NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Neurosciences;Social Determinants of Health;Women's Health Research

ORG_STATE: NC

PHR: Narrative This study examines the long-term impact of adversity and psychosocial intervention on women’s stress system function and internalizing symptoms. Findings can clarify the risk and protective factors influencing women’s well-being.

PI_NAMEs: BARANOV, VICTORIA ;MASELKO, JOANNA  (contact)

PROGRAM_OFFICER_NAME: TALKOVSKY, ALEXANDER MAXWELL

PROJECT_TERMS: 8 year old;Adverse event;Anxiety Disorders;anxiety symptoms;Asia;Birth;burden of illness;Child;childhood adversity;Chronic;cohort;cost effective;COVID-19;Cultural Diversity;Data;Data Collection;Data Set;dehydroepiandrosterone;Depressive disorder;depressive symptoms;Disease;diversity and equity;early life adversity;Effectiveness;Ensure;Event;experience;Exposure to;follow-up;Funding;Gender;Goals;Hair;Hormones;Hydrocortisone;hypothalamic-pituitary-adrenal axis;implementation strategy;improved;Infrastructure;insight;Intervention;intervention effect;intimate partner violence;Knowledge;Life;Life Cycle Stages;Long-Term Effects;Longitudinal Studies;low and middle-income countries;maternal depression;Mediating;Mental Depression;Mental Health;Modeling;novel;Pakistan;Personal Satisfaction;Persons;Postpartum Period;Poverty;Pregnancy;protective factors;psychological symptom;psychosocial;Public Health;Randomized;Randomized, Controlled Trials;recruit;Regulation;Reporting;Research;Resources;Risk Factors;Role;Rural;Sampling;Shapes;social culture;Social Environment;Stress;stressor;Symptoms;System;Techniques;Testing;Third Pregnancy Trimester;Time;United States National Institutes of Health;Woman;women versus men;Women's study;Work

PROJECT_TITLE: Women's adversity exposure, HPA axis regulation, and internalizing symptoms: a longitudinal study of a depression intervention

STUDY_SECTION: MESH

STUDY_SECTION_NAME: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Genetics;Infectious Diseases;Prevention;Tickborne Diseases;Vector-Borne Diseases

ORG_CITY: HATTIESBURG

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF SOUTHERN MISSISSIPPI

ORG_STATE: MS

PHR: PROJECT NARRATIVE Tick-borne diseases are on the rise due to climatic changes and are predicted to increase. The increase in tick- borne diseases poses a significant threat to public health in the absence of preventive measures. This project aims to identify tick immune cells (hemocytes) subtypes with distinct molecular signatures and validate these characterizations using various bioinformatics and experimental molecular tools.

PI_NAMEs: KARIM, SHAHID  (contact)

PROGRAM_OFFICER_NAME: PERDUE, SAMUEL S

PROJECT_TERMS: Address;Amblyomma;antibiotic tolerance;Bioinformatics;Biological Assay;Biology;Blood;Cell Lineage;cell type;Cells;Cellular biology;Cellular Immunity;Classification;climate change;Code;Communicable Diseases;comparative;Data;Data Set;Diagnostic tests;differential expression;Early Diagnosis;Encapsulated;experimental study;Genes;Genetic Markers;gulf coast;Hemocytes;Hemolymph;high reward;high risk;human pathogen;Immune;Immunologic Factors;Immunology;Impairment;Infection;Innate Immune System;Insecta;Invaded;Invertebrates;Ixodidae;Knowledge;Leukocytes;Literature;Mediating;Microbe;microbial;Mission;Molecular;Molecular Profiling;National Institute of Allergy and Infectious Disease;neglect;novel;Outcome;Ovary;pathogen;Phagocytes;Phagocytosis;Phase;Play;Population;Prevalence;prevent;Preventive measure;Preventive vaccine;Public Health;Publishing;Reagent;Recombinant Proteins;Regulation;Research;Resolution;response;Rickettsia;Rickettsia Infections;Rickettsia parkeri;RNA;RNA Interference;Role;Saliva;Salivary Glands;single-cell RNA sequencing;spotted fever;Technology;tick-borne;Tick-Borne Diseases;tick-borne pathogen;Ticks;Tissues;tool;trafficking;transcriptome sequencing;transmission process;Treatment Efficacy;United States;United States National Institutes of Health;vector;vector competence;vector transmission;Vertical Transmission

PROJECT_TITLE: The Role of Hemocytes in tick Rickettsia parkeri infection

STUDY_SECTION: TVZ

STUDY_SECTION_NAME: Transmission of Vector-Borne and Zoonotic Diseases Study Section [TVZ]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF MEDICINE

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

ORG_CITY: KANSAS CITY

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: Project Narrative The ovulatory surge of luteinizing hormone (LH) induces a plethora of events within the ovary that ultimately result in release of a fertilizable oocyte and conversion from an estrogen to a progesterone producing tissue, both of which are essential for fertility. LH accomplishes this through many mechanisms and our laboratory has recently determined that circular RNAs are induced by LH and that they may play a key role in this process. Our study focuses on understanding how LH regulates circRNA biogenesis in ovarian follicular (granulosa) cells and how specific circRNA mediate functional impacts in ovarian events, such as hormone production and release of the oocyte.

PI_NAMEs: CHRISTENSON, LANE K. (contact);VEERA RAGHAVULU, PRAVEEN CHAKRAVARTHI

PROGRAM_OFFICER_NAME: TAYMANS, SUSAN

PROJECT_TERMS: Address;age related changes;Antral;Aromatase;Binding Sites;Biogenesis;Bioinformatics;Biological;Biological Assay;Biotin;Cell Differentiation process;Cell Physiology;Cells;circular RNA;corpus luteum;Coupled;crosslink;Data;Development;differential expression;Disease;Elements;Estrogens;Etiology;Event;Exhibits;Female;female fertility;Fertility;Genes;Genetic Transcription;granulosa cell;hormonal contraception;Hormones;Human;Immunoprecipitation;in vivo;Infertility;Introns;Knock-out;Knockout Mice;Knowledge;Laboratories;Luteinization;Luteinizing Hormone;Mediating;Methods;MicroRNAs;Molecular;Mus;oocyte maturation;Oocytes;Ovarian;Ovarian Follicle;Ovarian Granulosa Cell;Ovarian Tissue;Ovary;Ovulation;Phenotype;piRNA;Play;Polycystic Ovary Syndrome;Porifera;posttranscriptional;primary ovarian insufficiency;Probability;Process;Production;Progesterone;Protein Isoforms;Proteins;Regulation;Reporting;reproductive success;reproductive system disorder;response;RNA;RNA Binding;RNA Recognition Motif;RNA-Binding Proteins;Role;Series;Signal Transduction;SRC-associated p68 protein;System;Testing;Tissues;Transcript;transcriptome sequencing;Translating;Translations;Untranslated RNA;Up-Regulation;Woman

PROJECT_TITLE: Circular RNA Role in Ovarian Follicular Development and Fertility

STUDY_SECTION: ICER

STUDY_SECTION_NAME: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Biotechnology;Cancer;Dental, Oral, and Craniofacial Disease;Genetics;Immunotherapy;Orphan Drug;Precision Medicine;Rare Diseases;Substance Misuse

ORG_CITY: PHILADELPHIA

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

ORG_STATE: PA

PHR: PROJECT NARRATIVE Head and neck cancers arise from cells that line the mucosal surfaces of the head and neck mainly due to alcohol and tobacco use or HPV infection. The aim of this project is to demonstrate proof of concept that small extracellular vesicles or exosomes can be engineered to target specific proteins on cancer cells and deliver miRNAs that would render the cells more susceptible to killing and death.

PI_NAMEs: MAHONEY, MY GEORGIA (contact)

PROGRAM_OFFICER_NAME: CHEN, ZHONG

PROJECT_TERMS: Address;Alcohol consumption;angiogenesis;Annual Reports;antigen binding;antitumor effect;Binding;Biological Markers;Biology;burden of illness;Cadherins;cancer cell;cancer therapy;cell growth;Cell Line;cell motility;Cell secretion;Cell Survival;Cells;Cessation of life;checkpoint therapy;Chemotherapy and/or radiation;chimeric antigen receptor T cells;Chimeric Proteins;chronic alcohol ingestion;Clinical;Clinical Trials;combinatorial;Complex;Data;design;desmoglein 2;Development;Diagnosis;Disease;Dose;Encapsulated;Engineering;Etiology;Excision;exosome;extracellular vesicles;Goals;Head and Neck Cancer;Head and Neck Squamous Cell Carcinoma;Head and neck structure;high risk;Human papilloma virus infection;Human Papillomavirus;Immune checkpoint inhibitor;immunoregulation;Immunotherapy;improved;improved outcome;In Vitro;in vivo;Inflammatory;Inhibition of Cell Proliferation;innovation;insight;intercellular communication;interest;Knowledge;Link;Malignant - descriptor;Malignant Neoplasms;Membrane;Messenger RNA;Metastatic/Recurrent;Methods;MicroRNAs;migration;miRNA expression profiling;Modeling;Molecular;Monoclonal Antibodies;Mucous Membrane;Neoplasm Metastasis;neoplastic cell;novel;novel therapeutics;Oncogenic;Operative Surgical Procedures;overexpression;Pathogenicity;Patient-Focused Outcomes;Patients;PD-1 inhibitors;PD-1/PD-L1;personalized medicine;Phenotype;Plasma;Postoperative Period;posttranscriptional;predictive marker;Predisposition;Process;Prognosis;programmed cell death ligand 1;programmed cell death protein 1;Proliferating;protein expression;Proteins;Publishing;receptor;receptor mediated endocytosis;research clinical testing;Research Personnel;Resistance;resistance mechanism;restraint;Role;Signal Pathway;Signal Transduction;Smoking;Solid;standard of care;Surface;Talents;targeted treatment;Technology;Therapeutic;therapy outcome;therapy resistant;Tobacco use;tool;Translations;treatment response;tumor;tumor growth;tumor microenvironment;tumor progression;Work;Xenograft Model

PROJECT_TITLE: Targeting miRNA-loaded exosomes to HNSCC with Dsg2-directed scFv fusion proteins

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 TIR-W (01)]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Digestive Diseases;Liver Disease;Organ Transplantation;Transplantation

ORG_CITY: Woodland Hills

ORG_NAME: TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION

ORG_STATE: CA

PHR: PROJECT NARRATIVE Despite the tremendous advancement in organ-on-a-chip technologies, liver allograft rejection on-a-chip models have not been developed. Therefore, the overarching goal of this proposal is to engineer a vascularized liver- on-a-chip model comprised of multicellular organotypic microstructures that will recapitulate the pathophysiology of cellular and humoral rejection of liver allografts. Our goal is to offer a novel platform for studying transplant immunology, particularly the kinetics of donor-recipient interactions leading to rejection or tolerance.

PI_NAMEs: JUCAUD, VADIM  (contact)

PROGRAM_OFFICER_NAME: FEHR, TUBA HALISE

PROJECT_TERMS: 3-Dimensional;Acceleration;Allogenic;allograft rejection;Allograft Tolerance;Allografting;Antibodies;antibody-mediated rejection;Autologous;Binding;Biological Markers;Blood;Cell Line;Cell model;Cells;Clinic;Clinical;Clinical Research;Coculture Techniques;cost effective;cytokine;cytotoxicity;design;Development;Devices;disease model;donor-specific antibody;drug development;Drug Screening;end-stage organ failure;Endothelial Cells;endothelial stem cell;Endothelium;Engineering;Extravasation;Fibrin;Fibroblasts;Functional disorder;Genotype;Goals;Growth Factor;Heart Diseases;Hepatocyte;Histocompatibility Antigens Class I;HLA Antigens;Human;Human Characteristics;human model;Hypoxia;Immune;Immune response;Immune system;Immune Tolerance;Immunosuppression;Immunosuppressive Agents;In Vitro;in vitro Model;in vivo;in vivo Model;Incidence;Infection;Infiltration;innovation;Kinetics;Lead;Life;Liver;liver allograft;liver transplantation;Malignant Neoplasms;manufacture;Measurement;Mediating;Methods;Microcirculatory Bed;Microfabrication;Microfluidic Microchips;Microfluidics;migration;Modeling;novel;Organ;organ on a chip;Organ Transplantation;Organoids;Pathologic;Patients;Perfusion;personalized medicine;Pharmaceutical Preparations;Physiological;Pre-Clinical Model;preclinical study;Predisposition;prevent;Protocols documentation;Quality of life;Regimen;renal damage;Research;response;side effect;Site;Solid;spheroids;Structure;success;T cell infiltration;T-Lymphocyte;Techniques;Technology;Testing;Tissues;Translating;Translations;Transplant Recipients;Transplantation;Transplantation Immunology;Transplantation Tolerance;Validation;Vascularization

PROJECT_TITLE: Vascularized liver on-a-chip modeling cellular and humoral rejection of allografts

STUDY_SECTION: ISD

STUDY_SECTION_NAME: Instrumentation and Systems Development Study Section[ISD]


ED_INST_TYPE: UNIVERSITY-WIDE

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

ORG_CITY: PULLMAN

ORG_NAME: WASHINGTON STATE UNIVERSITY

ORG_STATE: WA

PHR: PROJECT NARRATIVE Antibodies are critical mediators of immune protection against pathogens, simultaneously acting to neutralize entry and activate innate immune cells through interaction between the antibody Fc domain and Fc-receptors on innate immune cells. Our proposal aims to define the underlying mechanisms and pathways through which antibodies leverage different innate immune cell types to provide protection through the temporal analysis of gene regulatory pathways induced by a panel of SARS-CoV-2 monoclonal antibodies that will contribute to our fundamental understanding of how antibodies orchestrate immunity which can be applied to current and future monoclonal antibody therapeutics against infectious diseases.

PI_NAMEs: GUNN, BRONWYN MEI (contact)

PROGRAM_OFFICER_NAME: CASTLEMAN, MORIAH JOVITA

PROJECT_TERMS: 2019-nCoV;Affinity;Anti-viral Response;Antibodies;Antibody Activation;antibody engineering;Antibody Therapy;Antibody-Dependent Enhancement;Atlases;Biological Models;Biological Response Modifiers;cell type;Cells;combinatorial;Communicable Diseases;design;Development;Disease;Ebola virus;Engineering;Equilibrium;Event;Fc domain;Fc Receptor;Foundations;Future;Gene Expression Profile;Gene Expression Profiling;Genes;Genetic Transcription;Goals;Hour;Human;Immune;Immune system;Immunity;Immunoglobulin A;Immunoglobulin G;Immunotherapeutic agent;Immunotherapy;in vivo;Individual;Infection;infectious disease treatment;Inflammation;innate immune mechanisms;Kinetics;Knowledge;Ligation;Link;Maps;Mediating;Modeling;Monoclonal Antibodies;Monoclonal Antibody Therapy;monocyte;Natural Immunity;novel strategies;pathogen;Pathology;Pathway interactions;Play;programs;receptor;receptor binding;Regulatory Pathway;Research;RNA;Role;Safety;SARS-CoV-2 infection;Shapes;Signal Transduction;Small RNA;Therapeutic;Therapeutic antibodies;Therapeutic Monoclonal Antibodies;TLR4 gene;tool;transcription factor;Transcription Factor AP-1;Transcription Initiation Site;Transcriptional Activation;transcriptome sequencing;transcriptomics;Translating;Vaccination;vaccine response;Viral;Virus Diseases;Work

PROJECT_TITLE: Dissecting mechanisms of antibody-Fc interactions that shape innate immune antiviral responses.

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Immunotherapy;Infectious Diseases;Orphan Drug;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: LA JOLLA

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Head and neck squamous cell carcinoma (HNSCC), driven by tobacco and alcohol use as well as HPV infection, is the sixth most common cancer worldwide. This debilitating disease presents a significant health care challenge as cases are rapidly rising in the United States and around the world. The proposed studies will decipher the mechanisms driving immune suppression in HNSCC and will develop new therapeutic approaches that can offer new promise for the successful treatment of this deadly disease.

PI_NAMEs: GOLD, KATHRYN ANN;VARNER, JUDITH A (contact)

PROGRAM_OFFICER_NAME: UNDALE, ANITA H

PROJECT_TERMS: Alcohol consumption;angiogenesis;antagonist;anti-CTLA-4 therapy;anti-PD-1;anti-PD1 therapy;anti-tumor immune response;Antibodies;Antitumor Response;Archives;arginase;Automobile Driving;B-Lymphocytes;bench to bedside;Biological Markers;Bone Marrow;cancer diagnosis;Cancer Etiology;Cancer Patient;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Survival;cell type;Cells;Cellular Assay;Chemotactic Factors;chemotherapy;Chemotherapy and/or radiation;circulating biomarkers;Clinical Treatment;Clinical Trials;Country;cytotoxic;Developing Countries;Disease;Disease Outcome;effector T cell;Exhibits;Funding;Future;granulocyte;Head and Neck Cancer;Head and Neck Squamous Cell Carcinoma;Healthcare;HPV oropharyngeal cancer;HPV positive;HPV-negative head and neck cancer;Human;Human papilloma virus infection;Human Papilloma Virus-Related Malignant Neoplasm;Human Papillomavirus;Immune;immune cell infiltrate;Immune checkpoint inhibitor;immune resistance;Immune response;Immunologic Memory;Immunooncology;Immunosuppression;Immunotherapy;improved;improved outcome;Incidence;Inflammatory;inhibitor;Integrins;Interleukin-10;Leukocytes;Macrophage;Malignant Neoplasms;Maps;Mediating;Memory;Modeling;Molecular;Monitor;monocyte;Morbidity - disease rate;mortality;mouse model;Mus;Myeloid Cells;Myeloid-derived suppressor cells;Nature;Neoplasm Metastasis;neoplastic cell;Newly Diagnosed;novel;novel therapeutic intervention;Operative Surgical Procedures;oral HPV-positive head and neck cancers;Pathway interactions;Patients;peripheral blood;Phase;Phase I Clinical Trials;Phase II Clinical Trials;Phosphatidylinositol 4,5-Diphosphate;Phosphotransferases;PIK3CG gene;Prognosis;programmed cell death protein 1;Proliferating;Protein Isoforms;Proteomics;Quality of life;Radiation therapy;recruit;Regimen;Regulatory T-Lymphocyte;Resistance;resistance factors;resistance mechanism;response biomarker;Serum;single-cell RNA sequencing;Slice;Survival Rate;synergism;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;therapeutic development;therapeutic target;therapeutic vaccine;therapy resistant;Tissues;Tobacco;Tobacco use;transcriptomics;triple negative cancer;tumor;Tumor Biology;Tumor-associated macrophages;United States;Up-Regulation;Urothelium

PROJECT_TITLE: Therapeutic Targeting of Macrophage PI3Kgamma in HNSCC

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 TIO-D (01)]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

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

ORG_CITY: MERCED

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA, MERCED

PHR: PROJECT NARRATIVE Parasitic diseases are responsible for great morbidity worldwide, yet there is only one partially protective vaccine currently in use for malaria prevention. Here, we will explore using mRNA vaccines as a tool to achieve protection against parasitic infection not previously possible with other technologies. We propose to test targets that are highly shared between parasites to elicit antibody responses that block the invasion process in Toxoplasma gondii and to prevent diseases caused by Apicomplexa parasites with information gleaned from this project.

PI_NAMEs: JENSEN, KIRK DAVID CHRISTIAN (contact)

PROGRAM_OFFICER_NAME: MO, ANNIE X  Y

PROJECT_TERMS: Animals;Antibodies;Antibody Response;Antigens;Apical;Apicomplexa;Biochemistry;Blocking Antibodies;Bypass;C-Type Lectins;CD46 Antigen;Cells;Complex;cross reactivity;Disease;Drug resistance;Environment;Ephrins;Epidermal Growth Factor Receptor;Eukaryota;Exposure to;extracellular;fitness;Glean;Glycosylphosphatidylinositols;Goals;GPI Membrane Anchors;Grant;Human;Humoral Immunities;Immune response;Immune system;Immunity;Immunization;Immunize;immunogenicity;Immunologics;Immunology;improved;in vivo;Infection;insight;Interruption;Invaded;Knockout Mice;Kringles;Ligand Binding Domain;liposomal formulation;Malaria prevention;Mediating;Membrane;Membrane Proteins;Messenger RNA;Methods;Molecular;Molecular Conformation;Morbidity - disease rate;mRNA Stability;Mus;Nature;parasite invasion;Parasites;Parasitic Diseases;Parasitic infection;Parasitology;Pathway interactions;Pattern Recognition;Peptide Signal Sequences;Plasma Proteins;Prevalence;prevent;Process;Production;Proteins;rational design;receptor;Resistance development;rhoptry;RNA vaccination;RNA vaccine;Role;Source;Surface;Surface Antigens;Technology;Testing;TLR2 gene;TLR4 gene;tool;Toxoplasma gondii;Toxoplasmosis;Transmembrane Domain;transmission process;Untranslated Regions;Vaccinated;Vaccination;Vaccine Design;vaccine development;vaccine efficacy;vaccine evaluation;vaccine formulation;Vaccines;vaccinology;Virulent;Work

PROJECT_TITLE: Targeting Conserved Molecular and Structural Features of Apicomplexans Towards a Rational Vaccine Design

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

ORG_CITY: GOLDEN

ORG_DEPT: CHEMISTRY

ORG_NAME: COLORADO SCHOOL OF MINES

ORG_STATE: CO

PHR: PROJECT NARRATIVE  The proposed research is relevant to public health because it involves developing drug-like molecules that target the SUF-like pathway of iron-sulfur cluster biogenesis, which was recently identified as a potentially viable target for new antibacterial agents for which there is not yet resistance. The proposed work includes the first known systematic screen of small molecules against the SUF-like pathway as well as hit-to-lead development to create first-in-class, lead-like molecules that are metabolically stable and effective against S. aureus, E. faecalis, and S. pneumoniae. Lead-like molecules generated by this work have the potential to combat other pathogens that also rely on the SUF-like pathway, such as M. tuberculosis and parasites that cause malaria, adding a powerful new tool to improve human health and well-being.

PI_NAMEs: HOLZ, RICHARD C (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Acrylamides;Active Sites;Anabolism;analog;Animal Model;Anti-Bacterial Agents;Antibiotic Resistance;antibiotic resistant infections;Antimicrobial Resistance;Bacillus;Bacteria;Bacterial Infections;Binding;Binding Proteins;Biochemistry;Biogenesis;Biological Assay;Cell Survival;Cells;Centers for Disease Control and Prevention (U.S.);Cessation of life;cofactor;Collaborations;combat;cost;Cysteine;cysteine desulfurase;Data;Dedications;Development;Dose;drug candidate;Drug Design;drug development;Drug Kinetics;drug metabolism;Drug resistance;Drug Targeting;drug-like compound;Enterococcus faecalis;Enzymes;Foundations;Future;Goals;Gram-Positive Bacteria;Health;Human;Impairment;improved;In Vitro;in vivo;Infection;inhibitor;innovation;Iron;Lead;Leukocytes;Libraries;Malaria;Metabolic;Modality;Mycobacterium tuberculosis;Names;new therapeutic target;novel;novel therapeutics;Organism;Outcome;Parasites;pathogen;Pathway interactions;Personal Satisfaction;Pharmaceutical Preparations;Productivity;Property;Proteins;Public Health;rational design;Research;Resistance;response;Safety;scaffold;screening;small molecule;small molecule inhibitor;Specificity;Staphylococcus aureus;Streptococcus pneumoniae;Structure;Sulfur;Testing;therapy resistant;tool;Validation;Work;X-Ray Crystallography

PROJECT_TITLE: First-in-class rationally designed inhibitors of the SUF-like pathway of iron-sulfur cluster biosynthesis for treating infections caused by S. aureus and other Gram-positive bacteria

STUDY_SECTION: DMPA

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology A Study Section [DMPA]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Understanding enzymes—their physical and chemical properties and evolutionary trajectories— is fundamental to biology and of profound practical importance to industry and medicine, yet no current tools provide the in-depth biochemical analysis at the scale needed to achieve the next levels of conceptual, empirical, and practical understanding. We present a suite of new tools that meet this challenge, providing kinetic and thermodynamic data for thousands of enzymes with the precision and information content of traditional enzymology but at a small fraction of the time and cost. Applying these tools to multiple enzymes, we will systematically dissect energetic coupling to the active site and throughout the enzyme and do so for multiple functional parameters, while also providing a wealth of “ground truth” measurements to thoroughly test existing and emerging models.

PI_NAMEs: FORDYCE, POLLY MORRELL;HERSCHLAG, DANIEL  (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Active Sites;Affect;Alanine Racemase;Alkaline Phosphatase;Alleles;Amino Acids;Architecture;base;Binding;Biochemical;Biology;Catalysis;chemical property;Classification;clinically relevant;Collaborations;Communities;Computer Models;computerized tools;cost;Coupled;Coupling;Data;Development;Disease;Distal;Engineering;Enzymatic Biochemistry;Enzyme Kinetics;enzyme model;Enzyme Stability;Enzymes;Evolution;Exhibits;experimental study;genetic variant;Genomics;Goals;Grant;Health;high throughput technology;Human;Industrialization;Industry;inhibitor;innovation;insight;Kinetics;Maps;Measurement;Medical;Medicine;member;Microfluidics;Modeling;Motion;mutant;Mutation;natural language;Nature;Nucleotides;Phosphoric Monoester Hydrolases;physical property;Positioning Attribute;Post-Translational Protein Processing;practical application;predictive modeling;Property;Protein Tyrosine Phosphatase;Proteins;Protons;PTPN1 gene;PTPN11 gene;Recombinants;Roentgen Rays;Site;Structure;Structure-Activity Relationship;Surface;synergism;System;Techniques;Temperature;Testing;Therapeutic;Thermodynamics;Time;tool;Urea;Variant;variant of unknown significance;Work

PROJECT_TITLE: Quantitative, High-throughput Mechanistic Enzymology

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

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

ORG_CITY: Aurora

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

PHR: Project Narrative Postsynaptic kinase/phosphatase networks in amyloid b-induced synaptic dysfunction  In Alzheimer’s disease (AD) overproduction of amyloid beta (Ab) protein fragments from the amyloid precursor protein (APP) is thought to interfere with the normal signaling functions of brain synapses during aging to interfere with learning and memory and cause dementia. Elucidating how Ab interferes with synaptic function is an important first step for understanding the mechanisms underlying cognitive impairments associated with AD and could result in the identification of novel drug targets and therapies. However, very little research to date has shed any light on the mechanisms by which Ab engages and interacts with specific, local synaptic signaling pathways to cause neuronal dysfunction and cognitive impairment. Here, with the use of assortment of innovative cellular and molecular imaging methods and genetic manipulations, we will test the novel idea that Ab activates signaling that impairs synaptic and cognitive function through a type of postsynaptic receptor called a Calcium-permeable AMPA receptor (CP-AMPAR) that is in turn regulated by a protein called Protein Kinase A (PKA) that is specifically anchored at synapses by a protein called AKAP150. Importantly, these studies will investigate whether targeted disruption of AKAP150-anchored PKA signaling regulation of CP-AMPARs and/or interfering with additional upstream regulators and downstream targets could be worth exploring as viable therapies for preventing synaptic and cognitive dysfunction in AD.

PI_NAMEs: DELL'ACQUA, MARK L (contact);KENNEDY, MATTHEW J

PROGRAM_OFFICER_NAME: MCGAVERN, LINDA

PROJECT_TERMS: A kinase anchoring protein;abeta accumulation;abeta oligomer;Abeta synthesis;Acute;Adrenergic Agents;Aging;Alzheimer's Disease;Alzheimer's disease model;AMPA Receptors;Amyloid beta-Protein;Amyloid beta-Protein Precursor;Anatomy;Behavioral;Binding;Biochemical;Biological Assay;Biosensor;Brain;Calcineurin;Calcium;calmodulin-dependent protein kinase II;cellular imaging;Chronic;cognitive function;Coupled;CRISPR/Cas technology;Cyclic AMP-Dependent Protein Kinases;Data;Defect;Dementia;Dendritic Spines;Dose;Electrophysiology (science);Excision;Excitatory Synapse;Exclusion;familial Alzheimer disease;Functional disorder;Funding;G-Protein-Coupled Receptors;Genetic;genetic manipulation;genome editing;Glutamate Receptor;GTP-Binding Proteins;Hippocampus;Human;Image;imaging modality;Impaired cognition;Impairment;in vivo;Individual;innovation;Learning;Link;Long-Term Depression;Long-Term Potentiation;Mediating;Memory;Mental Depression;Metabotropic Glutamate Receptors;Molecular Genetics;molecular imaging;mouse model;Mus;Mutation;neurobehavioral;Neuronal Dysfunction;new therapeutic target;novel;Optics;Permeability;pharmacologic;Pharmacotherapy;Phosphoric Monoester Hydrolases;Phosphotransferases;Physiological;Play;postsynaptic;prevent;Protein Fragment;Proteins;receptor;Receptor Signaling;recruit;Regulation;Research;Role;Scaffolding Protein;Signal Pathway;Signal Transduction;Slice;superresolution imaging;Synapses;synaptic function;Synaptic Receptors;Testing;trafficking;Vertebral column

PROJECT_TITLE: Postsynaptic kinase/phosphatase networks in amyloid beta-induced synaptic dysfunction

STUDY_SECTION: NDPR

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


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

ORG_CITY: SALT LAKE CITY

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Narrative Aging worsens outcomes of acute ischemic stroke. We evaluate the hypothesis that age-dependent reductions in endothelial cell (EC) autophagy account for this relationship. Moreover, we explore the possibility that restoring EC autophagy or its ability to regulate EC nitric oxide generation and arterial vasodilation will serve as a novel therapeutic strategy for mitigating stroke outcomes.

PI_NAMEs: CAMPBELL, ROBERT A;SYMONS, JOHN DAVID (contact)

PROGRAM_OFFICER_NAME: BARRETT, PAUL JOHN

PROJECT_TERMS: Acute;adenovirus mediated delivery;Adult;age related;age-related disease;Aging;aging related;Animals;Arteries;ATG3 gene;Autophagocytosis;Basal metabolic rate;Blood;Blood flow;Brain;brain endothelial cell;bryostatin;Cell Physiology;Cell Reprogramming;Cells;Cellular Metabolic Process;cerebral artery;cerebrovascular;cerebrovascular health;Clinical Trials;combat;Complex;Data;Defect;Dependovirus;Depressed mood;Development;Disease;Endothelial Cells;Equilibrium;Exhibits;femoral artery;FRAP1 gene;Functional disorder;Generations;Genetic;Human;Impairment;improved;improved outcome;Infarction;inhibition of autophagy;innovation;Intervention;Ischemic Stroke;knock-down;Lead;Link;macromolecule;Maps;Mediating;Metabolic;Motor;Mus;neurobehavioral;Nitric Oxide;NOS3 gene;novel;novel therapeutic intervention;novel therapeutics;Nutrient;old mice;older adult;Older Population;Organelles;Outcome;overexpression;Oxygen;parenchymal arterioles;Pathway interactions;Perfusion;Peripheral;Pharmaceutical Preparations;Phenotype;Production;Proteins;Publishing;receptor;Receptor Activation;Recovery;Recycling;Refractory;Rejuvenation;Reperfusion Therapy;Reporting;Repression;Signal Transduction;Site;SLC2A1 gene;stroke outcome;Testing;Therapeutic;therapeutic development;therapeutic target;Tissues;Toxic effect;Up-Regulation;vascular factor;Vasodilation

PROJECT_TITLE: Targeting endothelial cell metabolism to improve recovery from acute ischemic stroke in older mice.

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative Trypanosoma brucei and related trypanosomes are deadly pathogens that cause tremendous human suffering worldwide. Transmission and pathogenesis of trypanosomes requires signal transduction systems to enable the parasites to adapt to diverse external environments in the mammalian host and insect vectors that transmit them, but the underlying signaling mechanisms are very poorly understood. cAMP signaling has emerged as an important pathway for transmission and infection by T. brucei and in the current project we will define mechanisms of cAMP signaling in these parasites.

PI_NAMEs: HILL, KENT L (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: Adenylate Cyclase;Affect;Africa South of the Sahara;African Trypanosomiasis;Area;Attention;Binding;Binding Proteins;Biological Assay;Biology;Catalytic Domain;Cell Communication;cell motility;Cells;Chemotaxis;Cilia;cilium motility;Cyclic AMP;Data;Diagnostic;Diffusion;Disease;Drug Targeting;Economic Burden;Environment;Epithelial Cells;Exhibits;extracellular;Extracellular Domain;Fluorescence Resonance Energy Transfer;G-Protein-Coupled Receptors;Generations;genetic manipulation;Genome;Goals;Human;Image;imaging platform;improved;In Vitro;Individual;Infection;innovation;Insect Vectors;insight;intercellular communication;Knowledge;Leishmania;Ligand Binding;Ligands;Mastigophora;Mediating;Medical;model organism;Modeling;Motility;Movement;mutant;Neurons;novel;olfactory bulb;Organism;Parasites;pathogen;Pathogenesis;Pathogenicity;Pathway interactions;Periplasmic Binding Proteins;Pharmacotherapy;Phosphoproteins;phosphoproteomics;phosphoric diester hydrolase;Phosphorylation;Phosphorylation Site;Positioning Attribute;Production;Protein Binding Domain;Proteins;Protozoa;receptor;renal epithelium;response;Role;rural area;segregation;sensor;Signal Transduction;Signal Transduction Pathway;Site;Source;Stimulus;System;temporal measurement;Testing;Tetrahymena;Tissues;tool;Transmembrane Domain;transmission process;Trypanosoma;Trypanosoma brucei brucei;Trypanosoma cruzi;Tsetse Flies;Vaccines;vector;vector transmission;vector-borne pathogen;Vector-transmitted infectious disease;Visualization;Work

PROJECT_TITLE: Flagellar cAMP signaling in Trypanosoma brucei

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Drug Abuse (NIDA only);HIV/AIDS;Neurodegenerative;Neurosciences;Substance Misuse

ORG_CITY: BOYS TOWN

ORG_NAME: FATHER FLANAGAN'S BOYS' HOME

ORG_STATE: NE

PHR: Project Narrative Persons infected with HIV now have a life expectancy near that of the general population, but they remain at a significantly higher risk of developing cognitive impairment. Recent human neuroimaging studies have identified the cortical brain circuits that are centrally involved in such cognitive decline, but the underlying pathways and molecular mechanisms remain poorly understood, and the potential therapeutic options are very limited. The current project builds on several recent discoveries and will use advanced dynamic functional brain mapping, systems biology approaches, and high-dimensional structural equation modeling to identify whether parameters of inflammasome activation and/or the mitochondrial redox environment drive cognitive and brain dysfunction in persons with HIV, and whether regular cannabis use therapeutically modulates these parameters.

PI_NAMEs: WILSON, TONY W (contact)

PROGRAM_OFFICER_NAME: BORGMANN, KATHLEEN RUTH

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Address;Adult;Affect;Anatomy;Area;attentional modulation;Automobile Driving;Behavior;Behavioral;Biological Markers;Brain;brain dysfunction;Brain Mapping;Brain region;Cannabis;Cognition;cognitive function;cognitive performance;comorbidity;Complication;Coupled;Coupling;cytokine;Data;Data Analyses;Disease;Economics;Elements;Environment;Epidemic;Equation;Exhibits;Foundations;Functional disorder;General Population;Goals;Heel;high dimensionality;high risk;HIV;HIV/AIDS;Human;Illicit Drugs;Immunity;Impaired cognition;Impairment;Inflammasome;Inflammation;Inflammatory;innovation;instrumentation;Interleukin-1 beta;Knowledge;Life Expectancy;Link;Maps;marijuana use;Mediating;medication compliance;Methods;Mitochondria;Modeling;Molecular;molecular marker;neural;neural circuit;neuroAIDS;neuroimaging;neuroimaging marker;neuroinflammation;Neurologic;Neuronal Dysfunction;Neuropsychological Tests;Oxidation-Reduction;Participant;Pathologic;Pathway interactions;Performance;Persons;Pharmaceutical Preparations;Population;Quality of life;Reporting;Request for Proposals;Research;Risk;Role;Sampling;Scientific Advances and Accomplishments;selective attention;Seminal;Short-Term Memory;Substance Use Disorder;Superoxides;System;Systems Biology;Targeted Research;Therapeutic;Therapeutic Effect;Therapeutic Uses;Unemployment;Viral;virtual;Work

PROJECT_TITLE: Coupling of Inflammasome Cascades and Aberrant Neural Oscillatory Dynamics in NeuroHIV

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 JRB-N (O1)]


ADMINISTERING_IC: DP

IC_NAME: NATIONAL CENTER FOR CHRONIC DISEASE PREVENTION AND HEALTH PROMOTION

ORG_CITY: SPRINGFIELD

ORG_NAME: ILLINOIS STATE DEPT OF PUBLIC HEALTH

ORG_STATE: IL

PHR: Component A: Core Surveillance Illinois PRAMS Project Narrative  By monitoring the behaviors and experiences of women before, during, and after pregnancy, the Illinois Pregnancy Risk Assessment Monitoring System (PRAMS) surveillance project provides epidemiologic surveillance that enables analysis of trends, identification of emerging issues, and demonstration of priority need areas. State and local maternal and child health programs, academic partners, and others rely on this information to identify priorities, to plan health programs, and to create policies that improve the health and well-being of women and infants and reduce morbidity and mortality.

PI_NAMEs: KOECHLE, JENNIFER  (contact)

PROJECT_TITLE: DP21-001 Component A Core Surveillance: Illinois Pregnancy Risk Assessment Monitoring System (PRAMS) project to collect and analyze survey data to improve maternal and infant outcomes 2021-2026


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_DEPT: SURGERY

PHR: PROJECT NARRATIVE We have seen reduction of a molecule called miR320 in human muscle that is developing weakness due to disuse, and we showed that changes in miR320 has the potential to be causing this weakness. We have now created a knockout mouse with reduced amounts of miR320 in muscle. This project proposes to use this mouse, and other models, to investigate the role of miR320 in muscle growth and maintenance. The work promises to lead to new candidates for treatment of muscle wasting diseases.

PI_NAMEs: SHRAGER, JOSEPH B (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: 3' Untranslated Regions;Address;Anabolism;Apoptosis;Area;Atrophic;Attenuated;Autophagocytosis;Bioinformatics;Catabolism;Cell Culture Techniques;Cell Death;Cell Physiology;Cells;Cessation of life;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Co-Immunoprecipitations;Complex;Data;Denervation;Differentiation and Growth;disabling disease;Disease;Electroporation;Embryo;Equilibrium;Event;F-Box Proteins;Family member;fatty acid metabolism;FBXO32 gene;Fiber;Genes;Genetic;Genetic Transcription;Growth;Hindlimb;Human;in vivo;in vivo Model;Individual;interest;Intervention;Investigation;Isometric Exercise;Knock-out;Knockout Mice;Life;Limb structure;Luciferases;Maintenance;Measures;Messenger RNA;Metabolism;Microprocessor;microRNA delivery;MicroRNAs;Microscopy;Modeling;Molecular;Morbidity - disease rate;Morphology;mortality;mouse model;multicatalytic endopeptidase complex;Mus;Muscle;Muscle Cells;Muscle Development;Muscle Fibers;muscle form;Muscle Weakness;Muscular Atrophy;myogenesis;Myopathy;Pathway Analysis;Pathway interactions;Perinatal mortality demographics;Phenotype;Physiological;Play;Post-Transcriptional Regulation;posttranscriptional;Primary Cell Cultures;Process;Proliferating;protein degradation;Proteins;reduced muscle mass;Regulation;Reporter;Reporter Genes;Research;Respiratory Diaphragm;RNA;Role;Signal Pathway;Signal Transduction;Skeletal Muscle;skeletal muscle growth;skeletal muscle metabolism;skeletal muscle wasting;Supplementation;System;targeted sequencing;Therapeutic;therapeutic target;transcription factor;transcriptome sequencing;transcriptomics;TRIM Motif;Ubiquitin;Ubiquitination;Untranslated Regions;wasting;Wasting Syndrome;Work

PROJECT_TITLE: Investigation of the Functional Roles of MicroRNA-320 in Skeletal Muscle

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: Prostate cancer is the common cancer diagnosed in the Veterans population. African American (AA) men represent ~1/3 of all Veterans diagnosed with prostate cancer. In the U.S., AA men are more likely to be diagnosed with and die from prostate cancer compared to European American (EA) men. It is not well understood what differences in prostate tumors might contribute to these large disparities. To develop a molecular understanding of prostate cancers in AA men, we will perform state-of-the-art sequencing of prostate cancers from AA men to determine the genetic changes that are associated with ancestry and with aggressive prostate cancers. To study how certain genes drive prostate cancer, we will develop new prostate organoid models derived directly from prostate tissue and test the effects of altering these genes. Overall, these studies will advance our understanding of the mechanisms of prostate cancer in AA veterans and all veterans and will inform new strategies to reduce prostate cancer disparities.

PI_NAMEs: HUANG, FRANKLIN W (contact)

PROJECT_TERMS: advanced disease;Affect;African American;African American population;African ancestry;Age of Onset;American;Biological;Biopsy;black men;Cancer Biology;cancer diagnosis;cancer health disparity;cancer heterogeneity;Castrate sensitive prostate cancer;cell growth;Cell Line;Cell model;cell type;Cells;Clinical;cohort;Communities;CRISPR/Cas technology;Data;Death Rate;Diagnosis;Diagnostic;Disease;Disparity;Dissection;DNA Sequence Alteration;Epithelial Cells;Epithelium;ETV3 gene;European;European ancestry;Exhibits;Frequencies;Future;Genes;genetic information;Genome;genome sequencing;health care availability;Healthcare Systems;Heterogeneity;high risk;Hormones;Immune;Immune system;Immunologics;Immunotherapy;improved;Incidence;Individual;innovative technologies;insight;Invaded;Knowledge;Link;Malignant neoplasm of prostate;Malignant Neoplasms;Measures;Medical center;men;Meta-Analysis;military veteran;Modeling;Molecular;mortality;mortality risk;Mutation;novel;novel marker;Oncogenes;Oncogenic;Open Reading Frames;Organoids;Outcome;participant enrollment;Pathway interactions;Patients;Population;Prostate;prostate cancer risk;Prostatectomy;Prostatic Neoplasms;PTEN gene;racial population;Radical Prostatectomy;recruit;Research;Resources;Role;San Francisco;single-cell RNA sequencing;Socioeconomic Status;socioeconomics;Specimen;System;targeted treatment;Testing;Therapeutic;Therapeutic Trials;therapy resistant;Tissues;TMPRSS2 gene;transcriptome;transcriptomics;tumor;tumor-immune system interactions;United States;United States Department of Veterans Affairs;Veterans;Veterans Health Administration;whole genome;ZFHX3 gene

PROJECT_TITLE: Investigating the mechanisms of aggressive prostate cancer in African American Veterans


ORG_CITY: OMAHA

ORG_NAME: OMAHA VA  MEDICAL CENTER

PHR: Although Colorectal Cancer (CRC) endangers males and females of all the population, Veterans show a higher incidence rate of colon cancer than the general population. It is estimated that each year the Veterans Affairs manages and treats ~175,000 CRC patients. It is therefore an urgent necessity to find novel early detection and therapeutic strategies to curb CRC-malignancy to increase the survival and quality of life for Veterans diagnosed with this disease. Identifying markers that are highly specific to the premalignant/malignant precursor lesions and the metastatic CRC to develop novel early detection and therapeutic approaches would not only decrease patient mortality among VA-CRC patients but will also help reduce associated financial burden for the Veterans Administration. We hypothesize that CLDN-1 can serve as a powerful adjunct for imaging SSA/P polyps and resection of metastasis.

PI_NAMEs: BOUVET, MICHAEL ;DHAWAN, PUNITA  (contact)

PROJECT_TERMS: Adenocarcinoma;adenoma;Adjuvant;American;Antibodies;antibody conjugate;Biodistribution;Biology;biomarker identification;cancer invasiveness;cancer recurrence;cancer surgery;cancer therapy;claudin-1 protein;Clinical;clinical efficacy;Colon;colon cancer cell line;colon cancer patients;colon cancer progression;colon cancer screening;Colon Carcinoma;Colonic Adenoma;Colonic Neoplasms;Colonoscopy;Colorectal Cancer;colorectal cancer metastasis;colorectal cancer progression;colorectal cancer risk;colorectal cancer screening;Consensus;Detection;detection sensitivity;Development;Diagnosis;Diagnostic Neoplasm Staging;Disease;Disease Progression;Distant;Drug Kinetics;Dyes;Early Diagnosis;efficacy evaluation;Endoscopy;Evaluation;ex vivo imaging;Excision;Exhibits;Female;Financial Hardship;Fluorescence;fluorescence imaging;fluorescence-guided surgery;Fluorescent Probes;fluorophore;Frequencies;General Population;Goals;high risk;Image;image guided;Image-Guided Surgery;imaging probe;Imaging technology;improved;In Vitro;in vivo;Incidence;KRASG12D;Label;Laboratories;Laparoscopy;Lesion;male;Malignant - descriptor;Malignant Neoplasms;metastatic colorectal;Metastatic Neoplasm to the Liver;Modality;Modeling;mortality;mouse model;Mus;Neoplasm Metastasis;novel;Operative Surgical Procedures;Outcome;Patient imaging;Patient-Focused Outcomes;Patients;Peptides;Phase I Clinical Trials;Polypectomy;Polyps;Population;pre-clinical assessment;preclinical efficacy;preclinical safety;preclinical study;premalignant;Process;Productivity;Proteins;Quality of life;Recurrence;Reporting;Research;Risk Reduction;Role;Sampling;screening;Sensitivity and Specificity;Signal Transduction;Societies;subcutaneous;success;Surgical margins;targeted imaging;Therapeutic;Tight Junctions;Time;Tissues;tool;Toxic effect;tumor;Tumor Tissue;United States Department of Veterans Affairs;Veterans;Visualization;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Novel Tools for Colon Cancer Detection and Therapy


ORG_CITY: BALTIMORE

ORG_NAME: BALTIMORE VA MEDICAL CENTER

ORG_STATE: MD

PHR: New approaches to suicide prevention are much needed in US Veterans, given their persistent increased suicide risk relative to demographically matched general population. Increasing evidence links suicide with persistent inflammation, oxidative stress and endothelial dysfunction. These physio-pathological processes are ameliorated by statins , independent of their known metabolic and cardiovascular benefits. Add on statins have been reported to be beneficial in mental illness (depression, schizophrenia, cognitive disorders) and for common immune-mediated conditions (IMCs) - infections, allergies, and autoimmune disease – and traumatic brain injury (TBI) . These upregulate inflammation, and have been predictively associated with suicidal behavior. Our three aims are to examine: 1) if IMCs and TBI interact synergistically in elevating suicide risk, 2) if persistent statin treatment reduces the hazard of suicide and 3) what are the characteristics of the Veterans who would benefit the most from statin add-on treatment to ameliorate their suicide risk.

PI_NAMEs: POSTOLACHE, TEODOR T (contact)

PROJECT_TERMS: Age;attenuation;Autoimmune;Autoimmune Diseases;Bipolar Disorder;Blood;Brain;Cardiovascular system;Categories;Cells;Characteristics;Clinical;clinical encounter;Code;Cognition Disorders;comorbidity;Computerized Medical Record;Cox Proportional Hazards Models;Data;design;Development;Diagnosis;Diagnostic;disability;Disease susceptibility;Dose;drug repurposing;Encephalitis;endothelial dysfunction;Epidemic;Epidemiology;Equation;Evaluation;evidence base;excitotoxicity;Future;Gender;General Population;hazard;Hematology;High Prevalence;Histologic;Hypersensitivity;Immune;immune activation;immunoregulation;Impairment;improved;indexing;Individual;Infection;Inflammation;inflammatory marker;inpatient psychiatric treatment;Intervention;Laboratory Markers;LDL Cholesterol Lipoproteins;Link;Machine Learning;machine learning algorithm;Measures;Mediating;Mediation;Medical;Medical center;member;Mental Depression;Mental disorders;Mental Health;Metabolic;Methodology;Microglia;Modeling;Modification;Molecular;neuroinflammation;neuroprotection;novel;novel strategies;Outcome;Oxidative Stress;Pharmaceutical Preparations;Pharmacodynamics;pharmacologic;physical conditioning;Post-Traumatic Stress Disorders;Prevention;Process;protective effect;Proxy;psychologic;Randomized;randomized, clinical trials;Recording of previous events;Regimen;Relative Risks;Reporting;Reproducibility;Research;Research Project Grants;resilience;Retrospective cohort;Risk;Risk Factors;Risk Management;Schizophrenia;Self Direction;Severities;suicidal;suicidal behavior;suicidal morbidity;suicidal risk;Suicide;Suicide attempt;Suicide prevention;suicide rate;synergism;Testing;Therapeutic;Time;trait;Traumatic Brain Injury;treatment duration;United States;Veterans;Veterans Health Administration;Violence;Vitamin D Deficiency

PROJECT_TITLE: Suicide risk modification by statin prescriptions in US Veterans with common inflammation-mediated clinical conditions- a controlled, quasi-randomized epidemiological approach


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Biotechnology;Breastfeeding, Lactation and Breast Milk;Digestive Diseases;Immunization;Microbiome;Nutrition;Pediatric;Prevention;Women's Health Research

ORG_CITY: SEATTLE

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF WASHINGTON

PHR: Project Narrative Breast feeding is associated with intestinal health, but the specific components of breast milk and the mechanisms underlying these associations are not fully understood. Building from our novel discovery that offspring fed with antibody deficient breast milk generate dysregulated intestinal immune responses, I propose to understand the consequences of these dysregulated responses as they relate to host-microbe mutualism. The resulting data may help advance the development of treatments or therapeutics aimed at promoting beneficial host-microbiome interactions in early life, particularly in children who are not breastfed.

PI_NAMEs: PECHA, BINGJIE BETH (contact)

PROGRAM_OFFICER_NAME: RUSSO, DENISE

PROJECT_TERMS: Activities of Daily Living;adaptive immune response;Advanced Development;Affinity;Antibodies;Antigens;B-Cell Activation;B-Lymphocytes;Bacteria;Biological Models;Birth;Breast Feeding;Cell Communication;Cells;Child;Colitis;colonization resistance;commensal microbes;Coupled;cytokine;Data;Development;Digestion;Disease;Elements;Enteral;Estrogen Receptors;Flow Cytometry;Fostering;Genetic;Germ-Free;Growth Factor;gut bacteria;gut microbes;gut microbiota;Health;Helper-Inducer T-Lymphocyte;Homeostasis;host microbiome;host microbiota;Human Milk;humoral immunity deficiency;Immune;Immune response;Immune system;Immunity;immunoregulation;Impairment;inducible Cre;Infant;Inflammation;insight;Intestinal Diseases;intestinal homeostasis;Intestines;Knock-out;Label;Lactation;Life;Link;Location;Lymphoid Tissue;Maternal antibody;Mediating;Memory B-Lymphocyte;mesenteric lymph node;Metabolic;Metabolic Diseases;Methods;Microbe;microbial colonization;microbiota;microbiota composition;mouse model;Mucosal Immunity;Mucous Membrane;Mus;mutualism;Neonatal;neonate;novel;Nutrient;offspring;Outcome;pathogenic bacteria;Phenotype;Physiology;Plasma;Predisposition;Process;pup;response;Risk;Salmonella typhimurium;Shapes;Structure;Structure of germinal center of lymph node;System;T-Lymphocyte;Testing;Therapeutic;therapy design;therapy development;Tissues;Variant;Weaning;Wild Type Mouse;Work

PROJECT_TITLE: Effects of breast milk antibodies on neonatal intestinal immunity and host-microbe mutualism


NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

PI_NAMEs: SUNDQUIST, WESLEY I. (contact)

PROGRAM_OFFICER_NAME: NOVAK, LEIA KAYE

PROJECT_TERMS: Address;Affinity;AMOT gene;analog;ATP phosphohydrolase;Binding;Binding Proteins;Binding Sites;Biochemical;Biochemistry;Biogenesis;Biological Assay;Cells;Collaborations;Complex;constriction;Cryoelectron Microscopy;Deposition;design;Diameter;Endosomes;Excision;F-Actin;Family;Family member;Filament;Funding;gag Gene Products;Genetic;genetic analysis;Goals;HIV;HIV Budding;HIV-1;Homo;Homologous Gene;Human;Image;Impairment;in vitro testing;Infection;inhibitor;Innate Immune System;Instruction;Integration Host Factors;Mammals;Mediating;member;Membrane;membrane assembly;membrane model;Modeling;Molecular;monomer;Neck;pathogen;Pathway interactions;Process;Progress Reports;protein function;Proteins;Reaction;reconstitution;recruit;Reporting;Research;Resolution;Retrotransposition;Site;Sorting;Structure;System;targeted treatment;Testing;Therapeutic Intervention;Toxic effect;Ubiquitin;ubiquitin-protein ligase;Variant;Viral;Virion;Virus;virus envelope;Work

PROJECT_TITLE: Biochemistry of HIV-1 Budding

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Diabetes;Microbiome;Nutrition;Obesity;Physical Activity;Prevention

ORG_CITY: BOSTON

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

ORG_STATE: MA

PHR: PROJECT NARRATIVE This grant builds upon a large ongoing randomized clinical trial (PREDIMED-Plus) to examine the effects of an intensive lifestyle intervention consisting of an energy-reduced Mediterranean diet, increased physical activity and weight loss on changes in body composition, plasma and stool metabolites, and risk of type 2 diabetes. It will also evaluate whether the benefits of the lifestyle intervention on diabetes risk differ by individuals’ metabolic profile. The findings may enhance our understanding of the metabolic pathways through which lifestyle interventions reduce diabetes risk including changes in metabolites and gut microbiome and inform the development of more effective personalized nutrition and lifestyle interventions for the prevention of diabetes.

PI_NAMEs: HU, FRANK B (contact);RUIZ-CANELA, MIGUEL ;SALAS SALVADO, JORDI

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Accelerometer;Adipose tissue;aged;Ancillary Study;Attenuated;Behavioral;Bioinformatics;Body Composition;Body Weight;Body Weight decreased;Cardiovascular system;Chronic Disease;comparison control;Consumption;Control Groups;Development;Diabetes prevention;diabetes prevention program;diabetes risk;Diet;dietary;Dietary Intervention;disorder prevention;Dual-Energy X-Ray Absorptiometry;Fatty acid glycerol esters;Feces;fitness;follow-up;Functional disorder;Glycosylated hemoglobin A;Grant;group intervention;gut microbiome;healthy lifestyle;improved;Incidence;Individual;Intervention;intervention effect;Life Style;lifestyle intervention;Measures;Mediating;Mediterranean Diet;men;Metabolic Pathway;metabolic profile;microbiome;multi-ethnic;Nested Case-Control Study;non-diabetic;Non-Insulin-Dependent Diabetes Mellitus;Olive oil preparation;Participant;personalized intervention;Physical activity;Physical Fitness;Placebos;Plasma;Population;precision nutrition;Prevention;Prevention trial;prospective;Random Allocation;randomized, clinical trials;Recommendation;recruit;Risk;secondary endpoint;Statistical Methods;stool sample;Testing;tyrosol;urinary;Visceral;Woman

PROJECT_TITLE: Lifestyle Interventions, metabolites, microbiome, and diabetes risk

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-F(02)]


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Dental, Oral, and Craniofacial Disease;Infectious Diseases;Nanotechnology;Natural Products;Regenerative Medicine

ORG_CITY: PORTLAND

ORG_DEPT: DENTISTRY

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: NARRATIVE  Collagen degradation mediated by proteolytic endogenous enzymes is strongly associated with the progression of periodontal disease and the breakdown of the dental substrate/restorative material interface, which together are the cause for almost 80% of the tooth extractions in the United States. This project aims to develop two independent cutting- edge platforms based on polyphenols sequestered in enzyme-responsive nanomicelles and nanobodies immune proteins, in order to modulate metalloproteinases (MMPs) -2, -8, and -9 activity in periodontal pockets and at dentin-adhesive interfaces and, ultimately, prevent/cease undesirable dental tissues. It is expected that this proposal leads to the development of biologically-responsive and immunomodulatory-based dental biomaterials capable of suppressing the collagen enzymatic degradation activity in different therapeutic niches while addressing the NIDCR priorities to develop interdisciplinary, unique, and innovative approaches to promote oral health.

PI_NAMEs: PIOVEZAN FUGOLIN, ANA PAULA  (contact)

PROGRAM_OFFICER_NAME: LOPEZ, ORLANDO

PROJECT_TERMS: Address;Adhesives;alveolar bone;Amino Acid Sequence;Animal Model;Antibodies;Bacteria;Binding;Biochemistry;Biocompatible Materials;Biodegradation;Biology;Biotechnology;Chemicals;Clinical;clinical care;Collagen;collagenase;Complex;cytokine;delivery vehicle;Dental;dental adhesive;Dental caries;Dental Restoration Failure;dental structure;Dentin;Dentistry;design;design verification;Development;Diffusion;Disease;Drug Delivery Systems;efficacy evaluation;Employment;Encapsulated;Enzyme Inhibition;Enzyme Inhibitor Drugs;Enzymes;Epigallocatechin Gallate;experimental study;Extracellular Matrix;forging;Formulation;functional group;Gel;Gelatinases;Generations;Goals;Heart Diseases;Human body;Hydrogels;Immune;Immunology;immunoregulation;improved;Infiltration;inhibitor;innovation;Llama;Maintenance;Malignant Neoplasms;materials science;Matrix Metalloproteinases;Mediating;Medical;Medicine;Metalloproteases;metastatic colorectal;Micelles;microbial;Morphogenesis;Mucous Membrane;multidisciplinary;nanobodies;nanomicelles;nanomolar;nanoparticle;National Institute of Dental and Craniofacial Research;oral condition;Oral health;oral tissue;Organ;particle;Pathogenicity;Pathologic;Pathway interactions;Patient Care;Peptide Hydrolases;Peptides;Periodontal Diseases;Periodontal Pocket;Periodontitis;Pharmaceutical Preparations;Physiological;Play;Polymers;polyphenol;preservation;prevent;Procedures;Process;Proteins;Public Health;Quercetin;Recurrence;repaired;Research;Research Personnel;restorative material;Role;Rupture;screening;Sepsis;skills;Specificity;stem;System;Techniques;Technology;Therapeutic;Therapeutic Agents;Time;Tissue Engineering;Tissue Preservation;tissue regeneration;Tissues;tool;Tooth Extraction;Tooth Loss;Tooth structure;Translating;Translations;treatment strategy;tumor;United States;Vulnerable Populations;Water

PROJECT_TITLE: Bio-Responsive and Immune Protein-Based Therapies for Inhibition of Proteolytic Enzymes in Dental Tissues


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Colorectal Cancer;Complementary and Integrative Health;Digestive Diseases;Health Disparities and Racial or Ethnic Minority Health Research;Microbiome;Nutrition;Obesity;Prevention;Racial and Ethnic Minority Health Research

ORG_CITY: Chicago

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: PROJECT NARRATIVE African Americans (AAs) have the highest colorectal cancer (CRC) incidence and mortality that we hypothesize can be attributed to their higher prevalence of obesity, intake of low fiber, high animal protein and saturated fat diets and a higher abundance of gut bacteria known to metabolize bile acids to metabolites that are genotoxic and tumor promoting. Obesity and diet determine the extent to which bile acid metabolism is a risk factor for CRC. This proposal will determine if the largely plant-based Mediterranean Diet alone, weight loss alone or the two interventions combined can affect the bile acid-gut microbiome axis ultimately revealing critical information on how weight loss and diet can address CRC risk in AAs, but also in other high-risk populations.

PI_NAMEs: FITZGIBBON, MARIAN L. (contact);TUSSING-HUMPHREYS, LISA

PROGRAM_OFFICER_NAME: KIM, YOUNG S

PROJECT_TERMS: Acids;Address;Adherence;Adult;Affect;African;African American population;Amino Acids;Animals;anti-cancer;Antineoplastic Agents;arm;Bacteria;bile acid metabolism;Bile Acids;Bilophila wadsworthia;Biometry;Body Weight decreased;Butyrates;Caloric Restriction;Calories;cancer health disparity;carcinogenesis;Cell Proliferation;Cells;Cellular biology;Clinical Research;Clostridium;Colon;colon bacteria;Colorectal Cancer;colorectal cancer prevention;colorectal cancer risk;Computational Biology;Controlled Study;Coupled;Data;Deoxycholic Acid;Development;Diet;Dietary Factors;Dietary Fiber;Dietary Practices;dietary restriction;Disparity;DNA Repair;Epithelial Cells;evidence base;Exhibits;Fiber;Fostering;Gene Expression;Gene Expression Profile;Genes;Genomic Instability;genotoxicity;Glycine;Growth;gut bacteria;gut microbes;gut microbiome;gut microbiota;High Prevalence;high risk population;Human;Hydrogen Sulfide;Incidence;Inflammation;innovation;Intake;Intervention;intervention effect;intestinal epithelium;Intestines;lifestyle intervention;Link;Mediating;Medical;Medicine;Mediterranean Diet;Metabolic;Metabolism;microbial;microbial composition;Microbiology;microbiota composition;modifiable risk;Molecular;mortality;Mucositis;multidisciplinary;Not Hispanic or Latino;nutrition;Obesity;Observational Study;Pathway interactions;Pattern;personalized approach;Persons;Physiology;Plants;post intervention;Primates;Production;Proliferating;Proteins;Psychology;Public Health;Race;Randomized;response;Risk Factors;Risk Reduction;Sampling;saturated fat;Structure;Subgroup;Taurine;Testing;Translating;Tumor Promoters;Tumor Promotion;Weight;Weight maintenance regimen

PROJECT_TITLE: Mediterranean Diet and Weight Loss: Targeting the Bile Acid/Gut Microbiome Axis to Reduce Colorectal Cancer Risk

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


NIH_SPENDING_CATS: Aging;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Health Services;Patient Safety;Prevention;Women's Health Research

ORG_CITY: ANN ARBOR

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Treatment of premenopausal women at high risk of breast cancer recurrence with endocrine therapy plus ovarian suppression decreases breast cancer recurrence. However, a high proportion of patients discontinue treatment early, primarily because of aggravating symptoms. Identifying an effective approach that improves persistence with therapy and reduces development of bothersome toxicity has the potential to improve disease outcomes while maintaining quality of life for young women with breast cancer.

PI_NAMEs: HENRY, NORAH LYNN (contact)

PROGRAM_OFFICER_NAME: MITCHELL, SANDRA A

PROJECT_TERMS: Ablation;Address;Adherence;adjuvant endocrine therapy;Advanced Malignant Neoplasm;Adverse event;Belief;Breast Cancer Risk Factor;breast cancer survival;Breast Cancer survivor;cancer recurrence;Cancer Research Network;cancer therapy;Central America;Client satisfaction;Clinic Visits;cohort;Community Clinical Oncology Program;cost effective;Data;Development;Disease;Disease Outcome;Disease-Free Survival;Drug Prescriptions;Early identification;Early treatment;Educational Intervention;Effectiveness;effectiveness evaluation;Electronics;Enrollment;experience;Frequencies;Funding;Future;Goals;group intervention;Gynecologic;Health;health related quality of life;high risk;High Risk Woman;hormone receptor-positive;hormone therapy;improved;improved outcome;Internet;Intervention Studies;Knowledge;Latin America;Malignant Breast Neoplasm;Malignant Neoplasms;Menopausal Symptom;Methodology;Monitor;mortality;multi-ethnic;Musculoskeletal;Musculoskeletal Pain;Newly Diagnosed;oncology program;Online Systems;Outcome Assessment;Ovarian;Ovarian Ablation;pain symptom;Patient Education;Patient Outcomes Assessments;patient-clinician communication;Patients;Pharmaceutical Preparations;Population;premature;Premenopause;programs;psychological symptom;Quality of life;Questionnaires;Randomized;randomized trial;Reporting;Research;Resources;Risk;risk prediction model;Self Efficacy;Series;Severities;Site;South America;Southwest Oncology Group;Spanish/English;Symptom Burden;symptom management;symptomatic improvement;Symptoms;Tamoxifen;Toxic effect;treatment optimization;Treatment-related toxicity;United States;Vasomotor;web-based tool;Woman;young woman

PROJECT_TITLE: Active Symptom Monitoring and Endocrine Therapy Persistence in Young Women with Breast  Cancer

STUDY_SECTION: ICSC

STUDY_SECTION_NAME: Interdisciplinary Clinical Care in Specialty Care Settings Study Section[ICSC]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Bioengineering;Nanotechnology;Obesity

ORG_CITY: CHAMPAIGN

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

PHR: NARRATIVE Classification of cells within human tissues is essential for understanding states of health and disease. In this proposal, we will develop a new class of fluorescent label that increases the number of molecular classification markers for cells by an order of magnitude. These labels function within intact, three-dimensional tissue, an attribute that we will use to map the local environments of adipose tissue immune cells that are thought to determine comorbid outcomes of obesity.

PI_NAMEs: SMITH, ANDREW MICHAEL (contact)

PROGRAM_OFFICER_NAME: ATANASIJEVIC, TATJANA

PROJECT_TERMS: 3-Dimensional;Address;Adipose tissue;Animal Model;Applications Grants;Binding;Biological;Biological Sciences;Biomedical Engineering;biomedical imaging;Biophysics;Categories;cell dimension;cell type;Cells;Cellular Immunology;Characteristics;Chemicals;Classification;Code;Color;comorbidity;Computer software;Cytometry;Cytoplasm;deep learning algorithm;design;Dimensions;Disease;Disparity;Dyes;Electronics;Engineering;Environment;Exhibits;Flow Cytometry;Fluorescence;fluorescence imaging;Fluorescent Probes;fluorophore;Goals;Health;Heart Diseases;high dimensionality;human tissue;Image;Immune;Immunoglobulin Fragments;Immunophenotyping;improved;In Situ;Individual;insight;Label;Light;Location;Maps;Measurement;Measures;Membrane;Methods;Microscope;Microscopy;Molecular;molecular marker;Molecular Probes;nanocrystal;Nature;Non-Insulin-Dependent Diabetes Mellitus;Nucleic Acids;Obesity;optical imaging;Optics;Outcome;Pattern;Property;Proteins;Proteomics;Quantum Dots;Research Personnel;Research Project Grants;Resolution;Rodent Model;Scientist;Semiconductors;Signal Transduction;Specificity;Stains;Technology;technology platform;Testing;Thick;Thinness;Time;Tissue imaging;Tissues;tool;tumor-immune system interactions;Validation;Work

PROJECT_TITLE: Hyperplexed Quantum Dots for Multidimensional Cell Classification in Intact Tissue

STUDY_SECTION: EBIT

STUDY_SECTION_NAME: Enabling Bioanalytical and Imaging Technologies Study Section[EBIT]


FUNDING_MECHANISM: OTHERS

PHR: Suicide prevention is VA’s highest clinical priority, and, yet, little is known about causal factors and mechanisms for suicide; and, thus, little progress on salient interventions reducing risk of suicide. The proposed CDA-1 will provide necessary and relevant knowledge on causal factors associated with suicide risk in mid-to-late-life Veterans—a subpopulation that encompasses the greatest number of Veteran lives lost to suicide. This project will leverage an existing cohort of 5 million Veterans 50 years and older with multiple linked national large-scale datasets, including national suicide data. The current longitudinal cohort includes ~12,000 suicide deaths and over 20,000 nonfatal suicide attempts. The CDA-1 proposal is directly aligned with VA’s mandate to prioritize research that helps to develop targeted suicide interventions by finding out why certain Veterans are at risk of suicide and eliciting expert knowledge to improve upon the clinical utility of such information; ultimately, advancing the current landscape of VA’s suicide prevention and intervention programs.

PI_NAMEs: RUDERMAN, MICHAEL ALAN (contact)

PROJECT_TERMS: aged;Award;career;Clinical;Clinical Research;Clinical Trials;cohort;Complex;Computational Technique;Computer Analysis;cost;Data;Data Analyses;Data Linkages;Data Set;demographics;design;effective intervention;empowerment;Ensure;Ethics;Etiology;Focus Groups;Frequencies;Goals;improved;innovation;Inpatients;insight;Intention;Intervention;intervention program;Intervention Trial;Investigational Therapies;K-Series Research Career Programs;Knowledge;large scale data;large-scale database;late life;lens;Link;Longitudinal cohort;longitudinal dataset;machine learning prediction;Mentors;Methods;military veteran;Modeling;Morbidity - disease rate;National Institute of Mental Health;Occupations;Outcome;Outpatients;Patients;Pattern;Pharmaceutical Preparations;Phase;Positioning Attribute;Post-Traumatic Stress Disorders;Predictive Analytics;Prevention program;Prevention strategy;Prognostic Factor;programs;Protocols documentation;Provider;Psychiatrist;reducing suicide;Research;Research Methodology;Research Personnel;Research Priority;Research Project Grants;Risk Reduction;Role;Scientist;screening;suicidal morbidity;suicidal risk;Suicide;Suicide attempt;Suicide prevention;Techniques;Testing;Training;Training Activity;Veterans;Vulnerable Populations

PROJECT_TITLE: Approximating Mechanisms of Suicide Risk to Innovate Interventions for Mid-to-Late-Life Veterans


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Clinical Research;Contraception/Reproduction;Genetics;Heart Disease;Human Genome;Hypertension;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Precision Medicine;Pregnancy;Prevention;Women's Health Research

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Preeclampsia is a severe disorder that affects 5% of all pregnancies and is characterized by elevated blood pressure and increased urinary protein; treatment options remain limited. Here, we propose to leverage a large multi-ethnic study with genomic and intermediate molecular phenotypes (metabolites and circulating microparticle transcripts and proteins) to identify maternal and fetal determinants of preeclampsia and causal biologic pathways altered in pregnancy. Since preeclampsia is a leading cause of maternal mortality and preterm birth worldwide, and increases women’s future cardiometabolic disease risk 2-4-fold, improved preventative and therapeutic interventions based on underlying mechanisms have a great potential to positively impact public health.

PI_NAMEs: SAXENA, RICHA  (contact)

PROGRAM_OFFICER_NAME: YAN, YE

PROJECT_TERMS: Address;adverse pregnancy outcome;Affect;Age of Onset;antenatal;Award;Biological;Blood;blood pressure elevation;Boston;Cardiometabolic Disease;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;case control;Clinical;clinical care;clinical phenotype;Cluster Analysis;cohort;Cohort Studies;Collection;Colombia;Colombian;Data;Development;Discipline of obstetrics;Disease;disease heterogeneity;disorder risk;Etiology;Exclusion;fetal;Fetal Growth;Functional disorder;Funding;Future;gene discovery;Genes;Genetic;Genetic Risk;genetic risk factor;genetic variant;Genome;genome sequencing;genome wide association study;Genomics;Gestational Age;Grant;Heritability;Histopathology;Human Genetics;Hypertension;improved;Individual;insight;interest;Laboratory Study;lifetime risk;Link;maternal morbidity;Maternal Mortality;Mediating;Metabolic;metabolomics;Molecular;molecular phenotype;Molecular Profiling;molecular subtypes;mortality;multi-ethnic;multidisciplinary;multiple omics;Myocardial Ischemia;National Heart, Lung, and Blood Institute;neonatal morbidity;novel;Onset of illness;Outcome Study;particle;pathophysiology of preeclampsia;Pathway interactions;Patients;personalized approach;Phenotype;Placenta;Plasma;polygenic risk score;Pre-Eclampsia;precision medicine;Predisposition;Pregnancy;Pregnancy Trimesters;Premature Birth;prevent;Prevention approach;preventive intervention;Proteins;Proteinuria;Proteomics;Public Health;Publishing;Quantitative Trait Loci;rare variant;Risk;Risk Factors;risk variant;Sample Size;Sampling;severe maternal morbidity;Severities;Stroke;Subgroup;Symptoms;Testing;Therapeutic;Therapeutic Intervention;Trans-Omics for Precision Medicine;Transcript;transcriptomics;United States National Institutes of Health;urinary;Variant;whole genome;Woman;Women's Health

PROJECT_TITLE: Integrative omics of preeclampsia in TOPMED and maternal cardiovascular health

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-N(90)]


NIH_SPENDING_CATS: Autoimmune Disease;Behavioral and Social Science;Bioengineering;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Diabetes;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Pediatric;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

ORG_STATE: NY

PHR: PROJECT NARRATIVE This project proposes to adapt the community health worker model to encourage and support use of advanced diabetes technologies in young adults from underrepresented minority groups (YA-URMs) with type 1 diabetes (T1D). Community health workers are a cost-effective intervention that enhance team-based care by leveraging their unique position between communities and health systems to advocate for underserved patients and provide extra support for providers. This proposal is the natural next step to testing a model of T1D care aimed at root causes of disparities to reduce inequity in care delivery and outcomes.

PI_NAMEs: AGARWAL, SHIVANI  (contact)

PROGRAM_OFFICER_NAME: THORNTON, PAMELA L

PROJECT_TERMS: Accounting;Address;Adoption;Advocate;Affect;aged;base;Black race;care delivery;care outcomes;Caring;Clinical;clinical practice;Clinical Trials;Communities;Community Health Aides;Community Healthcare;Competence;Continuous Glucose Monitor;cost;cost effective;cost effective intervention;Costs and Benefits;Data;Diabetes Mellitus;Diabetic Ketoacidosis;Disease;Disparity;Distal;Educational Technology;effective intervention;emerging adult;Endocrinologist;Endocrinology;ethnic disparity;Evaluation;evidence base;experience;flexibility;Foundations;Future;Glycosylated hemoglobin A;Goals;Health;Health Benefit;health inequalities;Health Personnel;Health system;Healthcare;Hearing;high risk;Hispanic;Hospitalization;Hospitals;implementation outcomes;implementation science;improved;Inequity;Insulin Infusion Systems;Insulin-Dependent Diabetes Mellitus;Insurance;Insurance Coverage;Intervention;Knowledge;Link;Lived experience;Measures;Mediator;member;Methods;Minority Groups;Mission;Modeling;mortality;mortality risk;National Institute of Diabetes and Digestive and Kidney Diseases;next generation;Outcome;outreach;patient oriented;patient-level barriers;Patients;peer support;Population;Positioning Attribute;pragmatic trial;Primary Care;primary care practice;primary care provider;Proctor framework;programs;Provider;provider-level barriers;Race;racial disparity;Randomized;Randomized, Controlled Trials;recruit;Reporting;Research;Resources;response;Risk;safety net;Self Determination;shared decision making;social;Social support;Socioeconomic Status;standard of care;System;system-level barriers;team-based care;Technology;Testing;theories;Time;treatment as usual;Trust;Underrepresented Minority;underserved community;Underserved Population;United States;uptake;Work;young adult

PROJECT_TITLE: T1DTechCHW: Enhancing the Community Health Worker (CHW) Model to Promote Diabetes Technology Use in Young Adults from Underrepresented Minority Groups (YA-URMs) with Type 1 Diabetes (T1D)


NIH_SPENDING_CATS: Brain Disorders;Epilepsy;Genetics;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: AUSTIN

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

ORG_STATE: TX

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it seeks to understand how genetic mutations cause brain cell hyperexcitability and change the way these cells process information and learn, leading to seizures, developmental delays, and cognitive impairments. Our research will define how deficits in neuron excitability and synaptic communication interact to alter plasticity in a transgenic mouse model of Generalized Epilepsy with Febrile Seizures Plus and Dravet syndrome, severe childhood epilepsy disorders. Our work aligns with the mission of the NINDS because we seek to uncover causes of neurodevelopmental disease, discover avenues for therapy development, and ease the burden of this disorder on patients, their families, and society.

PI_NAMEs: HOWARD, MACKENZIE A (contact)

PROGRAM_OFFICER_NAME: MATOS GALICIA, HEIDI YANICE

PROJECT_TERMS: Action Potentials;brain cell;Brain region;Cell Physiology;Cells;Cellular Morphology;Cessation of life;Childhood;childhood epilepsy;Cognitive;Cognitive deficits;Communication;Complex;Data;Dendrites;Developmental Delay Disorders;Disease;Distal;DNA Sequence Alteration;dravet syndrome;Epilepsy;Exhibits;experimental study;Family;Febrile Convulsions;Foundations;Functional disorder;gamma-Aminobutyric Acid;Generalized Epilepsy;Genes;Genetic;Goals;hippocampal pyramidal neuron;Immunohistochemistry;Impaired cognition;Impairment;information processing;Interruption;Intractable Epilepsy;Ion Channel;Knock-out;Knockout Mice;Learning;Link;Measures;Medical;Memory;Memory impairment;Mission;Morphology;mouse model;Mutation;National Institute of Neurological Disorders and Stroke;neural;neural circuit;neural information processing;Neurodevelopmental Disorder;neuronal excitability;Neurons;neurophysiology;neuropsychiatry;Outcome;Output;Patients;Pattern;Phenocopy;Phenotype;Physiological;Physiology;Process;Property;Proteins;Public Health;Research;response;Seizures;Shapes;Societies;Somatic Cell;Source;Stimulus;Structure;Synapses;Synaptic plasticity;Testing;therapy development;trafficking;Transgenic Mice;Translations;voltage;Whole-Cell Recordings;Work

PROJECT_TITLE: Mechanisms of altered synaptic integration and plasticity underlying cellular and circuit dysfunction in genetic epilepsy disorders

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences;Physical Injury - Accidents and Adverse Effects;Physical Rehabilitation;Rehabilitation;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: STANFORD

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: STANFORD UNIVERSITY

PHR: Narrative Spinal injury that involves the cervical cord can severely impair hand function in humans and result in loss of independence. We use clinically relevant models of spinal injury in the monkey and rat to study central neural mechanisms responsible for the recovery of hand function. Our findings will provide novel insight into the neuronal reorganization that takes place post-injury, which is needed if patients with spinal injuries are to be treated more effectively.

PI_NAMEs: DARIAN-SMITH, CORINNA  (contact)

PROGRAM_OFFICER_NAME: DOPERALSKI, ADELE ELIZABETH

PROJECT_TERMS: Address;Afferent Neurons;Anatomy;Animals;Behavior;Behavioral;behavioral response;Bilateral;Brain;Brain Stem;Central Nervous System;Cervical;Chronic;Clinical;clinically relevant;Compensation;confocal imaging;Confocal Microscopy;Corticospinal Tracts;Data;Deafferentation procedure;Development;Digit structure;effective therapy;Electron Microscopy;Electrophysiology (science);Esthesia;Evoked Potentials;experimental study;Fingers;Future;Genetic Complementation Test;Goals;Grant;Hand;hand dysfunction;Hand functions;hand rehabilitation;Human;Hypersensitivity skin testing;Impairment;improved;indexing;Individual;Injury;insight;Intervention;Lesion;Macaca;Maps;Measures;Mediating;Modeling;Monkeys;Motivation;Motor;Motor Pathways;Nerve;Nerve Fibers;nerve supply;Neural Conduction;Neuroanatomy;neuromechanism;neuronal circuitry;Neurons;nonhuman primate;novel;Pathway interactions;Patients;Peripheral;Peripheral Nerves;Peripheral Nervous System;Persons;Population;Primates;Process;Rattus;receptor;Recovery;Recovery of Function;Reproducibility;Research;Resolution;response;Rodent;Role;Sensory;sensory input;Shapes;Skin;Societies;somatosensory;Specificity;Spinal Cord;Spinal cord injury;Spinal cord injury patients;Spinal Injuries;Statistical Models;Synapses;System;Techniques;therapy development;Thumb structure;Time;Tracer;treatment optimization;Work

PROJECT_TITLE: Neuronal and behavioral responses to spinal cord injury

STUDY_SECTION: MFSR

STUDY_SECTION_NAME: Motor Function, Speech and Rehabilitation Study Section[MFSR]


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

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because it focuses on identifying a novel pathway that regulates CD8+ T cells, which are critical immune cells that provide protection and long-term immunity against viral infections. This proposal will define how maintenance of appropriate protein quality control regulates CD8+ T cells at homeostasis and following viral infection. An understanding of pathways that regulate CD8+ T cell immunity will provide mechanistic insights to guide design of therapeutic strategies to enhance protective T cell responses, such as following infectious diseases or vaccination.

PI_NAMEs: CARTY, SHANNON A. (contact)

PROGRAM_OFFICER_NAME: MALLIA, CONRAD M

PROJECT_TERMS: Acute;Antigens;Apoptotic;Area;arm;Biochemical Pathway;CD8-Positive T-Lymphocytes;Cell Death;Cell Survival;Cells;Cessation of life;Chronic;Communicable Diseases;Complex;Cytosol;Data;design;Endoplasmic Reticulum;endoplasmic reticulum stress;Epigenetic Process;Equilibrium;experience;Genetic;Genetic Transcription;Goals;Homeostasis;Human;Immune;Immune response;Immunity;improved;In Vitro;in vivo;Infection;inhibitor;insight;Knockout Mice;Knowledge;Lymphocytic choriomeningitis virus;Maintenance;Malignant Neoplasms;Measurement;Mediating;Mediator;Memory;Metabolic dysfunction;Metabolism;misfolded protein;mitochondrial metabolism;Molecular;Mus;new therapeutic target;novel;pathogen;Pathway interactions;pharmacologic;preservation;prevent;Proteins;proteostasis;Public Health;Quality Control;Reporter;Research;response;Rest;Role;Signal Pathway;Signal Transduction;T cell differentiation;T cell response;T-Lymphocyte;Testing;Therapeutic;Transgenic Organisms;tumor;Ubiquitin;Vaccination;vaccine response;Virus Diseases;Work

PROJECT_TITLE: The role for ER associated degradation (ERAD) in T cell homeostasis and memory

STUDY_SECTION: CMIB

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


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Kidney Disease;Nutrition;Patient Safety;Prevention;Urologic Diseases

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE Kidney stone patients are at risk for future symptomatic kidney stone episodes. Preventive interventions can reduce recurrence risk, however selective therapy as guided by 24-hour urine studies have not been evaluated against empiric therapy. This study will evaluate comparative effectiveness of selective versus empiric intervention strategies on urinary risk profiles of kidney stone patients.

PI_NAMEs: HSI, RYAN  (contact)

PROGRAM_OFFICER_NAME: KIRKALI, ZIYA

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Address;Adherence;Adverse effects;Adverse event;American College of Physicians;Calcium;Calcium Oxalate;calcium phosphate;care costs;Caring;Child;Chronic;Clinical;comparative effectiveness;compare effectiveness;Complex;Confusion;cost;Data;Diet;Disease;Event;Flank Pain;follow-up;Future;Goals;Guidelines;Health;Healthcare;High Prevalence;high risk;Hour;improved;Incidence;Infection;Injury to Kidney;Insurance Carriers;Intervention;Kidney Calculi;Knowledge;longitudinal, prospective study;medical specialties;Methodology;Minority;Nature;Nephrology;Outcome;Pain;Participant;Patient Compliance;Patient Recruitments;Patients;Pharmaceutical Preparations;pharmacologic;Placebos;Population;potassium citrate;Prevalence;prevent;Prevention;Prevention strategy;preventive intervention;Preventive treatment;primary outcome;Publishing;Quality of life;Randomized;randomized trial;randomized, clinical trials;Recommendation;recruit;Recurrence;Regimen;Research;Risk;Safety;secondary outcome;side effect;standard of care;Symptoms;Test Result;Testing;thiazide;urinary;Urinary Calculi;Urine;Urology;Woman;Work

PROJECT_TITLE: Randomized Trial of Empiric Versus Selective Preventative Strategies for Kidney Stone Disease

STUDY_SECTION: KUFD

STUDY_SECTION_NAME: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]


NIH_SPENDING_CATS: Aging;Arthritis;Biomedical Imaging;Chronic Pain;Digestive Diseases;Microbiome;Obesity;Osteoarthritis;Pain Research;Precision Medicine

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Public health relevance Our current knowledge base regarding knee osteoarthritis (KOA) cannot clearly distinguish between individuals who will progress and those that will not. Accumulating data suggest that lipid mediators may be central mechanistic mediators of chronic low-grade synovial inflammation and joint pathobiology. The utilization of mass spectrometry will allow us to characterize these inflammatory mediators in a large cohort of individuals at high risk of KOA, the Osteoarthritis Initiative (OAI) cohort, and address the question of whether circulating bile acids has the potential to effectively predict KOA progression in this cohort.

PI_NAMEs: GUMA, MONICA  (contact);LANE, NANCY E

PROGRAM_OFFICER_NAME: ZHENG, XINCHENG

PROJECT_TERMS: Acceleration;Acids;Address;Affect;Arthritis;bile acid metabolism;Bile Acids;Biological Markers;Cartilage;cartilage degradation;cell type;Cells;Chenodeoxycholic Acid;Cholesterol;Cholic Acids;Chronic;Clinical;cohort;Data;Degenerative polyarthritis;Deoxycholic Acid;Development;Diagnostic tests;effusion;Elderly;Elements;experimental study;Fatty acid glycerol esters;Foundations;Goals;gut microbiota;High Prevalence;high risk;host microbiota;Human;indexing;Individual;Inflammation;Inflammation Mediators;Inflammatory;interest;Intestinal permeability;Investigation;joint inflammation;Joints;Knee;Knee joint;Knee Osteoarthritis;knee pain;knowledge base;Link;lipid mediator;Lipids;lipopolysaccharide-binding protein;Lipopolysaccharides;Lithocholic Acid;Magnetic Resonance Imaging;Mass Spectrum Analysis;Mediating;Mediator;Metabolic;microbiome;Morbidity - disease rate;Natural Immunity;Non obese;novel;nutrient absorption;Obesity;Outcome;Pain;pain score;Participant;Pathogenesis;Pathway Analysis;Pathway interactions;Patients;personalized intervention;personalized medicine;Phenotype;Populations at Risk;predictive marker;public health relevance;radiological imaging;receptor;Reporting;Risk Factors;Role;sample archive;Sampling;Serum;Severities;Signaling Molecule;Stratification;Synovial joint;Synovitis;Tissues;web site;Western Ontario and McMaster Universities Arthritis Index

PROJECT_TITLE: Can circulating bile acids predict knee OA progression?

STUDY_SECTION: MRS

STUDY_SECTION_NAME: Musculoskeletal Rehabilitation Sciences Study Section[MRS]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Project Narrative New strategies are needed to attack deadly microbes such as Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). Because of their unique cell wall, mycobacteria can survive in human hosts under conditions that would kill most microbes; therefore, the focus of this project is on understanding how mycobacteria build and remodel their cell envelope. By uncovering the weak links in the mycobacterial cell wall, new antimycobacterial strategies that exploit these vulnerabilities can be discovered.

PI_NAMEs: KIESSLING, LAURA L (contact)

PROGRAM_OFFICER_NAME: BOYCE, JIM P

PROJECT_TITLE: Chemical Probes of Mycobacteria

STUDY_SECTION: SBCA

STUDY_SECTION_NAME: Synthetic and Biological Chemistry A Study Section[SBCA]


ORG_CITY: PROVIDENCE

ORG_NAME: PROVIDENCE VA  MEDICAL CENTER

ORG_STATE: RI

PHR: There are over 1,600 major limb amputations to-date in military operations OEF, OIF, and OND (CRS Report). Additionally, in 2013 alone there were nearly 27,000 (QUERI) Veterans with spinal injuries (SCI) and related disorders cared for by Veterans Affairs who all stand to benefit directly from this project. This Merit Award project aims to build fundamental knowledge of how motor cortex (MI) controls voluntary, as well as stereotypic, lower limb movements, and then to design both a brain-spine interface leveraging a fully implanted hardware system combining wireless neural recording, stimulation, and motion capture technologies borrowed from industry and born from our laboratory, with the mathematical tools to explore use of a neuroprosthetic for therapeutic delivery of spinal stimulation. By establishing a robust understanding of the cortical control of hind limb movement, and piloting a fully implanted brain-spinal interface, we will have obtained the critical scientific information needed to advance toward a first-in-human study of a restorative BSI in Veterans with paraplegia.

PI_NAMEs: BORTON, DAVID ALLENSON (contact)

PROJECT_TERMS: Address;Affect;Amputation;Amputees;Animals;Area;Attention;Automobile Driving;Award;Axon;Behavior;Behavioral;Body mass index;Brain;brain control;brain machine interface;Breathing;Calibration;Caring;Classification;Clinical Research;clinical translation;Cortical Cord;Custom;Data;Data Set;design;Development;disabled;Disease;Economics;Electric Stimulation;Electrocorticogram;Electromyography;Electronics;Failure;feature extraction;first-in-human;flexibility;Follow-Up Studies;foot;functional restoration;Future;Gait;Health;Home;Hospital Costs;Human;human study;Implant;Individual;Industry;insight;instrument;Intention;Joints;kinematics;Knowledge;Laboratories;Lead;Leg;Life;limb amputation;limb loss;limb movement;Limb Prosthesis;Limb structure;Location;Locomotion;locomotor tasks;Lower Extremity;Macaca;Macaca mulatta;Malignant Neoplasms;Maps;Mathematics;Medical;Methods;Microelectrodes;military operation;military veteran;Modality;Modeling;Motion;Motor;motor control;Motor Cortex;motor rehabilitation;Movement;Muscle;Nervous System;Nervous System Trauma;neural;neural implant;Neurons;neuroprosthesis;Neurostimulation procedures of spinal cord tissue;neurotechnology;nonhuman primate;Palpable;Paraplegia;Pathway interactions;Pattern;Performance;Periodicity;Persons;Phase;Physiologic pulse;Play;Population;Positioning Attribute;pre-clinical;Primates;Process;Prosthesis;Publishing;Quality of life;Rehabilitation therapy;Reporting;Robotics;Role;Rotation;sensor;Signal Transduction;Silicon;social;spatiotemporal;Spinal;Spinal Cord;Spinal cord injury;Spinal Injuries;Stereotyping;System;Technology;technology platform;Therapeutic;Time;tool;Training;training data;Translations;transmission process;Trauma;treadmill;two-dimensional;United States;United States Department of Veterans Affairs;Upper Extremity;Upper limb movement;Validation;Vascular Diseases;Vertebral column;Veterans;Walking;wireless;wireless data transmission;Work

PROJECT_TITLE: The Role of M1 Leg Area in Volitional and Stereotyped Control of the Lower Limb

STUDY_SECTION_NAME: Rehabilitation Engineering & Prosthetics/Orthotics [RRD5]


NIH_SPENDING_CATS: Asthma;Clinical Research;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Lung;Pediatric;Social Determinants of Health

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: PROJECT NARRATIVE Our proposal focuses on the frequent exacerbator phenotype of asthma. This asthma subgroup, disproportionately affects urban populations, is responsible for considerable asthma morbidity and healthcare costs, and is grossly understudied. Our studies will use multilayered omics approaches to delineate the pathogenomics of the frequent exacerbator.

PI_NAMEs: KHURANA HERSHEY, GURJIT K. (contact)

PROGRAM_OFFICER_NAME: DONG, GANG

PROJECT_TERMS: Acute;acute care;Affect;Asthma;asthma exacerbation;asthmatic;Biological;Characteristics;Child;Childhood;Childhood Asthma;Chronic;Clinical;Clinical Research;Complex;cost;County;Data;design;Deterioration;differential expression;Disparity;DNA;Economics;experience;Family;Frequencies;Genes;Goals;Health;Health Care Costs;High Prevalence;high risk;hospitalization rates;improved;Infrastructure;inner city;innovation;lower income families;Medicaid;Methylation;methylome;methylomics;microbial;Morbidity - disease rate;mortality;multidisciplinary;multiple omics;Nasal Epithelium;Nose;novel;Ohio;Pathway interactions;Patients;Pattern;Phenotype;psychologic;Public Health;pulmonary function;repository;Research Project Grants;research study;Risk;Site;social;Steroids;Stress;Subgroup;success;Symptoms;System;targeted treatment;Testing;Therapeutic Intervention;transcriptomics;Translational Research;Urban Community;Urban Population;Visit

PROJECT_TITLE: Multi-omics of the Frequent Exacerbator Asthmatic


ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative Legg-Calvé-Perthes disease is one of the most serious conditions affecting the pediatric hip as 50% of patients will develop debilitating osteoarthritis. The project will develop new necrotic bone reconditioning and immunomodulatory treatments to target chronic inflammatory macrophage response that hinders bone regeneration in this hip disorder. Successful completion of this project will have immediate clinical impact by providing a proof-of-concept for the minimally invasive, yet potentially highly effective, tissue engineering strategies to overcome current barriers to successful bone regeneration in Legg-Calvé-Perthes disease.

PI_NAMEs: KIM, HARRY K.W. (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Acceleration;Adolescent;Affect;Age;analytical method;Biocompatible Materials;Biological Products;Biology;Blood flow;BMP2 gene;bone;Bone necrosis;Bone Regeneration;bone repair;Cell Death;Cell Differentiation process;Cells;Child;Childhood;Chronic;Clinical;clinical application;Clinical Trials;conditioning;controlled release;Cues;Deformity;Degenerative polyarthritis;diabetic rat;Disease;effective therapy;Environment;Exhibits;experimental study;femur head;Fibrosis;Goals;healing;Hip region structure;Hydrogels;IL4 gene;Immune;immunomodulatory strategy;immunomodulatory therapies;immunoregulation;Impairment;In Vitro;in vivo;Inflammatory;Inflammatory Response;Injectable;Injury;insight;Interleukin-4;Ischemia;Legg-Perthes Disease;Liquid substance;Longevity;Macrophage;mesenchymal stromal cell;Methods;Microspheres;minimally invasive;Molecular;Necrosis;novel;optimal treatments;Osteogenesis;Osteotomy;Outcome;Pathologic;Patients;Pattern;Phenotype;Play;porcine model;prevent;Process;recruit;regenerative;repaired;response;RNA;Role;Stimulus;System;Teenagers;Testing;Therapeutic Effect;Tissue Engineering;Tissues;Total Hip Replacement;Work

PROJECT_TITLE: Immunomodulation of juvenile femoral head osteonecrosis

STUDY_SECTION: MTE

STUDY_SECTION_NAME: Musculoskeletal Tissue Engineering Study Section[MTE]