Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1383&sort=keywords
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=keywords", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1397&sort=keywords", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=keywords", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1382&sort=keywords" }, "data": [ { "type": "Grant", "id": "8414", "attributes": { "award_id": "3R01MH109648-05S1", "title": "Neurobiology of Autism With Macrocephaly", "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": 24179, "first_name": "David M", "last_name": "Panchision", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-06-01", "end_date": "2022-04-30", "award_amount": 373118, "principal_investigator": { "id": 24180, "first_name": "FLORA M", "last_name": "VACCARINO", "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": [], "awardee_organization": { "id": 452, "ror": "https://ror.org/03v76x132", "name": "Yale University", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "Major goals of the parent application (R01 MH109648-04, entitled “Neurobiology of Autism with Macrocephaly) are to investigate developmental alterations in ASD with large brain size (macrocephaly) and normal brain size (normocephaly) in order to understand whether these represent biologically distinct subtypes of ASD. To this end, we are collecting and analyzing neurobiological measures, transcriptome and gene regulatory element (enhancers) activities in induced pluripotent stem cell (iPSC)- derived organoids obtained from ASD patients with macrocephaly or normocephaly. Differential gene expression and network analyses in an initial set of macrocephalic and normocephalic proband-control pairs suggest that more than 75% of differentially expressed genes between probands and their unaffected fathers were specific to the macrocephalic or normocephalic groups, confirming our hypothesis that these represent different subtypes of ASD, and validating our approach to separately analyze these sets of families and compare their neurobiology. However, power analysis indicate that, in order to discover 90% of the predicted total number of enhancer elements active in our model, we need to analyze primary datasets from 10 additional macrocephalic and 7 additional normocephalic proband-control pairs. For macrocephalic individuals, 8 families are already available, requiring the recruitment of only 2 additional families. For normocephalic families, all 7 need to be newly enrolled. All together, under the auspices of this supplement we will recruit 9 families (18 subjects), generate iPSC lines, and produce transcriptome and enhancer datasets. Thus, this supplement application requests funds to complete recruitment, produce iPSC lines, and generate primary data which has been halted by the COVID pandemic. Over the years, the Vaccarino lab has a demonstrated ability to perform this research, as shown by deposition in the NIMH Stem Cell Resource at Infinity BiologiX LLC of a total of 82 primary cell lines and 121 iPSC lines from families with ASD (NDA collections C1201 and C2424).", "keywords": [ "ASD patient", "Award", "Biological", "COVID-19 pandemic", "Cell Line", "Cell Proliferation", "ChIP-seq", "Chromatin", "Clinical Data", "Clone Cells", "Collection", "Data", "Data Set", "Deposition", "Development", "Electrophysiology (science)", "Elements", "Enhancers", "Enrollment", "Family", "Family member", "Fathers", "Funding", "Gene Expression", "Generations", "Genes", "Genetic Enhancer Element", "Goals", "Head circumference", "Individual", "Interruption", "Link", "Macrocephaly", "Measures", "Modeling", "National Institute of Mental Health", "Neurobiology", "Organoids", "Parents", "Pathway Analysis", "Phenotype", "Production", "Regulator Genes", "Regulatory Element", "Request for Applications", "Research", "Resources", "Severities", "Speed", "Time", "Tissue-Specific Gene Expression", "Untranslated RNA", "autism spectrum disorder", "base", "brain size", "differential expression", "epigenome", "human subject", "induced pluripotent stem cell", "phenotypic data", "power analysis", "proband", "recruit", "sample collection", "screening", "stem cells", "synaptogenesis", "transcriptome", "transcriptome sequencing" ], "approved": true } }, { "type": "Grant", "id": "10276", "attributes": { "award_id": "1R41AI162477-01A1", "title": "Point-of-care microdevices for simultaneous detection of multiple pertussis-like respiratory diseases from Bordetella species", "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": 9776, "first_name": "Xin-Xing", "last_name": "Gu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-19", "end_date": "2024-01-31", "award_amount": 259565, "principal_investigator": { "id": 26234, "first_name": "Xiujun", "last_name": "Li", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1907, "ror": "", "name": "MICROBIOCHIP DIAGNOSTICS LLC", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Pertussis, also known as whooping cough, caused by B. pertussis and B. parapertussis, is the only vaccine-preventable infection that remains endemic in the U.S. Since pertussis vaccine- induced immunity is not permanent, the immunized host is vulnerable to re-infection later in life. Worldwide, there are an estimated 24.1 million cases of pertussis, and about 160,700 deaths per year from pertussis in children, most of which are from developing nations. These two Bordetella species are highly contagious and cause similar clinical symptoms, making them difficult to diagnose. Although B. parapertussis infection manifests in milder symptoms to B. pertussis- derived infection, both infections can be deadly, especially to children, the elderly, and immunocompromised patients. Current diagnostic methods are either slow or require costly instruments. Low-cost point-of-care (POC) detection of these two whooping cough-causing pathogens is greatly needed to meet the unmet demand for rapid diagnosis of whooping cough in resource-limited settings. During our recent preliminary study, we, for the first time, developed a low-cost microfluidic technology integrated with the loop-mediated isothermal DNA amplification (LAMP) for rapid POC detection of B. pertussis. Herein, the goal of this proposal is to develop a new low-cost paper/polymer hybrid microfluidic POC device integrated with LAMP for rapid, specific, and sensitive diagnosis of two major whooping cough-causing Bordetella species (B. pertussis and B. parapertussis) that can be used in various venues such as physicians’ offices, schools, and other low-resource settings. Our central hypothesis is that the integration of a low- cost portable paper-based microfluidic technology with specific DNA testing assays can provide a fast, accurate, and rapid diagnosis in resource-poor settings (US patent # 10,875,024). To accomplish our goal, we have developed three specific aims: (1) Develop and optimize LAMP assays for simultaneous detection of B. pertussis and B. parapertussis; (2) Develop a low-cost paper/polymer hybrid microfluidic POC device for the simultaneous instrument-free detection of B. pertussis and B. parapertussis; and (3) Verify the POC device for rapid detection of Bordetella species using clinical samples. The proposed methodology will allow for the confirmation of suspected cases of whooping cough caused by different Bordetella species at the point of care, filling a gap of current diagnostic methods in whooping cough. Furthermore, our biochip has great potential for the rapid detection of a variety of other respiratory infectious diseases such as COVID-19 in resource-poor settings.", "keywords": [ "Aspirate substance", "Biological", "Biological Assay", "Biomedical Engineering", "Bordetella", "Bordetella parapertussis", "Bordetella pertussis", "Businesses", "COVID-19", "Case Study", "Cellular Phone", "Cessation of life", "Child", "Clinical", "Clinical Pathology", "Communicable Diseases", "Complex", "Consumption", "Cytolysis", "DNA", "DNA amplification", "Detection", "Developing Countries", "Development", "Devices", "Diagnosis", "Diagnostic Procedure", "Diagnostic Specificity", "Ensure", "Eye", "Freezing", "Goals", "Health Care Costs", "Hospitalization", "Hour", "Hybrids", "Immunize", "Immunocompromised Host", "Infection", "Legal patent", "Life", "Liquid substance", "Los Angeles", "Mediating", "Methodology", "Microbiology", "Microfluidics", "Paper", "Pediatric Hospitals", "Performance", "Pertussis", "Pertussis Vaccine", "Phase", "Physicians&apos", "Offices", "Polymers", "Predictive Value", "Publishing", "Reagent", "Resource-limited setting", "Respiratory Disease", "Sampling", "Schools", "Specificity", "Symptoms", "Syndrome", "Temperature", "Testing", "Time", "Vaccines", "Visual", "Work", "accurate diagnosis", "base", "biochip", "clinical diagnostics", "cost", "cost effective", "design", "detection limit", "detection sensitivity", "diagnostic panel", "diagnostic platform", "disorder prevention", "economic impact", "fluorexon", "health economics", "instrument", "microdevice", "microfluidic technology", "microorganism", "mortality", "multiplex detection", "nasopharyngeal swab", "new technology", "older patient", "pathogen", "patient population", "point of care", "point-of-care detection", "point-of-care diagnosis", "point-of-care diagnostics", "portability", "prevent", "prototype", "rapid detection", "rapid diagnosis", "respiratory", "success", "vaccine-induced immunity" ], "approved": true } }, { "type": "Grant", "id": "6651", "attributes": { "award_id": "5R35GM118097-07", "title": "Mechanism of Immune Dysfunction and Morbid Outcomes in Response to Shock/Sepsis", "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": 22300, "first_name": "XIAOLI", "last_name": "Zhao", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2016-05-01", "end_date": "2026-04-30", "award_amount": 562793, "principal_investigator": { "id": 22301, "first_name": "Alfred", "last_name": "Ayala", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1416, "ror": "https://ror.org/01aw9fv09", "name": "Rhode Island Hospital", "address": "", "city": "", "state": "RI", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1416, "ror": "https://ror.org/01aw9fv09", "name": "Rhode Island Hospital", "address": "", "city": "", "state": "RI", "zip": "", "country": "United States", "approved": true }, "abstract": "At last count, sepsis was reported to be the leading cause of death in U.S hospital intensive care units (ICU); accounting for ~1 in 5 deaths world-wide; its incidence is anticipated to rise as the populations in developed countries age; and it was the consensus cause of death assigned to those dying from COVID-19 infection. Most frustrating, is that while we continue to optimize the supportive care for these critically ill patients, we have yet to see a novel molecular etiology-based therapy make a sustained impact on overall septic morbidity/ mortality. Excitingly, while working for years on defining numerous defects of components of both adaptive and innate immune responsiveness induced by shock and/or sepsis, we have uncovered novel role(s) for a number of the B7-family of cell-associated co-inhibitory receptors, Programmed Cell Death Receptor-1 [PD-1], B-/T- Lymphocyte Attenuator [BTLA], recently, V-domain Immunoglobulin Suppressor of T cell Activation [VISTA, a.k.a., B7-H5, PD-1H] and their respective cell surface ligands; popularly referred to as checkpoint proteins. In this competitive renewal of our MIRA program, we propose to continue to push forward the 3 project areas we brought together previously under the over-arching concept that by understanding the mechanism(s) of injury/shock and/or sepsis that serve to predispose animals (experimentally) or critically ill/injured patients to develop morbid outcomes, we can elucidate not only novel prognostic markers of patient’s course, but uncover unique therapeutic targets for their treatment. In the 1st Project area we will determine how the select expression of PD-1, BTLA or VISTA, on myeloid as opposed to lymphoid cells alters the development of morbid events associated with sepsis; then, how the expression of ligands for these co-inhibitory molecules, on leukocytes and/or endothelial/epithelial cells, contribute to the onset of septic liver, intestine and/or kidney dysfunction. In our 2nd Project area, we will utilize a novel murine model of indirect-acute lung injury (iALI)(dual insults of hemorrhage shock followed by cecal ligation & puncture [CLP]) to ask how checkpoint protein expression not only effect the patho-mechanisms driving the development of iALI, but how are these co- inhibitors alter cell ‘priming’/’innate immune memory’/function by following pulmonary immune/non-immune cell transcriptomic/epigenomic fate/programing. Finally, (3rd Project) since the neonate possesses a unique/naïve immune system and is more susceptible to morbid response in the face of infectious challenge; we ask how the expression of members of the B-7 family of proteins and/or their ligands not only have a comparative impact on the response to septic insult, but how this alters their microbiota and epigenetic makeup/immune function as survivors mature? To do this we will interrogate these 3 cogent models of sepsis, shock/sepsis and/or neonatal sepsis, by applying a combination genetic/Cre-Lox mouse models, adoptive transfer, single cell RNA-seq/ATAC- seq, 16S microbiota RNA-seq and bisulfite/pyrosequencing to examine these questions/hypotheses along with select observational clinical studies in the critical ill patient population.", "keywords": [ "ATAC-seq", "Accounting", "Acute Lung Injury", "Adoptive Transfer", "Age", "Animals", "Anti-Inflammatory Agents", "Apoptosis", "Area", "Automobile Driving", "Cause of Death", "Cell surface", "Cells", "Cessation of life", "Clinical Research", "Consensus", "Cre-LoxP", "Critical Illness", "Defect", "Developed Countries", "Development", "Endothelium", "Epigenetic Process", "Epithelial Cells", "Etiology", "Event", "Family", "Genetic", "Hemorrhagic Shock", "Hospitals", "Immune", "Immune System Diseases", "Immune system", "Immunoglobulin Domain", "Immunologic Memory", "Incidence", "Injury", "Intensive Care Units", "Intestines", "Leukocytes", "Ligands", "Liver", "Lung", "Lymphoid Cell", "Modeling", "Molecular", "Morbidity - disease rate", "Multiple Organ Failure", "Myelogenous", "Outcome", "Patients", "Population", "Prognostic Marker", "Protein Family", "Proteins", "Reporting", "Role", "SARS-CoV-2 infection", "Sepsis", "Shock", "Supportive care", "Suppressor-Effector T-Lymphocytes", "Surgical Intensive Care", "Survivors", "T-Cell Activation", "T-Lymphocyte", "base", "bisulfite", "cecal ligation puncture", "comparative", "design", "epigenomics", "immune function", "inhibitor/antagonist", "injured", "kidney dysfunction", "member", "microbiota", "mortality", "mouse model", "neonatal sepsis", "neonate", "novel", "organ growth", "organ injury", "patient population", "programs", "protein expression", "pyrosequencing", "receptor", "response", "septic", "single-cell RNA sequencing", "therapeutic target", "transcriptome sequencing", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "10786", "attributes": { "award_id": "1R01HL166245-01", "title": "Defining PRC2 complex epigenomic control in alveolar progenitor cells", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 22589, "first_name": "CHRISTIAN RENE", "last_name": "Gomez", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-12-15", "end_date": "2027-11-30", "award_amount": 556110, "principal_investigator": { "id": 26862, "first_name": "William John", "last_name": "Zacharias", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 897, "ror": "", "name": "CINCINNATI CHILDRENS HOSP MED CTR", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "The alveolar region of the mammalian lung is a complex, precisely structured tissue required for the primary functions of the respiratory system, gas exchange and tissue oxygenation. Damage to the alveolar epithelium plays a central role in human lung diseases including Acute Respiratory Distress Syndrome (ARDS), a prevalent, high impact clinical disorder that affects up to 5% of mechanically ventilated patients in the developed world. The mortality rate of ARDS approaches 40%, and the recovery for ARDS survivors is arduous, with a substantial burden of multi-system disability continuing 5 or more years following hospitalization. Critically, while many ARDS survivors recover lung function, a subset of patients develops persistently abnormal pulmonary function, imaging evidence of pulmonary scarring, and pulmonary symptoms even years after ARDS. To date, no data exists regarding the mechanisms that guide ARDS recovery. These challenges have been made more acute by the coronavirus pandemic, which has exposed a large proportion of the human population to acute lung injury. An enormous population of patients is at risk of both acute and chronic lung consequences of lung injury following coronavirus infection, emphasizing the clear and urgent need for new regenerative therapies to promote recovery from acute lung disease. Regeneration in many organs is driven by adult facultative progenitor cells. We recently discovered a facultative progenitor cell in the mouse and human lung which participates in regeneration after viral injury we call alveolar epithelial progenitors (AEPs). Progenitor cells control their chromatin carefully, as they must maintain more broad potential than fully differentiated cells, and so a hallmark of progenitor chromatin state is regions of active regulation between fully open and fully closed states, so called poised chromatin. Unique preliminary data from our laboratory and review of the literature support the idea that the chromatin modifying complex PRC2 is a critical regulator of the progenitor chromatin state of AEPs. In this application, using a combination of advanced lung organoids and genetic mouse injury models, we will identify the temporal and functional requirements for PRC2 function in lung progenitors, define the key binding partners and targets of the PRC2 complex in maintenance of AEP progenitor state, and evaluate the genomic loci regulated by PRC2 complex activity necessary for AEP-mediated alveolar regeneration. Understanding these fundamental mechanisms will provide the framework needed to understand alveolar regenerative biology at a granular level and develop therapeutic strategies to maintain and restore AT2 progenitor function to drive repair following infection and environmental stress.", "keywords": [ "ATAC-seq", "Acute", "Acute Lung Injury", "Acute Respiratory Distress Syndrome", "Adult", "Affect", "Alveolar", "Animals", "Attention", "Automobile Driving", "Binding", "Biology", "Cell Differentiation process", "Cells", "Chemicals", "Chromatin", "Chromatin Remodeling Factor", "Chronic", "Clinical", "Co-Immunoprecipitations", "Complex", "Computer Analysis", "Coronavirus Infections", "Data", "Deposition", "Disease", "Drug Targeting", "Ensure", "Epigenetic Process", "Epithelial Cells", "Future", "Gases", "Genes", "Genetic", "Genetic Transcription", "Genome", "Genomics", "Grant", "Homeostasis", "Hospitalization", "Human", "Image", "In Vitro", "Infection", "Influenza", "Injury", "Laboratories", "Literature", "Longevity", "Lung", "Lung diseases", "Maintenance", "Mechanical ventilation", "Mediating", "Modeling", "Molecular Conformation", "Mus", "Natural regeneration", "Organ", "Organoids", "Patients", "Pharmaceutical Preparations", "Phenotype", "Play", "Pneumonia", "Population", "Process", "Proteomics", "Publishing", "RNA", "Recovery", "Regulation", "Respiratory System", "Respiratory physiology", "Review Literature", "Risk", "Role", "SARS-CoV-2 infection", "Specificity", "Stable Populations", "Stress", "Structure", "Survivors", "Testing", "Therapeutic", "Time", "Tissues", "Ventilator", "Viral", "Work", "alveolar epithelium", "combinatorial", "disability", "epigenomics", "epithelium regeneration", "exhaustion", "fibrotic lung", "genomic locus", "healing", "improved", "in vivo", "influenza infection", "insight", "lung injury", "lung regeneration", "mortality", "novel", "pandemic coronavirus", "patient population", "patient subsets", "premature", "prevent", "progenitor", "pulmonary function", "pulmonary symptom", "regeneration potential", "regenerative", "regenerative biology", "regenerative therapy", "repaired", "self-renewal", "stem cells", "therapeutic development", "tissue oxygenation" ], "approved": true } }, { "type": "Grant", "id": "10370", "attributes": { "award_id": "1K99HL164960-01", "title": "Endothelial cell signaling in regeneration of the lung", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 26342, "first_name": "MARISOL", "last_name": "Espinoza-Pintucci", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-09-01", "end_date": "2024-08-31", "award_amount": 161690, "principal_investigator": { "id": 26343, "first_name": "Terren Kathryn", "last_name": "Niethamer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 232, "ror": "https://ror.org/00b30xv10", "name": "University of Pennsylvania", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "A critical function of the lung at homeostasis is delivery of oxygen to the blood through a process called gas exchange. When the lung is functioning normally, type I alveolar epithelial cells and capillary endothelial cells (ECs) lining blood vessels in the distal lung form a tight interface to exchange oxygen and carbon dioxide between them. However, when the lung is damaged by chronic disease, cancer, or infections such as influenza or COVID-19, this process can be hindered or even prevented. After lung injury, progenitor cells can regenerate the cell types required for gas exchange, but cell-cell communication is also essential to form a functional structure that restores delivery of oxygen to the blood. Development of improved regenerative therapies in the lung will therefore require a detailed knowledge of not only the specific cell types that are present, but also how they communicate to drive cell self-organization and morphogenesis. We have shown that capillary ECs in the distal lung are heterogeneous; one population acts as an EC progenitor and proliferates after acute injury (CAP2s), while a second population does not proliferate significantly after injury and possesses a larger, more complex morphology and high expression of signaling molecules (CAP1s). These EC subtypes clearly contribute differently to regeneration, but how distinct EC fates are established and maintained, the mechanisms that promote the preferential proliferation of CAP2s, and the signaling function of CAP1s remain unknown. In addition, the EC signaling mechanisms within the alveolar niche that are required to effect morphogenesis and rebuild the gas exchange interface remain incompletely understood. The proposed research will further develop my skills in transcriptomic and epigenomic analysis to address these questions and will integrate these skills with my previous training in mouse genetics, signaling, and cell behavior to establish a strong foundation on which to build an independent research career. My research program will focus on the role of EC signaling and behavior in regeneration of functional alveolar structures in the lung after acute injury. My primary mentor is Dr. Edward Morrisey, an internationally renowned scientist in the study of lung regeneration who has defined many key regulators of cell fate and signaling mechanisms in the lung. I have also assembled an advisory committee of experts in vascular biology, mouse and human organoid culture, epigenetics, and bioinformatics who will assist me with additional training in these areas. The proposed work will be conducted at the University of Pennsylvania, where I will benefit from the rich intellectual environment, extensive resources, collaborative scientific community in pulmonary and vascular biology, and the full support of the institution. Together, my proposed research and career development plans will facilitate a better understanding of the role of EC signaling in lung regeneration and aid in establishing my career as an independent investigator in pulmonary vascular biology.", "keywords": [ "ATAC-seq", "Acute", "Acute Lung Injury", "Address", "Advisory Committees", "Alveolar", "Alveolar Cell", "Alveolus", "Architecture", "Area", "Bioinformatics", "Biology", "Blood", "Blood Vessels", "Blood capillaries", "COVID-19", "Candidate Disease Gene", "Capillary Endothelial Cell", "Carbon Dioxide", "Cardiovascular system", "Cell Communication", "Cell Differentiation process", "Cell Line", "Cell Proliferation", "Cells", "Cellular biology", "Chronic Disease", "Communication", "Communities", "Complex", "Data", "Development", "Development Plans", "Distal", "Elastases", "Endothelial Cells", "Endothelium", "Environment", "Epigenetic Process", "Epithelial", "Epithelial Cells", "Foundations", "Functional Regeneration", "Gases", "Genetic Transcription", "Heterogeneity", "Homeostasis", "Human", "Image", "Immune", "Individual", "Infection", "Influenza", "Injury", "Institution", "International", "KDR gene", "Knock-out", "Knowledge", "Ligands", "Lung", "Lung diseases", "Malignant Neoplasms", "Mammals", "Mentors", "Mesenchymal", "Morphogenesis", "Morphology", "Mus", "Natural regeneration", "Organ", "Organoids", "Oxygen", "Patients", "Pennsylvania", "Phase", "Population", "Positioning Attribute", "Process", "Proliferating", "Pulmonary alveolar structure", "Pulmonary function tests", "Receptor Signaling", "Regenerative capacity", "Research", "Research Personnel", "Resources", "Role", "Scientist", "Signal Pathway", "Signal Transduction", "Signaling Molecule", "Site", "Structure", "Structure of parenchyma of lung", "Time", "Tissues", "Training", "Universities", "Vascular regeneration", "Viral", "Work", "alveolar epithelium", "career", "career development", "cell behavior", "cell regeneration", "cell type", "endothelial stem cell", "epigenomics", "genetic approach", "improved", "in vivo", "influenza infection", "injured", "injury and repair", "insight", "lung injury", "lung regeneration", "mouse genetics", "novel", "post-doctoral training", "prevent", "progenitor", "programs", "pulmonary function", "pulmonary vascular cells", "receptor", "reconstruction", "regenerative", "regenerative therapy", "repaired", "research and development", "response", "self organization", "severe injury", "single-cell RNA sequencing", "skills", "stem cells", "transcriptome sequencing", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "5860", "attributes": { "award_id": "3U01AI141993-03S1", "title": "Human Vaccine Durability using Integrated Bioinformatics and a Novel in vitro Bone Marrow Mimic", "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": 20084, "first_name": "Conrad M.", "last_name": "Mallia", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-09-01", "end_date": "2022-12-31", "award_amount": 253978, "principal_investigator": { "id": 20085, "first_name": "Frances Eun-Hyung", "last_name": "Lee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 265, "ror": "https://ror.org/03czfpz43", "name": "Emory University", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "Human Vaccine Durability using Integrated Bioinformatics and a Novel in vitro Bone Marrow Mimic. Abstract: Long-lived plasma cells (LLPC) sustain protective antibody production for a lifetime and are the cellular basis of vaccine durability and require the bone marrow (BM) microniche to sustain survival. In our lab, we have definitively linked the long-lived viral serum antibodies to the BM cellular compartment within the healthy human BM (CD19-CD38hiCD138+) PC subset thereby establishing the LLPC compartment. We have also developed in vitro BM microniche cultures that mimic the BM microenvironment to sustain PC survival. In this application, we plan (1) to develop a novel in vitro biomarker of vaccine durability using this novel in vitro BM mimic and to dissect the mechanisms of early blood ASC of long-lived vaccines, acute viral infections, compared to short-lived vaccines, (2) to identify the unique identity of LLPC precursors in the blood early after vaccination, and (3) to study mechanisms of LLPC generation in disease models of Systemic Lupus Erythematosis which is characterized by high levels of long-lived antibodies and an abundance of LLPC. In summary, these studies will distinguish the cellular and molecular programs of LLPC generation and maintenance after immunization.", "keywords": [ "ATAC-seq", "Acute", "Affinity", "Antibodies", "Antibody Formation", "Antibody Repertoire", "Aspirate substance", "Autoantibodies", "Autoimmune Diseases", "B-Cell Antigen Receptor", "B-Lymphocytes", "Behavior", "Bioinformatics", "Biological Markers", "Blood", "Blood Circulation", "Bone Marrow", "CD19 gene", "Cell Compartmentation", "Cell Differentiation process", "Cell Maturation", "Cell Survival", "Cells", "Cellular Morphology", "Disease model", "Elderly", "Epigenetic Process", "Flow Cytometry", "Generations", "Genetic Transcription", "Hepatitis B", "Heterogeneity", "Homing", "Human", "Hypoxia", "Immune", "Immunization", "Immunoglobulin-Secreting Cells", "In Vitro", "Infection", "Interferon Type II", "Interleukin-6", "Kinetics", "Life", "Link", "Lupus", "Maintenance", "Measles", "Mediating", "Methods", "Molecular", "Mumps", "Pathway interactions", "Patients", "Peripheral", "Plasma Cells", "Population", "Production", "Property", "Reaction", "Rubella", "Serum", "Smallpox", "Streptococcus pneumoniae", "Structure of germinal center of lymph node", "Survivors", "Systemic Lupus Erythematosus", "T-Lymphocyte", "Tetanus", "Time", "Vaccination", "Vaccines", "Viral", "Virus Diseases", "Yellow Fever Vaccine", "cytokine", "epigenome", "human disease", "imprint", "influenza infection", "influenza virus vaccine", "insight", "lymph nodes", "mesenchymal stromal cell", "next generation sequencing", "novel", "novel marker", "pandemic influenza", "programs", "reconstruction", "response", "transcriptome", "transcriptome sequencing", "transcriptomics", "vaccine evaluation", "vaccine response" ], "approved": true } }, { "type": "Grant", "id": "5073", "attributes": { "award_id": "3U01AI141993-04S1", "title": "Human Vaccine Durability using Integrated Bioinformatics and a Novel in vitro Bone Marrow Mimic", "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": 18127, "first_name": "Conrad M.", "last_name": "Mallia", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-09-01", "end_date": "2022-12-31", "award_amount": 255683, "principal_investigator": { "id": 18128, "first_name": "Frances Eun-Hyung", "last_name": "Lee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 265, "ror": "https://ror.org/03czfpz43", "name": "Emory University", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "Human Vaccine Durability using Integrated Bioinformatics and a Novel in vitro Bone Marrow Mimic. Abstract: Long-lived plasma cells (LLPC) sustain protective antibody production for a lifetime and are the cellular basis of vaccine durability and require the bone marrow (BM) microniche to sustain survival. In our lab, we have definitively linked the long-lived viral serum antibodies to the BM cellular compartment within the healthy human BM (CD19-CD38hiCD138+) PC subset thereby establishing the LLPC compartment. We have also developed in vitro BM microniche cultures that mimic the BM microenvironment to sustain PC survival. In this application, we plan (1) to develop a novel in vitro biomarker of vaccine durability using this novel in vitro BM mimic and to dissect the mechanisms of early blood ASC of long-lived vaccines, acute viral infections, compared to short-lived vaccines, (2) to identify the unique identity of LLPC precursors in the blood early after vaccination, and (3) to study mechanisms of LLPC generation in disease models of Systemic Lupus Erythematosis which is characterized by high levels of long-lived antibodies and an abundance of LLPC. In summary, these studies will distinguish the cellular and molecular programs of LLPC generation and maintenance after immunization.", "keywords": [ "ATAC-seq", "Acute", "Affinity", "Antibodies", "Antibody Formation", "Antibody Repertoire", "Aspirate substance", "Autoantibodies", "Autoimmune Diseases", "B-Cell Antigen Receptor", "B-Lymphocytes", "Behavior", "Bioinformatics", "Biological Markers", "Blood", "Blood Circulation", "Bone Marrow", "CD19 gene", "Cell Compartmentation", "Cell Differentiation process", "Cell Maturation", "Cell Survival", "Cells", "Cellular Morphology", "Disease model", "Elderly", "Epigenetic Process", "Flow Cytometry", "Generations", "Genetic Transcription", "Hepatitis B", "Heterogeneity", "Homing", "Human", "Hypoxia", "Immune", "Immunization", "Immunoglobulin-Secreting Cells", "In Vitro", "Infection", "Interferon Type II", "Interleukin-6", "Kinetics", "Life", "Link", "Lupus", "Maintenance", "Measles", "Mediating", "Methods", "Molecular", "Mumps", "Pathway interactions", "Patients", "Peripheral", "Plasma Cells", "Population", "Production", "Property", "Reaction", "Rubella", "Serum", "Smallpox", "Streptococcus pneumoniae", "Structure of germinal center of lymph node", "Survivors", "Systemic Lupus Erythematosus", "T-Lymphocyte", "Tetanus", "Time", "Vaccination", "Vaccines", "Viral", "Virus Diseases", "Yellow Fever Vaccine", "cytokine", "epigenome", "human disease", "imprint", "influenza infection", "influenza virus vaccine", "insight", "lymph nodes", "mesenchymal stromal cell", "next generation sequencing", "novel", "novel marker", "pandemic influenza", "programs", "reconstruction", "response", "transcriptome", "transcriptome sequencing", "transcriptomics", "vaccine evaluation", "vaccine response" ], "approved": true } }, { "type": "Grant", "id": "8440", "attributes": { "award_id": "1F32HL156516-01", "title": "Defining the role of IRF5 in inflammatory hemophagocyte differentiation", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 24201, "first_name": "Allison", "last_name": "Gillaspy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-07-07", "end_date": "2022-07-06", "award_amount": 76053, "principal_investigator": { "id": 24202, "first_name": "Susan Priscilla", "last_name": "Canny", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disorder associated with anemia, thrombocytopenia, and leukopenia and systemic hyperinflammation. Secondary HLH can be triggered by a range of diseases, including infections, cancer, or rheumatic disease. When triggered by rheumatic disease, it is often referred to as macrophage activation syndrome (MAS). HLH/MAS involves a hyperinflammatory response in which activated macrophages phagocytose red blood cells, white blood cells and platelets. Research in the Hamerman lab has revealed a critical role for cell-intrinsic Toll-like receptor (TLR) 7 signaling in the development of inflammatory hemophagocytes, a monocyte-derived macrophage that drives HLH/MAS in a mouse model. IRF5, which mediates TLR7 signaling in monocytes, contributes to differentiation of these hemophagocytes in the mouse although the signals driving differentiation of these cells in humans are unknown. This application aims to elucidate the role of IRF5 in the development of inflammatory hemophagocytes in both mice (Aim 1) and humans (Aim 2) and to further define the mechanism of cells of the monocyte lineage in cytokine storm syndromes. The proposed research will result in a better understanding of the role of myeloid cells in secondary HLH and may provide novel therapeutic targets or approaches. The fellowship training will take place at the Benaroya Research Institute, which focuses on understanding immune-mediated diseases, under the guidance of Dr. Jessica Hamerman and Dr. Jane Buckner. The training plan described in the supporting documents will provide essential steps toward preparing me for a career as an independent scientist. At the completion of my postdoctoral training, I will be able to transition to independence as a physician scientist.", "keywords": [ "ATAC-seq", "Address", "Anemia", "Aspirate substance", "Automobile Driving", "Blood Platelets", "Bone Marrow", "Bone Marrow Transplantation", "CD14 gene", "Cell Differentiation process", "Cells", "Complication", "DNA Sequence Alteration", "Data", "Development", "Disease", "Dose", "Erythrocytes", "FCGR3B gene", "Fellowship", "Functional disorder", "Gene Expression", "Genetic Transcription", "Haplotypes", "Heme", "Human", "Immune", "Individual", "Infection", "Inflammatory", "Interferon Type II", "Interferons", "Interleukin-1", "Interleukin-18", "Interleukin-6", "Kinetics", "Leukocytes", "Leukopenia", "Life", "Macrophage Colony-Stimulating Factor", "Macrophage activation syndrome", "Malignant Neoplasms", "Mediating", "Metabolic Diseases", "Modeling", "Mus", "Myelogenous", "Myeloid Cells", "Natural Killer Cells", "Organ", "Pathogenesis", "Pathogenicity", "Pathologic", "Pathway interactions", "Patients", "Pharmaceutical Preparations", "Physicians", "Receptor Signaling", "Refractory", "Research", "Research Institute", "Rheumatism", "Risk", "Role", "Scientist", "Secondary to", "Signal Transduction", "Signaling Molecule", "Splenic Red Pulp", "Steroids", "Stimulus", "Syndrome", "T-Lymphocyte", "TLR7 gene", "TLR8 gene", "Testing", "Therapeutic", "Thrombocytopenia", "Time", "Toll-like receptors", "Training", "Work", "bone cell", "career", "chemotherapy", "cytokine", "cytokine release syndrome", "cytopenia", "familial hemophagocytic lymphohistiocytosis", "in vivo", "inhibitor/antagonist", "macrophage", "monocyte", "mouse model", "new therapeutic target", "p65", "post-doctoral training", "response", "transcription factor" ], "approved": true } }, { "type": "Grant", "id": "5134", "attributes": { "award_id": "1R01AI162643-01A1", "title": "Molecular Basis of cDC1 Development", "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": 18278, "first_name": "Nancy", "last_name": "Vazquez-Maldonado", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-06-17", "end_date": "2027-05-31", "award_amount": 559854, "principal_investigator": { "id": 18279, "first_name": "Kenneth M", "last_name": "Murphy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "The initial adaptive immune response to tumors and many viruses relies on the priming of CD8 T cells to gen- erate cytolytic effector T cells that can specifically target tumors or virally infected cells. The priming of CD8 T cells to these agents is carried out in vivo by a particular type of antigen presenting cell that is a component of the myeloid system and a member of the family of dendritic cells. Classical dendritic cells (cDCs) comprise several closely related lineages that are clearly distinct from other myeloid cells such as macrophages, mono- cytes or granulocytes. Primarily, cDCs serve to activate T cells against infections in the central lymphoid tis- sues, rather than carrying out direct effector functions at sites of infections as the other myeloid lineages do. The cDCs are themselves comprised of at least two major branches, now called cDC1 and cDC2. The cDC1 is a lineage that specializes in the uptake and processing of cell-associated antigens, such as from tumors of virally infected cells and the expression of peptide epitopes on its cell surface in conjunction with MHC-I mole- cules. This form of antigen:MHC-I complex is able to activate CD8 T cells, and not CD4 T cells. This process is called cross-presentation. The cDC2 is not capable of carrying out cross-presentation to viruses or tumors in vivo. The cDC1 has many genetic and molecular differences from cDC2; cDC1 require a distinct set of tran- scription factors for their development that are not required for cDC2. This includes dependence on the tran- scription factors Nfil3, Id2, Irf8 and Batf3. Our recent work showed that the genetic hierarchy among these fac- tors has Nfil3 as the first and initiating factor, acting to indirectly induce Id2 and Batf3 via the suppression of the repressor Zeb2. However, it is still unknown how Nfil3 is induced to initiate this process, and how Nfil3 works to suppress Zeb2 expression. It has recently become important to understand these details because of the clini- cal interest to apply Flt3L administration as a therapeutic in expanding the in vivo population of cDC1. It has been known for some time that Fl3L can expand dendritic cells in general and expand cDC1 in particular. But we have uncovered a surprising and worrisome fact; Flt3L administration will expand cDC1-like cells even in Nfil3-deficient mice, which completely lack cDC1 beforehand. The expansion of cDC1 in Nfil3-deficent mice produced by Flt3L is of the same magnitude as the expansion in WT mice. Thus, Flt3L is inducing cDC1 by a different genetic route than normal cDC1 development. There has been no test of whether such cDC1 cells function normally and will boost an immune response. This application will systematically address this issue by Aim 1) defining the normal process by which Nfil3 is induced, Aim 2) define the mechanism by which NFIL3 drives cDC1 development, and Aim 3) determine whether Flt3-induced cDC1 function normally and determine the mechanism by which Flt3L bypasses the normal requirement for Nfil3 in cDC1 development.", "keywords": [ "ATAC-seq", "Address", "Antigen-Presenting Cells", "Antigens", "Binding", "Bypass", "CCAAT-Enhancer-Binding Proteins", "CD8-Positive T-Lymphocytes", "CRISPR/Cas technology", "Cell physiology", "Cell surface", "Cells", "ChIP-seq", "Chimeric Proteins", "Clinical", "Complex", "Critiques", "Cross Presentation", "Data", "Dendritic Cells", "Dependence", "Development", "Elements", "Enhancers", "Epitopes", "Exhibits", "FLT3 gene", "FLT3 ligand", "Family member", "Gene Targeting", "Generations", "Genes", "Genetic", "Genetic Transcription", "Goals", "Homeostasis", "Human", "Immune response", "Immunity", "In Vitro", "Infection", "Literature", "Lymphoid Tissue", "MHC antigen", "Methods", "Mole the mammal", "Molecular", "Molecular Genetics", "Mus", "Myelogenous", "Myeloid Cells", "Output", "Pathway interactions", "Peptides", "Population", "Process", "Production", "Proteins", "Publishing", "Reagent", "Reporter", "Reporting", "Role", "Route", "Signal Transduction", "Site", "Specific qualifier value", "Suggestion", "System", "T cell response", "T-Lymphocyte", "Testing", "Therapeutic", "Time", "Tumor-Derived", "Vaccines", "Viral", "Virus", "Work", "adaptive immune response", "design", "effector T cell", "granulocyte", "in vivo", "interest", "macrophage", "novel", "progenitor", "response", "stem cells", "tool", "transcription factor", "tumor", "uptake" ], "approved": true } }, { "type": "Grant", "id": "5209", "attributes": { "award_id": "3R01AI048638-22S1", "title": "Metabolic imprinting of dendritic cell fate and function in tissues", "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": 18435, "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": "2001-03-01", "end_date": "2025-01-31", "award_amount": 118275, "principal_investigator": { "id": 18436, "first_name": "BALI", "last_name": "PULENDRAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 266, "ror": "https://ror.org/00f54p054", "name": "Stanford University", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Dendritic cells (DCs) play a central role in sensing pathogens and tuning immune responses. Functionally distinct subsets of DCs can stimulate different types of immune responses, but DCs also display functional plasticity in response to microbial stimuli or signals from the tissue microenvironment. However, it is now clear that DCs sense not just microbial stimuli, but also various stress signals (e.g. amino acid starvation), through ancient stress sensing mechanisms, leading to a metabolic reprogramming of their function. In particular our recent work has revealed fundamental roles for two major amino acid sensors GCN2 and mTOR, in programming DCs to modulate adaptive immunity and inflammation. We have shown that GCN2 plays a role in programming DCs to respond to viral vaccination, and in controlling intestinal inflammation by promoting autophagy and suppressing inflammasome activation in gut APCs and epithelial cells. Furthermore, our recent data demonstrates that GCN2 regulates allergic inflammation in the lung. In addition to these effects of GCN2, we have recently shown that mTOR regulates developmental fate of DCs and alveolar macrophages (AMs) in the lung, and reprograms their metabolic state to modulate the outcome of allergic inflammation. In the following aims, we will determine the mechanisms of this metabolic imprinting. Aim 1: To determine the mechanisms by which mTOR controls the homeostasis and function of lung DCs and AMs in the steady state and during allergic inflammation. Our recent work demonstrates that in mice in which mTOR is genetically ablated in CD11c+ cells (mTORAPC mice): (i) CD103+ DCs and AMs in the lung are greatly reduced in number, in the steady state. (ii) Although the lung CD11c+CD11b+ DCs were numerically unaffected, they were skewed in their transcriptional identity towards the macrophage/monocytic profile. (iii) Lung allergic Th2 inflammation was skewed toward the Th17/neutrophilic phenotype. In the present aim, we will investigate the mechanisms underlying these effects, and investigate the potential role of 4E-BP3 dependent translational control, lipid metabolism and epigenetic reprograming in mediating the effects of mTOR signaling. Aim 2: To determine the mechanisms by which GCN2 regulates Th2 responses and allergic inflammation. Our preliminary data demonstrate that GCN2 knockout mice display markedly reduced allergic inflammation in the lung. In this aim we will determine the molecular mechanisms underlying this effect. The successful completion of these aims will yield rich mechanistic insights about metabolic imprinting of DC fate and function.", "keywords": [ "ATAC-seq", "Adoptive Transfer", "Allergic", "Allergic inflammation", "Alveolar Macrophages", "Amino Acids", "Autophagocytosis", "Bone Marrow", "Cell physiology", "Cells", "Cellular biology", "Chimera organism", "Data", "Dendritic Cells", "Development", "EIF4EBP1 gene", "Epigenetic Process", "Epithelial Cells", "FRAP1 gene", "Genetic Transcription", "Genetic Translation", "Hematopoietic", "Homeostasis", "ITGAM gene", "ITGAX gene", "Immune response", "Immunity", "In Situ", "Infection", "Inflammasome", "Inflammation", "Knockout Mice", "Lung", "Lymphoid Cell", "Mediating", "Metabolic", "Modeling", "Molecular", "Mus", "Natural Killer Cells", "Nature", "Organ", "Outcome", "Pathway interactions", "Phenotype", "Play", "Raptors", "Role", "Signal Pathway", "Signal Transduction", "Spleen", "Starvation", "Stimulus", "Stress", "Tissues", "Vaccination", "Viral", "Work", "adaptive immunity", "cell type", "conditional knockout", "functional plasticity", "gene repression", "imprint", "inflammatory disease of the intestine", "insight", "lipid metabolism", "mTOR Signaling Pathway", "macrophage", "metabolic profile", "microbial", "monocyte", "neutrophil", "pathogen", "programs", "pulmonary function", "receptor", "response", "sensor", "transcription factor" ], "approved": true } } ], "meta": { "pagination": { "page": 1383, "pages": 1397, "count": 13961 } } }