biospecimens from established human cohorts of respiratory infections and vaccinations in the US and Argentina as well as from vaccine trials in the US (provided by the Clinical Core, Core B). In addition, validation experiments using human tonsils sourced from healthy individuals and exposed ex vivo to the different vaccine types will be conducted. Three complementary, well-integrated projects will produce in-depth human immune profiles and signatures of SARS-CoV-2 vaccinations and infections (Project 1), seasonal influenza vaccinations and infections (Project 2) as well as dengue vaccine and human challenge studies (Project 3). Unique in our approach is the use of longitudinal cohorts for in vivo profiling, supported by ex vivo human tonsillar histoculture (HC) models for infection and vaccination. Our holistic approach will provide cutting- responses to vaccinations and infections by the Immune Phenotyping Core (Core C), genomics/transcriptomics, including scRNAseq, CITEseq and spatial tissue transcriptomics by the Genomics Core (Core D), and experimental vaccinations in primary human tonsillar histocultures (HC) in Projects 1, 2 and 3. Data mining, bioinformatics to identify the network components and infer their interactions and correlations important for vaccine outcomes will be done by the Data management and Analysis Core (Core E). The VIVA HIPC will make the data, analyses and immune profiles generated available to the scientific community by coupling our local data infrastructure to ImmPort (directly or through the HIPC Coordinating Center). This integration will ensure full and timely release of clinical, sample, and experimental metadata in synchrony with genomic data releases to standard data repositories including SRA, GEO, and Genbank (Core E). The VIVA team (Drs. Krammer, Garcia-Sastre, Durbin, Gamarnik, van Bakel and Sebra) led by Dr. Fernandez-Sesma and Dr. Simon includes physicians, physician scientists and scientists with complementary expertise in viral immunology, viral pathogenesis, vaccinology, genomics, data analysis and a proven track record of collaboration and excellence.", "keywords": [ "2019-nCoV", "Area", "Argentina", "Bioinformatics", "Biological Assay", "Biological Models", "COVID-19 vaccination", "COVID-19 vaccine", "Cells", "Cellular Indexing of Transcriptomes and Epitopes by Sequencing", "Characteristics", "Classification", "Clinical", "Clinical Trials", "Collaborations", "Communicable Diseases", "Communities", "Coupling", "Cryopreserved Cell", "Data", "Data Analyses", "Data Set", "Dengue", "Dengue Vaccine", "Dengue Virus", "Development", "Differentiation Antigens", "Ensure", "Enzyme-Linked Immunosorbent Assay", "Epidemic", "Flow Cytometry", "Foundations", "Frequencies", "Genbank", "Generations", "Genes", "Genomic approach", "Genomics", "Goals", "Human", "Immune", "Immune response", "Immune system", "Immunity", "Immunization", "Immunoglobulins", "Immunologic Memory", "Immunologics", "Immunology", "Individual", "Infection", "Influenza A virus", "Influenza B Virus", "Influenza vaccination", "Innate Immune Response", "Investigation", "Learning", "Longitudinal cohort", "Lymphoid Tissue", "Maintenance", "Maps", "Measures", "Mediating", "Metadata", "Methods", "Modeling", "Morbidity - disease rate", "Pathway interactions", "Peripheral Blood Mononuclear Cell", "Phenotype", "Physicians", "Physiological", "Plasma", "Population", "Population Characteristics", "Prevention strategy", "Public Health", "Qualifying", "Research Personnel", "Respiratory Tract Infections", "SARS coronavirus", "Sampling", "Scientist", "Seasons", "Serology", "Serotyping", "Source", "Standardization", "System", "Techniques", "Technology", "Testing", "Tissues", "Tonsil", "Vaccinated", "Vaccination", "Vaccinee", "Vaccines", "Validation", "Viral", "Viral Antigens", "Viral Pathogenesis", "Virus", "Virus Diseases", "World Health", "adaptive immune response", "adaptive immunity", "cell type", "cohort", "data infrastructure", "data management", "data mining", "data repository", "data standards", "experimental study", "genomic data", "holistic approach", "human disease", "immunological status", "in vivo", "influenza infection", "influenzavirus", "live attenuated influenza vaccine", "mortality", "mosquito-borne", "network models", "next generation", "novel", "pandemic disease", "pathogen", "pathogenic virus", "phenotypic data", "predictive modeling", "programs", "response", "seasonal influenza", "sequencing platform", "tool", "transcriptomics", "vaccination outcome", "vaccine candidate", "vaccine immuno" ], "approved": true } }, { "type": "Grant", "id": "12038", "attributes": { "award_id": "5R01AG074307-02", "title": "Viral IncRNAs Regulate Host Genomic Transcriptional Programs Associated with Sporadic Alzheimer's Disease", "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": 26177, "first_name": "Maja", "last_name": "Maric", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-07-01", "end_date": "2027-06-30", "award_amount": 400697, "principal_investigator": { "id": 25575, "first_name": "MICHAEL G", "last_name": "ROSENFELD", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 760, "ror": "https://ror.org/0168r3w48", "name": "University of California, San Diego", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Alzheimer’s disease (AD) presents a formidable therapeutic challenge, as current interventions have failed to slow disease progression. The majority of AD genetic risk variants identified by GWAS reside in non- coding regions of the genome, suggesting that alterations in gene expression contribute to susceptibility for sporadic AD. Multiple reports now suggest that Herpes Simplex Virus 1 (HSV1) and other microbes can accumulate in the brain to increase the incidence of AD/dementia. While there is evidence linking reactivation of latent HSV1 infection to AD, the pathological potential of the latent state per se has not been addressed. Furthermore, there is now concern that COVID-19, which is caused by the pandemic SARS-CoV-2 and can include neurological and neurocognitive sequelae, might impact the onset or course of AD. Here we propose to advance recent findings by employing powerful new genomic technologies to characterize the cell type-specific transcriptional impact and cell autonomous vs non-cell autonomous effects of specific viral gene products, including HSV1 latency lncRNA transcripts and the SARS-CoV-2 Spike protein, that contribute to neurotoxic programs characteristic of sporadic AD. Using a modified single-nucleus sequencing approach, which allows for DNA accessibility and global transcription to be assessed simultaneously in the same nucleus, we will continue our interrogation of human control and AD brain samples to reveal cell type-specific aging vs pathological trajectory trees for each CNS cell type in sporadic AD, ultimately allowing for the identification of the key transcription factors acting at implicated regulatory enhancers. This will enable us to elucidate how viral gene products alter enhancer landscapes and transcriptional networks related to sporadic AD in various neuronal and non-neuronal cell types and subtypes. In addition, we will investigate the hypothesis that the sense (S) and antisense (AS) LATs impact transcription by associating with specific regulatory elements in the host genome in collaboration with the co-regulator KAP1 to impact expression of multiple AD susceptibility loci. We further hypothesize that the S-LAT influences the AD process by causing neuronal dysfunction and inflammatory glial activation, at least in part, through down-regulation of gene clusters encoding KRAB zinc-finger proteins (KZFPs) that normally repress human endogenous retrovirus (HERV) repeats, whereas the AS-LAT tempers these deleterious effects by promoting an anti-inflammatory gene expression profile and can further mitigate the innate immune response as well as cell death programs through direct inhibition of the AD-associated, sentinel kinase PKR in a non-genomic fashion. Collectively, the proposed studies will yield crucial cell type-specific insights into pathological trajectories in sporadic AD that may be subject to modulation by diverse infectious as well as non- microbial insults to the brain.", "keywords": [ "2019-nCoV", "Address", "Affect", "Aging", "Alzheimer&apos", "s Disease", "Alzheimer&apos", "s disease brain", "Alzheimer&apos", "s disease model", "Alzheimer&apos", "s disease pathology", "Alzheimer&apos", "s disease patient", "Alzheimer&apos", "s disease risk", "Amyloid", "Anti-Inflammatory Agents", "Appearance", "Astrocytes", "Attention", "Binding", "Biological Models", "Brain", "COVID-19", "COVID-19 pandemic", "Cell Death", "Cell Nucleus", "Cells", "Characteristics", "Collaborations", "DNA", "Data", "Dementia", "Deposition", "Disease Progression", "Disease susceptibility", "Double-Stranded RNA", "Down-Regulation", "Ectopic Expression", "Endogenous Retroviruses", "Enhancers", "Etiology", "Event", "Female", "Future", "Gene Cluster", "Gene Expression", "Gene Expression Profile", "Gene Proteins", "Genes", "Genetic", "Genetic Risk", "Genetic Transcription", "Genetic Variation", "Genome", "Genomics", "Glean", "Herpesvirus 1", "Human", "Immune", "Impaired cognition", "Incidence", "Individual", "Infection", "Inflammatory", "Innate Immune Response", "Intervention", "Investigation", "Link", "Microbe", "Microglia", "Molecular", "Mus", "Neurocognitive", "Neurofibrillary Tangles", "Neuroglia", "Neurologic", "Neuronal Dysfunction", "Neurons", "Nucleic Acid Regulatory Sequences", "Pathologic", "Pathway interactions", "Phosphotransferases", "Predisposition", "Process", "Proteins", "Public Health", "Regulation", "Regulatory Element", "Reporting", "Repression", "Research", "Retrotransposon", "Role", "SARS-CoV-2 spike protein", "Sampling", "Sentinel", "Susceptibility Gene", "Technology", "Testing", "Therapeutic", "Therapeutic Intervention", "Transcript", "Transcription Alteration", "Trees", "United States", "Untranslated RNA", "Up-Regulation", "Viral", "Viral Genome", "Viral Proteins", "Virus", "Virus Diseases", "Zinc Fingers", "aged", "biological specimen archives", "cell type", "extracellular", "gene repression", "genome wide association study", "genome-wide analysis", "glial activation", "insight", "latency associated transcript", "latent infection", "male", "neuroinflammation", "neuron loss", "neuropathology", "neurotoxic", "non-genomic", "novel", "novel strategies", "outcome prediction", "programs", "promoter", "reactivation from latency", "recruit", "risk variant", "single nucleus RNA-sequencing", "transcription factor" ], "approved": true } } ], "meta": { "pagination": { "page": 1405, "pages": 1424, "count": 14236 } } }