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

ORG_CITY: HACKENSACK

ORG_NAME: HACKENSACK UNIVERSITY MEDICAL CENTER

ORG_STATE: NJ

PHR: Candida glabrata is an opportunistic fungal pathogen whose incidence is increasing due to its high intrinsic resistance to azole antifungals, and it also rapidly evolves resistance to echinocandins, leading to multi-drug resistant strains that are virtually impossible to treat. C. glabrata is also notable for its remarkable genetic diversity, which is hypothesized to be driven by the same mechanisms as its ability to rapidly evolve drug resistance. The proposed study will elucidate these mechanisms in C. glabrata by identifying factors that mediate the formation and processing of mutagenic DNA double-strand breaks.

PI_NAMEs: SHOR, ERIKA  (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: anti-fungal agents;Antibodies;Azole resistance;Azoles;biological systems;Candida;Candida glabrata;Cell division;Cells;ChIP-seq;chromatin immunoprecipitation;Chromosome Fragile Sites;Chromosomes;Collaborations;CRISPR/Cas technology;Data Analyses;Data Set;DNA;DNA Damage;DNA Double Strand Break;DNA Repair;DNA Sequence;Double Strand Break Repair;Drug resistance;Epitopes;Evolution;experience;experimental study;Exposure to;fungus;G-Quartets;gastrointestinal;gene repair;Genes;Genetic;genetic evolution;Genetic Polymorphism;genetic variant;Genetic Variation;Genome;Genome Stability;Genomics;Haploidy;homologous recombination;Impairment;In Vitro;Incidence;Karyotype;Knowledge;Lesion;Macrophage;Malignant Neoplasms;Maps;Mass Spectrum Analysis;Measurement;Mediating;Mediator;metabolomics;Mitosis;Modeling;mortality;Multi-Drug Resistance;Mus;mutant;Mutation;New York;next generation sequencing;Nucleotides;Open Reading Frames;pathogenic fungus;Phenotype;Phosphotransferases;Pilot Projects;Point Mutation;Poly(ADP-ribose) Polymerase Inhibitor;prevent;Probability;Process;Proteins;Proteomics;Pulsed-Field Gel Electrophoresis;Reporter;Reporting;Resistance;resistance frequency;resistance mutation;resistant strain;Resolution;response;Role;S phase;Saccharomyces cerevisiae;Signal Transduction;Site;Source;Structure;success;Techniques;Testing;therapeutically effective;Transfer RNA;Universities;Variant;virtual

PROJECT_TITLE: Elucidating mediators of genetic instability in Candida glabrata

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


ADMINISTERING_IC: MH

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Genetics;Mental Health;Neurosciences;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: FORT COLLINS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOCHEMISTRY

ORG_FIPS: US

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: Modified Public Health Relevance Section The cellular function of Neuroligin-4 (NLGN4), a human-specific synaptic protein, remains unclear due to its poor expression and minimal sequence conservation in conventional rodent models. We will derive human neuronal subtypes from pluripotent stem cells to determine NLGN4’s role at synapses, and examine how different domains and residues regulate NLGN4’s mechanistic properties. Our approach will provide novel insights into NLGN4-dependent unique synaptic processes that operate specifically in a human brain.

PI_NAMEs: CHANDA, SOHAM  (contact)

PROGRAM_OFFICER_NAME: PANCHISION, DAVID M

PROJECT_TERMS: Adverse effects;Affect;Affinity;Amino Acid Sequence;Amino Acids;Arginine;Binding;Biochemical;Biological Assay;Biological Models;Biological Process;Biotinylation;Birth;Brain;Brain Stem;Cause of Death;Cell Adhesion Molecules;Cell Aggregation;Cell Physiology;Cell Reprogramming;Cells;Cerebral cortex;Characteristics;Clustered Regularly Interspaced Short Palindromic Repeats;Co-Immunoprecipitations;confocal imaging;Conserved Sequence;Data;Defect;density;differentiation protocol;Electrophysiology (science);Embryo;Environment;Epigenetic Process;Epitopes;Excitatory Synapse;Exhibits;experimental study;Extracellular Domain;Family member;Gene Targeting;Genes;Genetic;Genetic Engineering;Glutamine;glycosylation;Human;human interactome;human model;human stem cells;Image;induced pluripotent stem cell;Inhibitory Synapse;insight;Knockout Mice;Knowledge;Laboratories;Link;loss of function;loss of function mutation;Mass Spectrum Analysis;Mediating;Methods;Modeling;Molecular;Morphology;Mus;Mutagenesis;mutant;Mutate;N-Glycosylation Site;neural;neural circuit;Neurons;Neurotransmitter Receptor;novel;Orthologous Gene;Output;overexpression;Play;Pluripotent Stem Cells;Post-Translational Protein Processing;postsynaptic;presynaptic;Process;Property;Protein Isoforms;Proteins;public health relevance;Recombinants;Research;Respiratory Center;Rodent;Rodent Model;Role;scaffold;Series;Single Nucleotide Polymorphism;small molecule;species difference;Specificity;stem;stem cells;Structure;Synapses;System;Techniques;Technology;trafficking;transcription factor;transmission process;Variant;X Chromosome

PROJECT_TITLE: Cellular Mechanisms of Neuroligin-4 Gene in Human Neurons


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Prostate Cancer;Urologic Diseases

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

ORG_STATE: CA

PHR: Prostate cancer remains to be one of the leading causes of cancer-related death in U.S. men, largely due to resistance to current therapeutics. Therefore, there is an urgent need of more effective therapeutics that can provide sustained benefits or cure to the patients. Our studies aim to achieve a relatively thorough understanding of the aberrant role of a circadian clock regulator in driving the lethal form of prostate cancer and offer a new therapy strategy for effective treatment of the lethal form of prostate cancer.

PI_NAMEs: CHEN, HONGWU  (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Acetylation;advanced prostate cancer;androgen independent prostate cancer;antagonist;ASCL1 gene;Automobile Driving;Biological Assay;Biological Process;Cancer Etiology;cancer stem cell;cancer subtypes;cancer type;Carcinogens;Cell Lineage;Cells;Cessation of life;ChIP-seq;Chromatin;chromatin modification;Chromatin Structure;circadian;Circadian Dysregulation;circadian pacemaker;Circadian Rhythms;Complex;Data;Disease;DNA Binding;Drug resistance;effective therapy;efficacy evaluation;enzalutamide;Epigenetic Process;Gene Activation;Generations;Genes;Genetic Transcription;Genomic approach;Growth;In Vitro;in vivo;inhibitor;innovation;insight;knock-down;Link;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;men;Metabolism;Metastatic Prostate Cancer;Modeling;Molecular;Neoplasm Metastasis;neoplastic cell;Neuroendocrine Prostate Cancer;Neurosecretory Systems;new therapeutic target;novel;novel therapeutics;overexpression;pancreatic cancer cells;patient derived xenograft model;Patients;Pharmaceutical Preparations;programs;prostate cancer cell;prostate cancer model;Proteins;recruit;Regulation;Regulator Genes;Resistance;Resistance development;Risk;Role;Safety;Series;Site;small molecule;small molecule inhibitor;Squamous Cell Lung Carcinoma;stem-like cell;stemness;success;Testing;Therapeutic;therapeutic development;therapeutic target;therapeutically effective;therapy resistant;Time;transcriptome sequencing;triple-negative invasive breast carcinoma;tumor;tumor growth;tumorigenic

PROJECT_TITLE: Targeting aberrant circadian regulator in advanced prostate cancer

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Sleep Research

ORG_CITY: LOS ANGELES

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative The public health implications of this project are two-fold: First, this project will examine the functional role for sleep in selecting and removing synapses from the brain to maintain optimal neural function. Second, we will investigate the role for sleep in pruning damaged neurites after injury and examine the potential for manipulating sleep after injury as an intervention to protect synapses after trauma.

PI_NAMEs: DONLEA, JEFFREY MICHAEL (contact)

PROGRAM_OFFICER_NAME: HE, JANET

PROJECT_TERMS: Acute;Adult;Astrocytes;Axon;axon injury;axonal degeneration;Axotomy;Back;Biological Assay;Brain;Cell membrane;cell type;confocal imaging;Data;Development;Drosophila genus;Drosophila melanogaster;Endocytosis;Excision;experimental study;fly;Gene Expression;Genes;Genetic;genetic regulatory protein;injured;Injury;insight;Intervention;Libraries;Mediating;Membrane;memory encoding;Microglia;Modeling;Molecular;Mushroom Bodies;mutant;Mutation;Nerve;Nerve Degeneration;nerve injury;nerve transection;neural;Neurites;neurochemistry;Neuroglia;neuromechanism;Neuronal Injury;Neuronal Plasticity;Neurons;Neuropeptides;Neurophysiology - biologic function;neuroprotection;Neurotransmitters;Olfactory Receptor Neurons;Peptide Receptor;Peptides;Phagocytes;Phagocytosis;presynaptic;prevent;Process;programs;Proteins;Public Health;receptor;Recovery;Regulator Genes;response;response to injury;Role;Signal Transduction;Sleep;Sleep Deprivation;Sleep disturbances;sleep regulation;Sleeplessness;Synapses;Synaptic plasticity;synaptic pruning;synthetic enzyme;Tachykinin;Testing;Trauma;Wallerian Degeneration

PROJECT_TITLE: Investigating the role of sleep in synaptic reorganization after neural injury

STUDY_SECTION: NDPR

STUDY_SECTION_NAME: Neurodifferentiation, Plasticity, Regeneration and Rhythmicity Study Section[NDPR]


ADMINISTERING_IC: HL

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Genetics;Hematology;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: CHICAGO

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Non-toxic and tailored therapeutic options are severely limited for patients with high-risk myelodysplastic syndrome (MDS). CUX1 is deficient or frequently inactivated in MDS and is a critical regulator of hematopoietic stem cell homeostasis. The proposed research is expected to reveal novel upstream regulators of CUX1 and identify druggable molecular pathways to restore its levels as a way of reversing anemia and dysplasia in MDS patients.

PI_NAMEs: SENAGOLAGE, MADHAVI DUSHYANTHI (contact)

PROGRAM_OFFICER_NAME: HILL-PRYOR, CRYSTAL DARLEANE-ROBIN

PROJECT_TERMS: Alleles;Anemia;arm;Biological;Biology;Biometry;Blood;Blood Cells;Bone Marrow;career;CD34 gene;Cell Line;Cell Lineage;Cells;Chromosome 7;chromosome 7 loss;chromosome 7q loss;Chromosome abnormality;Clinical;Communication;computerized tools;CRISPR/Cas technology;Cytogenetics;cytopenia;Data;Defect;Deficiency Diseases;Development;Differentiation Therapy;Disease;disease model;Dysmyelopoietic Syndromes;Dysplasia;efficacy evaluation;efficacy testing;Erythroid;erythroid differentiation;Foundations;Genes;genome-wide;Glycogen Synthase Kinase 3;Goals;Grant;granulocyte;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Hemorrhage;high risk;Homeobox;Human;Impairment;improved outcome;in vivo;Ineffective Hematopoiesis;Infection;inhibitor;innovation;knock-down;leukemia;leukemic transformation;loss of function;Mediating;Megakaryocytes;Mentors;Modeling;Molecular;Monosomy 7;Morbidity - disease rate;mouse model;Mus;Mutation;Mutation Analysis;Myeloid Cells;Myeloproliferative disease;novel;Online Systems;Pathway interactions;patient retention;Patients;Pharmaceutical Preparations;pharmacologic;Phosphotransferases;Post-Translational Protein Processing;Prognosis;Protein Isoforms;Proteins;Regulation;Regulatory Pathway;Research;Residual state;restoration;Risk;Signs and Symptoms;Site;stem cell differentiation;stem cell homeostasis;Testing;Therapeutic;therapeutic effectiveness;therapeutic evaluation;Training;Transcript;transcription factor;Tumor Suppressor Proteins;Work;Writing

PROJECT_TITLE: Functional characterization of CUX1 regulators for the treatment of myelodysplastic syndromes


NIH_SPENDING_CATS: Anorexia;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Eating Disorders;Mental Health;Mental Illness;Nutrition;Precision Medicine;Rehabilitation;Serious Mental Illness

ORG_CITY: LOUISVILLE

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF LOUISVILLE

ORG_STATE: KY

PHR: PROJECT NARRATIVE This project will collect data on the feasibility, acceptability, efficacy, and target engagement of a personalized treatment for eating disorders. The proposed research has significant public health relevance, as it will directly lead to a highly accessible and deployable personalized treatment that can improve treatment response rates and decrease the high societal burden associated with eating disorders. The proposed research is relevant to NIH’s strategic aim 3.3b, as it will lead to the creation of a personalized treatment consistent with NIH’s precision treatment initiative.

PI_NAMEs: LEVINSON, CHERI ALICIA (contact)

PROGRAM_OFFICER_NAME: SWEENEY, MARY MARGARET

PROJECT_TERMS: acceptability and feasibility;Address;Adult;Aftercare;Anorexia Nervosa;Behavior Disorders;Binge Eating;Binge eating disorder;Body mass index;Bulimia;Caring;Cellular Phone;Cessation of life;Clinical;clinical efficacy;cognitive enhancement;Cognitive Therapy;comorbidity;Complex;Data;Death Rate;Development;Diagnosis;Diagnostic;Dropout;Eating Disorders;economic cost;evidence base;Evidence based treatment;feeding;follow-up;Fright;Goals;Heterogeneity;Impairment;improved;Individual;individualized medicine;innovation;Intervention;Investigation;Judgment;Lead;Left;long term recovery;Mental disorders;Methodology;Methods;mobile computing;Modeling;novel;Outcome;Participant;Pathology;Pathway Analysis;Pattern;personalized medicine;Population;Precision therapeutics;Prediction of Response to Therapy;prevent;Psychiatry;Psychotherapy;public health relevance;Quality of life;Randomized;Research;response;severe mental illness;smartphone based assessment;societal costs;Specific qualifier value;standard care;Structure;Symptoms;Testing;theories;therapy development;Time;Translating;treatment optimization;Treatment outcome;treatment planning;treatment response;United States National Institutes of Health;user friendly software;virtual;Visualization;Weight Gain;Work

PROJECT_TITLE: A Pilot Investigation of Network-Informed Personalized Treatment for Eating Disorders versus Enhanced Cognitive Behavioral Therapy and Dynamic Mechanisms of Change


NIH_SPENDING_CATS: Aging;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Biomedical Imaging;Brain Disorders;Clinical Research;Epilepsy;Mental Health;Neurodegenerative;Neurosciences;Patient Safety;Prevention

ORG_CITY: LA JOLLA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: NARRATIVE This project will investigate how advanced, multimodal neuroimaging can be used to evaluate memory reorganization in patients with epilepsy and to estimate personalized risk for memory decline following different surgical approaches. This research will be accomplished by combining information from functional magnetic resonance imaging, diffusion imaging, structural MRI and task-based intracranial recordings to identify brain networks that contribute to associative and non-associative memory, which will enable us to develop models for predicting memory decline. The information gained from this investigation may facilitate surgical planning and reduce the potential for postoperative cognitive morbidity in patients with epilepsy.

PI_NAMEs: MCDONALD, CARRIE R (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Ablation;Address;adverse outcome;Age;Amygdaloid structure;Anterior;Anterior Temporal Lobectomy;Association Learning;Benchmarking;Bilateral;Blood Vessels;Brain;Brain region;Clinical;Cognitive;cognitive neuroscience;Contralateral;Decision Making;dentate gyrus;Diffusion;Diffusion Magnetic Resonance Imaging;diffusion weighted;Disparate;Electroencephalography;Elements;Employment Status;Epilepsy;Episodic memory;Event;Excision;executive function;experience;Face;Fiber;Frequencies;Functional disorder;Functional Imaging;Functional Magnetic Resonance Imaging;functional outcomes;Funding;Goals;Grain;Grant;Health;Health Care Costs;Health Status;Healthcare Systems;high risk;Hippocampus;Image;imaging approach;imaging modality;Impairment;improved;Individual;Individual Differences;individual patient;innovation;Investigation;Ipsilateral;Language;language impairment;Lasers;Lead;Learning;Left;life span;Magnetic Resonance Imaging;Measures;medial temporal lobe;Memory;Memory impairment;Memory Loss;minimally invasive;Modeling;Morbidity - disease rate;multi-scale modeling;Multimodal Imaging;multimodal neuroimaging;multimodality;Names;National Institute of Neurological Disorders and Stroke;Neocortex;neocortical;Nervous System Disorder;neural network;Neuroanatomy;Neurons;novel;Operative Surgical Procedures;Outcome;Parahippocampal Gyrus;Pathology;Patient Care;Patients;Pattern;Performance;personalized approach;Postoperative Period;Predictive Factor;predictive modeling;preservation;prevent;Procedures;Process;Public Health;Quality of life;Refractory;Research;Residual state;resilience;response;Risk;Risk Assessment;Risk Estimate;risk minimization;Role;Sampling;Seizures;Semantic memory;sex;spatiotemporal;Specificity;Stress;Structure;surgery outcome;Technology;Temporal Lobe;Temporal Lobe Epilepsy;Testing;Time;Tissues;Validation;white matter

PROJECT_TITLE: Multimodal imaging of memory  in epilepsy from whole brain networks to local neuronal responses: Implications for surgical decision-making

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Genetics

ORG_CITY: BATON ROUGE

ORG_DEPT: BIOLOGY

ORG_NAME: LOUISIANA STATE UNIV A&M COL BATON ROUGE

ORG_STATE: LA

PHR: Project Narrative Peroxisomes execute essential functions in a cell, such as lipid processing and toxin removal, but they are also routed for autophagic degradation under certain conditions. Utilizing a fluorescent tool to track peroxisome autophagy (‘pexophagy’) in living, intact animals, we recently discovered, unexpectedly, that peroxisome degradation occurs during early aging at non-canonical tubular lysosomes, and that preventing age-dependent peroxisome degradation increases animal lifespan. This project aims to clarify the signals and machinery underlying pexophagy activation under natural contexts, including during aging, and the ways by which the rate of this process may ultimately define animal longevity.

PI_NAMEs: BOHNERT, KENNETH ADAM (contact)

PROGRAM_OFFICER_NAME: OROSZ, ANDRAS

PROJECT_TERMS: Acceleration;Affect;Age;age related;age-related disease;Aging;aging biomarker;aging process;Animals;Autophagocytosis;Binding;Biology;Caenorhabditis elegans;Cell Culture Techniques;Cells;Cellular biology;Collection;Digestion;Disease;Elements;Ensure;Event;Excision;expectation;extend lifespan;gene function;Genes;Genetic;Genetic Screening;Goals;Health;human old age (65+);Impairment;Intestines;knock-down;Knowledge;Life;life span;Link;Lipids;Longevity;longevity gene;Longevity Pathway;Lysosomes;macromolecule;Mammalian Cell;mature animal;model organism;Molecular;Morphology;Mutagenesis;mutant;Mutation;Nematoda;novel;Organelles;Participant;Pathology;peroxisome;peroxisome membrane;Physiological;Plants;Positioning Attribute;premature;prevent;Process;Proteins;Reaction;Regulation;Regulator Genes;Reporter;Research Project Grants;Role;Route;screening;Signal Transduction;Specific qualifier value;Specificity;Starvation;Stimulant;Structure;Subcutaneous Tissue;support network;System;Testing;Time;Tissues;tool;Toxin;Tubular formation;uptake;Yeasts;young adult

PROJECT_TITLE: Pexophagy regulation in live animals and its role in aging and longevity

STUDY_SECTION: CMAD

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Hematology;Infectious Diseases;Rare Diseases;Sepsis

ORG_CITY: SEATTLE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: PROJECT NARRATIVE Melioidosis is a bacterial infection that occurs in tropical regions around the world and causes significant mortality. The objective of this project is to test a new diagnostic for melioidosis. The knowledge gained from this proposal can help to reduce the burden of melioidosis and ultimately improve public health.

PI_NAMEs: CHANTRATITA, NARISARA ;GHARIB, SINA A;WEST, TIMOTHY EOIN (contact)

PROGRAM_OFFICER_NAME: MUKHOPADHYAY, SUMAN

PROJECT_TERMS: accurate diagnosis;accurate diagnostics;Area;Bacteremia;Bacterial Infections;Blood;Burkholderia pseudomallei;case control;Cessation of life;Classification;Clinical;cohort;Cohort Studies;Communicable Diseases;Death Rate;Dengue;Detection;Development;Diagnosis;Diagnostic;diagnostic accuracy;diagnostic tool;E. coli bacteremia;Environment;Etiology;Goals;high risk;Hospitalization;Hour;Human;Immunology;improved;Infection;Ingestion;Inhalation;Klebsiella pneumoniae;Knowledge;Malaria;Measures;Melioidosis;metabolome;metabolomics;Microbiology;Modeling;mortality;mortality risk;Multicenter Studies;North America;novel diagnostics;Patients;Performance;Plasma;Pneumonia;Probability;Process;prospective;Prospective cohort;Public Health;Puerto Rico;Random Allocation;recruit;Research Infrastructure;Resource-limited setting;Sampling;Sepsis;Soil;Southeastern Asia;Specimen;Staphylococcus aureus;Testing;Thailand;tool development;Universities;Washington

PROJECT_TITLE: A plasma metabolite diagnostic for melioidosis

STUDY_SECTION: CRFS

STUDY_SECTION_NAME: Clinical Research and Field Studies of Infectious Diseases Study Section[CRFS]


NIH_SPENDING_CATS: Genetics;HIV/AIDS;Infectious Diseases

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: Project Narrative Human Immunodeficiency Virus (HIV) has infected 76 million people since the beginning of the epidemic and current treatments fail to cure patients of infection due to the ability of the virus to undergo latency during antiretroviral therapy. This study will identify the cell types that make up the early latent reservoir, the transcriptional states that support latency and the integration sites of latently infected cells in peripheral blood and lymphoid tissue. Understanding the mechanisms that regulate HIV latency during acute infection will allow us to better target the latent reservoir, bringing the field closer to finding a cure for HIV.

PI_NAMEs: DOANMAN, DONALD  (contact)

PROGRAM_OFFICER_NAME: LAWRENCE, DIANE M

PROJECT_TERMS: Acute;acute infection;Animal Model;antiretroviral therapy;Cause of Death;CD4 Positive T Lymphocytes;Cell Line;Cell Lineage;Cell surface;cell type;Cells;chronic infection;Complex;Cues;Data;DNA;effective therapy;Epidemic;Eukaryotic Initiation Factor-2;experimental study;Fluorescence;FRAP1 gene;Gene Expression Profile;Gene Silencing;Generations;Genes;Genetic;Genetic Transcription;Goals;Grant;HIV;HIV Infections;HIV-1;Hour;humanized mouse;In Vitro;in vivo;Individual;Infection;innovation;insight;Integration Host Factors;integration site;Kinetics;Knowledge;Laboratories;latent HIV reservoir;Lymphoid Tissue;Maps;medication compliance;Memory;Modeling;mRNA Expression;new technology;novel;Pathway interactions;Patients;peripheral blood;Peripheral Blood Mononuclear Cell;Persons;Phenotype;Population Heterogeneity;Provirus Integration;Proviruses;Recording of previous events;Reporter;Reporting;Rest;Retroviridae;Role;Signal Transduction;single cell analysis;single-cell RNA sequencing;Site;System;T memory cell;T-Cell Activation;T-Lymphocyte;T-Lymphocyte Subsets;targeted treatment;Technology;Testing;Time;Tissues;tool;Viral;Viral Genes;Viral Load result;Viral Markers;viral rebound;Viral reservoir;Virus;Virus Integration

PROJECT_TITLE: Single Cell Analysis of HIV-1 Latent reservoir establishment in Humanized Mice


ORG_CITY: WORCESTER

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: Narrative This proposal seeks to elucidate how the immune system recognizes and responds to cell injury and death in ways that stimulate sterile inflammation and cause tissue damage. The proposed studies will investigate the role of histones released from dying cells and their newly discovered receptors in these processes. The information gained by these studies may lead to new treatments to prevent or treat a number of diseases, including stroke, heart attacks, infectious diseases and cancers.

PI_NAMEs: ROCK, KENNETH L (contact)

PROGRAM_OFFICER_NAME: VAZQUEZ-MALDONADO, NANCY

PROJECT_TERMS: Applications Grants;Automobile Driving;Binding;Biological;Biology;C Type Lectin Receptors;Cell Death;cell injury;Cells;Communicable Diseases;Disease;DNA;Endosomes;extracellular;Goals;Health;Histones;Homologous Gene;Host Defense;Human;Immune;Immune system;in vivo;Infarction;Inflammation;Inflammatory Response;Injury;Innate Immune Response;insight;Ischemia;Kidney;Ligands;Literature;Liver;Malignant Neoplasms;Mediating;Molecular;Molecular Target;Morbidity - disease rate;mortality;Mus;Myocardial Infarction;Nature;neutrophil;novel;Nucleosomes;Organ;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pattern;Pharmaceutical Preparations;Play;prevent;Process;receptor;receptor binding;receptor function;Receptor Signaling;Reperfusion Injury;Reperfusion Therapy;response;Role;Sepsis;Specificity;Sterility;Stroke;Testing;tissue injury;Tissues;Toll-like receptors;Translating;Trauma;Work

PROJECT_TITLE: Novel histone-binding C-type lectin receptors and their role in sterile inflammation and tissue injury

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: NARRATIVE This project leverages our humanized mouse models to achieve two goals: 1) Determine treatment efficacy of adoptive γδT cell transfer for melanoma. 2) Stimulate endogenous γδT cells for melanoma therapy. We expect that HuMice will allow us to test Vγ9Vδ2+ T cells-based cancer therapy for the first time in a suitable model system and our new therapies are effective and may be optimized and tested in future clinical trials.

PI_NAMEs: HERLYN, MEENHARD F;XU, XIAOWEI  (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: adaptive immune response;Adoptive Cell Transfers;Adoptive Immunotherapy;Adoptive Transfer;Affect;Affinity;Aftercare;Agonist;Alleles;Animal Model;Animals;anti-cancer research;anti-PD-1;Antigen Presentation;Antigens;Antitumor Response;Autologous Transplantation;B-Lymphocytes;Biological;Biological Models;Blood;cancer immunotherapy;cancer therapy;CD34 gene;CD8-Positive T-Lymphocytes;Cell Line;Cell Maturation;Cells;Cellular immunotherapy;chimeric antigen receptor;chimeric antigen receptor T cells;Clinical;Clinical Trials;combinatorial;cytokine;Data;Diphosphates;Disease;Fetal Liver;Future;Genetic;Genetic Models;Goals;Growth Factor;Hematopoietic;HLA Antigens;HLA-A gene;Human;human fetal hematopoietic stem cells;humanized mouse;immune checkpoint;Immune system;Immunophenotyping;Implant;improved;in vivo;Infiltration;Innate Immune Response;isopentenyl pyrophosphate;Laboratories;Liquid substance;mast cell;Melanoma;Melanoma Cell;Melanoma patient;Methods;Modeling;Monoclonal Antibodies;mouse model;Mus;Mutation;Myeloid Cells;Myeloid-derived suppressor cells;Natural Killer Cells;Neoplasm Transplantation;neoplastic cell;Normal Cell;novel;novel therapeutics;Organ;patient derived xenograft model;Patients;preservation;Primates;programmed cell death ligand 1;programmed cell death protein 1;Proteins;Receptor Cell;reconstitution;resiquimod;response;Solid Neoplasm;Study models;T cell therapy;T-Lymphocyte;Testing;Thymus Gland;Time;tissue tropism;TLR7 gene;TNFRSF10B gene;Toxic effect;translational potential;treatment comparison;Treatment Efficacy;Treatment outcome;tumor;tumor heterogeneity;tumor microenvironment;tumor-immune system interactions;γδ T cells

PROJECT_TITLE: Gamma delta T cell based melanoma therapies


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative Antibiotic resistance in Gram-negative bacteria poses an urgent threat to human health. We will investigate how a specific conserved protein mediates resistance to the cephalosporin group of beta-lactam antibiotics, characterize how likely the important human pathogen, Serratia marcescens, is to develop resistance to cephalosporins during treatment, and identify novel proteins and pathways necessary for this kind of resistance.

PI_NAMEs: LAZARUS, JACOB ERIC (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Address;Affect;Affinity;Alleles;amidase;Anti-microbial susceptibility;Antibiotic Resistance;antibiotic resistant infections;Antibiotics;Bacteria;beta-Lactam Resistance;beta-Lactamase;beta-Lactams;Binding;Biochemistry;Biology;carbapenem resistant Enterobacterales;carbapenemase;Carbapenems;career;Categories;Cause of Death;Cell Membrane Permeability;Cells;Cellular biology;Cephalosporin Resistance;Cephalosporins;Cessation of life;Clinical;clinical practice;clinically relevant;Collection;Communicable Diseases;Critical Pathways;crosslink;Data;derepression;design;Down-Regulation;Drug Design;Enterobacter cloacae;Eukaryotic Cell;General Hospitals;Genetic;Genetic Screening;Genomics;Goals;Gram-Negative Bacteria;Health;health care settings;Hospitalization;Hospitals;Human;human pathogen;improved;in vivo;Infection;K-Series Research Career Programs;Klebsiella aerogenes;Learning;Mass Spectrum Analysis;Massachusetts;Mediating;medical schools;Membrane;Mentors;Modification;Molecular;mutant;Mutation;novel;Organism;overexpression;pathogen;pathogenic bacteria;Pathway interactions;Patients;Peptidoglycan;periplasm;Persons;Predisposition;Prokaryotic Cells;protein function;Proteins;Proteomics;Research;Research Personnel;Resistance;Resistance development;Resources;response;Scientist;Serratia marcescens;Sorting;System;Techniques;Testing;Training;transcriptomics;VDAC1 gene;Woman

PROJECT_TITLE: Intrinsic modifiers of beta-lactam resistance in nosocomial Enterobacterales

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


NIH_SPENDING_CATS: Biotechnology;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: KANSAS CITY

ORG_NAME: CHILDREN'S MERCY HOSP (KANSAS CITY, MO)

ORG_STATE: MO

PHR: Project Narrative Developing a safe and effective HIV-1 vaccine is a top global health priority and a key component of a protective vaccine is eliciting broadly neutralizing antibodies (bnAbs). We observed that natural killer (NK) cells are more dysfunctional,in HIV-1-infected individuals that developed bnAbs and that depletion of NK cells in monkeys improved germinal center responses. We will determine key molecular pathways and receptor- ligand interactions that are critical for NK cell immunoregulation of the HIV antibody response that can be targeted during future vaccine strategies to improve elicitation of bnAbs.

PI_NAMEs: BRADLEY, TODD CHRISTOPHER (contact)

PROGRAM_OFFICER_NAME: PALIN, AMY COLLEEN

PROJECT_TERMS: Activated Natural Killer Cell;Address;Affect;Affinity;Animals;Antibody Response;antigen binding;Antigens;B cell repertoire;B-Lymphocytes;Cell Count;Cell Physiology;Cells;chronic infection;Coculture Techniques;cytotoxicity;Data;Development;Environment;Exhibits;Frequencies;Functional disorder;Future;global health;Health Priorities;Helper-Inducer T-Lymphocyte;HIV;HIV Antibodies;HIV envelope protein;HIV immunization;HIV-1;HIV-1 vaccine;Human;Immune response;Immunization;Immunoglobulin Genes;Immunoglobulin Somatic Hypermutation;Immunologics;immunoregulation;Impairment;improved;In Vitro;in vivo;Individual;Infection;innovation;Learning;Ligands;Macaca;Macaca mulatta;Mediating;Memory;Metabolism;Molecular;Monkeys;Mus;Mutate;Mutation;Natural Killer Cells;neutralizing antibody;novel;Pathway interactions;permissiveness;Phenotype;Plasmablast;Publications;receptor;Receptor Cell;Recombinants;Regulation;response;Stimulus;Structure of germinal center of lymph node;System;T-Cell Receptor;T-Lymphocyte;Testing;Vaccinated;Vaccination;vaccination strategy;vaccine strategy;Vaccines

PROJECT_TITLE: Natural killer cell regulation of the germinal center HIV neutralizing antibody response

STUDY_SECTION: HIVD

STUDY_SECTION_NAME: HIV Immunopathogenesis and Vaccine Development Study Section[HIVD]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Depression;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Social Determinants of Health;Substance Misuse

ORG_CITY: BROOKLYN

ORG_NAME: SUNY DOWNSTATE MEDICAL CENTER

PHR: PROJECT NARRATIVE Social connections are critical to human well-being, and people lacking in actual connections or who perceive that they are lacking these connections are more likely to suffer from substance abuse disorders and other mental health problems, and among those living with HIV infection, to have lower medication adherence and decreased quality of life. Applying a longitudinal, mixed-methods, and community-engaged framework in a nationally-representative study of persons living with HIV, and encompassing patterns of social connection both prior to and during the COVID-era, this project will examine understudied pathways linking social connections to substance use disorders and depression, and to HIV outcomes. A better understanding of these mechanisms will address a critical gap in the literature on social connections and will advance the ability to design effective interventions in this important area.

PI_NAMEs: MEYERS, JACQUELYN LEIGH;WILSON, TRACEY ELIZABETH (contact)

PROGRAM_OFFICER_NAME: GREENWOOD, GREGORY LOUIS

PROJECT_TERMS: Address;Adherence;African American;Age;Area;behavior prediction;biopsychosocial;Black race;Buffers;Cessation of life;Chronic Disease;Clinical;Cohort Studies;Communities;Consensus;Coupled;COVID-19;COVID-19 impact;COVID-19 pandemic;COVID-19 risk;Data;Data Collection;design;Diagnostic;dimensional analysis;Dimensions;Disease;Education;Educational Status;effective intervention;Emotional;Ethnic Origin;Ethnic Population;Evaluation;Family;Friends;Gender;genome-wide;genomic predictors;Geography;Goals;Health;high risk;HIV;HIV Infections;Human;Impairment;implementation intervention;Income;indexing;Insurance Coverage;Intervention;Interview;Knowledge;Laboratories;lens;Link;Literature;Loneliness;longitudinal analysis;longitudinal design;Measures;Mediating;Mediator;medication compliance;Mental Depression;Mental Health;Meta-Analysis;Methods;Modeling;mortality;multilevel analysis;Neighborhoods;Outcome;Pathway interactions;Pattern;Perception;Personal Satisfaction;Persons;polygenic risk score;Population;Population Density;Population Heterogeneity;Poverty;Premature Mortality;Prevention;primary outcome;Public Health;Quality of life;Race;racial population;Recording of previous events;Reporting;Research;Risk;Science;secondary outcome;Self Management;Site;social;social integration;Social Interaction;Social isolation;social relationships;socioeconomics;Standardization;Strategic Planning;stressor;Substance abuse problem;Substance Use Disorder;Surveys;Time;United States National Institutes of Health;Update;Viral Load result;Vulnerable Populations;Woman;Work

PROJECT_TITLE: Social connections, risk for COVID-era psychiatric and substance use disorders, and HIV control


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Chronic Liver Disease and Cirrhosis;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Liver Disease;Nutrition;Obesity;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases

ORG_CITY: TUCSON

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Rates of non-alcoholic fatty liver disease (NAFLD), a modifiable premalignant state associated with hepatocellular carcinoma are highest in the nation for Mexican-American men, the fastest growing Hispanic sub-group. The training and proposed research will utilize a NAFLD-specific weight loss intervention to reduce the burden of this disease and improve health outcomes for this high-risk population.

PI_NAMEs: GARCIA, DAVID O. (contact)

PROGRAM_OFFICER_NAME: MARTIN, IMAN

PROJECT_TERMS: Adherence;Affect;Alleles;Arizona;Attitude;Behavior;behavior change;Belief;black men;Body mass index;Body Weight;Body Weight decreased;burden of illness;cancer risk;cardiometabolism;career;carrier status;Categories;Characteristics;cohort;Communication;Consumption;Counseling;County;Data;Data Set;design;Development;diabetes prevention program;Diet;dietary;Dietary Sugars;Disclosure;Disease;Disease Management;disorder risk;elastography;Environment;Evaluation;Fatty acid glycerol esters;FDA approved;Foundations;Frequencies;Gender;Genes;Genetic;Genetic Carriers;Genetic Predisposition to Disease;Genotype;Goals;Guidelines;Health;Health behavior;high risk;high risk population;Hispanic;imaging biomarker;improved;Incidence;Individual;Intervention;intervention delivery;Interview;Knowledge;Life Style;Life Style Modification;lifestyle intervention;Literature;Liver;male;men;Mentored Research Scientist Development Award;Mentors;Mentorship;Metabolic;Methodology;Mexican Americans;Modeling;Monitor;National Institute on Minority Health and Health Disparities;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;non-invasive imaging;Not Hispanic or Latino;Obesity;Obesity associated cancer;Obesity associated disease;Outcome;Participant;Pathogenicity;Pathway interactions;patient engagement;Pharmacologic Substance;Phenotype;Phospholipase;Physical activity;physical inactivity;Play;Population;Positioning Attribute;Precancerous Conditions;Predisposition;Prevention therapy;Primary carcinoma of the liver cells;programs;Proteins;Qualitative Research;Recommendation;recruit;Reporting;Research;Research Design;Research Methodology;Resources;Risk;Risk Assessment;Risk Estimate;Risk Factors;Risk Reduction;risk variant;Role;satisfaction;Severities;skill acquisition;skills;sociocultural determinant;statistics;stem;Structure;Subgroup;sugar;sweetened beverage;Therapeutic Intervention;therapeutically effective;therapy design;Time;Training;Universities;weight loss intervention;Weight maintenance regimen;Work

PROJECT_TITLE: A gender and culturally specific approach to reduce NAFLD in Mexican American men


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Immunotherapy;Liver Disease;Orphan Drug;Pancreatic Cancer;Rare Diseases

PHR: Project Narrative T cell immunotherapy has yet to produce clinical benefit for most patients with pancreatic cancer. In this proposal, we investigate (i) mechanisms of primary resistance to immunotherapy with a focus on the liver as a known immunoregulatory organ and (ii) therapeutic implications of the liver in shaping cancer immunogenicity and the efficacy of immunotherapy. The proposed studies will use clinically relevant mouse models of cancer and human tissues to inform the design of novel strategies to broaden the efficacy of cancer immunotherapy.

PI_NAMEs: BEATTY, GREGORY L (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: Acute-Phase Proteins;Address;Amyloid;Antigens;Applications Grants;Biology;cancer cell;cancer immunotherapy;carcinogenesis;CD8B1 gene;Cell Physiology;Cellular biology;Clinical;clinically relevant;Data;Dendritic Cells;Deposition;design;Development;effector T cell;Environment;Exposure to;Extracellular Matrix Proteins;Funding;Genetic;Grant;Hepatic Stellate Cell;Hepatocyte;Homeostasis;human cancer mouse model;human disease;human tissue;immune checkpoint blockade;Immune Evasion;Immunobiology;immunogenicity;Immunologic Surveillance;Immunologics;immunoreaction;immunoregulation;Immunosuppression;Immunotherapy;Impairment;improved outcome;Infiltration;Interleukin-6;Knowledge;KPC model;KRASG12D;Kupffer Cells;Liver;liver inflammation;Macrophage;Malignant neoplasm of gastrointestinal tract;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant Neoplasms;Melanoma;Metastatic Neoplasm to the Liver;Modeling;Molecular;mouse model;Mus;Myeloid Cells;Neutrophil Infiltration;Non-Malignant;novel;novel strategies;Organ;Outcome;Pancreas;pancreatic cancer patients;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;Patients;peripheral tolerance;Play;Portal vein structure;Primary Neoplasm;Process;Productivity;Proteins;Reproducibility;Resistance;Retrospective Studies;Role;Serum;Shapes;Signal Pathway;Soil;STAT3 gene;Stromal Cells;systemic inflammatory response;T cell infiltration;T-Lymphocyte;Therapeutic;tool;trafficking;tumor;Tumor Escape;tumor microenvironment;tumor-immune system interactions;Variant

PROJECT_TITLE: Targeting the liver for immunotherapy in pancreatic cancer

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


ADMINISTERING_IC: AR

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Clinical Research;Machine Learning and Artificial Intelligence;Osteoporosis;Women's Health Research

ORG_DEPT: BIOMEDICAL ENGINEERING

PHR: Project Narrative Osteoporosis is a disease that effects around 200 million people worldwide and causes catastrophic hip fractures, which have a one-year mortality rate of 20% and are associated with substantial morbidity. Clinical methods of bone densitometry have many limitations and are poor predictors of osteoporotic fracture. I propose a method to quantify bone material composition in the hip which could help to better inform clinicians treating osteoporosis and improve research efforts investigating the progression of bone disease.

PI_NAMEs: JONES, BRANDON CLINTON (contact)

PROGRAM_OFFICER_NAME: VINCENT, ISAAH S

PROJECT_TERMS: 3-Dimensional;absorption;Affect;age related;Anatomy;Binding;Biomechanics;bone;Bone Density;Bone Diseases;bone health;bone quality;Bone remodeling;bone strength;Bone structure;Brain imaging;Cadaver;Calcium;Clinical;Clinical assessments;clinical translation;Clinical Treatment;clinically relevant;cohort;Complex;Computing Methodologies;cone-beam computed tomography;convolutional neural network;Death Rate;deep learning;Densitometry;Diagnosis;Disease;Dual-Energy X-Ray Absorptiometry;efficacy evaluation;Enrollment;Europe;Evaluation;experience;experimental study;falls;Fatty acid glycerol esters;Femur;Fracture;fracture risk;Functional disorder;Funding;Future;Gold;Health;health assessment;Hip Fractures;Hip region structure;Human;Image;imaging biomarker;improved;in vivo;inhibitor;Intervention;Intervention Studies;Ionizing radiation;Lumbar Regions;lumbar vertebra bone structure;Magic;magnetic field;Magnetic Resonance Imaging;Magnetism;Maps;Marrow;Measurement;Measures;Mechanics;Metals;Methods;Minerals;Modeling;Morbidity - disease rate;Morphology;mortality;Network-based;Neural Network Simulation;novel;Obesity;Observational Study;Organ;Osteoclasts;Osteoporosis;osteoporosis with pathological fracture;Osteoporotic;Participant;Pelvis;Persons;pharmacologic;Pharmacologic Substance;Physiologic pulse;Porosity;Postmenopause;Predisposition;Property;Protocols documentation;Radiation;radiological imaging;Reproducibility;Research;Research Design;Sampling;Scanning;Site;skeletal disorder;Specimen;Structure;success;Techniques;Testing;tibia;Time;Tissues;treatment effect;United States;United States National Institutes of Health;Validation;validation studies;Water;Woman;Work;X-Ray Computed Tomography;Zoledronic Acid

PROJECT_TITLE: Bone health assessment through magnetic susceptibility mapping


NIH_SPENDING_CATS: Genetics;Infectious Diseases;Malaria;Rare Diseases;Vector-Borne Diseases

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

PHR: The proliferation of the malaria parasite, Plasmodium falciparum, within the red blood cell is central for the parasite’s survival and transmission, and may be altered in response to host metabolites, such as changes in host lactate levels. We have discovered that a new post-translational modification of proteins, lactylation, is found on histone tails of P. falciparum, proteins that can influence the expression of specific sets of genes. In this proposal, we will assess the ability of histone lactylation to act as a code linking changes in lactate metabolism to gene expression underlying the pathogenesis of P. falciparum parasites.

PI_NAMEs: DURAISINGH, MANOJ T (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: aerobic glycolysis;anaerobic glycolysis;Anopheles Genus;asexual;Bacterial Infections;Biology;Blood;Blood Circulation;Cell Hypoxia;Cell Physiology;Cells;Cleavage Under Targets and Release Using Nuclease;Code;Complex;Culicidae;Daughter;Development;Disease;Environment;Epigenetic Process;Erythrocytes;Etiology;Family;Gene Expression;Genes;Genetic Transcription;Glycolysis;Growth;Histone Code;Histones;Human;Human Bites;Immune;In Vitro;India;Infection;Investigation;Laboratories;Lactic Acidosis;Life;Link;Lysine;Macrophage;Malaria;malaria infection;Mammalian Cell;Maps;Mediating;Mediator;Metabolic;Metabolism;Mus;novel;Parasites;Pathogenesis;Pathway interactions;Patient Isolation;Phenotype;Physiological;Plasmodium;Plasmodium falciparum;Post-Translational Protein Processing;Production;programs;Proliferating;Proteins;Pyruvate;Reporting;response;Role;Severity of illness;Sirtuins;Symptoms;Tail;transcriptome sequencing;transmission process;Virulence;virulence gene;Work

PROJECT_TITLE: Linking metabolite sensing and gene expression in malaria parasites


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_NAME: RESEARCH INST OF FOX CHASE CAN CTR

PHR: PROJECT NARRATIVE Gene amplifications are associated with a number of diseases. This application studies how chromatin factors, epigenetic states and nuclear organization impact DNA copy gains. Our studies will provide molecular insights into copy number alterations, while identifying therapeutic targets associated with amplification driven diseases.

PI_NAMEs: WHETSTINE, JOHNATHAN R. (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Amplifiers;Automobile Driving;Behavior;cancer cell;Cells;Characteristics;Chemicals;Chromatin;Coupled;Data;Diploidy;Disease;DNA;DNA amplification;DNA Sequence Alteration;Enzymes;Epigenetic Process;epigenome;Event;extrachromosomal DNA;Gene Amplification;Generations;Genetic;Genome;Genomics;Goals;Heart Diseases;Heterogeneity;Histones;Human Genome;Individual;insight;Knowledge;Laboratories;Lysine;Malignant Neoplasms;Maps;Methyltransferase;Microscopy;Molecular;Mutation;National Institute of General Medical Sciences;Nervous System Disorder;new therapeutic target;novel marker;Nuclear;Oncogenes;Pathologic;Pathway interactions;Population;prevent;Process;RNA;Role;Site;therapeutic target;tool;treatment response

PROJECT_TITLE: Deciphering Networks Controlling DNA Amplification

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: HOUSTON

ORG_NAME: RICE UNIVERSITY

ORG_STATE: TX

PHR: Colletotrichum camelliae filamentous virus 1 (CcFV-1) is considered an outlier among dsRNA viruses due to its filamentous morphology departing from the typical icosahedral capsids observed in other dsRNA viruses. In this grant, we will carry out a series of biochemical and structural biology experiments to determine the organization of genomic dsRNA inside the CcFV-1 virion and the mechanism of viral RNA transcription/replication. Results from our research will lead to new paradigms that apply to CcFV-1 and other potentially undiscovered filamentous, dsRNA viruses with practical engineering applications for dsRNA packaging and delivery.

PI_NAMEs: TAO, YIZHI JANE (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Agriculture;Amino Acids;Anti-viral Response;Biochemical;Biochemistry;Birnavirus;Capsid;Capsid Proteins;China;Colletotrichum;Complex;Cryoelectron Microscopy;Data;Defense Mechanisms;Diameter;dimer;Double Stranded RNA Virus;Double-Stranded RNA;Engineering;experimental study;Filament;fungus;Genes;Genetic Transcription;Genome;genomic RNA;Genomics;Goals;Grant;guanylyltransferase;In Situ;Methyltransferase;monomer;Morphology;mRNA capping;Open Reading Frames;particle;Penicillium;Picobirnavirus;Plants;Polymerase;Property;Proteins;Publications;Recombinant Proteins;Recombinants;reconstruction;Reovirus;Research;Resolution;RNA;RNA-Directed RNA Polymerase;RNA-Protein Interaction;Rotavirus;S-Adenosylhomocysteine;S-Adenosylmethionine;Sampling;Series;Shapes;stoichiometry;structural biology;Structure;Tea;Techniques;Universities;Viral;Viral Genome;viral RNA;Virion;Virus;Virus Replication;X-Ray Crystallography

PROJECT_TITLE: Mechanisms of genome packaging and replication by a filamentous dsRNA virus

STUDY_SECTION: MSFC

STUDY_SECTION_NAME: Macromolecular Structure and Function C Study Section[MSFC]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Cancer;Cancer Genomics;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome;Immunization;Immunotherapy;Infectious Diseases;Precision Medicine;Sexually Transmitted Infections

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Title: Noninvasive imaging of anti-tumor immune response Project Narrative This proposal exploits new imaging approaches, specifically immuno-positron emission tomography (immuno- PET) using small antibody fragments called nanobodies, to improve diagnosis and treatment of cancer. The use of immuno-PET as a prognostic tool can provide mechanistic insights into possible reasons for success or failure of immunotherapy, while the very same agents used for diagnosis can also be equipped with payloads that may improve the anti-tumor immune response.

PI_NAMEs: PLOEGH, HIDDE L. (contact)

PROGRAM_OFFICER_NAME: WANG, YISONG

PROJECT_TERMS: Address;Affinity;Animals;anti-CTLA4 antibodies;anti-PD-1;anti-PD1 therapy;anti-tumor immune response;Antibodies;antigen detection;antigen-specific T cells;Antigens;Blocking Antibodies;cancer imaging;Cancer Model;cancer therapy;CD8-Positive T-Lymphocytes;CD8B1 gene;Cells;Cellular biology;Chemicals;Chemistry;chemokine;chemokine receptor;Chemotactic Factors;Chimeric Proteins;Colorectal Neoplasms;comparative;Coupled;CRISPR/Cas technology;CTLA4 gene;CXCL10 gene;CXCL9 gene;CXCR3 gene;cytokine;Cytotoxic T-Lymphocytes;Data;design;Development;Diagnosis;Diagnostic;differential expression;Disparity;effective therapy;Effectiveness;effector T cell;Engineering;Ensure;Equilibrium;Etiology;experimental study;Failure;Fibronectins;Gene Expression;Genes;Genetic;Half-Life;HPV screening;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;Human papillomavirus 16;Image;image reconstruction;imaging agent;imaging approach;Imaging Device;Immune;immune cell infiltrate;immune checkpoint blockade;immunoengineering;Immunoglobulin Fragments;immunological intervention;immunological status;ImmunoPET;Immunotherapy;improved;Infiltration;innovation;insight;interest;Isotopes;ITGAM gene;knockout gene;Ligands;Macrophage;Malignant Neoplasms;manufacture;MC38;Melanoma;Methods;MHC Class I Genes;Modeling;Modification;Molecular Analysis;Monitor;Mus;Myelogenous;Myeloid Cells;nanobodies;nanosized;neovasculature;new technology;Non-Invasive Detection;non-invasive imaging;novel;Outcome;patient subsets;Penetration;Play;Positron-Emission Tomography;pre-clinical;Predisposition;prognostic tool;programmed cell death ligand 1;prospective;Proteins;PTPRC gene;receptor;recruit;responders and non-responders;response;RNA Splicing;Role;single cell analysis;single-cell RNA sequencing;Specificity;success;Surface;T cell therapy;T-Lymphocyte;Technology;Th1 Cells;theranostics;Therapeutic Effect;therapy outcome;Tissues;tool;transcriptome;treatment response;tumor;Tumor Antigens;tumor microenvironment;Tumor-infiltrating immune cells;Validation;Variant

PROJECT_TITLE: Non-invasive imaging of the anti-tumor immune response

STUDY_SECTION: IPCA

STUDY_SECTION_NAME: Imaging Probes and Contrast Agents Study Section[IPCA]


PHR: Narrative The production of immunoglobulin A (IgA) is a hallmark of the intestinal humoral response: we discovered that germinal center reaction in Peyer’s patches is controlled by surface expression of IgA, which mediates an isotype-dependent intracellular signaling following antigen recognition. This proposal aims to map the effect of IgA-specific B cell receptor on generation of mucosal immunity to both pathogens and commensals, and to elucidate the role of the cell death Fas-FasL axis in shaping the IgA repertoire. Data generated from this proposal will produce accurate insights into IgA-centered activation of B lymphocytes at the mucosal interface during both homeostasis and enteric infection.

PI_NAMEs: REBOLDI, ANDREA  (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Adaptive Immune System;adaptive immunity;Affinity;Antibodies;Antibody Response;antigen binding;Antigen Receptors;Antigens;autoinflammation;B cell differentiation;B Cell Proliferation;B-Cell Activation;B-Cell Antigen Receptor;B-Lymphocyte Subsets;B-Lymphocytes;Bacterial Antigens;Biochemical;Cell Compartmentation;Cell Death;cell motility;Cell Survival;Cells;Chronic;Clone Cells;Complex;Data;deep sequencing;enteric infection;enteric pathogen;Equilibrium;Event;Exclusion;expectation;experience;flexibility;Follicular Dendritic Cells;Foundations;Gastrointestinal tract structure;Generations;gut microbiome;Helper-Inducer T-Lymphocyte;Homeostasis;Homing;Humoral Immunities;IgA Deficiency;Immune system;immunogenic;immunogenicity;Immunoglobulin A;Immunoglobulin-Secreting Cells;Immunology;imprint;In Vitro;in vivo;in vivo Model;Individual;Infection;insight;intestinal homeostasis;Intestines;intravital microscopy;Light;Maintenance;Maps;Mediating;Membrane;Memory;Memory B-Lymphocyte;microbiome composition;microorganism antigen;Molecular;Mucosal Immunity;Mucous Membrane;Mus;novel;overexpression;pathogen;Peptides;permissiveness;Peyer's Patches;Phenotype;Plasma Cells;Predisposition;prevent;Process;Production;Reaction;Receptor Signaling;recruit;Reporter;resident commensals;Resistance;response;Role;secondary lymphoid organ;Shapes;Signal Transduction;Specificity;Step Tests;Structure of germinal center of lymph node;Surface;Surface Immunoglobulins;System;Techniques;Testing;Time;Tissues;Toxin

PROJECT_TITLE: Intestinal IgA B cell receptor-specific signals integrate germinal center selection with humoral responses to commensals

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Neurosciences;Rare Diseases

ORG_CITY: SAN FRANCISCO

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Adult malignant gliomas are deadly brain tumors with limited treatment options. This project proposes a new strategy for identifying the genes that these tumors use to grow and survive in the human brain. This information is important for developing new ways to attack these tumors.

PI_NAMEs: OLDHAM, MICHAEL CLARK (contact)

PROGRAM_OFFICER_NAME: GANGULY, ANIRUDDHA

PROJECT_TERMS: Adult;Architecture;Astrocytoma;Biological Markers;Biopsy Specimen;Brain;Brain Neoplasms;cancer cell;Cell Differentiation process;Cell Separation;Cells;Cerebral cortex;Collaborations;Complementary DNA;Data;design;Diffuse;Dissociation;DNA Methylation;Exhibits;experimental study;Frozen Sections;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Gene Frequency;Genes;Genetic study;Genetic Transcription;Genotype;Glioblastoma;Glioma;Gliomagenesis;Goals;Histologic;Histology;Human;in silico;Individual;insight;Malignant - descriptor;Malignant Glioma;Malignant neoplasm of brain;Malignant Neoplasms;malignant phenotype;Maps;Meta-Analysis;metaplastic cell transformation;Methods;Molecular;molecular phenotype;multiple omics;mutant;Mutation;Nature;Neurosciences;Non-Malignant;novel;novel strategies;novel therapeutic intervention;oligodendroglioma;Oncogenic;Outcome;Phenotype;Qualifying;Recurrence;Reproducibility;Research;RNA;Sampling;Sampling Biases;single nucleus RNA-sequencing;Site;Specimen;subclonal heterogeneity;Testing;Therapeutic;Tissue Sample;Tissues;Transcript;transcriptome;treatment strategy;tumor;Variant

PROJECT_TITLE: Decoding the molecular basis of cellular identity in adult malignant gliomas

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OBT-K(02)M]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Immunization;Infectious Diseases;Prevention;Sexually Transmitted Infections;Vaccine Related;Women's Health Research

ORG_CITY: BIRMINGHAM

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: The primary goals of my K24 midcareer investigator award renewal application are to enable me, William Geisler, M.D., M.P.H., to: 1) broaden my mentoring knowledge and develop new research skills, 2) continue providing patient-oriented research mentoring to early career stage clinical investigators, and 3) expand my research program in new directions. The public health importance of the research is that it addresses the need to improve chlamydia prevention and control efforts by advancing chlamydia vaccine development, providing important knowledge on factors that will influence acceptability of a chlamydia vaccine, and evaluating biomarkers that could be used to guide chlamydia screening strategies. Mentoring provided by me should advance the research skills and career development of many early career stage clinical investigators.

PI_NAMEs: GEISLER, WILLIAM M (contact)

PROGRAM_OFFICER_NAME: CHUANG, ELEANORE JENNIFER

PROJECT_TERMS: Address;Adolescent;Affect;African American population;Age;Alabama;Antibodies;antigen test;Antigens;Area;Atopobium vaginae;Award;Behavioral;bench to bedside;Biological Markers;Blood;career;career development;Chlamydia;Chlamydia trachomatis;chlamydia vaccine;Clinic;Clinical Investigator;clinical practice;commercialization;COVID-19 vaccine;design;Development;disparities in women;DNA;Doctor of Medicine;early experience;Education;Educational process of instructing;Enrollment;Entrepreneurship;Enzyme-Linked Immunosorbent Assay;experience;Female;Frequencies;Funding;Genitalia;Goals;Gynecology;Health;HIV risk;HLA-DQ Antigens;HLA-DQB1;Human Papilloma Virus Vaccine;Immunity;Immunogenetics;immunogenic;improved;Infection;Infection Control;Infection prevention;infection rate;infection risk;insight;interest;Interferon Type II;International;Interview;Knowledge;Leadership;Linkage Disequilibrium;male;Master of Public Health;Mediating;Mentors;Mentorship;MicroRNAs;Mid-Career Clinical Scientist Award (K24);Midcareer Investigator Award in Patient-Oriented Research;Mucous Membrane;patient oriented research;Patients;perinatal morbidity;Physicians;Population;Positioning Attribute;predictive marker;Prevention;programs;psychosocial;Public Health;Publications;recruit;Reporting;reproductive;reproductive morbidity;Research;Research Activity;Research Personnel;Research Project Grants;research study;Respondent;response;Risk;Risk Marker;sample collection;Scientist;screening;Secure;Serum;skill acquisition;skills;Source;Specimen;Students;success;Surveys;Swab;T cell response;T-Lymphocyte;Testing;Time;TNFSF15 gene;Training;Translating;United States National Institutes of Health;Universities;vaccine acceptance;vaccine access;vaccine candidate;vaccine development;vaccine trial;Vaccines;Variant;Visit;Woman;young woman

PROJECT_TITLE: Midcareer Mentoring Award for Patient-Oriented Research in Chlamydia trachomatis Infection


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

ORG_CITY: ALBUQUERQUE

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR

ORG_STATE: NM

PHR: PROJECT NARRATIVE Malaria caused by the parasite Plasmodium falciparum is a major threat to global public health. In this project, we will engineer prophylactic malaria vaccines that target the pre-erythrocytic stage of the malaria lifecycle by targeting vulnerable epitopes in the circumsporozoite protein using a virus-like particle (VLP)-based vaccine platform.

PI_NAMEs: CHACKERIAN, BRYCE C (contact)

PROGRAM_OFFICER_NAME: MO, ANNIE X  Y

PROJECT_TERMS: 5 year old;Adjuvant;Animal Model;Antibodies;Antibody Response;Antigens;Antiparasitic Agents;Area;Avidity;B-Cell Antigen Receptor;B-Lymphocytes;Bacteriophages;Blood;Cause of Death;Cessation of life;Child;circumsporozoite protein;Clinical Trials;Data;design;Development;Disease;effectiveness measure;Engineering;Epitopes;Erythrocytes;Event;experience;Falciparum Malaria;fighting;Goals;Hepatocyte;Hour;Immune;Immune response;Immune Targeting;Immunity;Immunize;immunogenic;immunogenicity;Immunology;Infection;Invaded;Life Cycle Stages;Liver;liver infection;Malaria;malaria infection;Malaria Vaccines;Measures;Mediating;Minor;Modeling;Monitor;Monoclonal Antibodies;Morbidity - disease rate;mortality;Motility;mouse model;Mus;N-terminal;nanoparticle;novel;Parasites;Passive Immunization;pathogen;Persons;Phenotype;Plasmodium;Plasmodium falciparum;prevent;prophylactic;protective efficacy;Proteins;Public Health;Publishing;Research Personnel;response;Site;Source;Sporozoites;Surface;Techniques;technology platform;Testing;Time;tool;Transgenic Organisms;transmission process;vaccine candidate;vaccine effectiveness;vaccine platform;vaccine-induced antibodies;Vaccines;Virus-like particle;Work

PROJECT_TITLE: Virus-like Particle based malaria vaccines targeting vulnerable epitopes in the circumsporozoite protein

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Rehabilitation

PHR: Project Narrative Speech and communication disorders often result in aberrant timing in speech production, such as improper stops at places where they should not be. Our understanding of how the brain controls the timing of speech, including the control for making a stop, is still limited. This work proposes to identify key neural circuits that give rise to the control of speech timing and improves the understanding of healthy and disease states of speech neural control in the brain.

PI_NAMEs: ZHAO, LINGYUN  (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TITLE: Neural mechanisms for stopping ongoing speech production

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: Abnormal blood flow patterns and inflammation have been shown to cause disease of blood vessels, but are not currently studied in the routine evaluation of patients. With innovative new imaging techniques, we aim to study how aberrant flow patterns, biomechanical stresses and transient inflammation may render veterans at increased risk for potentially life-threatening vascular disease. We will target a common vascular disease in our veteran population, abdominal aortic aneurysm, a pathologic dilation of the central artery in the belly, which effects 5% of people over 55 years old.

PI_NAMEs: MITSOURAS, DIMITRIOS  (contact)

PROJECT_TERMS: 3-Dimensional;Abdominal Aortic Aneurysm;Affect;Aging;anatomic imaging;Anatomy;Aneurysm;Aorta;Aortic Diseases;biomechanical model;biomechanical test;Biomechanics;Blood flow;Blood Vessels;Central Artery;Cessation of life;Clinical;Computer Models;contrast enhanced;Data;data modeling;Descriptor;Diameter;Dimensions;Disease;Disease Progression;Early Intervention;Evaluation;experience;Functional Imaging;Future;Goals;Growth;Hematological Disease;hemodynamics;Image;Imaging Techniques;improved;improved outcome;Inflammation;Inflammatory;innovation;Intervention;Life;Magnetic Resonance Imaging;male;Measurement;Mechanics;military veteran;Morphology;Motivation;older men;Operative Surgical Procedures;Outcome;Pathologic;patient stratification;Patients;Pattern;Persons;Phase;Process;Protocols documentation;rapid growth;Regimen;Reporting;Resolution;Resources;Risk;Risk Assessment;risk stratification;Role;Rupture;Ruptured Abdominal Aortic Aneurysm;screening;screening program;Series;shear stress;Stress;Stretching;Structure;surveillance imaging;Time;ultrasound;Vascular Diseases;Veterans

PROJECT_TITLE: Advanced MRI Evaluation of Abdominal Aortic Aneurysms


ORG_CITY: DAYTON

ORG_NAME: DAYTON VA MEDICAL CENTER

ORG_STATE: OH

PHR: PROJECT NARRATIVE  Actinic neoplasia is the most common diagnosis in VA dermatology clinics and is growing in incidence and treatment cost. The goal of these studies is to define the mechanisms that are responsible for skin cancer development in older individuals. Our previous and preliminary data suggest that age-dependent reductions in the production of the hormone IGF-1 (insulin-like growth factor-1) predisposes geriatric skin to carry out a more mutagenic form of DNA synthesis. This work may ultimately lead to the development of new therapeutic strategies aimed at preventing and treating skin cancers, which will ultimately improve veteran care. Though skin is the focus of this work, the similar biology of other epithelial tissues suggest that our findings will be relevant to other epithelial-based cancers associated with exposure to environmental and dietary DNA damaging agents.

PI_NAMEs: KEMP, MICHAEL GEORGE (contact)

PROJECT_TERMS: Actinic keratosis;Address;Affect;Age;age effect;age related;Age Years;aged;Aging;Apical;ATR gene;Biology;cancer initiation;cancer risk;carcinogenesis;Caring;Cause of Death;Cell Cycle Progression;Cells;Clinic;Clinical;Colon;Colon Carcinoma;cost;cytokine;Data;Defect;Dermal;Dermatology;Development;Diagnosis;dietary;DNA;DNA biosynthesis;DNA Damage;DNA mapping;DNA photoproducts;DNA Repair;DNA-Directed DNA Polymerase;Elderly;Epidermis;Epithelium;Erythrocytes;Excision;Excision Repair;experience;Exposure to;Failure;Fibroblasts;Financial Hardship;General Population;Genome;genome-wide analysis;Genomic DNA;genomic locus;Genomics;Goals;Growth Factor;Healthcare Systems;Hormones;Human;human disease;improved;In Vitro;in vivo;Incidence;Individual;Injections;innovation;Insulin;Insulin deficiency;Insulin-Like Growth Factor I;Insulin-Like-Growth Factor I Receptor;Intervention;keratinocyte;Knowledge;Lasers;Lung;Maintenance;Malignant neoplasm of esophagus;Malignant neoplasm of lung;Malignant Neoplasms;military veteran;Modeling;Morbidity - disease rate;mortality;Mutagenesis;Neoplasms;novel;novel therapeutic intervention;Nucleotides;Older Population;organ transplant recipient;Outcome;Pathogenesis;Pathway interactions;patient population;Phenotype;Phosphotransferases;photolesion;Physiological;Play;Population;premalignant;prevent;Production;programs;Property;Publishing;Pyrimidine;Pyrimidine Dimers;Qualifying;Receptor Activation;Receptor Signaling;Rejuvenation;repaired;replication stress;Research;Resolution;response;Risk Factors;Role;senescence;Signal Transduction;Skin;skin biopsy;Skin Cancer;Skin Carcinogenesis;Skin Carcinoma;skin disorder;skin wound;Solid;Source;Stress Response Signaling;Sun Exposure;Sunlight;Testing;Tissues;Treatment Cost;tumorigenesis;tumorigenic;Ultraviolet B Radiation;ultraviolet damage;Ultraviolet Rays;UV carcinogenesis;UV Mutagenesis;UV Radiation Exposure;UVB induced;Veterans;Work;young adult

PROJECT_TITLE: Mapping DNA Repair and Error-Prone DNA Synthesis in Geriatric Skin


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Biotechnology;Genetics;Osteoporosis

ORG_CITY: FARMINGTON

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: Endogenous glucocorticoids are critical for normal bone physiology, while glucocorticoid excess, due to systemic administration or syndromes such as Cushing’s disease, causes bone loss and metabolic disorder. We identified miR-433 as negative regulator of glucocorticoid signaling in bone forming osteoblasts. In this proposal, we will determine the function of miR-433 in bone in vivo and the mechanisms by which miR-433 regulates sensitivity to glucocorticoids.

PI_NAMEs: DELANY, ANNE M (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: Adverse effects;Aging;Animals;Biology;bone;bone health;bone loss;bone repair;Calvaria;candidate selection;Cell Nucleus;Cells;circadian;cortical bone;Corticosterone;CREB1 gene;Critical Pathways;crosslink;Data;design;differentiation in vitro;Energy Metabolism;Enzyme-Linked Immunosorbent Assay;Female;Gene Expression;Gene Expression Profiling;Genes;Glucocorticoid Receptor;Glucocorticoids;Histology;Immunoprecipitation;In Vitro;in vivo;inhibitor;Investigation;knock-down;male;MAP Kinase Gene;Mesenchymal;Messenger RNA;Metabolic Diseases;microCT;MicroRNAs;Molecular;Molecular Chaperones;Mus;novel;novel strategies;osteoblast differentiation;Osteoblasts;Osteocalcin;Osteogenesis;Osteopenia;p38 Mitogen Activated Protein Kinase;Pathway interactions;Periodicity;Peripheral;Phenotype;Physiology;Pituitary-dependent Cushing's disease;Predisposition;prednisolone;Receptor Signaling;Regulation;Repression;residence;response;RNA;Role;Serum;Signal Pathway;Signal Transduction;skeletal;Skeleton;substantia spongiosa;Syndrome;Testing;therapeutic miRNA;Thick;Tissues;transcriptome sequencing;Transgenic Mice;Translational Repression;virtual;Work

PROJECT_TITLE: MicroRNA regulation of osteoblast physiology and glucocorticoid signaling

STUDY_SECTION: SBDD

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


FUNDING_MECHANISM: OTHERS

PHR: Impulsive behavior is associated with posttraumatic stress disorder (PTSD) in Veterans and is linked to a host of negative outcomes. We aim to examine the impulsivity-PTSD relationship using functional brain imaging and functional connectivity analysis. The importance of this proposed work lies in its potential to lead to the development of new treatments targeting impulsive behavior and its subdomains in Veterans with PTSD.

PI_NAMEs: YOUNG, DMITRI A. (contact)

PROJECT_TERMS: adverse outcome;Aggressive behavior;Anger;Anterior;Area;Arousal;Behavior;Behavior assessment;Behavioral;behavioral disinhibition;Behavioral inhibition;Brain;Brain imaging;career development;cingulate cortex;Clinical;Clinical Research;Cognitive;cognitive neuroscience;Corpus striatum structure;Data Analyses;design;Development;Dimensions;discounting;Dorsal;Exhibits;experience;Frequencies;frontal lobe;Functional disorder;Functional Magnetic Resonance Imaging;Goals;Health;high risk sexual behavior;Impairment;Impulsive Behavior;Impulsivity;indexing;individualized medicine;Inferior;interest;Intervention;intimate partner violence;Investigation;Knowledge;Lateral;Link;Mediating;Mentors;military veteran;Modeling;multidisciplinary;network dysfunction;neural;neural circuit;neural network;Neuroanatomy;Neurobiology;neuropathology;Neurosciences;Neurosciences Research;novel;Outcome;Participant;Pathway interactions;patient oriented;Post-Traumatic Stress Disorders;Prefrontal Cortex;Public Health;reinforcer;Research;Research Personnel;response;Rewards;Risk Taking;Self Destructive Behavior;Self-control as a personality trait;Severities;skills;Startle Reaction;Stimulus;Substance abuse problem;Suicide;Symptoms;System;Theoretical model;tool;Training;Trauma;Ventral Striatum;Veterans;Violence;Work

PROJECT_TITLE: Neurofunctional Differences in Cognitive and Behavioral Impulsivity in Veterans with PTSD


ORG_CITY: SALT LAKE CITY

ORG_NAME: VA SALT LAKE CITY HEALTHCARE SYSTEM

ORG_STATE: UT

PHR: Veterans have a two-fold greater risk of developing heart failure (HF) than non-Veterans. In fact, HF is one of the top causes of hospitalization across the VA healthcare system, and is associated with markedly high annual medical costs. Heart failure with preserved ejection fraction (HFpEF) accounts for greater than 50% of all heart failure (HF) cases nationwide, and the prevalence of this form of HF relative to heart failure with reduced ejection fraction (HFrEF) is growing by approximately 10% per decade. The proposed project seeks to evaluate the mechanisms responsible for disease-related vascular dysfunction and exercise intolerance in Veterans with HFpEF, which will be accomplished through selective pharmacologic targeting of distinct pathways known to regulate vascular inflammation and nitric oxide (NO) signaling. Findings from the proposed work hold the promise of identifying novel therapeutic approaches for enhanced vascular health and exercise tolerance in Veterans with HFpEF, which may lead to an improved quality of life and better prognosis in this patient group.

PI_NAMEs: WRAY, D. WALTER (contact)

PROJECT_TERMS: Activities of Daily Living;Address;Area;Arginine;atorvastatin;Biological Availability;Biological Markers;Blood Vessels;Cardiac;Chronic;Circulation;Citrulline;Clinical;Clinical Trials;cofactor;comorbidity;Coupling;Crossover Design;Disease;disease natural history;Double-Blind Method;Dyspnea;EFRAC;Endothelium;Enteral;exercise intolerance;Exercise Tolerance;Exertion;experimental study;Functional disorder;Goals;Health;Healthcare Systems;Heart failure;heart failure with reduced ejection fraction;hospital admission rate;Hospitalization;Hospitals;Hydroxymethylglutaryl-CoA reductase;Impairment;improved;improved outcome;in vivo;Inflammation;inhibitor;Intervention;Knowledge;Link;Mechanics;Mediating;Medical Care Costs;Methodology;Mortality Decline;Nitric Oxide;Nitric Oxide Donors;NOS3 gene;novel;novel strategies;novel therapeutic intervention;oxidation;Oxidative Stress;Pathway interactions;Patients;Peripheral;Peroxonitrite;pharmacologic;Pharmacotherapy;Physical Capacity;Physical Function;Play;preservation;Prevalence;Production;Prognosis;Property;Quality of life;Randomized;Reactive Oxygen Species;readmission rates;Research;Risk;Role;Series;Signal Transduction;stem;Symptoms;Testing;tetrahydrobiopterin;Therapeutic;therapeutic target;Translating;vascular contributions;Vascular Diseases;vascular inflammation;Veterans;Work

PROJECT_TITLE: Novel Approaches for Improving Vascular Function in Veterans with HFpEF


ORG_CITY: PITTSBURGH

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Public Health Significance Schizophrenia is a chronic and severely debilitating brain disorder with poor outcome. Treatments are symptomatic and the causes are unknown. The associated disability and morbidity adds to major public health burden of severe mental illness. Gaining a greater understanding of the underlying mechanisms associated with cognitive impairments could lead to identification of novel targets for innovative treatments. The proposed effort is driven by intriguing data from diffusion tensor imaging and magnetic resonance spectroscopy. The goal of this proposal to combine these modalities of imaging to understand the neural circuitry resilience – adaptation of neurons to internal and external changes, among SZ that may modulate cognitive impairments that contribute significantly to poor outcome. Currently available treatments minimally affect cognitive impairments. Therefore, the results of this study can potentially help improve long term outcome.

PI_NAMEs: PRASAD, KONASALE M (contact)

PROJECT_TERMS: 3-Dimensional;Acute;Affect;Age;Anatomy;Anisotropy;Architecture;Attention;Attentional deficit;Autopsy;Axon;Bilateral;Biological Response Modifiers;Brain;Brain Diseases;Brain region;C-reactive protein;Cells;Characteristics;Chronic;Cognitive;Cognitive deficits;cognitive enhancement;cognitive performance;cohort;Compensation;Complement component C4a;Complex;cost;Data;Dendrites;density;design;Deterioration;Development;Diffusion;diffusion anisotropy;Diffusion Magnetic Resonance Imaging;disability;Disease;Electric Stimulation;Environment;evidence base;extracellular;Favorable Clinical Outcome;Fiber;Forcep;gene complementation;Gene Dosage;Genetic Markers;genetic selection;genome-wide;Goals;gray matter;Hereditary Disease;IL6 gene;Image;imaging modality;imaging study;Impaired cognition;Impairment;improved;improved outcome;Inflammation;inflammatory marker;innovation;Interleukin-6;Interneurons;Intervention;Lipid Bilayers;loss of function;magnetic field;Magnetic Resonance Spectroscopy;Measures;Medical;Membrane;Methods;Minor;Morbidity - disease rate;Morphology;multimodal neuroimaging;multimodality;Nature;neural circuit;neural model;Neurites;Neurocognitive;Neuroglia;neuroimaging;neuronal cell body;Neurons;Neuropil;Noise;novel;novel strategies;Outcome;Parietal Lobe;Pathology;Pathway interactions;patient subsets;Patients;Performance;Peripheral;Phospholipids;Phosphorus;Pilot Projects;Prefrontal Cortex;Process;protein expression;Psychotic Disorders;Public Health;Publishing;Recovery;Reporting;resilience;Resistance;Rodent;Schizophrenia;schizophrenia risk;severe mental illness;sex;Signal Transduction;Social outcome;structural imaging;Structure;Superior temporal gyrus;sustained attention;symptom treatment;Synapses;synaptic pruning;Techniques;therapy design;Tissues;transcranial direct current stimulation;Transcranial magnetic stimulation;Variant;Veterans;water diffusion;white matter;young adult

PROJECT_TITLE: Neural Circuitry Resilience in Psychotic Disorders: A Multimodal Ultra-High Field Neuroimaging Study


PHR: MRI, through improved depiction of plaque features, can significantly improve determination of stroke risk compared with carotid stenosis measurements. This proposal will address the limitations to widespread MRI implementation including the need for gadolinium contrast agents, long exam time and steep learning curve required to interpret multi-contrast MRI. Our 5 expert centers will develop a novel MRI method for non-contrast quantitative carotid imaging that will rapidly, automatically and accurately identify vulnerable plaque components. The MRI software and hardware techniques developed will be transferable to other MRI platforms and applicable to imaging other vascular territories and nonvascular tissue. This novel non-contrast MRI protocol should fundamentally change the clinical management of cerebrovascular disease.

PI_NAMEs: TREIMAN, GERALD S (contact)

PROJECT_TERMS: Address;Algorithms;Arterial Fatty Streak;Blood Vessels;Brain imaging;calcification;Carotid Arteries;Carotid Artery Plaques;Carotid Stenosis;cerebrovascular;Cerebrovascular Disorders;clinical application;Clinical Management;Collaborations;Community Hospitals;Computer software;contrast enhanced;Contrast Media;density;Development;Diameter;Diffusion;Disease;Evaluation;experience;Gadolinium;Goals;Hemorrhage;Histology;Image;imaging modality;improved;individualized medicine;Injections;Intervention;Learning;Lipids;Magnetic Resonance Imaging;Maps;Measurement;Measures;Medical center;Methods;Neck;Necrosis;neurovascular;novel;Patients;Performance;Physiologic pulse;Protocols documentation;Protons;Relaxation;Research;Research Personnel;Rupture;Scanning;Shapes;Signal Transduction;Stroke;stroke risk;surgical risk;Techniques;Technology;Testing;Thinness;Time;Tissues;Training;Vendor;Veterans;Visit

PROJECT_TITLE: Development of a practical quantitative non-contrast approach for cerebrovascular MRI


ORG_NAME: BIRMINGHAM VA MEDICAL CENTER

PHR: Post-traumatic stress disorder (PTSD) can range from 10% to as high as 31% in the Veteran population depending on the service era of the Veteran. Those diagnosed with PTSD have a higher risk of stroke compared to those without a diagnosis of PTSD. There are over 7 million people living with stroke in the United States. Per year, approximately 17,000 veterans are admitted to the VA for acute stroke. Those veterans with PTSD that suffer stroke, will tend to have worsening PTSD and stroke outcomes. Of major concern, Veterans with stroke are typically excluded from PTSD clinical trials due to their stroke. Methylphenidate has been shown to improve PTSD symptom severity and stroke clinical outcomes, separately. This proposal aims to fill this gap in knowledge by investigating the impact and mechanism of methylphenidate on clinical outcomes after stroke in Veterans with PTSD.

PI_NAMEs: LIN, CHEN  (contact)

PROJECT_TERMS: Activities of Daily Living;acute stroke;Admission activity;Adverse event;Aerobic Exercise;Age;avoidance behavior;Brain;Caring;Central Nervous System Stimulants;Chronic;Clinical;Clinical Investigator;Clinical Trials;comorbidity;Data;Diagnosis;Dopamine;dopamine transporter;double-blind placebo controlled trial;DSM-V;effective intervention;efficacy study;Eligibility Determination;Evidence based treatment;Exclusion;Exclusion Criteria;Exercise;Experimental Designs;Extinction;Face;fear memory;follow-up;Fright;Functional Magnetic Resonance Imaging;functional outcomes;Genetic;Goals;Guidelines;High Prevalence;high risk;improved;Intervention;Ischemic Stroke;Knowledge;Magnetic Resonance Imaging;Measures;Mediator;memory consolidation;Mentors;military veteran;Modeling;mood symptom;Moods;Motor;Multivariate Analysis;Neurology;Neurons;Neurosciences;noradrenaline transporter;novel therapeutics;Outcome;Outcomes Research;Pain;pain reduction;Participant;Pathogenesis;Patients;Persons;Phase;Placebo Control;Placebos;Play;post stroke;post stroke pain;Post-Traumatic Stress Disorders;Prefrontal Cortex;psychiatric comorbidity;Psychiatry;psychologic;Randomized;randomized placebo controlled trial;Recording of previous events;Recurrence;reduce symptoms;Regimen;Research;Research Design;resilience;Risk;Ritalin;Role;Safety;screening;Services;Severities;Short-Term Memory;Signal Transduction;Site;social;stressor;Stroke;Stroke Belt;stroke clinical trials;stroke outcome;stroke recovery;stroke risk;Structure;success;symptom treatment;symptomatic improvement;Symptoms;System;Therapeutic Effect;therapy development;Training;United States;vascular risk factor;Veterans;Vietnam;Withdrawal;Work

PROJECT_TITLE: A randomized placebo-controlled trial of methylphenidate in Veterans with a diagnosis of post traumatic stress disorder and recent cerebral stroke.


ED_INST_TYPE: UNIVERSITY-WIDE

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Program Director (Last, first, middle): Kleinfeld, David We propose to delineate the nature of blood flow in the brain, with the goal of relating flow dynamics to the topology of the underlying vasculature. This provides a basis for understanding how different brain areas are perfused, how different brain areas are susceptible to occlusions to flow, as occur during stroke, and how different brain areas control their own flow of blood. The proposed work further bears on determining the biophysical basis for coordinated patterns of flow across the brain, which define functional connections and may be used to detect normal versus dysfunctional neuronal signaling.

PI_NAMEs: KLEINFELD, DAVID  (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TITLE: Resilient versus fragile aspects of blood flow in the mammalian brain


NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Cancer;Digestive Diseases;Esophageal Cancer;Orphan Drug;Rare Diseases;Stomach Cancer

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE This proposal seeks to validate caveolin-1 as a complementary biomarker of HER2 and to determine sensitivity or resistance of the tumor-targeting anti-HER2 antibody trastuzumab when administrated in combination with the common cholesterol-depleting drug lovastatin in the treatment of esophagogastric cancer. Retrospective clinical and preclinical analyses will be performed using patient HER2+ tumor samples and patient-derived EG xenografts treated with statin alone, trastuzumab alone, or the combination of the two. The long-term goal will be to inform future therapeutic strategies that can prevent or delay the emergence of trastuzumab resistance.

PI_NAMEs: JANJIGIAN, YELENA Y;LEWIS, JASON S. (contact)

PROGRAM_OFFICER_NAME: WU, YICONG

PROJECT_TERMS: Antibodies;Binding;Biological Markers;cancer cell;caveolin 1;Cell membrane;Cholesterol;Classification;Clinical;Clinical Data;clinical imaging;Clinical Research;clinical translation;Clinical Trials;Combined Modality Therapy;Copy Number Polymorphism;Cytotoxic Chemotherapy;Data;Disease Progression;Dose;dosimetry;Drug Kinetics;Drug resistance;drug sensitivity;Endocytosis;ERBB2 gene;Exhibits;Fluorine;Foundations;Future;gastroesophageal cancer;Goals;Heterogeneity;Human;humanized antibody;Image;improved;Incidence;Investigation;Label;Lovastatin;Lutetium;Malignant Neoplasms;Mediating;Medical Records;Membrane;Methods;Modeling;Molecular;molecular imaging;Mus;Mutation;neoplastic cell;non-invasive imaging;novel;Organoids;patient response;Patient Selection;Patients;Pharmaceutical Preparations;Pharmacodynamics;pharmacologic;Population;Positron-Emission Tomography;pre-clinical;preclinical study;prevent;protein expression;Protein Overexpression;Proteins;Radiation Dose Unit;Radiation therapy;Radiolabeled;radioligand;Radionuclide therapy;Randomized;receptor;receptor internalization;Resistance;Resistance development;resistance mechanism;response;Saline;Sampling;Site;Stains;Structure;Surface;Survival Analysis;targeted imaging;Testing;Therapeutic;Therapeutic antibodies;therapy resistant;Time;Tissues;Translations;Trastuzumab;Treatment Efficacy;treatment response;tumor;uptake;Validation;Xenograft procedure;young man;Zirconium

PROJECT_TITLE: Improving radiolabeled imaging and targeting of HER2 positive EG cancers using lovastatin


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases;Pediatric;Prevention;Rare Diseases

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Cryptosporidium is one of the most important causes of diarrheal disease in the U.S. and around the world. This project will unravel the immune mechanisms that control the parasite and offer protection.

PI_NAMEs: HUNTER, CHRISTOPHER A;STRIEPEN, BORIS  (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: adaptive immunity;Adult;Affect;Age;Antigens;antimicrobial;Area;asexual;Biological Models;Biology;Bioterrorism;C57BL/6 Mouse;Categories;Cause of Death;Cell Communication;Cell Physiology;Cells;Child;Child Development;Child Mortality;chlorination;Communities;Cryptosporidiosis;Cryptosporidium;Data;Defect;Dendritic Cells;Development;diarrheal disease;Disease;Disease Outbreaks;Drops;Engineering;enteric pathogen;Enterobacteria phage P1 Cre recombinase;Enterocytes;Epidemiology;Epithelial Cells;Etiology;experience;Gene Expression Profile;Gene Expression Profiling;genetic manipulation;Genomics;Growth;Human;Hyperplasia;Immune;immune clearance;Immune response;Immune system;Immunity;Immunocompetent;Immunologics;Immunologist;in vivo;Incidence;Individual;Infection;Inflammatory;interest;Interferon Type II;Intestinal Diseases;Knowledge;Life;Life Cycle Stages;Literature;LoxP-flanked allele;Malignant - descriptor;Malnutrition;Mediating;Methods;Modeling;Molecular;mouse model;Mus;neglect;novel;Organism;Organoids;Parasite Control;Parasites;pathogen;Pathway interactions;Patients;Play;Population;Predisposition;prevent;Prevention;Process;Production;programs;Reporter;Research;Resistance;resistance mechanism;response;Role;single-cell RNA sequencing;STAT1 gene;System;T cell response;T-Cell Development;T-Lymphocyte;Testing;tool;Translations;transmission process;vaccine development;Vaccines;villin;Water;waterborne illness

PROJECT_TITLE: Immunity to Cryptosporidium

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: EAST LANSING

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: Project Narrative V(D)J recombination is a fundamental immune process that protects us from pathogens by generating diverse antibody repertoires, but can also make errors by targeting undesired genomic loci. This study aims to investigate the key mechanisms that ensure properly targeted V(D)J recombination activity for generation of antibodies, and thereby suppress unwanted genomic lesions underlying lymphoid malignancies.

PI_NAMEs: ZHANG, YU  (contact)

PROGRAM_OFFICER_NAME: LEITNER, WOLFGANG W

PROJECT_TERMS: 3-Dimensional;abl Oncogene;adaptive immunity;Alleles;Animal Model;Antibodies;Antibody Repertoire;Antigen Receptors;Automobile Driving;B-Cell Development;B-Lymphocytes;Bar Codes;base;Biological Assay;Cell Line;Cells;Chromatin;Chromatin Loop;cohesin;Complex;conditional knockout;Data;Distal;driving force;Elements;endonuclease;Ensure;flexibility;Generations;Genetic Recombination;Genetic study;Genome;genomic locus;Genomics;Heavy-Chain Immunoglobulins;humoral immunity deficiency;IGH@ gene cluster;Immune;insight;Intercistronic Region;Knockout Mice;Knowledge;Lesion;Lymphoid;Malignant lymphoid neoplasm;Maps;Mediating;Molecular;mouse model;novel;pathogen;Peptide Signal Sequences;Physiological;Play;prevent;Process;progenitor;Rag1 Mouse;Rapid screening;Receptor Gene;Regulatory Element;release factor;residence;Resolution;Role;Scanning;System;T-cell receptor repertoire;T-Lymphocyte;Testing;Time;Trans-Activators;V(D)J Recombination;Variant;Work

PROJECT_TITLE: Chromatin looping directed RAG targeting during V(D)J recombination


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Liver Disease

ORG_CITY: SHREVEPORT

ORG_NAME: LOUISIANA STATE UNIV HSC SHREVEPORT

PHR: PROJECT NARRATIVE: Non-alcoholic fatty liver disease (NAFLD), characterized by abnormal hepatic lipid accumulation, hepatocyte ballooning, inflammation, and fibrosis, is the leading cause of liver failure in the world, affecting 25% of the global population. Our work has uncovered a novel role for the receptor tyrosine kinase EphA2 in NAFLD, with potential implications in late stage NASH Therefore, this project may identify a new therapeutic target for the treatment of NAFLD.

PI_NAMEs: PEARSON, BRENNA H (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: Affect;Arterial Fatty Streak;axon guidance;Body Weight;Cell Adhesion;Cell Culture Techniques;cell type;Cells;chronic liver disease;Cirrhosis;Data;Development;Disease;Disease Progression;Enzymes;Eph Family Receptors;EphA Receptors;EphA2 Receptor;Ephrin B Receptor;Ephrins;Event;Family;fatty acid oxidation;Fatty Liver;feeding;Fibrosis;Hepatic;Hepatocyte;High Fat Diet;Homeostasis;Human;Inflammation;knock-down;Knock-out;Knockout Mice;Left;leukocyte homing;Ligands;Lipids;Lipoproteins;Liver;Liver Failure;liver function;liver inflammation;liver injury;mammalian genome;Mediating;Metabolism;migration;Mitochondria;Modeling;mouse model;Mus;Neoplasm Metastasis;new therapeutic target;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;Nonesterified Fatty Acids;novel;overexpression;Pathogenesis;Patients;Pattern;Phosphorylation;Phosphotransferases;Population;preclinical trial;Primary carcinoma of the liver cells;Process;Proliferating;protein expression;Receptor Protein-Tyrosine Kinases;response;Role;Signal Transduction;Single Nucleotide Polymorphism;Testing;Therapeutic;Tissues;Tyrosine;uptake;Viral;Weight;Work

PROJECT_TITLE: EphA2 in Non-Alcoholic Fatty Liver Disease


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Among HAIs, Clostridioides difficile infection (CDI) is responsible for approximately 500,000 infections per year, of which 66% are healthcare-associated, and undiagnosed patients who are colonized with C. difficile are increasingly recognized as a potential source of infection in the hospital setting. The overall objective of this proposal is to prospectively deploy our validated machine learning risk model for hospital-acquired CDI to gain an increased understanding of 1) how the risk of CDI relates to colonization status and 2) its utility in guiding management and improving outcomes. This can lead to a paradigm shift in how CDI is prevented in hospitals and serve as a model to combat other infections.

PI_NAMEs: RAO, KRISHNA  (contact);WIENS, JENNA

PROGRAM_OFFICER_NAME: LIN, LEYI

PROJECT_TITLE: Data-Driven Interventions for Reducing C. difficile Incidence

STUDY_SECTION: HSQR

STUDY_SECTION_NAME: Healthcare Patient Safety and Quality Improvement Research[HSQR]


NIH_SPENDING_CATS: Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Dissemination and Implementation Research;Health Services;Mental Health;Mental Illness;Post-Traumatic Stress Disorder (PTSD);Social Determinants of Health;Violence Against Women;Violence Research;Women's Health Research

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC

PHR: PROJECT NARRATIVE Adapting mental health treatments to address modifiable interpersonal problems has the potential to improve and sustain outcomes in low-resource settings where treatment gaps persist. This K23 Award will prepare the candidate to become an independent investigator with high-impact public health research and expertise in couple-based interventions that address interrelated mental health problems and intimate partner violence in couples by gaining expertise in engagement and treatment of men, adapting an evidence-based treatment for common mental disorders to address IPV in couples, designing and conducting randomized controlled trials with couples, and professional skills development. This work has applicability for low-resource low-income countries and US populations that experience couple-based violence and the mental health treatment gap. With its focus on intimate partners, the intervention also has the potential to benefit health and wellbeing of children.

PI_NAMEs: MOOTZ, JENNIFER J (contact)

PROGRAM_OFFICER_NAME: SENN, THERESA ELAINE

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Africa South of the Sahara;Aftercare;AIDS prevention;Anxiety;Anxiety Disorders;Brief Psychotherapy;career;Caring;Child Welfare;Clinic;common treatment;Competence;Consolidated Framework for Implementation Research;Counseling;Country;Couples;court;Data;depressive symptoms;design;Disproportionately impacts women;Disputes;Educational workshop;efficacy testing;Eligibility Determination;Enrollment;Evidence based treatment;Exclusion;experience;Exposure to;feasibility testing;Female;Focus Groups;follow-up;Future;Gender;Gender Role;gender-based violence;Goals;Health;Health Benefit;Health Personnel;Health Professional;High Prevalence;HIV anti-retroviral;implementation strategy;improved;Individual;International;Intervention;Interview;intimate partner violence;low and middle-income countries;low income country;Manuals;Manuscripts;Measures;men;Mental Depression;Mental disorders;Mental Health;Mental Health Services;Mentored Patient-Oriented Research Career Development Award;Mentorship;Methods;Modality;Mood Disorders;Mozambique;novel;Outcome;Patients;Persons;Population;Post-Traumatic Stress Disorders;primary outcome;Procedures;Protocols documentation;Provider;Province;psychosocial stressors;Public Health;public health research;Publications;Randomized;Randomized, Controlled Trials;Recommendation;Reporting;Research;Research Personnel;research study;Resolution;Resource-limited setting;Resources;retention rate;Risk Factors;satisfaction;scale up;secondary outcome;Severities;skill acquisition;skills;social determinants;symposium;Symptoms;Training;Training Programs;treatment as usual;Violence;Woman;Work;Zambia

PROJECT_TITLE: Treating Common Mental Disorders in Women in Mozambique by Addressing Intimate Partner Violence in Couples

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences

PHR: PROJECT NARRATIVE  This application combines structural, biochemical and cell biological approaches to characterize the mechanisms underlying two lysosomal ion transport proteins - TMEM175 and CLC-7/OSTM1. This research will aid in understanding the molecular mechanisms underlying the function of TMEM175 and CLC-7/OSTM1 and start to determine how their dysregulation can lead to Parkinson’s Disease, osteopetrosis and other diseases.

PI_NAMEs: HITE, RICHARD KEVIN (contact)

PROGRAM_OFFICER_NAME: NIE, ZHONGZHEN

PROJECT_TERMS: Albers-Schonberg disease;alpha synuclein;antiporter;Autophagocytosis;Binding;Biochemical;Biological;Biological Assay;Biophysics;Carrier Proteins;Cells;Cellular Immunity;Chloride Channels;Chlorides;CLC Gene;Complex;constriction;Cryoelectron Microscopy;Cytosol;cytotoxic;Data;Defect;detection of nutrient;Development;Developmental Delay Disorders;Disease;Electrophysiology (science);Enzymes;experimental study;Family;Foundations;Functional disorder;Goals;Health;Homeostasis;Human;human disease;Hydrophobicity;improved;In Vitro;in vitro Assay;insight;Ion Transport;Ions;Lead;Ligands;Lipids;Lysosomal Storage Diseases;Lysosomes;macromolecule;member;Membrane;Membrane Potentials;Metabolism;Molecular;molecular dynamics;Mus;Mutation;Nerve Degeneration;Neurodegenerative Disorders;Neurons;Nutrient;Organelles;Osteoclasts;Parkinson Disease;Pathology;pH Homeostasis;Phosphatidylinositols;Phosphotransferases;Physiological;Physiology;Point Mutation;Potassium Channel;potassium ion;Predisposition;Process;Proteins;Protons;RAC-Alpha Serine/Threonine Kinase;Recycling;Regulation;repaired;Reporting;Research;Risk Factors;Role;Signal Transduction;Stimulus;Stress;Structure;tau Proteins;vacuolar H+-ATPase;voltage

PROJECT_TITLE: Mechanisms of lysosomal ion transport proteins involved in pH homeostasis

STUDY_SECTION: BBM

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