ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Depression;Major Depressive Disorder;Maternal Health;Maternal Morbidity and Mortality;Mental Health;Mental Illness;Serious Mental Illness;Sleep Research;Women's Health Research

ORG_CITY: ANN ARBOR

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Postpartum depression is common, undertreated, and has far reaching consequences for both mother and child; thus, novel, in-home treatments that remove barriers to care and target modifiable underpinnings are urgently needed. This study will test the efficacy of wearable bright light therapy for postpartum depression and determine how changes in sleep and circadian timing influence treatment response. Findings from the study will inform treatment targets to reduce the major burden of postpartum depression, with long-term benefits for women and their offspring.

PI_NAMEs: SWANSON, LESLIE M (contact)

PROGRAM_OFFICER_NAME: RUDORFER, MATTHEW V

PROJECT_TERMS: actigraphy;Address;Affect;Aftercare;anti-depressive agents;Area;Arousal and Regulatory Systems;barrier to care;caregiving;Cessation of life;Child;Child Care;circadian;Circadian desynchrony;Circadian Rhythms;Clinic;depressive symptoms;Development;Devices;Disease remission;efficacy testing;Estrogens;Excessive Daytime Sleepiness;Exposure to;Foundations;Freedom;Functional impairment;Glass;Hamilton Rating Scale for Depression;Health Services Accessibility;High Prevalence;Home;Hour;Impairment;improved;improved outcome;Infant;Infant Care;innovation;Intervention;Lactation;Light;Measures;Mediating;Mediator;Melatonin;Mental Depression;Mental disorders;Mothers;Movement;Napping;National Institute of Mental Health;Newborn Infant;Nonpharmacologic Therapy;novel;offspring;Participant;perinatal mental health;Pharmacotherapy;Phase;Phototherapy;pilot test;Placebos;Population;Postpartum Depression;Postpartum Period;Postpartum Women;Pregnancy Complications;primary outcome;Progesterone;Randomized, Controlled Trials;Recurrence;Research Domain Criteria;response;Salivary;satisfaction;Seasons;secondary outcome;self-reported depression;side effect;Sleep;Sleep Wake Cycle;Social Functioning;standard care;Suicide;System;technological innovation;Testing;Time;Travel;treatment adherence;treatment effect;treatment response;United States;uptake;wearable device;Woman;women's outcomes;Work;Wrist

PROJECT_TITLE: A Wearable Morning Light Treatment for Postpartum Depression: Confirming Efficacy and Mechanisms


ADMINISTERING_IC: HL

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Lung;Neurosciences

ORG_CITY: STORRS-MANSFIELD

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PHYSIOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

ORG_STATE: CT

PHR: PROJECT NARRATIVE Respiratory disfunction has been identified as a key symptom in the clinical profile of patients with pathogenic variants of the potassium channel KCNQ2. The role of KCNQ2 channels in respiratory homeostasis remains unexplored. The proposed research will identify the roles of KCNQ2 channels as well as KCNQ2 pathogenic variants in respiratory homeostasis, thus providing an integrated model of the respiratory circuit in the context of KCNQ2 function, which will serve as a foundation for potential therapeutic targets in respiratory disease which include but are not limited to KCNQ2 encephalopathy. .

PI_NAMEs: SOTO, JASEPH  (contact)

PROGRAM_OFFICER_NAME: LAPOSKY, AARON D

PROJECT_TERMS: Affect;Animals;Apnea;Behavior;Brain;Breathing;Carbon Dioxide;Cell Nucleus;cell type;Chemoreceptors;Chronic;Clinical;Clinical Data;Clinical Research;congenital central hypoventilation syndrome;Disease;Electrophysiology (science);Elements;Encephalopathies;epileptic encephalopathies;Exhibits;Foundations;Functional disorder;gain of function;gain of function mutation;Generations;Genes;Goals;Homeostasis;Hypoventilation;Impairment;infancy;insight;Lead;loss of function;loss of function mutation;Modeling;Molecular;Motor Neurons;Motor output;mouse model;Mus;Mutation;Neonatal;neonatal brain;Neurons;Neurotransmitters;novel;Nucleus solitarius;Output;Pathogenicity;Patients;Pharmacology;Phenotype;Positioning Attribute;Potassium Channel;preBotzinger complex;profiles in patients;Rattus;Recurrence;Research;Research Personnel;Respiration Disorders;respiratory;Respiratory Disease;response;Role;Slice;Symptoms;Syndrome;System;Testing;therapeutic target;therapy development;Training;Transgenic Mice;Variant;Work

PROJECT_TITLE: Proposed roles of KCNQ2 Channels in Respiratory Homeostasis


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Cancer

ORG_CITY: SAINT LOUIS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative The EGF receptor is mutated or over-expressed in a variety of human tumors. Different tumors express structurally different forms of the EGFR as well as different ligands. To fully understand how the EGFR signals growth, it is necessary to understand how the different parts of the EGFR contribute to the biochemical changes that it induces in cells and how the different ligands can modify that biochemistry.

PI_NAMEs: PIKE, LINDA JOY (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Adjuvant Therapy;Agonist;Binding;Binding Proteins;Binding Sites;Biochemical;Biochemistry;Biological;C-terminal;Cell Proliferation;Cell Surface Receptors;Cells;Clinical;Computer Models;Coupled;Data;Dependence;Dimerization;Disease;Distant;EGF gene;Elements;Epidermal Growth Factor Receptor;ERBB2 gene;Exhibits;experimental study;extracellular;Extracellular Domain;Generations;Glioblastoma;Goals;Growth;Heterodimerization;Homo;Homodimerization;Human;Laboratories;Ligand Binding Domain;Ligands;Malignant neoplasm of lung;Mediating;Metabolic;Methods;Modeling;Molecular Conformation;mutant;Mutate;Mutation;Oncogenic;Outcome;overexpression;Pathway interactions;Phosphorylation;Phosphotransferases;Phosphotyrosine;protein structure;Protein Tyrosine Kinase;Proteins;PTB Domain;receptor;receptor binding;Receptor Protein-Tyrosine Kinases;Receptor Signaling;response;Signal Pathway;Signal Transduction;Signaling Protein;Site;src Homology Region 2 Domain;Study models;Surface;Tail;Tertiary Protein Structure;trafficking;tumor;tumor growth;Tyrosine;Variant

PROJECT_TITLE: Intrinsic Disorder and Agonist Bias in EGF Receptor Signaling

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-C(02)M]


ORG_CITY: CHICAGO

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: The secretory pathway plays a central role in processing and sorting cellular proteins, but there are major gaps in our understanding of how this pathway is organized and how it operates. By using budding yeasts and cultured mammalian cells, we aim to elucidate conserved core principles of secretory pathway function. This knowledge will illuminate key aspects of cell biology while providing improved tools for basic and translational biomedical research.

PI_NAMEs: GLICK, BENJAMIN S (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Age;Biomedical Research;Cells;Cellular biology;Clathrin Adaptors;Coat Protein Complex I;Communication;Cytoplasm;Development;Early Endosome;Engineering;Fluorescence Microscopy;genome editing;Goals;Golgi Apparatus;Image;improved;Individual;insight;Integral Membrane Protein;Kinetics;Knowledge;Link;lipid metabolism;Logic;Mammalian Cell;Mediating;Membrane Protein Traffic;Molecular;mutant;novel;Organelles;Pathway interactions;Play;Process;Productivity;Property;protein distribution;Proteins;Recycling;Role;Saccharomyces cerevisiae;Saccharomycetales;SNAP receptor;Sorting;Structure;System;tool;trans-Golgi Network;Transcription Factor AP-1;unpublished works;Vesicle;Visit;Visualization;Work;Yeasts

PROJECT_TITLE: Deciphering the logic circuit for Golgi membrane traffic

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Contraception/Reproduction;Genetics;Infertility;Neurosciences;Pediatric;Polycystic Ovary Syndrome (PCOS);Women's Health Research

PHR: Project Narrative Polycystic ovary syndrome (PCOS) is the leading cause of infertility in the USA and around the world, with hyperandrogenic forms of PCOS conservatively affecting 8-10% of women, and all forms of PCOS affecting up to 25%. The proposed research investigates the origins and mechanisms underlying how the typical regulation of reproduction by the brain in prenatally androgenized mice, which exhibit several symptoms that resemble PCOS. The goals are to produce new knowledge of the changes in the brain in this model, studies that cannot be done in humans, and to identify new therapeutic approaches to treat both infertility and other aspects of this disorder.

PI_NAMEs: MOENTER, SUZANNE M (contact)

PROGRAM_OFFICER_NAME: RAVINDRANATH, NEELAKANTA

PROJECT_TERMS: Action Potentials;Adult;Affect;Age;Androgenization;Androgens;Animal Model;Anterior Pituitary Hormones;Automobile Driving;biophysical properties;Biophysics;Brain;Calcium;Cell Physiology;Cell Separation;Cells;comparison control;Complement;Comprehension;Data;Development;Disease;DNA Methylation;Drops;Electrophysiology (science);Epigenetic Process;epigenetic profiling;Exhibits;Exposure to;Failure;Feedback;Female;Female infertility;Fertility;Follicle Stimulating Hormone;Frequencies;Functional disorder;Funding Mechanisms;Future;gamma-Aminobutyric Acid;genome-wide;girls;Goals;Gonadotropin Hormone Releasing Hormone;Gonadotropins;histone methylation;Homeostasis;Human;Hyperandrogenemia;Infertility;insight;Knowledge;Lead;Libraries;Luteinizing Hormone;Messenger RNA;Methods;Modeling;Molecular;Mus;Nature;neural;neurobiological mechanism;Neurobiology;neurodevelopment;neuroendocrine phenotype;Neurons;Neurosecretory Systems;neurotransmission;novel therapeutic intervention;Output;Ovarian;Ovariectomy;Ovary;Pathology;Pathway interactions;Pattern;Phenotype;Physiologic pulse;Physiological;Polycystic Ovary Syndrome;Positioning Attribute;Potassium;Pregnancy;prenatal;prenatal exposure;prepuberty;Prevention;Process;Property;Protocols documentation;Puberty;Regulation;Reproduction;reproductive;reproductive function;Research;response;Role;Steroids;Symptoms;Synapses;Systems Development;Testing;transmission process;Variant;voltage;Woman;Work

PROJECT_TITLE: Development of the GnRH neuronal network and effects of prenatal androgen exposure

STUDY_SECTION: NNRS

STUDY_SECTION_NAME: Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section[NNRS]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: BIRMINGHAM

ORG_NAME: BIRMINGHAM VA MEDICAL CENTER

ORG_STATE: AL

PHR: Women are the fastest growing subgroup of U.S. Veterans. There is a notably high incidence of breast cancer among younger military women (20% to 40% higher). The incident rate of breast cancer for active duty women is seven times higher than the average incident rate of fifteen other cancer types across all service members. Thus, there is an urgent unmet need to effectively diagnose, manage and cure breast cancer in the veteran population. Triple negative breast cancer (TNBC) is prevalent among young women veterans, and shows a tendency to rapidly metastasize. Despite a short favorable management with chemotherapy, patients with metastatic disease have a median overall survival of about 18 months. While Wnt/β-catenin signaling has been one of the major factors driving TNBC metastases, therapeutic strategies are still evolving. Our research efforts will advance this field and unravel critical information that identifies novel drug targets. Our efforts are congruent with the mission of the VA women's health initiative.

PI_NAMEs: SAMANT, RAJEEV S (contact)

PROJECT_TERMS: active duty;Automobile Driving;beta catenin;Biogenesis;Breast Cancer Cell;breast cancer metastasis;cancer cell;cancer type;Cell Nucleolus;Cells;Cessation of life;Chemicals;chemotherapy;Clinical;cohort;Databases;design;Diagnosis;Disease;DNA Polymerase I;Dose;Genetic;Genetic Transcription;Hypertrophy;Incidence;inhibitor;insight;Investigation;Knock-out;Knockout Mice;Knowledge;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Mammary Neoplasms;Mesenchymal;Metabolic;military veteran;military women;Mission;Modeling;mortality;Neoplasm Metastasis;neoplastic cell;new therapeutic target;novel;Pathologic;Pathway interactions;Patients;pre-clinical;Pre-Clinical Model;prognostic;Proteins;Proteomics;Research;Ribosomal DNA;Ribosomal Proteins;Ribosomal RNA;Ribosomes;RNA;RNA chemical synthesis;RNA Polymerase I;Role;service member;Signal Transduction;Site;Small Nucleolar RNA;Specimen;Stains;Subgroup;Survival Rate;Testing;Therapeutic;tool;triple-negative invasive breast carcinoma;tumor;tumor diagnosis;tumor progression;Tumor Tissue;Veterans;Woman;Women's Health;Work;young woman

PROJECT_TITLE: Mechanisms that impact metastatic progression of triple negative breast cancer


ORG_CITY: TUCSON

ORG_NAME: SOUTHERN ARIZONA VA HEALTH CARE SYSTEM

ORG_STATE: AZ

PHR: PROJECT NARRATIVE Acute kidney injury (AKI) remains an enormous public health concern, as no effective therapies have proven useful after renal injury has occurred. Mitochondrial biogenesis, the process of replacing dysfunctional mitochondria with new mitochondria, represents a novel approach to stimulate cell and organ repair/regeneration after renal injury, and accelerate the return of renal function. We will study the mechanisms and efficacy by which serotonin receptor signaling induces mitochondrial biogenesis and vascular and renal recovery in AKI. This novel approach may not only lead to new therapeutic approaches to treat AKI injury but also other acute organ failures (e.g. VETERAN traumatic brain injury, stroke, and myocardial infarction), chronic organ failures (e.g. VETERAN post-traumatic stress disorder, metabolic syndrome, neurodegenerative diseases) and mitochondrial diseases.

PI_NAMEs: SCHNELLMANN, RICK G (contact)

PROJECT_TERMS: Acceleration;Acute;Acute Renal Failure with Renal Papillary Necrosis;aerobic glycolysis;Agonist;angiogenesis;Attention;Biogenesis;Blood Vessels;cell injury;cell type;Cells;Chronic;Chronic Disease;Cre lox recombination system;Cyclic GMP;Data;Disease;Drug toxicity;effective therapy;Endothelial Cells;Endothelium;experimental study;Extravasation;FDA approved;Goals;Homeostasis;Impairment;improved;in vivo;Inflammatory;Injury;Injury to Kidney;Ischemia;Kidney;kidney vascular structure;Knockout Mice;Laboratories;Lead;LoxP-flanked allele;Mediating;MEKs;Metabolic syndrome;Metabolism;military veteran;Mitochondria;Mitochondrial Diseases;mitochondrial dysfunction;mortality;Mus;Myocardial Infarction;Natural regeneration;Neurodegenerative Disorders;normoxia;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Nutrient;Organ;Organ failure;organ repair;Oxidants;Oxidative Phosphorylation;Oxygen;Oxygen Consumption;Pathway interactions;Pharmaceutical Preparations;Pharmacological Treatment;Pharmacotherapy;Physiological;Post-Traumatic Stress Disorders;Process;Proliferating;Proto-Oncogene Proteins c-akt;Public Health;receptor;receptor expression;Receptor Signaling;Recovery;Renal function;repaired;Reperfusion Injury;Reperfusion Therapy;response;Role;Sepsis;Serotonin;serotonin receptor;Signal Induction;Signal Pathway;Stroke;Testing;Therapeutic;tissue repair;Tissues;Toxicant exposure;Trauma;Traumatic Brain Injury;Tubular formation;Vascular Endothelium;Work;wound closure

PROJECT_TITLE: 5-HT Stimulation of Mitochondrial Biogenesis and Acute Kidney Injury


PHR: As with the overall national population, colorectal cancer remains the second leading cause of cancer death in the US veteran population. During the last 40 years, the proportion of colorectal cancer has increased by about 15% in the veteran population and thus constitutes a significant health risk for all veterans and their family members including women especially over 50 years of age. The aberrant regulation of tumor suppressor genes and oncogenes plays a pivotal role in the transformation of normal epithelium into carcinoma in situ and metastatic cancer. STRAP, a cellular protein, is upregulated in colon cancer, promotes cell proliferation, tumorigenicity, metastasis, cancer stem-like cell (CSC) self-renewal, and drug resistance, thus contributing to worse survival of patients with chemotherapy. This study will discover novel and less toxic nanoparticles targeting STRAP, which will be used to codeliver 5-FU and Oxaliplatin. The proposed research is very crucial for the development of successful therapeutic strategies for colon cancer.

PI_NAMEs: DATTA, PRAN K (contact)

PROJECT_TERMS: Adjuvant Therapy;Age Years;Area;beta catenin;Biodistribution;Biomedical Research;Cancer Etiology;Carcinoma in Situ;cell growth;Cell Proliferation;Cells;Cessation of life;Chemoresistance;chemotherapy;colon cancer metastasis;colon cancer patients;Colon Carcinoma;Colonic Neoplasms;Colorectal Cancer;colorectal cancer metastasis;colorectal cancer progression;conditional knockout;copolymer;Data;Development;Disseminated Malignant Neoplasm;Drug Kinetics;Drug resistance;Epithelial Cells;Epithelium;Family member;Fluorouracil;Genetic;Health;Healthcare;Human;human model;improved;In Vitro;in vivo;Induction of Apoptosis;Inhibition of Apoptosis;Injections;innovation;interest;intestinal epithelium;Intestinal Neoplasms;Invaded;Knock-in Mouse;Knock-out;Lipids;Malignant Neoplasms;Mediating;MEKs;men;migration;military veteran;Modeling;mouse model;Mus;nano;nanocarrier;nanoformulation;nanoparticle;nanotherapy;Neoplasm Metastasis;novel;novel therapeutics;Oleic Acids;Oncogenes;Oncogenic;Organoids;oxaliplatin;Pathway interactions;Patients;Pharmaceutical Preparations;Phenotype;Physiological;Play;Polyps;Population;pre-clinical;protein expression;Proteins;Ras/Raf;Rectal Cancer;Regulation;Research;Research Priority;Risk;Risk Behaviors;Role;self-renewal;serine-threonine kinase receptor-associated protein;Signal Transduction;Signaling Protein;Small Interfering RNA;Smoking;stem;stem-like cell;targeted treatment;Testing;Therapeutic;Therapeutic Effect;therapeutic target;Transforming Growth Factor beta;transgene expression;translational potential;tumor;Tumor Promotion;Tumor Suppression;Tumor Suppressor Genes;tumor xenograft;Tumor-Derived;Tumorigenicity;Up-Regulation;Veterans;Woman;Xenograft Model

PROJECT_TITLE: Colon cancer nanotherapy targeting STRAP


ORG_CITY: BOSTON

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

ORG_STATE: MA

PI_NAMEs: SMIRNAKIS, STELIOS MANOLIS (contact)

PROJECT_TERMS: Adult;Area;Calcium;cell type;Cells;Chronic;Clinical;Cognitive;Cognitive deficits;Communication;comorbidity;Complex;Computer Models;Development;Dimensions;disability;Disabling;Disease;Drug resistance;Electrophysiology (science);Epilepsy;Epileptogenesis;Event;Excision;Functional disorder;GABA Receptor;Goals;High Frequency Oscillation;Hippocampus;Image;Imaging Techniques;immunocytochemistry;Impaired cognition;In Vitro;in vivo;Interneurons;Interruption;Intervention;Light;Maps;Measures;Mediating;Memory;Methods;military veteran;Modeling;Monitor;Morbidity - disease rate;Neocortex;neocortical;Neurons;neuropsychiatry;Operative Surgical Procedures;Opsin;optogenetics;Parvalbumins;patch clamp;Pathologic;Patients;Pattern;Pharmaceutical Preparations;Photic Stimulation;Photons;Pilocarpine;Play;Post-Traumatic Epilepsy;prevent;receptor expression;recruit;Reporting;Research Design;Resistance;Resolution;Role;Seizures;side effect;Slice;Synapses;Techniques;Temporal Lobe Epilepsy;Time;two photon microscopy;two-photon

PROJECT_TITLE: CMA: Network plasticity in acquired epileptogenesis


ORG_CITY: MINNEAPOLIS

ORG_NAME: MINNEAPOLIS VA  MEDICAL CENTER

ORG_STATE: MN

PHR: Prostate cancer (PCa) is one of the major health issues for the aging Veterans population warranting investigations to further advance knowledge of the disease pathobiology to benefit PCa patients, which accords with the VA Healthcare mission. Resistance to current androgen pathway-targeting drugs is a major aspect of PCa progression from castration-sensitive to the fatal castration-resistant PCa (CRPC). Increased expression levels of tumor-addictive pro-survival protein kinase CK2 (formerly casein kinase II or 2) correlate with advanced PCa. We have discovered an exciting aspect of crosstalk between this kinase and androgenic pathway targeting in PCa. The proposed investigation of the mechanism of protein kinase CK2 interaction with this pathway and ensuing changes in nuclear proteomic landscape will yield novel knowledge that has the potential of being rapidly translated to the clinic for therapy in PCa patients.

PI_NAMEs: AHMED, KHALIL  (contact)

PROJECT_TERMS: abiraterone;advanced disease;advanced prostate cancer;Affect;Aging;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;androgenic;Androgens;Automobile Driving;Biology;cancer cell;Cancer Patient;casein kinase;casein kinase II;Castration;Cell Death;cell growth;Cell Nucleus;Cell Physiology;Cell Survival;chemotherapy;Clinic;Clinical;Clinical Trials;Data;Death Rate;deprivation;design;Diagnosis;Disease;Disease Progression;Drug resistance;Drug resistance pathway;drug sensitivity;Drug Targeting;enzalutamide;Exhibits;experimental study;Growth;Health;Healthcare;Immunotherapy;improved;inhibitor;insight;Investigation;Knowledge;Malignant neoplasm of prostate;Malignant Neoplasms;Measures;Mediating;men;Messenger RNA;military veteran;Mission;Modeling;Molecular;Mus;Neoplasm Metastasis;next generation;Normal Cell;novel;Nuclear;Oral;p65;Pathogenesis;Pathway interactions;patient derived xenograft model;Patients;Peptides;Pharmaceutical Preparations;phosphoproteomics;Phosphotransferases;Play;prevent;PRKR gene;Proliferating;Prostate;prostate cancer cell;prostate cancer prevention;prostate cancer progression;Prostatectomy;Protein Dynamics;protein function;Protein Kinase;protein kinase inhibitor;Proteins;Proteome;Proteomics;Resistance;Resistance development;response;Role;Serum;Signal Transduction;small molecule;small molecule inhibitor;standard of care;Stress;success;targeted cancer therapy;targeted treatment;Testing;Testis;therapy resistant;Time;Tissues;Translating;Translations;treatment response;tumor;tumor xenograft;Validation;virtual;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Dynamics of protein kinase CK2 signaling in prostate cancer pathogenesis


ORG_CITY: CLEVELAND

ORG_NAME: LOUIS STOKES CLEVELAND VA MEDICAL CENTER

ORG_STATE: OH

PHR: The major microvascular complications of diabetes include diabetic retinopathy, diabetic kidney disease and diabetic peripheral neuropathy, each of which can significantly reduce quality of life and increase mortality by causing blindness, end-stage renal disease and lower-limb amputation, respectively. Because nearly 25% of veterans are affected by diabetes, it is important to identify ways to prevent these complications. The goals of this proposal are to (1) determine whether systemic reduction of the facilitative glucose transporter, Glut1, prevents these complications, (2) to determine whether the addition of Glut1 reduction to the current standard of care for Type 2 diabetes augments protection against each complication and (3) to elucidate mechanisms that regulate Glut1 in each tissue.

PI_NAMEs: SAMUELS, IVY S (contact)

PROJECT_TERMS: Advanced Glycosylation End Products;Affect;Amputation;Blindness;Blood Glucose;blood glucose regulation;Blood Vessels;Blood-Retinal Barrier;Breeding;Caring;cell injury;Cells;Chronic;Clinical Research;Clinical Trials;cohort;combinatorial;comorbidity;Complication;cost;Development;Diabetes Mellitus;diabetic;Diabetic Angiopathies;Diabetic mouse;Diabetic Nephropathy;diabetic patient;Diabetic Retinopathy;disease phenotype;effective therapy;Effectiveness;End stage renal failure;Endothelial Cells;Etiology;euglycemia;experimental study;Eye;FOXO1A gene;Functional disorder;Future;genetic approach;Genetic Polymorphism;Genetic Transcription;Glucose;glucose transport;Glucose Transporter;GLUT-1 protein;glycemic control;Goals;Hyperglycemia;Hypertension;in vivo;insight;Insulin;Insulin-Dependent Diabetes Mellitus;Kidney;limb amputation;Low Prevalence;Lower Extremity;Measures;Mediating;mesangial cell;Messenger RNA;Metabolic;Metformin;Microvascular Dysfunction;Modeling;mortality;mouse model;multicatalytic endopeptidase complex;Mus;Nephrons;Nerve;new therapeutic target;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutics;Nucleotides;Oxidative Stress;Pathology;Pathway interactions;Peripheral Nerves;Peripheral Nervous System Diseases;Pharmacology;Phenotype;prevent;Preventive;Production;Quality of life;Ramipril;Regulation;Renal tubule structure;Retina;Risk;Risk Factors;Role;Schwann Cells;Severities;Signal Transduction;Small Interfering RNA;Sodium;Sorbitol;standard of care;Streptozocin;symporter;Testing;therapy design;Tissues;transcription factor;translational impact;type I and type II diabetes;Ubiquitin;Veterans

PROJECT_TITLE: Glut1 and the microvascular complications of diabetes


ORG_CITY: TAMPA

ORG_NAME: JAMES A. HALEY VA MEDICAL CENTER

ORG_STATE: FL

PHR: Obesity, a chronic disease in Veterans, promotes comorbidities such as cardiovascular diseases, metabolic syndrome and type 2 diabetes mellitus. Obese subjects with COVID19 have 33% fatality rate. 61-83% of Veterans and DoD beneficiaries are overweight or obese, a significantly higher percent compared to civilians. The healthcare costs of obesity and its related diseases exceeds $1.7 billion annually for the VA. Of note is that even though women veterans are only 10% of the total veteran population, 44% women veterans are obese. Furthermore, a startling 75% of Iraq and Afghanistan veterans are overweight or obese and approximately 30% of Gulf War and Gulf Era veterans are morbidly obese (BMI>40) (VA/DoD statistics). As part of personalized, proactive Veteran‐driven care, treatment of obesity is consistent with the priorities outlined by the Department of Veterans Affairs (VA/DoD Clinical Guidelines, 2014).

PI_NAMEs: JOHNSON, RUDOLPH C;PATEL, NIKETA A. (contact)

PROJECT_TERMS: Adipocytes;adipose derived stem cell;Adipose tissue;Adult;Affect;Afghanistan;beneficiary;Biochemical;Biology;Blood Vessels;Body mass index;Cardiovascular Diseases;Caring;Cause of Death;Cells;Chronic;Chronic Disease;Clinical;comorbidity;Core Facility;COVID-19;COVID-19 pandemic;Data;Death Rate;Department of Defense;Development;Diabetes Mellitus;diet-induced obesity;differentiation in vitro;Disease;Endocrine;Evaluation;experience;experimental study;Fatality rate;frontier;Genes;Genetic;genetic makeup;Genomic medicine;Glucocorticoid Receptor;Goals;growth arrest specific transcript 5;Guidelines;Gulf War;Health;Health Care Costs;Health Expenditures;Homeostasis;Human;Hyperplasia;Hypertrophy;In Vitro;in vivo;individual patient;Inflammation;Inflammatory;Insulin;Insulin Receptor;Insulin Resistance;insulin signaling;interdisciplinary approach;Iraq;Knowledge;lipid biosynthesis;Malignant Neoplasms;Mediating;Metabolic;Metabolic Diseases;Metabolic dysfunction;Metabolic Pathway;Metabolic stress;Metabolic syndrome;Metabolism;military veteran;Molecular;Morbid Obesity;mortality;mouse model;Mus;Non-Insulin-Dependent Diabetes Mellitus;Nonsense-Mediated Decay;novel therapeutics;Obese Mice;obese patients;obese person;Obesity;obesity treatment;overexpression;Overweight;Pathology;Pathway interactions;Pattern;Physiological;Plasmids;Population;pre-clinical;prevent;Public Health;receptor;Regulator Genes;Reporting;Research;Research Personnel;Risk Factors;RNA;Role;screening;Severities;Small Interfering RNA;small molecule;small molecule therapeutics;statistics;stem cell biomarkers;stem cell differentiation;stem cell niche;Thinness;Tissue Differentiation;tool;transcriptomics;United States Department of Veterans Affairs;United States National Center for Health Statistics;Untranslated RNA;Veterans;Woman;Work

PROJECT_TITLE: Adipose stem cells' niche in obesity


ORG_CITY: LOS ANGELES

ORG_NAME: VA GREATER LOS ANGELES HEALTHCARE SYSTEM

ORG_STATE: CA

PHR: Project Narrative In the US, an estimated 39.6 million people (~13%), including 8.5 million Veterans are 65 or older and at risk for developing chronic sleep disturbance, a frequent and challenging problem of aging. Fragmented and poor sleep is associated with adverse health outcomes, including increased risk of fall, anxiety, depressive disorders, cognitive decline, and Alzheimer's disease. Also, aging Veterans have a high prevalence of medical and psychiatric disorders that can further aggravate sleep disruption. This research program will use cutting edge approaches to determine if disruption of hypothalamic neurogenesis causes the dysfunction of critical sleep-regulatory systems and consequent sleep disturbance in aging; and if sleep disruption in aging could be mitigated by improving hypothalamic neurogenesis and anti-inflammatory measures. These preclinical studies may help develop novel therapeutic options for optimizing sleep health in elderly Veterans.

PI_NAMEs: ALAM, NOOR  (contact)

PROJECT_TERMS: Aging;Alzheimer's Disease;Anti-Inflammatory Agents;Anxiety;Attenuated;Calcium;Cell Differentiation process;Cell Proliferation;Cells;Chronic;Ciliary Neurotrophic Factor;circadian;Cytosine;Data;Depressive disorder;Dorsal;Dose;Elderly;Elements;Environment;Exhibits;experimental study;Exposure to;fall risk;functional decline;Functional disorder;Galanin;gamma-Aminobutyric Acid;Genetic;Health;High Prevalence;Human;human old age (65+);Hypothalamic structure;Image;immunoreactivity;Impaired cognition;Impairment;improved;improvement on sleep;Inflammation;Inflammatory;inflammatory marker;Infusion procedures;insight;interdisciplinary approach;Internal Ribosome Entry Site;Lipofuscin;Lipopolysaccharides;Measures;Medial;Medical;Mental disorders;migration;Mus;Nerve Regeneration;Neurites;neurogenesis;neuroinflammation;Neurons;novel;novel therapeutics;old mice;Optics;Outcome;Pathology;Persons;pharmacologic;Phenotype;Physiological;poor sleep;preclinical study;precursor cell;Preoptic Areas;programs;Quality of life;Recovery;Regulation;Research;response;Risk;Role;senescence;Series;Sleep;Sleep Architecture;Sleep Deprivation;Sleep disturbances;Sleep Fragmentations;sleep health;Sleep Wake Cycle;System;Therapeutic;TNF gene;Treatment Factor;Veterans

PROJECT_TITLE: Preoptic/Hypothalamic Mechanisms of Sleep-Wake Regulation


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Genetics;Kidney Disease;Rare Diseases

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Narrative Pathophysiologic disturbances in phosphate homeostasis involving the hormone FGF23, and its co-receptor Klotho, such as those in rare Mendelian disorders autosomal dominant hypophosphatemic rickets (ADHR) and hyperphosphatemic familial tumoral calcinosis (hfTC), or common disorders such as chronic kidney disease (CKD), lead to severe mineral disease. These disorders currently have inadequate treatments. We expect that our proposed studies will reveal new mechanisms involved in phosphate homeostasis, providing novel therapeutic targets.

PI_NAMEs: WHITE, KENNETH E (contact)

PROGRAM_OFFICER_NAME: CHAN, KEVIN E

PROJECT_TERMS: Acceleration;Acute;Affect;Alleles;autosome;beta-site APP cleaving enzyme 1;Binding Proteins;Biochemical;Biological Process;Biology;Breeding;Cell surface;cell type;Cells;Cellular Membrane;Chronic;Chronic Kidney Failure;Clinical;Complex;CRISPR/Cas technology;Data;Data Set;Defect;design;dietary;Disease;Dissection;Etiology;Event;Exhibits;Experimental Genetics;extracellular;Familial hypophosphatemic bone disease;Familial tumoral calcinosis;FGFR1 gene;fibroblast growth factor 23;Fibroblast Growth Factor Receptors;Fracture;Functional disorder;functional loss;Genes;Genetic;Genetic Crosses;Genetic Models;Homeostasis;Hormones;Human;Hypophosphatemia;Impairment;improved;In Vitro;in vivo;in vivo Model;Individual;Injections;inorganic phosphate;insight;Kidney;Kidney Diseases;Knockout Mice;Lead;life span;loss of function mutation;LoxP-flanked allele;MAP Kinase Gene;Mediating;Membrane;Metabolism;Minerals;Modeling;Molecular;mortality;Mus;Mutation;Nephrons;new therapeutic target;novel;novel therapeutics;nuclear factors of activated T-cells;Onset of illness;Organ;Osteomalacia;Pathogenesis;Pathologic;Pathway interactions;Patients;Peptide Hydrolases;Phenotype;Physiological;Plasma;Play;positional cloning;prevent;Prevention;Production;Protein Isoforms;Proximal Kidney Tubules;rare mendelian disorder;receptor;Regulation;Renal Mass;Reporting;Resistance;Resolution;response;Rickets;Role;Secondary to;sequencing platform;Serum;Severities;Signal Transduction;single-cell RNA sequencing;Site;Structure;Syndrome;Techniques;Testing;Time;tissue injury;Tissues;Validation;Vascular calcification;wasting

PROJECT_TITLE: Targeting sKlotho-FGF23 Interactions to Improve Pathological Phosphate Handling in CKD

STUDY_SECTION: KMBD

STUDY_SECTION_NAME: Kidney Molecular Biology and Genitourinary Organ Development[KMBD]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Emergency Care;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Physical Injury - Accidents and Adverse Effects;Prevention;Screening and Brief Intervention for Substance Misuse;Social Determinants of Health;Substance Misuse

ORG_CITY: DURHAM

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE Globally, alcohol causes 3.3 million deaths and is a leading risk factor for injury among young adults. Currently in low-resource settings like Tanzania, alcohol-related treatment and resources are scarce while the use of alcohol and the harms caused by alcohol are growing exponentially. This proposal evaluates a Brief Intervention for alcohol for patients suffering an alcohol-related injury who present for care to the Emergency Department at Kilimanjaro Christian Medical Center in Moshi, Tanzania.

PI_NAMEs: STATON, CATHERINE ANN (contact)

PROGRAM_OFFICER_NAME: KWAKO, LAURA ELIZABETH

PROJECT_TERMS: Accident and Emergency department;Acute;addiction;Adoption;Alcohol abuse;alcohol abuse therapy;Alcohol consumption;alcohol related consequences;alcohol-related injury;Alcohols;arm;Behavior;behavioral clinical trial;Behavioral Sciences;binge drinking;Biological;brief alcohol intervention;brief intervention;care seeking;Caring;Cellular Phone;Cessation of life;clinical care;Clinical Sciences;Clinical Trials;Clinical Trials Design;cost;cost effective;Data;Development;drinking behavior;Effectiveness;effectiveness evaluation;Effectiveness of Interventions;Emergency Situation;evidence base;Evidence based treatment;Frequencies;Goals;Guidelines;Harm Reduction;Health;high risk;high risk population;improved;Injury;innovation;Intervention;intervention cost;intervention effect;K-Series Research Career Programs;Language;low and middle-income countries;Low income;Mediation;Mediator;Medical center;Mental Health;Methods;mHealth;Modification;Motivation;motivational enhancement therapy;National Institute on Alcohol Abuse and Alcoholism;Nature;Nurses;patient level intervention;patient population;Patients;Phase;post intervention;Pragmatic clinical trial;pragmatic trial;Protocols documentation;psychosocial;Public Health;Randomized;reduced alcohol use;Reporting;Research;Resource-limited setting;Resources;Risk;Risk Factors;Standardization;Tanzania;Testing;Text;Translating;treatment as usual;treatment services;Underserved Population;United States National Institutes of Health;Work;young adult

PROJECT_TITLE: PRACT: A Pragmatic Randomized Adaptive Clinical Trial to Investigate Controlling Alcohol related harms in a Low-Income Setting; Emergency Department Brief Interventions in Tanzania

STUDY_SECTION: AA

STUDY_SECTION_NAME: Clinical, Treatment and Health Services Research Study Section[AA-3]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: LA JOLLA

ORG_NAME: SCRIPPS RESEARCH INSTITUTE, THE

PHR: Program Narrative A broadly effective vaccine is needed to eradicate hepatitis C. Circulating hepatitis C virus is highly diverse genetically and a working vaccine must be able to protect against diverse viral strains. This research program will solve structures of important viral envelope proteins in order to facilitate rational design of a vaccine to focus immune responses on conserved, vulnerable sites on the virus for maximal protection.

PI_NAMEs: LAW, MANSUN  (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: Animal Model;animal resource;Animals;Anti-viral Agents;Antibodies;Antibody Response;Antibody Specificity;Antigen Presentation;Antigens;Autoimmune;B-Lymphocytes;Binding Sites;Biochemical;Biological Assay;biophysical properties;Case Study;CD81 gene;Communication;Complex;Computer Models;Cost efficiency;Electron Microscopy;Electrons;Engineering;Epidemic;Epitope Mapping;Epitopes;Face;Future;Generations;Genes;Genetic;Genetic Variation;Genotype;Glycoproteins;Goals;Hepatitis C;Hepatitis C Vaccine;Hepatitis C virus;Human;Human Volunteers;Immune;Immune response;Immune system;Immunization;Immunize;immunogenicity;improved;Infection;innovation;interdisciplinary approach;Knowledge;Laboratories;Liver Cirrhosis;Macaca;Macaca mulatta;Malignant neoplasm of liver;Maps;Microscopic;Modeling;mouse model;Mutagenesis;nanoparticle;neutralizing antibody;nonhuman primate;novel;polyclonal antibody;Population;pre-clinical;preclinical evaluation;Production;Program Research Project Grants;programs;rational design;Reagent;receptor;receptor binding;Recombinants;Reproducibility;Research;research clinical testing;Research Project Grants;Resolution;Resources;Role;Scanning;self assembly;single molecule;Site;spatial relationship;Standardization;Structure;success;synergism;Vaccinated;Vaccination;Vaccine Antigen;vaccine candidate;Vaccine Design;vaccine development;vaccine immunogenicity;Vaccines;Viral;Viral Envelope Proteins;viral transmission;virology;Virus;virus envelope;Visual

PROJECT_TITLE: Broadly Effective HCV Vaccine


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

PROJECT_TERMS: Area;Budgets;Collaborations;Communication;Communities;cost effective;Data;Ensure;Equilibrium;Fostering;Goals;Hepatitis C Transmission;Hepatitis C Vaccine;Infrastructure;Manuscripts;meetings;member;Monitor;nonhuman primate;outreach;Preparation;Primates;Productivity;Program Research Project Grants;programs;Publications;Reagent;Research;Research Activity;Research Personnel;Research Project Grants;Research Support;Sampling;Site;synergism;United States National Institutes of Health;Vaccine Antigen;Vaccines;Work

PROJECT_TITLE: Admin Core


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

PROJECT_TERMS: Acceleration;Animals;Antibodies;Antibody Response;Antibody Specificity;Antibody titer measurement;Antigens;B-Lymphocytes;Biological Assay;Blood specimen;Cell Survival;Collection;Communication;Complex;Cost efficiency;Data;data quality;Databases;design;Ensure;Enzyme-Linked Immunosorbent Assay;experimental study;Foundations;Freezing;Glycoproteins;Goals;Hepatitis C Antibodies;Hepatitis C Vaccine;Hepatitis C virus;Human;Immunize;Immunology procedure;improved;International;Laws;Lead;Libraries;Liquid substance;Macaca;Maps;member;Methods;Monitor;Mus;mutant;Nitrogen;Peer Review;Peripheral Blood Mononuclear Cell;Plasma;Plasmablast;Primates;Procedures;Process;Program Research Project Grants;programs;Protocols documentation;Publications;Quality Control;Reagent;Recombinants;Reproducibility;Reproducibility of Results;Research;Research Personnel;Research Project Grants;Resources;response;Running;Sampling;Standardization;Structure;synergism;System;Time;Vaccine Antigen;vaccine development;Vaccine Research;vaccine trial;virology;Virus;Western Blotting;Work

PROJECT_TITLE: Core 001 - Virology Core


NIH_SPENDING_CATS: Biotechnology;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Hepatitis - C;Immunization;Infectious Diseases;Liver Disease;Prevention;Vaccine Related

PI_NAMEs: CHEN, CHRISTOPHER YEH (contact)

PROJECT_TERMS: Affect;Animal Euthanasia;Animal Model;Animals;Antibodies;Antibody Response;Antigens;Awareness;biobank;Biomedical Research;Blood;Blood specimen;Breeding;Callithrix;Chronic;Chronic Hepatitis C;chronic infection;Clinical;Collaborations;Collection;Complex;Computing Methodologies;Data;design;Diagnosis;Experimental Designs;experimental study;Genetic;Germ Lines;Goals;Hepatitis C Vaccine;Hepatitis C virus;Human;Immune;Immune response;Immunization;immunogenicity;Individual;Institution;Laboratories;Liver Cirrhosis;Macaca mulatta;Malignant neoplasm of liver;member;Modeling;nanoparticle;nonhuman primate;novel;novel vaccines;Papio;Parents;Persons;Preclinical Testing;Predictive Value;prevent;Primates;Procedures;programs;protocol development;rational design;Recording of previous events;Regimen;Research;Research Institute;Research Personnel;Research Project Grants;Resources;Safety;Sampling;self assembly;Site;Structure;Testing;Texas;Tissue Sample;Tissues;Toxic effect;Training;Vaccinated;Vaccination;Vaccine Antigen;vaccine candidate;Vaccine Research;Vaccines;Viral Antigens

PROJECT_TITLE: Core-002 - Non-Human Primate Core


PI_NAMEs: STANFIELD, ROBYN L (contact)

PROJECT_TERMS: Alanine;Animals;Antibodies;Antibody Response;Antigens;Binding;Binding Sites;CD81 gene;Cell Culture Techniques;Cells;Chronic;chronic liver disease;Complex;Cryoelectron Microscopy;Data;design;Electron Microscopy;Engineering;env Gene Products;Epitope Mapping;Epitopes;Face;Flavivirus;flexibility;Glycoproteins;Goals;Hepatitis C Vaccine;Hepatitis C virus;Human;Immune;Immune response;Immune system;Immunize;improved;Length;Location;Malignant neoplasm of liver;Maps;Mediating;Membrane Fusion;Methods;Molecular;Molecular Conformation;Monoclonal Antibodies;Negative Staining;neutralizing antibody;next generation;Pan Genus;particle;Pathway interactions;Patients;polyclonal antibody;Population;prevent;Production;protein complex;Protein Engineering;protein expression;Proteins;Public Health;Publishing;rational design;receptor;Reporting;Research;Resolution;Role;Scanning;spatial relationship;structural biology;Structural Models;Structure;Surface;Surface Antigens;System;Techniques;Testing;Vaccine Antigen;vaccine candidate;Vaccine Design;vaccine trial;Vaccines;Viral;Virion;Virus;virus envelope;Virus Replication;X-Ray Crystallography

PROJECT_TITLE: Antigenic structures of HCV envelope glycoproteins (Env)


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Digestive Diseases;Hepatitis;Hepatitis - C;Immunization;Infectious Diseases;Liver Disease;Nanotechnology;Prevention;Vaccine Related

PI_NAMEs: ZHU, JIANG  (contact)

PROJECT_TERMS: Animal Model;Anti-viral Agents;Antibodies;Antibody Response;Antibody-mediated protection;Antigen Presentation;Antigens;Artificial nanoparticles;B cell repertoire;B-Lymphocytes;Binding;Biological Assay;Cell Separation;Cirrhosis;clinical development;Clinical Trials;combat;Complex;Computer Models;cost effective;Data;design;Developing Countries;Development;Engineering;Epitopes;Face;flexibility;Genetic;Genotype;Glycoproteins;Goals;Hepatitis C Vaccine;Hepatitis C virus;Heterodimerization;Human;Immune system;Immunization;Immunize;Immunodominant Epitopes;immunogenicity;improved;In Vitro;in vivo;in vivo evaluation;Infection;Knowledge;Macaca mulatta;marginalization;Modeling;Modification;Molecular Conformation;mouse model;Mus;Mutagenesis;nanoparticle;neutralizing antibody;next generation sequencing;nonhuman primate;novel;Outcome;pandemic virus;Polysaccharides;Population;Predisposition;preference;Primary carcinoma of the liver cells;Production;Property;protein folding;Proteins;Public Health;rational design;Reaction;Recombinants;response;Scaffolding Protein;Scanning;self assembly;Site;social group;Structure;Surface;Transmembrane Domain;Vaccination;Vaccine Antigen;vaccine candidate;Vaccine Design;vaccine development;vaccine immunogenicity;vaccine-induced antibodies;Vaccines;Viral;Viral Antigens;Viral Envelope Proteins;Virus;virus envelope

PROJECT_TITLE: Novel HCV vaccine antigens and nanoparticles


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Neurosciences;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Narrative: This proposal aims to understand the mechanisms by which mutations in the O-GlcNAc Transferase (OGT) gene lead to X-Linked Intellectual Disability (XLID). Within the United States, one in 500 males are affected with XLID, which is characterized by limitations in intellectual functioning and adaptive behavior. Understanding the underlying mechanisms behind this neurodevelopmental phenotype would provide insight into the role of OGT in transcription regulation and early development.

PI_NAMEs: MAYFIELD, JOHNATHAN MARTIN (contact)

PROGRAM_OFFICER_NAME: SURPRIS, MARIPIERRE PAYEN

PROJECT_TERMS: Academia;Adaptive Behaviors;Address;Affect;Binding;Biochemical;Biology;Carbohydrates;career;casein kinase II;Catalytic Domain;causal variant;Cell Physiology;Cells;Cellular Assay;Characteristics;ChIP-seq;chromatin remodeling;Clinical;Complex;CRISPR/Cas technology;Critical Thinking;Cytoplasmic Protein;Data;design;Development;Developmental Gene;differential expression;Disability phenotype;Disease;DNA;embryonic stem cell;Engineering;Environment;Enzymatic Biochemistry;Enzymes;Excision;experience;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Global Change;Glycobiology;glycosylation;glycosyltransferase;Goals;human embryonic stem cell;Human Engineering;human male;in vitro Assay;insight;Kinetics;Laboratories;Lead;Learning;Link;male;Mass Spectrum Analysis;Mentorship;Metabolic;Methylation;Missense Mutation;Modeling;Mutation;N-terminal;nerve stem cell;neural;neurodevelopment;Neurodevelopmental Disability;Neurodevelopmental Disorder;Neuronal Differentiation;novel;Nuclear;Nuclear Proteins;Nutrient;O-GlcNAc transferase;Outcome;Patients;peptide O-linked N-acetylglucosamine-beta-N-acetylglucosaminidase;Phenotype;Positioning Attribute;Post-Translational Protein Processing;protein protein interaction;Proteins;Recombinants;Research;response;Role;sensor;Serine;skills;Technical Expertise;Testing;Threonine;Transcriptional Regulation;transcriptome sequencing;transcriptomics;United States;Universities;Variant;Western Blotting;Work;X Chromosome;X-linked intellectual disability

PROJECT_TITLE: Utilizing Causal X-Linked Intellectual Disability Variants to Gain Insight into the O-GlcNAc Transferase Enzyme


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: STANFORD

ORG_DEPT: BIOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Synaptic connections are the basis of brain function, and these synapses need to be maintained throughout development and adulthood. This project will study the mechanisms that keep synaptic connections stable, by investigating how the components of the synapse are organized and regulated. Understanding how synapses are maintained will provide insight into how to protect synaptic connections in neurodegenerative diseases and during aging.

PI_NAMEs: HERBST, WENDY  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Adult;Aging;Auxins;Behavioral Assay;Biochemical;Biological;Biological Models;Biotinylation;Brain;Caenorhabditis elegans;Calcium;candidate identification;cell type;Cells;Cellular biology;Cognition;Communication;Development;Disparity;ELK1 gene;experience;Fluorescence;gene conservation;Genetic;genetic manipulation;Genetic Screening;Image;insight;Knowledge;Label;Laboratories;Life;life span;Maintenance;Mammals;Mass Spectrum Analysis;Measures;Memory;Microscopy;Movement;Nerve Degeneration;Nervous System;neural circuit;Neurodegenerative Disorders;Neurons;Neurophysiology - biologic function;Neurosciences;Organism;Phenotype;Phosphoric Monoester Hydrolases;Phosphotransferases;Physiologic pulse;preservation;presynaptic;Protein Biosynthesis;protein degradation;Proteins;Proteomics;Role;Scaffolding Protein;Structure;Synapses;Synaptic Vesicles;synaptogenesis;System;Testing;Therapeutic;therapeutic target;Time;tool;training opportunity;ubiquitin ligase;Universities;Visual;Visualization;Work

PROJECT_TITLE: Mechanisms of Presynaptic Maintenance in C. elegans

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-2 Study Section [NST-2]


NIH_SPENDING_CATS: Genetics

ORG_CITY: HOUSTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE Mutations in RNA processing and degradation enzymes (RNases) have been shown to cause human disease. Yet, there are many proteins involved in RNA degradation and processing pathways that have not been previously identified as RNases, and for some enzymes that have been identified, their targets and mechanisms of action remain obscure. This study will characterize a group of RNases to better understand the link between dysfunctional RNA processing and degradation, and the development of human disease.

PI_NAMEs: NOTICE, LEE-ANN SHARI (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: 3-Dimensional;Acute;Affect;Attention;Bioinformatics;biological adaptation to stress;carbohydrate metabolism;Cartilage-hair hypoplasia;Catalytic Domain;Cell Cycle;Cell Differentiation process;Cell Nucleolus;Cell Nucleus;Cell Physiology;Cells;Cellular Stress;Characteristics;ciliopathy;Complex;Cytoplasm;Data;Development;developmental disease;Disease;endonuclease;Endoribonucleases;Ensure;Enzymes;Essential Genes;Exonuclease;Gene Expression;Gene Expression Regulation;Genes;Genetic Transcription;Goals;Hereditary Disease;Homeostasis;human disease;In Vitro;in vivo;insight;Link;Malignant Neoplasms;Mediating;Mendelian disorder;Messenger RNA;Methods;Molecular;mutant;Mutation;Neurodegenerative Disorders;Normal Cell;Ontology;Pathway interactions;Physiological;Pontocerebellar hypoplasia;Post-Transcriptional Regulation;posttranscriptional;prevent;Process;Protein Biosynthesis;protein function;Proteins;Quality Control;Research;Ribonucleases;RNA;RNA analysis;RNA Decay;RNA Degradation;RNA Processing;Role;Site;Specificity;stem;Stress;structural determinants;Structure;targeted nucleases;Techniques;Testing;Transcript;Transfer RNA;Translating;Untranslated RNA;Yeasts

PROJECT_TITLE: The Roles of Rnt1 and Putative Endoribonucleases in mRNA Processing and Degradation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F08-M(20)L]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Health Effects of Indoor Air Pollution;Infectious Diseases;Lung;Neurodegenerative;Neurosciences;Social Determinants of Health

ORG_DEPT: PHARMACOLOGY

PHR: PROJECT NARRATIVE These findings will reveal key mechanisms (IL-5, HMGB1, and TREM2) in the Th2 Lung-Brain Axis responsible for how the Th2 pulmonary response, A. versicolor, and the peripheral immune compartment affect the brain and augment AD processes, identifying key opportunities to mitigate AD neuropathology.

PI_NAMEs: OBLAK, ADRIAN LYNN (contact)

PROGRAM_OFFICER_NAME: MARIC, MAJA

PROJECT_TERMS: Affect;Agonist;Air Pollution;Alzheimer's Disease;Alzheimer's disease risk;Amyloid beta-Protein;amyloid pathology;Antibodies;Aspergillus;Asthma;Attenuated;Automobile Driving;beta amyloid pathology;Brain;C57BL/6 Mouse;Cells;Central Nervous System Diseases;Circulation;Cognition;cohort;Data;Dementia;Disease Marker;Disease Progression;Elderly;Environment;Environmental Exposure;Environmental Risk Factor;eosinophil;Etiology;experimental study;Exposure to;frontal lobe;Genetic;Genetic Transcription;HMGB1 gene;Human;Immune;immune cell infiltrate;Immune response;Indoor environment;Inhalation;Inhalation Exposure;inhibiting antibody;inhibitor;Interleukin-5;Link;loss of function;loss of function mutation;Lung;Lung immune response;Measures;Memory;Microglia;Modification;Molds;Morphology;Mus;Mutation;Myeloid Cells;Neurites;Neurodegenerative Disorders;Neuroimmune;neuroinflammation;neuropathology;Pathogenesis;Pathology;Peripheral;Physiology;pollutant;Process;Pulmonary Inflammation;Pulmonary Pathology;receptor;Respiratory Disease;response;Role;Senile Plaques;Testing;TLR4 gene;TREM2 gene

PROJECT_TITLE: The Role of Aspergillus versicolor and the Th2 Lung-Brain Axis in Alzheimer's Disease-like Neuropathology

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ORG_CITY: La Jolla

ORG_NAME: SALK INSTITUTE FOR BIOLOGICAL STUDIES

PHR: PROJECT NARRATIVE Dexterous movements require significant coordination of muscle groups across multiple joints, and the cerebellum is critical for ensuring that these behaviors are smooth and precise. This proposal seeks to define the contributions of an underexplored cerebellar output pathway to the spinal cord to the rapid refinement of skilled forelimb movements. By expanding our knowledge of how the cerebellum facilitates the speed and precision of forelimb behaviors, this work will provide valuable insight into the neural basis of dexterous movement, and lay the groundwork for improved diagnosis and treatment of cerebellar pathologies.

PI_NAMEs: WILCOX, OREN FAIRLEE (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TITLE: Defining the contributions of cerebello-spinal projection neurons to dexterous movement


ORG_CITY: BOISE

ORG_NAME: BOISE VA MEDICAL CENTER

ORG_STATE: ID

PHR: Within the Veterans Affairs healthcare system, around 25% of military veterans have diabetes. Despite innovations in both wound care and diabetes management, diabetic wounds remain the leading cause of amputation for VA patients. The loss of mobility and independence in these veterans has a significant impact on their quality of life and that of their caregivers. With this proposal, we will study stalled healing in diabetic patients by identifying correlated biomarkers. These biomarkers will be the foundation for a preclinical algorithm, enabling translation of our biomarker matrix into a clinically relevant, predictive model for wound healing. Ultimately, the long-term goal of this research will help future developments of low-cost, non-invasive treatment protocols that utilize personalized tools of assessment and can be readily implemented throughout the Veterans Affairs healthcare system.

PI_NAMEs: AMMONS, MARY CLOUD BOSWORTH (contact)

PROJECT_TERMS: Activities of Daily Living;Address;Algorithms;Amputation;Anti-Inflammatory Agents;Assessment tool;Benchmarking;Biological Assay;Biological Markers;biomarker discovery;biomarker identification;biomarker selection;Blinded;candidate marker;candidate selection;Caregivers;Caring;Cellular Metabolic Process;Characteristics;chemokine;Chronic;Clinical;clinical care;clinically actionable;clinically relevant;Collecting Cell;Complex;Computer Models;computerized tools;cost;cytokine;Data;Debridement;design;Development;diabetes management;Diabetes Mellitus;diabetic;diabetic patient;diabetic ulcer;disabled;Economic Burden;economic cost;efficacy testing;Etiology;Fluorescent in Situ Hybridization;Foundations;Functional disorder;functional plasticity;Future;Gene Expression;Gene Expression Profile;Goals;Growth Factor;healing;Health;Healthcare Systems;high dimensionality;Human;Immunity;Immunohistochemistry;immunoregulation;In Situ;Individual;Inflammation;Inflammatory;innovation;Knowledge;limb amputation;lipidomics;Lower Extremity;Machine Learning;Macrophage;Medical;Metabolic;metabolic phenotype;metabolic profile;Metabolism;metabolomics;microbiome;military veteran;Modeling;Molecular;Myelogenous;Natural Immunity;neutrophil;new therapeutic target;non-healing wounds;novel;novel diagnostics;Patients;Phenotype;Population;pre-clinical;precision medicine;predictive modeling;predictive tools;Process;Proteomics;Quality of life;random forest;Research;Research Project Grants;Resolution;responders and non-responders;Role;Sampling;Serum;Skin;Specimen;standard of care;statistics;System;Systems Biology;targeted biomarker;temporal measurement;Testing;Therapeutic;Therapeutic Intervention;Time;Tissues;tool;Translating;Translations;Treatment Protocols;Veterans;Veterans Health Administration;wound;wound care;wound healing;Wound models;wound treatment

PROJECT_TITLE: Metabolic Immunomodulation of Wound-Associated Macrophage Functional Plasticity as a Novel Diagnostic Target in Diabetic Veterans


ORG_CITY: RICHMOND

ORG_NAME: VA VETERANS ADMINISTRATION HOSPITAL

ORG_STATE: VA

PHR: Obesity, diabetes, and their pathological sequelae are a tremendous burden to the population in general but especially so for the Veteran population. Adipose tissue excess contributes to these health problems. This proposal addresses adipose tissue specifically with respect to adaptive thermogenesis, or ‘browning’. It is increasingly appreciated that adult humans have ‘brown fat’—highly metabolically active fat depots that metabolize lipids to generate heat. Brown adipose depots also clear glucose and triacylglycerols form circulation, secrete beneficial hormones, and contribute in other ways to overall health. Recent observations show that white fat, e.g. abdominal and subcutaneous, can transdifferentiate to a brown-like phenotype. This may be an attractive strategy to reduce body fat and improve metabolic health. We have identified new pathways that regulate the white to brown-like conversion and will determine the mechanisms by which this occurs and test whether we can manipulate this pathway in mouse models to improve overall metabolic health.

PI_NAMEs: COWART, LAUREN ASHLEY (contact)

PROJECT_TERMS: Abdomen;Address;Adipocytes;adipokines;Adipose tissue;Adrenal Cortex Hormones;Adrenergic Receptor;Adult;Attention;Attenuated;Award;Binding;Biogenesis;Biology;Body fat;Body System;Brown Fat;Cardiovascular Diseases;Circulation;Data;Dexamethasone;Diabetes Mellitus;diet-induced obesity;Disease;disease phenotype;Disease Resistance;Endocrine;Energy consumption;Energy Metabolism;Exercise;Fatty acid glycerol esters;Fatty Acids;fatty liver disease;Functional disorder;Genes;Genetic Transcription;Glucocorticoids;Glucose;Goals;Health;Health system;Heart;Histone Deacetylase Inhibitor;Homeostasis;Hormones;Human;Hypertrophy;improved;in vivo;Infant;Inflammation;Insulin Resistance;interest;Knockout Mice;Knowledge;Link;lipid metabolism;Lipids;Liver;Liver diseases;Lysophospholipids;Mediating;Metabolic;Metabolic Diseases;Metabolic Pathway;metabolic phenotype;Metabolism;Methods;military veteran;Mitochondria;Mitochondrial Proteins;Molecular;mouse model;Mus;Nature;non-alcoholic fatty liver disease;Obesity;obesogenic;Organism;Outcome;Oxidative Phosphorylation;p38 Mitogen Activated Protein Kinase;Pathologic;Pathology;Pathway interactions;Phenotype;Phosphotransferases;Physiologic Thermoregulation;Population;Post-Traumatic Stress Disorders;prevent;Process;Production;programs;Property;Regulation;Research;Research Support;Resistance;response;Rodent;Role;Series;side effect;Sphingolipids;sphingosine kinase;SPHK1 enzyme;Stimulus;subcutaneous;Testing;Thermogenesis;transdifferentiation;Triglycerides;Up-Regulation;Veterans;Weight Gain;Work

PROJECT_TITLE: Sphingolipids in the Pathophysiology of Obesity and Diabetes


ORG_CITY: BALTIMORE

ORG_NAME: BALTIMORE VA MEDICAL CENTER

ORG_STATE: MD

PHR: The VA patient population is characterized by a high number of patients suffering from age-related degenerative diseases including disorders of bone metabolism, obesity, and diabetes. The investigator’s recent work and that of others has demonstrated an endocrine link between bone and glucose and fatty acid metabolism. The studies proposed in this renewal application examine novel functions of the bone- derived protein sclerostin in adipose tissue physiology. This information will help clarify how the skeleton communicates with other energy consuming tissues and may explain the close association between bone disease and diabetes/obesity in humans; which should have an immediate impact on the management and treatment of these related metabolic disturbances in aging Veterans.

PI_NAMEs: RIDDLE, RYAN C (contact)

PROJECT_TERMS: adipocyte differentiation;Adipocytes;Adipose tissue;Adrenergic Agents;Adrenergic Agonists;Adrenergic Receptor;age related;Aging;Anti-diabetic Drugs;Biological Products;blood glucose regulation;Body Composition;bone;Bone Diseases;bone loss;bone mass;Bone Matrix;Brown Fat;Cardiovascular system;Chronic;clinically significant;cohort;cold stress;Communication;Data;Degenerative Disorder;Dependovirus;Deposition;desensitization;design;Development;Diabetes Mellitus;Diagnosis;Endocrine;Energy consumption;Energy Supply;Exhibits;experimental study;Fatty acid glycerol esters;fatty acid metabolism;Feedback;fracture risk;Functional disorder;Funding;Gene Expression;Genes;Genetic;Genetic Transcription;Global Change;Glucose;glucose uptake;Growth;High Fat Diet;Homeostasis;Hormone secretion;Housing;Human;Impairment;improved;in vivo;inhibitor;insulin sensitivity;Ions;Link;Lipids;Lipolysis;Locomotion;loss of function mutation;LoxP-flanked allele;Mediating;Metabolic;Metabolic Bone Diseases;Metabolic Diseases;Metabolic dysfunction;Metabolism;military veteran;Minerals;Modeling;Morphology;Mus;novel;Obesity;Organ;Osteoblasts;Osteocalcin;Osteocytes;Osteogenesis;Osteopenia;Osteoporosis;overexpression;patient population;Patients;pharmacologic;Phenotype;Physiologic calcification;Physiological;Physiology;Prevention;Production;Proteins;Regulation;Reporting;Research Personnel;response;Serum;side effect;Signal Transduction;Skeleton;Stimulus;subcutaneous;synergism;Testing;Thiazolidinediones;Thinness;Tissues;transcription factor;transcriptome sequencing;Veterans;Weight Gain;WNT Signaling Pathway;Work

PROJECT_TITLE: Endocrine Actions of Sclerostin


PHR: Temporal lobe epilepsy is frequently caused by head trauma, including war-time head trauma and affects thousands of veterans today. Many patients with temporal lobe epilepsy have frequent seizures and do not respond to medications. Many of these patients are also not candidates for epilepsy surgery. Most of these patients also develop severe problems with their memory and mood. Therefore better treatments are needed to prevent the development of epilepsy as well as the memory and mood difficulties after head trauma. How the brain develops the tendency to have repeated seizures after head trauma is not understood. This proposal will use new miniaturized microscope and electrical recordings to understand how different cell types in the brain change their activity in the first few weeks after injury. By understanding which cells malfunction, we hope to target the activity of these cells specifically and prevent the development of epilepsy, memory problems, and depression after head injury.

PI_NAMEs: GOLSHANI, PEYMAN  (contact)

PROJECT_TERMS: Adult;Affect;Animals;Anticonvulsants;axonal sprouting;Biological Markers;Brain;Calcium;Cell Death;cell type;Cells;Chronic;Code;Cognitive;Cognitive deficits;Communication;comorbidity;Complex;Computer Models;Craniocerebral Trauma;D Cells;Development;Devices;Dimensions;disability;Disabling;Disease;Disinhibition;Electrophysiology (science);Epilepsy;Epileptogenesis;Excision;excitatory neuron;extracellular;Fire - disasters;GABA Receptor;Goals;High Frequency Oscillation;hippocampal pyramidal neuron;Hippocampus;Image;Imaging Device;immunocytochemistry;Impaired cognition;In Vitro;in vivo;inhibitory neuron;Injury;Interneurons;Intervention;Laboratories;Learning;Measures;Memory;Mental Depression;Microscope;military veteran;miniaturize;Moods;neocortical;neural circuit;Neurons;open source tool;Operative Surgical Procedures;optogenetics;Parvalbumins;patch clamp;Pathologic;Patients;Pattern;Pharmaceutical Preparations;Physiological;Pilocarpine;place fields;Population;prevent;receptor expression;recruit;Recurrence;Seizures;side effect;Slice;Somatostatin;Source;Status Epilepticus;Synapses;Techniques;Temporal Lobe Epilepsy;therapy development;Time;tool;two-photon;Veterans

PROJECT_TITLE: CMA: Network plasticity in acquired epileptogenesis


ORG_CITY: CHARLESTON

ORG_NAME: RALPH H JOHNSON VA MEDICAL CENTER

ORG_STATE: SC

PHR: Vascular cognitive impairment and dementia (VCID) is one of the most common etiology of dementia in the growing elderly population including veterans. At present several risk factors of VCID have been identified and there is growing evidence that these risk factors involve elevation of ADMA, a metabolic waste of proteins causing vascular disease, in the blood. This study is designed to delineate the role and mechanism of ADMA-induced brain microvessel disease and to evaluate ADMA as a potential of drug target for VCID therapy.

PI_NAMEs: SINGH, AVTAR K (contact)

PROJECT_TERMS: abeta deposition;Age;age related;aged;Alzheimer's Disease;Alzheimer's disease patient;American;Amyloid;Animal Model;Attention;Biological Markers;Blood;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood Vessels;blood-brain barrier disruption;blood-brain barrier function;Brain;Brain Diseases;Brain Pathology;Catabolism;Cell Culture Techniques;Cerebral Amyloid Angiopathy;cerebral hypoperfusion;cerebral microvasculature;Cerebrovascular Circulation;Cerebrum;Chronic;Cognition;Complex;Dementia;design;dimethylargininase;Disease;Drug Targeting;early onset;Elderly;Endothelial Cells;endothelial dysfunction;Endothelium;Enzymes;Etiology;Expectancy;F-Actin;Functional disorder;Genetic;Goals;Health;Heart Diseases;hemodynamics;Hemorrhage;Homeostasis;Human;Hypertension;hypoperfusion;Impaired cognition;Impairment;Inflammation;inhibitor;insight;Investigation;Ischemia;Knockout Mice;Laboratories;Maintenance;Mediating;Metabolic;Metabolic syndrome;Metabolism;Mission;mouse model;mutant;Mutant Strains Mice;N,N-dimethylarginine;Neurocognitive;neurocognitive disorder;neuroinflammation;Neurons;neurovascular;Nitric Oxide;nitrosative stress;Non-Insulin-Dependent Diabetes Mellitus;NOS3 gene;Obesity;Oxidation-Reduction;Pathogenesis;Pathologic;Pathology;Peroxonitrite;pharmacologic;Play;Population;Production;Proteins;Regulation;Reporting;Research;Risk Factors;Role;S-Nitrosoglutathione;Stress Fibers;Study models;Syndrome;Therapeutic;therapeutic target;Transgenic Mice;United States Department of Veterans Affairs;Validation;vascular cognitive impairment and dementia;Vascular Diseases;Vascular Endothelium;Veterans;wasting

PROJECT_TITLE: Mechanism of Vascular Impairment in Neurocognitive Disorders


PHR: Cardiovascular disease is a devastating disorder that has a major impact on length and quality of life. The population is aging and between the years 2020 and 2060, the number of people over the age of 65 is expected to increase by 68% in the United States. The number of heart and vascular procedures (balloon angioplasties and vascular grafts) that will be performed in 2040 is expected to be more than twice the number performed in 2008. Similar increases will occur in the Veteran population. Regardless of whether the veterans undergo endovascular management or open surgical intervention, the long-term results are limited by throm- bosis or restenosis. If endothelial cells migrate across the injured area and create an intact endothelial surface that prevents clotting and scar formation inside the blood vessels, the outcome for veterans undergoing procedures to treat heart and vascular disease will improve significantly. Improving outcomes will decrease the need for reintervention and improve veterans’ quality of life, leading to a very high reward for the project.

PI_NAMEs: ROSENBAUM, MICHAEL AARIC (contact)

PROJECT_TERMS: Adaptor Signaling Protein;Age;Aging;American;American Heart Association;Angioplasty;Area;Arterial Injury;Arteries;atherogenesis;Balloon Angioplasty;Binding Proteins;Blood Vessels;Calcium;Calcium ion;Calpain;Cardiovascular Diagnostic Techniques;Cardiovascular Diseases;Cardiovascular system;Carotid Artery Injuries;Cell membrane;cell motility;Cell Proliferation;Cells;Cicatrix;clinical practice;Clinical Trials;Coagulation Process;Cytoskeletal Proteins;Data;Disease;early onset;Effectiveness;effectiveness testing;Endothelial Cells;Endothelium;Functional disorder;Goals;healing;Heart;Heart Diseases;heart disorder diagnosis;High Fat Diet;high reward;human old age (65+);hypercholesterolemia;Hyperplasia;improved;improved outcome;In Vitro;in vivo;inhibitor;injured;Injury;inorganic phosphate;Intervention;kinase inhibitor;Knock-out;Length;Life;Link;Lipids;Lysophosphatidylcholines;Mediating;Membrane;migration;military veteran;Morbidity - disease rate;mortality;Mus;Operative Surgical Procedures;Outcome;oxidation;oxidized lipid;oxidized low density lipoprotein;Persons;Phosphatidylinositols;Phosphorylation;Phosphorylation Site;Phosphotransferases;PIK3CG gene;Play;Population;preservation;prevent;Procedures;protein activation;Quality of life;receptor;restenosis;Role;Site;Site-Directed Mutagenesis;Small Interfering RNA;Smooth Muscle Myocytes;src-Family Kinases;Stents;success;Surface;Testing;therapeutic target;therapy outcome;thrombogenesis;Thrombosis;Treatment Protocols;TRP channel;United States;Vascular Diseases;Vascular Graft;Veterans;voltage gated channel;Wild Type Mouse

PROJECT_TITLE: Endothelial Healing is Inhibited by Activation of TRPC6 Channels


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

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: PROJECT NARRATIVE Sleep is a crucial variable in neurodegenerative disease: disease progression disrupts sleep, and disrupted sleep worsens brain degeneration. This research will define cellular and molecular links between sleep and degeneration of the brain, with the ultimate goal of leveraging sleep as a modifiable risk factor for Alzheimer’s and other dementias.

PI_NAMEs: BONINI, NANCY M;KAYSER, MATTHEW S (contact)

PROGRAM_OFFICER_NAME: MACKIEWICZ, MIROSLAW

PROJECT_TERMS: abeta accumulation;Affect;age effect;Alzheimer's Disease;Alzheimer's disease risk;Animals;Behavior Therapy;Behavioral;Behavioral Model;Brain;Brain Diseases;combat;Coupled;Data;Defect;Degenerative Disorder;Dementia;Deterioration;Dimensions;Disease;Disease Progression;Drosophila genus;Enhancers;epitranscriptomics;fly;Foundations;Frontotemporal Dementia;Functional disorder;gene interaction;Genes;Genetic;genetic approach;Genetic Screening;Genomics;Goals;Human;human disease;Impaired cognition;improvement on sleep;insight;Intervention;Investigation;knock-down;life span;Link;Mechanics;Modality;Modeling;modifiable risk;Modification;Molecular;Motor Neuron Disease;Mus;Nerve Degeneration;Neurodegenerative Disorders;Neuroglia;Neurons;new therapeutic target;novel;novel therapeutics;Pathology;Pathway interactions;Phenotype;Process;Property;protein TDP-43;Proteins;Research;resilience;Risk Factors;RNA Interference;SCA2 protein;Series;Sleep;sleep abnormalities;Sleep Deprivation;Sleep Disorders;Sleep disturbances;sleep regulation;Sleeplessness;System;TDP-43 aggregation;Testing;Therapeutic;Time;Toxic effect;Work

PROJECT_TITLE: Deciphering the molecular interplay of sleep and neurodegeneration with Drosophila

STUDY_SECTION: BNRS

STUDY_SECTION_NAME: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Clinical Research;Comparative Effectiveness Research;Emergency Care;Health Services;Neurosciences;Patient Safety;Physical Injury - Accidents and Adverse Effects

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: The Yale-Metropolitan Emergency Trial network to advance patient Outcomes (Yale-METRO) is comprised of a primary Hub Yale-New Haven Health System and 5 geographically proximate Spokes that are all part of integrated health systems: Hartford Health, Rhode Island/Brown University Health System; Mount Sinai Health System, New York Presbyterian/Weill Cornell Medicine, and Montefiore Health System, with over 1.6 million ED visits combined. Covering a densely populated area of more than 8 million people throughout Connecticut, Rhode Island, Southern Massachusetts, Southeast New York and 4 boroughs of New York City, Yale-METRO provides a large diverse population for any clinical trial proposed by the SIREN network. Using innovative technological strategies this experienced team of researchers is uniquely poised to test new interventions and therapies.

PI_NAMEs: D'ONOFRIO, GAIL  (contact);SHETH, KEVIN NAVIN

PROGRAM_OFFICER_NAME: SCOTT, GRETCHEN CARLYLE

PROJECT_TERMS: Acute;Adult;advanced disease;Agreement;Applications Grants;Area;Blood Vessels;Cardiac;Cardiovascular system;Catchment Area;Cessation of life;Clinical;Clinical and Translational Science Awards;clinical center;Clinical Trials;Clinical Trials Network;Collaborations;collaborative environment;Communities;Connecticut;COVID-19 pandemic;Data;Data Collection;Data Coordinating Center;data management;data standards;design;Detection;Diagnosis;disability;Electronics;Emergency Care;Emergency Department Physician;Emergency department visit;Emergency Medicine;Emergency Situation;Enrollment;Ensure;experience;Faculty;Funding;Future;Generations;Geography;Health;Health system;Healthcare;Hematologist;Hematology;Home;hospital care;Hospitals;Hour;improved;Injury;innovation;innovative technologies;Institution;Institutional Review Boards;Integrated Health Care Systems;interest;Intervention;Lead;Leadership;Life;Long-Term Care;Longterm Follow-up;Lung;Massachusetts;medical specialties;Medicine;Mentors;metropolitan;Monitor;Morbidity - disease rate;Multi-Institutional Clinical Trial;Multicenter Trials;multidisciplinary;Neurologic;Neurologist;Neurology;Neurosurgeon;New England;New York;New York City;Outcome;participant enrollment;patient population;Patient-Focused Outcomes;pediatric emergency;Pediatric Hospitals;pediatric patients;Persons;Population;Population Heterogeneity;Prehospital Emergency Care;Presbyterian Church;Principal Investigator;Procedures;Process;quality assurance;Quality Control;recruit;Reporting;Research;Research Personnel;Research Proposals;respiratory;Rhode Island;Scientist;Seasons;skills;Stroke;success;Surgeon;synergism;System;Talents;Technology;Testing;Time;Training;Trauma;United States National Institutes of Health;Universities;uptake;Vision

PROJECT_TITLE: Yale-METRO Metropolitan Emergency Trial netwoRK to advance patient Outcomes


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Clinical Research;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Pediatric;Prevention

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Narrative Orofacial clefts (OFCs) are characterized by a split or opening of the lip and/or palate during prenatal development and are among the most common birth defects in the world. In this project we will leverage a large diverse OFC cohort (n = 24,195) composed of 5 distinct ethnic groups to study genetic risk factors of OFC and perform novel gene discovery. In addition, we will explore the genetic influence of 3D facial variation on OFC.

PI_NAMEs: BRAND, HARRISON  (contact)

PROGRAM_OFFICER_NAME: CHOU, ALICIA YESIU

PROJECT_TERMS: 3-Dimensional;Accounting;African;American;Bayesian Method;Bioinformatics;Biology;care burden;Case/Control Studies;Categories;Child;Cleft Lip;Cleft lip with or without cleft palate;Cleft Palate;cohort;Communities;Complex;Congenital Abnormality;Copy Number Polymorphism;craniofacial;Data;Data Set;design;detection method;Development;diagnostic screening;Disease;disorder subtype;East Asian;Ensure;ethnic diversity;Ethnic Population;European;Face;Family;family structure;gene discovery;Generations;Genes;Genetic;genetic architecture;Genetic Counseling;Genetic Predisposition to Disease;Genetic Risk;genetic risk factor;Genetic study;genetic variant;genome sequencing;genome wide association study;genomic locus;Genotype;Goals;Heritability;improved;Individual;innovation;Life;Lip structure;Maps;Measures;Methods;Modeling;Nasal cavity;notch protein;novel;Operative Surgical Procedures;Oral cavity;orofacial cleft;orofacial development;Palate;Parents;Pathogenicity;Pathway interactions;Patients;Persons;polygenic risk score;Population Control;Population Heterogeneity;Population Study;prenatal;prenatal testing;rare variant;Research;Research Design;Risk;Risk Estimate;Sampling;Scoring Method;Series;Shapes;Signal Transduction;SNP array;South Asian;Statistical Methods;Structure;success;Techniques;Testing;trait;transmission process;Variant;variant detection;whole genome

PROJECT_TITLE: Integration of polygenic risk and facial morphometrics to decipher the genetic susceptibility of orofacial clefting

STUDY_SECTION: GHD

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Mental Illness;Neurosciences;Pediatric;Social Determinants of Health;Violence Research;Youth Violence

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE. Emotional abuse (EA) during childhood and adolescence increases risk for depression and is particularly common among sexual minority youth (SMY; individuals with same sex romantic identities and attractions), a population disproportionately affected by depression. Adolescent depression is associated with alterations in the brain systems that process reward and self-relevant information, and those alterations could explain how EA contributes to the development of depression. The present follow-up study will examine the impact of EA on reward and self-biased processing neural systems and associated depressive systems among SMY, a high-risk population for whom there is a public health imperative to address depression disparities.

PI_NAMEs: ECKSTRAND, KRISTEN  (contact)

PROGRAM_OFFICER_NAME: BECHTHOLT, ANITA JEAN

PROJECT_TERMS: Address;Adolescence;Adolescent;Affect;affective neuroscience;Affective Symptoms;Age;Amygdaloid structure;Anisotropy;Anterior;Anxiety;associated symptom;Behavior;Biological Models;Biometry;Brain;career;Characteristics;child depression;Childhood;Clinical;clinical practice;Cognitive;Communities;comorbidity;comparison group;Corpus Callosum;depression model;depressive symptoms;Detection;Development;Diffusion Magnetic Resonance Imaging;Dimensions;Disparity;Dorsal;emotional abuse;Environment;Environmental Risk Factor;Exhibits;experience;Follow-Up Studies;Functional Magnetic Resonance Imaging;Future;Goals;health disparity;Heterosexuals;high risk;high risk population;high school;Individual;innovation;Insula of Reil;Internal Capsule;Intervention;Knowledge;Link;Measurable;Measures;Medial;Mediating;Mental Depression;Mental Health;Mentorship;Methods;Minority Groups;Modeling;Mood Disorders;neural;neural circuit;neuroimaging;neuroregulation;non-verbal;novel;Participant;peer;Perception;Population;Prefrontal Cortex;prevent;Process;programs;Psychiatry;Psychopathology;Puberty;Public Health;recruit;Research;Research Support;response;reward processing;Rewards;Risk;Same-sex;Severities;sex;sexual minority youth;social;social model;Specificity;Stimulus;System;Testing;theories;Time;Training;Trauma;trauma exposure;Ventral Striatum;verbal;white matter;young adult;Youth

PROJECT_TITLE: Neural circuitry underlying emotional abuse and depression in sexual minority youth

STUDY_SECTION: CPDD

STUDY_SECTION_NAME: Child Psychopathology and Developmental Disabilities Study Section[CPDD]


ED_INST_TYPE: GRADUATE SCHOOLS

ORG_CITY: DAVIS

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: NARRATIVE E-cadherin is an essential adhesion protein that mediates complex cell movement during tissue formation and wound healing; mutations in E-cadherin are characteristic of certain cancers. However, little is known about how E-cadherin structure and adhesion are regulated. This proposal will provide a detailed molecular-level understanding of how cells regulate E-cadherin adhesion and identify E-cadherin structures that are important in tissue formation, wound healing and cancer.

PI_NAMEs: SIVASANKAR, SANJEEVI  (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: 3-Dimensional;Actins;Adhesions;Adhesives;alpha catenin;Binding;Binding Proteins;Biomechanics;Cadherins;cancer cell;Cancer Cluster;Cell Adhesion Molecules;cell motility;Cell Physiology;Cell-Cell Adhesion;Cells;Characteristics;Complex;Coupled;Cytoplasmic Protein;Cytoplasmic Tail;Cytoskeleton;Data;Dissociation;E-Cadherin;Epithelial Cells;Epithelium;Exhibits;extracellular;Functional disorder;genetic regulatory protein;insight;Intercellular Junctions;Invaded;Knowledge;Laboratories;Link;Malignant Neoplasms;Measures;Mediating;Membrane;migration;Modeling;Molecular;Molecular Conformation;monolayer;Movement;mutant;Mutation;Natural regeneration;Neoplasm Metastasis;Pattern;Property;Proteins;Regulation;Research;Role;single molecule;Structural Models;Structure;Time;tissue regeneration;Tissues;tumor progression;tumorigenesis;Vertebral column;Vinculin;wound closure;wound healing

PROJECT_TITLE: Mechanosensitive cadherin adhesion and its regulation

STUDY_SECTION: ICI

STUDY_SECTION_NAME: Intercellular Interactions Study Section[ICI]


FUNDING_MECHANISM: OTHERS

ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: Stroke is a major cause of morbidity and mortality among Veterans in the United States, and results in permanent brain injury due to a lack of blood flow. I have studied the genetics of one of nature's most resilient animals, the Arctic ground squirrel, which survives extreme environmental conditions as well as dramatically reduced blood flow as a natural part of hibernation. I aim to discover precisely how adaptations in Arctic ground squirrel proteins can help brain cells survive a stroke.

PI_NAMEs: SINGHAL, NEEL  (contact)

PROJECT_TERMS: Acute;Acute Brain Injuries;Amino Acid Substitution;Amino Acids;Animal Model;Animals;Annexins;Apoptosis;arctic ground squirrel;Behavioral;Binding;Biochemical;Bioenergetics;biological adaptation to stress;Biological Assay;Biology;Blood flow;brain cell;Brain Diseases;Brain Injuries;Brain Ischemia;Candidate Disease Gene;career;career development;Caring;CASP3 gene;cDNA Expression;Cell Death;Cell Survival;Cells;Cellular Assay;cellular resilience;Cerebral Ischemia;clinical training;Clustered Regularly Interspaced Short Palindromic Repeats;comparative genomics;Complement;Complex;complex IV;COX7A2L gene;COX7A2L Protein;CRISPR/Cas technology;Cytoprotection;Data;deprivation;Development;Development Plans;disability;Engineering;Evaluation;experience;experimental study;Exposure to;Female;functional improvement;Funding;Genes;Genetic;Genetic study;genome editing;Glucose;Goals;Hand;Health;Hibernation;Human;improved;improved outcome;in vitro Model;in vivo;in vivo Model;Individual;Injury;insight;interest;Ischemia;Ischemic Stroke;K-Series Research Career Programs;Knock-in;Link;male;Mammals;Measurement;Measures;Mediating;Membrane Potentials;Mentors;Mentorship;Metabolic;metabolic phenotype;Metabolic stress;Middle Cerebral Artery Occlusion;military veteran;Mitochondria;mitochondrial membrane;Morbidity - disease rate;mortality;Mus;Nature;Nervous System Disorder;neural;neuron loss;neuronal metabolism;neuronal survival;Neurons;neuroprotection;Neuroprotective Agents;neurovascular;new therapeutic target;novel;novel therapeutic intervention;Outcome;oxidative damage;Oxygen;Pathway interactions;Patient-Focused Outcomes;Permeability;Physicians;Physiological;Physiology;Positioning Attribute;prevent;programs;promote resilience;Property;protein expression;protein function;Proteins;Public Health;Research;Research Personnel;resilience;Resistance;respiratory;RIPK3 gene;Role;Signal Pathway;statistics;stressor;Stroke;stroke model;Techniques;Technology;Testing;Time;timeline;tool;Toxin;Training;Training Programs;translational potential;treatment strategy;United States;Variant;Veterans;Visualization;Work

PROJECT_TITLE: Resilience mechanisms of Arctic ground squirrel neurons


ORG_CITY: MILWAUKEE

ORG_NAME: CLEMENT J. ZABLOCKI VA MEDICAL CENTER

ORG_STATE: WI

PHR: Dysfunctional breathing is the major cause of morbidity and mortality after traumatic cervical spinal cord injury (cSCI). It often necessitates assisted ventilation, thus stressing the need to develop strategies to restore breathing. Individuals with cSCI continue to suffer from respiratory complications throughout life. As the incidence of spine trauma has been increasing in modern warfare and the incidence of progressive cervical spinal cord injury increases due to an aging veteran population, SCI will continue to provide a significant challenge to the Veterans affairs. This proposal examines a novel and clinically impactful treatment option with a particular focus on promoting respiratory plasticity of the spared respiratory neural network at a late stage after cSCI. Promoting recovery in the chronic phase is an extremely challenging task. By improving the respiratory function of military veterans who have sustained a cervical SCI, a significant number of health complications and mortality will be prevented.

PI_NAMEs: KURPAD, SHEKAR N. (contact)

PROJECT_TERMS: Aging;Anatomy;Area;Brain Stem;Breathing;Cell Nucleus;Cervical;Cervical spinal cord injury;Cervical spinal cord structure;Cholera Toxin Protomer B;Chronic;Chronic Phase;Clinical;Communication;Communities;Data;Dependence;designer receptors exclusively activated by designer drugs;Development;Devices;Electromyography;Elements;Ensure;experimental study;Face;Goals;Health;health care delivery;high risk;Impairment;improved;Incidence;Individual;Injury;innovation;insight;Interneurons;Knowledge;Life;Long term disability;Maintenance;Maps;Mechanical ventilation;Military Personnel;military veteran;Modernization;Modification;Morbidity - disease rate;mortality;Motor Neurons;Motor output;Mus;Muscle;neural;neural network;Neuronal Plasticity;Neurons;Neurosciences;novel;novel strategies;novel therapeutic intervention;Operative Surgical Procedures;Outcome;Output;Patients;Penetration;Pharmacogenetics;Phase;Play;Population;prevent;Publishing;Quality of life;Recovery;Recovery of Function;Respiration Disorders;respiratory;Respiratory Center;Respiratory Diaphragm;respiratory examination;Respiratory Insufficiency;Respiratory physiology;Role;sex as a biological variable;Shapes;Spinal;Spinal Cord;Spinal cord injury;Spinal cord injury patients;Stress;Survivors;Synapses;Techniques;Technology;Therapeutic;therapeutic target;therapy development;Time;Tracer;Transgenic Mice;treatment strategy;United States;United States Department of Veterans Affairs;ventilation;Ventilator;Veterans;Viral;Weaning;Whole Body Plethysmography;Work

PROJECT_TITLE: Stimulation of Cervical Excitatory Interneurons to Restore Breathing After Chronic Cervical Spinal Cord Injury


ORG_CITY: BUFFALO

ORG_NAME: VA WESTERN NEW YORK HEALTHCARE SYSTEM

ORG_STATE: NY

PHR: The proposed research is relevant to the public health because CRPC and advanced CaP, are increasingly becoming refractory and difficult to treat, represents a major national cost measured by both patient suffering and economic burden; and despite significant advances in care, clinical data suggest that refractory rates are at 30%. Upon conclusion, we will understand the role for co-delivery of chemotherapeutic agent and gene silencing agent in treatment outcomes for refractory and advanced CaP, and this discovery will stimulate the opening of a new avenue in nanoparticle based targeted therapeutics for prostate cancer.

PI_NAMEs: SCHWARTZ, STANLEY A (contact)

PROJECT_TERMS: ABCB1 gene;Acids;advanced prostate cancer;Affinity;Age;agent orange;Aging;American;androgen deprivation therapy;androgen independent prostate cancer;Animal Model;Apoptosis;Azides;Binding;Biodistribution;biomaterial compatibility;Bypass;cancer cell;Cancer Etiology;Caring;Cell Culture System;Cell Survival;Cessation of life;Charge;chemical synthesis;Chemistry;chemotherapeutic agent;chemotherapy;Clinical Data;copolymer;Copper;Cost Measures;cytotoxicity;Data;Development;Diagnosis;Dimensions;Disease;docetaxel;Dose;Dose Limiting;Doxorubicin;Drug Carriers;Drug Delivery Systems;Drug Kinetics;Economic Burden;effective therapy;Electrostatics;Encapsulated;Engineering;Exposure to;FDA approved;FOLH1 gene;Gene Silencing;gene therapy;General Population;Goals;Healthcare Systems;Herbicides;Histone Deacetylase Inhibitor;Human;human model;Hydrophobicity;IL8 gene;imaging agent;improved;In Vitro;in vivo;Incidence;innovation;Knock-out;Ligands;Liver;liver metabolism;male;Malignant neoplasm of lung;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;men;Microtubules;military veteran;molecular recognition;Multi-Drug Resistance;multimodality;nano;nanocarrier;nanoparticle;Nature;North America;novel;novel therapeutics;Operative Surgical Procedures;overexpression;Paclitaxel;Patients;Pharmaceutical Preparations;Pharmaceutical Solutions;Pharmacodynamics;pharmacokinetics and pharmacodynamics;pharmacologic;Pharmacotherapy;Physiological;Polysaccharides;pre-clinical;Pre-Clinical Model;Primary Neoplasm;Prognosis;Proliferating;promoter;prostate cancer cell;prostate cancer cell line;prostate cancer model;prostate cancer risk;Prostate Cancer therapy;Prostatic Neoplasms;Public Health;Radiation;Reaction;Refractory;Research;response;Risk;Role;side effect;Site;Small Interfering RNA;small molecule;specific biomarkers;Specificity;Surface;Survival Rate;System;targeted delivery;targeted treatment;theranostics;Therapeutic;therapeutic gene;Therapeutic Index;therapeutically effective;Time;Toxic effect;Treatment outcome;tumor;tumor growth;Tumor Markers;Tumor Volume;Tumor Weights;vector;Veterans;Veterans Health Administration;Work;Xenograft procedure

PROJECT_TITLE: A Multimodal Hierarchical Theranostic Nanoparticle for Castration Resistant Prostate Cancer


ORG_CITY: SAN DIEGO

ORG_NAME: VA SAN DIEGO HEALTHCARE SYSTEM

PHR: This project seeks to improve the prevention and treatment of sensorineural hearing loss (SNHL) in Veterans. The impacts of hearing loss on quality of life, psychological status and employability are of profound importance to Veterans, as military service carries a high risk of SNHL. This risk increases rapidly, since the degree and nature of military noise exposure has grown. In addition, SNHL and tinnitus are high-probability consequences of blast injury. An unfortunately high percentage of military personnel returning from Middle East duty have significant SNHL, with threshold shift and/or tinnitus. There are also profound financial implications for the VA. VA rehabilitation costs for hearing loss and tinnitus are high and rising rapidly. Disability payments for hearing disorders are higher than for any other disability, with costs exceeding $2.0 billion/year and estimated to reach $3 billion/year in the near future. Hearing- related disorders are the fastest growing disability, currently affecting more than a million veterans.

PI_NAMEs: RYAN, ALLEN F. (contact)

PROJECT_TERMS: Address;Affect;afferent nerve;Aging;Aminoglycosides;Antibiotics;ATP Receptors;Auditory Brainstem Responses;Blast Injuries;cell injury;Cell Physiology;Cell Survival;Cells;Cellular biology;Chronic;Clinical;Cochlea;Cochlear Hearing Loss;combat zone;Complex;cost;Cytoprotection;Data;Development;disability;disability payment;Disease;Ear;Environment;Etiology;Evaluation;Exposure to;Funding;Future;Gene Expression Regulation;gene therapy;Genetic;Goals;hair cell regeneration;Hair Cells;Health;Hearing;Hearing Aids;hearing impairment;hearing loss risk;Hearing problem;Hearing Tests;high risk;Human;improved;In Vitro;in vivo;in vivo Model;Individual;Intervention;Isotopes;knockout animal;knockout gene;Libraries;Mediating;Methodology;Methods;Microprocessor;Middle East;Military Personnel;military service;Morphology;mouse model;Nature;Nerve Endings;Noise;noise exposure;Noise-Induced Hearing Loss;novel;Organ of Corti;osmotic minipump;otoacoustic emission;ototoxicity;Outcome;Outer Hair Cells;Pathology;Pathway interactions;Peer Review;Perilymph;pharmacologic;Pharmacotherapy;prevent;prevent hearing loss;Prevention;Prevention therapy;Probability;Process;Progress Reports;Proteins;Proteomics;psychologic;Publications;Quality of life;Rehabilitation therapy;Research;Research Design;Resolution;Risk;round window;screening;Sensorineural Hearing Loss;Signal Transduction;sound;Source;Stimulus;targeted treatment;Temporary Threshold Shift;Testing;Therapeutic Intervention;Tinnitus;Tissues;Veterans

PROJECT_TITLE: Basic Mechanisms on Hearing Loss of Cochlear Origin


ORG_CITY: PORTLAND

ORG_NAME: PORTLAND VA MEDICAL CENTER

ORG_STATE: OR

PHR: This proposal will investigate the ability of a novel Neurotherapy called DRQ that is being developed by the Vandenbark laboratory to inhibit a newly implicated proinflammatory factor (TREM-1) and pathogenic T cells that can worsen clinical and histological signs of paralytic disease in a mouse model for multiple sclerosis (MS) called experimental autoimmune encephalomyelitis (EAE). The proposal will also evaluate the ability of DRQ to stimulate neuroprotective and regenerative pathways to help repair damaged myelinated axons during the DRQ-induced EAE recovery process. These studies will provide new insights into the pathogenic processes in EAE and MS and expand our understanding of the recovery and healing mechanisms stimulated by DRQ therapy that may also be applicable to other CNS conditions of interest to the VA, including stroke, methamphetamine use disorder and traumatic brain injury.

PI_NAMEs: VANDENBARK, ARTHUR A. (contact)

PROJECT_TERMS: Acute;Address;Animal Model;Applications Grants;Axon;Binding;Biological;Cells;Central Nervous System;chemokine;Chronic;Clinical;Clinical Trials;CNS Demyelinating Autoimmune Diseases;commercialization;complement pathway;Complex;Coupled;CX3CL1 gene;CXCL1 gene;CXCR;CXCR4 gene;cytokine;design;Designer Drugs;Disease;Dopachrome isomerase;Experimental Autoimmune Encephalomyelitis;extracellular;Female;Funding;Future;Generations;Genotype;Goals;healing;Health;Histologic;HLA-DR2 Antigen;Homologous Gene;Human;IL17 gene;IL8RB gene;Immune;Immunoglobulins;immunoregulation;improved;Individual;Inflammatory;insight;interest;Interferon Type II;Interleukin-2;Kinetics;Knockout Mice;Laboratories;Ligands;Light;Macrophage Activation;male;member;Methamphetamine use disorder;migration;Migration Inhibitory Factor;Monoclonal Antibodies;mouse model;Multiple Sclerosis;multiple sclerosis treatment;Mus;Myelin;Myeloid Cells;neurofilament;Neurofilament-L;Neurons;neuroprotection;novel;oligodendrocyte progenitor;Paralysed;Pathogenicity;Pathway interactions;Patients;Peptides;Persons;Phase;Phosphorylation;Phosphotransferases;Process;Production;Proliferating;receptor;Recovery;Regenerative pathway;remyelination;repaired;Resources;response;Risk;Rodent;Role;screening;Severities;Severity of illness;Signal Transduction;Solid;Spleen;Stress;Stroke;Stromal Cell-Derived Factor 1;System;T-Cell Receptor;T-Lymphocyte;Therapeutic;Tissues;Transgenic Mice;Traumatic Brain Injury;Treatment Efficacy;TREM2 gene;Variant

PROJECT_TITLE: Immunoregulation of Myelin Specific T Lymphocytes


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Clinical Research;Lung;Neurosciences;Sleep Research

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative/Relevance to Public Health: Sleep apnea patients with excessive daytime sleepiness are at highest risk for crashes related to drowsy driving. This proposal aims to identify the brain regions most impacted by sleep apnea and understand the underlying causes of individual differences in impact of sleep apnea. The long-term goal of this K25 is for Dr. Parekh to become an independent quantitative investigator capable of using cutting-edge mathematical tools to develop night-time biomarkers for daytime sleepiness.

PI_NAMEs: PAREKH, ANKIT ASHOK (contact)

PROGRAM_OFFICER_NAME: ALFINI, ALFONSO JOSEPH

PROJECT_TERMS: Adherence;Age;Area;Biological Markers;Brain region;career;career development;Cessation of life;Clinical;Complex;Continuous Positive Airway Pressure;Coupling;Data;design;Development;Doctor of Philosophy;Dose;Drowsiness;Drowsy Driving;educational atmosphere;Electroencephalography;Ensure;Excessive Daytime Sleepiness;experience;Experimental Designs;Feasibility Studies;Foundations;Functional disorder;Functional Magnetic Resonance Imaging;functional MRI scan;Funding;Goals;Grant;high risk;Hospitalization;Hypoxia;image processing;imaging biomarker;Impairment;Individual;Individual Differences;inter-individual variation;International;Intervention Studies;Learning;Link;Maps;Mathematics;Measures;Mediating;medical schools;Medicine;Memory;Mentors;Methodology;Modeling;multidisciplinary;multimodality;Nerve Degeneration;neurobehavioral;Neurobiology;neuroimaging;Neurologic Dysfunctions;neuromechanism;Neuropsychology;novel;Obstructive Sleep Apnea;patient oriented research;Patients;Performance;performance tests;predicting response;Prefrontal Cortex;pressure;Public Health;Reaction Time;recruit;Research;Research Personnel;Residual state;Risk;risk stratification;Severities;signal processing;Sleep;Sleep Apnea Syndromes;Sleep Deprivation;Sleep Fragmentations;sleep physiology;sustained attention;Testing;Thalamic structure;Therapeutic;tool;Training;treatment response;United States National Institutes of Health;vigilance;Withdrawal;Work

PROJECT_TITLE: Sustained Attention Neuroimaging in Sleep Apnea

STUDY_SECTION: MTI

STUDY_SECTION_NAME: NHLBI Mentored Transition to Independence Study Section[MTI(OA)]