Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1383&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=1394&sort=title", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=title", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1382&sort=title" }, "data": [ { "type": "Grant", "id": "4236", "attributes": { "award_id": "1616178", "title": "What Controls Selenenic Acids? Understanding the Biochemistry of Selenocysteine", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Biological Sciences (BIO)", "Molecular Biophysics" ], "program_reference_codes": [], "program_officials": [ { "id": 14297, "first_name": "Jaroslaw", "last_name": "Majewski", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2016-08-15", "end_date": "2021-07-31", "award_amount": 498780, "principal_investigator": { "id": 14298, "first_name": "Sharon", "last_name": "Rozovsky", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 442, "ror": "https://ror.org/01sbq1a82", "name": "University of Delaware", "address": "", "city": "", "state": "DE", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 442, "ror": "https://ror.org/01sbq1a82", "name": "University of Delaware", "address": "", "city": "", "state": "DE", "zip": "", "country": "United States", "approved": true }, "abstract": "TITLE: What Controls Selenenic Acids? Understanding the Biochemistry of Selenocysteine\n\nThis project studies the fundamental biochemistry of selenium containing proteins in order to uncover the unique advantages gained from employing selenium instead of sulfur and which ultimately make selenoproteins essential constituents of cellular life. During the course of these scientific efforts an undergraduate student with disabilities will be continuously trained. Starting in the freshmen year, the student will be provided with far-reaching mentoring and training by the research group. In addition, the student will receive support through an extensive network that originated from our accompanying REU program for students facing similar challenges and that is aimed at increasing participation of students with disabilities in the STEM disciplines. Experiences will be widely shared with both STEM students and professionals in order to raise awareness and to ultimately increase opportunities and participation of the disability community in the scientific, social and financial structure of our society. Likewise, society will benefit from increased acceptance of such minorities and subgroups, promoting infusion of their ideas, influences and expertise.\n\nThe element selenium, incorporated into the rare amino acid selenocysteine, is used by nature to expand the chemical versatility of enzymes beyond what is available through the 20 canonical amino acids. The resulting selenoproteins are mostly enzymes that are involved in cellular signal transduction, detoxification, and maintenance of oxidants. While it is widely assumed that the use of selenium in proteins must impart unique properties and particular advantages, the key differences that set selenoproteins apart remain to be systematically studied and described. This research will focus on the reaction intermediate, selenenic acid, that is formed when selenocysteine reacts with oxidants. These highly reactive acids can undergo numerous reactions with nearby thiols, amines, amides and oxidants, which will affect selenoproteins interactions with itself and other proteins and ultimately modulate their function in signaling cascades. In order to understand this effect on biological function, 77Se NMR spectroscopy and mass spectrometry will be used to study the lifetimes of selenenic acid, their tendency to be further oxidized by oxidants and their interactions with protein partners. Together this forms a research plan that is designed to illuminate how selenoproteins control this unusual semi-metallic amino acid, selenocysteine, and harness its chemical properties for cellular use.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "359", "attributes": { "award_id": "2224086", "title": "What explains ambitious climate policy? Comparing updated climate targets and Covid-19 recovery packages and their drivers", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Social, Behavioral, and Economic Sciences (SBE)" ], "program_reference_codes": [], "program_officials": [ { "id": 650, "first_name": "Kwabena", "last_name": "Gyimah-Brempong", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-05-15", "end_date": "2024-04-30", "award_amount": 200000, "principal_investigator": { "id": 651, "first_name": "Jonas", "last_name": "Meckling", "orcid": null, "emails": "[email protected]", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 176, "ror": "", "name": "University of California-Berkeley", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 176, "ror": "", "name": "University of California-Berkeley", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Many countries updated their national climate targets or Nationally Determined Contributions (NDCs) during the COVID-19 pandemic. At the same time, these countries introduced vast COVID-19 economic recovery packages and fiscal reforms that may either serve to strengthen or upset existing carbon-intensive economic systems. This project will study how long-term climate goals, as indicated in countries’ NDCs, and short-term implementation of climate policies through pandemic recovery spending plans affect each other and why some countries lead in climate policy implementation, while others lag. The study is based on the collection of and analyses of large data sets across several countries. This study, to be carried out by research teams from several countries, will help identify opportunities for policymakers and international financial institutions on how to promote and implement climate change policy ambitions. In addition to helping to understand cross country differences in climate policy implementation, the results of this research will provide inputs into formulating efficient and innovative climate policies in the US.This research project will study two inter-related issues. First, it studies the links between long-term national climate ambitions enshrined in NDC updates and short-term implementation plans embedded in COVID-19 recovery packages, and fiscal reform. Second, it investigates the political and economic drivers underlying differences in climate ambitions and implementation abilities in these types of policy intervention across countries. To do so, the project integrates political science and economics, focusing on the role of policy feedback and financing conditions in driving climate ambition and climate policy interventions. In a mixed-methods design, the project combines descriptive statistical analyses with qualitative comparative case studies in the three analytical tasks. The intellectual merit of this project lies in identifying patterns in the relationship of long-term climate targets and plans (NDCs) and short-term implementation (economic recovery spending) as well as the causes of cross-national variation in this relationship. The results of this research will provide inputs into formulating efficient and innovative climate policies in the US.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14771", "attributes": { "award_id": "1R21AI180456-01", "title": "What is the human antibody response to measles virus vaccination?", "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": 6054, "first_name": "Eun-Chung", "last_name": "Park", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-12-01", "end_date": "2025-10-31", "award_amount": 247050, "principal_investigator": { "id": 24413, "first_name": "Erica Ollmann", "last_name": "Saphire", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 777, "ror": "", "name": "LA JOLLA INSTITUTE FOR IMMUNOLOGY", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 777, "ror": "", "name": "LA JOLLA INSTITUTE FOR IMMUNOLOGY", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Vaccines are the greatest bang for our public health buck, yet vaccine development is still sometimes hit or miss. Recent efforts with SARS-CoV-2 demonstrated that acceleration of vaccine programs is possible, especially when supported by prior studies characterizing successful immune responses against related prototype pathogens. The measles virus vaccination campaign is a global success story; the live-attenuated vaccine developed in the 1960’s still elicits highly protective antibodies to strains circulating today. Yet Measles outbreaks persist due to obstacles in vaccination programs such as global health inequities, vaccine hesitancy, extreme weather events related to climate change, and the SARS-CoV-2 pandemic. Furthermore, a growing population with compromised immune systems cannot receive live-attenuated viral vaccines. Thus, the threat of measles remains (there are still approximately 9-10 million cases annually), and innovative solutions will be needed to achieve global measles eradication. However, very little is known about the human antibody response to measles infection or vaccination beyond neutralizing antibody titers. Importantly, there are no structures of any antibodies in complex with any measles virus antigens. As a result, we do not know which sites on measles virus are immunodominant and protective. Much of this fundamental knowledge is lacking largely because measles was effectively eradicated from developed nations before needed scientific tools had been developed. In this work, we will use state-of-the-art tools to directly visualize the structure of human antibodies from vaccinee polyclonal sera bound to measles surface glycoproteins to understand which antigenic sites dominate in the human vaccinee response. We will also use microfluidics and rapid microscale multiplexed competition analyses to rapidly discover and analyze individual human monoclonal antibodies against measles virus for the first time. This work will reveal what components of the human immune response to this prototype paramyxovirus lead to vaccine-mediated protection, and will help guide development of modern vaccines for the immunocompromised and other vaccines against paramyxoviruses yet to emerge.", "keywords": [ "2019-nCoV", "Acceleration", "Anti-viral Agents", "Antibodies", "Antibody Response", "Antibody Therapy", "Antibody titer measurement", "Antigens", "Attenuated", "Attenuated Live Virus Vaccine", "Attenuated Vaccines", "B-Lymphocytes", "Binding", "Binding Sites", "COVID-19", "COVID-19 pandemic", "Complex", "Dedications", "Developed Countries", "Development", "Disease", "Disease Outbreaks", "Ebola virus", "Electron Microscope", "Electron Microscopy", "Epitope Mapping", "Epitopes", "Event", "Family", "Funding", "Glycoproteins", "Hemagglutinin", "Human", "Immune response", "Immune system", "Immunization", "Immunization Programs", "Immunocompromised Host", "Immunodominant Epitopes", "Individual", "Infection", "Interruption", "Kinetics", "Knowledge", "Lassa virus", "Lead", "Learning", "Maps", "Measles", "Measles virus", "Mediating", "Membrane Glycoproteins", "Microfluidics", "Modernization", "Monoclonal Antibodies", "Mus", "Mutagenesis", "Mutation", "National Institute of Allergy and Infectious Disease", "Nature", "Negative Staining", "Paramyxovirus", "Peptides", "Population", "Public Health", "RNA Viruses", "RNA vaccine", "Rapid screening", "Serology", "Severe Acute Respiratory Syndrome", "Site", "Structure", "Surface Antigens", "Therapeutic", "Time", "Vaccination", "Vaccinee", "Vaccines", "Viral Antigens", "Viral Vaccines", "Virus", "Visualization", "Work", "climate change", "comparative", "experience", "extreme weather", "global health", "group competition", "health inequalities", "human monoclonal antibodies", "innovation", "instrumentation", "murine antibody", "murine monoclonal antibody", "nanoparticle", "neutralizing antibody", "new therapeutic target", "novel", "novel vaccines", "pathogen", "polyclonal antibody", "polyclonal human antibody", "programs", "prototype", "receptor binding", "response", "success", "tool", "vaccine development", "vaccine hesitancy" ], "approved": true } }, { "type": "Grant", "id": "15576", "attributes": { "award_id": "5R21AI180456-02", "title": "What is the human antibody response to measles virus vaccination?", "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": 6054, "first_name": "Eun-Chung", "last_name": "Park", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-12-01", "end_date": "2025-10-31", "award_amount": 221888, "principal_investigator": { "id": 24413, "first_name": "Erica Ollmann", "last_name": "Saphire", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 777, "ror": "", "name": "LA JOLLA INSTITUTE FOR IMMUNOLOGY", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 777, "ror": "", "name": "LA JOLLA INSTITUTE FOR IMMUNOLOGY", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Vaccines are the greatest bang for our public health buck, yet vaccine development is still sometimes hit or miss. Recent efforts with SARS-CoV-2 demonstrated that acceleration of vaccine programs is possible, especially when supported by prior studies characterizing successful immune responses against related prototype pathogens. The measles virus vaccination campaign is a global success story; the live-attenuated vaccine developed in the 1960’s still elicits highly protective antibodies to strains circulating today. Yet Measles outbreaks persist due to obstacles in vaccination programs such as global health inequities, vaccine hesitancy, extreme weather events related to climate change, and the SARS-CoV-2 pandemic. Furthermore, a growing population with compromised immune systems cannot receive live-attenuated viral vaccines. Thus, the threat of measles remains (there are still approximately 9-10 million cases annually), and innovative solutions will be needed to achieve global measles eradication. However, very little is known about the human antibody response to measles infection or vaccination beyond neutralizing antibody titers. Importantly, there are no structures of any antibodies in complex with any measles virus antigens. As a result, we do not know which sites on measles virus are immunodominant and protective. Much of this fundamental knowledge is lacking largely because measles was effectively eradicated from developed nations before needed scientific tools had been developed. In this work, we will use state-of-the-art tools to directly visualize the structure of human antibodies from vaccinee polyclonal sera bound to measles surface glycoproteins to understand which antigenic sites dominate in the human vaccinee response. We will also use microfluidics and rapid microscale multiplexed competition analyses to rapidly discover and analyze individual human monoclonal antibodies against measles virus for the first time. This work will reveal what components of the human immune response to this prototype paramyxovirus lead to vaccine-mediated protection, and will help guide development of modern vaccines for the immunocompromised and other vaccines against paramyxoviruses yet to emerge.", "keywords": [ "2019-nCoV", "Acceleration", "Anti-viral Agents", "Antibodies", "Antibody Response", "Antibody Therapy", "Antibody titer measurement", "Antigens", "Attenuated Live Virus Vaccine", "Attenuated Vaccines", "B-Lymphocytes", "Binding", "Binding Sites", "COVID-19", "COVID-19 pandemic", "Complex", "Dedications", "Developed Countries", "Development", "Disease", "Disease Outbreaks", "Ebola virus", "Electron Microscope", "Electron Microscopy", "Epitope Mapping", "Epitopes", "Event", "Family", "Funding", "Glycoproteins", "Hemagglutinin", "Human", "Immune response", "Immune system", "Immunization", "Immunization Programs", "Immunocompromised Host", "Immunodominant Epitopes", "Individual", "Infection", "Interruption", "Kinetics", "Knowledge", "Lassa virus", "Lead", "Learning", "Maps", "Measles", "Measles virus", "Mediating", "Membrane Glycoproteins", "Microfluidics", "Modernization", "Monoclonal Antibodies", "Mus", "Mutagenesis", "Mutation", "National Institute of Allergy and Infectious Disease", "Nature", "Negative Staining", "Paramyxovirus", "Peptides", "Population", "Public Health", "RNA Viruses", "RNA vaccine", "Rapid screening", "Serology", "Severe Acute Respiratory Syndrome", "Site", "Structure", "Surface Antigens", "Therapeutic", "Time", "Vaccination", "Vaccinee", "Vaccines", "Viral Antigens", "Virus", "Visualization", "Work", "climate change", "comparative", "experience", "extreme weather", "global health", "group competition", "health inequalities", "human monoclonal antibodies", "innovation", "instrumentation", "murine antibody", "murine monoclonal antibody", "nanoparticle", "neutralizing antibody", "new therapeutic target", "novel", "novel vaccines", "pathogen", "polyclonal antibody", "polyclonal human antibody", "programs", "prototype", "receptor binding", "response", "success", "tool", "vaccine development", "vaccine hesitancy" ], "approved": true } }, { "type": "Grant", "id": "13485", "attributes": { "award_id": "2127822", "title": "What limits visual working memory?", "funder": { "id": 3, "ror": "https://ror.org/021nxhr62", "name": "National Science Foundation", "approved": true }, "funder_divisions": [ "Social, Behavioral, and Economic Sciences (SBE)", "Build and Broaden" ], "program_reference_codes": [], "program_officials": [ { "id": 25900, "first_name": "Enrique", "last_name": "Pumar", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-01-01", "end_date": null, "award_amount": 158339, "principal_investigator": { "id": 29606, "first_name": "Paulina", "last_name": "Kulesz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 29605, "first_name": "Paulina A", "last_name": "Kulesz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 231, "ror": "https://ror.org/048sx0r50", "name": "University of Houston", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).<br/><br/>Remembering and thinking about things seen moments beforehand—termed visual working memory (VWM)—is surprisingly difficult. People continuously use their limited VWM for basic tasks like navigating a car or rapidly finding the eyeglasses they just put down. Because VWM is associated with intelligence, VWM affects academic and professional performance. VWM degrades with aging, disorders (like ADHD or schizophrenia), and brain injuries. Like a tune-up or repair of a mechanical system needs some understanding of how the system is built, an intervention to improve VWM would benefit from knowledge of the working memory system’s architecture. To gain a more full understanding of VWM’s structure and its relationships to other aspects of thinking, new research infrastructure is needed. This infrastructure will then enable future examination of how little-studied VWM capacity limits (beyond the amount of information that can be stored) are related to thinking and perception, which will in turn indicate if what is known about the well-studied VWM storage capacity generalizes to these other important limits on VWM. To enable this future examination, the present research will iteratively devise and pilot component research tasks to ultimately form an approximately 8-hour extensible suite of cognitive tests that will serve as infrastructure for the aforementioned future VWM research in healthy young adults. Moreover, this infrastructure will eventually enable further research on how VWM changes over the lifespan and in populations of disorder and/or neurological injury.<br/><br/>To date, the vast majority of VWM research has focused on storage capacity, but neglected how information moves from visual perception into VWM (termed consolidation) and how memories for items that are near one another are kept separate (termed resolution). Consolidation determines if seen items make it into memory before being disrupted by distraction. Resolution determines whether remembering an item means that memory for additional, nearby items is less accurate. Understanding these limits is critical for generalizing from the lab to the real world, where objects and events are close to one another and distraction is frequent. This research will enable future measurement of individual differences in storage, consolidation, and resolution; other kinds of working memory; attention; and executive control using computerized tasks. These data could then be used to determine how these distinct capacity limits relate to one another. This is important to science because it is vigorously debated whether working memory should be thought of as limited by a single resource that is shared for different kinds of memory representations and processes, versus being a series of distinct systems, each with their own separate capacity limits. The novel inclusion of consolidation and resolution measures in the new research infrastructure (test suite) will allow a much more complete and accurate picture compared to past research. This, in turn, is important to society because it could greatly change how therapies or interventions are targeted. For instance, intervention strategies would be different if verbal training could benefit visual memory, compared to if verbal and visual memory were independently limited. Present evaluations of working memory typically either focus on VWM storage capacity, or on verbal versus visuospatial memory span; when these are considered together, VWM consolidation and resolution are not included. The test suite that will be the product of the present research will overcome this limitation.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "13150", "attributes": { "award_id": "1R21AI175883-01A1", "title": "What Precursors Become Lung-Resident CD4 Memory that Protect Against Respiratory Infections or Cause Lung Pathology?", "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": 7248, "first_name": "Wendy F.", "last_name": "Davidson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-11-22", "end_date": "2025-10-31", "award_amount": 226125, "principal_investigator": { "id": 29185, "first_name": "Priyadharshini", "last_name": "Devarajan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 790, "ror": "", "name": "UNIV OF MASSACHUSETTS MED SCH WORCESTER", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "What Precursors Become Lung-Resident CD4 Memory that Protect Against Respiratory Infections or Cause Lung Pathology? Respiratory viruses such as SARS-CoV1, Influenza and recently SARS-CoV2 (COVID-19) have caused the major pandemics in the 21st century and influenza causes high levels of death from yearly circulating outbreaks. T cells can target internal viral proteins, that mutate less frequently. Thus, T cell memory induced by previous vaccination or infection can still be effective against emerging mutant viral strains. Tissue resident memory (TRM) cells, that develop in the lung are at the first line of defense of our adaptive immune response against respiratory infections because of their location. However, lung CD8 TRM, which are most- studied, are short- lived. The few studies that have examined lung CD4 TRM suggest that they may decay less rapidly. We know relatively little about lung CD4 TRM longevity and mechanisms of function, though they are known to protect against many respiratory infections such Influenza, Sendai, B.pertussis, pneumococcal pneumonia and tuberculosis infections. Moreover, we know little about the CD4 effectors that are precursors to the lung CD4 TRM. If CD4 lung TRM are longer-lived, they might compensate over the long-term for the rapid decline in CD8 lung TRM, thus making them good vaccine targets to provide strong more durable immunity. A majority of the CD4 and CD8 T cells in human lung express TRM features, so it is vital to understand their impact when they are reactivated during an immune response, both their positive effect on protection against pathogens and negative effects on lung function and tissue damage. In many respiratory infections such as influenza and COVID-19 there is also potential for severe lung damage leading to poor prognosis. We show that cytotoxic CD4 T cells, that are resident effectors in the lung and that contribute to damage, can be precursors oflung CD4 TRM. Thus, it is vital that we learn how CD4 TRM can both protect and cause lung pathology on reactivation, especially if they are maintained long-term. Here, we propose to identify the precursors of CD4 lung TRM from CD4 lung effectors, and better define their protective and pathogenic potentials. We will phenotypically and molecularly characterize the CD4 TRM formed from subsets of lung CD4 effectors. We will study their longevity and their maintenance via mechanisms such as homeostatic proliferation and recruitment from circulation. Finally, we will study in detail their functional mechanisms of eliciting protection vs those causing lung immunopathology by direct cytolysis, inflammation and helper function. Understanding mechanisms/conditions driving protection and pathology by CD4 TRM will enable design of interventions like vaccines and immunotherapies, that favor the development of protection while minimizing pathology. Identifying precursor CD4 effectors that give rise to protective CD4 TRM will also allow us to finetune vaccine approaches that drive generation of those CD4 effector subsets. In future studies, we will use the knowledge gained here, to identify transcriptional networks that regulate the development of CD4 TRM from CD4 effectors and naïve CD4.", "keywords": [ "2019-nCoV", "Acute respiratory infection", "Automobile Driving", "B-Lymphocytes", "Bacterial Infections", "Bordetella pertussis", "CD4 Positive T Lymphocytes", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "COVID-19", "COVID-19 patient", "Cell physiology", "Cells", "Cessation of life", "Circulation", "Compensation", "Cytolysis", "Data", "Deterioration", "Development", "Disease Outbreaks", "Down-Regulation", "Epithelial Cells", "Future", "Gene Expression Profile", "Generations", "Genetic Transcription", "Grant", "Human", "Immune", "Immune response", "Immunity", "Immunotherapeutic agent", "Immunotherapy", "Infection", "Inflammation", "Influenza", "Interleukin-15", "Interleukin-2", "Knowledge", "Learning", "Location", "Longevity", "Lung", "Lung immune response", "MHC Class I Genes", "Maintenance", "Mediating", "Memory", "Memory Loss", "Modeling", "Molecular", "Morbidity - disease rate", "Mus", "Mutate", "Pathogenicity", "Pathologic", "Pathology", "Pathway interactions", "Pattern", "Phenotype", "Play", "Pneumococcal Pneumonia", "Population", "Prognosis", "Proliferating", "Pulmonary Pathology", "Respiratory Tract Infections", "Respiratory distress", "Respiratory physiology", "Risk", "Role", "SARS coronavirus", "Severe Acute Respiratory Syndrome", "Signal Transduction", "Site", "Structure of parenchyma of lung", "T memory cell", "T-Lymphocyte", "Tissues", "Tuberculosis", "Vaccination", "Vaccines", "Viral", "Viral Proteins", "Virus Diseases", "adaptive immune response", "cell type", "cytotoxic", "cytotoxicity", "design", "experimental study", "fighting", "helminth infection", "immunopathology", "influenza infection", "influenza outbreak", "insight", "lung injury", "mortality", "mutant", "pandemic disease", "pandemic influenza", "pathogen", "preservation", "pressure", "pulmonary function", "recruit", "respiratory virus", "response", "therapy design", "tissue resident memory T cell", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "15581", "attributes": { "award_id": "5R21AI175883-03", "title": "What Precursors Become Lung-Resident CD4 Memory that Protect Against Respiratory Infections or Cause Lung Pathology?", "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": 31609, "first_name": "Hariharan", "last_name": "Subramanian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-11-22", "end_date": "2025-10-31", "award_amount": 190131, "principal_investigator": { "id": 29185, "first_name": "Priyadharshini", "last_name": "Devarajan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1415, "ror": "", "name": "STATE UNIVERSITY NEW YORK STONY BROOK", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "What Precursors Become Lung-Resident CD4 Memory that Protect Against Respiratory Infections or Cause Lung Pathology? Respiratory viruses such as SARS-CoV1, Influenza and recently SARS-CoV2 (COVID-19) have caused the major pandemics in the 21st century and influenza causes high levels of death from yearly circulating outbreaks. T cells can target internal viral proteins, that mutate less frequently. Thus, T cell memory induced by previous vaccination or infection can still be effective against emerging mutant viral strains. Tissue resident memory (TRM) cells, that develop in the lung are at the first line of defense of our adaptive immune response against respiratory infections because of their location. However, lung CD8 TRM, which are most- studied, are short- lived. The few studies that have examined lung CD4 TRM suggest that they may decay less rapidly. We know relatively little about lung CD4 TRM longevity and mechanisms of function, though they are known to protect against many respiratory infections such Influenza, Sendai, B.pertussis, pneumococcal pneumonia and tuberculosis infections. Moreover, we know little about the CD4 effectors that are precursors to the lung CD4 TRM. If CD4 lung TRM are longer-lived, they might compensate over the long-term for the rapid decline in CD8 lung TRM, thus making them good vaccine targets to provide strong more durable immunity. A majority of the CD4 and CD8 T cells in human lung express TRM features, so it is vital to understand their impact when they are reactivated during an immune response, both their positive effect on protection against pathogens and negative effects on lung function and tissue damage. In many respiratory infections such as influenza and COVID-19 there is also potential for severe lung damage leading to poor prognosis. We show that cytotoxic CD4 T cells, that are resident effectors in the lung and that contribute to damage, can be precursors oflung CD4 TRM. Thus, it is vital that we learn how CD4 TRM can both protect and cause lung pathology on reactivation, especially if they are maintained long-term. Here, we propose to identify the precursors of CD4 lung TRM from CD4 lung effectors, and better define their protective and pathogenic potentials. We will phenotypically and molecularly characterize the CD4 TRM formed from subsets of lung CD4 effectors. We will study their longevity and their maintenance via mechanisms such as homeostatic proliferation and recruitment from circulation. Finally, we will study in detail their functional mechanisms of eliciting protection vs those causing lung immunopathology by direct cytolysis, inflammation and helper function. Understanding mechanisms/conditions driving protection and pathology by CD4 TRM will enable design of interventions like vaccines and immunotherapies, that favor the development of protection while minimizing pathology. Identifying precursor CD4 effectors that give rise to protective CD4 TRM will also allow us to finetune vaccine approaches that drive generation of those CD4 effector subsets. In future studies, we will use the knowledge gained here, to identify transcriptional networks that regulate the development of CD4 TRM from CD4 effectors and naïve CD4.", "keywords": [ "2019-nCoV", "Acute respiratory infection", "Automobile Driving", "B-Lymphocytes", "Bacterial Infections", "Bordetella pertussis", "CD4 Positive T Lymphocytes", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "COVID-19", "COVID-19 patient", "Cell Physiology", "Cells", "Cessation of life", "Circulation", "Compensation", "Cytolysis", "Data", "Deterioration", "Development", "Disease Outbreaks", "Down-Regulation", "Epithelial Cells", "Future", "Gene Expression Profile", "Generations", "Genetic Transcription", "Grant", "Human", "Immune", "Immune response", "Immunity", "Immunotherapeutic agent", "Immunotherapy", "Infection", "Inflammation", "Influenza", "Interleukin-15", "Interleukin-2", "Knowledge", "Learning", "Location", "Longevity", "Lung", "Lung immune response", "MHC Class I Genes", "Maintenance", "Mediating", "Memory", "Memory Loss", "Modeling", "Molecular", "Morbidity - disease rate", "Mus", "Mutate", "Pathogenicity", "Pathologic", "Pathology", "Pathway interactions", "Pattern", "Phenotype", "Play", "Pneumococcal Pneumonia", "Population", "Prognosis", "Proliferating", "Pulmonary Pathology", "Respiratory Tract Infections", "Respiratory distress", "Respiratory physiology", "Risk", "Role", "SARS coronavirus", "Severe Acute Respiratory Syndrome", "Signal Transduction", "Site", "Structure of parenchyma of lung", "T memory cell", "T-Lymphocyte", "Tissues", "Tuberculosis", "Vaccination", "Vaccines", "Viral", "Viral Proteins", "Virus Diseases", "adaptive immune response", "cell type", "cytotoxic", "cytotoxicity", "design", "experimental study", "fighting", "helminth infection", "immunopathology", "influenza infection", "influenza outbreak", "insight", "lung injury", "mortality", "mutant", "pandemic disease", "pandemic influenza", "pathogen", "preservation", "pressure", "pulmonary function", "recruit", "respiratory virus", "response", "therapy design", "tissue resident memory T cell", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "15582", "attributes": { "award_id": "3R21AI175883-03S1", "title": "What Precursors Become Lung-Resident CD4 Memory that Protect Against Respiratory Infections or Cause Lung Pathology?", "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": 31609, "first_name": "Hariharan", "last_name": "Subramanian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-11-22", "end_date": "2025-10-31", "award_amount": 92708, "principal_investigator": { "id": 29185, "first_name": "Priyadharshini", "last_name": "Devarajan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1415, "ror": "", "name": "STATE UNIVERSITY NEW YORK STONY BROOK", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "What Precursors Become Lung-Resident CD4 Memory that Protect Against Respiratory Infections or Cause Lung Pathology? Respiratory viruses such as SARS-CoV1, Influenza and recently SARS-CoV2 (COVID-19) have caused the major pandemics in the 21st century and influenza causes high levels of death from yearly circulating outbreaks. T cells can target internal viral proteins, that mutate less frequently. Thus, T cell memory induced by previous vaccination or infection can still be effective against emerging mutant viral strains. Tissue resident memory (TRM) cells, that develop in the lung are at the first line of defense of our adaptive immune response against respiratory infections because of their location. However, lung CD8 TRM, which are most- studied, are short- lived. The few studies that have examined lung CD4 TRM suggest that they may decay less rapidly. Relatively little is known about lung CD4 TRM longevity and mechanisms of function, though they are known to protect against many respiratory infections such Influenza, Sendai, B.pertussis, pneumococcal pneumonia and tuberculosis infections. Moreover, it is unclear which CD4 effectors precursors become lung CD4 TRM. If CD4 lung TRM are longer-lived, they might compensate over the long-term for the rapid decline in CD8 lung TRM, thus making them good vaccine targets to provide strong more durable immunity. A majority of the CD4 and CD8 T cells in human lung express TRM features, so it is vital to understand their impact when they are reactivated during an immune response, both their positive effect on protection against pathogens and negative effects on lung function and tissue damage. In many respiratory infections such as influenza and COVID-19 there is also potential for severe lung damage leading to poor prognosis. We show that cytotoxic CD4 T cells, that are resident effectors in the lung and that contribute to damage, can be precursors of lung CD4 TRM. Thus, an understanding of how CD4 TRM can both protect and cause lung pathology on reactivation, especially if they are maintained long-term, is vital. Here, the research proposed will identify the precursors of CD4 lung TRM from CD4 lung effectors, and better define their protective and pathogenic potentials. It will phenotypically and molecularly characterize the CD4 TRM formed from subsets of lung CD4 effectors. It will study their longevity and their maintenance via mechanisms such as homeostatic proliferation and recruitment from circulation. Finally, it will study in detail their functional mechanisms of eliciting protection vs those causing lung immunopathology by direct cytolysis, inflammation andhelper function. Understanding mechanisms/conditions driving protection and pathology by CD4 TRM will enable design of interventions like vaccines and immunotherapies, that favor the development of protection while minimizing pathology. Identifying precursor CD4 effectors that give rise to protective CD4 TRM will also allow to finetune vaccine approaches that drive generation of those CD4 effector subsets. In future studies, the knowledge gained here, will allow identification of transcriptional networks that regulate the development of CD4 TRM from CD4 effectors and naïve CD4.", "keywords": [ "2019-nCoV", "Automobile Driving", "Bordetella pertussis", "CD4 Positive T Lymphocytes", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "COVID-19", "Cells", "Cessation of life", "Circulation", "Compensation", "Cytolysis", "Development", "Disease Outbreaks", "Future", "Generations", "Genetic Transcription", "Grant", "Human", "Immune", "Immune response", "Immunity", "Immunotherapy", "Infection", "Inflammation", "Influenza", "Knowledge", "Location", "Longevity", "Lung", "Maintenance", "Memory", "Molecular", "Morbidity - disease rate", "Mutate", "Pathogenicity", "Pathology", "Pathway interactions", "Phenotype", "Pneumococcal Pneumonia", "Prognosis", "Proliferating", "Pulmonary Pathology", "Research", "Respiratory Tract Infections", "SARS coronavirus", "Severe Acute Respiratory Syndrome", "Structure of parenchyma of lung", "T memory cell", "T-Lymphocyte", "Tissues", "Tuberculosis", "Vaccination", "Vaccines", "Viral", "Viral Proteins", "adaptive immune response", "cell type", "cytotoxic", "immunopathology", "influenza outbreak", "insight", "lung injury", "mortality", "mutant", "pandemic disease", "pandemic influenza", "pathogen", "pulmonary function", "recruit", "respiratory virus", "therapy design", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "15429", "attributes": { "award_id": "7R21AI175883-02", "title": "What Precursors Become Lung-Resident CD4 Memory that Protect Against Respiratory Infections or Cause Lung Pathology?", "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": 31609, "first_name": "Hariharan", "last_name": "Subramanian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-11-22", "end_date": "2025-10-31", "award_amount": 123405, "principal_investigator": { "id": 29185, "first_name": "Priyadharshini", "last_name": "Devarajan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1415, "ror": "", "name": "STATE UNIVERSITY NEW YORK STONY BROOK", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "What Precursors Become Lung-Resident CD4 Memory that Protect Against Respiratory Infections or Cause Lung Pathology? Respiratory viruses such as SARS-CoV1, Influenza and recently SARS-CoV2 (COVID-19) have caused the major pandemics in the 21st century and influenza causes high levels of death from yearly circulating outbreaks. T cells can target internal viral proteins, that mutate less frequently. Thus, T cell memory induced by previous vaccination or infection can still be effective against emerging mutant viral strains. Tissue resident memory (TRM) cells, that develop in the lung are at the first line of defense of our adaptive immune response against respiratory infections because of their location. However, lung CD8 TRM, which are most- studied, are short- lived. The few studies that have examined lung CD4 TRM suggest that they may decay less rapidly. We know relatively little about lung CD4 TRM longevity and mechanisms of function, though they are known to protect against many respiratory infections such Influenza, Sendai, B.pertussis, pneumococcal pneumonia and tuberculosis infections. Moreover, we know little about the CD4 effectors that are precursors to the lung CD4 TRM. If CD4 lung TRM are longer-lived, they might compensate over the long-term for the rapid decline in CD8 lung TRM, thus making them good vaccine targets to provide strong more durable immunity. A majority of the CD4 and CD8 T cells in human lung express TRM features, so it is vital to understand their impact when they are reactivated during an immune response, both their positive effect on protection against pathogens and negative effects on lung function and tissue damage. In many respiratory infections such as influenza and COVID-19 there is also potential for severe lung damage leading to poor prognosis. We show that cytotoxic CD4 T cells, that are resident effectors in the lung and that contribute to damage, can be precursors oflung CD4 TRM. Thus, it is vital that we learn how CD4 TRM can both protect and cause lung pathology on reactivation, especially if they are maintained long-term. Here, we propose to identify the precursors of CD4 lung TRM from CD4 lung effectors, and better define their protective and pathogenic potentials. We will phenotypically and molecularly characterize the CD4 TRM formed from subsets of lung CD4 effectors. We will study their longevity and their maintenance via mechanisms such as homeostatic proliferation and recruitment from circulation. Finally, we will study in detail their functional mechanisms of eliciting protection vs those causing lung immunopathology by direct cytolysis, inflammation and helper function. Understanding mechanisms/conditions driving protection and pathology by CD4 TRM will enable design of interventions like vaccines and immunotherapies, that favor the development of protection while minimizing pathology. Identifying precursor CD4 effectors that give rise to protective CD4 TRM will also allow us to finetune vaccine approaches that drive generation of those CD4 effector subsets. In future studies, we will use the knowledge gained here, to identify transcriptional networks that regulate the development of CD4 TRM from CD4 effectors and naïve CD4.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14354", "attributes": { "award_id": "5R01MH130238-02", "title": "When are in-person HIV services worth the risk of COVID-19 and other communicable illnesses? Optimizing choices when virtual services are less effective", "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": 24064, "first_name": "Lori", "last_name": "Scott-Sheldon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-09-01", "end_date": "2027-07-31", "award_amount": 725525, "principal_investigator": { "id": 26279, "first_name": "Anna", "last_name": "Bershteyn", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 832, "ror": "", "name": "NEW YORK UNIVERSITY SCHOOL OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "ABSTRACT/SUMMARY Sub-Saharan Africa (SSA) is home to two-thirds of all people living with HIV (PLHIV). During the COVID-19 pandemic, HIV services in sub-Saharan Africa have been adapted to lower-contact alternatives that reduce exposure to SARS-CoV-2, which maintained the effectiveness of some services but reduced the effectiveness of others. For example, multi-month dispensing of antiretroviral therapy (ART) did not reduce retention or viral load suppression, whereas many services involving navigation, social support, and mental health became less effective when delivered in lower-contact manners. Three such services critical to achieving the HIV treatment and prevention targets are HIV testing, treatment of depression, and ART adherence support. In-person HIV counseling and testing was adapted into remote self-testing, with lower rates of linkage to care and commensurate declines in HIV treatment initiation. In-person psychotherapy for depression (a condition affecting 10-15% of PLHIV in SSA) was adapted into teletherapy, with reduced treatment completion and effectiveness. In-person peer support for ART adherence was adapted into telephone and telehealth adherence support, with lower rates of adherence and viral load suppression. As of mid-2021, SSA countries continue to implement these lower-contact alternatives and lack evidence regarding when, and for whom, higher-contact services should resume. We will partner with the Ministries of Health of Zambia and Kenya and local NGOs to identify services that have been adapted into lower-contact alternatives and estimate (Aim 1) incremental effectiveness at treating and preventing HIV, (Aim 2) incremental exposure to COVID-19, tuberculosis, and influenza, and (Aim 3) which patients should use lower-contact services at what times. To estimate incremental effectiveness, we will use program data to compare outcomes in terms of service-specific indicators such as HIV tests performed, changes in depression scores, and changes in ART retention and viral load suppression. Using an HIV transmission and progression model, we will translate these service-specific indicators into comparable estimates of disability-adjusted life-years. To estimate SARS-CoV-2, tuberculosis, and influenza exposure through different service alternatives, we will perform in-field visits to obtain parameters for a Wells-Riley model of respiratory disease transmission. We will combine these estimates with mathematical modeling to the risk of exposure under different pandemic conditions and the resulting risk to health in terms of disability-adjusted life years. Finally, we will compare HIV-related benefits and SARS-CoV-2- related risks for different COVID-19 pandemic conditions and patient sub-populations in order to determine thresholds when higher-contact services should resume. We will furthermore establish targets for how much the effectiveness of lower-contact services would need to improve in order to be widely recommended in the era of COVID-19.", "keywords": [ "2019-nCoV", "Adherence", "Affect", "Africa South of the Sahara", "African", "Air Movements", "Benefits and Risks", "COVID-19", "COVID-19 mortality", "COVID-19 pandemic", "COVID-19 risk", "Caring", "Cause of Death", "Clinic", "Clinical", "Collaborations", "Communicable Diseases", "Counseling", "Country", "Crowding", "Data", "Decision Making", "Depression screen", "Disease", "Effectiveness", "Epidemic", "Evaluation", "Frequencies", "Guidelines", "HIV", "HIV/AIDS", "Harm Reduction", "Health", "Health Benefit", "Home", "Hospitalization", "Human immunodeficiency virus test", "Infection", "Influenza", "Kenya", "Mental Depression", "Mental Health", "Mental Health Services", "Modeling", "Outcome", "Patients", "Performance", "Persons", "Policies", "Population", "Prevention", "Psychotherapy", "Recommendation", "Research", "Respiratory Disease", "Respiratory Tract Infections", "Risk", "SARS-CoV-2 exposure", "SARS-CoV-2 transmission", "Services", "Social support", "Telephone", "Teletherapy", "Testing", "Translating", "Tuberculosis", "United States National Institutes of Health", "Viral Load result", "Visit", "Work", "World Health Organization", "Zambia", "adherence rate", "antiretroviral therapy", "disability-adjusted life years", "disease transmission", "experience", "health assessment", "improved", "infection risk", "interest", "mHealth", "mathematical model", "pandemic disease", "pandemic potential", "patient population", "patient subsets", "peer support", "preservation", "prevent", "priority pathogen", "programs", "response", "retention rate", "self testing", "telehealth", "temporal measurement", "therapy adherence", "transmission process", "virtual" ], "approved": true } } ], "meta": { "pagination": { "page": 1383, "pages": 1394, "count": 13934 } } }