Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1393&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=1419&sort=keywords", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1394&sort=keywords", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=keywords" }, "data": [ { "type": "Grant", "id": "6130", "attributes": { "award_id": "3K99NS112575-02S1", "title": "Dissecting the action learning process with dopaminergic reinforcement", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 20836, "first_name": "Debra J.", "last_name": "Babcock", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2019-07-01", "end_date": "2022-06-30", "award_amount": 90828, "principal_investigator": { "id": 20837, "first_name": "Jonathan", "last_name": "Tang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 781, "ror": "", "name": "COLUMBIA UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 781, "ror": "", "name": "COLUMBIA UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Understanding the process by which animals learn to perform specific actions from rewarding experiences is important for identifying the neural and behavioral patterns that indicate system dysregulation; such knowledge can help lead to the development of diagnostics and therapy for conditions where action learning is impaired. Dopaminergic neurons and their targets have been implicated as major contributors to action learning. Though it is well known that stimulation of dopaminergic neurons can reinforce behavior, it is less clear how stimulated dopaminergic activities guide the animal to behaviorally search the world for the action that produces reward. The goal of this proposal is to characterize the role of dopaminergic activity in shaping behavior that hones in on a specific action or action sequences for reward. A key to this proposal is the combination of optogenetics and objective, unsupervised behavioral clustering to develop a closed loop reinforcement system in which reward in the form of dopaminergic stimulation is delivered to the VTA of animals as they learn to perform specific actions or action sequences. The K99 phase of the application will involve characterization of the behavioral patterns underlying single action and action sequence learning, followed by imaging of the dorsolateral striatum (known to represent the action space) in freely moving mice to understand the neural correlates of the action learning process. Functional circuit dissection will also be performed to elucidate which specific VTA projection pathways mediate action learning. Following mastering of these techniques, the applicant will enter the R00 phase and continue studying the role of specific VTA projection pathways on the action learning process. Chemogenetics in combination with closed loop reinforcement will be performed to dissect the pathways necessary for action learning. Neuronal activity imaging will then be performed on dopaminergic targets found to be important for action learning. The training plan, under the joint mentorship of Dr. Rui Costa and Dr. Stefano Fusi at Columbia University, will provide a complete set of neuroscience tools and the necessary career development resources for the applicant to obtain a faculty position and start an independent research program to explore the role of VTA dopaminergic neurons on the action learning process.", "keywords": [ "Animals", "Behavior", "Behavioral", "Brain", "Corpus striatum structure", "Dementia", "Development", "Diagnostic", "Dissection", "Dopaminergic Cell", "Faculty", "Goals", "Huntington Disease", "Image", "Impairment", "Joints", "Knowledge", "Lead", "Learning", "Life", "Mammals", "Mediating", "Mentorship", "Motor", "Movement", "Mus", "Neurologic", "Neurons", "Neurosciences", "Parkinson Disease", "Pathway interactions", "Pattern", "Phase", "Positioning Attribute", "Process", "Psychological reinforcement", "Research", "Resource Development", "Rewards", "Role", "Shapes", "Signal Transduction", "System", "Techniques", "Training", "Universities", "base", "career development", "dopaminergic neuron", "experience", "neural correlate", "optogenetics", "programs", "reinforced behavior", "relating to nervous system", "sequence learning", "tool" ], "approved": true } }, { "type": "Grant", "id": "6714", "attributes": { "award_id": "5R01MH125870-02", "title": "Investigating neurobehavioral consequences of COVID-19 related stressors on maternal mental health and infant development", "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": 22462, "first_name": "Julia L", "last_name": "Zehr", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-06-01", "end_date": "2025-03-31", "award_amount": 733744, "principal_investigator": { "id": 22463, "first_name": "Natalie Hiromi", "last_name": "Brito", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 167, "ror": "https://ror.org/0190ak572", "name": "New York University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22464, "first_name": "Moriah E", "last_name": "Thomason", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 167, "ror": "https://ror.org/0190ak572", "name": "New York University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Societal consequences of the COVID-19 pandemic are unprecedented. The global community has been crippled by a public health emergency that has had deleterious health and economic impacts, the scope of which has yet to be determined. As a result of the current crisis, pregnant women and new mothers are currently experiencing dramatic loss of medical, financial, and social support, resulting in higher rates of emotional distress. It is well established that chronic stress can be embedded in the developing neurobiological system, particularly during sensitive periods of life, but how the timing of maternal stressors and pathways through which these experiences impact child neurobehavioral development are unclear. The central objective of this proposal is to examine the association between perinatal COVID-19 stress and longitudinal postnatal brain development, and to rigorously evaluate timing of exposure, underlying biological mechanisms and postnatal protective factors. We will enroll 300 women and children from the New York City (NYC) COVID-19 Perinatal Experiences (COPE) cohort into a longitudinal protocol that will measure child biobehavioral outcomes at 12-, 24-, and 36-months. The COPE cohort is comprised of more than 900 women that were enrolled into a longitudinal assessment protocol at the height of the pandemic, approximately half of which were pregnant (54%) and half of which were new mothers (46%). The primary aims of this project are to (i) identify key windows of perinatal stress vulnerability; (ii) evaluate biological pathways that underlie associations between maternal COVID-19 stressors and infant neurocognition; and (iii) isolate protective factors in the postnatal environment that promote resilient outcomes in children exposed to extreme perinatal stress. We will selectively recruit the proposed subsample for this study based on balance of timing of exposure, severity of stressors, and sociodemographic factors. We will thus be able to meaningfully evaluate biological consequences of perinatal stress with control over both timing and aggregate risk. Such work would constitute a substantial advance in our understanding of the longitudinal effects of maternal perinatal stress on early human brain development and would also offer potential avenues for promoting healthy outcomes in children born at the height of history’s most significant perinatal stressor.", "keywords": [ "Animals", "Behavioral", "Biological", "Brain", "Buffers", "COVID-19", "COVID-19 pandemic", "Caring", "Child", "Child Development", "Chronic stress", "Collection", "Communities", "Contracts", "Data", "Data Set", "Development", "Economics", "Electroencephalography", "Enrollment", "Environment", "Environmental Risk Factor", "Equilibrium", "Event", "Exposure to", "Family", "Financial Support", "Foundations", "Future", "Goals", "Hair", "Health", "Heart Rate", "Height", "Human", "Human Milk", "Hydrocortisone", "Individual", "Infant", "Infant Development", "Inflammation", "Intervention", "Lead", "Life", "Link", "Long-Term Effects", "Longitudinal Studies", "Measures", "Medical", "Mental Health", "Mother-Child Relations", "Mothers", "Neurobiology", "Neurocognition", "Neurocognitive", "New York City", "Outcome", "Parent-Child Relations", "Pathway interactions", "Pattern", "Perinatal", "Personal Satisfaction", "Physiological", "Population", "Postpartum Women", "Pregnancy", "Pregnant Women", "Protocols documentation", "Psychopathology", "Recording of previous events", "Research", "Resources", "Rest", "Risk", "Severities", "Social support", "Stress", "Surveys", "System", "Testing", "Time", "Toddler", "United States", "Virus", "Woman", "Work", "anxious behavior", "base", "biobehavior", "brain behavior", "caregiving", "cognitive function", "cohort", "coronavirus disease", "early life stress", "economic impact", "emotional distress", "experience", "gut microbiome", "gut microbiota", "health economics", "improved", "infancy", "inflammatory marker", "interest", "maternal stress", "neurobehavioral", "neurodevelopment", "neuropsychiatry", "pandemic disease", "perinatal period", "postnatal", "pregnant", "prenatal", "prospective", "protective factors", "psychosocial", "public health emergency", "recruit", "response", "social", "social norm", "sociodemographic factors", "sociodemographics", "stressor", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "8360", "attributes": { "award_id": "1R01MH125870-01", "title": "Investigating neurobehavioral consequences of COVID-19 related stressors on maternal mental health and infant development", "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": 6363, "first_name": "Julia L", "last_name": "Zehr", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-06-01", "end_date": "2025-03-31", "award_amount": 762824, "principal_investigator": { "id": 22463, "first_name": "Natalie Hiromi", "last_name": "Brito", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 167, "ror": "https://ror.org/0190ak572", "name": "New York University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 20865, "first_name": "Moriah E", "last_name": "Thomason", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 167, "ror": "https://ror.org/0190ak572", "name": "New York University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Societal consequences of the COVID-19 pandemic are unprecedented. The global community has been crippled by a public health emergency that has had deleterious health and economic impacts, the scope of which has yet to be determined. As a result of the current crisis, pregnant women and new mothers are currently experiencing dramatic loss of medical, financial, and social support, resulting in higher rates of emotional distress. It is well established that chronic stress can be embedded in the developing neurobiological system, particularly during sensitive periods of life, but how the timing of maternal stressors and pathways through which these experiences impact child neurobehavioral development are unclear. The central objective of this proposal is to examine the association between perinatal COVID-19 stress and longitudinal postnatal brain development, and to rigorously evaluate timing of exposure, underlying biological mechanisms and postnatal protective factors. We will enroll 300 women and children from the New York City (NYC) COVID-19 Perinatal Experiences (COPE) cohort into a longitudinal protocol that will measure child biobehavioral outcomes at 12-, 24-, and 36-months. The COPE cohort is comprised of more than 900 women that were enrolled into a longitudinal assessment protocol at the height of the pandemic, approximately half of which were pregnant (54%) and half of which were new mothers (46%). The primary aims of this project are to (i) identify key windows of perinatal stress vulnerability; (ii) evaluate biological pathways that underlie associations between maternal COVID-19 stressors and infant neurocognition; and (iii) isolate protective factors in the postnatal environment that promote resilient outcomes in children exposed to extreme perinatal stress. We will selectively recruit the proposed subsample for this study based on balance of timing of exposure, severity of stressors, and sociodemographic factors. We will thus be able to meaningfully evaluate biological consequences of perinatal stress with control over both timing and aggregate risk. Such work would constitute a substantial advance in our understanding of the longitudinal effects of maternal perinatal stress on early human brain development and would also offer potential avenues for promoting healthy outcomes in children born at the height of history’s most significant perinatal stressor.", "keywords": [ "Animals", "Behavioral", "Biological", "Brain", "Buffers", "COVID-19", "COVID-19 pandemic", "Caring", "Child", "Child Development", "Chronic stress", "Collection", "Communities", "Contracts", "Data", "Data Set", "Development", "Economics", "Electroencephalography", "Enrollment", "Environment", "Environmental Risk Factor", "Equilibrium", "Event", "Exposure to", "Family", "Financial Support", "Foundations", "Future", "Goals", "Hair", "Health", "Heart Rate", "Height", "Human", "Human Milk", "Hydrocortisone", "Individual", "Infant", "Infant Development", "Inflammation", "Intervention", "Lead", "Life", "Link", "Long-Term Effects", "Longitudinal Studies", "Measures", "Medical", "Mental Health", "Mother-Child Relations", "Mothers", "Neurobiology", "Neurocognition", "Neurocognitive", "New York City", "Outcome", "Parent-Child Relations", "Pathway interactions", "Pattern", "Perinatal", "Personal Satisfaction", "Physiological", "Population", "Postpartum Women", "Pregnancy", "Pregnant Women", "Protocols documentation", "Psychopathology", "Recording of previous events", "Research", "Resources", "Rest", "Risk", "Severities", "Social support", "Stress", "Surveys", "System", "Testing", "Time", "Toddler", "United States", "Virus", "Woman", "Work", "anxious behavior", "base", "biobehavior", "brain behavior", "caregiving", "cognitive function", "cohort", "coronavirus disease", "early life stress", "economic impact", "emotional distress", "experience", "gut microbiome", "gut microbiota", "health economics", "improved", "infancy", "inflammatory marker", "interest", "maternal stress", "neurobehavioral", "neurodevelopment", "neuropsychiatry", "pandemic disease", "perinatal period", "postnatal", "pregnant", "prenatal", "prospective", "protective factors", "psychosocial", "public health emergency", "recruit", "response", "social", "social norm", "sociodemographic factors", "sociodemographics", "stressor", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "7596", "attributes": { "award_id": "3R01AI135270-03S1", "title": "Structural and functional analysis of the coronavirus spike protein fusion peptide", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6011, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-04-21", "end_date": "2022-07-31", "award_amount": 229985, "principal_investigator": { "id": 3886, "first_name": "Susan", "last_name": "Daniel", "orcid": null, "emails": "[email protected]", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 279, "ror": "https://ror.org/05bnh6r87", "name": "Cornell University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 3885, "first_name": "Gary R", "last_name": "Whittaker", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 279, "ror": "https://ror.org/05bnh6r87", "name": "Cornell University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 279, "ror": "https://ror.org/05bnh6r87", "name": "Cornell University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "/ Abstract Enveloped viruses access their host cells by binding to receptors on the plasma membrane and then undergoing fusion with the host membrane. Both binding and fusion are mediated by a specific viral “spike” protein that is typically primed for fusion activation by proteolytic cleavage to expose the fusion peptide. Coronavirus fusion spike protein (CoV S) is a complex biomolecular machine that has a novel fusion peptide with has a great deal of inherent flexibility in its fusion reaction. This is exploited by these viruses in their diverse entry pathways and is a primary determinant of viral tropism. We have pioneered the concept that that the proteolytic cleavage events in S that lead to membrane fusion occur both at the interface of the receptor binding (S1) and fusion (S2) domains (called S1/S2), as well as adjacent to a structurally and functionally novel fusion peptide within S2 (called S2’). Thus, there are notable differences between CoV S and most other class I fusion proteins including: 1) that the proteolytic events liberating the fusion peptide are diverse, and 2) that the fusion peptide itself is atypical in sequence compared to other fusion peptides, containing a mixture of important hydrophobic and negatively- charged residues, and may represent a larger than normal fusion “platform” instead of a defined “peptide”. Thus fusion peptide activity is likely controlled by reorganization of the fusion platform, based on both hydrophobic (i.e. lipid-binding) and ionic (i.e. Ca2+) interactions. Despite the recent availability of S structures in their pre- fusion state, there remains a very limited mechanistic understanding of membrane fusion for the CoV family, or any structural information to correlate structural biology aspects of S to its function in membrane fusion. This information is critical to understanding viral pathogenesis and CoV emergence into the human population. We propose an integrated biophysical, biochemical, and in vivo approach to study the unique cleavage-activated regulation of CoV S protein, using Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) as primary models. We will use state-of-the-art spectroscopy and an innovative single particle tracking technique to study S protein fusion peptide function, and combine these with in vivo infectivity studies, including at BSL3, will allow a complete picture of CoV fusion activation. These approaches will reveal how structure and function vary depending on the key activators of S; i.e. receptor binding, protease availability and the local ionic environment. These studies will allow us to determine common principals that can be applied to all CoVs, moving the field forward with these innovative studies will provide critical knowledge about CoV entry and tropism needed to safeguard human health from an emerging pathogen likely to cause severe outbreaks, and for which few or no medical countermeasures exist.", "keywords": [ "Animals", "Binding", "Biochemical", "Biological Assay", "Biological Models", "Biophysics", "Cell fusion", "Cell membrane", "Cell surface", "Cells", "Charge", "Chimeric Proteins", "Cleaved cell", "Communicable Diseases", "Complex", "Coronavirus", "Coronavirus Infections", "Coronavirus spike protein", "Cryoelectron Microscopy", "Data", "Disease Outbreaks", "Ebola virus", "Electron Spin Resonance Spectroscopy", "Endosomes", "Environment", "Event", "Exposure to", "Family", "Goals", "HIV", "Health", "Human", "Hydrophobicity", "Infection", "Influenza Hemagglutinin", "Ions", "Knowledge", "Lead", "Lipid Bilayers", "Lipid Binding", "Lipids", "Mediating", "Membrane", "Membrane Fusion", "Methods", "Middle East Respiratory Syndrome", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Monitor", "Mutagenesis", "NMR Spectroscopy", "Nature", "Pathogenesis", "Pathway interactions", "Peptide Hydrolases", "Peptides", "Play", "Population", "Process", "Property", "Proteins", "Reaction", "Regulation", "Research Personnel", "Resources", "Role", "Route", "SARS coronavirus", "Severe Acute Respiratory Syndrome", "Site", "Spectrum Analysis", "Structure", "Structure-Activity Relationship", "Techniques", "Testing", "Tissues", "Tropism", "Viral", "Viral Fusion Proteins", "Viral Pathogenesis", "Virus", "Virus Receptors", "Zoonoses", "base", "biophysical techniques", "cell type", "experimental study", "flexibility", "fluorescence microscope", "in vivo", "innovation", "medical countermeasure", "mutant", "novel", "novel coronavirus", "novel virus", "particle", "pathogen", "peptide I", "peptide structure", "protein function", "receptor", "receptor binding", "structural biology", "transmission process", "virus envelope" ], "approved": true } }, { "type": "Grant", "id": "6188", "attributes": { "award_id": "3R01AI135270-04S1", "title": "Structural and functional analysis of the coronavirus spike protein fusion peptide", "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": 20987, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-04-21", "end_date": "2022-07-31", "award_amount": 174298, "principal_investigator": { "id": 20988, "first_name": "Susan", "last_name": "Daniel", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 20989, "first_name": "Gary R", "last_name": "Whittaker", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 279, "ror": "https://ror.org/05bnh6r87", "name": "Cornell University", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "/ Abstract Enveloped viruses access their host cells by binding to receptors on the plasma membrane and then undergoing fusion with the host membrane. Both binding and fusion are mediated by a specific viral “spike” protein that is typically primed for fusion activation by proteolytic cleavage to expose the fusion peptide. Coronavirus fusion spike protein (CoV S) is a complex biomolecular machine that has a novel fusion peptide with has a great deal of inherent flexibility in its fusion reaction. This is exploited by these viruses in their diverse entry pathways and is a primary determinant of viral tropism. We have pioneered the concept that that the proteolytic cleavage events in S that lead to membrane fusion occur both at the interface of the receptor binding (S1) and fusion (S2) domains (called S1/S2), as well as adjacent to a structurally and functionally novel fusion peptide within S2 (called S2’). Thus, there are notable differences between CoV S and most other class I fusion proteins including: 1) that the proteolytic events liberating the fusion peptide are diverse, and 2) that the fusion peptide itself is atypical in sequence compared to other fusion peptides, containing a mixture of important hydrophobic and negatively- charged residues, and may represent a larger than normal fusion “platform” instead of a defined “peptide”. Thus fusion peptide activity is likely controlled by reorganization of the fusion platform, based on both hydrophobic (i.e. lipid-binding) and ionic (i.e. Ca2+) interactions. Despite the recent availability of S structures in their pre- fusion state, there remains a very limited mechanistic understanding of membrane fusion for the CoV family, or any structural information to correlate structural biology aspects of S to its function in membrane fusion. This information is critical to understanding viral pathogenesis and CoV emergence into the human population. We propose an integrated biophysical, biochemical, and in vivo approach to study the unique cleavage-activated regulation of CoV S protein, using Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) as primary models. We will use state-of-the-art spectroscopy and an innovative single particle tracking technique to study S protein fusion peptide function, and combine these with in vivo infectivity studies, including at BSL3, will allow a complete picture of CoV fusion activation. These approaches will reveal how structure and function vary depending on the key activators of S; i.e. receptor binding, protease availability and the local ionic environment. These studies will allow us to determine common principals that can be applied to all CoVs, moving the field forward with these innovative studies will provide critical knowledge about CoV entry and tropism needed to safeguard human health from an emerging pathogen likely to cause severe outbreaks, and for which few or no medical countermeasures exist.", "keywords": [ "Animals", "Binding", "Biochemical", "Biological Assay", "Biological Models", "Biophysics", "Cell fusion", "Cell membrane", "Cell surface", "Cells", "Charge", "Chimeric Proteins", "Cleaved cell", "Communicable Diseases", "Complex", "Coronavirus", "Coronavirus Infections", "Coronavirus spike protein", "Cryoelectron Microscopy", "Data", "Disease Outbreaks", "Ebola virus", "Electron Spin Resonance Spectroscopy", "Endosomes", "Environment", "Event", "Exposure to", "Family", "Goals", "HIV", "Health", "Human", "Hydrophobicity", "Infection", "Influenza Hemagglutinin", "Ions", "Knowledge", "Lead", "Lipid Bilayers", "Lipid Binding", "Lipids", "Mediating", "Membrane", "Membrane Fusion", "Methods", "Middle East Respiratory Syndrome", "Middle East Respiratory Syndrome Coronavirus", "Modeling", "Monitor", "Mutagenesis", "NMR Spectroscopy", "Nature", "Pathogenesis", "Pathway interactions", "Peptide Hydrolases", "Peptides", "Play", "Population", "Process", "Property", "Proteins", "Reaction", "Regulation", "Research Personnel", "Resources", "Role", "Route", "SARS coronavirus", "Severe Acute Respiratory Syndrome", "Site", "Spectrum Analysis", "Structure", "Structure-Activity Relationship", "Techniques", "Testing", "Tissues", "Tropism", "Viral", "Viral Fusion Proteins", "Viral Pathogenesis", "Virus", "Virus Receptors", "Zoonoses", "base", "biophysical techniques", "cell type", "emerging pathogen", "experimental study", "flexibility", "fluorescence microscope", "in vivo", "innovation", "medical countermeasure", "mutant", "novel", "novel coronavirus", "novel virus", "particle", "peptide I", "peptide structure", "protein function", "receptor", "receptor binding", "structural biology", "transmission process", "virus envelope" ], "approved": true } }, { "type": "Grant", "id": "15791", "attributes": { "award_id": "1R21AI186055-01A1", "title": "UTS-1401: A Novel Mitigator of Radiation Injury", "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": 32876, "first_name": "ANDREA L", "last_name": "DICARLO-COHEN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2027-07-31", "award_amount": 431750, "principal_investigator": { "id": 32877, "first_name": "Stephen L", "last_name": "Brown", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32878, "first_name": "FREDERICK Augustus", "last_name": "VALERIOTE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2633, "ror": "", "name": "HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Abstract: Our long term objective is to develop a new class of radiation mitigating agents with attractive chemical, physical and biological characteristics required to be an effective drug that can be distributed widely. We have identified a small molecule, UTS-1401 [5-(methylthiomethyl) isoxazole-3-carboxylic acid] which demonstrates mitigation of hematopoietic stem cell death when administered at either 24h or 48h following whole body irradiation (WBI). Using the endogenous spleen colony assay we demonstrated a significant mitigating effect (ratio of colony number with and without UTS-1401) when drug was given 24h or 48h after radiation. We have also recently demonstrated a significant radioprotection for both mouse survival and hematopoietic stem cells for this compound for up to 72h before irradiation (Valeriote et al, Radiation Research, 202:16-25, 2024). In this application, we propose to examine solely the mitigating effect to both the hematopoietic acute radiation syndrome (H-ARS) in specific aim 1 and the gastrointestinal acute radiation syndrome (GI-ARS) in specific aim 2 following WBI (with 5% bone marrow protection for specific aim 2). Swiss mice will receive a series of graded doses of WBI around the LD50 for both syndromes with and without the administration of 150 mg/kg UTS- 1401. The single dose of UTS-1401 being used in all studies is the highest dose administrable due to its aqueous solubility (in tartrate buffered saline). The radiation mitigation factors will be calculated as the ratio of the LD50 for radiation plus UTS-1401 versus radiation alone. The degree of mitigation will be examined at 24, 48 and 72 h following WBI to determine the timeframe of mitigation after radiation exposure. Three routes of drug delivery, intravenous (iv), oral, and subcutaneous (sc), will be examined and compared. For all specific aims, both male and female mice will be separately studied. Radiation will be delivered by electrons from a Linac. In specific aim 3, we will examine the pharmacokinetics (PK) for 150 mg/kg UTS-1401 comparing the iv, oral, and sc routes to obtain a determination of both the drug kinetics and bioavailability. The AUC values will be correlated with the extent of mitigation. Finally, in specific aim 4, we will address the mechanism of action with studies focused on the role of specific cytokines induced by radiation in the so-called “cytokine storm”. We will assess the time course changes of TNF-α, IL-1β, IL-6, CSF and TGF-β in blood as well as bone marrow and intestinal mucosa over 20 days following: UTS-1401 alone, 10 Gy irradiation, and the combination of UTS-1401 and radiation at a 24h interval. The results from these studies are expected to demonstrate an effective first-in-class compound, UTS-1401, which has a small molecular weight, is chemically stable, nontoxic, aqueous soluble and inexpensive with radiation mitigating properties which extend for a number of days following irradiation. The mechanism studies are expected to demonstrate UTS-1401 as a new class of agents for mitigating the cytokine storm consequent to the irradiation.", "keywords": [ "Animals", "Biologic Characteristic", "Biological", "Biological Assay", "Biological Availability", "Blood", "Bone Marrow", "Buffers", "Carboxylic Acids", "Cell Death", "Characteristics", "Chemicals", "Complex", "Data", "Development", "Dose", "Drug Delivery Systems", "Drug Kinetics", "Effectiveness", "Electrons", "Exposure to", "FDA approved", "Female", "Femur", "Formulation", "Gender", "Goals", "Hematopoietic", "Hematopoietic System", "Hematopoietic stem cells", "Hour", "Individual", "Inflammatory", "Interleukin-1 beta", "Interleukin-6", "Intestinal Mucosa", "Intestines", "Intravenous", "Ionizing radiation", "Isoxazoles", "Lethal Dose 50", "Measures", "Methods", "Molecular Weight", "Mus", "Nuclear", "Nuclear Accidents", "Nuclear Weapon", "Oral", "Pharmaceutical Preparations", "Plasma", "Property", "Radiation", "Radiation Accidents", "Radiation Dose Unit", "Radiation Injuries", "Radiation Protection", "Radiation Toxicity", "Radiation exposure", "Refrigeration", "Research", "Role", "Route", "Saline", "Sampling", "Series", "Solubility", "Spleen", "Swiss Mice", "Syndrome", "TNF gene", "Tartrates", "Technology", "Terrorism", "Testing", "Time", "Tissues", "Transforming Growth Factor beta", "United States National Institutes of Health", "War", "Weight", "Whole-Body Irradiation", "aqueous", "chemical stability", "cost effective", "cytokine", "cytokine release syndrome", "flexibility", "gastrointestinal", "gender difference", "intravenous administration", "irradiation", "male", "medical countermeasure", "mouse model", "novel", "radiation countermeasure", "radiation mitigation", "radiation mitigator", "radioprotected", "small molecule", "stem cells", "subcutaneous", "success" ], "approved": true } }, { "type": "Grant", "id": "12296", "attributes": { "award_id": "1C06OD036029-01", "title": "UNC BSL3 Core Facility", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 28173, "first_name": "YONG", "last_name": "Chen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-06", "end_date": "2028-05-31", "award_amount": 7916788, "principal_investigator": { "id": 28195, "first_name": "Craig A", "last_name": "Fletcher", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 817, "ror": "", "name": "UNIV OF NORTH CAROLINA CHAPEL HILL", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT: The central goal of this project is to construct a 10,000 square feet biosafety level 3 (BSL3) research laboratory core facility to promote readiness to respond to future pandemics. Infectious diseases pose a severe and increasing threat to human health, especially in communities that lack access to health care. UNC programs will soon exceed current infrastructure capacity due to increase demand. A strategic review of our microbial pathogenesis and infectious disease community concluded that urgent action was essential to support the high containment programs. Among the barriers to the growth of research was a lack of access to critical technologies and animal space within the existing BSL3 laboratories. This transformative BSL3 core facility will allow UNC to expand to meet current and projected research needs in the UNC School of Medicine, School of Pharmacy, and Gillings School of Global Public Health. UNC has engaged multiple stakeholders across the research community to design and construct a centralized BSL3 suite to characterize the immune responses to coronavirus and other emerging viral pathogens and learn about what drives immune response, disease progression, and protection against future infection. The proposal will attain four objectives: 1. Design and construct a high containment facility to bring investigators working on emerging and re-emerging infections together; 2. Enable access to specialized instrumentation including aerobiology and imaging equipment for supporting high containment research; 3. Create institution-wide core space to allow recruitment of new investigators to the infectious disease research community by increasing usable laboratory space in the BSL3 facility and purchasing new equipment that will serve investigators within the many UNC centers, institutes, and departments and their nationwide collaborators; 4. Enhance UNC's ability to lead the rapid response generating new therapeutics and vaccines to save lives on a local, national, and even global level.", "keywords": [ "Animals", "Communicable Diseases", "Communities", "Containment", "Core Facility", "Coronavirus", "Disease Progression", "Equipment", "Future", "Gills", "Goals", "Growth", "Health", "Human", "Image", "Immune response", "Infection", "Infectious Diseases Research", "Infrastructure", "Institution", "Laboratories", "Laboratory Research", "Learning", "Pathogenesis", "Pharmacy Schools", "Public Health", "Readiness", "Research", "Research Personnel", "Research Project Grants", "Schools", "Technology", "biosafety level 3 facility", "design and construction", "future pandemic", "health care availability", "instrumentation", "medical schools", "microbial", "novel therapeutics", "novel vaccines", "pathogenic virus", "programs", "recruit", "response", "square foot", "usability" ], "approved": true } }, { "type": "Grant", "id": "9214", "attributes": { "award_id": "3RM1HG009490-04S1", "title": "Center for Genome Editing and Recording", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Human Genome Research Institute (NHGRI)" ], "program_reference_codes": [], "program_officials": [ { "id": 24952, "first_name": "COLIN F", "last_name": "FLETCHER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-09-01", "end_date": "2021-05-31", "award_amount": 19236, "principal_investigator": { "id": 24218, "first_name": "JENNIFER A", "last_name": "DOUDNA", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 917, "ror": "", "name": "J. DAVID GLADSTONE INSTITUTES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1079, "ror": "", "name": "UNIVERSITY OF CALIFORNIA BERKELEY", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "UC Berkeley and the Doudna Lab are incredibly fortunate this year to organize the annual CEGS conference. The event falls at a time when we will be commemorating the 30th anniversary of the launch of the Human Genome Project and the publication of the NHGRI's new strategic plan. We think that this is an opportunity to strengthen the Program and NHGRI's global outreach and impact as we embark on a new era of science and technology. Indeed, as new fields emerge, the CEGS Program, and its researchers, will continue to evolve and create greater impact in the world. Furthermore, the COVID-19 pandemic brought great uncertainty among scientists and people across the world. While countries locked down, we saw many of our colleagues and fellow researchers starting collaborating and fiercely contributing to the growing issue. With no fewer than 400 participants this year, the CEGS conference is consequently an opportunity for true engagement at such a pivotal and momentous time. We do not want this conference to be a sequence of scientific reports and presentations. We want this conference to reflect the new NHGRI's strategic vision. We want to challenge our audience and engage them into conversations around ethics, technology, and diversity. Conversations that set a precedent not only for our research scope but for how we choose to engage with science at a societal level. There has never been a better time to encourage and facilitate these conversations. We have the great honor of doing so with some of the greatest minds in science and we want to take full advantage of this and provide all the necessary tools to create collaboration opportunities and set the stage for considerable scientific progress. In fact, it has been proven that projects centered in collaboration among researchers from different institutions are more frequently cited and novel. We think that the shelter-in-place and the mandate to make the CEGS conference “go virtual” gives us an opportunity to envision a different kind of conference — a conference that zeroes in on what motivates scientists to go to conferences in the first place: to share ideas, to forge collaborations, and to make connections. New formats and tools are now available so that researchers from all sorts of backgrounds and at a variety of career stages can interact, connect, and network. Given this, we can provide a space for conversation and innovation that would not otherwise be possible or likely in general assembly. This is why we favor a more reliable infrastructure accessible to all with a networking friendly user interface that is easy to navigate. We truly believe that the perceived “limitations” of a virtual meeting can actually put us at a great advantage. We are going to enable the technology afforded to us to realize these advantages. Our goal is to create real collaboration across disciplines, specialties, and levels of leadership. The event will be planned and executed with this ultimate goal in mind.", "keywords": [ "Anniversary", "COVID-19 pandemic", "Collaborations", "Country", "Discipline", "Ethics", "Event", "Goals", "Human Genome Project", "Infrastructure", "Institution", "Leadership", "Mind", "National Human Genome Research Institute", "Participant", "Publications", "Reporting", "Research", "Research Personnel", "Science", "Scientist", "Shelter facility", "Strategic Planning", "Technology", "Time", "Uncertainty", "Vision", "career", "falls", "genome editing", "innovation", "medical specialties", "meetings", "novel", "outreach", "programs", "symposium", "tool", "user-friendly", "virtual" ], "approved": true } }, { "type": "Grant", "id": "15675", "attributes": { "award_id": "1R01EB037031-01", "title": "Point-of-care DNA diagnostics from raw samples", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Biomedical Imaging and Bioengineering (NIBIB)" ], "program_reference_codes": [], "program_officials": [ { "id": 32518, "first_name": "KRISTIN HEDGEPATH", "last_name": "GILCHRIST", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-04-05", "end_date": "2029-03-31", "award_amount": 257807, "principal_investigator": { "id": 32519, "first_name": "Robert M", "last_name": "Cooper", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 760, "ror": "https://ror.org/0168r3w48", "name": "University of California, San Diego", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The proposed project will develop living biosensors for detecting and analyzing DNA at the single- base level, without requiring sample purification or any equipment. DNA is the prime information carrier for life, and DNA analysis provides valuable information for, e.g., diagnosing microbial infections or tracking disease outbreaks. Many techniques exist for detecting and analyzing DNA, but these generally require processing steps to extract and purify samples, and most require expensive equipment and significant training and expertise. This proposal will transfer that complexity into the biosensor itself, harnessing functions that evolved into living bacteria over billions of years to pull DNA out of raw samples, analyze it, and produce easily read output. The biosensors will pull in DNA using natural competence, and analyze it with single-base precision using their endogenous CRISPR-Cas system. Upon detecting a target sequence, the living biosensors will release thousands of signal molecules that can be detected using a lateral flow assay, similar to a consumer pregnancy or Covid-19 test. Several target DNA sequences will be used for demonstrations: urinary tract pathogens, E. coli, and Salmonella. The target uropathogens are difficult to diagnose with standard culture tests. Using single-base sequence analysis, the biosensors will subtype E. coli as likely pathogenic or likely commensal. A similar strategy will be employed to detect single-base mutations responsible for the majority of fluoroquinolone-resistant Salmonella isolates. DNA biosensing will be demonstrated in clinically relevant human samples, without the extensive purification required by other methods. The result will be a hybrid living biosensor / lateral flow assay that requires minimal sample preparation, produces rapid results, and can achieve single-base resolution. The biosensors developed in this project could find applications any time DNA monitoring is needed that is inexpensive, requires minimal sample preparation, equipment, and expertise, or takes place at the point of care. Examples include clinical diagnostics, monitoring disease outbreaks for public health, or environmental monitoring, with particular benefits where resources are limited.", "keywords": [ "Antibiotic Resistance", "Architecture", "Bacteria", "Base Sequence", "Binding", "Biological", "Biological Assay", "Biosensing Techniques", "Biosensor", "Blood", "Buffers", "COVID-19 test", "Clinic", "Clinical", "Clustered Regularly Interspaced Short Palindromic Repeats", "Colon", "Colorectal Neoplasms", "Competence", "Complex", "Coupled", "Custom", "DNA", "DNA Sequence", "DNA analysis", "Detection", "Diagnosis", "Diagnostic", "Disease Outbreaks", "Engineering", "Ensure", "Environment", "Environmental Monitoring", "Epitopes", "Equipment", "Escherichia coli", "Genetic", "Genomic DNA", "Goals", "Human", "Hybrids", "In Situ", "In Vitro", "Infection", "Lateral", "Life", "Medical", "Methods", "Monitor", "Mus", "Mutation", "Mutation Detection", "Oncogenic", "Output", "Pathogenicity", "Performance", "Pregnancy Tests", "Preparation", "Proteins", "Public Health", "Publishing", "RNA", "Rapid diagnostics", "Readability", "Reporter", "Resolution", "Resource-limited setting", "Resources", "Salmonella", "Salmonella enterica", "Sampling", "Scheme", "Science", "Sensitivity and Specificity", "Sequence Analysis", "Signal Transduction", "Signaling Molecule", "Source", "Specificity", "Sputum", "Synthetic Genes", "System", "Techniques", "Testing", "Time", "Training", "Urinary tract", "Urinary tract infection", "Urine", "Uropathogen", "Work", "base", "cancer cell", "clinical diagnostics", "clinically relevant", "cost", "diagnostic platform", "fluoroquinolone resistance", "improved", "in vivo", "interest", "lateral flow assay", "microbial", "nanoshell", "pathogen", "point of care", "point-of-care diagnostics", "screening", "tumor" ], "approved": true } }, { "type": "Grant", "id": "5891", "attributes": { "award_id": "3R21AI144315-02S1", "title": "Mechanisms of immune dysregulation in human PI3Kgamma deficiency", "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": 20158, "first_name": "Deborah", "last_name": "Hodge", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-08-14", "end_date": "2021-12-31", "award_amount": 125624, "principal_investigator": { "id": 20159, "first_name": "Carrie L.", "last_name": "Lucas", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "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": "Primary immunodeficiency diseases (PIDs) have great potential to provide mechanistic insights into the molecules and pathways fundamentally important for maintenance of human immune health, and the unbiased nature of forward genetics makes these studies particularly exciting to pursue. The phosphoinositide 3-kinase (PI3K) signaling pathway plays important roles in many aspects of cell behavior within and outside the immune system. Both gain-of-function and loss-of-function mutations in the genes encoding the p110δ and p85α PI3K subunits have been identified in PID patients and have shed light on basic PI3K biology and underpinnings of inherited immunodeficiency. However, no mutations in the other PI3K genes have been described in inherited human disorders. We have now identified novel loss-of-function mutations in a new PI3K gene, PIK3CG, and our preliminary studies highlight its importance in immune competence and regulation of tissue inflammation in this disorder we have termed Inactivated PI3Kγ Syndrome (IPGS). Using primary human cells and cutting-edge `dirty' mouse modeling approaches that recapitulate human disease by combining genetic manipulation and natural pathogen exposure, two specific aims will be pursued. Aim 1) To define the roles for PI3Kγ in regulating T cell-intrinsic and -extrinsic signals that modulate T cell activation and differentiation. Aim 2) To dissect the mechanistic basis for antibody defects. The results of these investigations will provide significant insights into this novel PID and PI3K signaling in general and will lay the groundwork to improve physiologically relevant models for translational research in PIDs and other human disease contexts.", "keywords": [ "Antibodies", "Antibody Formation", "Antibody Response", "Asthma", "Autoimmune", "Autoimmune hemolytic anemia", "Autoimmunity", "BLR1 gene", "Binding", "Biochemical", "Biology", "CD3 Antigens", "CD4 Positive T Lymphocytes", "CXCL10 gene", "CXCL9 gene", "CXCR3 gene", "Catalytic Domain", "Cell Line", "Cells", "Chemotactic Factors", "Clinical", "Complex", "Critical Pathways", "Defect", "Development", "Disease", "Equilibrium", "Exhibits", "Exposure to", "G-Protein-Coupled Receptors", "Genes", "Genomic DNA", "Goals", "Housing", "Human", "Human Biology", "Hypersensitivity", "Immune", "Immune System Diseases", "Immune system", "Immunocompetence", "Immunologic Deficiency Syndromes", "In Vitro", "Individual", "Infection", "Infiltration", "Inflammation", "Inflammatory", "Inherited", "Interleukin-12", "Investigation", "Letters", "Leukocytes", "Light", "Link", "Loss of Heterozygosity", "Lung", "Lymphocyte", "Maintenance", "Modeling", "Mononuclear", "Mus", "Mutation", "Myeloid Cells", "Nature", "PASLI disease", "PIK3CG gene", "Pathologic", "Pathway interactions", "Patients", "Pattern", "Phagocytes", "Phenotype", "Phosphatidylinositols", "Phosphotransferases", "Physiological", "Play", "Process", "Production", "Proteins", "Reporting", "Resources", "Role", "Serum", "Signal Pathway", "Signal Transduction", "Stimulus", "Structure of germinal center of lymph node", "Syndrome", "T cell differentiation", "T cell response", "T-Cell Activation", "T-Lymphocyte", "Testing", "Th1 Cells", "Therapeutic", "Tissues", "Translational Research", "Tumor-infiltrating immune cells", "Work", "cell behavior", "chemokine", "clinical phenotype", "congenital immunodeficiency", "cytokine", "cytopenia", "exome sequencing", "forward genetics", "gain of function", "gain of function mutation", "genetic manipulation", "human disease", "human model", "hypogammaglobulinemia", "immune health", "immunoregulation", "improved", "in vivo", "innovation", "insight", "interleukin-23", "loss of function mutation", "macrophage", "monocyte", "mouse model", "next generation sequencing", "novel", "pathogen", "pathogen exposure", "patient response", "peripheral blood", "polarized cell", "profiles in patients", "public health relevance", "response", "translational model", "unpublished works" ], "approved": true } } ], "meta": { "pagination": { "page": 1393, "pages": 1419, "count": 14184 } } }