NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Cardiovascular;Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Prevention;Social Determinants of Health

PHR: PROJECT NARRATIVE This project will advance knowledge about the impact of power outages on cardiovascular outcomes in the context of climate change. We plan to examine the role of power outages on cardiovascular disease, to understand the effects of outages during anomalously hot and anomalously cold temperatures, and to identify communities especially vulnerable to the effect of outages on cardiovascular disease outcomes. Our project can shape approaches to minimize outage-related morbidity and inform equitable preparedness strategies, emergency response, and energy policies.

PI_NAMEs: DO, VIVIAN  (contact)

PROGRAM_OFFICER_NAME: PURKISER, KEVIN

PROJECT_TERMS: Acute;Address;Adult;Affect;Age;Air;American;Area;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;Cardiovascular system;Cause of Death;Censuses;Characteristics;Climate;climate adaptation;climate change;Code;cold temperature;Color;Communities;community engagement;Confounding Factors (Epidemiology);Cross-Over Studies;Data;design;Devices;Diagnostic;disability;Disasters;disease disparity;Disease Outcome;Disparity;Economics;Electricity;Emergency response;environmental justice;Equity;Event;experience;Exposure disparity;Exposure to;extreme temperature;Face;Future;Goals;Health;health data;health difference;health disparity;health equity;High temperature of physical object;Hospitalization;Hour;Human body;human disease;Hurricane;indexing;Individual;Infrastructure;insight;Knowledge;Life;Literature;Logistic Models;Low income;marginalized community;Measures;Morbidity - disease rate;Myocardial Infarction;National Heart, Lung, and Blood Institute;National Institute of Environmental Health Sciences;neighborhood disadvantage;Neighborhoods;New York;New York City;novel;Outcome;outcome disparities;Pathway interactions;Policies;Population;population health;predictive modeling;Race;Racial Segregation;Readiness;Research;Research Design;Research Support;Resolution;response;Role;segregation;severe weather;Shapes;social;social vulnerability;sociodemographics;spatiotemporal;Strategic Planning;Stressful Event;Stroke;System;Temperature;Time;tool;vulnerable community;Vulnerable Populations;warm temperature

PROJECT_TITLE: The effects of power outages on cardiovascular outcomes in New York State

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F18-E (20)]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: ATLANTA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_FIPS: US

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Our comprehensive proposed studies using our large COVID-19 cohort will assess innate, and humoral and cellular immunity over an 8-year period. This provides an extraordinary and unprecedented look at the durability and evolution of human T and B cell memory after vaccination and infection. This will provide insight into the underlying mechanisms of long-term immune memory and also inform how we develop optimal vaccination strategies against emerging viral infections.

PI_NAMEs: AHMED, RAFI  (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: 2019-nCoV;adaptive immunity;Address;age effect;aged;Antigens;B-Lymphocytes;Biometry;Blood specimen;booster vaccine;breakthrough infection;Cancer Center;Cellular Immunity;Clinical;clinical research site;cohort;COVID-19;COVID-19 patient;Epigenetic Process;Evolution;Genomics;Goals;Human;Humoral Immunities;Immunity;Immunologic Memory;immunosenescence;Individual;Infection;insight;Institution;longitudinal analysis;Memory B-Lymphocyte;Messenger RNA;Myeloid Cells;Natural Immunity;Patients;Persons;programs;recruit;Research Personnel;response;Sampling;SARS-CoV-2 infection;T cell response;T-Lymphocyte;Time;Universities;Vaccination;vaccination strategy;Vaccines;Virus Diseases;Washington

PROJECT_TITLE: Vaccine and Infection Induced Immunity in the Young and Aged

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


PHR: The Administrative Core is designed to play a central role in the coordination of both scientific and administrative activities among the various institutions represented at the Emory University CCHI and to promote synergistic interactions.

PROJECT_TERMS: aged;Applications Grants;Biometry;Clinical;Communication;conflict resolution;Data;data management;Deposition;design;Ensure;Environment;Fostering;Genomics;Goals;Human;Immunity;Immunologic Memory;Immunology;immunosenescence;Infection;Infrastructure;Institution;Intellectual Property;material transfer agreement;meetings;Natural Immunity;operation;Play;Policies;Process;Productivity;Progress Reports;Property Rights;Recommendation;Research;Research Personnel;Research Project Grants;Role;success;symposium;synergism;United States National Institutes of Health;Universities;Vaccines

PROJECT_TITLE: CORE A: ADMINISTRATIVE CORE


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Vaccines;Emerging Infectious Diseases;Genetics;Human Genome;Immunization;Infectious Diseases;Prevention;Vaccine Related

PHR: The Genomics Core will enable single-cell technology capable of integrating the transcriptome. leverage novel technology development with the PIs by applying it to each project, and will adapt existing, emergent technology to address the specific objectives of each Project.

PROJECT_TERMS: 2019-nCoV;Acceleration;Adaptive Immune System;Address;aged;Algorithms;Antibodies;Antibody-mediated protection;Antigens;ATAC-seq;B cell repertoire;B-Lymphocytes;Bar Codes;Benchmarking;Bioinformatics;Biological Assay;Cadaver;Cells;Cellular biology;Chromatin;cohort;Complex;Coronavirus spike protein;COVID-19 pandemic;COVID-19 vaccination;Data;Development;DNA;Emerging Technologies;Epitopes;Evolution;Funding;Gene Expression;Gene Expression Profile;Genetic Transcription;genome-wide;genomic profiling;Genomics;Goals;Growth;high dimensionality;Human;human data;Humoral Immunities;Immune;Immune response;Immunity;Immunoglobulin Genes;Immunoglobulins;Immunologic Receptors;Immunology;Individual;Infection;Innate Immune System;insight;Libraries;Link;Macrophage;Maps;Measures;Methodology;Methods;Modality;Modernization;multimodality;Neighborhoods;neutralizing antibody;new technology;novel;Oligonucleotides;Phenotype;Population;protein profiling;Proteins;public repository;receptor;Regimen;Research;Resolution;response;Role;Sampling;SARS coronavirus;SARS-CoV-2 antibody;SARS-CoV-2 pathogenesis;SARS-CoV-2 spike protein;SARS-CoV-2 variant;senescence;single cell genomics;single cell technology;single-cell RNA sequencing;Specificity;Surface;T-Lymphocyte Subsets;Technology;technology development;Tissues;tool;transcription factor;transcriptome;transcriptomics;Vaccination;Vaccinee;Vaccines;Validation;Variant;Work

PROJECT_TITLE: CORE B: GENOMICS CORE


NIH_SPENDING_CATS: Aging;Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Immunization;Infectious Diseases;Post-Acute Sequelae of SARS-CoV-2 infection (PASC) including Long COVID;Prevention;Vaccine Related

PHR: The Clinical/statistical Core remains a vital component of the Emory CCHI program and continues to support the CCHI scientific agenda for over 15 years. The clinical units of the Core will manage the Covid-19 cohort and support the projects providing sample collection to support the CCHI scientific agenda.

PROJECT_TERMS: adaptive immunity;age group;aged;Aging;biological specimen archives;Biometry;Biostatistics Core;Bone Marrow Aspiration;Cancer Center;Characteristics;Clinic;Clinical;clinical infrastructure;Clinical Practice Guideline;Clinical Protocols;Clinical Research;cohort;Collaborations;Communicable Diseases;complex data;COVID-19;Data;Data Collection;data management;Data Set;data sharing;Data Storage and Retrieval;Development;Enrollment;Ensure;experience;Fine needle aspiration biopsy;Future;Goals;Good Clinical Practice;Grant;Health;Human;human coronavirus;Immune;Immune response;Immunity;Immunologic Memory;Immunologics;Immunology procedure;immunosenescence;improved;Infection;insight;Institution;interest;Knowledge;Long COVID;longitudinal analysis;Longitudinal cohort;Longterm Follow-up;lymph nodes;Measures;Methods;Modeling;Monitor;Mucous Membrane;Natural Immunity;novel;pandemic disease;Parameter Estimation;Participant;participant enrollment;participant retention;pathogen;Patients;Phase;Plasma Cells;Procedures;programs;Public Health;Reproducibility;Research;Research Design;Research Personnel;Research Support;sample collection;Sampling;SARS-CoV-2 immunity;Severity of illness;Site;skills;Specimen;Statistical Data Interpretation;success;Symptoms;Tissues;Universities;Vaccination;vaccine trial;Vaccines;Viral

PROJECT_TITLE: CORE C: CLINICAL AND BIOSTATISTICS CORE


NIH_SPENDING_CATS: Aging;Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Vaccines;Emerging Infectious Diseases;Genetics;Immunization;Infectious Diseases;Prevention;Vaccine Related

PHR: Our proposed studies using our large COVID-19 cohort will assess humoral and cellular immunity over an 8- year period. This provides an extraordinary and unprecedented look at the durability and evolution of human T and B cell memory after vaccination and infection and will provide insight into the underlying mechanisms of long-term immune memory and also inform how we develop optimal vaccination strategies against emerging viral infections.

PROJECT_TERMS: 2019-nCoV;adaptive immune response;aged;Antibody Response;Antigens;Binding;Biostatistics Core;Blood specimen;Bone Marrow;Bone Marrow Aspiration;booster vaccine;breakthrough infection;Cancer Center;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Differentiation process;Cellular Immunity;Clinical;clinical research site;cohort;Collaborations;COVID-19;COVID-19 patient;Epigenetic Process;Evolution;experience;Genetic Transcription;Genomics;Goals;Human;Humoral Immunities;Immunity;Immunologic Memory;Immunology;immunosenescence;Individual;Infection;insight;Institution;Knowledge;Longevity;Longitudinal cohort;Memory;Memory B-Lymphocyte;memory CD4 T lymphocyte;Molecular;Mucous Membrane;Natural Immunity;neutralizing antibody;Patients;Phenotype;Plasma Cells;programs;recruit;Research Personnel;response;RNA vaccine;Sampling;SARS-CoV-2 infection;Secondary Immunization;success;T cell differentiation;T-Lymphocyte;Time;translational study;Universities;Vaccination;vaccination strategy;Vaccines;variants of concern;Virus;Virus Diseases

PROJECT_TITLE: PROJECT 1: IMMUNE MEMORY


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Vaccines;Emerging Infectious Diseases;Genetics;Immunization;Infectious Diseases;Influenza;Pneumonia and Influenza;Prevention;Vaccine Related

PHR: We will use novel systems biological approaches to determine whether the evolutionarily ancient innate immune system has “immunological memory,” long thought to be a unique feature of the adaptive immune system. This will be explored in humans in the context of SARS-CoV-2 infection and vaccination.

PROJECT_TERMS: 2019-nCoV;Adaptive Immune System;Address;Adjuvant;aged;Attenuated Vaccines;Behavior;biological systems;Blood;Cell Lineage;cell type;Cells;Chromatin;cohort;COVID-19;COVID-19 vaccination;COVID-19 vaccine;cytokine;Dendritic Cells;Dengue Virus;Epigenetic Process;epigenomics;Evolution;Exposure to;Frequencies;Genes;Genetic Transcription;Grant;Health Personnel;Human;Immune;Immune response;Immunity;Immunization;Immunologic Memory;Immunologic Receptors;imprint;In Vitro;Infection;Inflammatory;Influenza A Virus, H5N1 Subtype;influenza virus vaccine;Innate Immune System;Interferons;Knockout Mice;Ligands;longitudinal analysis;Lymphoid Tissue;Memory;monocyte;Mucous Membrane;Mus;Myelogenous;Myeloid Cells;Natural Immunity;nonhuman primate;novel;Organ Donor;pandemic disease;pandemic influenza;pathogen;Peripheral Blood Mononuclear Cell;Pfizer-BioNTech COVID-19 vaccine;post SARS-CoV-2 infection;receptor;Resistance to infection;Resources;response;RNA vaccination;Sampling;SARS-CoV-2 infection;single cell analysis;single cell ATAC-seq;Time;Tissues;Training;transcription factor;Transcription Factor AP-1;Vaccination;Vaccines;Virus;Zika Virus

PROJECT_TITLE: PROJECT 2: INNATE IMMUNITY


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Mental Health;Neurosciences

ORG_CITY: STANFORD

ORG_DEPT: PSYCHIATRY

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: PROJECT NARRATIVE We need new methods to track mental health symptoms that can be obtained passively, objectively, remotely, and continuously. Here, we combine video recordings, invasive brain measurements, and frequent symptom assessment to model mood using continuous video-derived facial and speech patterns as well as map the brain activities underlying these patterns. This objective mood classifier can aid in diagnostic screening, treatment optimization, and relapse prediction.

PI_NAMEs: KELLER, COREY J (contact);PARVIZI, JOSEF

PROGRAM_OFFICER_NAME: TILGHMAN, JESSICA IRENE

PROJECT_TERMS: Acute;acute symptom;Address;Affect;Affective;Amygdaloid structure;Area;Behavior;Behavioral;Blinded;Blood Pressure;Brain;Brain Mapping;Classification;Clinic;Clinic Visits;Clinical;Clinical assessments;clinical care;comorbid depression;comorbidity;Complement;Computer Vision Systems;Consumption;cost;Data;deep learning model;Dependence;Depressed mood;depressive symptoms;Descriptor;Diabetes Mellitus;diagnostic screening;Disease;Dose;Electric Stimulation;Electroencephalography;Electrophysiology (science);Emotions;Enrollment;Epilepsy;Evaluation;Face;Facial Muscles;Frequencies;Friends;Functional Magnetic Resonance Imaging;Glucose;Goals;Hallucinogens;Home;Hour;Human;Hypertension;implantation;improved;individual variation;Inpatients;insight;Insula of Reil;Intervention;Joints;Label;Linear Regressions;Link;Major Depressive Disorder;Manuals;Maps;Measurement;Measures;Mental Health;Methods;Modeling;Monitor;Mood Disorders;Moods;Movement;National Institute of Mental Health;Nature;Negative Valence;neural;neural correlate;Neurons;neuroregulation;novel;Operative Surgical Procedures;Outpatients;Output;Parietal Lobe;Patient Self-Report;patient stratification;Patients;Pattern;Performance;Physiology;predictive modeling;Property;Provider;Psychiatric therapeutic procedure;relapse prediction;remote health care;Research;Resources;rumination;Sampling;Severities;Speech;Speech Acoustics;standard of care;Standardization;Statistical Models;Structure;suicidal risk;Surveys;Symptoms;System;Technology;telehealth;Testing;Time;Training;treatment optimization;Variant;Video Recording

PROJECT_TITLE: Behavioral and Neuronal Correlates of Human Mood States

STUDY_SECTION: NPAS

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


ADMINISTERING_IC: CA

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Epilepsy;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE Gliomas are aggressive brain tumors with a dismal prognosis. Recent evidence has shown that neuronal activity promotes glioma proliferation and progression, but the mechanisms that mediate these effects are poorly understood and it is unclear how different types of neuronal activity, including seizures and stimulus-evoked neuronal activity, may affect glioma cells. This proposal aims to investigate and target a novel mechanism of glioma-neuron crosstalk to advance our understanding of how neuronal activity contributes to glioma progression.

PI_NAMEs: PEREIRA, BRIANNA  (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Acute;Address;Affect;Agonist;awake;barrel cortex;Biopsy;Brain;Brain imaging;Brain Neoplasms;brain tissue;Calcium;calcium indicator;Calcium Signaling;cancer cell;career;Cell Proliferation;Cells;cellular engineering;clinical application;clinical training;Collaborations;Color;Dedications;Development;Diffuse;Electrophysiology (science);Epilepsy;Event;ex vivo imaging;excitatory neuron;Exhibits;extracellular;Family;Fellowship;Foundations;Genetic;genetically modified cells;Glioma;Goals;Growth;Herbert Irving Comprehensive Cancer Center;Home;Hospitals;Human;Hyperactivity;Image;improved;In Vitro;in vitro Assay;in vivo;in vivo two-photon imaging;Induced Neurons;Infiltration;inhibitor;insight;Ion Channel Gating;Knock-out;Knowledge;Ligands;Maps;Mediating;Medical center;Mentorship;Modeling;Molecular;Mus;neuro-oncology;Neuroglia;Neurologic;neuronal tumor;Neurons;Neurosciences;neurotransmission;New York;novel;novel therapeutic intervention;novel therapeutics;Nursing Faculty;Optics;P2X-receptor;Pathologic;Pathology;PDGFA gene;Permeability;pharmacologic;Physicians;Physiological;Presbyterian Church;Primary Brain Neoplasms;Prognosis;Proliferating;prototype;Purines;Purinoceptor;receptor;Receptor Activation;receptor expression;Reporter;Research;research faculty;Research Training;Resources;response;Role;Scientist;Seizures;sensor;Sensory;sensory stimulus;Signal Transduction;skills;Slice;Stimulus;System;Testing;Time;Training;tumor;Tumor Biology;tumor microenvironment;tumor progression;Tumor Promotion;two-photon;Universities;Vibrissae

PROJECT_TITLE: Targeting Purinergic Signaling to Block the Effects of Seizures on Glioma Progression

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


NIH_SPENDING_CATS: Microbiome

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE Human gut commensals Bacteroides spp. produce spherical membranous structures known as outer membrane vesicles (OMVs), which are proposed to participate in essential physiological roles like nutrient degradation and immunomodulation. However, our understanding of bacterial vesiculation is still in its infancy, and, therefore, determining the physiological relevance of Bacteroides OMVs has been challenging. In this project, we will investigate a family of regulators and proteins involved in OMV production. By employing OMV markers as tools, we will also investigate vesicle production in vivo and assess the impact it has on bacterial fitness and colonization.

PI_NAMEs: FELDMAN, MARIO  (contact)

PROGRAM_OFFICER_NAME: RANALLO, RYAN

PROJECT_TITLE: Biogenesis of outer membrane vesicles in human gut bacteria

STUDY_SECTION: PCMB

STUDY_SECTION_NAME: Prokaryotic Cell and Molecular Biology Study Section[PCMB]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Macular Degeneration;Neurodegenerative;Neurosciences;Orphan Drug;Prevention;Rare Diseases

ORG_CITY: SAN FRANCISCO

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: NARRATIVE Inherited retinal degenerations, caused by mutations in over 300 genes, lead to progressive vision loss in people between 15-45 years of age and most are currently untreatable. We have identified a common mechanism that drives disease pathology in diverse inherited retinal degenerations. This research will investigate the efficacy of two small molecule drugs that target this mechanism for their ability to prevent inflammation, retinal degeneration, and vision loss in mouse models of disease.

PI_NAMEs: LAKKARAJU, APARNA  (contact)

PROGRAM_OFFICER_NAME: SHEN, GRACE L

PROJECT_TERMS: acid sphingomyelinase;adiponectin;Age Years;Agonist;Binding;Biogenesis;bisphosphonate;Blindness;Catabolism;Cells;Cellular Metabolic Process;Ceramidase;Ceramides;Cholesterol;cholesterol biosynthesis;Clinical;Complement;Defect;Desipramine;Disease;disease model;drug action;drug candidate;drug distribution;Drug Targeting;efficacy evaluation;Endosomes;Evaluation;Face;FRAP1 gene;Functional disorder;Gene Expression;gene therapy;gene-editing approach;Generations;Genes;Genetic;genetic approach;Genetic Predisposition to Disease;glial activation;GRN gene;Heterogeneity;Homeostasis;Infiltration;Inflammation;Inherited;inherited retinal degeneration;inhibitor;Injury;insight;intravital imaging;Lead;lipidomics;Lipids;Mediating;Metabolic;mevalonate;Microglia;Mitochondria;Modeling;Molecular Target;mouse model;Mus;Mutation;novel;Osteoporosis;Pathogenicity;Pathologic;Pathology;Pathway interactions;Persons;Pharmaceutical Preparations;Phenotype;photoreceptor degeneration;Photoreceptors;prenylation;prevent;Publishing;receptor;Regulation;Research;Retina;Retinal Degeneration;Retinal Dystrophy;Safety;Signal Transduction;small molecule;Spielmeyer-Vogt Disease;Stargardt's disease;Structure;Structure of retinal pigment epithelium;superresolution imaging;Techniques;Testing;Therapeutic;therapeutic development;therapeutic evaluation;therapeutic target;therapeutically effective;transcriptomics;Treatment Efficacy;Tricyclic Antidepressive Agents;Variant;Vision;Zoledronic Acid

PROJECT_TITLE: Triple threat therapeutics for inherited retinal degenerations

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Lung;Pneumonia;Pneumonia and Influenza;Urologic Diseases

PHR: PROJECT NARRATIVE Acinetobacter baumannii (Ab) is a bacterium that is highly resistant to antibiotics and often causes outbreaks in hospitals. We propose that new Ab strains are introduced into hospitals by patients previously infected with this bacterium which can remain dormant in the patient, reemerging upon hospital treatments that weaken their immune systems. In this proposal we will employ mice models to investigate how and where Ab survives within the patients.

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Acinetobacter baumannii;Alveolar Macrophages;Antibiotic Resistance;Antibiotic Therapy;Bacteria;Bacterial Infections;Bladder;Blood Circulation;Catheterization;Catheters;Cells;Chemicals;Clinical;Communities;Development;Disease Outbreaks;Epithelial Cells;Equipment;Evaluation;Event;Exhibits;Future;Genetic;Gram-Negative Bacteria;Health;health care settings;Hospitalization;Hospitals;Hour;Human;Human body;Immune system;Immunocompetent;Immunocompromised Host;Immunosuppression;In Vitro;Infection;Inflammatory Response;Intervention;Kidney;Lead;Lung;Lung infections;Macrophage;Measures;Mechanical ventilation;Medical;Microscopic;Modeling;Modernization;mouse model;Multi-Drug Resistance;Multiple Bacterial Drug Resistance;Mus;Names;Nosocomial Infections;Nosocomial pneumonia;Organ;pathogen;Pathogenesis;Patients;Pneumonia;pneumonia model;prevent;Preventive treatment;Pulmonary Inflammation;Reporting;Resolution;respiratory;Respiratory System;Respiratory Tract Infections;Role;secondary infection;soft tissue;Source;Sterilization;Surface;surveillance strategy;Testing;Touch sensation;transmission process;Tube;urinary;Urinary tract;Urinary tract infection;Urine;Uropathogen;Vacuole;Ventilator;ventilator-associated pneumonia

PROJECT_TITLE: Acinetobacter baumannii reservoirs within the host

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IIDB-P (02)]


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative  Human O-GlcNAcase (OGA) is an essential enzyme, and its dysregulation has been detected in numerous diseases including cancer. This application aims to elucidate novel structures and mechanisms underlying OGA’s complex regulations and pave the way for development of more selective and effective therapies for challenging diseases.

PI_NAMEs: JIANG, JIAOYANG  (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Acetylation;Architecture;Binding;Binding Sites;Biochemical;Biology;Catalytic Domain;cell growth regulation;Cells;Complex;Consensus Sequence;Coupling;Development;Discrimination;Disease;Drug Targeting;effective therapy;Enzymes;Fostering;Foundations;Goals;histone acetyltransferase;Human;Hydrolysis;insight;interest;Intervention;Investigation;Length;Malignant Neoplasms;Modeling;mutant;Mutation;Nerve Degeneration;novel;Nucleic Acid Regulatory Sequences;Nutrient;Pathway interactions;peptide O-linked N-acetylglucosamine-beta-N-acetylglucosaminidase;Peptides;Play;Post-Translational Protein Processing;programs;Protein Acetylation;protein complex;Protein Dynamics;Protein Glycosylation;Proteins;Proteomics;Regulation;Research;Resolution;response;Role;Series;Site;Specificity;Stress;structural biology;Structural Models;Structure;Substrate Interaction;synergism;therapeutic target

PROJECT_TITLE: Structural insights into the functional regulation of O-GlcNAcase

STUDY_SECTION: MSFB

STUDY_SECTION_NAME: Macromolecular Structure and Function B Study Section[MSFB]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Congenital Structural Anomalies;Genetics;Lymphatic Research;Pediatric

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

ORG_STATE: WA

PHR: Project Narrative Lymphatic malformations (LMs) are a common developmental malformation consisting of a mass of overgrown lymphatic channels. Mutations in the oncogene PIK3CA drive the formation of LMs, but surprisingly these mutations are typically present in less than 10% of cells in the lesion. By better understanding the precise location of the mutant cells and their corresponding gene expression programs within intact human LM tissues we will advance our understanding of how these malformations develop, improve the development of novel therapies, and improve the lives of individuals with vascular malformations and other mosaic disorders in general.

PI_NAMEs: LOY, KELSEY ALEXANDRA (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: Affect;airway obstruction;AKT Signaling Pathway;Alleles;Architecture;Automobile Driving;Bioethics;Blood Vessels;Cell Communication;cell type;Cells;Child;Clinical;cohort;Communication;Complex;Congenital Abnormality;Cortical Dysplasia;Data;Deglutition;Development;Diagnosis;Diameter;Disease;Distant;DNA sequencing;experimental study;Functional disorder;Gene Expression;Genetic;Genetic Heterogeneity;Genetic Transcription;Genotype;Grant;Growth;Head and neck structure;Heterogeneity;Human;Impairment;improved;In Situ;In Vitro;in vivo;Individual;innovation;interest;Investigation;Knowledge;Lesion;Life;Live Birth;Location;lymphatic development;Lymphatic Endothelial Cells;lymphatic malformations;lymphatic vessel;malformation;Malignant Neoplasms;Manuscripts;Measurement;Measures;Mediating;Mentorship;Methods;Molecular;Molecular Diagnosis;Morphogenesis;mosaic;Mosaicism;mutant;Mutate;Mutation;mutational status;nano-string;new therapeutic target;novel;novel therapeutics;Oncogenes;Outcome;Paracrine Communication;Pathway interactions;PECAM1 gene;Phenotype;PIK3CA gene;PIK3CG gene;podoplanin;Preparation;programs;protein expression;Proteins;Proto-Oncogene Proteins c-akt;Research;Research Training;Resolution;RNA;RNA analysis;Spatial Distribution;Speech;Stains;statistics;Structure;targeted treatment;Techniques;Tissue Sample;Tissues;Training;Training Programs;transcriptomics;tumor heterogeneity;Up-Regulation;Work;Writing

PROJECT_TITLE: Spatial Heterogeneity in PIK3CA-Mutated Lymphatic Malformations

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Cancer

ORG_CITY: SILVERTHORNE

ORG_NAME: KEYSTONE SYMPOSIA

ORG_STATE: CO

PHR: PROJECT NARRATIVE Cancer is a major cause of mortality worldwide. Increased understanding of mechanisms that drive and sustain cancer will provide new avenues to reduce incidence and to treat the disease. This Keystone Symposia conference on Tumor Metabolism will advance the field by bringing together investigators from related yet distinct areas of research to explore the important roles of metabolism in cancer.

PI_NAMEs: SHEPPARD, TERRY L. (contact)

PROGRAM_OFFICER_NAME: LUO, RUIBAI

PROJECT_TERMS: Alberta province;Area;Biology;Canada;cancer cell;career;career development;Cells;Collaborations;Communities;Dependence;Development;Disease;Drug Industry;Educational workshop;Electronic Medical Records and Genomics Network;Emerging Technologies;Environment;Environmental Risk Factor;Event;Fostering;Goals;Growth;Health;Image;In Vitro;in vivo;Incidence;industry partner;Integration Host Factors;interest;International;Learning;Link;Lysosomes;Malignant Neoplasms;Measures;member;Membrane;Metabolic;Metabolism;Mitochondria;mortality;multidisciplinary;neoplastic cell;Nutrient;Organ;Organelles;Outcome;Participant;Pathway interactions;Patients;Physiology;posters;pre-clinical;Process;programs;Research;Research Personnel;Role;Scientist;Signal Transduction;Site;sound;Standardization;stressor;symposium;Techniques;Thinking;Tissues;tool;Translating;tumor metabolism;tumor microenvironment;tumor progression;Work

PROJECT_TITLE: Tumor Metabolism

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 PCRB-9 (O1)]


NIH_SPENDING_CATS: Biotechnology;Cardiovascular

ORG_CITY: BOSTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

ORG_STATE: MA

PHR: PROJECT NARRATIVE  GPCRs are the largest class of membrane proteins in humans and have been linked with many cardiovascular disorders. While GPCRs make up a third of all FDA-approved drugs, including for example widely prescribed anti-hypertensives, many potentially druggable GPCRs remain intractable because they lack known ligands to modulate their activity. Here, I propose a platform to systematically generate probes to modulate understudied GPCRs, which would serve as a steppingstone to study them and develop new therapeutic agents.

PI_NAMEs: FITZSIMMONS, ARI BENJAMIN (contact)

PROGRAM_OFFICER_NAME: HUANG, LI-SHIN

PROJECT_TERMS: Agonist;antagonist G;Anti-Hypertensive Agents;Antibodies;Area;Asthma;autocrine;Autocrine Communication;Bacteria;Basic Science;Benchmarking;Binding;Biological Products;Biology;Bioreactors;Biosensor;Cardiovascular Diseases;Cardiovascular Physiology;Cardiovascular system;Cell surface;Cells;Chemicals;Clinic;Cloning;Collection;Coronary heart disease;Data;Development;Devices;Directed Molecular Evolution;Drug Prescriptions;druggable target;efficacy evaluation;Ensure;Evolution;Family;FDA approved;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Goals;GPER gene;Growth;GTP-Binding Proteins;Guidelines;Heart failure;Hormones;Human;Human Genome;Hypertension;Immunoglobulin Fragments;in silico;innovation;Libraries;Ligands;Link;Lipids;Mammalian Cell;Membrane;Membrane Proteins;Molecular Evolution;nanobodies;new technology;novel therapeutics;Optics;Orphan;Peptides;Pharmaceutical Preparations;pharmacologic;Pharmacology;Photons;promoter;Proteins;Protons;prototype;receptor;receptor binding;receptor expression;reconstitution;Reporter;Research;Respiratory Disease;Role;Running;Saccharomyces cerevisiae;scale up;screening;Signal Transduction;Signaling Molecule;small molecule;Specificity;success;synthetic protein;System;Testing;Therapeutic;Therapeutic Agents;therapeutic candidate;Thrombosis;tool;Variant;Yeasts

PROJECT_TITLE: Molecular evolution of synthetic probes for orphan GPCRs

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-D (21)]


ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: Project Narrative Cardiac fibrosis can compromise cardiac function and eventually lead to heart failure, and chimeric antigen receptor (CAR) T cells represent a potential strategy for ablating pathologically activated fibroblasts that can cause cardiac fibrosis. This project aims to explore the feasibility of T cell engaging therapies in cardiac fibrosis, and also identify the mechanisms and effects of CAR T cell cross talk with other cardiac cellular populations. These findings will provide insights into the effects of cellular immunotherapies in cardiac fibrosis, and help identify ways to maximize their therapeut ic potential in this novel setting.

PI_NAMEs: YANG, STEVEN  (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: Ablation;Acute;Affect;Angiotensin II;Attenuated;bi-specific T cell engager;Cardiac;Cardiovascular Diseases;Cause of Death;Cell Communication;Cells;Cellular immunotherapy;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;chimeric antigen receptor T cells;Chronic;Collagen;coronary fibrosis;Cytokine Signaling;cytotoxicity;Data;Development;engineered T cells;Environment;Event;Excision;experience;experimental study;fibroblast-activating factor;Fibroblasts;Fibrosis;Generations;Genetic;Genetic Transcription;Heart;heart cell;Heart Diseases;Heart failure;heart function;Heart Injuries;heart preservation;high throughput screening;Human;hypertensive;IFNGR1 gene;Immune;immunoregulation;Impairment;improved;Inflammation;Inflammatory;insight;Interferon Type II;Interleukin-4;Knockout Mice;Label;Laboratories;Macrophage;Measures;Modeling;mouse model;Mouse Strains;multimodality;Mus;Myocardial;Myocardium;neutralizing antibody;novel;Outcome;Pathologic;Patients;pharmacologic;Phenylephrine;Population;prevent;Production;receptor;Relaxation;Reporter;Safety;Shapes;Signal Pathway;Signal Transduction;Source;Stromal Cells;Surface;T cell therapy;T-Cell Receptor Therapy;T-Lymphocyte;targeted treatment;TCR Activation;Techniques;Technology;Testing;Therapeutic;Therapeutic Effect;TNFSF5 gene;tool;transcriptomics;Treatment Failure;treatment strategy

PROJECT_TITLE: Exploring the immunomodulatory effects of anti-FAP CAR T cells in cardiac fibrosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10A-K (20)]


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Pancreatic Cancer;Rare Diseases

ORG_CITY: CORAL GABLES

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE

ORG_STATE: FL

PHR: Project Narrative Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate of all major cancers in the United States. Based on preliminary results my research will assess how MTH1 modulates PDAC tumorigenesis by evaluating both tumor intrinsic and tumor extrinsic responses using novel mouse models and in vitro models. Successful completion of this study will validate MTH1 as a new pharmacologically actionable target for PDAC and validate novel MTH1 conditional KO as a tool to study KRAS-driven cancers.

PI_NAMEs: MATEO-VICTORIANO, BEATRIZ  (contact)

PROGRAM_OFFICER_NAME: ADAMS, GREGORY

PROJECT_TERMS: Address;Affect;Animal Experimentation;Animals;Apoptotic;Area;Biology;cancer cell;Cancer Etiology;Cancer Model;cell injury;Cell Line;Cell Proliferation;Cells;Cessation of life;Chemoresistance;chemotherapy;Clinic;Clinical;cohort;conditional knockout;COVID-19;cytokine;Data;Death Rate;Development;Disease;Disease-Free Survival;DNA;DNA Damage;Epidermal Growth Factor Receptor;Epithelial Cells;experimental study;Flow Cytometry;Genomic DNA;Genotype;Germ Lines;Homologous Gene;Human;Immune;in vitro Model;in vivo;Infiltration;inhibitor;knockout animal;KRAS oncogenesis;KRAS2 gene;KRASG12D;Link;LoxP-flanked allele;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;metabolic profile;Modeling;Molecular;Molecular Analysis;mouse model;Mutation;Myeloid-derived suppressor cells;neoplastic cell;Normal Cell;Normal tissue morphology;novel;novel therapeutics;Nucleotides;Oncogenes;Oncogenic;Oncoproteins;Outcome;overexpression;Oxidation-Reduction;oxidative damage;Oxidative Stress;Oxidative Stress Induction;Pancreas;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;paracrine;Pathway interactions;Patients;Pattern;pharmacologic;prevent;Proliferating;Proteins;Radiation;RAS driven tumor;Reactive Oxygen Species;repaired;Reporting;Research;Resistance;response;Role;sample archive;senescence;Signal Transduction;single-cell RNA sequencing;small hairpin RNA;small molecule;Standard Model;standard of care;Stress;Survival Rate;Testing;The Cancer Genome Atlas;Therapeutic;Therapeutic Intervention;therapeutically effective;Time;Tissues;tool;tumor;Tumor Burden;tumor microenvironment;tumor progression;Tumor Promotion;Tumor Tissue;tumor-immune system interactions;tumorigenesis;Tumorigenicity;United States;Validation

PROJECT_TITLE: Defining Novel Redox Stress Mechanisms to Inhibit KRAS-driven Pancreatic Ductal Adenocarcinoma


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Social Determinants of Health

ORG_CITY: CHICAGO

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Community Engagement: A Short Course to Optimize Research Endeavors (CE-SCORE) will enhance the knowledge and skills of contemporary behavioral and social science researchers (BSSR) around community- engaged research and practice to advance public health goals in the United States. Current students, scholars, practitioners, and educators at various stages of their careers will engage in critical adult education learning cohorts and join a new community of practice. This community of practice will foster multi-directional mentoring relationships between students, scholars, practitioners and educators to sustain an intentional focus on prioritizing community agency in BSSR scholarship and practice.

PI_NAMEs: NEUBAUER, LEAH C;PHILLIPS, GREGORY L. (contact)

PROGRAM_OFFICER_NAME: VAN VOORHEES, COURTE CHRISTIAN WIRTH

PROJECT_TERMS: Academic Training;Address;Adopted;Adult;Applications Grants;Area;Behavioral;behavioral and social science;career;cohort;Communities;community based participatory research;community building;Community Consents;community empowerment;community engaged research;community engagement;community involvement;Community of Practice;community organizations;community partnership;comorbidity;contextual factors;Course Content;Data;demographics;design;Development;Discipline;Documentation;E-learning;Education;education research;educational atmosphere;Educational Curriculum;empowerment;Equity;Evaluation;follow-up;Fostering;Foundations;Future;Generations;Goals;Health;health equity;health goals;health inequalities;Healthcare;HIV;Impact evaluation;improved;Individual;innovation;Institution;Intervention;Knowledge;knowledge translation;Learning;learning community;learning outcome;Lived experience;Malpractice;marginalization;marginalized community;Medical;member;Mental disorders;Mentors;Mentorship;Methodology;Methods;minority health disparity;Movement;Outcome;Participant;Pattern;Philosophy;Policies;Politics;Population;Procedures;Process;Program Evaluation;programs;Public Health;Research;Research Design;Research Methodology;Research Personnel;Research Project Grants;research to practice;response;Risk;scale up;Scholarship;Scientist;Self Efficacy;skills;social;Social Change;Social Environment;Social Justice;social science research;Students;substance misuse;Teaching Method;Testing;theories;Theory of Change;time use;Training;Translational Research;Trust;United States;virtual;Voice;Work

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BP-R (50)]


ORG_DEPT: OTHER BASIC SCIENCES

PHR: PROJECT NARRATIVE  Angiogenesis is crucial for tissue homeostasis and growth, yet it remains unclear how angiogenesis is spatially and temporally regulated to drive proper neovascularization therapeutically in settings such as tissue ischemia, or to block vascularization of tumors. This study will use innovative tissue-engineered human microvessels and sophisticated molecular and imaging approaches to deepen our understanding of endothelial control systems that enable angiogenesis, and inform future efforts towards development of new therapeutic interventions for driving or blocking tissue vascularization.

PI_NAMEs: MAYO, LAKYN NICOLE (contact)

PROJECT_TERMS: 3-Dimensional;Actins;Actomyosin;Adaptor Signaling Protein;Adherens Junction;Adhesives;angiogenesis;Angiogenic Factor;Automobile Driving;Binding;Biological;Biology;Biomimetics;Biotinylation;Blood Vessels;cadherin 5;California;Cardiovascular system;career;cell motility;Cell-Cell Adhesion;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Co-Immunoprecipitations;CRISPR/Cas technology;Cues;Cytoskeletal Modeling;Cytoskeleton;Defect;Development;Endocytosis;Endothelial Cells;Endothelium;Engineering;Epithelium;Event;Exhibits;experience;Future;gain of function;genome editing;Germ Lines;Goals;Growth;Homeostasis;Human;Human Engineering;Image;imaging approach;innovation;Intercellular Junctions;interdisciplinary approach;Ischemia;Knock-out;Light;Literature;loss of function;Mass Spectrum Analysis;Mediating;Mentorship;Microscopy;migration;Modeling;Molecular;Morphogenesis;Mus;Myosin Type II;neovascularization;new growth;non-muscle myosin;Nonmuscle Myosin Type IIB;novel therapeutic intervention;Phenocopy;Phosphorylation;Physicians;Process;Proteins;Recycling;Regulation;Research;Research Institute;response;Role;San Francisco;scaffold;Scientist;Signal Transduction;Stimulus;Structure;superresolution microscopy;System;Testing;Therapeutic;Tissue Engineering;Tissues;Training;tumor;Universities;Vascular Endothelial Cell;Vascular System;Vascularization;Work

PROJECT_TITLE: Elucidating the role of Scribble in angiogenic symmetry breaking and adherens junction remodeling


NIH_SPENDING_CATS: Cardiovascular;Estrogen;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Heart Disease - Coronary Heart Disease;Hypertension;Prevention;Women's Health Research

ORG_CITY: JACKSON

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF MISSISSIPPI MED CTR

ORG_STATE: MS

PHR: Narrative: Gender-Affirming Hormone Therapy (GAHT) for transgender women, which involves estrogen supplementation combined with anti-androgen therapy, is associated with an increased risk for cardiovascular diseases compared to the general population. Yet, the mechanisms involved are unknown. This project will investigate the etiology of increased cardiovascular risk in transgender women on GAHT using a novel and innovative model of GAHT in the male rat that mimics the effect of elevated estradiol with androgen suppression.

PI_NAMEs: CRUDUP, BRELAND  (contact)

PROJECT_TERMS: Acute;Address;Adult;Age;Aging;Androgen Antagonists;Androgen Suppression;Angiotensin II;Angiotensins;Animal Model;Anti-androgen Therapy;arm;Basic Science;Biological;biological sex;Birth;Blood Pressure;blood pressure control;blood pressure regulation;Blood Vessels;Body Weight;Brain;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cardiovascular system;Castration;Cerebrovascular Disorders;Characteristics;Chronic Disease;cis-male;clinically relevant;cohort;Communication;Complex;Coupled;Creatinine;Data;Development;Down-Regulation;Echocardiography;Endocrine;epidemiology study;Equilibrium;Estradiol;Estrogens;Etiology;Experimental Models;Exposure to;Female;Feminization;follow-up;Gender;gender affirming hormone therapy;gender dysphoria;Gender Identity;General Population;Goals;Gonadal Steroid Hormones;Grant;Guidelines;Healthcare;Heart;heart damage;Heart Injuries;Hormonal;hormone therapy;Human;Hypertension;Inbred SHR Rats;Individual;innovation;Investigation;Kidney;Knowledge;Laboratories;Lactose;Learning;Long-Term Effects;Longitudinal Studies;male;Male Castration;Measurement;Mediating;Methods;Modeling;Myocardial Infarction;Myocardial Ischemia;normotensive;novel;Orchiectomy;Organ;organ injury;Outcome;Oxidoreductase;Participant;Pathway interactions;Phosphotransferases;Physicians;Physiological;Population;Predisposition;Prevalence;Rat Strains;Rattus;Renin-Angiotensin System;Reperfusion Therapy;Reporting;response;Risk;Risk Assessment;Rodent Model;Scientist;sex;Sex Characteristics;skills;Societies;Spironolactone;Sprague-Dawley Rats;Steroid therapy;Supplementation;System;Technical Expertise;Testing;Testis;Testosterone;Thinness;Training;transgender;transgender women;Ultrasonography;United States;Up-Regulation;Vasoconstrictor Agents;Vasodilator Agents;Weight;young adult

PROJECT_TITLE: Cross Sex Steroid Therapy and Cardiovascular Risk in the Transgender Female


ADMINISTERING_IC: DK

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Diabetes;Pediatric

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

PHR: Project Narrative  Type 1 diabetes is an autoimmune condition in which the insulin producing beta cells are selectively targeted for destruction. The specific autoantigens that are critical for disease onset have yet to be identified, however, we have identified autoantigens that may play a significant role in the development of disease. The current proposal aims to determine the origin of these autoantigens and to study if the level of these autoantigens can affect the pathogenesis of type 1 diabetes. Results from these studies may allow us to establish a disease-critical role of the antigens in the pathogenesis of diabetes.

PI_NAMEs: GROEGLER, JASON  (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Affect;Aliquot;Amines;Amino Acid Sequence;Animal Model;Antigen Targeting;Antigens;Autoantibodies;Autoantigens;Autoimmune;Autoimmune Diseases;Autoimmune Responses;Automobile Driving;autoreactivity;Beta Cell;Binding;C-Peptide;carboxypeptidase C;career;Cathepsins;CD4 Positive T Lymphocytes;Cellular Assay;Chromatography;Clone Cells;Deficiency Diseases;Detection;Development;Diabetes Mellitus;diabetes pathogenesis;diabetic;Disease;Disease Progression;Enzymes;experimental study;Family;Gene Modified;Genes;Human;Hybrids;immune cell infiltrate;Immunologics;Immunology;Inbred NOD Mice;Incidence;Incubated;Individual;inhibitor;insight;Insulin;insulin dependent diabetes mellitus onset;Insulin-Dependent Diabetes Mellitus;interest;islet;Islets of Langerhans;Isoleucine;Leucine;Link;Mass Spectrum Analysis;Mediating;Methods;Monitor;Mus;Mutation;N-terminal;neoantigens;new therapeutic target;Non obese;non-diabetic;non-genomic;Onset of illness;Organ Donor;Pancreas;Pathogenesis;Pathogenicity;Patients;Peptide Fragments;Peptide Hydrolases;Peptides;peripheral blood;Play;prevent;Process;Proinsulin;protein aminoacid sequence;Proteins;Proteome;Proteomics;Reaction;Recombinants;Research;Research Design;Research Personnel;Residual state;Risk Factors;Role;Sampling;Serum;Site;skills;Specificity;Subgroup;success;T cell response;T-Lymphocyte;Testing;therapeutic target;Thymus Gland;transpeptidation;Wild Type Mouse;Work

PROJECT_TITLE: Study the role and origin of hybrid insulin peptides in the pathogenesis of type 1 diabetes

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-2 (O1)]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Clinical Research;Contraception/Reproduction;Fibroid Tumors (Uterine);Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Racial and Ethnic Minority Health Research;Women's Health Research

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE We know very little about the role of germline variants in fibroid tumorigenesis despite fibroids being highly heritable, prevalent in the population, and recently identified variants having associated with risk. Despite the significant disparities and impact of fibroids among Black women, little progress has been made relative to other complex diseases, despite federal research agencies including the NIH, ORWH, and AHRQ recognizing fibroids among their priority women’s health topics. To our knowledge our study will be the first and largest evaluation of overall and cell-specific myometrial gene expression associated with fibroid risk among Black women, that leverages existing GWAS data and RNA sequencing approaches.

PI_NAMEs: EDWARDS, TODD L;MOHAMMED, AMINU ZAKARI;VELEZ EDWARDS, DIGNA R (contact)

PROGRAM_OFFICER_NAME: TINGEN, CANDACE M

PROJECT_TERMS: Affect;Africa;African;African American;African ancestry;Age;Asian population;Atlases;Benign;Black Populations;black women;cell type;Cells;clinical diagnosis;clinical risk;Code;Complex;cost effective;Data;differential expression;Disease;Disparity;Environmental Risk Factor;Estrogens;Etiology;European ancestry;Evaluation;Fibroid Tumor;Funding Agency;Gene Expression;gene expression database;gene function;Genes;Genetic study;Genetic Variation;Genome;genome wide association study;genome-wide;Genotype;Geographic Locations;Germ Lines;Germ-Line Mutation;Goals;Grant;Health Care Costs;Heritability;high risk;HMGA2 gene;Hysterectomy;Individual;Insulin;interest;Locales;Mediating;Mediation;Menopause;Menstruation;MicroRNAs;Modeling;Myometrial;myometrium;next generation sequencing;Nigeria;Nigerian;novel;Pain;Participant;Pathway interactions;Pelvic Pain;Population;predictive modeling;Pregnancy Complications;pressure;racial health disparity;Reproductive Health;Research;Research Infrastructure;Research Priority;Risk;Risk Factors;risk variant;RNA;Role;Running;Sampling;single-cell RNA sequencing;statistics;Testing;Tissue Banks;Tissue-Specific Gene Expression;Tissues;trait;transcriptome sequencing;Tumor Tissue;tumorigenesis;Twin Studies;United States Agency for Healthcare Research and Quality;United States National Institutes of Health;Uterine Fibroids;Uterine Neoplasms;Uterus;Validation;Variant;White Women;Whole Blood;Woman;Women's Health

PROJECT_TITLE: Evaluating the impact of altered gene expression on uterine fibroid risk in African ancestry populations

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


NIH_SPENDING_CATS: Cancer;Genetics;Immunotherapy;Orphan Drug;Rare Diseases;Skin Cancer

ORG_DEPT: DERMATOLOGY

PHR: Project Narrative Merkel cell carcinoma is the most aggressive and fatal skin cancer with rapidly rising incidence. The mechanism by which some patients respond, relapse, or resist immunotherapy is not understood. This project aims to identify biomarkers of immunotherapy response and the mechanism by which this occurs.

PI_NAMEs: REINSTEIN, ZACHARY ZALE (contact)

PROJECT_TERMS: Adverse event;Alleles;Antigen Targeting;antigen-specific T cells;Antigens;Antitumor Response;Automobile Driving;Binding;Bioinformatics;Biological Assay;Biological Markers;biomarker identification;carcinogenesis;career;case-by-case basis;CD8-Positive T-Lymphocytes;cell killing;Cells;Cellular Immunology;central tolerance;chemotherapy;Clinical;Clinical Trials;combinatorial;Combined Modality Therapy;Communication;cytotoxicity;Data;Data Set;Databases;Development;Disease;DNA Damage;experimental study;Fellowship;fighting;Foundations;Future;Genetic Predisposition to Disease;Goals;Heterogeneity;Histocompatibility;Human;Image;immune checkpoint;immune checkpoint blockade;Immune response;Immunofluorescence Immunologic;Immunology;Immunotherapy;In Situ;Incidence;Infiltration;Knock-out;Knowledge;Large T Antigen;Ligands;Malignant Neoplasms;Mediating;Memory;Mentors;Merkel cell carcinoma;Merkel Cells;Modeling;Mutation;neoantigens;neoplastic cell;neuroendocrine cancer;novel;novel marker;novel therapeutic intervention;patient response;Patients;PD-1/PD-L1;Peptides;Phenotype;Physicians;Polyomavirus;Population;predicting response;Privatization;prognostic;Protein Analysis;rational design;receptor;Relapse;Research;Resistance;resistance mechanism;Resolution;Resources;response;Sampling;Scientist;screening;single-cell RNA sequencing;skills;Skin Cancer;Small T Antigen;Somatic Mutation;Survival Rate;T cell response;T cell therapy;T-Cell Receptor;T-Lymphocyte;T-Lymphocyte Subsets;therapy design;Thymus Gland;tissue resident memory T cell;Tissues;Training;tumor;Tumor Antigens;tumor microenvironment;United States;Vaccines;Viral;Viral Oncogene;Viral Tumor Antigens;Virus

PROJECT_TITLE: Identifying the Mechanism of Resistance to Immunotherapy in Merkel Cell Carcinoma (for Zachary Reinstein)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09C-Z (20)]


NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Cancer;Lung;Neuroblastoma;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: PITTSBURGH

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: PROJECT NARRATIVE Intraoperative molecular imaging (IMI) with 111In-dinutuximab-IR800 could assist in localizing and completely resecting GD2-expressing pediatric cancers such as high-risk neuroblastoma and metastatic osteosarcoma, which currently have 5-year-survival rates of only 50% and 20%, respectively. Here, we propose to optimize probe manufacturing, evaluate safety, and test the ability to detect pulmonary osteosarcoma metastases of our group’s recently designed GD2-targeted IMI probe, 111In-dinutuximab-IR800. We will use results from these aims to prepare an IND and design an early phase clinical trial for intraoperative use of 11In-dinutuximab-IR800 in the surgical resection of neuroblastoma and osteosarcoma metastases.

PI_NAMEs: ROSENBLUM, LAUREN TAYLOR (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: Adolescent;Biodistribution;Biological;bone;cancer type;Chemistry;Childhood;chimeric antibody;Clinical;clinical translation;Clinical Trials;Complement;design;Detection;detector;Disease;Disseminated Malignant Neoplasm;Dose;early phase clinical trial;Excision;experience;FDA approved;Fluorescence;Fluorescent Dyes;fluorophore;Future;Goals;high risk;Image;imaging agent;imaging probe;improved;in vivo;Label;Legal patent;Lesion;Localized Disease;Location;Lung;lymph nodes;Maintenance Therapy;Malignant Childhood Neoplasm;Malignant Neoplasms;manufacture;Measures;melanocyte;Mentors;Metastatic Neoplasm to the Lung;Metastatic Osteosarcoma;Methods;molecular imaging;mouse model;Mus;Neoplasm Metastasis;Neuroblastoma;Normal tissue morphology;Operative Surgical Procedures;Organ;Orphan Drugs;Osteosarcoma;overexpression;Palpation;Pathology;Pediatric Neoplasm;Pentetic Acid;Peripheral;Pharmacology;Pharmacology and Toxicology;Phase I Clinical Trials;Preparation;primary bone cancer;Primary Lesion;Protocols documentation;Radioisotopes;Radiolabeled;Recurrence;research clinical testing;Resected;Safety;Sprague-Dawley Rats;Surface;Surgeon;Survival Rate;targeted imaging;Testing;Thoracotomy;Tissues;Toxic effect;Toxicology;Translating;tumor;Tumor Antigens;Visual;Visualization;Xenograft procedure

PROJECT_TITLE: Intraoperative Molecular Imaging of Metastatic Osteosarcoma with 111In-dinutuximab-IR800


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Natural killer (NK) cells are crucial for host defense against viral infection, and patients with primary NK cell deficiencies have been shown to have significant morbidity and mortality from unresolved viral infections. However, the molecular regulators that promote optimal effector function in human NK cells, and the associated metabolic changes that are required to meet the increased energy demands of activated NK cells remain poorly understood. Our proposed studies will describe how a novel transcriptional regulator of cytokine-induced metabolic adaptation promotes NK cell antiviral function, expanding our understanding of the molecular and metabolic mechanisms that regulate NK cell antiviral activity.

PI_NAMEs: LI, JOEY H. T. (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Acetates;Activated Natural Killer Cell;Address;Anti-viral Agents;Anti-viral Response;Anti-viral Therapy;antiviral immunity;Binding;Carbon;Cell Proliferation;Cells;Cellular biology;Cellular Metabolic Process;chronic infection;Clinical;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;COVID-19;CRISPR screen;CRISPR/Cas technology;cytokine;Cytokine Activation;Cytolysis;Cytomegalovirus;Cytomegalovirus Infections;cytotoxicity;Data;Effector Cell;enhancing factor;Equilibrium;extracellular;Fibroblasts;FRAP1 gene;Gas Chromatography;Genetic Transcription;Glucose;Glycolysis;Hepatitis C;Herpesviridae;Herpesviridae Infections;Herpesvirus Type 3;HIV-1;Homeostasis;Host Defense;Human;immunodeficiency;Impairment;improved;In Vitro;in vivo;Incubated;Infection;Infection Control;Inflammatory;Interferon Type II;Interleukin-15;Interleukin-2;Knock-out;Link;Lipids;Mediating;Mediator;Metabolic;Metabolic Pathway;Metabolism;Molecular;Morbidity - disease rate;mortality;Murid herpesvirus 1;Mus;Muscle Cells;Muscle Fibers;Natural Killer Cells;NK Cell Activation;novel;Oxidative Phosphorylation;Patients;penis foreskin;Phosphotransferases;preclinical study;Predisposition;Production;Proliferating;Protein Family;Regulation;response;Ribonucleoproteins;Role;Signal Transduction;SRE-1 binding protein;Supplementation;tandem mass spectrometry;Testing;Transcript;transcription factor;Transcriptional Regulation;Up-Regulation;uptake;Viral;Viral Physiology;Virus Diseases

PROJECT_TITLE: Transcriptional regulation of NK cell metabolism and effector function by MEF2C

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


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Biotechnology;Brain Disorders;Depression;Digestive Diseases;Mental Health;Mental Illness;Nanotechnology;Neurosciences;Pain Research

ORG_NAME: NEW YORK UNIVERSITY

PHR: Although selective serotonin reuptake inhibitors (SSRIs) are a primary therapy for individuals with Disorders of gut-brain interaction (DGBIs) and mood disorders, they have severe limitations (e.g., low efficacy and adverse effects [GI pain, dysmotility, and (paradoxical) anxiety]) that we found are due to their systemic absorption beyond the gut epithelium. Specifically, our published and preliminary data show that: (A) beneficial SSRI effects (anxiolytic, anti-depressive, anti-nociceptive) result from SERT antagonism in the GI epithelium and may involve vagal- and 5-HT3-mediated signaling and; (B) surprisingly, detrimental SSRI effects result from ENS or CNS SERT antagonism (anxiety, dysmotility, pain), implying that selective pharmacologic blockade of GI epithelial SERT could be beneficial for treating DGBIs +/- mood disorders without producing negative and efficacy-reducing effects linked to systemic SSRI exposure. We now propose to: (Aim 1) elucidate the roles of vagal signaling in linking gut epithelial 5-HT to beneficial effects on GI motility and pain sensitivity as well as mood; (Aim 2) examine how ENS SERT ablation affects DGBI symptoms and mood, to determine if avoidance of ENS SERT antagonism is necessary to prevent the negative and efficacy-reducing effects associated with systemic SSRI use and; (Aim 3) determine whether a state-of-the-art SSRI delivery platform that we have recently created, that maximally disperses and retains SSRI locally on the intestinal epithelium and minimizes systemic absorption, provides the beneficial mood effects of SSRIs while avoiding deleterious effects on GI pain, GI motility and mood.

PI_NAMEs: ANSORGE, MARK SASCHA;LEONG, KAM W;MARGOLIS, KARA GROSS (contact)

PROGRAM_OFFICER_NAME: SHEA-DONOHUE, TEREZ

PROJECT_TERMS: Ablation;absorption;Acute;Adverse effects;Affect;affective disturbance;antagonist;Anti-Anxiety Agents;antinociception;Anxiety;base;bench-to-bedside translation;Brain Stem;Central Nervous System;Chronic;Clinical Research;Cognition;comorbidity;Constipation;Data;Defect;depressive symptoms;Development;Diagnosis;Diarrhea;Disease;Disease remission;disorder risk;disorders of gut-brain interaction;Drug Delivery Systems;Drug Design;Drug Kinetics;Enteral;Enteric Nervous System;Epithelium;Esthesia;experimental study;FDA approved;fetal;Functional disorder;Future;gastrointestinal;gastrointestinal epithelium;gastrointestinal function;Gastrointestinal Motility;gastrointestinal symptom;gut-brain axis;Individual;intestinal epithelium;Link;Mediating;Mental Depression;Modeling;Mood Disorders;mood regulation;mood symptom;Moods;Morbidity - disease rate;Motility;motility disorder;Mus;nanoneedle;nanoparticle;novel;novel therapeutics;Outcome;Pain;pain sensitivity;particle;Patients;pharmacologic;Play;prevent;Publishing;Recurrence;Regulation;Resolution;reuptake;Role;Selective Serotonin Reuptake Inhibitor;Serotonin;Signal Transduction;Symptoms;System;Testing;Time;Translating;transmission process;Vagotomy

PROJECT_TITLE: Differentiating the roles and underlying mechanisms of serotonin in the gut epithelium and ENS to create a novel drug delivery system to treat disorders of gut-brain interaction and mood dysfunction

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 KUDS-W (03)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Gene Therapy;Genetics;Hematology;Immunotherapy;Lymphatic Research;Lymphoma;Rare Diseases

PHR: Project Narrative: Adoptive cellular therapies have limited efficacy in solid tumors which account for 90% of adult cancers. The CARD protein-BCL10-MALT1 signaling complex is an essential mediator of T cell activation, and the novel CARD11-PIK3R3 fusion identified by our group has demonstrated robust and dramatic anti-tumor efficacy in vivo. This proposal aims to understand the mechanisms by which CARD11-PIK3R3 improves T cell fitness and anti-tumor efficacy in order to advance our understanding of T cell biology, elucidate mechanisms to engineer more effective T cell therapies, and ultimately provide more efficacious treatment options for patients.

PI_NAMEs: CHENG, KATHLEEN  (contact)

PROJECT_TERMS: Address;Adoptive Cell Transfers;Adult;Affect;Antibodies;Antigens;BCL10 gene;Biological Assay;cancer cell;CAR T cell therapy;career;CD8B1 gene;Cell model;Cell Therapy;Cells;Cellular biology;Cellular Immunology;chimeric antigen receptor T cells;Chimeric Proteins;Communication;Complex;cytokine;cytotoxic;Data;Development;efficacious treatment;engineered T cells;Engineering;eosinophil;Epigenetic Process;exhaust;exhaustion;Fellowship;Fibrinogen;fitness;Foundations;Future;Gene Fusion;Genetic;Genetic Engineering;Genetic Transcription;genome wide screen;Goals;Hematologic Neoplasms;Hematopoietic Neoplasms;Immune;Immune system;Immunocompetent;improved;In Vitro;in vivo;in vivo Model;Individual;innovation;insight;Knowledge;Laboratories;Libraries;lymphoid neoplasm;Lymphoma;Lymphomagenesis;Malignant Neoplasms;Mediator;Mentors;Metabolic;Metabolism;Methods;Mitochondria;mitochondrial dysfunction;Modeling;Modification;mouse model;Mucosa- associated lymphoid tissue lymphoma translocation protein-1;multiple omics;Mus;mutant;Mutation;neoplastic cell;NF-kappa B;novel;novel therapeutic intervention;Outcome;Pathway interactions;patient subsets;Patients;Phenotype;Physicians;PIK3R3 gene;Population;Proteins;recruit;Research;RNA;role model;Scientist;screening;Screening Result;sialic acid binding Ig-like lectin;Signal Pathway;Signal Transduction;skills;Solid Neoplasm;Source;stemness;Surface;T cell infiltration;T cell therapy;T-Cell Activation;T-Cell and NK-Cell Neoplasm;T-Cell Lymphoma;T-Lymphocyte;TCF Transcription Factor;Toxic effect;Training;transcription factor;Transcription Factor AP-1;Transgenic Mice;Treatment Efficacy;tumor;Tumor Immunity;tumor microenvironment;Tumor-Infiltrating Lymphocytes

PROJECT_TITLE: Investigating mechanisms of CARD11 mutants in enhanced anti-tumor immunity and T cell fitness (For Kathleen Cheng)


NIH_SPENDING_CATS: Antimicrobial Resistance;Cystic Fibrosis;Infectious Diseases;Lung;Orphan Drug;Rare Diseases

ORG_DEPT: PHARMACOLOGY

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because: 1) it will directly lead to an improved understanding of how Pseudomonas aeruginosa, an important lung pathogen, regulates drug metabolism and disposition in the infected host, 2) it will give us unprecedented information into structure-function relationships between the P. aeruginosa cytochrome P450 enzymes and their substrates and inhibitors, and 3) it will provide leads to design inhibitors to the P. aeruginosa CYP enzymes that may eventually serve as adjuvant therapy to treat antibiotic resistant P. aeruginosa infections. These achievements are directly related to the goals of the NIH to reduce human disease and suffering and discover novel therapeutic drug candidates to treat the infectious pathogen, P. aeruginosa. Additionally, our proposal provides an opportunity to make fundamental discoveries related to the treatment of P. aeruginosa infections and serves as a basis for improving human health.

PI_NAMEs: LAMPE, JED NOAH (contact)

PROGRAM_OFFICER_NAME: UPADHYAY, MEENU MISHRA

PROJECT_TERMS: Achievement;Adjuvant;Adjuvant Therapy;Affect;anti-microbial drug;Antibiotic Resistance;Antibiotics;Binding;Biomolecular Nuclear Magnetic Resonance;Cells;Ciprofloxacin;CYP1A2 gene;cystic fibrosis patients;Cytochrome P450;Data;design;Disease;drug candidate;drug development;drug disposition;drug metabolism;Drug Modulation;Drug Targeting;Effectiveness;Environment;Enzymes;Goals;Growth;Health;host microbiome;Human;human disease;improved;Individual;Infection;inhibitor;Knowledge;Lung;Lung infections;lung pathogen;Metabolic;microbiome;mortality;Mycobacterium tuberculosis;NMR Spectroscopy;novel;novel therapeutics;opportunistic pathogen;pathogen;pathogenic microbe;patient population;Pharmaceutical Preparations;Pharmacotherapy;Process;Proliferating;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Public Health;Pulmonary Cystic Fibrosis;Regulation;Reporting;Research;Role;secondary metabolite;Site;Specificity;Structure-Activity Relationship;Substrate Specificity;Testing;Treatment outcome;United States National Institutes of Health;Work

PROJECT_TITLE: Impact of Pseudomonas aeruginosa cytochrome P450 enzymes and secondary metabolites on drug metabolism and disposition in the cystic fibrosis patient

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 KUDS-Y (04)]


PI_NAMEs: DAVIS, MARK MORRIS (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: 2019-nCoV;Acceleration;Adult;American;Antibodies;Antigens;B-Lymphocytes;Bioinformatics;Blood;Blood specimen;Cells;Cessation of life;Clinical;cohort;Collection;Communities;COVID-19 pandemic;COVID-19 patient;COVID-19 vaccination;COVID-19 vaccine;Data;design;Development;Diabetes Mellitus;diabetic patient;Explosion;flu;Functional disorder;gene conservation;General Population;Genes;genetic signature;glycosylation;Government;Head;Health;high risk population;Home;Hospitalization;Human;human subject;Immune;Immune response;Immune system;immunodeficiency;Immunologic Monitoring;improved;In Vitro;in vitro Model;in vivo;Individual;Infection;Influenza;influenza infection;Influenza vaccination;influenza virus vaccine;insight;Lung;Lung infections;Mediating;Methods;Modeling;Molecular;new technology;Non obese;novel;novel vaccines;obese patients;Obesity;Organoids;Outcome;pandemic disease;Paper;pathogen;Pathway interactions;Persons;Phenotype;prevent;Publishing;Pulmonary Inflammation;recruit;Resources;respiratory virus;response;Risk;RNA vaccine;Sampling;SARS-CoV-2 antibody;SARS-CoV-2 antigen;SARS-CoV-2 infection;Seminal;Sequence Analysis;severe COVID-19;Skin;Spleen;Structure;System;T-Lymphocyte;Technology;technology development;Testing;Tissues;trend;Twin Multiple Birth;Vaccinated;Vaccination;vaccine access;vaccine candidate;vaccine efficacy;vaccine immunogenicity;vaccine response;Vaccines;Virus;Work

PROJECT_TITLE: Understanding Influenza and SARS-CoV-2 vaccine responses, in vivo and in vitro

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


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

PROJECT_TERMS: Collaborations;collaborative environment;Communication;COVID-19 vaccine;Data;data management;data sharing;Decision Making;Deposition;Effectiveness;Evaluation;In Vitro;in vivo;Influenza;Institution;Intellectual Property;Lead;Leadership;Licensing;Mollies;Monitor;Periodicals;Procedures;Resolution;Resource Allocation;Resources;Role;success;Technology;vaccine response

PROJECT_TITLE: Administrative Core


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

PI_NAMEs: CHINTHRAJAH, R. SHARON (contact)

PROJECT_TERMS: 2019-nCoV;Adherence;Adult;biobank;Bioinformatics;Blood;Blood Cells;Case Report Form;Cataloging;central database;Clinic;Clinical;Clinical Data;Clinical Investigator;Clinical Protocols;Clinical Research;clinical training;cohort;Collaborations;Collection;comparative;comparative efficacy;COVID-19 vaccine;Data;Data Analyses;Data Collection;data exchange;data integrity;data management;Data Set;Databases;design;Diagnosis;electronic data;Electronics;Enrollment;Evaluation;expectation;experience;follow-up;Goals;Good Clinical Practice;Health Insurance Portability and Accountability Act;Hospitals;Human;Human Resources;human subject;Immune response;Immunologic Monitoring;Immunology;improved;In Vitro;in vivo;Individual;Infection;Influenza;Information Dissemination;Information Management;Infrastructure;innate immune mechanisms;Institutional Review Boards;investigator training;Label;Laboratories;Lead;Longitudinal Studies;Lung;Modeling;Monitor;National Institute of Allergy and Infectious Disease;Organoids;Participant;participant enrollment;payment;Performance;Peripheral Blood Mononuclear Cell;Pfizer-BioNTech COVID-19 vaccine;Plasma;Practice Guidelines;preventable death;Protocols documentation;quality assurance;Quality Control;recruit;Registries;Research;Research Project Grants;Respiratory Disease;Rights;sample collection;Sampling;SARS-CoV-2 infection;screening;Services;Skin;Skin Tissue;Specific qualifier value;Specimen;Spleen;Structure of parenchyma of lung;Technology;Tissues;Tonsil;Translating;Translational Research;United States;United States National Institutes of Health;Update;Vaccination;vaccine response;vaccine-induced immunity;Vaccines;Venous blood sampling;Viral;Whole Blood;Work;Writing

PROJECT_TITLE: Clinical Core


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

PI_NAMEs: MAECKER, HOLDEN T. (contact)

PROJECT_TERMS: Archives;biobank;Biological Assay;Blood;Blood specimen;Cells;Clinical;clinical database;Clinical Research;Collaborations;complex data;Consultations;COVID-19 vaccine;Custom;cytokine;Cytometry;Data;data format;data integration;data mining;Data Set;data standards;Databases;DNA;Equipment and supply inventories;Flow Cytometry;Hemagglutinin;Human;human data;Immunologic Monitoring;Immunologics;Immunology procedure;In Vitro;in vivo;Individual;Inflammation;Influenza;influenza virus vaccine;Infrastructure;Metadata;Mission;multiple omics;Peripheral Blood Mononuclear Cell;Persons;Phenotype;Plasma;Procedures;Process;Protocols documentation;Resources;RNA;Sampling;Serum;service organization;Signal Transduction;Source;Specimen;Standardization;System;Tissues;transcriptome sequencing;Translational Research;vaccine response;vaccine trial;Visualization;web portal;Whole Blood;Work

PROJECT_TITLE: Human Immune Monitoring Center (HIMC) Core


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

PI_NAMEs: WANG, TAIA  (contact)

PROJECT_TERMS: 2019-nCoV;Activities of Daily Living;Address;Adult;Aftercare;anti-influenza;Antibodies;antibody-dependent cell cytotoxicity;Antigen Presentation;Antigen Presentation Pathway;Antigen-Antibody Complex;Antigens;Cell Physiology;Cells;chemokine;Clinical Research;Collaborations;Communicable Diseases;COVID-19 vaccination;COVID-19 vaccine;cytokine;design;Diabetes Mellitus;diabetic;Effector Cell;Engineering;Equilibrium;experimental study;Fc domain;follow-up;Foundations;Hemagglutinin;Heterogeneity;high risk;Human;Immune Sera;Immunity;Immunoglobulin G;Immunologics;immunoregulation;In Vitro;in vivo;Individual;Infection;Inflammatory;Influenza;Influenza Hemagglutinin;influenza infection;influenzavirus;Lung;Mediating;Modeling;Monoclonal Antibodies;mouse model;Mouse Strains;Mus;Non obese;non-diabetic;Obesity;Organoids;Outcome;Persons;Phagocytosis;Phenotype;Polysaccharides;Proteins;receptor;recruit;Regulation;response;Risk;SARS-CoV-2 infection;SARS-CoV-2 spike protein;Severe Acute Respiratory Syndrome;Signal Transduction;Spleen;Structure;Technology;Testing;Therapeutic Monoclonal Antibodies;Tonsil;transcriptomics;Vaccination;vaccine response;Variant;Work

PROJECT_TITLE: Regulation of antibody-mediated effector functions


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

PI_NAMEs: BARNES, CHRISTOPHER O'NEIL (contact)

PROJECT_TERMS: 2019-nCoV;adaptive immune response;Adult;Affinity;Antibodies;Antibody Response;Antibody-mediated protection;Antigen-Antibody Complex;Antigens;B-Lymphocytes;Binding;Biochemical;Bioinformatics;Biological Models;Canis familiaris;Child;Collaborations;Complement;Complex;Coronavirus;Coronavirus Infections;coronavirus vaccine;COVID-19;COVID-19 vaccination;COVID-19 vaccine;cross reactivity;Cryoelectron Microscopy;design;Development;Diabetes Mellitus;Directed Molecular Evolution;Effectiveness;Effector Cell;electron crystallography;Electron Microscopy;Engineering;Epidemic;Epitope Mapping;Epitopes;Evaluation;Event;Family suidae;Feedback;flu;FOXP3 gene;Future;Generations;Genetic;Germ Lines;Haitian;Health;Hemagglutinin;Human;human coronavirus;human disease;Human Metapneumovirus;Humoral Immunities;Immune;Immune response;Immune system;Immunity;Immunization;Immunoglobulin G;Immunology;Immunotherapy;imprint;In Vitro;in vivo;Infection;Influenza;Influenza A virus;Influenza Hemagglutinin;innovation;insight;Integration Host Factors;Intervention;Lung;Measures;member;Memory B-Lymphocyte;Modeling;Molecular;Monoclonal Antibodies;Morbidity - disease rate;mortality;nanoparticle;Negative Staining;neutralizing antibody;new pandemic;Obesity;Organoids;pandemic disease;pandemic potential;pandemic response;particle;Peripheral Blood Mononuclear Cell;Plasma;Population;Probability;Protein Engineering;receptor binding;Resolution;respiratory;respiratory virus;response;Risk;Risk Factors;RNA Viruses;Role;Sarbecovirus;SARS-CoV-2 antibody;SARS-CoV-2 spike protein;seasonal influenza;Seasons;Site;Specificity;Speed;spillover event;Spleen;structural biology;Structure;Structure of germinal center of lymph node;Subunit Vaccines;Symptoms;synergism;T cell response;T-Lymphocyte;Techniques;Technology;Testing;three dimensional structure;transmission process;Vaccinated;Vaccination;vaccination strategy;vaccine platform;vaccine response;Vaccinee;Vaccines;Variant;Viral;viral epidemic;viral pandemic;Virus;Virus Diseases;Virus Replication;weapons;Work;Zoonoses;zoonotic coronavirus;zoonotic spillover

PROJECT_TITLE: Leveraging human organoid models for the development of broad interventions to mitigate emergent respiratory viral pandemics


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Coronaviruses;Coronaviruses Diagnostics and Prognostics;Coronaviruses Disparities and At-Risk Populations;Coronaviruses Vaccines;Diabetes;Emerging Infectious Diseases;Genetics;Immunization;Infectious Diseases;Influenza;Machine Learning and Artificial Intelligence;Nutrition;Obesity;Orphan Drug;Pneumonia and Influenza;Prevention;Rare Diseases;Vaccine Related

PI_NAMEs: KHATRI, PURVESHKUMAR  (contact)

PROJECT_TERMS: 2019-nCoV;Ablation;Adopted;Affect;Anti-viral Agents;Anti-viral Therapy;Antibodies;Antibody titer measurement;Antigen-Antibody Complex;Bacterial Infections;Biological;biological heterogeneity;Biology;Blood;Blood specimen;cell type;Cells;chikungunya;Clinical;clinical heterogeneity;cohort;Cohort Analysis;Cohort Studies;Collaborations;computer framework;Computing Methodologies;Consumption;COVID-19 vaccination;COVID-19 vaccine;CRISPR/Cas technology;Data;Data Set;Databases;Development;Diabetes Mellitus;Diagnostic;diagnostic signature;Disease;Disease Outbreaks;Ebola;gene conservation;Gene Expression;Gene Expression Profile;Genes;genetic signature;Goals;Heterogeneity;Human;Hybrids;Immune;Immune response;Immunology;improved;In Vitro;in vivo;Infection;Inflammatory;Influenza;Influenza A Virus, H1N1 Subtype;Knock-in;Knock-out;machine learning method;Methods;Middle East Respiratory Syndrome Coronavirus;neural;new outbreak;next generation;novel;novel virus;Obesity;Organoids;Outcome;pandemic disease;pandemic preparedness;pathogen;Pathway interactions;Patients;peripheral blood;Pharmaceutical Preparations;Process;profiles in patients;prognostic;Proteins;response;Risk;risk prediction;Risk Reduction;Sampling;SARS coronavirus;Severities;single-cell RNA sequencing;Spleen;statistical and machine learning;System;T cell response;Technology;Testing;Therapeutic;Time;Tonsil;transcriptome;Vaccination;vaccine immunogenicity;vaccine response;Vaccines;Viral Load result;Virus;Virus Diseases;ZIKA

PROJECT_TITLE: Identifying and understanding the mechanisms for increased risk of severe infection in obesity and diabetes


PROJECT_TERMS: 2019-nCoV;Algorithms;Aliquot;Anti-CD40;Antibodies;Antigen Receptors;Antigens;Attenuated;B-Lymphocytes;Binding;Biological Assay;Biopsy;Biotinylation;Blood;Body mass index;CD8-Positive T-Lymphocytes;cell type;Cells;Clinical;Coculture Techniques;Collaborations;COVID-19 vaccine;CRISPR/Cas technology;Dendritic Cells;DNA;Epitopes;experience;Exposure to;flu;follow-up;Formalin;Genes;Genetic Transcription;Grant;Human;human subject;Immune;Immune response;Immunoglobulin Class Switching;Immunoglobulin G;Immunoglobulin M;Immunologics;improved;In Vitro;in vivo;Inbred Mouse;Individual;Infection;Infiltration;Influenza;influenza virus vaccine;Interleukin-10;Left;Link;lumazine;Lung;Lymphocyte;Methods;migration;monomer;Mus;Norway;novel;novel vaccines;Organoids;pathogen;Peptide/MHC Complex;Phenotype;prevent;Process;Protocols documentation;Reagent;Resources;response;RNA vaccine;sample fixation;SARS-CoV-2 variant;self assembly;Sequence Analysis;single cell analysis;single cell technology;Skin;Specificity;Specimen;Spleen;Stains;Standardization;Stimulus;Streptavidin;Surveys;System;T cell response;T-cell receptor repertoire;T-Lymphocyte;Technology;technology development;Testing;Time;tissue fixing;Tissues;Tonsil;tool;vaccination outcome;vaccine efficacy;vaccine evaluation;vaccine failure;vaccine immunogenicity;vaccine response;Vaccines;Virus Diseases;Work;Yellow Fever Vaccine

PROJECT_TITLE: Advancing immune organoid technology and organoid combinations


ORG_CITY: LA JOLLA

ORG_NAME: LA JOLLA INSTITUTE FOR IMMUNOLOGY

PHR: OVERALL COMPONENT NARRATIVE Our LJI CCHI was first funded in April of 2019 and it has been highly impactful in human immunology research in the past < 4 years, particularly during the COVID pandemic in the areas of COVID and COVID vaccines immune responses. The adaptive immune system is important for control of most viral infections. Improvements in controlling COVID remain somewhat impaired by our limited understanding of immune memory and upper airways immunity to SARS2, and the overarching focus connecting the three Projects in this LJI CCHI renewal proposal is immune memory, with emphasis on COVID and upper airways protective immunity.

PI_NAMEs: CROTTY, SHANE P (contact)

PROJECT_TERMS: 2019-nCoV;Acute;Adaptive Immune System;adaptive immunity;Address;Adenoidal structure;Affect;age effect;American;anti-PD1 therapy;Antibodies;Antibody Response;Antigens;Area;Aspergillus;Automobile Driving;B-cell receptor repertoire sequencing;B-Lymphocytes;Back;Biology;Blood specimen;breakthrough infection;Candida;Cause of Death;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cells;Cellular biology;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Cessation of life;Clinical;Clonality;cohort;comorbidity;Complement;COVID-19;COVID-19 pandemic;COVID-19 vaccine;cross reactivity;Data;Development;Diabetes Mellitus;Disasters;Evolution;exhaustion;experience;FluMist;Frequencies;Funding;Generations;global health;Human;human old age (65+);Human Papillomavirus;Immunity;Immunization;Immunobiology;Immunologic Memory;Immunology;immunoregulation;Impairment;improved;in vivo;Infection;Influentials;Influenza;innovation;insight;interest;Life;Living Donors;Malignant Neoplasms;Measures;Memory;Memory B-Lymphocyte;Metapneumovirus;Methodology;Mucosal Immunity;Mucous Membrane;multimodality;nasopharyngeal swab;Nature;neutralizing antibody;Operative Surgical Procedures;pandemic influenza;Paper;Parainfluenza;pathogen;pathogenic virus;Pertussis;Phenotype;Play;Policies;Positive Test Result;Property;Proteome;Public Health;Publishing;Research;respiratory pathogen;respiratory virus;response;Rest;Role;Route;Sampling;Shapes;single cell analysis;Smoking;Source;Structure of germinal center of lymph node;Surface;T cell response;T memory cell;T-Lymphocyte;Testing;Time;Tissues;transcriptome sequencing;Upper respiratory tract;Vaccinated;Vaccination;vaccine immunogenicity;vaccine response;Vaccines;Variant;Viral;Viral Respiratory Tract Infection;virtual;Virus;Virus Diseases;War

PROJECT_TITLE: Human immune memory to COVID-19, vaccines, and respiratory pathogens


NIH_SPENDING_CATS: Coronaviruses;Coronaviruses Vaccines;Emerging Infectious Diseases;Genetics;Human Genome;Immunization;Infectious Diseases;Lung;Prevention;Vaccine Related

PROJECT_TERMS: Accounting;B-cell receptor repertoire sequencing;Budgets;Cellular Assay;Clinical Research;Collaborations;Core Facility;COVID-19;COVID-19 vaccine;data sharing;data submission;Fine needle aspiration biopsy;Flow Cytometry;Funding;Goals;high dimensionality;Home;Human;human subject;Immune response;Immunologic Memory;Information Technology;Institution;interest;Knowledge;Laboratories;lymph nodes;Manuscripts;meetings;Memory;Occupations;Paper;programs;Publishing;Research Personnel;respiratory pathogen;Sampling;single-cell RNA sequencing;symposium;synergism;System;T cell receptor repertoire sequencing;T-Lymphocyte;Technology;Tissues;Training;United States National Institutes of Health;Update;Vaccines;Work


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

PI_NAMEs: SETTE, ALESSANDRO  (contact)

PROJECT_TERMS: 2019-nCoV;Adenoidal structure;Adherence;Adult;Antigens;Axillary lymph node group;B-Lymphocytes;Benign;Biopsy;Blood donor;booster vaccine;Cells;Clinical;clinical center;Clinical Immunology;clinical investigation;Clinical Research;Code;cohort;Collaborations;Collection;COVID-19;COVID-19 vaccine;design;Disease;Enrollment;Ensure;Epithelium;experimental study;Fine needle aspiration biopsy;FluMist;Foundations;Goals;Head and neck structure;Helper-Inducer T-Lymphocyte;Home;Human;Immune response;Immunization;Immunize;Immunologic Memory;Immunology;Individual;influenza virus vaccine;Institution;Institutional Review Boards;Intramuscular;Longitudinal Studies;Lymph Node of Head, Face and Neck;lymph nodes;Maintenance;Malignant - descriptor;Memory B-Lymphocyte;minimally invasive;nasopharyngeal swab;Operative Surgical Procedures;Participant;pathogen;Patients;Peripheral Blood Mononuclear Cell;Plasma;Population;Preparation;programs;Property;Protocols documentation;Quality Control;recruit;Research Institute;Resources;respiratory pathogen;response;RNA vaccine;Sampling;SARS-CoV-2 infection;Source;Structure of germinal center of lymph node;success;T memory cell;T-Lymphocyte;Time;tissue resident memory T cell;Tissue Sample;Tissues;Translational Research;Universities;Upper respiratory tract;Vaccinated;Vaccination;Vaccines;Whole Blood;Work

PROJECT_TITLE: Clinical Studies Core


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

PROJECT_TERMS: 2019-nCoV;Acute;acute COVID-19;adaptive immune response;adaptive immunity;Address;Adenoidal structure;Affinity;Antibodies;Antibody Formation;Antigens;B-Lymphocytes;Biology;Blood;booster vaccine;breakthrough infection;CD27 Antigens;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Cycle Kinetics;Cells;Characteristics;Circulation;cohort;Complement;COVID-19;COVID-19 vaccination;COVID-19 vaccine;Data;Exhibits;experimental study;FluMist;Frequencies;Human;Immune response;Immunity;Immunization;Immunologic Memory;Immunologics;Immunology;improved;Infection;Influenza;influenza infection;innovation;Intervention;Kinetics;Knowledge;Link;longitudinal analysis;lymph nodes;Lymphoid Tissue;Measures;Memory;Memory B-Lymphocyte;Mucosal Immunity;mucosal site;Mucous Membrane;Nasal Epithelium;nasal swab;neutralizing antibody;nirmatrelvir;pathogen;pathogenic virus;Paxlovid;Phenotype;Population;post SARS-CoV-2 infection;Property;Proteins;respiratory pathogen;response;Ritonavir;RNA vaccination;RNA vaccine;Role;Sampling;SARS-CoV-2 infection;SARS-CoV-2 spike protein;SARS-CoV-2 variant;Series;Site;Source;Structure of germinal center of lymph node;Surface;Swab;T memory cell;T-Lymphocyte;Testing;Time;Upper respiratory tract;Vaccination;Vaccines;Virus

PROJECT_TITLE: Implications of long germinal centers (GC) for T and B cell memory and mucosal immunity


NIH_SPENDING_CATS: Aging;Biodefense and Related Countermeasures;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Immunization;Infectious Diseases;Lung;Prevention;Vaccine Related

PROJECT_TERMS: 2019-nCoV;Affect;Age;age effect;aged;antigen test;Antigens;Blood;Blood Component Removal;Blood Donations;breakthrough infection;Cause of Death;Clinical;cohort;COVID-19;Cross Infection;cross reactivity;Development;Enrollment;Epitopes;Evolution;exhaustion;experience;Frequencies;functional loss;Funding;global health;Human;Immunity;Immunization;Immunologic Memory;Immunologics;Impairment;imprint;in vivo;Individual;Infection;Leukapheresis;Life;Living Arrangement;Longevity;Longitudinal cohort;Longitudinal Studies;Measures;Memory;Methodology;novel;Outcome;Pattern;Peer Review;Persons;Population;pre-pandemic;preservation;Proteins;Proteome;Publications;Recording of previous events;recruit;Reporting;respiratory pathogen;response;Rest;Sampling;SARS-CoV-2 antigen;SARS-CoV-2 exposure;SARS-CoV-2 immunity;SARS-CoV-2 infection;SARS-CoV-2 variant;T cell response;T memory cell;T-Cell Development;T-cell receptor repertoire;T-Lymphocyte;Test Result;Testing;Time;Vaccinated;Vaccination;vaccination outcome;Vaccines;Variant;Work

PROJECT_TITLE: Immune memory to SARS2 in a changing landscape


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

PI_NAMEs: VIJAYANAND, PANDURANGAN  (contact)

PROJECT_TERMS: 2019-nCoV;Address;Age;anti-PD1 therapy;Antigen Presentation;antigen-specific T cells;ATAC-seq;Automobile Driving;B-Lymphocytes;Bacteria;Benign;Biological Assay;Biology;Blood;booster vaccine;Cell Separation;Cells;Chickenpox;Circulation;Clinical;cohort;comorbidity;Complement;COVID-19;COVID-19 vaccine;Defect;Diabetes Mellitus;Disease;Enrollment;Excision;Exposure to;Frequencies;fungus;Generations;Head and neck structure;Health;Herpes zoster disease;Herpesvirus Type 3;Human;human old age (65+);Human Papilloma Virus Vaccine;Human Papillomavirus;human tissue;Hypersensitivity;immune activation;Immunologic Memory;Immunology;immunoregulation;Infection;Influenza;influenza virus vaccine;insight;Intervention;Larynx;Life;Link;Living Donors;Lung;Lymphoid;Malignant - descriptor;Malignant Neoplasms;Metapneumovirus;model organism;Molecular;mouse model;Mucosal Immunity;Mucous Membrane;Muscle;Nasopharynx;Nature;Observational Study;Operative Surgical Procedures;Oropharyngeal;Parainfluenza;pathogen;pathogenic fungus;Peptides;Peripheral Blood Mononuclear Cell;Pertussis;Pertussis Vaccine;Phenotype;Play;Property;prospective;recruit;Reporting;Research;respiratory pathogen;Respiratory syncytial virus;response;Role;Route;Science;Severity of illness;single-cell RNA sequencing;Smoking;Smoking Status;Specificity;T cell receptor repertoire sequencing;T cell response;T memory cell;T-Cell Receptor;T-Lymphocyte;Technology;Testing;Tetanus Vaccine;Time;tissue resident memory T cell;Tissue Sample;Tissues;transcriptomics;Vaccinated;Vaccination;vaccine formulation;vaccine response;Vaccines;Viral;Virus;Virus Diseases;Work;Zoster Vaccine

PROJECT_TITLE: Factors influencing TRM responses in upper airway tissue


NIH_SPENDING_CATS: Infectious Diseases;Machine Learning and Artificial Intelligence;Microbiome

PHR: PROJECT NARRATIVE This proposal will enable us to view the molecular components of infectious disease with unprecedented resolution through the development of a new multimodal imaging platform. The proposed technologies will improve throughput and molecular specificity, enable automated high-precision and high-accuracy image alignment, and allow for more accurate descriptions of molecular signals through the fusion of multi-modal imaging data sources. These studies will uncover new targets for therapeutic intervention and antibiotic development and the techniques developed as a result of this proposal will be broadly applicable to all physiologically relevant processes, profoundly impacting biomedical research.

PI_NAMEs: SKAAR, ERIC P (contact);SPRAGGINS, JEFFREY M

PROGRAM_OFFICER_NAME: HUNTLEY, CLAYTON C

PROJECT_TERMS: 3-Dimensional;Abscess;Anatomy;animal imaging;Anterior nares;Antibiotics;antimicrobial;Appearance;Architecture;Bacteria;bacterial community;Biology;Biomedical Research;Cells;commensal bacteria;Communicable Diseases;Communities;Community-Acquired Infections;Computer Analysis;Computer Vision Systems;Data;Data Sources;design;Development;differential expression;Disease;Disease Marker;Disparate;Environment;environmental stressor;Equipment and supply inventories;Exhibits;experience;experimental study;Exposure to;Genes;Genetic;Genus staphylococcus;Glean;Heterogeneity;Histology;Hospitals;Human;human pathogen;human tissue;Image;image registration;imaging capabilities;imaging modality;imaging platform;Immune;Immune response;Immunology;improved;Infection;Innate Immune Response;innovation;Knowledge;Lesion;Life Cycle Stages;Lipids;Machine Learning;Maps;mass spectrometric imaging;Mass Spectrum Analysis;Methodology;Methods;microbial;Microbial Biofilms;microbial community;Modality;Molecular;molecular imaging;Molecular Profiling;Morbidity - disease rate;mortality;mouse model;Multi-Drug Resistance;multimodal fusion;Multimodal Imaging;multimodality;neutrophil;new therapeutic target;next generation;Organism;pathogen;Pathologic;Physiological;Population;Positioning Attribute;Prevention;Process;Proteins;Research;resistant strain;Resolution;response;Signal Transduction;Site;small molecule;Source;Specificity;Staphylococcal Infections;Staphylococcus aureus;Staphylococcus aureus infection;stressor;Structure;supervised learning;targeted treatment;Techniques;Technology;Testing;Therapeutic;therapeutic development;Therapeutic Intervention;therapeutic target;therapeutic vaccine;Time;Tissues;tool;Transcript;Vaccine Design;Variant;virtual;Visualization;Work

PROJECT_TITLE: Molecular mapping of microbial communities at the host-pathogen interface by multi-modal 3-dimensional imaging mass spectrometry

STUDY_SECTION: BV

STUDY_SECTION_NAME: Bacterial Virulence Study Section [BV]


NIH_SPENDING_CATS: Infectious Diseases

PHR: PROJECT NARRATIVE Fungal infections represent significant causes of morbidity and mortality in vulnerable patients across the globe. This Keystone Symposia meeting will bring together scientists in the mycology field to better understand the mechanisms of host-fungal interactions. This is a timely gathering of experts from diverse scientific backgrounds related to fungal biology and fungal immunology who share an ultimate goal of decreasing the burden of fungal infections and improving patient outcomes.

PI_NAMEs: SHEPPARD, TERRY L. (contact)

PROGRAM_OFFICER_NAME: STRICKLER-DINGLASAN, PATRICIA M

PROJECT_TERMS: acquired immunodeficiency;adaptive immune response;Alberta province;Animal Model;anti-fungal agents;Autoimmune Diseases;Biology;Canada;career development;cell type;clinical development;clinical implementation;Clinical Management;clinical practice;clinical prognosis;clinically relevant;Collaborations;combat;Communities;congenital immunodeficiency;Development;Disease;Disease Outbreaks;Educational workshop;Electronic Medical Records and Genomics Network;frontier;fungus;Future;Goals;Health care facility;Hematopoietic stem cells;HIV/AIDS;Human;Immune system;Immunity;Immunologist;Immunology;improved;interdisciplinary approach;interest;International;Investigation;Knowledge;Learning;Life;meetings;member;Methodology;Molecular;Morbidity - disease rate;mortality;Multi-Drug Resistance;multidisciplinary;Mycoses;Myeloablative Chemotherapy;neoplastic;novel;Organ Transplantation;Outcome;Participant;Pathogenesis;pathogenic fungus;Pathway interactions;patient population;Patient-Focused Outcomes;Patients;posters;Predisposition;prophylactic;Public Health;Regulation;Research;Research Personnel;resistance in Candida auris;risk stratification;Running;Scientist;Site;Solid;Symbiosis;symposium;targeted treatment;Technology;The science of Mycology;Therapeutic;Therapeutic immunosuppression;Time;Tissues;trait;Translations;treatment strategy;vaccination strategy;Virulence;Work

PROJECT_TITLE: Fungal Pathogens: Emerging Threats and Future Challenges

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 BJM-D (S2)]


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

PHR: PROJECT NARRATIVE Therapeutic genome engineering holds the potential to revolutionize the treatment of genetic diseases, from ultra-rare diseases to common leading causes of death, such as heart disease and cancer. It will also lead to significant advances in drug discovery by allowing researchers to more accurately model diseases, identify potential drug targets and test new therapies. This Keystone Symposia conference will bring together experts in technology development, therapeutic applications, and clinical translation to foster deeper understanding of what the current tools are capable of and how best to deploy them to treat human disease.

PROGRAM_OFFICER_NAME: CHEN, ALICE

PROJECT_TERMS: Alberta province;Area;base editing;Canada;Cause of Death;Clinic;Clinical;clinical development;clinical practice;clinical translation;Collaborations;COVID-19 pandemic;design;Development;Disease;disease model;DNA;drug discovery;Drug Targeting;drug testing;Educational workshop;Engineered Gene;Environment;Enzymes;Epigenetic Process;forging;Fostering;Gene Delivery;gene editing technology;Gene Targeting;Genes;Genetic Diseases;Genome;genome editing;Genome engineering;Genomic medicine;Health;Heart Diseases;Human;human disease;implementation barriers;improved;Industrialization;innovation;insight;interest;Joints;Knowledge;Learning;Malignant Neoplasms;meetings;Mentors;Methodology;multidisciplinary;novel;novel therapeutics;nucleic acid delivery;nucleic acid-based therapeutics;Outcome;Participant;Patients;Persons;posters;pre-clinical;preclinical development;prime editing;programs;prospective;Rare Diseases;Reagent;Research;Research Personnel;Science;Scientist;symposium;Techniques;Technology;technology development;Therapeutic;tool;Translations

PROJECT_TITLE: Precision Genome Engineering

STUDY_SECTION_NAME: Special Emphasis Panel[ZTR1 CG-4 (02)]


NIH_SPENDING_CATS: Biomedical Imaging;Cardiovascular;Childhood Obesity;Clinical Research;Diabetes;Heart Disease;Nutrition;Obesity;Pediatric;Prevention

ORG_DEPT: PEDIATRICS

PHR: PROJECT NARRATIVE Epicardial adipose tissue has been suggested as a new cardiometabolic risk factor due to its anatomical proximity to the heart and coronary circulation and appears to be higher in adults with type 2 diabetes. Our lab utilizes novel, state-of-the-art MRI methods to assess cardiac structure and function, including specific fat depots. The proposed research will determine the relationship between epicardial adipose tissue and cardiometabolic health in youth with type 2 diabetes and investigate the impact of bariatric surgery on epicardial adipose tissue and cardiometabolic risk factors, independent of overall weight loss.

PI_NAMEs: DOBBS, TYLER J (contact)

PROJECT_TERMS: Abdomen;Address;Adipose tissue;Adolescent;Adolescent obesity;Adult;Age;Agonist;Anatomy;Aorta;bariatric surgery;Behavioral;Beta Cell;Blood Vessels;Body Composition;Body mass index;Body Weight decreased;Cardiac;Cardiac health;cardiac magnetic resonance imaging;cardiometabolic risk;cardiometabolism;cardioprotection;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;Cardiovascular system;Chronic Disease;Closure by clamp;comorbidity;Coronary artery;Coronary Circulation;Data;Dedications;Diabetes Mellitus;Disease;Dual-Energy X-Ray Absorptiometry;Dyslipidemias;Echocardiography;Event;Fasting;Fatty acid glycerol esters;follow-up;Functional disorder;Future;Gastrectomy;Geometry;glucagon-like peptide 1;glycemic control;Goals;Health;Heart;heart circulation;Hepatic;Hyperglycemia;Hypertension;Image;improved;incretin hormone;Inflammation;Inflammatory;Insulin Resistance;Intervention;Investigation;Knowledge;Laboratories;Magnetic Resonance Imaging;Measurement;Measures;Mediating;Mediation;Mediator;Metabolic;Metabolism;Methods;Morbid Obesity;Myocardium;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;Operative Surgical Procedures;Outcome;Overweight;Participant;Pharmaceutical Preparations;pharmacologic;Phase;Physical assessment;Physiology;Prevalence;prevent;Publications;radiation risk;Research;Resistance;response;Risk;Risk Factors;Structure;subcutaneous;Techniques;Testing;Thick;Thinness;Tissues;transcriptome;Visceral;Visceral fat;X-Ray Computed Tomography;young adult;Youth

PROJECT_TITLE: Epicardial Adipose Tissue and Cardiometabolic Risk Factors in Youth-Onset Type 2 Diabetes Undergoing Bariatric Surgery

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