ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Cardiovascular;Climate-Related Exposures and Conditions;Lung;Prevention

ORG_CITY: BOSTON

ORG_NAME: NORTHEASTERN UNIVERSITY

ORG_STATE: MA

PHR: PROJECT NARRATIVE Wildland fire smoke inhalation has been linked to disease of the cardiopulmonary system, but the contribution of exposure frequency and duration, as well as smoke composition remain unknown. With the occurrence and severity of wildland fires on the rise, there is an urgent need to understand the negative health consequences of smoke inhalation, in order to properly inform and protect at risk populations. In this proposal, we evaluate changes in the cardiopulmonary function of adult mice after prolonged fire smoke inhalation, modeling conditions at wildland urban interface regions.

PI_NAMEs: OAKES, JESSICA M (contact)

PROGRAM_OFFICER_NAME: NADADUR, SRIKANTH

PROJECT_TERMS: Acute;Adult;Advocate;Aerosols;Animals;Aorta;Apolipoprotein E;Area;Atherosclerosis;Automobile Driving;Awareness;Behavior;Biological;Biology;biomass smoke;biomechanical test;Blood;Blood Pressure;California;Cardiac;Cardiopulmonary;Cardiovascular Diseases;Cardiovascular Physiology;Cardiovascular system;career;career development;Case Manager;Cells;Characteristics;Chemicals;Chemistry;chemokine;Chronic;Circulation;Communities;Complex;Complex Mixtures;Computer Models;cost;Coupling;cytokine;Dangerousness;density;Deposition;Development;Disease;Dose;EFRAC;Elasticity;Engineering;epidemiologic data;Exposure to;fine particles;Fire - disasters;Fostering;Frequencies;Functional disorder;Gases;Generations;Goals;Grant;Health;health assessment;Healthcare;Heart;Household;Housing;Human;hypercholesterolemia;in vivo imaging;Individual;Infiltration;Inflammation;Inflammatory;Inhalation;Inhalation Toxicology;Interdisciplinary Study;Knowledge;Life;Link;Lung;Measures;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;novel;Obstructive Lung Diseases;Organ;Outcome;particle;Particle Size;Particulate;Particulate Matter;Persons;Policies;Policy Maker;pollutant;Polymethyl Methacrylate;polyurethane foam;Population;Populations at Risk;Predisposition;pressure;programs;Pseudotsuga menziesii;Public Health;Pulmonary Heart Disease;Recurrence;Research;Research Personnel;respiratory;Respiratory Disease;Respiratory Mechanics;response;Risk Assessment;risk stratification;Rodent;Role;Serum;Severities;Smoke;smoke inhalation;Source;Stream;symposium;System;Testing;Tissues;Toxin;Trace metal;ultrafine particle;Wildfire;Wood material

PROJECT_TITLE: Cardiopulmonary Risk Assessment from Smoke Exposure at the Wildland Urban Interface


ADMINISTERING_IC: AI

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Cancer;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Hepatitis - B;Infectious Diseases;Liver Cancer;Liver Disease;Rare Diseases

ORG_CITY: PROVIDENCE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: RHODE ISLAND HOSPITAL

ORG_STATE: RI

PHR: Project narrative  Both large and middle envelope proteins of hepatitis B virus contain the preS2 domain, and late stage of chronic infection often selects for deletions to remove part of the preS2 domain. We will perform transfection and infection experiments in cell culture to critically test our hypothesis that such deletions escape neutralizing antibodies, which block viral infection by binding to either large or middle envelope protein. If proven, immune escape could explain the selection of such deletion mutants and their close association with liver cancer development.

PI_NAMEs: LI, JISU  (contact)

PROGRAM_OFFICER_NAME: FLORES, AMANDA CHRISTINE

PROJECT_TERMS: Affinity;Amino Acid Substitution;Animals;Antibodies;Applications Grants;Binding;Biological;Blocking Antibodies;Cell Culture Techniques;Cells;Childhood Liver Cancer;Chronic Hepatitis B;chronic infection;Clinical;Codon Nucleotides;Development;DNA Viruses;driving force;env Gene Products;Epitopes;Escape Mutant;experimental study;Genotype;Heparan Sulfate Proteoglycan;Hepatitis B Infection;Hepatitis B Virus;HepG2;Human;Immune;immunogenicity;In Vitro;Infection;Integration Host Factors;liver cancer patient;Liver diseases;Malignant neoplasm of liver;Mediating;Methodology;multiple myeloma M Protein;mutant;Mutation;N-terminal;Na(+)-taurocholate-cotransporting peptide;neutralizing antibody;Pan Genus;particle;Patients;Point Mutation;Polymers;Positioning Attribute;Predisposition;prevent;Primary carcinoma of the liver cells;Probability;Production;Property;protein expression;Proteins;receptor;Research Personnel;Serum Albumin;Testing;Transfection;Viral;Virion;Virus;Virus Diseases;Virus Receptors;Western Blotting;Work

PROJECT_TITLE: Explore hepatitis B virus preS2 mutants as immune escape mutants

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Genetics;Neurosciences

ORG_CITY: TUCSON

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Beginning at birth, the activity of eight different tongue muscles must be precisely coordinated for the successful performance of diverse tasks such as breathing, suckling, and swallowing but how this is accomplished is unknown. Tongue muscles are innervated by motor neurons in the hypoglossal motor nucleus of the brainstem, which is a bilateral collection of seven motor neuron pools, with motor neurons in each pool innervating a different tongue muscle. The proposed basic science studies will reveal unique physiologic and genetic properties of the motoneurons that supply a given muscle, which can then be targeted to activate or inhibit specific tongue muscles.

PI_NAMEs: FREGOSI, RALPH FRANK (contact)

PROGRAM_OFFICER_NAME: KOPF, LISA MARIE

PROJECT_TERMS: Action Potentials;Address;Age;Anatomy;Basic Science;Behavior;Bilateral;Birth;Brain Stem;brain tissue;Breathing;Cell Nucleus;Cells;Collection;Complex;Data;Deglutition;Dendrites;Electrophysiology (science);experimental study;Fluorescence-Activated Cell Sorting;Foundations;Gene Expression;Gene Expression Profile;Genetic;genioglossus muscle;Human;Immunohistochemistry;In Vitro;Individual;innovation;Intervention;Ion Channel;Knowledge;Maps;Mastication;Membrane;Membrane Potentials;Molecular;Molecular Target;Morphology;Motor;Motor Neurons;Movement;Muscle;Nature;Neonatal;Neuroanatomy;Neurons;Neurotransmitter Receptor;next generation;novel;Outcome;patch clamp;Pattern;Performance;pharmacologic;Phenotype;Physiological;Property;Publishing;Rattus;receptor expression;Reporter;Rest;Role;Sleep;Slice;Speech;suckling;Synapses;Techniques;therapeutic development;therapy development;Tissue-Specific Gene Expression;Tongue;Tracer;transcriptome;transcriptome sequencing;transcriptomics;voltage;Work

PROJECT_TITLE: Functional and Structural Diversity in Hypoglossal Motoneurons

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-A(03)]


ADMINISTERING_IC: VA

FUNDING_MECHANISM: OTHERS

IC_NAME: Veterans Affairs

ORG_CITY: White River Junction

ORG_NAME: WHITE RIVER JUNCTION VA MEDICAL CENTER

ORG_STATE: VT

PHR: The proposed research is highly relevant to Veterans’ health because it will test a [novel intervention that addresses two key contributors to suicide risk after psychiatric hospitalization: poor social connectedness and engagement in care.] There is overwhelming evidence that one of the highest risk periods for suicide in Veterans is the three months following psychiatric hospitalization. The proposed suicide prevention strategy, [Prevention of suicide: Education, Awareness, Connection, and Engagement (PEACE), directly addresses this high-risk phase of care by coupling a mobile health intervention targeting social connectedness with a manual- based approach to support engagement in care after discharge.] This proposed research has the potential [to be highly scalable] and could have a large, positive impact on the health and well-being of Veterans by preventing suicide in Veterans who are at high risk for suicide. The proposed research is also highly relevant to the VA’s top clinical priority, namely suicide prevention in Veterans.

PI_NAMEs: RIBLET, NATALIE  (contact)

PROJECT_TERMS: Address;Alternative Therapies;Award;Awareness;brief intervention;career;career development;Caring;Clinical;Clinical Management;Clinical Research;Clinical Trials;Coupling;Data;design;Education;efficacy evaluation;efficacy study;efficacy testing;Eligibility Determination;Equation;Event;experience;Feeling suicidal;follow-up;Future;Goals;Health;Health Technology;Healthcare Systems;high risk;Hospitalization;Hospitals;improved;inpatient psychiatric treatment;insight;interest;Intervention;intervention effect;K-Series Research Career Programs;Knowledge;Learning;Manuals;Medical center;Mentorship;mHealth;mhealth interventions;military veteran;Mobile Health Application;Modeling;multi-site trial;novel;Outcome;patient engagement;Patients;Personal Satisfaction;Phase;Prevention Research;Prevention strategy;Program Development;programs;Psychiatric Hospitals;Randomized;Randomized, Controlled Trials;recruit;reducing suicide;Research;Research Personnel;Research Project Grants;response;Risk Factors;Site;skills;social;standard care;suicidal;suicidal morbidity;suicidal risk;Suicide;Suicide attempt;Suicide prevention;Testing;Time;time use;United States Department of Veterans Affairs;Veterans;Veterans Health Administration;Work;World Health Organization

PROJECT_TITLE: Prevention of Suicide in Veterans Through Brief Intervention and Contact (VA-BIC)


ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

ORG_STATE: CA

PHR: Major Depressive Disorder is the leading cause of disability in the United States for ages 15-44, with associated substantial healthcare system costs. Estimates among the Veteran population for major depressive disorder prevalence are about 11%. This study will provide insights into whether reward processing measures of brain functioning and behavior are useful for improving aspects of treatment planning, suicide risk assessment, and cognitive-behavioral therapy response prediction. Mental healthcare practitioners need treatment predictors that account for the full extent of depressed individuals seen in the clinic in order to realize the goal of personalized healthcare. Studies like the one proposed here are vital to this larger effort in that they are poised to discover biomarkers to account for neurobiological variation presumably underlying distinct individual clinical responses. A refined depression taxonomy, informed by clinical neuroscience, could then be harnessed to improve diagnosis, increase treatment precision, or enhance prediction of suicide risk.

PI_NAMEs: FRYER, SUSANNA  (contact)

PROJECT_TERMS: Age;Anhedonia;Behavior;Behavior assessment;Behavioral;Biological Markers;biomarker discovery;biotypes;Brain;case control;Choice Behavior;Classification;Clinic;Clinical;clinically relevant;Cognitive;Cognitive Therapy;comparison group;Complex;cost;Data;Decision Making;Depressed mood;depressive symptoms;Diagnosis;disability;discounting;Disease;disease classification;Electroencephalography;Evaluation;Event;Feedback;Feeling suicidal;Frequencies;Functional disorder;Functional Magnetic Resonance Imaging;functional magnetic resonance imaging/electroencephalography;Goals;Healthcare Systems;hedonic;Heterogeneity;ideation;improved;Individual;individual variation;insight;Major Depressive Disorder;Measures;Mental Depression;Mental Health Services;Methodology;Methods;military veteran;Modality;Motivation;multimodality;neural;neurobiological mechanism;Neurobiology;neuromechanism;Neurosciences;Output;Pattern;personalized health care;personalized medicine;pleasure;Precision therapeutics;Prediction of Response to Therapy;Prevalence;Process;psychiatric comorbidity;Psychiatric therapeutic procedure;Recurrence;resilience;response;reward anticipation;reward processing;Rewards;Risk Assessment;segregation;Severities;Subgroup;suicidal;suicidal risk;Suicide attempt;Symptoms;System;Taxonomy;Testing;therapy resistant;Time;trait;treatment planning;treatment response;United States;unsupervised learning;Variant;Veterans;Work

PROJECT_TITLE: Reward processing and depressive subtypes:  Identifying neural biotypes related to suicide risk, resilience, and treatment response


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: Heart failure is a chronic cardiovascular condition with periods of stability interrupted by episodes of acute decompensation that frequently result in hospitalization. Approximately 350,000 Veterans are living with chronic heart failure, while there are almost 90,000 hospitalizations for acute heart failure in the VA system annually. During a hospitalization for acute heart failure, one third of patients will have a rise in creatinine that reflects worsening kidney function. Currently, this change in kidney function could be a benign hemodynamic effect from treatments given for acute heart failure or true kidney injury; there are currently no tools available to distinguish these two situations. This proposal will apply novel kidney biomarkers found in urine to discriminate between these two scenarios, a finding that could change the management of acute heart failure and improve treatment outcomes.

PI_NAMEs: WETTERSTEN, NICHOLAS  (contact)

PROJECT_TERMS: Acute;Acute Renal Failure with Renal Papillary Necrosis;Address;Admission activity;adverse outcome;American;Award;Benign;Biological Markers;biomarker panel;Biometry;Blood Pressure;blood pressure intervention;Cardiorenal syndrome;Cardiovascular system;Cell Death;cell injury;Cell Physiology;Cessation of life;Chronic;Clinical;clinical translation;Clinical Trials;college;Congestive Heart Failure;Creatinine;Data;design;Deterioration;Dialysis procedure;Diuresis;Diuretics;Educational workshop;Enrollment;Evaluation;Excision;experience;Extracellular Fluid;Functional disorder;Future;glomerular filtration;Glomerular Filtration Rate;Goals;Health Status;Health system;Heart;Heart failure;hemodynamics;hospital readmission;Hospitalization;Hospitals;Impairment;improved;Injury;Injury to Kidney;Intensive Care Units;Interruption;Intervention Studies;Intervention Trial;K-Series Research Career Programs;Kidney;Kidney Diseases;Lead;Learning;Length of Stay;Measurable;Measures;Mentors;Mentorship;Monitor;Morbidity - disease rate;mortality;muscle form;novel;Outcome;Pathology;Patient Admission;Patients;Persons;Pilot Projects;Pragmatic clinical trial;premature;Process;prospective;Proteins;Randomized;recruit;renal damage;Renal function;Renal tubule structure;Research;Research Personnel;Research Project Grants;response;Risk;Risk Factors;Serum;Site;skill acquisition;skills;Specimen;Study Subject;Symptoms;System;Testing;tool;Training;Translating;Translational Research;treatment effect;Treatment Failure;Treatment outcome;treatment response;treatment strategy;Tubular formation;Universities;urinary;Urine;Venous;Venous Insufficiency;Ventilator;Veterans;Weight Gain;Work;Writing

PROJECT_TITLE: Discriminating Causes of Creatinine Change in Acute Heart Failure


ORG_CITY: AUGUSTA

ORG_NAME: CHARLIE NORWOOD VA MEDICAL CENTER

ORG_STATE: GA

PHR: Project Narrative Approximately one million veterans aged 50 and older will develop colorectal cancer over the remainder of their lives and nearly 433,000 will die from it. On a national basis, the relative five year survival with colorectal cancer was estimated at only approximately 40% among veterans, substantially lower than the 60% survival rate among the general population. Myeloid cell accumulation is a hallmark of human colorectal cancer and PD-L1 is a major immune suppressive ligand of MDSCs. In the preliminary studies, we determined that PD-L1 engages PD-1 of myeloid cells to inhibit type I interferon signaling to suppress CTL tumor infiltration. Therefore, it is critical to study type I interferon signaling in myeloid cells in human colorectal cancer patients. The proposed studies have the potential to determine the role of tPD-L1 and mPD-1 in colon cancer immune evasion and will provide the basis for molecular mechanism-based development of IFNA13CO01 for human colon cancer immunotherapy.

PI_NAMEs: LIU, KEBIN  (contact)

PROJECT_TERMS: aged;anti-PD-1;Antigens;Binding;Biochemical;Biodistribution;Bone Marrow;cancer immunotherapy;cancer therapy;Cell Communication;Chimera organism;Codon Nucleotides;Colon;colon cancer metastasis;colon cancer patients;colon cancer treatment;Colon Carcinoma;Colonic Neoplasms;Colorectal Cancer;Colorectal Neoplasms;Cytotoxic T-Lymphocytes;design;Development;DNA;Dose;Drug Kinetics;efficacy evaluation;Encapsulated;Exhibits;FDA approved;Funding;Gene Expression Profiling;General Population;Genetic Transcription;genome-wide;Growth;Human;IFNAR1 gene;Immune;Immunocompetent;Immunologic Surveillance;Immunotherapy;Impairment;in vivo;Infiltration;Interferon Type I;Knock-out;Knockout Mice;Large Intestine Carcinoma;Ligands;lipid nanoparticle;Liposomes;Lung;Lymphocyte Activation;Lytic;Malignant Neoplasms;Metastatic Neoplasm to the Liver;Metastatic Neoplasm to the Lung;Molecular;mortality;mouse model;Mus;Myeloid Cells;Neoplasm Metastasis;neoplastic cell;Pathway interactions;patient derived xenograft model;patient response;PD-1 blockade;PD-1/PD-L1;Primary Neoplasm;Prodrugs;Productivity;programmed cell death ligand 1;programmed cell death protein 1;promoter;Proteins;Recombinant Proteins;reconstitution;recruit;Regulation;Repression;Research Design;Resistance;response;RNA;Role;Signal Transduction;single-cell RNA sequencing;Site;STAT1 gene;STAT3 gene;Survival Rate;systemic toxicity;T-Lymphocyte;Testing;Tissues;Toxic effect;Toxicology;tumor;Tumor Escape;tumor growth;tumor microenvironment;tumor progression;Tumor-Infiltrating Lymphocytes;type I interferon receptor;Veterans

PROJECT_TITLE: Type I Interferon Regulation of Tumor Cell and Immune Cell Interaction in Human Colon Cancer


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Antimicrobial Resistance;Infectious Diseases;Malaria;Rare Diseases;Vector-Borne Diseases

ORG_CITY: WINSTON-SALEM

ORG_DEPT: BIOLOGY

ORG_NAME: WAKE FOREST UNIVERSITY

ORG_STATE: NC

PHR: Malaria is a disease caused by a protozoan parasite that replicates within the vasculature of multiple organs including those with lower oxygenation (e.g., brain, bone marrow) and those with higher oxygenation (e.g., lung, liver). While laboratory-based studies suggest that malaria parasites grow fastest in environments with low oxygen, much less is known about their growth in highly oxygenated environments. This research will help us understand how tissue oxygenation may affect the malaria parasite’s replication rate and susceptibility to antimalarial drug treatment.

PI_NAMEs: BEI, AMY KRISTINE;CORDY, REGINA J (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: Acute;Affect;Amino Acids;Anti-malarial drug resistance;Anti-malarials;Antioxidants;Artemisinins;Atmosphere;Biochemical;Biology;Blood;Bone Marrow;Brain;cell injury;Cell Physiology;Cessation of life;confocal imaging;Cysteine;Data;Death Rate;Devices;direct application;Disease;DNA Sequence Alteration;Dose;drug efficacy;Drug resistance;Environment;Environmental Risk Factor;Equilibrium;Erythrocytes;Etiology;Free Radicals;Gases;Gene Expression;Genes;Genetic Transcription;Glutamine;Glutathione;glutathione synthase;Glycine;Goals;Growth;Human;Hydrogen Peroxide;In Vitro;in vivo;Individual;Infection;Investigation;Kidney;Laboratories;Length;Liver;Lung;Macaca mulatta;Malaria;malaria infection;Measures;Microscopy;Mitochondria;Modeling;Molecular;Morbidity - disease rate;Morphology;mortality;multiple omics;nonhuman primate;Organ;Outcome;Oxidation-Reduction;Oxidative Stress;Oxygen;Parasites;pathogen;Pharmacotherapy;Physiological;Plasma;Plasmodium;Plasmodium falciparum;Plasmodium knowlesi;Predisposition;Production;Pulse Oximetry;Quinolones;Reactive Oxygen Species;Reduced Glutathione;Research;Resistance development;response;Role;Senegal;Severity of illness;Site;small molecule;Superoxides;System;Testing;tissue oxygenation;Tissues;Uncertainty;Variant;Work

PROJECT_TITLE: Investigating the role of oxygen on Plasmodium multiplication rate

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Digestive Diseases;Genetics;Human Genome;Immunotherapy;Inflammatory Bowel Disease

ORG_CITY: NEW YORK

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE Long non-coding RNAs (lncRNAs) have recently emerged as important regulators of a plethora of biological processes, ranging from development to immunity. Using a discovery pipeline that integrates information from genome-wide association studies, evolutionary conservation and differential gene expression, we have identified a novel lncRNA that exhibits a pattern of selective expression in regulatory T cells (Tregs) and is genetically implicated in two intestinal auto-immune diseases, Crohn’s disease and ulcerative colitis. Here, we propose to explore the role of this lncRNA in Treg biology.

PI_NAMEs: GHOSH, SANKAR  (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Affect;Alleles;Animals;Anti-Inflammatory Agents;Anti-sense RNA;Autoimmune;Autoimmune Diseases;Binding Sites;Biological Process;Biological Response Modifiers;Body Weight decreased;Bone Marrow;Cell Physiology;Cell Separation;Cells;Cellular biology;Chimera organism;Chromatin;Chronic;Clinical;clinically significant;Colitis;Coupled;Crohn's disease;cytokine;Data;design;Development;dextran sulfate sodium induced colitis;differential expression;Disease;Disease Progression;DNA sequencing;effector T cell;Exhibits;experimental study;Functional disorder;Gene Expression Profile;Genes;genome wide association study;gut inflammation;Homeostasis;Human;human disease;Immune;Immune system;Immunity;Immunologics;Immunosuppression;Impairment;in vivo;Inflammation;Inflammatory;Interleukin-10;Intestines;knock-down;Knockout Mice;Lamina Propria;Link;lymph nodes;Maps;Mass Spectrum Analysis;Modeling;Molecular;Monitor;mouse model;Mucous Membrane;Mus;Names;new therapeutic target;novel;novel therapeutic intervention;overexpression;Pathology;Pattern;Phenotype;Physiological;Predisposition;Proliferating;Property;Proteins;Rag1 Mouse;Regulatory T-Lymphocyte;RNA;Role;selective expression;Single Nucleotide Polymorphism;Spleen;Synteny;T-Cell Development;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Time;Tissue-Specific Gene Expression;Tissues;Transcript;transcriptome;transcriptome sequencing;Ulcerative Colitis;Untranslated RNA

PROJECT_TITLE: Exploring the role of a novel autoimmune disease-associated lncRNA in Treg biology

STUDY_SECTION: CMIA

STUDY_SECTION_NAME: Cellular and Molecular Immunology - A Study Section[CMIA]


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

ORG_STATE: PA

PHR: NARRATIVE The studies proposed in this application will greatly enhance our understanding of skin-homing NK cells and ILC1 and improve our ability to manipulate skin-specific immune responses in cutaneous pathologies ranging from infection and cancer to inflammation. As such, they are of public health importance

PI_NAMEs: DEBES, GUDRUN PHILOMENA (contact);SIGAL, LUIS J

PROGRAM_OFFICER_NAME: VAZQUEZ-MALDONADO, NANCY

PROJECT_TERMS: Affect;Animal Model;Antitumor Response;Autoimmunity;B-Lymphocytes;Blood;Cannulations;cell motility;Cell Surface Proteins;cell type;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;chemokine receptor;Circulation;Crohn's disease;Cutaneous;Distant;experimental study;Flow Cytometry;Future;Gene Expression Profile;Genetic;Granzyme;Group Homes;Homing;Host Defense;Hypersensitivity;Immune response;Immunity;Immunologic Surveillance;improved;Individual;Infection;Infectious Skin Diseases;Inflammation;inflammatory modulation;Integrin alpha4beta1;Integrins;Intestines;Ligands;Lymph;Lymphocyte;Lymphoid Cell;Malignant Neoplasms;Mesentery;migration;Migration Assay;Modeling;mouse model;Mouse Pox Virus;Mus;Natural Killer Cells;novel strategies;Organ;pathogen;Pathology;Pattern;Physiological;Population;Poxviridae;protein expression;Public Health;receptor;Resistance;response;Rodent;Role;Route;Sheep;sheep model;single cell sequencing;Site;Skin;skin disorder;T memory cell;T-Lymphocyte;T-Lymphocyte Subsets;Technology;Testing;Tissues;trafficking;transcriptome sequencing;vaccine strategy;Vaccinia virus;Vascular Cell Adhesion Molecule-1;vector-borne pathogen;Viral;Virus;Visit;Work

PROJECT_TITLE: Skin-homing Group-1 innate lymphoid cells in viral defense

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Genetics

ORG_CITY: Auburn

ORG_NAME: AUBURN UNIVERSITY AT AUBURN

ORG_STATE: AL

PHR: NARRATIVE Bacteria use non-canonical mechanisms of protein synthesis, such as leaderless mRNAs, to rapidly remodel their proteome. However, very little is known about how this process occurs and how it is regulated. Here, we are using single-molecule microscopy to reveal these mechanisms and bridge this gap.

PI_NAMEs: PETROV, ALEXEY  (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: 5' Untranslated Regions;Address;Affect;analog;Antibiotic Resistance;Archaea;Bacteria;Bacterial Physiology;Base Pairing;Binding;Biochemical;biological adaptation to stress;Cells;Codon Nucleotides;Dissection;Elements;Eukaryota;Fluorescence;Fluorescence Resonance Energy Transfer;Genus Mycobacterium;Guanosine Triphosphate;Hydrolysis;in vivo;Initiator Codon;Initiator tRNA;interest;Label;Messenger RNA;Methods;Microscopy;Modeling;Molecular;Molecular Conformation;mRNA Expression;mRNA Translation;mycobacterial;Nature;novel;Nucleotides;Paint;Pathway interactions;Peptide Initiation Factors;Play;Prevalence;Process;Protein Biosynthesis;Proteins;Proteome;recruit;Regulation;Ribosomal RNA;Ribosomes;Role;single molecule;Structure;System;Testing;Textbooks;Time;Transfer RNA;Translating;translation factor;Translation Initiation;Translations

PROJECT_TITLE: Mechanism of Translation Initiation on Leaderless mRNAs

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Climate-Related Exposures and Conditions;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Nutrition;Social Determinants of Health

ORG_CITY: CLEVELAND

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: Relevance to Public Health Fine particulate matter <2.5 µm (PM2.5) air pollution is a major environment-related health threat that leads to both acute and chronic diseases and a risk factor for cardiovascular disease. Very little is known on the effects of PM2.5 cessation or how to alleviate the detrimental effects of the air pollution through therapeutic or dietary interventions. This proposal will investigate a relationship between PM2.5 and resolution of inflammation caused by PM2.5 through a variety of approaches, including diet switch and a novel pharmacological mimic of exposure cessation.

PI_NAMEs: MAISEYEU, ANDREI  (contact);RAJAGOPALAN, SANJAY

PROJECT_TERMS: Acceleration;Acute Disease;air filter;Air Pollutants;Air Pollution;Animals;Anti-Inflammatory Agents;Antioxidants;Arterial Fatty Streak;Arteries;ATAC-seq;Atherosclerosis;attributable mortality;Bone Marrow Transplantation;Cardiometabolic Disease;cardiometabolic risk;Cardiovascular Diseases;cardiovascular effects;cardiovascular risk factor;Cells;ChIP-seq;Cholesterol;Chronic;Chronic Disease;cytokine;Data;Diet;dietary;Dietary Intervention;dietary manipulation;Disease Progression;Donor person;Environment;Environmental Risk Factor;Enzymes;epigenomics;Erythroid;Etiology;Exposure to;Fatty acid glycerol esters;fine particles;Fingerprint;Flow Cytometry;Fluorescence;GATA1 gene;Genes;Health;Human;Immune;Impairment;In Vitro;in vivo;Inflammation;Inflammatory;Ingestion;Inhalation;Injections;Intervention;irradiation;Laboratories;Lesion;Link;Lip structure;Lipids;Macrophage;Maps;Mass Spectrum Analysis;Mediating;Meta-Analysis;Metabolic;Metabolic Diseases;metabolomics;meter;Modeling;Molecular;monocyte;Morbidity - disease rate;mortality;Mus;Myelogenous;Myeloid Cells;Non-Insulin-Dependent Diabetes Mellitus;novel;Nuclear;nuclear factor-erythroid 2;oxidation;Particulate;Particulate Matter;Pathway interactions;peripheral blood;pharmacologic;Phenotype;Plasma;Play;Population;Predisposition;PTPRC gene;Public Health;Regimen;Resolution;response;Risk;Risk Factors;Role;Sampling;Series;Serum;Shapes;Sorting;Stress;systematic review;Testing;Therapeutic Intervention;Time;transcriptome sequencing;transcriptomics;Up-Regulation;Work

PROJECT_TITLE: Targets and targeting of immunometabolism in chronic PM2.5 exposure


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Emerging Infectious Diseases;Infectious Diseases;Malaria;Orphan Drug;Rare Diseases;Vector-Borne Diseases

ORG_CITY: AMES

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: IOWA STATE UNIVERSITY

ORG_STATE: IA

PHR: Project Narrative Malaria control and eradication efforts are hindered by persistent and emerging resistance to frontline anti-malarial drugs, highlighting the urgent need for understanding parasite biology to develop new therapeutic options. We have recently discovered that the parasite vacuolar protein UIS2 is required for protein export into the host cell and hypothesize that UIS2 establishes critical nutrient transport and protein export machinery in the vacuole membrane. This project will determine the role of UIS2 in these transport processes which represent new therapeutic targets that are essential for parasite survival and disease pathogenesis.

PI_NAMEs: BECK, JOSH RYAN (contact)

PROJECT_TERMS: Anti-malarials;biological adaptation to stress;Biological Assay;Biology;Blood;Catalytic Domain;Cells;Complex;conditional knockout;Cytoplasmic Granules;Cytosol;Data;Development;Disease;Drug resistance;Environment;Erythrocytes;Exocytosis;Fibroblasts;Genes;Growth;Host Defense;Human;In Vitro;in vitro activity;in vivo;Invaded;knock-down;Label;Liver;Malaria;Mediating;Membrane;Membrane Proteins;Metals;Modeling;Molecular Chaperones;mutant;new therapeutic target;novel;novel therapeutics;Nutrient;Orthologous Gene;Parasites;Parasitic Diseases;patch clamp;pathogen;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Peptide Hydrolases;Peptide Signal Sequences;Permeability;Phosphoric Monoester Hydrolases;Phosphorylation;Plasmodium;Plasmodium falciparum;Process;protein complex;Protein Dephosphorylation;Protein Export Pathway;protein function;Proteins;Public Health;purple acid phosphatase;Resistance;Role;Sequence Analysis;Serum;small molecule;Solubility;Sporozoites;Starvation;Testing;Toxoplasma;Translational Repression;Transmembrane Transport;Transport Process;uptake;Vacuole

PROJECT_TITLE: UIS2 function in establishing transport mechanisms at the malaria parasite-host cell interface


PHR: The proposed CDA-2 will provide Dr. Stout with the training, expertise and research support to examine the relatively unexplored neural circuit relationship between working memory and fear extinction, and how these mechanisms jointly contribute to posttraumatic stress disorder (PTSD). This project will be one of the first to leverage innovative multivariate neuroimaging analysis to better elucidate the symptoms of PTSD. The planned CDA-2 aims to create more robust neural circuit biomarkers that can be used to delineate the individual neurobiology of Veterans with PTSD. These aims support the VA mission of developing precision medicine tools for Veteran care and the identification of viable targets of treatment for PTSD and other trauma- related disorders.

PI_NAMEs: STOUT, DANIEL  (contact)

PROJECT_TERMS: Address;Affective;affective neuroscience;Anxiety;Award;Biological Markers;career;Caring;Categories;Characteristics;Clinical;clinical decision-making;Cognition;Cognitive;cognitive control;cognitive neuroscience;combat;comorbidity;Complex;Control Groups;Cues;Data;Diagnostic;Disease;emotion regulation;Emotional;Emotions;Etiology;experience;Extinction;Fright;Functional disorder;Functional Magnetic Resonance Imaging;fusiform face area;Future;Goals;Heterogeneity;high dimensionality;Hippocampus;Impairment;Individual;innovation;integrated circuit;interest;Joints;Learning;Link;Maintenance;Measures;Memory;Memory impairment;memory retrieval;Mental Health;Mentors;Methodology;Military Personnel;Mission;Modality;Modeling;multimodal fusion;multimodal neuroimaging;multimodality;multitask;Multivariate Analysis;neural;neural circuit;neural patterning;neurobiological mechanism;Neurobiology;Neurocognitive;neuroimaging;neuromechanism;neuropsychiatric disorder;neuropsychiatry;novel;Parietal Lobe;Pathology;Patients;Pattern;Performance;Population;Positioning Attribute;Post-Traumatic Stress Disorders;precision medicine;Prediction of Response to Therapy;Prefrontal Cortex;Preparation;Psyche structure;Reporting;Research;Research Personnel;Research Support;Resources;response;Sampling;Severities;Short-Term Memory;Signal Transduction;skills;symptom cluster;symptomatology;Symptoms;System;Techniques;Testing;tool;Training;Trauma;Veterans

PROJECT_TITLE: Identifying integrated circuit mechanisms of PTSD: Multimodal neuroimaging fusion of fear inhibition and cognitive control


ORG_CITY: NEW ORLEANS

ORG_NAME: SOUTHEAST LOUISIANA VETERANS HEALTH CARE

ORG_STATE: LA

PHR: This investigation has the potential to benefit Veterans and the Department of Veterans Affairs (VA) in several ways. Veterans will benefit from the Safety Aid Reduction Treatment Protocol for PTSD (START-PTSD) by engaging in an empirically based treatment designed to identify and eliminate safety aids. This will: a) lead to reductions in posttraumatic stress disorder (PTSD) symptom severity; and b) potentially prepare Veterans for more intensive trauma-focused treatments. In turn, this could yield long-term benefits for the VA by increasing evidence-based psychotherapy (EBP; i.e., prolonged exposure [PE] therapy and/or cognitive processing therapy [CPT]) initiation and enrollment.

PI_NAMEs: RAINES, AMANDA MEDLEY (contact)

PROJECT_TERMS: acceptability and feasibility;Address;Anxiety;Award;Behavioral;career;career development;Clinical;Clinical Research;Clinical Sciences;Clinical Trials;Cognitive;Cognitive Therapy;comparative efficacy;Coupled;Data;design;Diagnosis;Diagnostic;Effectiveness;efficacy evaluation;efficacy testing;Enrollment;Ensure;Etiology;evidence base;experience;Exposure to;Feedback;Focus Groups;follow-up;Fright;Funding;Goals;Grant;improved;Individual;Instruction;Intervention;Interview;Investigation;K-Series Research Career Programs;Knowledge;Lead;Maintenance;Manuals;Mentorship;Methods;Military Personnel;Minority;Participant;Pathological anxiety;Patients;Persons;Play;post intervention;Post-Traumatic Stress Disorders;prevent;Psychotherapy;Qualitative Methods;randomized, clinical trials;recruit;Research;research and development;Research Methodology;Research Personnel;Resistance;response;Role;Safety;Science;Scientist;Severities;skills;Stimulus;symptomatology;Symptoms;therapy design;Time;Training;Trauma;Treatment Protocols;trial comparing;United States Department of Veterans Affairs;Veterans;Waiting Lists;Writing

PROJECT_TITLE: Examination of a Safety Aid Reduction Protocol for Treatment Resistant PTSD among Veterans


ORG_CITY: HOUSTON

ORG_NAME: MICHAEL E DEBAKEY VA MEDICAL CENTER

ORG_STATE: TX

PHR: Antibiotic-resistant bacteria are a major public health concern. These bacteria cause infections that are often difficult to treat and lead to serious infections. Carbapenem-resistant Enterobacteriaceae (CRE) is a severe type of antibiotic-resistant bacteria because it is resistant to almost all antibiotics and can be very deadly. It is very important to identify which patients are at risk for CRE and to identify the best treatment for CRE. We propose to develop and test a tool that predicts whether a person carries CRE, and to identify the best treatment options for CRE infections. We will use large databases to find patients at risk for CRE and patient who have CRE infections. We will use computer programming and biostatistics to identify which patients are at risk and which treatments work best. At the end of the proposed work, we will have identified new avenues to prevent person-to-person transmission of CRE and improve therapy of CRE infections.

PI_NAMEs: CHOU, ANDREW  (contact)

PROJECT_TERMS: acute care;Adverse event;Antibiotic Resistance;antibiotic resistant infections;Antibiotic Therapy;Antibiotic-resistant organism;Antibiotics;Antimicrobial Resistance;Area;Awareness;Bacteria;Bacterial Antibiotic Resistance;Big Data;Big Data Methods;Bioinformatics;Biometry;Board Certification;carbapenem resistance;carbapenem-resistant Enterobacteriaceae;carbapenemase;Carbapenems;career;Categories;Ceftazidime;Centers for Disease Control and Prevention (U.S.);Cessation of life;Clinical;clinical risk;Clinical Trials;Clostridium difficile;college;combat;Combined Antibiotics;Combined Modality Therapy;Communicable Diseases;comorbidity;Complex;computer program;Dangerousness;Data;Data Science;Databases;Dedications;design;Disease Outbreaks;Doctor of Philosophy;Educational Status;Effectiveness;Enterobacter cloacae;Enterobacteriaceae Infections;Environment;evidence base;Exclusion;experience;Faculty;Formularies;Fostering;Future;Gram-Negative Bacteria;Guidelines;Health;Health Care Costs;Health care facility;high risk;Hospitalization;Hospitals;improved;Individual;Infection;Infection prevention;innovation;Institution;Intervention;Junior Physician;K-Series Research Career Programs;Klebsiella pneumoniae;Knowledge;Lead;Master of Science;Mathematics;Measures;Medical center;Medicine;Mentors;Meropenem;microbial genomics;Microbiology;mid-career faculty;military veteran;Modeling;Morbidity - disease rate;mortality;multi-drug resistant pathogen;nephrotoxicity;novel;Oncology;ototoxicity;Outcome;Patients;Performance;Persons;Physicians;Pilot Projects;Population;post-doctoral training;predictive tools;Prevalence;prevent;Prevention;Prevention program;Productivity;prospective;Public Health;Publications;Publishing;Recording of previous events;Regimen;Reporting;Research;Research Personnel;Research Priority;Resistance;resistant Klebsiella pneumoniae;Risk;Risk Factors;risk stratification;Safety;Scientist;screening;Sepsis;side effect;skills;Specialist;Statistical Models;statistics;success;surveillance strategy;Systems Biology;Techniques;Testing;tool;Training;transmission process;Treatment outcome;United States;United States Department of Veterans Affairs;Veterans;Veterans Health Administration;Virulence Factors;virus related cancer;Work

PROJECT_TITLE: Using Big-Data to Identify & Prevent Transmission of Carbapenem-Resistant Enterobacteriaceae within VHA


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Complementary and Integrative Health;Dietary Supplements;Digestive Diseases;Emerging Infectious Diseases;Infectious Diseases;Microbiome;Nutrition

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: PROJECT NARRATIVE Metabolites from the microbiota, probiotics and diet can inhibit the virulence of bacterial pathogens, but their mechanisms of actions have been not fully elucidated. Using innovative chemical biology, proteomic and gene editing methods, we will determine the protein targets of prominent bacterial and dietary metabolites and evaluate how they attenuate the virulence mechanisms of bacterial pathogens. Understanding how key metabolites affects bacterial pathogenesis may afford new therapeutic targets and anti-infective agents.

PI_NAMEs: HANG, HOWARD C (contact)

PROGRAM_OFFICER_NAME: ALEXANDER, WILLIAM A

PROJECT_TERMS: Acids;adaptive immunity;Affect;Animal Model;Animals;Anti-Infective Agents;Anti-Inflammatory Agents;Applications Grants;Aromatic Amino Acids;ATP phosphohydrolase;Attenuated;Bacteria;Bacterial Infections;Bile Acids;Biochemical;Biology;Cell Culture Techniques;Cell model;Chemicals;Chenodeoxycholic Acid;combat;Development;Diet;dietary;enteric infection;enteric pathogen;Gene Expression;gene-editing approach;Genes;genetic approach;Genetic Transcription;global health;Goals;Growth;Human;in vivo;Infection;Inflammation;innovation;interdisciplinary approach;Intestines;Laboratories;Mammalian Cell;Mammals;meter;Methods;microbiota;microbiota metabolites;Modeling;Molecular;Molecular Target;mouse model;Mucous Membrane;Natural Immunity;new therapeutic target;novel strategies;pathogen;Pathogenesis;pathogenic bacteria;Pathway interactions;prevent;Probiotics;Property;protein metabolite;Protein Secretion;Proteins;Proteomics;Regulation;Reporting;Salmonella typhimurium;secondary metabolite;Site;therapeutic target;transcription factor;Type III Secretion System Pathway;Virulence;Virulence Factors;virulence gene;Volatile Fatty Acids

PROJECT_TITLE: Microbiota, Probiotic and Dietary Metabolite Control of Enteric Pathogen Virulence


NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular;Chronic Liver Disease and Cirrhosis;Climate-Related Exposures and Conditions;Digestive Diseases;Hepatitis;Liver Disease;Social Determinants of Health

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE This project aims to dissect molecular pathways responsible for the development and progression of chronic inflammation, in contrast with those involved in the inhibition or resolution of it, a central component in the cardiovascular and metabolic toxicity induced by air pollution. Air pollution contains both gaseous and particulate components (particulate matter) and it appears that the latter ones are mostly responsible for its toxicity by promoting systemic oxidative stress and proinflammatory effects that result in triglyceride accumulation in the liver, lipid infiltration of the vasculature and development of inflammation in both tissues. This project aims to dissect molecular pathways responsible for the development and progression of chronic inflammation, in contrast with those involved in the inhibition or resolution of it, a central component in the cardiovascular and metabolic toxicity induced by air pollution.

PI_NAMEs: ARAUJO, JESUS ANTONIO (contact)

PROJECT_TERMS: Air Pollution;Alveolar;ambient particle;Animals;Anti-Inflammatory Agents;Antioxidants;Aorta;Apolipoprotein E;Arachidonate 5-Lipoxygenase;Arachidonic Acids;Atherosclerosis;Birth;Blood;Blood Vessels;Bronchoalveolar Lavage Fluid;Cardiology;cardiometabolism;Cardiovascular Diseases;Cardiovascular system;Cessation of life;Chronic;Critical Pathways;Data;design;Development;Diameter;Diesel Exhaust;Disease;Down-Regulation;Enzymes;Epidemiology;epidemiology study;Exposure to;Fatty Liver;fatty liver disease;Goals;Hepatic;Hepatitis;Hydroxyeicosatetraenoic Acids;Infiltration;Inflammation;Inflammatory;Inhalation;Inhalation Exposure;inhibitor;Isoprostanes;Knockout Mice;Knowledge;Lead;Leukotriene B4;Linoleic Acids;lipid metabolism;Lipid Peroxidation;Lipids;Lipoproteins;Lipoxins;Liver;Low-Density Lipoproteins;Lung;Macrophage;Mediating;Metabolic;Metabolic Pathway;Metabolism;meter;Molecular;Morbidity - disease rate;mortality;mRNA Expression;Mus;Organ;Outcome;Oxidative Stress;particle;particle exposure;Particulate;Particulate Matter;Pathway interactions;pharmacologic;Phase;Plasma;preventive intervention;prophylactic;protein expression;Protocols documentation;rational design;Reactive Oxygen Species;Reporting;Research;Resolution;response;Role;Steatohepatitis;Syndrome;Testing;Therapeutic;Therapeutic Intervention;Time;Tissues;Toxic effect;Triglycerides;Ultrafine;ultrafine particle;volatile organic compound;Work

PROJECT_TITLE: Dissecting the Role of Arachidonic Acid Metabolic Pathways Involved in Resolution Versus Progression of PM-Induced Cardiometabolic Toxicity


ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Chronic rejection of transplanted organs is the adverse outcome when graft blood vessels thicken, due to negative immune influences on the cells of the middle layer of arteries, smooth muscle cells (SMCs), which become dysregulated. This project focuses on defining which immune cell-produced factors have the greatest potential to promote healthy regulation of those SMCs, followed by enhancing their production through interference with influential regulatory small RNAs (microRNAs), to be tested in preclinical blood vessel transplant models. This would constitute a novel therapeutic approach to the maintenance of healthy organ transplants.

PI_NAMEs: BENDER, JEFFREY R. (contact)

PROGRAM_OFFICER_NAME: KEHN, PATRICIA J

PROJECT_TERMS: 3' Untranslated Regions;Adjuvant;adverse outcome;Alloantigen;allograft rejection;Allograft Tolerance;Allografting;Antigens;Aorta;Arteries;Binding;blood vessel transplantation;Blood Vessels;candidate identification;candidate selection;Cell Communication;cell dedifferentiation;Cell secretion;Cell Therapy;Cells;Chronic;Clonal Expansion;Clone Cells;Complex;Computer Analysis;Conditioned Culture Media;CTLA4 gene;cytokine;Data;design;Development;Endogenous Factors;enhancing factor;Environment;Female;FOXP3 gene;Gene Expression;Gene Expression Regulation;Generations;Goals;H-Y Antigen;Heterogeneity;Homeostasis;Immune;Immune response;Immunoassay;immunoregulation;Immunosuppression;improved;In Vitro;in vivo;in vivo Model;Inflammation;Influentials;Injury;Interleukin-10;Interleukin-2;Internal Ribosome Entry Site;Intervention;Ischemia;liquid chromatography mass spectrometry;locked nucleic acid;Maintenance;male;Mediating;Messenger RNA;Metabolism;MicroRNAs;Minor;Mitotic;Modeling;Molecular;mRNA Stability;mRNA Translation;Mus;novel;novel strategies;novel therapeutic intervention;Oligonucleotides;Organ failure;organ transplant rejection;Organ Transplantation;Outcome;Pathologic;Peptides;pharmacologic;Phenotype;Physiologic pulse;Post-Transcriptional Regulation;posttranscriptional;pre-clinical;preservation;prevent;Production;Proliferating;Proteins;Proteomics;Regulation;Regulatory T-Lymphocyte;release factor;Reporter;Research Design;response;RNA;RNA-Binding Proteins;secondary lymphoid organ;Signal Transduction;Site;Small RNA;Smooth Muscle Myocytes;Solid;Sorting;Specificity;success;T cell differentiation;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;Translational Repression;Translations;transplant model;Validation;Vascular remodeling;Vascular Smooth Muscle;vascular smooth muscle cell proliferation;Vascularization

PROJECT_TITLE: Immune cell skewing with RNA target site oligonucleotides to promote vascular smooth muscle cell homeostasis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Lung;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: There is an urgent but unmet medical need for novel treatment-shortening strategies for drug-susceptible and drug-resistant tuberculosis (TB). Using a forward genetic screen, we recently found that the cell wall-associated protein CaeA confers reduced susceptibility of Mycobacterium tuberculosis (Mtb) to the primary first-line sterilizing drug, rifampin. Using a combination of targeted and unbiased approaches, the current proposal is designed to identify the mechanism of CaeA-mediated Mtb tolerance to rifampin and, in proof-of-concept studies, to evaluate the potential utility of targeting CaeA as adjunctive therapy to shorten the duration of TB treatment.

PI_NAMEs: KARAKOUSIS, PETROS C (contact)

PROGRAM_OFFICER_NAME: LAUGHON, BARBARA E

PROJECT_TERMS: Address;Adherence;Animal Model;Antibiotic susceptibility;antibiotic tolerance;Antibiotics;bactericide;Biological;Biological Assay;C3HeB/FeJ Mouse;Candidate Disease Gene;carboxylesterase;Cause of Death;Cell Wall;Chronic;clinical practice;clinically relevant;Co-Immunoprecipitations;Collaborations;Combined Modality Therapy;Computer Models;design;DNA-Directed RNA Polymerase;Dose;drug development;Drug Efflux;Drug resistance in tuberculosis;Drug Targeting;efflux pump;Ethambutol;Exhibits;Exposure to;Genes;Genetic Screening;global health emergency;Homidium Bromide;Human;in vivo;Infection;interest;Investigation;Kinetics;Knock-out;Knowledge;Lesion;Libraries;lipidomics;Lipids;Lung;Mass Spectrum Analysis;Measures;Mediating;Medical;Metabolic;Metabolic Pathway;metabolomics;Microbiology;Modernization;Molecular;Morbidity - disease rate;mortality;mouse model;multidisciplinary;Mus;Mutagenesis;mutant;mycobacterial;Mycobacterium tuberculosis;Necrosis;new therapeutic target;Nitroimidazoles;novel;Nutrient;Pathogenesis;Pathway interactions;Penetration;Peptide Hydrolases;Permeability;persistent bacterial infection;Pharmaceutical Preparations;Phenotype;Physiological;Population;pre-clinical;Predisposition;Process;programs;Property;Proteins;Proteolysis;pulmonary granuloma;Pulmonary Pathology;Recombinants;Regimen;Regulatory Pathway;Relapse;relapse prevention;Reporting;Research;Research Personnel;Resistance;Reverse Transcriptase Polymerase Chain Reaction;Rifampin;Serine Protease;Streptomycin;Stress;success;Systems Biology;Testing;Time;transcriptomics;transmission process;Tuberculosis;tuberculosis drugs;tuberculosis treatment;Virulence;Virulence Factors

PROJECT_TITLE: Characterizing CaeA-mediated rifampin tolerance in MTB

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DDR-C(01)]


NIH_SPENDING_CATS: Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Clinical Research;Hearing Loss;Neurosciences;Pediatric;Prevention;Rehabilitation

ORG_CITY: MADISON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative  Many children who receive cochlear Implants (CIs) struggle to hear in everyday environments, and recent clinical care has shifted to prioritize bilateral CIs. Novel studies will lead to fresh insight into the role of auditory experience and inter-implant delay on outcomes. We will integrate perceptual and electrophysiological measures of binaural integrity with functional listening assessments and their association to cognition.

PI_NAMEs: LITOVSKY, RUTH Y (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TITLE: Binaural processing and hearing in children with cochlear implants


NIH_SPENDING_CATS: Cancer;Clinical Research;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: SAINT LOUIS

ORG_DEPT: PATHOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: RELEVANCE (See instructions): Serious clinical conditions can arise in the peritoneal cavity, ranging from the initiation and progression of sepsis to cancer. These diverse conditions rely on a functional immune compartment in the peritoneal space, but there is much that remains to be defined to better combat diseases in this space. This application focuses on host defense mediated by resident peritoneal macrophages.

PI_NAMEs: RANDOLPH, GWENDALYN J (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: 3-Dimensional;Adhesions;body cavity;Cell Death;Cells;Cessation of life;Clinical;Coagulation Process;combat;Disease;Environment;Factor V;Future;Greater sac of peritoneum;Host Defense;Human;Immune;Immunity;Immunologics;Infection;Inflammasome;Inflammation;Inflammatory;Instruction;interstitial;Left;Link;Liquid substance;Macrophage;macrophage procoagulant activity;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Membrane;Mesothelium;Microbe;microbial;Modeling;monocyte;Mus;Neoplasm Metastasis;ovarian neoplasm;pathogenic microbe;Peritoneal;Peritoneal Fluid;Peritoneal Macrophages;Peritoneum;Phagocytosis;Phase;Predisposition;Reaction;Sepsis;Stimulus;Testing;tumor;Tumor Expansion;tumor growth

PROJECT_TITLE: Differentiation and Function of Monocytes and Macrophages

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: BLACKSBURG

ORG_DEPT: NEUROSCIENCES

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

ORG_STATE: VA

PHR: Project Narrative – Lina Ni  Many insect vectors of diseases, such as mosquitoes, depend on their temperature-sensing molecules to detect the temperature of their warm-blooded hosts and use it to guide the blood- feeding behaviors through which they transmit human diseases. This project uses a powerful insect genetic model, fruit flies, to study a new class of warm-sensing molecules. These molecules are conserved between flies and mosquitoes so that they may serve as novel targets to control the blood-feeding behaviors of disease vectors.

PI_NAMEs: NI, LINA  (contact)

PROGRAM_OFFICER_NAME: STEPANEK, LAURIE ELIZABETH

PROJECT_TERMS: Afferent Neurons;Animals;avoidance behavior;base;Behavior;Behavioral;Behavioral Assay;Biological Models;Blood;Body Temperature;Calcium;Cells;cold temperature;Culicidae;Data;Disease Vectors;disorder control;Dorsal;driving force;Drosophila genus;Electrophysiology (science);Ensure;experimental study;Family;Feeding behaviors;fly;Ganglia;Genetic;Genetic Models;Goals;High temperature of physical object;human disease;Image;Immunohistochemistry;insect disease vector;insect genetics;Insecta;insight;Label;Larva;member;Molecular;Names;Neurons;novel;Organ;Physiological;Positioning Attribute;preference;Property;receptor;Research;response;Role;sensory mechanism;System;Temperature;Temperature Sense;Testing;transmission process;Vector-transmitted infectious disease;voltage;warm temperature

PROJECT_TITLE: Demonstrate the molecular receptor and functions of dorsal organ warm cells in flies

STUDY_SECTION: SPS

STUDY_SECTION_NAME: Somatosensory and Pain Systems Study Section[SPS]


ED_INST_TYPE: GRADUATE SCHOOLS

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: PROJECT NARRATIVE This project seeks to understand how the Piezo1 ion channels endow cells with the ability to sense mechanical forces in their environment. This ability underlies a wide range of physiological processes that are essential to life.

PI_NAMEs: MACKINNON, RODERICK  (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Address;Antibodies;Behavior;Biological Assay;Biology;blood pressure control;Body System;Cell Line;Cell membrane;Cell Physiology;Cell Shape;Cell Size;cell type;Cells;Cellular Morphology;Communication;Complex;Cryo-electron tomography;Cryoelectron Microscopy;Data;Dependence;Dimensions;Disease;Electron Microscope;Electron Microscopy;Endowment;Environment;Epitopes;Equilibrium;Eukaryotic Cell;Experimental Designs;experimental study;Geometry;Goals;Health;Hearing;Human;In Situ;Ion Channel;Ion Channel Gating;Label;Learning;learning strategy;Life;Light;Lipids;Mammalian Cell;mechanical force;mechanical stimulus;Mechanics;Membrane;Membrane Lipids;Membrane Proteins;method development;Methods;Modeling;Molecular;Molecular Conformation;Molecular Structure;Mus;nanoGold;Physics;Physiological;Physiological Processes;Piezo 1 ion channel;Piezo ion channels;polarized cell;Probability;Property;protein reconstitution;reconstitution;Sampling;Signal Transduction;Site;Structure;Systems Development;Testing;Touch sensation;Vesicle

PROJECT_TITLE: Molecular Structure and Function of the Piezo1 Ion Channel

STUDY_SECTION: BBM

STUDY_SECTION_NAME: Biochemistry and Biophysics of Membranes Study Section[BBM]


NIH_SPENDING_CATS: Asthma;Lung

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: PROJECT NARRATIVE Tissue-resident memory Th2 cells are critical in driving allergic asthma, the most common asthma subtype. This application proposes a research strategy to define the role of lipid shuttling in the development, identity, and function of tissue-resident memory Th2 cells in a murine model of allergic asthma. The successful completion of the proposed studies has the potential to identify novel therapeutic approaches for allergic diseases.

PI_NAMEs: RAHIMI, ROD AMIR (contact)

PROGRAM_OFFICER_NAME: SUBRAMANIAN, HARIHARAN

PROJECT_TERMS: Acyl Coenzyme A;Allergens;allergic airway inflammation;Allergic Disease;Allergic inflammation;Arachidonic Acids;Asthma;Automobile Driving;Binding;Biology;Caring;CD4 Positive T Lymphocytes;Cell Differentiation process;Cell Physiology;Cells;Coenzyme A Ligases;cytokine;Data;Development;Effector Cell;Eicosanoids;environmental allergen;Esterification;Exhibits;Extrinsic asthma;Family member;fatty acid metabolism;Genes;Genetic Transcription;Goals;Health Care Costs;Homeostasis;Human;imprint;in vivo;Inflammation;Interleukin-13;Interleukin-4;Interleukin-5;Journals;Laboratories;Ligands;lipid metabolism;Lipids;Lung;Maps;Medicine;Memory;Modeling;Morbidity - disease rate;mouse model;Mus;new therapeutic target;Nonesterified Fatty Acids;novel;novel therapeutic intervention;Nuclear Receptors;Pathway interactions;Peripheral;Polyunsaturated Fatty Acids;preference;prevent;programs;Protein Isoforms;Recurrence;Regulation;Research;response;Role;sensor;Source;Testing;Th2 Cells;Therapeutic;therapeutic target;Tissues;transcription factor;transcriptome sequencing;Work

PROJECT_TITLE: Lipid shuttling in memory Th2 cell fate and function in allergic asthma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIB-K(57)]


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Infectious Diseases;Lupus

ORG_NAME: BETH ISRAEL DEACONESS MEDICAL CENTER

PHR: Systemic lupus erythematosus afflicts more than a million Americans, primarily women, and presents with symptoms resulting from the involvement of practically every organ. The origin of the disease involves diverse factors which probably contribute variably to the expression of the disease in each patient. Understanding of the molecular underpinnings that lead to an aberrant immune response through this line of research will help us identify novel treatment targets and biomarkers.

PI_NAMEs: TSOKOS, GEORGE C (contact)

PROJECT_TERMS: Address;American;Autoimmunity;Biological Markers;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Physiology;Cells;Clinical Research;cohort;Consumption;cytotoxic;cytotoxicity;Defect;design;Development;Diagnosis;Disease;Drug Delivery Systems;Drug Targeting;experimental study;Gene Expression;Genes;Genetic Transcription;Glycolysis;Human;Immune;Immune response;Immune Tolerance;Immunologist;Immunosuppressive Agents;improved;Infection;infection rate;Link;Lupus;lupus prone mice;Membrane;Metabolic;Metabolism;Molecular;Morbidity - disease rate;mortality;Mus;Natural Killer Cells;Nicotinamide adenine dinucleotide;novel;Organ;Organelles;overexpression;Oxidative Phosphorylation;Pathology;Patients;Performance;Pilot Projects;Predisposition;Probability;prospective;Prospective Studies;Research;response;Role;Surface;Symptoms;Systemic Lupus Erythematosus;T-Lymphocyte;T-Lymphocyte Subsets;targeted delivery;Testing;translational scientist;Woman;Work

PROJECT_TITLE: T cells in Lupus

STUDY_SECTION: ACTS

STUDY_SECTION_NAME: Arthritis, Connective Tissue and Skin Study Section[ACTS]


ADMINISTERING_IC: MD

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: American Indian or Alaska Native;Arctic;Basic Behavioral and Social Science;Behavioral and Social Science;Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Maternal Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Racial and Ethnic Minority Health Research;Rural Health;Social Determinants of Health;Women's Health Research

ORG_CITY: ANCHORAGE

ORG_NAME: UNIVERSITY OF ALASKA ANCHORAGE

ORG_STATE: AK

PHR: PROJECT NARRATIVE (PUBLIC HEALTH RELEVANCE) Globally, complications of preterm birth are the single largest direct cause of neonatal deaths, accounting for 35% of over 3 million annual deaths. While the specific causes are poorly understood, many have identified disparities in preterm birth by maternal socio-demographic characteristics such as race, age, and educational attainment, and the independent and joint effects of social and environmental factors over the maternal life course, as contributing to the risk of adverse birth outcomes. A better understanding of the interaction between wildfire smoke exposure and social risk factors as they relate to birth outcomes and can support interventions to promote healthy fetal development in an era of increasing wildfires.

PI_NAMEs: HAHN, MICAH  (contact)

PROGRAM_OFFICER_NAME: ROUSSOS, GINA PATIENCE

PROJECT_TERMS: Accounting;adverse birth outcomes;Age;Air;Alaska;Alaska Native;Alaska Native Women;Alaskan;American Indian Women;Applied Research;Award;Biometry;Birth;Birth Records;career;Cessation of life;Characteristics;Child Development;climate change;climate impact;Communities;comorbidity;Critical Thinking;Data;Date of birth;Development;disability;Disparity;Ecology;Education;Educational Status;Environmental Epidemiology;Environmental Exposure;Environmental Health;environmental justice;Environmental Risk Factor;Epidemiology;experience;Exposure to;Faculty;Family;Fetal Development;Future;Geography;Goals;Health;health care availability;Health Disparities Research;health disparity;health equity;improve minority health;Incidence;Insurance Coverage;Interdisciplinary Study;Intervention;Joints;K-Series Research Career Programs;Lead;Life Cycle Stages;maternal cigarette smoking;maternal outcome;maternal stress;Measures;Medical;Mentors;Mentorship;Methodology;Methods;Mission;Modeling;Modification;Monitor;Mothers;National Institute on Minority Health and Health Disparities;National Oceanic and Atmospheric Administration;Neonatal Mortality;novel;Outcome;Output;parity;Population;Pregnancy;Pregnant Women;premature;Premature Birth;Prenatal care;prepregnancy;professor;programs;Public Health;public health relevance;Qualitative Methods;Race;Reduce health disparities;remote communities;Research;Research Institute;Research Methodology;Research Personnel;residence;Resources;response;Risk;Risk Assessment;Risk Factors;Role;Rural;Rural Community;Sampling;Smoke;social;social factors;sociodemographic group;sociodemographics;socioeconomics;Source;Statistical Methods;Stress;Stressful Event;stressor;success;System;tenure track;Testing;Time;Training;Training Support;Translational Research;Universities;Wildfire;Woman;Work

PROJECT_TITLE: Convergence of multiple exposures during pregnancy: Effect of wildfires and maternal stressors on birth outcomes among Alaskan women


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Biotechnology;Brain Disorders;Cancer;Dementia;Neurodegenerative;Neurosciences

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Narrative The research in this proposal will provide proof of concept for a novel approach for the treatment of Alzheimer’s disease using monoclonal antibodies. Specifically, we propose to develop conformation-specific monoclonal antibodies, which bind the a secretase ADAM10, activate amyloid precursor protein cleavage, and promote the non-amyloidogenic pathway in cell- and neuron-based assays. The studies will also provide the first high-resolution structural view of how ADAM10 interacts with and cleaves the amyloid precursor protein.

PI_NAMEs: NIKOLOV, DIMITAR B (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: alpha secretase;Alzheimer's Disease;Alzheimer's disease therapeutic;Amino Acids;Amyloid beta-Protein;Amyloid beta-Protein Precursor;amyloid formation;analytical ultracentrifugation;Binding;Biochemical;Biological Assay;Biophysics;Cell Death;Cell Line;Cell surface;Cells;Cognition Disorders;Colon Carcinoma;Complex;Cryoelectron Microscopy;Cysteine;Degenerative Disorder;Dementia;Development;Digestion;Disadvantaged;Disintegrins;Engineering;enthalpy;Ephrins;Epidermal Growth Factor Receptor;Equilibrium;Exhibits;Family;Free Energy;gamma secretase;Glioblastoma;Hand;Human;human monoclonal antibodies;improved;In Vitro;Kinetics;Ligands;Long-Term Potentiation;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;malignant stomach neoplasm;Mediating;member;Memory;Memory Loss;Metalloproteases;microcalorimetry;Molecular;Molecular Conformation;Molecular Mechanisms of Action;Monoclonal Antibodies;mouth squamous cell carcinoma;Mus;Names;neoplastic cell;neuroblastoma cell;Neurons;neuroprotection;neurotoxic;notch protein;novel;novel strategies;novel therapeutic intervention;Oncogenic;overexpression;Pathway interactions;PC12 Cells;Peptide Hydrolases;Peptides;Positioning Attribute;Pre-Clinical Model;Prevalence;Primary Bone Osteosarcoma;Property;Protease Domain;protein complex;Proteins;Proteolysis;Rattus;Reporting;Research;Resolution;secretase;Senile Plaques;sequential proteolysis;side effect;Signal Transduction;Spectrum Analysis;stoichiometry;Structure;Synapses;Tertiary Protein Structure;Therapeutic;Therapeutic Intervention;Thermodynamics;Toxic effect;Transfection;tumor;Up-Regulation;X-Ray Crystallography;Zinc

PROJECT_TITLE: Targeting the alpha secretase ADAM10 for the treatment of Alzheimer's disease

STUDY_SECTION: MSFB

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Immunotherapy

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Narrative Low responses rate to immune checkpoint blockade cancer therapy prompted us to find new strategy to efficiently target therapeutic molecules on cancer cells and immune cells. We recently discovered a new antibody H1A to PD-L1 that is expressed by both cancer cells and immune cells. We found H1A antibody induced PD-L1 depletion in cancer cells to make cancer cells more sensitive to chemotherapy, and in immune cells to generate strong antitumor immune responses. Our proposed studies will address the synergistic effects of H1A with chemotherapy to overcome cancer resistance to chemotherapy and immunotherapy. The new knowledge and tools produced by our proposed studies will help physicians to treat cancer patients with appropriate combination that would not benefit patients’ clinical outcomes.

PI_NAMEs: DONG, HAIDONG  (contact)

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: Advanced Malignant Neoplasm;Affect;anti-tumor immune response;Antibodies;Binding;Blocking Antibodies;cancer cell;Cancer Patient;cancer survival;cancer therapy;Cell surface;Cells;chemotherapy;Clinical;clinical application;cytokine;Cytotoxic Chemotherapy;Data;design;DNA Repair;effector T cell;exhaustion;extracellular;Future;Human;Immune;immune checkpoint;immune checkpoint blockade;Immune response;Immune Targeting;Immunotherapy;improved;In Vitro;in vivo;Interleukin-12;Knowledge;Ligation;Malignant Neoplasms;Mediating;Membrane;Metabolism;multicatalytic endopeptidase complex;Mus;Myelogenous;Myeloid Cells;neoplastic cell;New Agents;novel therapeutic intervention;novel therapeutics;Outcome;Patients;PD-1 blockade;Phase;Physicians;Production;programmed cell death ligand 1;programmed cell death protein 1;receptor;Recycling;Research;Resistance;response;Signal Pathway;Signal Transduction;synergism;T cell response;T-Cell Activation;T-Lymphocyte;targeted agent;targeted treatment;Testing;Therapeutic Agents;Therapeutic Effect;therapeutic evaluation;tool;Translating;tumor;tumor metabolism;Up-Regulation

PROJECT_TITLE: Targeting dual functions of PD-L1 for cancer therapy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-M(08)F]


NIH_SPENDING_CATS: Biotechnology;Infectious Diseases;Neurosciences;Prevention;Sexually Transmitted Infections

ORG_CITY: HANOVER

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: Project Narrative: Herpes simplex virus, the cause of common cold sores, also causes serious human diseases including blindness, infection of the brain, and organ damage in newborns. Once a primary infection takes hold, the virus shelters from the immune system in cells of the nervous system for the lifetime of the host, quiescent until reawakened by a stressor. We will examine the control over this quiescent state by a recently described weapon of the immune system that destroys viral components inside infected cells when they are recognized by antibodies that gain access to the cell interior.

PI_NAMEs: LEIB, DAVID A (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: Affinity;Agonist;Antibodies;antiviral immunity;Apoptosis;arm;Bacteria;Binding;Blindness;Brain;CD8-Positive T-Lymphocytes;Cell Culture Techniques;Cell Lineage;Cell membrane;Cell Nucleus;Cell surface;Cells;Cellular Membrane;Central Nervous System;Common Cold;Complement;Complex;Cytomegalovirus;Cytoplasmic Granules;Cytosol;cytotoxic;Data;design;Electroporation;endosome membrane;Equilibrium;experimental study;Fc Receptor;Ganglia;Genetic Transcription;Granzyme;Herpes Labialis;Herpes Simplex Virus Vaccines;Herpesvirus 1;HIV;Human;human disease;Human Herpesvirus 2;Human Herpesvirus 4;human model;human pathogen;Immune;Immune system;Immunity;Immunoglobulin A;Immunoglobulin G;Immunoglobulin M;immunological synapse;In Situ;In Vitro;in vitro Model;in vivo;Induced pluripotent stem cell derived human neuron;Infection;inhibitor;interest;latency associated transcript;Life Cycle Stages;Lymphocyte;Lytic;lytic gene expression;Mediating;Membrane Fusion;MicroRNAs;Modeling;Molecular;Monitor;mouse model;Mucous Membrane;multicatalytic endopeptidase complex;Nervous System;Nervous System Trauma;neuron loss;Neurons;neurotropic;Newborn Infant;Organ;pathogen;perforin;Peripheral Nervous System;prevent;Primary Infection;Production;Proteins;Recrudescences;Repression;residence;Resistance;Role;Route;seropositive;Shelter facility;Simplexvirus;stressor;Structure of trigeminal ganglion;Surface;tau Proteins;Testing;therapeutic target;Transcript;Translating;Viral;Viral Antigens;Viral Genome;Virus;Virus Latency;Virus Replication;Virus Shedding;weapons

PROJECT_TITLE: Does Antibody-Dependent Intracellular Neutralization Limit HSV-1 Reactivation?


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Serious Mental Illness

ORG_CITY: NEW YORK

ORG_DEPT: PSYCHIATRY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: This application proposes to advance the training of a cognitive neuroscientist and prepare her for a research career focused on the neurobiological mechanisms of aging and late-life mood disorders using computational methodology. The proposed study will investigate the effects of neurobiological changes of aging and depression, their impact on reward and salience network function, and the resultant cognitive distortions of late-life depression. Its findings may identify targets for future personalized treatments for late-life depression.

PI_NAMEs: VICTORIA, LINDSAY  (contact)

PROGRAM_OFFICER_NAME: CHAVEZ, MARK RAY

PROJECT_TERMS: Affective;Age;age effect;aged;Aging;aging mechanism;aging related;Amygdaloid structure;Anhedonia;Anterior;Association Learning;Attention;Behavior;behavior measurement;Behavior Therapy;Behavioral;Brain;career;Cognition;Cognitive;Cognitive deficits;Cognitive remediation;cognitive task;computational neuroscience;Computer Models;Computing Methodologies;Data;Depressed mood;depressive symptoms;design;Development;discount;Dorsal;Event;experience;Foundations;Functional disorder;Functional Magnetic Resonance Imaging;Future;Generations;geriatric depression;Goals;Impairment;Individual;Instruction;Insula of Reil;interest;Intervention;K-Series Research Career Programs;Knowledge;late life;Learning;Maintenance;Major Depressive Disorder;Mental Depression;Mentored Research Scientist Development Award;Mentors;Methodology;Mood Disorders;National Institute of Mental Health;network models;neural;neural network;neurobiological mechanism;Neurobiology;neuroimaging;normal aging;Nucleus Accumbens;older adult;Outcome;outcome prediction;Participant;Patient Self-Report;Performance;personalized medicine;Positive Valence;Predisposition;Process;Psychological reinforcement;Psychopathology;Punishment;Recording of previous events;Research;Research Design;Research Domain Criteria;Research Personnel;research study;Reversal Learning;reward expectancy;reward processing;Rewards;Role;Scientist;Series;Severities;skills;Statistical Models;Stimulus;Structure;Study models;symptomatology;System;Task Performances;Technical Expertise;Thalamic structure;Time;Training;Ventral Striatum;Weight;Work

PROJECT_TITLE: Prediction Error and Affective Salience Abnormalities in Aging and Late-Life Depression

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


NIH_SPENDING_CATS: Contraception/Reproduction;Immunization;Infectious Diseases;Infertility;Prevention;Sexually Transmitted Infections;Vaccine Related;Women's Health Research

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: The CDC estimates that Chlamydia is one of the most prevalent bacterial infections in the US and causes upper reproductive tract pathology in a growing number of otherwise health young women. Unfortunately, women with untreated Chlamydia infection can develop serious pelvic inflammatory disease (PID), infertility, chronic pelvic pain, or suffer from ectopic pregnancy. Given the high incidence of infection and the potential for serious pathology, the current consensus among scientists and clinicians is that an effective Chlamydia vaccine is needed. In order for a vaccine to be generated, we require a greater understanding of host immunity to Chlamydia infection in the upper reproductive tract. This application will utilize new antigen-specific reagents to study the mouse model of genital Chlamydia infection. We will use these reagents to examine the mechanism of circulating memory to Chlamydia in the female reproductive tract.

PI_NAMEs: MCSORLEY, STEPHEN J (contact)

PROGRAM_OFFICER_NAME: VINCENT, LEAH REBECCA

PROJECT_TERMS: Address;Antibodies;Antibody Response;Antigens;Bacterial Infections;Biological Models;Blindness;CD4 Positive T Lymphocytes;Cells;Centers for Disease Control and Prevention (U.S.);cervicovaginal;Chlamydia;Chlamydia Infections;Chlamydia trachomatis;chlamydia vaccine;chronic pelvic pain;Consensus;Cytoprotection;Data;Disease;Ectopic Pregnancy;effector T cell;experience;female reproductive tract;female reproductive tract infection;Foundations;Generations;Genitalia;Health;High Prevalence;human pathogen;Human Pathology;Immune response;Immunity;Immunization;Incidence;Individual;Infection;Infertility;Intervention;Intestines;Knowledge;Lymphoid Cell;Mediating;Memory;memory CD4 T lymphocyte;Modeling;mouse model;Mucous Membrane;Nature;novel vaccines;Pathology;Pelvic Inflammatory Disease;Population;Public Health;Publishing;Reagent;recruit;Reporting;reproductive;Reproductive Health;reproductive tract;response;Role;Route;Scientist;secondary infection;Serum;Sexually Transmitted Diseases;Surface;System;Testing;Th1 Cells;tissue resident memory T cell;Tissues;Transgenic Mice;Tropism;Vaccines;Visualization;Woman;young woman

PROJECT_TITLE: Developing mouse models to study circulating memory to Chlamydia infection

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


NIH_SPENDING_CATS: Nutrition

ORG_CITY: ANN ARBOR

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative The AMPK and mTOR complex 1 (mTORC1) protein kinases enable cells and tissues to respond to fluctuations in a variety of systemic cues. This proposal will define an unexpected role for the energy sensing kinase AMPK in cellular adaptation to nutrient stress caused by amino acid starvation through cooperation with mTORC1 to maintain metabolic function. This research using cultured cells and mouse models will advance our understanding of mTOR and AMPK in health and disease and may identify new therapeutic strategies for treatment of linked disorders, such as cancer and metabolic diseases.

PI_NAMEs: FINGAR, DIANE C. (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: 5'-AMP-activated protein kinase;Address;Alleles;Amino Acids;Amino Acids Activation;AMP-activated protein kinase kinase;Angioplasty;Autophagocytosis;Basal metabolic rate;Biochemical;Biogenesis;Biological;blood glucose regulation;cell growth;Cell model;Cell Physiology;Cell Survival;Cells;Cellular Metabolic Process;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Cues;Cultured Cells;Curiosities;Disease;energy balance;Engineering;Event;exercise capacity;FDA approved;feeding;FRAP1 gene;Genetic;glucophage;Glucose;Goals;Growth Factor;Health;Homeostasis;Human;improved;in vivo;inhibitor;Insulin;Knock-in;Knowledge;Lead;Link;Lipids;Lysosomes;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Membrane;Metabolic;Metabolic Control;Metabolic Diseases;Metabolism;Metformin;Mitochondria;Modeling;Molecular;Morphology;mouse model;Non-Insulin-Dependent Diabetes Mellitus;novel therapeutic intervention;Nutrient;Pathway interactions;Pharmaceutical Preparations;Phosphorylation;Phosphotransferases;Physiological;Process;Protein Kinase;Proteins;Recovery;Regulation;Renal Cell Carcinoma;Research;Respiration;response;restenosis;Role;Signal Transduction;Site;Skeletal Muscle;Starvation;Stents;Stress;Testing;Therapeutic;Tissues;treatment strategy;Tuberous Sclerosis;Tumor Promoters;Tumor Suppressor Proteins;tumorigenesis;Work

PROJECT_TITLE: Unexpected role for AMPK and mTORC1 in cellular adaptation to nutrient stress

STUDY_SECTION: MIST

STUDY_SECTION_NAME: Molecular and Integrative Signal Transduction Study Section[MIST]


NIH_SPENDING_CATS: Biotechnology;Immunization;Infant Mortality;Infectious Diseases;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE Fully differentiated plasma cells spontaneously secreting antibodies reactive to endemic pathogenic bacteria are detected in the thymus of human neonates. Our studies will investigate the composition and protective capabilities of these natural antibodies.

PI_NAMEs: ZORN, EMMANUEL  (contact)

PROGRAM_OFFICER_NAME: PRABHUDAS, MERCY R

PROJECT_TERMS: Anti-Bacterial Agents;Antibodies;Antibody Response;Antibody-Producing Cells;Apoptotic;Area;B-cell receptor repertoire sequencing;B-Lymphocytes;Bacteria;Birth;Blood;Bone Marrow;Cell Ontogeny;Cells;Cessation of life;Clonal Expansion;Clone Cells;combat;commensal bacteria;design;Developed Countries;experimental study;exposed human population;expression cloning;fetal;Fetus;Gut associated lymphoid tissue;Haemophilus influenzae;Human;Humoral Immunities;Immune;Immunity;Immunoglobulin D;Immunoglobulin G;Immunoglobulin M;Immunoglobulins;in utero;in vivo;Individual;Infant;Infection;Life;Liver;Lower Respiratory Tract Infection;Masks;Modeling;Monoclonal Antibodies;Mus;natural antibodies;Natural Source;Neonatal;neonatal infection;Neonatal Mortality;neonatal period;neonate;Newborn Infant;Organ;pathogen;pathogenic bacteria;Placenta;plasma cell development;plasma cell differentiation;Plasma Cells;Population;Pregnancy;Reaction;Recombinant Antibody;Recombinants;reconstitution;Reporting;Research;Rest;Sepsis;Serology;single-cell RNA sequencing;Site;Source;Spleen;Testing;Thymus Gland;transcriptome;Umbilical Cord Blood;unborn child;Uncertainty;Work

PROJECT_TITLE: Thymic plasma cells as a source of protective natural antibodies in human neonates

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIB-U(90)]


ORG_NAME: WM S. MIDDLETON MEMORIAL VETERANS HOSP

PHR: PUBLIC HEALTH RELEVANCE:         Following deployment to the Persian Gulf, nearly 250,000 Gulf War Veterans (GVs) now report an array of symptoms including fatigue, pain, and problems with cognitive function. Nearly 50% of GVs seek VA clinical care, and nearly 40% receive disability compensation. To date, the causes of these symptoms are not known, and as a result, no efficacious treatments are available. The proposed research addresses this problem by testing multiple physiological systems at rest and in response to exercise in GVs with Gulf War Illness (GWI). These studies will determine whether interactions among central nervous, autonomic, and immune systems explain symptoms at baseline and the worsening of symptoms that occur following exercise challenge (i.e., post-exertion malaise). Results from this research are intended to improve our understanding of the causes of GWI and to begin a path towards individualized treatment of this debilitating condition. These goals are directly in-line with the mission of the Department of Veterans Affairs to care for those who have served this country.

PI_NAMEs: COOK, DANE B. (contact);FALVO, MICHAEL J.

PROJECT_TERMS: Acute;Address;Afghanistan;autonomic nerve;Behavioral;Brain;Cardiac;Cardiovascular system;Caring;Central Nervous System;cerebrovascular;Cerebrovascular Circulation;Characteristics;Chronic;Chronic Fatigue Syndrome;clinical care;Cognition;cognitive function;cognitive task;Country;cytokine;Data;design;disability payment;efficacious treatment;Evidence Based Medicine;Exercise;Exertion;experience;Fatigue;Fibromyalgia;Functional disorder;Functional Magnetic Resonance Imaging;Gene Expression;Glucocorticoid Receptor;Goals;Gulf War veteran;Health;health care service utilization;Heart Rate;Homeostasis;Hour;Immune;Immune system;immunoregulation;Impaired cognition;Impairment;improved;individualized medicine;Inflammation Mediators;Inflammatory;Institute of Medicine (U.S.);instrument;Intervention;Iraq;Laboratories;Lasso;Leukocytes;Maintenance;Malaise;Measures;Medical;Metabolic;Methods;Mission;Modeling;Musculoskeletal Pain;neural;Pain;Pain Measurement;pain sensitivity;Paint;Pathway interactions;Patients;Persian Gulf;Persian Gulf Syndrome;personalized medicine;Physiological;Physiology;Positioning Attribute;Posture;public health relevance;Publishing;Regulation;Reporting;Research;Research Personnel;response;Rest;Stimulus;stressor;Study models;Symptoms;System;targeted treatment;Testing;therapy design;Time;Titrations;United States Department of Veterans Affairs;Veterans;Viscera;War;Work

PROJECT_TITLE: Post exertion malaise in GWI_Brain autonomic and behavioral interactions

STUDY_SECTION: SPLD

STUDY_SECTION_NAME: Special Emphasis - Research on Gulf War Veterans' Illnesses[SPLD]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

PHR: Project Narrative The opportunistic fungal pathogen Aspergillus fumigatus remains a health concern for critically ill patients and continues to have a high mortality rate despite improvements in anti-fungal therapies. This proposal seeks to investigate the role of heterogeneous conventional dendritic cells (cDCs) in generating adaptive immune responses to A. fumigatus. Understanding the mechanisms by which cDCs induce protective immunity may identify novel strategies for development of therapies and vaccines to mitigate the burden of A. fumigatus and other fungal pathogens.

PI_NAMEs: DEEP, DEEKSHA  (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Ablation;Acute;adaptive immune response;adaptive immunity;Adoptive Transfer;Allergic Bronchopulmonary Aspergillosis;Anatomy;anti-fungal agents;Anti-Inflammatory Agents;Antifungal Therapy;Antigen Presentation;Antigen-Presenting Cells;antigen-specific T cells;Antigens;Aspergillus fumigatus;attributable mortality;CD4 Positive T Lymphocytes;CD8B1 gene;Cells;Chronic;Clinical;clinically relevant;Complex;Computing Methodologies;Critical Illness;Cytometry;Data;Death Rate;Dendritic Cells;differential expression;Dimensions;draining lymph node;Exhibits;Flow Cytometry;Genetic;Genetic Transcription;Goals;Health;Helper-Inducer T-Lymphocyte;Heterogeneity;Human;human disease;Immune;Immune response;Immunity;Immunobiology;Immunocompromised Host;Immunofluorescence Immunologic;improved;In Vitro;in vivo;Infection;Infiltration;Inflammation;Inflammatory;ITGAM gene;Knowledge;Label;Lung;Mediastinal lymph node group;Mediator;Methods;MHC Class II Genes;Microscopy;mouse model;Mus;Mycoses;Natural Immunity;novel;novel strategies;novel therapeutic intervention;pathogen;pathogenic fungus;Pathogenicity;Pathologic Processes;patient population;Patients;Physicians;Physiological;Population;Positioning Attribute;Property;Regulation;Regulatory T-Lymphocyte;response;restraint;Role;Scientist;single cell analysis;Spatial Distribution;stem;Study models;Syndrome;System;T cell response;T-bet protein;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;Therapeutic Intervention;therapy development;tool;trafficking;Training;transcriptome sequencing;uptake;vaccine development;Vaccines;XCR1 gene

PROJECT_TITLE: Dendritic cell heterogeneity and its role in pulmonary fungal infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F07-U(20)L]


NIH_SPENDING_CATS: Biotechnology;Genetics;Immunization;Immunotherapy;Infectious Diseases;Orphan Drug;Prevention;Rare Diseases;Vaccine Related;Vector-Borne Diseases

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Visceral leishmaniasis is a devastating parasitic disease that causes death if left untreated and despite decades of research, efforts to develop a durable, effective vaccine have been unsuccessful. Rather than remaining “hidden” from the adaptive immune system, we have found that T cells undergo a state of dysfunction often described as “exhaustion” during visceral leishmaniasis, similar to what occurs during chronic viral infections and cancer. Thus, the goal of this study is to begin to understand why protective immunity against visceral leishmaniasis fails to develop and if T cell exhaustion can be reversed using therapeutic immunization and/or immunotherapy, which will contribute to our long-term goal of understanding how to improve vaccine design against and develop treatments for Leishmania infections.

PI_NAMEs: NICE, TIMOTHY J. (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: Acceleration;Adaptive Immune System;Animals;Antigens;Bacterial Infections;Biological Models;Cause of Death;CD4 Positive T Lymphocytes;Cell Physiology;Cellular Immunity;Cessation of life;Chronic;chronic infection;Complex;CTLA4 gene;Cutaneous;Cutaneous Leishmaniasis;cytokine;cytotoxic CD8 T cells;Data;Development;Disease;Epitopes;exhaust;exhaustion;Experimental Models;Functional disorder;functional restoration;Gene Expression Profile;Gene Expression Profiling;gene network;Genes;Genetic Transcription;Glycosome;Goals;Human;Immunity;Immunization;Immunize;Immunotherapy;improved;Infection;Inflammatory;Interleukin-10;Kinetics;Left;Leishmania;Leishmania donovani;Leishmaniasis;Liver;Longevity;Macrophage;Mediating;memory CD4 T lymphocyte;Molecular;Molecular Profiling;mouse model;Multiple Organ Failure;Mus;neglected tropical diseases;neutralizing antibody;Parasites;Parasitic Diseases;Parasitic infection;pathogen;Phenotype;Phosphoenolpyruvate Carboxylase;prevent;Production;programmed cell death protein 1;receptor;Reporter;Research;response;Signal Pathway;skin disorder;Spleen;Systemic disease;T cell response;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;therapeutic immunization;Therapeutic Uses;treatment strategy;Vaccination;Vaccine Design;vaccine development;Vaccine Therapy;Vaccines;Vaccinia virus;vaccinia virus vector;Viral;Viral Cancer;Virus Diseases;Visceral;Visceral Leishmaniasis

PROJECT_TITLE: CD4+ T cell dysfunction during visceral leishmaniasis


ORG_CITY: PHILADELPHIA

ORG_NAME: WISTAR INSTITUTE

ORG_STATE: PA

PHR: Project Narrative Many individuals develop cancers. The brain is one of the common organs for cancer recurrence. Unfortunately, cancer brain metastasis is increasingly becoming a significant clinical problem due to its rising incidence and limited efficacy of existing systemic therapies. Metastasis is the consequence of favorable interactions between the invaded cancer cells and the microenvironment in the distal organ. To cancer cells, the brain has the most unique microenvironment since almost all the cells in the brain do not exist in any other organs. Thus, this proposal is designed to study crosstalks between cancer cells and brain stromal cells. If we can identify key changes in this process, we can better target brain metastatic cancer cells, in order to eradicate them and provide more effective therapies for cancer patients.

PI_NAMEs: CHEN, QING  (contact)

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: Address;Agonist;aldehyde dehydrogenases;antagonist;Apoptosis;Arachidonic Acids;Astrocytes;astrogliosis;beta catenin;Binding;Biological Assay;Brain;brain cell;cancer cell;Cancer Patient;cancer recurrence;cell motility;cell type;Cells;Cephalic;Cessation of life;Clinic;Clinical;Coculture Techniques;Coin;Complex;Data;design;Disseminated Malignant Neoplasm;Distal;E-Cadherin;effective therapy;Epithelium;Experimental Models;experimental study;Fatty acid glycerol esters;Fatty Acids;Gene Expression Profiling;Genes;Genetic;Goals;Growth;In Vitro;in vitro Model;in vivo;Incidence;Individual;insight;intravital microscopy;Invaded;Kinetics;Location;Malignant neoplasm of brain;Malignant Neoplasms;Mass Spectrum Analysis;Mediator;Melanoma;Melanoma Cell;Melanoma patient;Mesenchymal;Metastatic malignant neoplasm to brain;Metastatic Melanoma;metastatic process;migration;Modeling;mouse model;Neoplasm Metastasis;Neuroglia;Neurons;novel;novel therapeutic intervention;Oleic Acids;Organ;Pathway interactions;Patients;Peroxisome Proliferator-Activated Receptors;pharmacologic;Phenotype;PPAR gamma;pre-clinical;Primary Neoplasm;Process;Production;Proliferating;promoter;receptor;Relapse;Reporter;Research;Response Elements;Role;Sampling;Signal Transduction;Site;small molecule inhibitor;Soil;spatiotemporal;Stains;Stromal Cells;Systemic Therapy;Techniques;Testing;therapeutic target;therapy resistant;Time;Unsaturated Fatty Acids;Xenograft procedure

PROJECT_TITLE: Understanding PPARgamma signaling in melanoma brain metastasis

STUDY_SECTION: TME

STUDY_SECTION_NAME: Tumor Microenvironment Study Section[TME]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Conditions Affecting the Embryonic and Fetal Periods;Drug Abuse (NIDA only);Genetics;Human Genome;Mental Health;Neurosciences;Opioid Misuse and Addiction;Opioids;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Substance Misuse;Women's Health Research

ORG_CITY: HIGHLAND HEIGHTS

ORG_NAME: NORTHERN KENTUCKY UNIVERSITY

ORG_STATE: KY

PHR: Project Narrative  Children exposed to opioids in utero, either through the mother’s opioid use/abuse or via medication- assisted treatment for opioid addiction (MAT, methadone or buprenorphine), are at an increased risk for cognitive deficits, particularly those related to attention and impulse control. No study has addressed this in an animal model so the goal of this proposal is to test how maternal opioid use, including MAT, affects offspring brain development and behavior in a mouse model. These studies will establish a foundation for future investigations into potential interventions to improve outcomes in opioid-exposed children.

PI_NAMEs: SMITH, BRITTANY L (contact)

PROGRAM_OFFICER_NAME: LIN, YU

PROJECT_TERMS: Address;Adolescence;Adult;Advisory Committees;Affect;Animal Model;Animals;Area;Attention;Attention deficit hyperactivity disorder;Automobile Driving;Behavior;Behavior assessment;Behavioral;Bioinformatics;Biological;biomedical informatics;Blood;Blood specimen;Brain;Brain region;Buprenorphine;career;certificate program;Child;Clinic;Clinical;Clinical Research;Cognition;Cognitive deficits;Complex;Complex Variables;Data;Development;Diagnosis;DNA;Electronic Health Record;Environment;Environmental Exposure;Epidemic;Epigenetic Process;epigenomics;Executive Dysfunction;executive function;experimental study;Exposure to;Fetal Development;Foundations;Future;Future Generations;Gene Expression;Gene Expression Profile;Genetic Transcription;genome-wide;Goals;Government-Sponsored Programs;Healthcare;help-seeking behavior;Hospital Charges;Hospitalization;Human;human data;human DNA;improved;improved outcome;Impulsivity;in utero;inattention;Incidence;Infant;innovation;Intervention;Investigation;Life;maternal opioid use;medication-assisted treatment;meetings;Mentors;Methadone;Methylation;Molecular;Molecular Profiling;Mothers;mouse model;Mus;Neonatal Abstinence Syndrome;neonate;Neurosciences;Newborn Infant;offspring;Opiate Addiction;Opioid;opioid abuse;opioid epidemic;opioid exposure;opioid use;Outcome;Pattern;Peripheral;Pharmaceutical Preparations;Phase;Placenta;polysubstance use;Population;pre-clinical;Prefrontal Cortex;Pregnancy;Pregnant Women;prenatal;Problem behavior;Prognosis;programs;Public Health;Reaction Time;Recording of previous events;Reporting;Research;Resources;response;Risk;Rodent;Rodent Model;Sampling;Self-control as a personality trait;Severities;Short-Term Memory;standard of care;Survival Rate;Swab;Testing;Therapeutic Intervention;therapeutically effective;Time;Training;Training Activity;transcriptome sequencing;Translational Research;translational scientist;translational study;treatment strategy;Whole Blood;Woman;Work

PROJECT_TITLE: Executive function in opioid-exposed offspring and subsequent molecular signatures


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Aging;Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Cardiovascular;Data Science;Heart Disease;Machine Learning and Artificial Intelligence;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Post-Traumatic Stress Disorder (PTSD);Prevention

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE By utilizing a unique, prospective, population-based registry cohort of over 1 million trauma-exposed individuals and harnessing leading data science analytic techniques, this study will identify the manifestations of posttraumatic psychopathology associated with cardiovascular disease (CVD) risk in a national sample of men and women. These findings will be used to inform the development of targeted CVD prevention efforts in trauma-exposed populations.

PI_NAMEs: GRADUS, JAIMIE L.;SUMNER, JENNIFER A (contact)

PROGRAM_OFFICER_NAME: DONZE, LAURIE FRIEDMAN

PROJECT_TERMS: 18 year old;Accidents;Accounting;Address;Affect;Anxiety;assault;Automobile Driving;Big Data;Cardiotoxicity;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cardiovascular system;Characteristics;cohort;comorbidity;Complex;Computerized Medical Record;Data;data registry;Data Science;Data Sources;Databases;Development;Diagnosis;Disease Outcome;Electronic Health Record;Event;Exposure to;follow-up;Future;Heart Diseases;Heart failure;Hypertension;improved;Incidence;Individual;Intervention;Investigation;Knowledge;Link;Literature;Machine Learning;Measures;men;Mental Depression;Mental disorders;mortality;Myocardial Infarction;National Heart, Lung, and Blood Institute;novel;novel strategies;Outcome;Pattern;Persons;Population;population based;Population-Based Registry;Post-Traumatic Stress Disorders;Prevalence;Prevention;primary outcome;prospective;psychiatric comorbidity;psychologic;Psychopathology;Public Health;Registries;Reporting;Research;resilience;Resources;Risk;Risk Factors;risk prediction model;Role;Sampling;secondary outcome;sex;Sex Differences;Smoking;Stroke;Substance abuse problem;substance misuse;Techniques;Time;Trauma;trauma exposure;traumatic event;United States;venous thromboembolism;virtual;Woman;Work;working group

PROJECT_TITLE: Identifying Cardiotoxic Manifestations of Posttraumatic Psychopathology: A Population-based Longitudinal Investigation

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Arthritis;Genetics;Osteoarthritis

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative The broad, long-term goal of this project is to develop a comprehensive understanding of the developmental events that dictate cell fate decisions in formation of the synovial joint. Within this broad area, this proposal focuses on the differentiation of articular cartilage, which plays a central role in maintaining the low-friction environment of the joint space. Successful completion of this proposal will provide fundamental new insight into the events that regulate the development of articular cartilage, with additional implications for regeneration of articular cartilage in degenerative joint diseases including osteoarthritis (OA) or rheumatoid arthritis (RA).

PI_NAMEs: LASSAR, ANDREW BRUCE (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Adult;Alleles;Area;Arthritis;articular cartilage;ATAC-seq;bZIP Domain;Cattle;Cells;Chondrocytes;Competence;Coupled;Degenerative polyarthritis;Development;DNA Binding Domain;Ectopic Expression;Embryo;Engineering;Environment;Epidermal Growth Factor Receptor;Epiphysial cartilage;Event;Exons;Fibroblasts;Friction;Gene Expression;Genes;Genetic Recombination;Genetic Transcription;Goals;Guide RNA;Hallmark Cell;Induced Mutation;inducible Cre;Infection;Injury;insight;joint formation;Joints;Knee joint;knock-down;Lentivirus;Limb Bud;long bone;lubricin;Maintenance;Mechanics;Mediating;Meniscus structure of joint;Mesenchyme;Mus;Natural regeneration;Newborn Infant;novel;p38 Mitogen Activated Protein Kinase;Physiologic Ossification;Play;postnatal;programs;Protein Binding Domain;protein expression;Proteins;Proteoglycan;Regulatory Element;Repression;response;Rheumatoid Arthritis;Role;Signal Pathway;Signal Transduction;small hairpin RNA;stem cell population;Synovial joint;tissue regeneration;Tissues;transcription factor;transcriptome sequencing;Transforming Growth Factor Beta 2;Work

PROJECT_TITLE: Elucidation of the Role of Creb5 in Synovial Joint Formation

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]