NIH_SPENDING_CATS: Regenerative Medicine;Wound Healing and Care

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Narrative We investigate the chemical and physical mechanisms by which animal tissues rapidly detect wounds, and initiate inflammation, resolution, repair, and regeneration in response. Failure in wound detection can cause acute and chronic conditions ranging from poorly healing wounds and infections to chronically inflamed skins, fibrosis and cancer. Understanding the underlying mechanisms will pave way for new therapies for these conditions.

PI_NAMEs: NIETHAMMER, PHILIPP MICHAEL (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Acute;animal tissue;Animals;Arachidonic Acids;Area;Biological;Biology;Biophysics;Bone Regeneration;Cells;Chemicals;Chronic;cytokine;Detection;Diffuse;Disease;Epithelium;extracellular;Failure;Fibrosis;flexibility;Funding;Growth Factor;healing;Hydrogen Peroxide;Image Analysis;Immune system;Infection;Inflammation;Inflammatory Response;Injury;interdisciplinary approach;interest;intravital imaging;Leukocytes;Malignant Neoplasms;Mammals;mathematical model;mechanotransduction;Mediating;Medical;Molecular;Natural regeneration;novel therapeutic intervention;novel therapeutics;Nuclear Envelope;Organism;Pathway interactions;Process;rapid detection;real-time images;repaired;Resolution;response;response to injury;Scheme;Signal Transduction;Skin;Tissues;transmission process;Vision;Work;wound;wound closure;wound healing;Wound models;wound response;Zebrafish

PROJECT_TITLE: Chemical and Physical Mechanisms of Wound Detection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-J(55)R]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Dental, Oral, and Craniofacial Disease;Genetics;Hematology;Pediatric;Pediatric Cancer;Prevention;Rare Diseases

ORG_CITY: CINCINNATI

ORG_COUNTRY: UNITED STATES

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CINCINNATI

ORG_STATE: OH

PHR: Project Narrative The molecular and metabolic processes that drive cancer cells to rapidly divide, invade, and metastasize dictate patient outcomes, treatment options, and quality of life. This study will address how loss of the Fanconi Anemia (FA) DNA repair pathway promotes the rapid development of aggressive head and neck squamous cell carcinoma (HNSCC) by re-wiring metabolism. In doing so, this project will establish a novel link between aberrant DNA damage repair and stimulation of 1-carbon (1C) metabolism, and define the therapeutic potential of targeting 1C metabolism to prevent progression of FA-deficient HNSCC.

PI_NAMEs: RUFFOLO, BIANCA  (contact)

PROGRAM_OFFICER_NAME: DAMICO, MARK W

PROJECT_TERMS: 3-Dimensional;Actins;Animals;Automobile Driving;Biological Models;Biomass;Cancer Biology;cancer cell;Carbon;Career Choice;Cell Line;Cell Proliferation;Cells;Cessation of life;Cheek structure;Chemicals;Clinical;college;crosslink;Cytoskeleton;Data;design;Development;Dietary Intervention;Disease;disease phenotype;DNA Interstrand Cross-Link Repair;DNA Repair;DNA Repair Pathway;DNA-dependent protein kinase;doctoral student;Engineering;Enzyme Tests;Enzymes;Epigenetic Process;Epithelium;experimental study;Fanconi Anemia pathway;Fanconi's Anemia;Folic Acid;folic acid metabolism;Formates;G(M3) Ganglioside;Gangliosides;General Population;Genes;Genomic Instability;Glycosphingolipids;Goals;graduate student;Growth;Guanosine Triphosphate Phosphohydrolases;Head and Neck Squamous Cell Carcinoma;Immunodeficient Mouse;In Vitro;in vivo;Inherited;inhibitor;Invaded;keratinocyte;knock-down;Laboratories;Lead;Link;loss of function mutation;Loss of Heterozygosity;Malignant Neoplasms;Measures;Medical center;Medicine;Mesenchymal;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Methotrexate;migration;Modeling;Modification;Molecular;molecular phenotype;monolayer;Mucous Membrane;Mutation;Neoplasm Metastasis;Nonhomologous DNA End Joining;nonsynonymous mutation;Normal Cell;novel;Outcome;Pathway interactions;Patient-Focused Outcomes;Patients;Pediatric Hospitals;Phenotype;Predisposition;prevent;Prevention;Process;Production;Prognosis;Proxy;Quality of life;Recurrence;Research;Research Project Grants;Role;Serine;Signal Pathway;Signal Transduction;Specificity;spheroids;Squamous cell carcinoma;stable isotope;System;Testing;Tetrahydrofolates;Therapeutic;therapeutic candidate;therapeutic target;Tracer;Transplantation;tumor;tumor behavior;tumor growth;tumor metabolism;tumor progression;Universities;Up-Regulation;Xenograft Model

PROJECT_TITLE: Metabolic reprogramming in Fanconi anemia-deficient head and neck squamous cell carcinoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09A-R (20)]


ADMINISTERING_IC: DA

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Genetics;Neurosciences;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: LEXINGTON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE Tobacco smoking is a leading cause of preventable death in the US, though most smokers who would like to quit are unable to do so with current available therapeutics. The molecular mechanisms underlying the failed successes of smokers attempting to quit remain a critical gap in our knowledge. This proposal aims to elucidate the roles of a novel signaling pathway (NRG3-ErbB4) during nicotine use and withdrawal in hopes of developing better therapeutics for nicotine dependence by specifically targeting affective disruption, thereby improving smoking cessation and outcomes.

PI_NAMEs: PRANTZALOS, EMILY  (contact)

PROGRAM_OFFICER_NAME: BABECKI, BETH

PROJECT_TERMS: Acoustics;addiction;Affective;animal tissue;Anxiety;anxiety-like behavior;Behavior;Behavioral;behavioral outcome;behavioral phenotyping;behavioral response;Biomedical Research;career;Chronic;college;Darkness;Data Analyses;Dedications;design;Development;Dimensions;Drosophila acetylcholine receptor alpha-subunit;EGF gene;ErbB4 gene;exhibitions;Exhibits;experience;Experimental Designs;experimental study;Exposure to;extracellular;Fellowship;field study;Functional disorder;Future;Genes;Genetic;Genetic study;Genetic Transcription;Goals;Government;graduate student;Hippocampus;improved;Individual;Industrialization;Injections;innovation;insight;interdisciplinary approach;Interruption;Kentucky;kinase inhibitor;knock-down;Knowledge;Ligands;Light;Link;Location;Mediating;member;Mental disorders;Mentors;Molecular;mouse model;mRNA Expression;multidisciplinary;Mus;neural;Neuregulins;neuroadaptation;Neurobiology;Neuropharmacology;new therapeutic target;Nicotine;Nicotine Dependence;nicotine treatment;nicotine use;Nicotine Withdrawal;Nicotinic Receptors;novel;NRG3 gene;Outcome;Pattern;Pharmaceutical Preparations;pharmacologic;Pharmacologic Substance;Pharmacotherapy;Pharmacy facility;Phenotype;Phosphotransferases;Precision therapeutics;Prefrontal Cortex;preventable death;programs;protein expression;psychiatric comorbidity;receptor;Receptor Protein-Tyrosine Kinases;Research;Reverse Transcriptase Polymerase Chain Reaction;Role;Science;Signal Pathway;Signal Transduction;Site;skills;Smoker;smoking cessation;Startle Reaction;Substance Use Disorder;success;Techniques;Testing;Therapeutic;Time;Tobacco smoking behavior;Training;Universities;Variant;Western Blotting;Withdrawal;Work

PROJECT_TITLE: Role of Dynamic Signaling of NRG3-ErbB4 in the Prefrontal Cortex in Mediating Nicotine Withdrawal Phenotypes

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03B-L (20)]


ADMINISTERING_IC: DK

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biotechnology;Digestive Diseases

ORG_CITY: MALVERN

ORG_NAME: PROGENRA, INC.

ORG_STATE: PA

PHR: Pancreatitis is an inflammatory disorder of the pancreas that is associated with high morbidity and mortality. No effective disease modifying therapy is available. One novel approach is to harness mitochondrial mechanisms to treat both acute and chronic pancreatitis. We have identified important roles for ubiquitin mediated regulation of mitochondrial health as a protective mechanism against pancreatitis. In this project we propose to fully leverage prior discoveries and to focus on developing novel disease modifying therapy for treating pancreatitis by modulating ubiquitin pathway and improving mitochondrial health.

PI_NAMEs: SURESH, KUMAR  (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: Acinar Cell;acute pancreatitis;Agonist;Animal Model;Autophagocytosis;Binding;Biological Assay;Calcium;Calcium Channel;Cardiac Myocytes;cell injury;Cell model;Cell Physiology;Cells;Cervix Carcinoma;chronic pancreatitis;cytotoxicity;Data;Development;Disease;drug discovery;enzyme pathway;Enzymes;Excision;experience;Fibroblasts;Fluorescence Resonance Energy Transfer;Goals;Grant;Health;healthspan;high throughput screening;Hospitals;Human;human induced pluripotent stem cells;Hyperactivity;Impairment;improved;In Vitro;in vivo;in vivo Model;induced pluripotent stem cell derived cardiomyocytes;Inflammatory;inhibitor;Kidney;Knock-in Mouse;Knockout Mice;life span;Mediating;Medical;Membrane Potentials;Mitochondria;mitochondrial membrane;Modeling;Molecular;Morbidity - disease rate;mortality;multicatalytic endopeptidase complex;Mus;Neuroblastoma;novel;novel strategies;novel therapeutics;overexpression;Pancreas;Pancreatic Diseases;Pancreatitis;Parkin;Pathway interactions;Phase;Phosphotransferases;PINK1 gene;PPAR gamma;preclinical development;Process;Production;Rattus;Regulation;research clinical testing;Resistance;Role;Safety;Small Business Innovation Research Grant;small molecule;small molecule libraries;Specificity;stressor;System;Therapeutic;Therapeutic Agents;Therapeutic Effect;Time;Ubiquitin;ubiquitin-protein ligase;Ubiquitination;Variant

PROJECT_TITLE: Ubiquitin pathway modulators for treating pancreatitis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 KUDS-R (10)]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse;Suicide

ORG_CITY: KINGSTON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF RHODE ISLAND

ORG_STATE: RI

PHR: Project Narrative  Due to small sample sizes and the persistent aggregation of Asian American and Pacific Islander data, there is a significant dearth of research on substance use and suicidal ideation in Native Hawaiian/Pacific Islander adults. The proposed project will: (1) provide essential training in conducting ethical research and collaborating with this highly minoritized community and (2) use a sequential mixed-methods methodology paired with community-based participatory research to explore the relationships between substance use, suicidal ideation, and historical trauma among Native Hawaiian/Pacific Islanders. Results will fill significant gaps in the extant literature related to health disparities within this understudied community.

PI_NAMEs: EGAN, ALANA  (contact)

PROGRAM_OFFICER_NAME: KURAMOTO-CRAWFORD, SATOKO JANET

PROJECT_TERMS: Adult;Advocacy;Asian Americans;Asian Pacific American;Asian Pacific Islander;Behavior;career;Categories;Collaborations;Communities;community advisory board;community based participatory research;Community Health;comorbidity;contextual factors;Data;demographics;Development;doctoral student;Educational Status;Environment;Equation;Ethics;European;Evidence based practice;Evidence based treatment;experience;Feeling suicidal;Focus Groups;Foundations;Funding;Future;Goals;Grant;Group Interviews;Health;health data;health disparity;improved;Individual;innovation;Intervention;Interview;Island;Learning;lens;Literature;low socioeconomic status;Measures;Mentorship;Methodology;Methods;minority communities;Minority Groups;model development;Modeling;Modernization;National Institute of Drug Abuse;Native Hawaiian;Native-Born;Pacific Island Americans;Pacific Islander;Participant;Persons;Policies;Population;Prevalence;Principal Investigator;Public Health;Reduce health disparities;reduced substance use;Research;Research Design;Research Methodology;Research Personnel;Research Training;Rhode Island;Role;Sample Size;Sampling;Severities;skills;social factors;State Government;Strategic Planning;Structure;substance use;suicidal behavior;suicidal risk;Suicide;Targeted Research;Technology;Testing;tool;Training;training opportunity;Translating;Trauma;Underserved Population;United States;United States National Institutes of Health;Universities;Work;Youth

PROJECT_TITLE: The Relationship Between Historical Trauma, Substance Use, and Suicidal Ideation in Native Hawaiian/Pacific Islander Adults: A Mixed-Methods Approach

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F16-H (20)]


ADMINISTERING_IC: NS

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences;Parkinson's Disease;Women's Health Research

ORG_CITY: NEW YORK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE The proposed studies will provide new details about the earliest pathophysiologically-driven changes in cholinergic innervation and signaling in prefrontal cortex of males and females and the impact of such early changes in cognitive decline associated with a Parkinson’s-linked mutation in LRRK2. These studies will reveal potentially new targets of early disease pathophysiology, define sex-specific differences in anatomical and behavioral trajectories, and characterize changes with age, potentially influencing diagnostics and treatments for a variety of neurodegenerative disorders in which early mild cognitive impairment is manifest.

PI_NAMEs: BENSON, DEANNA L;HUNTLEY, GEORGE W. (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Acetylcholine;Acetylcholinesterase Inhibitors;Address;Adult women;Age;age effect;age related changes;aged;Alzheimer's Disease;Alzheimer's disease related dementia;Anatomy;Area;Attention;Attentional deficit;Axon;Behavioral;Biochemical;biomarker identification;Biosensor;Birth;Caregivers;Cell Death;Cells;cholinergic;cholinergic neuron;Cholinergic Receptors;Clinical;clinical diagnosis;Cognition;Cognitive;cognitive change;cognitive control;Cognitive deficits;cognitive function;cognitive performance;cognitive reappraisal;cognitive task;Data;Dementia;dementia risk;density;Diagnostic;Disease;disorder risk;donepezil;early onset;Electrophysiology (science);executive function;experimental study;Female;Fiber;Functional disorder;Gene Mutation;Genetic;genetic risk factor;Goals;Human;Idiopathic Parkinson Disease;Impaired cognition;Impairment;improved;information processing;Inherited;Injections;insight;Intervention;Knock-in;Label;life span;Link;LRRK2 gene;male;Medial;Mediating;men;mild cognitive impairment;Modeling;Motivation;Motor;motor symptom;mouse model;Mus;Muscarinic Acetylcholine Receptor;mutant;Mutant Strains Mice;Mutation;nerve supply;Nervous System Disorder;Neurobehavioral Manifestations;Neurobiology;Neurodegenerative Disorders;Neurons;neuropathology;neurophysiology;Nicotine;Nicotinic Receptors;Operant Conditioning;Optics;optogenetics;Outcome;Parkinson Disease;Pathogenicity;Pathway interactions;Patients;Pattern;Performance;pharmacologic;Phosphotransferases;Photometry;Precision therapeutics;Prefrontal Cortex;preservation;prevent;processing speed;Quality of life;Receptor Signaling;remediation;response;Risk;Sensory;sex;Sex Differences;sexual dimorphism;Signal Transduction;Smoking;targeted treatment;Task Performances;Testing;Therapeutic Agents;Therapeutic Intervention;Time;touchscreen;Woman;young adult

PROJECT_TITLE: Investigating the Neurobiology of Early Cognitive Impairment

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ADMINISTERING_IC: EY

ED_INST_TYPE: GRADUATE SCHOOLS

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Aging;Bioengineering;Biotechnology;Eye Disease and Disorders of Vision;Gene Therapy;Genetics;Nanotechnology;Neurodegenerative;Neurosciences

ORG_CITY: FORT WORTH

ORG_NAME: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR

ORG_STATE: TX

PHR: Project Narrative Our proposed project seeks to address the limitations of current therapies for glaucoma, which suffer from poor bioavailability, limited specificity, and delivery barriers. Leveraging the unique properties of reconstituted high-density lipoprotein (rHDL) nanoparticles and a custom-made cholera toxin B subunit (CTB) – fatty acid conjugate, we aim to develop rHDL-ApoAI-CTB nanoparticles (rHAC NPs) with enhanced specificity for retinal ganglion cells (RGCs) by binding to GM1 gangliosides and the scavenger receptor class B1 (SR-B1) as dual targets. Compared to rHDL NPs, rHAC NPs have improved drug delivery capabilities and effectively penetrate biological barriers, leading to improved treatment outcomes for this debilitating disease.

PI_NAMEs: PETTY, ROLAND MAX (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: Address;Adult;Affect;Aftercare;Aging;Animal Model;Apolipoprotein A-I;Apoptotic;Binding;Biodistribution;Biological;Biological Assay;Biological Availability;biophysical properties;Blindness;Blood - brain barrier anatomy;Cell Separation;Cell Survival;cell type;Cells;Cessation of life;Cholera Toxin Protomer B;Custom;cytotoxicity;Development;Disease;Disease Progression;Dissociation;Dose;Drug Delivery Systems;Effectiveness;efficacy evaluation;Electroretinography;Encapsulated;Endothelin;Endothelin Receptor Antagonist;Endothelin-1;Ensure;experience;Eye;Fatty Acids;FDA approved;Fluorescent Dyes;Formulation;Ganglioside GM1;Gangliosides;Glaucoma;Half-Life;Health Care Costs;High Density Lipoproteins;Human;immunogenic;improved;In Vitro;in vivo;insight;Laboratories;Lecithin;Ligands;light scattering;Link;lipophilicity;MAPK8 gene;Mediating;Methodology;Methods;Modeling;Morphology;nanolipoprotein particles;nanoparticle;nanoparticle delivery;neoplastic cell;Nerve Degeneration;neuroprotection;Neuroprotective Agents;novel;novel strategies;novel therapeutics;Ocular Hypertension;Optic Nerve;Oral;Pathogenesis;Patient-Focused Outcomes;Pattern;Penetration;Peptides;Persons;Pharmaceutical Preparations;Phospholipids;Physiologic Intraocular Pressure;Pilot Projects;Preparation;prevent;Process;Property;Publishing;pup;Rattus;Rattus norvegicus;receptor;reconstitution;Regimen;response;Retina;Retinal Ganglion Cells;Rodent;scavenger receptor;Signal Transduction;Specificity;Spectrophotometry;Sprague-Dawley Rats;Stains;Surface;System;targeted delivery;Therapeutic;therapy development;Tissues;Topical application;Transmission Electron Microscopy;transmission process;Treatment outcome;uptake;Vasoconstrictor Agents;Vision;Visual;Visual evoked cortical potential;Visual Fields;Visual impairment;Western Blotting;Work

PROJECT_TITLE: Development of Reconstituted High-Density Lipoprotein Nanoparticles for Targeted Delivery of Neuroprotective Agents to Retinal Ganglion Cells


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: Program Narrative The inability to perturb, and then study the effects of specific immune pathways in humans has been a major limitation to alleviating the morbidity and mortality associated with infectious disease. In this Cooperative Center for Human Immunology, we “capture the human experiment” through focused profiling of the human immune system following key immune perturbations where the timing and nature of the perturbation can be carefully controlled or documented. Specifically, we will investigate persistent immune defects following acute viral infection with SARS-CoV-2 that contribute to Post-Acute Sequelae of COVID-19, long lasting defects developed during chronic HCV infection that persist even beyond cure, and alterations in vaccine responses in the context of precision PD-1-targeted immunotherapy.

PI_NAMEs: CHUNG, RAYMOND T (contact);LAUER, GEORG MICHAEL;WHERRY, E. JOHN

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: 2019-nCoV;Acute;Address;anti-PD-1;Antigens;antiviral immunity;Automobile Driving;Biological Models;Blood;CD8-Positive T-Lymphocytes;cell type;Cells;Chronic;Chronic Disease;Chronic Hepatitis C;chronic infection;Cicatrix;Clinical;cohort;Communicable Diseases;Complex;COVID-19;Database Management Systems;Defect;Development;Disease;experimental study;Fine needle aspiration biopsy;Fingerprint;fitness;Foundations;Goals;Health;Hepatitis C;Hepatitis C virus;high dimensionality;Human;human model;Immune;immune activation;immune health;Immune response;Immune system;Immune System Diseases;Immunity;Immunologic Memory;Immunology;immunoreaction;Immunotherapy;Infection;Inflammation;insight;Institutional Review Boards;Knowledge;latent virus activation;Learning;Link;Liver;lymph nodes;Maps;Morbidity - disease rate;mortality;Myeloid Cells;Nature;Pathogenesis;Pathologic;Pathway interactions;Patients;PD-1 pathway;Positioning Attribute;Post-Acute Sequelae of SARS-CoV-2 Infection;Productivity;programmed cell death protein 1;programs;Reaction;reactivation from latency;Resolution;Resources;response;RNA vaccine;sample collection;Sampling;Serology;Specimen;Standardization;Study Subject;Sum;System;Testing;Tissues;Vaccination;vaccine response;Vaccines;Viral;Virus;Virus Diseases;Vision;Work

PROJECT_TITLE: Durable Alteration of the Human Immune system after Infection or Immunotherapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 AM-I (J1)]


NIH_SPENDING_CATS: Coronaviruses;Immunotherapy

PI_NAMEs: CHUNG, RAYMOND T (contact)

PROJECT_TERMS: Administrative Personnel;Complex;gastrointestinal;General Hospitals;Goals;Group Meetings;Human;Human Resources;Immune;Immune system;Immunotherapy;Infection;Laboratories;Liver;Manuscripts;Massachusetts;material transfer agreement;meetings;Preparation;Principal Investigator;programs;Progress Reports;Publications;Reporting;Research Personnel;Resolution;Resource Sharing;Scientist;Speed;Structure;symposium;Travel;Visit

PROJECT_TITLE: Core A: Administrative Core


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Coronaviruses;Coronaviruses Therapeutics and Interventions;Coronaviruses Vaccines;Digestive Diseases;Emerging Infectious Diseases;Hepatitis;Hepatitis - C;Immunization;Immunotherapy;Infectious Diseases;Liver Disease;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID;Prevention;Vaccine Related

PHR: PROJECT NARRATIVE Furthering our understanding of the human immune system is dependent on availability of adequate research specimens from well-defined clinical cohorts of patients. Our group of researchers have built a robust infrastructure for recruiting key groups of patients who are undergoing real-world perturbations such as PASC, chronic viral infection, and immune therapies and have an expansive resource of immune cells in our biobanks. From these resources, a wide variety of experiments can be performed that will reveal the intricacies of our immune response against viruses and augment our ability to modulate our immune system or optimize vaccines.

PI_NAMEs: KIM, ARTHUR Y (contact)

PROJECT_TERMS: 2019-nCoV;Acute;Affect;Animal Model;anti-PD-1;Anti-viral Agents;Area;biobank;Biology;Blood;Catalogs;Cells;Chronic;chronic infection;Cicatrix;Clinical;Clinical Data;clinically relevant;cohort;Collection;comparison control;COVID-19 pandemic;COVID-19 patient;Cross-Sectional Studies;Data;Databases;design;Development;Dissection;Drug or chemical Tissue Distribution;empowerment;Enrollment;Excision;exhaustion;experimental study;Face;Generations;Goals;healing;Hepatitis B Virus;Hepatitis C;Hepatitis C virus;Human;human tissue;Immune;Immune checkpoint inhibitor;immune health;Immune response;Immune system;Immune System Diseases;Immunity;Immunobiology;Immunologic Memory;Immunologics;Immunology;immunoregulation;Immunotherapy;Infection;Influenza vaccination;influenza virus vaccine;Infrastructure;insight;Investigation;Left;Liver;longitudinal analysis;lymph nodes;Malignant Neoplasms;Measures;Molds;Nature;novel;Outcome;pathogenic virus;Pathway interactions;Patient Recruitments;Patients;PD-1 blockade;PD-1 pathway;Peripheral Blood Mononuclear Cell;Plasma;Post-Acute Sequelae of SARS-CoV-2 Infection;programmed cell death protein 1;Recording of previous events;recruit;repository;Research;Research Personnel;Resources;response;RNA vaccine;RNA Viruses;Role;sample collection;Sampling;Serology;Serum;Specimen;standard of care;Standardization;Structure of germinal center of lymph node;T-Lymphocyte;Therapeutic;Tissue Banks;Tissue Sample;Tissues;Translating;Translational Research;Vaccination;vaccine immunogenicity;Vaccines;Virus;Virus Diseases

PROJECT_TITLE: Core B: Clinical Core


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Vaccines;Digestive Diseases;Emerging Infectious Diseases;Hepatitis;Hepatitis - C;Immunization;Immunotherapy;Infectious Diseases;Liver Disease;Machine Learning and Artificial Intelligence;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID;Prevention;Vaccine Related

PHR: Project Narrative Non-genetic influences, like viral infections and environmental factors, shape the human immune system. It is not, however, clear how this heterogeneity influences responses future events, like vaccination or immunotherapy. Core C will perform high dimensional immune profiling with integrated analysis on all clinical samples to identify immunotypes associated with disease.

PI_NAMEs: GREENPLATE, ALLIE  (contact)

PROJECT_TERMS: 2019-nCoV;Acute;anti-PD-1;anti-PD1 therapy;Antibodies;antigen-specific T cells;Antigens;Autoantibodies;Autoantigens;B-Lymphocytes;Bar Codes;Blood;CD8-Positive T-Lymphocytes;cell type;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;chronic infection;Cicatrix;Clinical;Collection;cytokine;Cytomegalovirus;Cytometry;Data;Data Analyses;data infrastructure;Data Reporting;deep neural network;Disease;Environmental Risk Factor;Event;fitness;flu;Fluorescence;Foundations;Freeze Drying;Freezing;Frequencies;Funding;Future;Goals;Grant;Hepatitis C;Hepatitis C virus;Heterogeneity;high dimensionality;Human;Human Herpesvirus 4;Immune;immune health;Immune response;Immune system;Immunoglobulin Somatic Hypermutation;Immunologic Monitoring;Immunotherapy;Infection;inflammatory milieu;Influenza;Infrastructure;Intervention;Leukocytes;Libraries;Link;Maps;Measurement;Measures;Mission;Monoclonal Antibodies;Multicenter Studies;Myeloid Cells;non-genetic;Oligonucleotides;Pathway Analysis;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Population;Post-Acute Sequelae of SARS-CoV-2 Infection;programs;Quality Control;receptor binding;Recording of previous events;recurrent neural network;Reporting;repository;response;RNA vaccination;Sampling;Serology;Serum;Services;Shapes;single cell analysis;single cell sequencing;Specificity;Standardization;statistics;Structure of germinal center of lymph node;Study Subject;systemic inflammatory response;T-Cell Immunologic Specificity;Testing;Time;Tube;Vaccination;vaccine trial;vaccine-induced antibodies;Vaccines;Variant;Viral;Viral Antibodies;Virus;Virus Diseases

PROJECT_TITLE: Core C: Immune Monitoring Core


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Emerging Infectious Diseases;Immunotherapy;Infectious Diseases;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID

PHR: Project Narrative Post-Acute Sequelae of COVID-19 (PASC) affects ~20M Americans with long-term, often crippling, symptoms. Although PASC is now well-described clinically, the immune mechanisms are poorly-understood. Here, we will test the hypothesis that PASC is caused by viral persistence driving virus-specific immunological abnormalities in innate and adaptive immunity.

PI_NAMEs: LOCCI, MICHELA  (contact)

PROJECT_TERMS: 2019-nCoV;acute COVID-19;acute infection;adaptive immune response;adaptive immunity;Address;Affinity;American;Antigens;Autoimmunity;Automobile Driving;Autonomic Dysfunction;autoreactivity;B-Lymphocytes;Biological Assay;Biology;Biosensor;Blood;brain fog;Cardiovascular system;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Compartmentation;Cell Differentiation process;Cell Physiology;Characteristics;Chronic;chronic infection;Clinical;cost;COVID-19;COVID-19 impact;COVID-19 patient;Cytometry;Development;Disease;distraction;Economic Burden;Economics;Epigenetic Process;Event;Exertion;Exposure to;Fatigue;Financial Hardship;Fine needle aspiration biopsy;Flow Cytometry;flu;Foundations;Gene Expression Profiling;high dimensionality;Hospitalization;Human;Human Herpesvirus 4;Immune;Immune response;Immune system;Immunologic Stimulation;Immunologics;Immunotherapy;imprint;In Vitro;Individual;Infection;Inflammation;Inflammation Mediators;insight;Kinetics;latent virus activation;Link;lymph nodes;Malaise;Maps;Medical;Medical Care Costs;Memory;Modeling;monocyte;Morbidity - disease rate;mortality;Myeloid Cells;Myeloid-derived suppressor cells;Natural Immunity;Neurologic Symptoms;Pathogenesis;Persons;plasma cell differentiation;Population;Post-Acute Sequelae of SARS-CoV-2 Infection;programs;reactivation from latency;Recording of previous events;Reporting;response;Role;Sampling;SARS-CoV-2 infection;Services;single-cell RNA sequencing;Structure of germinal center of lymph node;Symptoms;synergism;T cell differentiation;T cell response;T-Cell Activation;Testing;Therapeutic;Vaccination;Viral;viral RNA;Virus;Virus Diseases;Virus Latency;Work

PROJECT_TITLE: Project 1: Durable impact of COVID on innate and adaptive immunity


NIH_SPENDING_CATS: Coronaviruses;Digestive Diseases;Hepatitis;Hepatitis - C;Immunization;Immunotherapy;Infectious Diseases;Liver Disease;Prevention;Vaccine Related

PHR: Project Narrative Chronic viral infections are associated with impaired host immunity and long-term health outcomes, even affecting immune responses against other pathogens or vaccines. However, the precise mechanisms driving immune dysregulation in these settings are poorly understood. In this Project, we will use chronic infection with hepatitis C virus as a paradigmatic persistent infection in humans to better dissect impact on host immunity and identify molecular targets for intervention to restore functional immunity.

PI_NAMEs: LAUER, GEORG MICHAEL (contact)

PROJECT_TERMS: acute infection;adaptive immunity;Adult;Affect;Animal Model;anti-PD-1;Anti-viral Agents;Anti-viral Response;antiviral immunity;Attention;Automobile Driving;Biological Models;Biomedical Research;Cell Physiology;cell type;Cells;Chronic;Chronic Disease;Chronic Hepatitis C;chronic infection;Cicatrix;cohort;COVID-19 pandemic;CRISPR/Cas technology;curative treatments;Data;Data Set;Defect;Disease;Disease Progression;Enhancers;Epigenetic Process;exhaust;exhaustion;fitness;Functional disorder;Functional impairment;functional restoration;Health;Hepatitis C;Hepatitis C virus;Human;Immune;immune health;Immune response;Immune system;Immune System Diseases;Immunity;Immunization;Immunologic Memory;Immunologics;immunomodulatory strategy;immunomodulatory therapies;Immunotherapy;Impairment;imprint;improved;Infection;Inflammation;Inflammatory;Innate Immune Response;Interferons;Intervention;Knowledge;long-term sequelae;Mediating;Memory;Molecular;Molecular Target;Myelogenous;Myeloid Cells;Natural Immunity;Outcome;pathogen;Pathway interactions;Population;prevent;programs;Reagent;Recording of previous events;Regulatory Pathway;response;Specificity;T cell differentiation;T cell response;T-Cell Development;T-Cell Immunologic Specificity;T-Lymphocyte;Testing;therapeutic vaccine;Vaccination;vaccine response;Vaccines;Viral;Viremia;Virus;Virus Diseases;Work

PROJECT_TITLE: Project 2: Durable impact of HCV on innate and adaptive immunity


NIH_SPENDING_CATS: Biotechnology;Coronaviruses;Coronaviruses Therapeutics and Interventions;Coronaviruses Vaccines;Emerging Infectious Diseases;Immunization;Immunotherapy;Infectious Diseases;Precision Medicine;Prevention;Vaccine Related

PHR: Project Narrative Here, we focus on testing how the PD-1 inhibitory receptor pathway influences vaccine-induced immunity. By capitalizing on patients treated with PD-1 inhibitors while getting standard of care vaccines, these studies will address a major gap in knowledge in human immunology about how PD-1 regulates vaccine-induced humoral and cellular immunity. This work will have implications for improving vaccines and for the fundamental regulation of immunological memory in humans.

PI_NAMEs: WHERRY, E. JOHN (contact)

PROJECT_TERMS: 2019-nCoV;Acceleration;adaptive immune response;adaptive immunity;Affinity;anti-PD-1;Antibodies;Antibody Formation;Antibody Response;antigen-specific T cells;Antigens;B-Lymphocytes;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cells;Cellular Immunity;cohort;COVID-19 pandemic;Data;design;Drug Targeting;exhaust;experimental study;Fine needle aspiration biopsy;flu;Future;gain of function;Genetic Transcription;Helper-Inducer T-Lymphocyte;Human;Humoral Immunities;Immune;Immune response;Immune system;Immunity;Immunobiology;Immunologic Memory;Immunology;immunoregulation;Immunotherapy;improved;Individual;Infection;Influenza;Influenza vaccination;insight;interest;Knowledge;Ligands;loss of function;Malignant Neoplasms;Memory;Memory B-Lymphocyte;Messenger RNA;Modality;Mus;Nature;Pathway interactions;patient subsets;Patients;PD-1 inhibitors;PD-1 pathway;personalized immunotherapy;programmed cell death ligand 1;programmed cell death protein 1;programs;receptor;Regulatory Pathway;Research Design;response;RNA vaccination;RNA vaccine;Role;Sampling;Services;Shapes;Signal Transduction;standard of care;Stimulus;Structure of germinal center of lymph node;success;synergism;T cell differentiation;T cell response;T memory cell;T-cell receptor repertoire;T-Lymphocyte;Testing;Therapeutic;therapeutic target;tumor;Tumor Immunity;Vaccination;vaccine-induced immunity;Vaccines;Work

PROJECT_TITLE: Project 3: Durable impact of precision immunotherapy on vaccine-induced adaptive immune memory


ORG_CITY: CHICAGO

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE – OVERALL Neutrophils are abundant yet poorly understood immune cells that drive lung diseases with enormous public health relevance. We hypothesize that cellular and humoral signals originating from the circulation and from specific niches within the injured lung microenvironment drive heterogeneous neutrophil phenotypes and functions that determine the balance between inflammation, injury, and repair in patients with neutrophilic lung and airways diseases. The Neu-Lung Consortium brings together experts in fundamental immunology, respiratory disease, clinical medicine, and computational biology who will synergize to test mechanistic hypotheses of neutrophilic disease pathogenesis using cutting-edge technologies applied to human lung, airway, and blood samples obtained from well-phenotyped patients with pneumonia, primary lung allograft dysfunction, and asthma.

PI_NAMEs: EISENBARTH, STEPHANIE CAROLINE (contact);MISHARIN, ALEXANDER ;SINGER, BENJAMIN DAVID

PROJECT_TERMS: Adaptive Immune System;Address;Airway Disease;airway epithelium;airway inflammation;airway remodeling;Alveolar;Alveolar Cell;Alveolitis;Alveolus;Anatomy;Animal Model;antimicrobial;Asthma;Blood specimen;Cause of Death;cell type;Cells;Chemotactic Factors;Chronic Disease;Chronic lung disease;Circulation;Clinical;Clinical Medicine;clinical phenotype;Communicable Diseases;Computational Biology;CSF3 gene;Data;differential expression;Disease;disease model;eosinophil;Equilibrium;Event;Exhibits;Failure;Functional disorder;Genetic Transcription;graft dysfunction;Heterogeneity;Host Defense;Human;human data;IL17 gene;IL8 gene;Immune;Immune response;Immune signaling;Immune system;Immunologics;Immunology;immunoregulation;Infection;Inflammation;Inflammatory;injured airway;Injury;Innate Immune System;Institution;Integrins;Interferon Type I;Interferon Type II;Interleukin-1 alpha;Interleukin-6;ITGAM gene;Knowledge;Life;Lung;lung allograft;Lung Diseases;lung injury;Lung Transplantation;Machine Learning;migration;Modeling;mouse model;Mucous body substance;Mucous Membrane;multiple omics;Mus;neutrophil;Neutrophil Activation;Neutrophil Infiltration;organ transplant recipient;Outcome;pathogen;Pathogenesis;Pathology;Patient-Focused Outcomes;Patients;Phenotype;Pneumonia;programs;Public Health;public health relevance;Publishing;Pulmonary Inflammation;recruit;repaired;Research;Research Personnel;Respiratory Disease;response;Role;sample collection;Sampling;Signal Transduction;single cell technology;Solid;Source;Squamous Metaplasia;Structure;success;synergism;Technology;Testing;tissue repair;Tissues;transcriptomics;United States;Work

PROJECT_TITLE: The Neu-Lung Consortium: Neutrophilic Mechanisms of Inflammation, Injury, and Repair in Lung and Airways Diseases


NIH_SPENDING_CATS: Coronaviruses;Lung

PHR: NARRATIVE A project narrative is not required for this component per instructions stated on the Funding Opportunity Announcement RFA-AI-22-069, “Project Narrative: Do not complete.”

PI_NAMEs: EISENBARTH, STEPHANIE CAROLINE (contact)

PROJECT_TERMS: Accountability;adaptive immunity;Airway Disease;Award;Biology;Collaborations;collaborative environment;Communication;Critical Care;Data;data sharing;disease model;Ensure;Environment;Expenditure;Faculty;FAIR principles;follower of religion Jewish;Fostering;Funding;Funding Opportunities;Goals;graduate student;Group Meetings;Human;Hybrids;Immune System Diseases;Immunobiology;Immunologist;Immunology;Inflammation;Infrastructure;Injury;Institution;Instruction;Interdisciplinary Study;Lung;Lung Diseases;medical schools;Medicine;meeting abstracts;meetings;member;Mentors;Mission;Monitor;multidisciplinary;National Institute of Allergy and Infectious Disease;Natural Immunity;neutrophil;next generation;Notification;Persons;Physicians;Postdoctoral Fellow;Preparation;programs;Protocols documentation;public database;Publications;Pulmonary Pathology;Recording of previous events;repaired;repository;Research;Research Personnel;Resources;Scientist;Site;Structure;student mentoring;synergism;Training;United States National Institutes of Health;Universities;web site;Work;working group

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Asthma;Clinical Research;Coronaviruses;Data Science;Genetics;Human Genome;Lung;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Organ Transplantation;Transplantation

PI_NAMEs: WALUNAS, THERESA L (contact)

PROJECT_TERMS: Adult;Airway Disease;Algorithms;analysis pipeline;analytical tool;Archives;Area;Asthma;asthmatic patient;Behavior;biomarker identification;Blood;Blood specimen;Caring;Child;Clinical;clinical care;Clinical Data;clinical phenotype;Clinical Research;clinical subtypes;Code;Communities;Complex;computerized tools;Data;data and analysis portal;Data Collection;data dissemination;Data Element;data integration;data modeling;data repository;Data Set;data sharing;database of Genotypes and Phenotypes;design;Development;disease model;electronic health information;Electronic Health Record;Environment;follower of religion Jewish;Functional disorder;Funding Opportunities;gene regulatory network;Genetic;Genomics;Goals;Health;Heart;Heterogeneity;high dimensionality;Inflammation;Injury;innovation;Instruction;integration site;Investigation;learning strategy;Lung;lung allograft;Lung Diseases;Lung Transplantation;Machine Learning;Maps;Metadata;Modeling;Molecular;Molecular Profiling;multidimensional data;Multiomic Data;multiple omics;National Institute of Allergy and Infectious Disease;neutrophil;novel;Online Systems;open source;Outcome;Participant;Patient Recruitments;patient subsets;Patient-Focused Outcomes;Patients;Persons;Phenotype;phenotypic data;Plant Leaves;Pneumonia;Population;programs;prospective;query tools;recruit;Registries;repaired;repository;Research;Research Infrastructure;Research Personnel;Research Project Grants;Resource Sharing;sample collection;Sampling;Site;Source Code;Space Models;Specimen;Structure of parenchyma of lung;Testing;Tissue Sample;tool;transcriptomics;Translating;Transplant Recipients;Universities;web portal;web-based tool;Work

PROJECT_TITLE: Clinical Phenotyping and Molecular Integration Core


PI_NAMEs: MULLER, WILLIAM A (contact)

PROJECT_TERMS: Adhesions;Affect;Air;Airway Disease;airway epithelium;Anti-Bacterial Agents;arm;Asthma;Bacteria;Biological Assay;Biology;Blood;Bronchoalveolar Lavage;Bronchoalveolar Lavage Fluid;Cell Line;cell type;Cells;chemokine;Chemotactic Factors;Chemotaxis;Clinical;Coculture Techniques;Collection;Communication;comorbidity;Complement;CSF3 gene;cytokine;Cytoplasmic Granules;Data;data integration;Defect;Detection;Disease;Disease Outcome;Emigrations;Endothelial Cells;Endothelium;Ensure;Epithelial Cells;experience;extracellular;Extracellular Matrix;extracellular vesicles;Flow Cytometry;follower of religion Jewish;Functional disorder;Funding Opportunities;Generations;Glycolysis;graft dysfunction;Growth Factor;Harvest;Hospitals;Human;imaging approach;immune function;Immunofluorescence Immunologic;Infection;Inflammation;Inflammatory Response;Injury;Innate Immune Response;Institution;Instruction;intercellular communication;Interferons;Lipids;Liquid substance;Location;Lung;Lung Diseases;Lung Transplantation;Mediator;Metabolism;migration;Mitochondria;Mucous body substance;multiple omics;neutrophil;Oxidants;participant enrollment;particle;pathogen;Pathologic;Patients;Peptide Hydrolases;Peptides;peripheral blood;Phagocytosis;Phenotype;Physiological;Physiology;Pneumonia;Production;Proteins;Reaction;Reactive Oxygen Species;Reagent;repaired;Reproducibility;response;Role;Running;Sampling;Services;Signal Transduction;Site;Specimen;Sputum;Stimulus;Surface;T cell response;T-Lymphocyte;Testing;Tissues;Training;transcriptomics;Umbilical cord structure;Work

PROJECT_TITLE: Neutrophil Physiology Core


PI_NAMEs: DULAI, PARAMBIR SINGH (contact)

PROJECT_TERMS: 2019-nCoV;Airway Disease;Alveolar;Autopsy;Back;Bacterial Infections;Biology;Biopsy;Blood;Bronchoalveolar Lavage;Cell Communication;Cells;Circulation;Classification;clinical phenotype;cohort;Colitis;Collaborations;Colorado;Complex;Computational Biology;Cryopreservation;Cues;Curettage procedure;Custom;Data;data integration;Data Set;Development;Disease;Disease Outcome;disease phenotype;Epithelium;Evaluation;experimental study;Fibrosis;Flow Cytometry;follower of religion Jewish;Formalin;Funding Opportunities;Gastroenterology;Gene Expression;Genetic Transcription;Genomics;Goals;Grant;Hepatology;Heterogeneity;Human Resources;Immune;Immunophenotyping;Infection;Inflammation;Influenza;Injury;injury and repair;Instruction;Libraries;Link;Lung;Lung Diseases;Lung infections;Measures;Mediating;metabolomics;Microbe;Mining;Molecular;molecular phenotype;Mucous Membrane;multiple omics;neutrophil;Nose;novel;Paraffin Embedding;pathogen;Patients;Peripheral;Phenotype;Physiology;precision medicine;Prognosis;programs;Proteins;Proteomics;Pulmonary Inflammation;repaired;RNA;Sampling;Shapes;single cell proteins;single cell sequencing;single-cell RNA sequencing;Site;spatial integration;Sputum;Structure;Structure of parenchyma of lung;targeted sequencing;Technology;Tissue Embedding;Tissues;transcriptomics;treatment response;Universities;Viral;Virus

PROJECT_TITLE: Technology Core


NIH_SPENDING_CATS: Clinical Research;Coronaviruses;Infectious Diseases;Lung;Organ Transplantation;Pneumonia;Pneumonia and Influenza;Transplantation

PI_NAMEs: MISHARIN, ALEXANDER  (contact)

PROJECT_TERMS: Acute Lung Injury;adaptive immune response;adaptive immunity;Age;Airway Disease;Alveolar;Alveolitis;Alveolus;Animal Model;arginase;Autopsy;B-Lymphocytes;Biological;Biological Assay;Biopsy Specimen;Blood specimen;Bone Marrow;Bronchoalveolar Lavage;Bronchoalveolar Lavage Fluid;Cause of Death;Cells;Cessation of life;Chronic;Circulation;Clinical;clinical care;clinical phenotype;Colony-Stimulating Factors;Communicable Diseases;cytokine;Data;Data Set;design;Development;Dimensions;Disease;Down-Regulation;Electronic Health Record;Endothelial Cells;Endothelium;Epithelial Cells;Etiology;Exhibits;Functional disorder;Funding Opportunities;Goals;graft dysfunction;Granulocyte Colony-Stimulating Factor;Growth Factor;Heterogeneity;Human;IL8 gene;IL8RB gene;Immunobiology;In Situ;Infection;Inflammasome;Inflammation;Inflammatory;Infrastructure;Injury;Instruction;Integrins;Interferon Type I;Interferon Type II;Interferons;ITGAM gene;Knowledge;Link;Lower Respiratory Tract Infection;Lung;lung allograft;Lung Diseases;lung injury;Lung Transplantation;Mediating;Methods;migration;Molecular;monocyte;Morbidity - disease rate;mortality;neutrophil;Neutrophil Activation;Neutrophilia;Outcome;Pathogenesis;pathogenic bacteria;pathogenic virus;Pathologic;Pathway interactions;Patients;Phenotype;Physiological;Pneumonia;Population;Positioning Attribute;programs;pulmonary function;repair function;repaired;Research;Resolution;response;Risk Factors;Role;sample collection;Sampling;secondary infection;Shapes;Signal Transduction;single cell sequencing;Source;Sterility;Steroids;Structure of parenchyma of lung;Syndrome;T-Lymphocyte;Technology;Testing;therapeutic target;tissue injury;tissue repair;Tissue Sample;Tissues;Transplant Recipients;Universities;ventilator-associated pneumonia

PROJECT_TITLE: Neutrophil Responses Drive Diseases of the Alveolar Space


PI_NAMEs: SEIBOLD, MAX A (contact)

PROJECT_TERMS: Acute;Affect;age group;Airway Disease;airway epithelium;airway inflammation;airway obstruction;airway remodeling;Asthma;asthmatic;asthmatic patient;Bacterial Infections;Biological Assay;Biological Products;Biological Response Modifier Therapy;Biopsy;Blood;Bronchoalveolar Lavage;Cells;Characteristics;chemokine;Chemotactic Factors;Chronic lung disease;Clinical;Coculture Techniques;Collection;Complement;Complement 5a;Cross-Sectional Studies;CSF3 gene;CXCL1 gene;cytokine;Data;Disease;Disease Progression;Environment;eosinophil;Epithelium;Exhibits;experience;follower of religion Jewish;Functional disorder;Funding Opportunities;Gene Activation;Genes;Growth Factor;Health Care Costs;Heterogeneity;IL17 gene;Immune;immune activation;immunoregulation;In Vitro;in vivo;in vivo evaluation;Individual;Infiltration;Inflammation;Inflammatory;inhibitor therapy;Injury;Instruction;Interferon Type II;Interleukin-1 alpha;Interleukin-13;Interleukin-4;Interleukin-5;Interleukin-6;Intervention;Leukotriene B4;Leukotrienes;Lung;Lung Diseases;Mediating;Metaplasia;Migration Assay;Modeling;Molecular;Mucous body substance;Mucous Membrane;neutrophil;Neutrophil Activation;Neutrophilia;novel;Organoids;pathogen;Patients;Pattern;Peptide Hydrolases;Phagocytes;Phenotype;Play;Population;programs;recruit;repaired;Research Infrastructure;Respiratory Mucosa;response;Role;Sampling;Signal Transduction;Sputum;Subgroup;Testing;Time;transcriptome sequencing;transcriptomics;Translational Research

PROJECT_TITLE: Neutrophil responses Drive Severe Asthma


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Dementia;Neurodegenerative;Neurosciences

ORG_CITY: WALTHAM

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: BRANDEIS UNIVERSITY

PHR: PROJECT NARRATIVE Dopamine is critical for prioritizing motivationally significant events in long-term memory so that past experiences can guide future choices. This project will investigate how dopamine impacts hippocampal- dependent reward memory in healthy older adults. If successful, this project will contribute to our understanding of basic mechanisms by which declines in dopamine function drive memory changes in aging.

PI_NAMEs: CIAMPA, CLAIRE  (contact)

PROGRAM_OFFICER_NAME: WAGSTER, MOLLY V

PROJECT_TERMS: Accounting;Affect;age related changes;Aging;Alzheimer's Disease;Alzheimer's disease pathology;Amyloid beta-Protein;Animal Model;Automobile Driving;Basic Science;Behavior;Berry;beta amyloid pathology;Binding;Brain;career;Cell Nucleus;classifier algorithm;clinically relevant;Cognition;Cognitive;cognitive performance;Communication;Corpus striatum structure;Data;Development;Dopamine;dopamine system;dopamine transporter;Dopamine Uptake Inhibitors;Event;experience;Faculty;Functional Magnetic Resonance Imaging;functional MRI scan;Future;General Hospitals;Genetic Transcription;healthy aging;high reward;Hippocampus;Human;imaging study;Impaired cognition;in vivo;Incentives;Individual;Individual Differences;inter-individual variation;interest;Joints;Link;long term memory;Long-Term Potentiation;Massachusetts;Measurement;Measures;member;Memory;memory consolidation;memory encoding;Mentorship;Midbrain structure;Modeling;Motivation;MRI Scans;neural;neuroimaging;Neuromodulator;Neurotransmitters;older adult;Oral;Parkinson Disease;Participant;Pathology;Pattern;Performance;Pharmaceutical Preparations;pharmacologic;Pharmacological Treatment;Placebos;Play;Positron-Emission Tomography;Procedures;Process;Protocols documentation;Raclopride;receptor density;Research;response;Rest;reward processing;Rewards;Ritalin;Rodent Model;Role;Sampling;Scanning;Series;Signal Transduction;statistics;System;tau Proteins;Techniques;Testing;Time;Tracer;Training;Universities;Variant;Work

PROJECT_TITLE: Dopaminergic mechanisms of reward memory in aging

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02B-Y (20)]


ED_INST_TYPE: UNIVERSITY-WIDE

ORG_CITY: PHILADELPHIA

ORG_NAME: DREXEL UNIVERSITY

PHR: Project Narrative Precise axonal-dendritic targeting of neuronal growth factors is critical for neuronal function, but how they are targeted is largely unknown. We have found that an ER stress sensor protein, PERK, and a kinase associated with neural plasticity and memory, CaMKII, cooperate to control localization of two neuroprotective growth factors. This project will test the relationship between PERK and CaMKII in this novel pathway, which will not only advance our understanding of protein localization in neurons, but also may explain how PERK is genetically linked to neurodegeneration.

PI_NAMEs: PERHACS, JULIA MARIE (contact)

PROGRAM_OFFICER_NAME: TYLER, WILLIAM A

PROJECT_TERMS: Address;Affect;Alleles;Alzheimer's Disease;Animals;Antibodies;Area;Axon;Biological;Biological Assay;Biomedical Research;Caenorhabditis elegans;Calcium;calmodulin-dependent protein kinase II;career;career development;Cells;Communication;Data;Dendrites;Dependence;disorder risk;EIF-2alpha;endoplasmic reticulum stress;Exhibits;Fellowship;gain of function;Genetic;Genetic Epistasis;genetic variant;Goals;Growth Factor;Impairment;In Vitro;insight;Laboratory Finding;Link;loss of function;Mammals;Mass Spectrum Analysis;Measures;Mediating;Memory;mimetics;Modeling;Molecular;Mus;mutant;Mutation;Nerve Degeneration;Neurites;Neuromodulator;neuron development;neuronal growth;Neuronal Plasticity;Neurons;Neuropeptides;neuroprotection;Neurosciences;novel;Pathology;Pathway interactions;PERK kinase;Phenocopy;Phenotype;Phosphorylation;Phosphorylation Site;Phosphotransferases;Play;pre-doctoral;Progressive Supranuclear Palsy;Proteins;Research;response;Risk Factors;RNA Interference;Role;sensor;Site;Somatomedins;Stimulus;Synapses;Tauopathies;Testing;trafficking;Training;Transforming Growth Factor beta;Universities;Writing

PROJECT_TITLE: ER stress sensor PERK functions in localization of neuronal growth factors through CaMKII

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03A-E (20)]


ORG_CITY: SAINT LOUIS

ORG_DEPT: PATHOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE – OVERALL The Washington University Cooperative Center on Human Immunology (WashU-CCHI) will define the cellular and molecular mechanisms governing generation of broad and durable T cell, memory B cell and bone marrow plasma cell responses to rapidly evolving respiratory viral pathogens. It will also determine the functional caliber of systemic and mucosal immune responses to influenza and SARS-CoV-2 vaccination and infection in humans. The assembled multi-disciplinary team of investigators has extensive expertise in immunology, virology, pathogenesis, universal vaccine development, proteomics, metabolic labeling, and structural biology as well as a well-established track record of successful collaborations.

PI_NAMEs: DIAMOND, MICHAEL S;ELLEBEDY, ALI HASSAN (contact)

PROJECT_TERMS: 2019-nCoV;Achievement;Adult;Antibodies;Antibody Response;B cell repertoire;B-Lymphocytes;Biopsy;Blood;Blood specimen;Bone Marrow;Bone Marrow Aspiration;Bronchoalveolar Lavage Fluid;Caliber;CD4 Positive T Lymphocytes;Cells;Clinical;Clinical Research;cohort;Collaborations;Communicable Diseases;Core Biopsy;COVID-19 pandemic;COVID-19 vaccination;COVID-19 vaccine;design;draining lymph node;Environment;Evaluation;Evolution;Fine needle aspiration biopsy;Fostering;Funding;Generations;Genetic;Genetic Transcription;Goals;Helper-Inducer T-Lymphocyte;Human;Human Subject Research;Immune;Immune response;Immunity;Immunize;Immunologic Memory;Immunologics;Immunology;imprint;Infection;Infection Control;Influenza;Influenza A virus;Influenza vaccination;influenzavirus;innovation;insight;Institution;Label;Medicine;Memory;Memory B-Lymphocyte;memory CD4 T lymphocyte;Metabolic;Molecular;Mucosal Immune Responses;Mucosal Immunity;mucosal vaccine;Mucous Membrane;multidisciplinary;Mutate;Nasal Lavage Fluid;Natural History;new outbreak;Nose;pathogen;Pathogenesis;pathogenic virus;Plasma Cells;programs;Proteins;Proteomics;Reaction;Recording of previous events;Research;Research Personnel;Research Project Grants;research study;respiratory;Respiratory System;respiratory virus;response;Saliva;Sampling;SARS-CoV-2 B.1.1.529;SARS-CoV-2 infection;Scientific Advances and Accomplishments;Scientist;Site;Specimen;Stable Isotope Labeling;structural biology;Structure;Structure of germinal center of lymph node;Swab;synergism;T cell response;T-Lymphocyte;Technology;theories;transcriptomics;universal vaccine;Universities;Upper respiratory tract;Vaccinated;Vaccination;vaccine candidate;vaccine development;vaccine immunogenicity;Vaccines;Viral;virology;Virus;Virus Diseases;Washington;World Health

PROJECT_TITLE: Mechanisms of Immune Protection Against Respiratory Viruses


PI_NAMEs: ELLEBEDY, ALI HASSAN (contact)

PROJECT_TERMS: Accountability;Advisory Committees;Budgets;Collaborations;collaborative environment;Communication;conflict resolution;Data;data management;data repository;data sharing;data submission;Development;Ensure;Funding;Goals;Grant;Guidelines;Human;Human Resources;Hybrids;Immune;Immunology;Individual;Institution;Link;Mediator;meetings;member;Mission;National Institute of Allergy and Infectious Disease;Participant;Persons;Preparation;programs;Progress Reports;public repository;Recommendation;recruit;Reporting;Research Activity;Research Personnel;Research Project Grants;Resource Allocation;respiratory virus;senior faculty;Services;Site;symposium;United States National Institutes of Health;Universities;virtual;Washington

PROJECT_TITLE: Core A - Administrative Core


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Coronaviruses;Coronaviruses Diagnostics and Prognostics;Coronaviruses Vaccines;Emergency Care;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Lung;Pneumonia and Influenza;Prevention;Vaccine Related

PI_NAMEs: PRESTI, RACHEL MARGARET (contact)

PROJECT_TERMS: 2019-nCoV;Accident and Emergency department;Acute;acute infection;Address;Age;Biopsy;Blood;Bone Marrow Aspiration;Bronchoalveolar Lavage;Bronchoscopy with Bronchoalveolar Lavage;Caring;Cells;Clinical;Clinical Immunology;Clinical Protocols;Clinical Research;Clinical Trials;cohort;Collaborations;Collection;Communicable Diseases;Core Biopsy;Coughing;COVID-19;COVID-19 vaccination;COVID-19 vaccine;Data;data management;design;Deuterium;Development;Diagnosis;Diagnostic tests;Doctor of Philosophy;Eligibility Determination;Emergency Medicine;Emergency research;Enrollment;experience;Faculty;Fever;Fine needle aspiration biopsy;Goals;Hematology;Hour;Human;human old age (65+);Human Resources;Human Subject Research;Immune;Immunization;Immunology;Individual;Infection;Influenza;Influenza A virus;influenza infection;Influenza vaccination;influenzavirus;Infrastructure;Institutional Review Boards;interest;Knowledge;Label;Laboratories;Laboratory Technicians;Leadership;Longitudinal Studies;lymph nodes;Medical;medical schools;Metabolic;multidisciplinary;nasal swab;nasopharyngeal swab;Oncology;Oral Administration;Participant;participant enrollment;Patients;Pharmacy facility;Physicians;Population;Positioning Attribute;Protocols documentation;Pulmonology;Radiology Specialty;Recommendation;Recording of previous events;Research;Research Personnel;Research Project Grants;research study;Resources;Respiratory Mucosa;Respiratory Signs and Symptoms;respiratory virus;Saliva;sample collection;Sampling;SARS-CoV-2 immunity;SARS-CoV-2 infection;Scientist;Specimen;Structure of mucous membrane of nose;Swab;Symptoms;Telephone;Testing;Translational Research;Universities;Vaccination;vaccine candidate;vaccine trial;Viral Respiratory Tract Infection;Visit;Washington;Water;Work

PROJECT_TITLE: Core B - Clinical Core


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Emerging Infectious Diseases;Immunization;Infectious Diseases;Lung;Prevention;Vaccine Related

PI_NAMEs: GEORGIOU, GEORGE GEORGIOU (contact)

PROJECT_TERMS: Address;Anatomy;Antibodies;Antibody Repertoire;Antigen-Antibody Complex;Antigens;aspirate;B cell repertoire;B-Cell Antigen Receptor;B-Lymphocyte Subsets;B-Lymphocytes;Binding;Biochemical;Bioinformatics;biophysical properties;biophysical techniques;Blood;Bone Marrow;Bone Marrow Aspiration;Bronchoalveolar Lavage;Charge;Circulation;Clonal Expansion;Collaborations;complementarity-determining region 3;Complementary DNA;Coronavirus spike protein;COVID-19 vaccination;Data;dimensional analysis;Dissociation;DNA sequencing;draining lymph node;Epitopes;Exhibits;experience;Fine needle aspiration biopsy;Flow Cytometry;Genes;Germ Lines;Hemagglutinin;high throughput analysis;High-Throughput Nucleotide Sequencing;Human;Hydrophobicity;IgG1;Immune;Immunoglobulin A;Immunoglobulin G;Immunoglobulin Somatic Hypermutation;Immunoglobulins;Immunology;In Vitro;Individual;Infection;Influenza Hemagglutinin;influenzavirus;interest;Length;Light;Liquid Chromatography;Liquid substance;Location;lymph nodes;Maps;Memory B-Lymphocyte;Methodology;Molecular;Mucous Membrane;neonatal Fc receptor;Peptides;peripheral blood;Physiological;Plasma;Plasma Cells;Plasmablast;Population;Property;Protein Chemistry;Protein Engineering;Proteins;Proteolysis;Proteomics;Recombinants;Resolution;respiratory;respiratory pathogen;Respiratory System;Respiratory Tract Infections;respiratory virus;response;Role;SARS-CoV-2 antibody;SARS-CoV-2 spike protein;Serology;Sorting;Specimen;Structure of germinal center of lymph node;tandem mass spectrometry;Technology;technology platform;Texas;Time;Tissues;tool;transcytosis;Universities;Vaccination;Vaccines;Washington;Work;Yeasts

PROJECT_TITLE: Core C - Proteomics Core


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Vaccines;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Lung;Pneumonia and Influenza;Prevention;Vaccine Related

PHR: PROJECT NARRATIVE - PROJECT 1 Vaccination-induced adaptive immunity protects against severe disease from SARS-CoV-2 and influenza, but these viruses continue to infect humans because of the limited duration of vaccine-induced immunity, which is exacerbated by viral antigenic drift. In Project 1, we address key gaps in our understanding of the cellular, molecular, and genetic mechanisms governing the generation and maintenance of the immune cells that confer durable immunity and the diversity of viral strains against which they protect.

PROJECT_TERMS: 2019-nCoV;adaptive immunity;Address;Adult;Affinity;Animals;Antibodies;Antibody Response;Antibody titer measurement;Antigen-Presenting Cells;Antigens;B-Cell Antigen Receptor;B-Lymphocytes;Binding;Blood;Blood specimen;Bone Marrow;Bone Marrow Aspiration;CD4 Positive T Lymphocytes;Cell Differentiation process;Cell Proliferation;Cells;Clone Cells;cohort;Complement;Core Biopsy;COVID-19 vaccination;COVID-19 vaccine;Data;design;Disease;draining lymph node;Epitopes;Evolution;Fine needle aspiration biopsy;Fostering;Frequencies;Future;Generations;Genetic;Genetic Transcription;Helper-Inducer T-Lymphocyte;Human;Humoral Immunities;Immune;Immune response;Immunity;Immunize;Immunologic Memory;Immunologics;imprint;Incubators;Influenza;Influenza vaccination;influenzavirus;innovation;Intervention;Kinetics;Knowledge;Licensing;Longevity;lymphoid structures;Maintenance;Masks;Mass Spectrum Analysis;Medical;Memory;Memory B-Lymphocyte;Modeling;Molecular;Monoclonal Antibodies;next generation sequencing;novel;novel vaccines;pathogenic virus;Phenotype;Plasma Cells;Plasmablast;Population;Population Dynamics;prevent;prospective;Proteomics;Reaction;Recording of previous events;respiratory;respiratory pathogen;respiratory virus;response;Sampling;seasonal influenza;Secondary Immunization;secondary lymphoid organ;Series;Severe Acute Respiratory Syndrome;Shapes;Signal Transduction;Specificity;Specimen;Stable Isotope Labeling;Structure of germinal center of lymph node;T cell response;T memory cell;T-Lymphocyte;Time;transcriptomics;Vaccinated;Vaccination;Vaccine Design;vaccine immunogenicity;vaccine-induced immunity;Vaccines;Variant;Viral;Viral Respiratory Tract Infection;Virus;Virus Replication;Vulnerable Populations

PROJECT_TITLE: Project 1


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Vaccines;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Pneumonia and Influenza;Prevention;Vaccine Related

PHR: PROJECT NARRATIVE – PROJECT 2 Despite widespread availability of vaccines against SARS-CoV-2 and influenza, these viruses continue to infect humans because of antigenic drift that evades pre-existing immunity. In Project 2, we address key gaps in our understanding of human antiviral immunity as it relates to durability, immunodominance, function, and breadth of vaccine-induced, infection-induced, and hybrid vaccination/infection-induced mucosal and systemic immunity.

PI_NAMEs: DIAMOND, MICHAEL S (contact)

PROJECT_TERMS: 2019-nCoV;Address;Adult;Affect;Antibodies;Antibody Response;Antigens;antiviral immunity;ATAC-seq;B-Lymphocytes;Binding;Biological Assay;Biopsy;Blood;booster vaccine;Bronchoalveolar Lavage Fluid;Caliber;CD8-Positive T-Lymphocytes;Clinical;cohort;Complement 1q;COVID-19 vaccine;cross reactivity;Development;Disease;Evaluation;experience;Genetic;Geography;Goals;Health;Hospitalization;Human;human pathogen;Hybrids;Immune;Immune response;Immunity;Immunization;Immunoglobulin A;Immunoglobulin G;Immunoglobulin Isotypes;imprint;Infection;Infection Control;Infectious Agent;Influenza;Influenza A virus;influenza infection;Influenza vaccination;influenza virus strain;influenza virus vaccine;influenzavirus;innovation;insight;Intramuscular;Knowledge;Location;Lung;Mass Spectrum Analysis;Mediating;Memory;Molecular;Monoclonal Antibodies;Morbidity - disease rate;mortality;Mucosal Immune Responses;Mucosal Immunity;mucosal site;mucosal vaccine;Mucous Membrane;Nasal Lavage Fluid;Natural History;neutralizing antibody;next generation sequencing;pandemic disease;pandemic potential;Peripheral Blood Mononuclear Cell;Persons;polyclonal antibody;Polysaccharides;Population;prevent;Recording of previous events;Respiratory System;respiratory virus;response;Saliva;Sampling;SARS-CoV-2 B.1.1.529;SARS-CoV-2 infection;Seasons;Serum;Site;Sorting;Specificity;Swab;T cell response;T memory cell;theories;transcriptome sequencing;Transgenic Mice;transmission process;Vaccinated;Vaccination;vaccine access;vaccine delivery;vaccine distribution;vaccine immunogenicity;vaccine platform;vaccine trial;vaccine-induced immunity;Vaccines;Variant;Viral;viral transmission;Virus;Virus Diseases

PROJECT_TITLE: Project 2


NIH_SPENDING_CATS: Cancer;Lung;Lung Cancer

ORG_CITY: STONY BROOK

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: PROJECT NARRATIVE Mesenchymal epithelial transition factor (c-MET/MET), a receptor tyrosine kinase, is an oncogenic driver in numerous tumor types, notably non-small cell lung cancer (NSCLC) and melanomas. On-target mutations drive resistance against small-molecule MET inhibitors. I aim to comprehensively profile the selectivity of clinically approved MET inhibitors against MET mutants, and determine combinations of inhibitors that maximize on-target activity and reduce off-target effects.

PI_NAMEs: OUTHWAITE, IAN  (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Affinity;Aspartate;Binding;Biological Assay;cancer therapy;Cell Line;Cell model;Cells;Clinical;cohort;combinatorial;Combined Modality Therapy;design;Development;Dissociation;Drug Combinations;Epidermal Growth Factor Receptor;Epithelium;Evolution;experimental study;Fluorescence;Glycine;Growth;in vitro Assay;in vivo;Individual;inhibitor;inhibitor therapy;interest;kinase inhibitor;Kinetics;Length;Lung Adenocarcinoma;Malignant neoplasm of lung;Malignant Neoplasms;Measurement;Measures;Melanoma;Mesenchymal;Methods;Modeling;Molecular;Molecular Conformation;mouse model;mutant;Mutation;Non-Small-Cell Lung Carcinoma;novel;Oncogenic;Outcome;Patients;Pharmaceutical Preparations;Phenylalanine;Phosphotransferases;Probability;Receptor Protein-Tyrosine Kinases;Resistance;Resistance development;resistance mechanism;resistance mutation;Scoring Method;Signal Transduction;small molecule;small molecule inhibitor;Specificity;targeted treatment;Testing;Therapeutic;therapeutic target;therapy resistant;Traction;tumor;Up-Regulation;Work

PROJECT_TITLE: Maximizing Selective Inhibition of Clinically Observed MET Mutants

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09B-Z (20)]


ADMINISTERING_IC: HD

IC_NAME: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Disability Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Neurosciences;Pediatric;Social Determinants of Health

ORG_CITY: CHARLESTON

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: NARRATIVE  Children from adverse developmental environments exhibit varied reading achievement. The proposed research examines how reading development is buffered or protected from atypical development across the population and within individuals in the context of a canalization conceptual framework. The proposed research also advances a data sharing resource that would include the distribution of data and cutting-edge methods established in this project.

PI_NAMEs: ECKERT, MARK ANDREW (contact)

PROGRAM_OFFICER_NAME: MILLER, BRETT

PROJECT_TERMS: Achievement;Biology;Brain;Buffers;Child;Child Development;Childhood;Clinical;Complex;Complex Analysis;Comprehension;computer infrastructure;Data;data access;Data Analyses;data repository;Data Set;data sharing;data sharing networks;deep learning;Development;Disability research;Dyslexia;Education;educational atmosphere;endophenotype;Ensure;Environment;Environmental Risk Factor;executive function;Exhibits;experimental study;FAIR principles;Funding;Genetic;Genetic Risk;high risk;Impairment;Individual;Infrastructure;Intelligence;Knowledge;Language;Language Development;large datasets;Literature;Low Prevalence;low socioeconomic status;Measures;Methods;Morphology;neural;Neural Canal;neuroimaging;novel;Online Systems;open data;Oral;Outcome;Performance;Phenotype;polygenic risk score;Population;Prevalence;Reading;reading ability;Reading Disabilities;Reproducibility;Research;Resource Sharing;Resources;Risk;risk variant;Role;service delivery;Site;skill acquisition;skills;social health determinants;Specificity;Structure;Support System;Task Performances;Testing;Vocabulary;Work;Writing

PROJECT_TITLE: Multi-site Study of Dyslexia

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BP-H (02)]


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences;Peripheral Neuropathy;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Communication between the cells of the peripheral nervous system and the immune system can determine the extent to which nerves recover after injury. The proposed project will identify key molecular mechanisms involved in the macrophage response to peripheral nerve injury and how these mechanisms contribute to nerve fiber repair. The results of this project will expand the knowledge base of the emerging field of neuroimmunology and provide potential therapeutic targets for the treatment of peripheral nerve injury and disease.

PI_NAMEs: HAFNER, HANNAH JULE (contact)

PROGRAM_OFFICER_NAME: KUMSA, DOE WONDWOSSEN

PROJECT_TERMS: Ablation;Acute;Adoptive Transfer;Adult;Anti-Inflammatory Agents;Apoptotic;Axon;axon regeneration;axonal degeneration;Behavioral Assay;Biochemical;Cell Death;Cell Separation;Cells;Central Nervous System;Communication;Complex;Crush Injury;Cytolysis;Debridement;Development;Disease;Disease Outcome;Distal;Environment;Excision;Exhibits;experimental study;functional outcomes;Gene Expression Profile;Genetic;Genetic Transcription;Goals;Growth;Health;Immune;Immune system;improved;Infiltration;Inflammation;Inflammatory;Inflammatory Response;injured;Injury;insight;knowledge base;Label;LDL-Receptor Related Protein 1;Lesion;Leukocytes;Ligands;Link;Lipoprotein Receptor;Macrophage;Mediating;Modeling;Molecular;Molecular Biology;monocyte;Motor;mouse model;Mus;Myelin;myelin degeneration;Myelin Sheath;Natural regeneration;Necrosis;Nerve;Nerve Fibers;nerve injury;Nerve Regeneration;nerve repair;Nervous System Trauma;neural;neural repair;neuroimmunology;neuron regeneration;neutrophil;novel therapeutic intervention;Pain;painful neuropathy;Peripheral nerve injury;peripheral nerve regeneration;Peripheral Nerves;Peripheral Nervous System;permissiveness;Phagocytes;Phagocytosis;Phenotype;Population;prevent;Process;Proteins;PTPRC gene;receptor;Recovery;Recovery of Function;regenerative;repaired;Reporter;Reporting;Research;Resolution;response;response to injury;Role;Schwann Cells;sciatic nerve;sciatic nerve injury;Sensory;single-cell RNA sequencing;Site;Techniques;Testing;therapeutic target;tissue repair;Tissues;Trauma;Traumatic injury;Wallerian Degeneration

PROJECT_TITLE: The contribution of macrophage subpopulations to axon degeneration, nerve inflammation, and regeneration of the injured sciatic nerve


NIH_SPENDING_CATS: Cancer;Genetics;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL GRADUATE SCHOOL OF BIOMEDICAL SCIENCES, LLC

ORG_STATE: TN

PHR: Project Narrative Rhabdomyosarcoma is the most common pediatric soft tissue sarcoma, and the survival rate has not increased for the past three decades. Our lab has shown that proteins called transcription factors can control the emergence and cell type of rhabdomyosarcoma through elegant mouse models. My project is specifically focused on understanding how the transcription factor SOX8 functions during normal muscle development and how rhabdomyosarcoma cells utilize SOX8 for tumor initiation and fate to potentially solidify a new therapeutic target for rhabdomyosarcoma.

PI_NAMEs: STEVENS, BRADLEY  (contact)

PROJECT_TERMS: academic program;Adult;aggressive therapy;Award;Biological Assay;Biology;Breast Cancer Cell;Breeding;Cancer Biology;career;Cell Line;cell type;Cells;chemotherapy;Child;Childhood Rhabdomyosarcoma;Childhood Soft Tissue Sarcoma;Cleavage Under Targets and Release Using Nuclease;Clinical Trials;Collection;Communication;comorbidity;Core Facility;Coupled;Data;design;Development;Developmental Biology;Dissection;Embryonic Development;Environment;Essential Genes;experimental study;gain of function;Gene Expression;Genes;Genetic Recombination;Genetic Transcription;Genetically Engineered Mouse;Goals;high risk;Human;In Vitro;in vitro Assay;in vivo;Individual;Injury;insight;Institution;interest;Laboratories;Learning;lens;loss of function;Malignant Childhood Neoplasm;Malignant Neoplasms;Mediating;Mentorship;Molecular;Molecular Biology;Molecular Target;mouse model;Mus;Muscle;Muscle Cells;Muscle Development;muscle progenitor cell;Myoblasts;myogenesis;new therapeutic target;novel;Operative Surgical Procedures;overexpression;Pathogenesis;Pathology;Patients;PAX7 gene;Play;pre-doctoral;Process;progenitor;programs;Proteins;Radiation;Research;Research Personnel;Rhabdomyosarcoma;Role;Saint Jude Children's Research Hospital;Skeletal Muscle;skills;SOX8 gene;spatiotemporal;Squamous cell carcinoma;stem cell fate;Survival Rate;Survivors;System;Techniques;Testing;therapeutic target;Training;transcription factor;Transcriptional Regulation;transcriptome sequencing;triple-negative invasive breast carcinoma;tumor;tumor initiation;tumorigenic;Tumorigenicity;Western Blotting

PROJECT_TITLE: Determining the Role of SOX8 in Myogenesis and Rhabdomyosarcomagenesis


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Clinical Research;Diabetes;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

ORG_CITY: DURHAM

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE  This proposal seeks to advance the state of the art in automated image guidance methods with optical coherence tomography (OCT) to improve diagnosis and treatment of diabetic retinopathy. We will develop novel robotically-aligned and handheld OCT devices to automatically measure retinal biomarkers currently not identified with standard of care OCT systems and to provide real-time 3D feedback to clinicians performing a novel, less invasive injection procedure. We believe our technologies will allow for increased access to new diagnostics and therapeutics for patients with diabetic retinopathy.

PI_NAMEs: NARAWANE, AMIT  (contact)

PROJECT_TERMS: 3-Dimensional;Accounting;Adoption;Adult;Angiography;Anterior;bevacizumab;Biological Markers;Blindness;Blood Vessels;care burden;Child;Clinical;clinical biomarkers;Compensation;Custom;Data;design;Development;Devices;Diabetes Mellitus;Diabetic Retinopathy;Diagnosis;Diagnostic;Diagnostic Procedure;Disease;Drug Delivery Systems;Evaluation;Eye;Face;Feedback;Fiber;gene therapy;Goals;Human;Image;image guided;imaging capabilities;imaging probe;improved;in vivo;Individual;Infant;Injectable;Injections;interest;Interferometry;invention;Measurement;Measures;Methods;Monitor;Motion;Nerve Degeneration;Neural Retina;neuron loss;noninvasive diagnosis;novel;novel diagnostics;novel therapeutics;Nuclear;Optical Coherence Tomography;Outcome;Patients;Pilot Projects;Positioning Attribute;prevent;Prevention;Procedures;Pupil;Real-Time Systems;Research;Resolution;Retina;Robotics;Sampling;Scanning;screening;Series;skills;software development;standard of care;Surface;System;Techniques;Technology;Therapeutic;Therapeutic Agents;Thick;Three-Dimensional Image;Time;Training;United States National Institutes of Health;user-friendly;Validation;vascular abnormality;Visit;Visualization;Work

PROJECT_TITLE: Robotic and handheld OCT imaging for diagnosis and treatment of diabetic retinopathy


NIH_SPENDING_CATS: Clinical Research;Orphan Drug;Rare Diseases

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Project Narrative This project interrogates clonal repertoire in delayed-type drug hypersensitivity reactions, which are a major yet understudied public health problem. This transformative study uses innovative translational approaches to advance understanding of pathobiology and work toward development of much-needed diagnostic tests.

PI_NAMEs: DIVITO, SHERRIE JILL (contact);GARBER, MANUEL

PROGRAM_OFFICER_NAME: SUBRAMANIAN, HARIHARAN

PROJECT_TERMS: adaptive immunity;Alleles;Antigen Presentation;Antigen-Presenting Cells;Antigens;Architecture;beta Chain Antigen T Cell Receptor;Biological Assay;Blood;Cells;Clinical;clinical care;clinical imaging;Clonal Expansion;Clonality;Clone Cells;cohort;Communicable Diseases;cross reactivity;Data;design;Development;Diagnostic tests;Disease;Drug Eruptions;Drug Exposure;Drug Hypersensitivity;Drug Tolerance;Ensure;Enzyme-Linked Immunosorbent Assay;Eosinophilia;Exposure to;General Population;Goals;Grant;high risk;Human;immunogenic;in vivo;Individual;Infection;innovation;innovative technologies;insight;Laboratories;Mediating;Morbidity - disease rate;mortality;new technology;Pathogenicity;patient population;patient screening;Patients;Peptides;Pharmaceutical Preparations;Phenotype;Physiologic pulse;prevent;prospective;protein aminoacid sequence;Proteins;Public Health;Publications;Publishing;Reaction;Recording of previous events;Research;Research Personnel;Resolution;Rest;Sample Size;Sampling;single-cell RNA sequencing;Skin;Source;Specificity;Specimen;Stevens-Johnson Syndrome;study population;Symptoms;Systemic disease;T cell receptor repertoire sequencing;T-Cell Activation;T-Lymphocyte;T-Lymphocyte Subsets;Testing;tissue resident memory T cell;Toxic Epidermal Necrolysis;translational approach;Translational Research;Work

PROJECT_TITLE: Interrogating Clonal Repertoire in Drug Hypersensitivity Reactions

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MSOS-L (02)]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PUBLIC HEALTH RELEVANCE STATEMENT Luciferases and luciferins are essential reagents for bioluminescence assays and imaging, which have broad applications in fundamental and preclinical biological and biomedical studies. In addition, this project will derive bioluminescence imaging tools for calcium, a ubiquitous second messenger. The new tools and reagents from this study can be used to develop new drugs, monitor bioactivities, understand new biology, and track disease progression in animal models.

PI_NAMEs: AI, HUIWANG  (contact)

PROGRAM_OFFICER_NAME: ATANASIJEVIC, TATJANA

PROJECT_TERMS: Address;Adoption;Affect;analog;animal imaging;Animal Model;Animals;aqueous;Area;awake;Benchmarking;Biological;Biological Assay;Biology;Bioluminescence;bioluminescence imaging;Brain;Buffers;Calcium;calcium indicator;carboxylesterase;Catalysis;Categories;Cells;chemical stability;coelenterazine;Consumption;Derivation procedure;design;Directed Molecular Evolution;Disease Progression;Dose;Elements;Energy Transfer;Engineering;Exhibits;experimental study;Family;Firefly Luciferases;fundamental research;Image;Imaging Device;imaging study;In Vitro;in vitro Assay;in vivo;Injections;Insecta;interest;Islets of Langerhans Transplantation;Kidney;Learning;Light;Liver;Luciferases;luciferin;Lung;marine;meter;Molecular;Monitor;mouse model;Mus;mutant;Neurons;next generation;non-invasive imaging;novel therapeutics;Optics;Outcome;oxidation;Oxygen;Penetration;Performance;Photons;Physiological;Polyethylene Glycols;Positioning Attribute;pre-clinical;prevent;Production;Promega;Proteins;public health relevance;Reagent;red fluorescent protein;redshift;Renilla Luciferases;Reporter;Reproducibility;Research;response;Second Messenger Systems;Sensory;Signal Transduction;Solubility;success;System;Tissues;tool;Toxic effect;tumor xenograft;viral gene delivery;Virus Diseases;Water;water solubility

PROJECT_TITLE: Next-Generation ATP-Independent Luciferases, Luciferins, and Bioluminescent Calcium Indicators

STUDY_SECTION: CBP

STUDY_SECTION_NAME: Chemical Biology and Probes Study Section[CBP]


NIH_SPENDING_CATS: Bioengineering;Brain Cancer;Brain Disorders;Cancer;Genetics;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurosciences;Rare Diseases

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

PHR: PROJECT NARRATIVE Label-free optical microscopy, combined with artificial intelligence (AI), has emerged as a promising method for the rapid imaging of fresh, unprocessed surgical specimens, bedside brain tumor diagnosis, margin delineation, and molecular genetic prediction. Existing AI methodologies are limited because they rely on weak, slide- or patient-level annotations for model training, and are therefore unable to capture the cellular complexity and spatial heterogeneity found in diffuse gliomas. The objective of this research is to develop an innovative AI-based system to learn single-cell optical image features and identify patient-level clusters, without weak supervision, in order to advance the role of AI in diffuse glioma research and enable better, and more personalized care.

PI_NAMEs: JIANG, CHENG  (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: Artificial Intelligence;artificial intelligence method;artificial intelligence model;Benchmarking;Biology;Brain Neoplasms;Cancer Biology;cell type;Cells;Chromatin Structure;Computer Vision Systems;convolutional neural network;Databases;deep learning;Detection;detection method;Diagnosis;Diagnostic;Diffuse;experience;Future;genetic predictors;Genomics;Glioma;Goals;Heterogeneity;Histologic;Histology;Histopathology;Human;Image;imaging modality;improved;innovation;Label;Learning;learning strategy;Machine Learning;Medical Imaging;Methodology;Methods;Microscopy;Modeling;Molecular;Molecular Diagnosis;Molecular Genetics;Morphology;novel;Nuclear;Operative Surgical Procedures;optical imaging;Optics;Pathologic;Patient-Focused Outcomes;Patients;personalized care;Phenotype;Physicians;Positioning Attribute;Primary Brain Neoplasms;rapid technique;Reproducibility;Research;Resolution;Role;self supervised learning;single cell analysis;single cell genomics;skills;Slide;Specimen;Subgroup;Supervision;System;Time;Tissue Fixation;tool;Training;tumor;Tumor Biology;tumor diagnosis;Validation;World Health Organization

PROJECT_TITLE: Single-cell optical phenotyping for diffuse gliomas using artificial intelligence and label-free microscopy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10C-D (20)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Contraception/Reproduction;Depression;Estrogen;Mental Health;Mental Illness;Neurosciences;Prevention;Women's Health Research

PHR: PROJECT NARRATIVE  More than 150 million women worldwide use oral contraceptives (OCs), and for about 10% of users, OCs trigger severe mood-related adverse consequences including depression. In this project, we will use a mouse model recently validated in our laboratory to understand how OCs contribute to depression vulnerability via modulation of the HPA axis. This research will allow for a personalized approach for prescribing OCs to limit adverse effects and enhance benefits.

PI_NAMEs: SCHUH, KRISTEN  (contact)

PROGRAM_OFFICER_NAME: KAUFMAN, STEVEN

PROJECT_TERMS: acute stress;Address;Adverse effects;adverse outcome;Affective;Anxiety;Behavior;behavior measurement;Behavioral;Binding;Biochemical;biological adaptation to stress;Brain;Brain region;Chronic;Contraceptive Agents;Contraceptive Usage;Corticosterone;Corticotropin;CRISPR/Cas technology;Data;Dorsal;Enzyme-Linked Immunosorbent Assay;Equilibrium;Estrogens;Ethinyl Estradiol;Ethinyl Estradiol/Levonorgestrel;Exhibits;Exposure to;Feedback;feeding;field study;Formulation;Future;Genetic Techniques;Glucocorticoid Receptor;Goals;Gonadal Hormones;Hippocampus;hormonal contraception;Hormones;Human;Hypothalamic structure;hypothalamic-pituitary-adrenal axis;Immunohistochemistry;improved;Individual;Intervention;knock-down;Knowledge;Laboratories;Levonorgestrel;Life;Limbic System;Measures;Mental Depression;Mental disorders;Mineralocorticoid Receptor;Molecular;Moods;mouse model;Mus;Oral Contraceptives;paraventricular nucleus;Peripheral;personalized approach;personalized medicine;Persons;Phenotype;Physiological;Post-Traumatic Stress Disorders;preference;Prevention;Progesterone;psychologic;Public Health;receptor;Receptor Activation;Receptor Signaling;Recording of previous events;Regulation;Research;resilience;response;Risk;Role;side effect;Signal Transduction;Stress;Stress and Coping;stress related disorder;stressor;Sucrose;Tacrolimus Binding Proteins;Time;Vulnerable Populations;Western Blotting;Woman

PROJECT_TITLE: Regulation of stress and depression by hormonal contraceptives

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F02A-W (20)]


ORG_CITY: Pittsburgh

ORG_NAME: MAGEE-WOMEN'S RES INST AND FOUNDATION

PHR: PROJECT NARRATIVE: Males suffering from non-obstructive azoospermia (NOA) have limited options to have biological children. In the future, AAV gene therapy could offer new promise and a therapeutic approach to cure infertility in NOA patients. I will demonstrate that AAV gene therapy can be implemented to safely and ethically treat NOA caused by Sertoli cell dysfunction without the risk of germline transmission and that this therapy has potential applications to humans. My project will help develop a bench to bedside approach to show a route forward for testicular somatic cell gene therapy to the clinic.

PI_NAMEs: ATKINS, GEORGIA RAE  (contact)

PROGRAM_OFFICER_NAME: KENT, TRAVIS JOHN

PROJECT_TERMS: Abnormal Karyotype;Academia;Address;adeno-associated viral vector;bench to bedside;beta Actin;biobank;Biological;Blood-Testis Barrier;Breeding;career;Cell Physiology;cell type;Cells;Chickens;Child;Clinic;Congenital Abnormality;Couples;CRISPR/Cas technology;Data;Defect;Dependovirus;Development;diagnostic development;diagnostic tool;Ejaculation;Embryo;Ethics;Exhibits;exome sequencing;Faculty;Failure;feasibility testing;Fertility;Foundations;Functional disorder;Funding;Future;Gene Modified;Gene Mutation;gene therapy;Genes;Genetic;genetic variant;Genome;Genotype;Germ Cells;Germ Lines;Grant;Histology;Human;human model;human tissue;Hypogonadism;Immunohistochemistry;in vivo;Infection;Infertility;insight;Intracytoplasmic Sperm Injections;Japan;KITLG gene;Klinefelter's Syndrome;Knock-out;Knowledge;Legal;leydig interstitial cell;male;Male Infertility;Mediating;Meiosis;Melanogenesis;men;Methods;Modeling;Modification;mouse genome;mouse model;Mus;Mutation;Natural regeneration;next generation sequencing;novel;Organ Culture Techniques;Patients;Phenotype;polycarbonate;Production;pup;Reporter Genes;Reporting;Research;Research Personnel;Risk;Route;Safety;safety and feasibility;screening;self-renewal;Seminiferous tubule structure;Serotyping;sertoli cell;skills;Somatic Cell;Somatic Gene Therapy;species difference;Specificity;sperm cell;Spermatogenesis;Spermiogenesis;System;Techniques;Technology;Testicular Tissue;Testing;Testis;Therapeutic;Toxic effect;Toxicity Tests;transduction efficiency;translation to humans;Translations;transmission process;Tubular formation;Variant;vector;whole genome;Work;Y chromosome deletion;Y chromosome microdeletions

PROJECT_TITLE: AAV gene therapy to restore fertility in mammalian Sertoli cell dysfunction models

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F06-L (20)]


ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE The major clinical obstacle in EGFR-targeted therapy of lung cancer is the development of acquired resistance that limits its long-term efficacy. Thus, understanding molecular mechanisms underlying the acquired resistance and accordingly developing mechanism-driven effective strategies to overcome acquired resistance are highly desirable and urgently needed in the clinic. This proposal will primarily focus on the critical impact of PGC1β/PPARγ modulation on therapeutic efficacy of EGFR-targeted cancer therapy with particular emphasis on identifying effective strategies for overcoming acquired resistance through targeting PGC1β/PPARγ.

PI_NAMEs: SUN, SHI-YONG  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Accounting;Affect;Agreement;antagonist;Area;Biological;Biology;Cancer cell line;Cell Line;Cell Physiology;Cells;Chemicals;Chemoresistance;Clinic;Clinical;Data;Development;Disease;Disease remission;Down-Regulation;Ectopic Expression;Energy Metabolism;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Event;FDA approved;FOSL1 gene;Gene Family;Generations;Genes;genetic approach;Genetic Suppression;improved;In Vitro;in vivo;in vivo Model;innovation;knock-down;Knowledge;lipid biosynthesis;lipid metabolism;lung cancer cell;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;Molecular;mutant;Mutation;Non-Small-Cell Lung Carcinoma;overexpression;patient subsets;Patients;Peroxisome Proliferator-Activated Receptors;Play;PPAR gamma;PPARG gene;promoter;Proteins;Regulation;Resistance;Resistance development;resistance mutation;response;Role;success;targeted cancer therapy;targeted treatment;Testing;Therapeutic;therapeutically effective;transcription factor;transcriptome sequencing;Treatment Efficacy;tumorigenesis

PROJECT_TITLE: Targeting PGC1β/PPARγ axis for overcoming acquired resistant to third generation EGFR-TKIs

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MCTC-S (01)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Genetics;Infectious Diseases;Rare Diseases

PHR: PROJECT NARRATIVE Ebola virus (EBOV), part of the Filoviridae family, causes periodic outbreaks of severe hemorrhagic fever and Ebola virus disease, with case fatality rates as high as 90%. There is increasing evidence that viruses can antagonize the immune response by interfering with host ubiquitin-dependent pathways, or by hijacking the host ubiquitination machinery to promote viral pathogenesis. In this proposal, I will show how EBOV VP35’s interaction with the host ubiquitin machinery affects its function and change host-viral dynamics.

PI_NAMEs: UWASE, GRACE  (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Address;Affect;antagonist;Binding;Biochemical;Biological;Biological Assay;Biology;Bioterrorism;Calorimetry;career;Case Fatality Rates;Category A pathogen;Cells;Clinical;Co-Immunoprecipitations;cofactor;Communicable Diseases;Communication;Complex;Data;design;Deuterium;Disease Outbreaks;Ebola;Ebola Hemorrhagic Fever;Ebola virus;Educational process of instructing;Enzymes;Eukaryota;Family;Filovirus;Future;Genetic Transcription;Goals;Health;Human;Hydrogen;Immune;Immune response;Immunofluorescence Immunologic;Immunologist;improved;Infection;inhibitor;Innate Immune Response;Integration Host Factors;Interferometry;Interferon Type I;Interferon-beta;Interferons;Kinetics;Knowledge;Life Cycle Stages;Ligase;Literature;Location;Mass Spectrum Analysis;Mediating;member;Mentors;Mentorship;microbial;Molecular;National Institute of Allergy and Infectious Disease;novel;pathogen;Pathogenesis;Pathogenicity;Pathway interactions;Patient Care;Periodicals;Phosphoproteins;Physicians;Play;Polymerase;Post-Translational Protein Processing;promoter;Property;prophylactic;protein purification;Proteins;Proteomics;response;RNA chemical synthesis;RNA Viruses;Role;Scientist;Shotguns;Signal Transduction;Site-Directed Mutagenesis;skills;structural biology;Symptoms;TBK1 gene;Techniques;Testing;Therapeutic;Thermodynamics;tool;Training;training opportunity;Transfection;Ubiquitin;ubiquitin isopeptidase;ubiquitin ligase;ubiquitin-protein ligase;Ubiquitinated Protein Degradation;Ubiquitination;Up-Regulation;vaccine development;Viral;Viral Genome;Viral Hemorrhagic Fevers;Viral Pathogenesis;Viral Proteins;Virulent;Virus;Virus Replication;Vocational Guidance;Work;Zoonoses

PROJECT_TITLE: Defining how ubiquitination of Ebola viral proteins affect host-viral dynamics

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07C-S (20)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative The coronavirus disease 2019 (COVID-19) associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently, and will continue to be, a major threat to public health. Given the rapid emergence of novel variants and the long-term complications associated with the recovery from COVID-19, the development of novel drug therapies for the treatment of COVID-19 is imperative. Virus replication is reliant on the expression of the p38β kinase and the research proposed here will characterize both the host- and virus-mediated mechanisms responsible in order to enhance the understanding of SARS-CoV-2 biology while identifying putative novel targets with therapeutic potential for COVID-19.

PI_NAMEs: HIGGINS, CHRISTINA  (contact)

PROGRAM_OFFICER_NAME: PLIMACK, MARY KATHERINE BRADFORD

PROJECT_TERMS: 2019-nCoV;Ablation;Acute respiratory failure;Affect;Affinity Chromatography;Agonist;Anti-viral Response;Attenuated;attenuation;Biology;Cell Line;Cells;Cessation of life;Characteristics;Chemicals;chemokine;combat;COVID-19;COVID-19 pandemic;COVID-19 treatment;COVID-19 vaccine;cytokine;Data;Development;Double-Stranded RNA;Down-Regulation;Drug Targeting;druggable target;Effectiveness;experimental study;Family;Generations;Genetic;Genetic Transcription;Goals;Human;IFIH1;Immune;Immune response;improved;Infection;Inflammation;Inflammatory;Inflammatory Response;inhibitor;Integration Host Factors;Interferon Type I;Interferons;Interleukin-6;Knock-out;MAPK11 gene;Mass Spectrum Analysis;Mediating;Messenger RNA;Mitogen-Activated Protein Kinases;Molecular Biology;Monitor;Mutation;novel;novel therapeutics;Nucleocapsid;Nucleocapsid Proteins;Organ failure;p38 Mitogen Activated Protein Kinase;Pathology;Pathway interactions;Pattern recognition receptor;Pharmacotherapy;Phenotype;Phosphopeptides;Phosphorylation;Phosphotransferases;Play;Population;pressure;prevent;Process;Production;Protein Isoforms;Proteins;Public Health;receptor;Recovery;Research;response;Role;SARS-CoV-2 antiviral;SARS-CoV-2 B.1.1.7;SARS-CoV-2 infection;SARS-CoV-2 variant;severe COVID-19;Signal Pathway;Signal Transduction;Signal Transduction Pathway;Site;Specificity;Stimulus;targeted treatment;Testing;Therapeutic;TNF gene;Translations;Variant;Vertebrates;Viral;Viral Proteins;Virus;Virus Diseases;virus host interaction;Virus Replication

PROJECT_TITLE: Characterization of the SARS-CoV-2-mediated piracy of p38ß


ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative Almost half of the identified genes underlying hereditary podocytopathies, which are clinically characterized by steroid-resistant nephrotic syndrome, encode for proteins involved in actin cytoskeletal functions. Mutations in α-actinin-4, a mechanically regulated actin crosslinker expressed in podocytes, cause focal segmental glomerulosclerosis (FSGS). This proposal aims to elucidate structural mechanisms of deficient actin mechanosensing by FSGS-causing α-actinin-4 variants via cryo-EM, and completing this project will advance mechanistic insights into how impairments in actin cytoskeletal functions drive podocytopathies.

PI_NAMEs: CHIN, ALFRED CHOON KIT (contact)

PROGRAM_OFFICER_NAME: MARIC-BILKAN, CHRISTINE

PROJECT_TERMS: Actin-Binding Protein;Actins;Adhesions;Affect;Affinity;alpha Actinin;autosome;Binding;Biochemical;Biological Assay;Biophysical Process;biophysical properties;Carbon;career;causal variant;Cells;Clinical;Complex;computer studies;crosslink;Crosslinker;Cryoelectron Microscopy;Cytoskeleton;Data;Development;Disease;Doctor of Philosophy;Elasticity;End stage renal failure;Exclusion;Exhibits;F-Actin;Fellowship;Film;Fluorescence Microscopy;Focal and Segmental Glomerulosclerosis;Foot Process;Genes;Genetic;Geometry;glomerular filtration;Goals;hemodynamics;human disease;Impairment;In Vitro;Inherited;Injury;innovation;insight;Institution;Length;mechanical force;Mechanics;mechanotransduction;Mediating;Mentorship;Methods;Modeling;Molecular;Molecular Conformation;Molecular Motors;Motor;mutant;Mutation;Myosin ATPase;Network-based;neural network;next generation sequencing;novel therapeutics;optic trap;optical traps;Patients;Physicians;Physiological;podocyte;programs;protein protein interaction;Proteins;reconstitution;Research;Research Personnel;response;Role;Scientist;Signal Transduction;single molecule;Steroid Resistance;Steroid-resistant idiopathic nephrotic syndrome;Structure;Students;synergism;Technology;Therapeutic immunosuppression;therapeutically effective;Training;Universities;Variant;Visualization

PROJECT_TITLE: Structural basis for deficient actin mechanosensing in ACTN4-driven podocytopathy

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-G (O1)]