ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Emerging Infectious Diseases;Infectious Diseases

ORG_CITY: Evanston

ORG_NAME: OPERA BIOSCIENCE, INC.

ORG_STATE: IL

PHR: Growth factors are essential components of pharmaceutical research, development, and manufacturing, supporting recombinant protein production and growth of live cellular therapies for myriad applications. Current protein expression technologies suffer from high costs or low yields of many growth factors, which cascades to increasing the cost, sometimes prohibitively, of therapeutic development and manufacturing. Here, we propose to prepare our engineered secretion-based protein production platform for industrial, commercial use by developing a robust, safe strain and optimal process conditions to solve the challenges of current protein expression systems by matching product yields, decreasing process complexity, and lowering costs.

PI_NAMEs: LIANG, JULIE MING (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Acceleration;Address;anti-microbial peptide;Attenuated;Bacterial Proteins;Bioinformatics;bioinformatics tool;Biological Assay;Biological Sciences;Biomedical Research;Bioreactors;Carrier Proteins;Cell Culture Techniques;Cell Therapy;Cells;Chemicals;chimeric antigen receptor T cells;Classification;commercial application;commercialization;cost;cost effective;cytokine;Cytolysis;Cytoplasmic Protein;Data;Development;Disease;disease phenotype;Drug Targeting;Elements;Engineering;Environment;Environmental Risk Factor;Enzymes;Escherichia coli;experience;Extracellular Space;Fermentation;flexibility;Fluorescence;Future;Genes;Genetic;genetic manipulation;genomic data;Genomics;Goals;Government Agencies;Growth;Growth Factor;high throughput screening;Immunoglobulin Fragments;improved;industrial production;Industrialization;inorganic phosphate;Laboratories;Life;manufacture;manufacturing cost;manufacturing technology;Measures;Mechanics;Microbial Biofilms;milligram;Modeling;non-Native;novel;novel therapeutics;Organism;Osmolar Concentration;Outcome;Oxygen;pathogen;Pathogenicity;Pathology;Performance;Pharmacologic Substance;Phase;Process;process optimization;Production;Productivity;promoter;protein aggregation;protein expression;Protein Secretion;Proteins;Publishing;Recombinant Growth Factor;Recombinant Proteins;Recovery;Research;research and development;response;Risk;Route;Safety;Salmonella typhimurium;Sampling;shear stress;Small Business Innovation Research Grant;Stimulus;Structure;Supporting Cell;Surface;Suspension Culture;System;targeted treatment;Technology;Temperature;Therapeutic;therapeutic candidate;therapeutic development;Therapeutic Intervention;Therapeutic Research;Therapeutic Uses;Time;timeline;tool;Treatment Cost;Type III Secretion System Pathway;United States National Institutes of Health;Virulence;Virulent;Work

PROJECT_TITLE: A new platform for inexpensive and scalable recombinant protein and growth factor production to support cell culture applications in therapeutics.

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MCST-G (15)]


ADMINISTERING_IC: VA

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: Veterans Affairs

ORG_CITY: BALTIMORE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: BALTIMORE VA MEDICAL CENTER

ORG_STATE: MD

PHR: High blood pressure - Hypertension (HTN) - and its sequelae heart failure (HFpEF) are common in US Veterans. Neither are optimally treated with current medicines. This proposal will test a novel therapy in animal models of HTN and HFpEF. The novel therapy is a conjugated anti-sense oligonucleotide (ASO). In the past few years, ASO and similar biologicals have been approved for the treatment of uncommon genetic diseases and most recently high cholesterol. Here we test an ASO that causes a shift in naturally occurring enzyme isoforms in blood vessel smooth muscle cells. It is predicted to make them more sensitive to the signals that dilate the blood vessel; thereby, lowering blood pressure and improving blood flow and ameliorating symptoms of heart failure. Advantages over current therapies could include greater potency by influencing multiple signlaing pathways, and prolonged duration of effect enabling infrequent treatment and improved patient compliance. If successful this novel gene therapy could improve and prolong the lives of the many US Veterans living with HTN and HFpEF.

PI_NAMEs: FISHER, STEVEN A. (contact)

PROJECT_TERMS: 5' Splice Site;Accounting;Affect;aged;Alternative Splicing;Amyloid;Angiotensin II;Animal Model;Antisense Oligonucleotides;Arteries;Binding;Blood Chemical Analysis;Blood flow;Blood Pressure;blood pressure control;blood pressure reduction;Blood Vessels;C-terminal;Cardiomyopathies;Cardiovascular system;Cholesterol;Clinical;Code;Cre-LoxP;Cyclic GMP;Cyclic GMP-Dependent Protein Kinases;Data;Defect;Deoxycorticosterone;design;Development;Diet;Dilator;Disease;Dose;Drug Design;Echocardiography;efficacy validation;EFRAC;Elderly;Enzymes;Exclusion;Exons;experimental study;Fatty acid glycerol esters;Felis catus;Female;gene therapy;Genes;Genetic Diseases;Group Therapy;Health system;Heart failure;high salt diet;Histologic;Human;human disease;Human Genetics;Hyperlipidemia;Hypertension;hypertension treatment;hypertensive;improved;indexing;Inflammatory;inflammatory marker;Injections;Kinetics;knock-down;Knowledge;Leucine Zippers;male;Measures;Mediating;Medicine;Messenger RNA;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;Muscle relaxation phase;Myosin ATPase;myosin phosphatase;Myosin S-1;Nitric Oxide;novel;novel strategies;novel therapeutics;Obesity;oligonucleotide therapeutics;Oligonucleotides;Osmosis;osmotic minipump;Pathway interactions;Patient Compliance;Peripheral Resistance;Pharmaceutical Preparations;Phosphotransferases;Pilot Projects;Prealbumin;premature;preservation;Prevalence;primary endpoint;Protein Dephosphorylation;protein function;Protein Isoforms;Reading Frames;Recovery;reduce symptoms;Renaissance;response;RNA;RNA Splicing;Rodent;Running;secondary endpoint;Signal Pathway;Signal Transduction;small molecule;Smooth Muscle;Smooth Muscle Myocytes;Sodium Chloride;Specificity;Terminator Codon;Testing;Therapeutic;Time;Transcript;treadmill;Vascular Smooth Muscle;Vasoconstrictor Agents;Vasodilation;Vasodilator Agents;Veterans;Western Blotting

PROJECT_TITLE: A splice blocking anti-sense oligonucleotide as a novel therapy for US Veterans with hypertension and heart failure (HFpEF)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 CARB-R (01)]


ADMINISTERING_IC: MD

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Networking and Information Technology R&D (NITRD);Nutrition;Obesity;Pediatric;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Rehabilitation;Rural Health;Telehealth

ORG_CITY: CLEMSON

ORG_NAME: MACHINE AND HUMAN INTERACTION LLC.

ORG_STATE: SC

PHR: Project Narrative Despite the prevalence of obesity among African American adolescents2, both access and adherence to intensive, evidence-based behavioral interventions are challenges, especially for those living in rural areas 32,33,34. DWN-FIT developed by Machine and Human Interaction proposes to address adolescent obesity using mobile technology and human-in-the-loop automation to deliver evidence-based interventions that increase this patient population’s access and adherence to treatment and their engagement in healthy behaviors.

PI_NAMEs: MCCLENDON, JEROME L (contact)

PROGRAM_OFFICER_NAME: JOHNSON, JARRETT AINSWORTH

PROJECT_TERMS: 17 year old;Address;Adherence;Adolescent;Adolescent obesity;Adult;African American;Age;American;Asian;Asthma;Automation;Behavior;Behavior Therapy;Behavioral;Body Weight decreased;cardiometabolism;Cardiovascular system;Caregivers;Child;Client;Cognitive;commercialization;Community Healthcare;contingency management;cost;Costs and Benefits;data dashboard;Development;diet and exercise;digital;digital health;digital intervention;economic impact;Education;Effectiveness of Interventions;Elements;Ethnic Population;Evaluation;evidence base;evidence based guidelines;Evidence based intervention;Evidence based treatment;Family;Family health status;Family member;feasibility testing;Focus Groups;Friends;Gender;Geographic Locations;Guidelines;Health;Health Personnel;Health Services Accessibility;Healthcare;Hispanic;Home;Human;human-in-the-loop;improved;Incentives;innovation;Inpatients;Internet;Intervention;Length;meetings;Metabolic;mobile application;mobile computing;Monitor;Motivation;motivational enhancement therapy;multi-component intervention;Nurses;Obesity;obesity in children;Outcome;outcome disparities;Outpatients;Participant;patient population;Patient-Focused Outcomes;Phase;Physical activity;physical model;Prevalence;primary caregiver;prototype;Public Health;racial population;randomized trial;randomized, clinical trials;Reporting;Research;research and development;Risk;Risk Factors;rural African American;rural area;Site;skills;skills training;Social support;Source;South Carolina;standard care;symposium;telehealth;therapy design;Translating;Transportation;Travel;United States;usability;Validation;virtual healthcare;wearable device;Work;Youth

PROJECT_TITLE: Digitalization of a Multicomponent Family-Based Behavioral Intervention (Digital Wellness Nurse - FIT Families) for African American Adolescents with Obesity

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 SCIL-D (10)]


FUNDING_MECHANISM: NON-SBIR/STTR RPGS

ORG_CITY: COLUMBIA

ORG_NAME: HARRY S. TRUMAN MEMORIAL VA HOSPITAL

ORG_STATE: MO

PHR: Lung cancer is by far the number one cause of cancer-related deaths. Veterans have a higher risk of lung cancer and worse survival than the general population. Nearly 8,000 Veterans are diagnosed and 5,000 Veterans die each year from lung cancer. Cancer cells can develop resistance against all current anti-cancer drugs, allowing them to survive and cause recurrences. Over half of the lung cancer patients who have surgery intended to cure a cancer confined to the lung develop a metastatic recurrence, or secondary tumor in another body tissue, later and ultimately lose their lives. There is an urgent need for more effective personalized treatments, particularly for Veterans. Molecular study of the cell types responsible for drug resistances using cutting-edge sequencing and cancer models created from Veterans' tumors promise to identify new drug targets to overcome these resistances. Data generated from the proposed studies will help cancer physicians treating Veterans to rapidly identify better therapies to increase the cure rates from this devastating cancer.

PI_NAMEs: KAIFI, JUSSUF THOMAS (contact)

PROJECT_TERMS: 3-Dimensional;Adjuvant Chemotherapy;alveolar epithelium;anti-cancer research;Antineoplastic Agents;biobank;Bioinformatics;Biological Assay;Blood;cancer cell;Cancer cell line;cancer drug resistance;Cancer Etiology;cancer initiation;Cancer Model;Cancer Patient;cancer recurrence;Carboplatin;Carcinoma;Cause of Death;Cell Line;cell type;Cells;cellular targeting;Cessation of life;Chemoresistance;chemotherapy;Clinical;Clinical Trials;combat;Complex;Curative Surgery;Data;Data Set;Deposition;Development;Diagnosis;Disease;Disease Progression;Disseminated Malignant Neoplasm;Distant;Drug resistance;Drug Targeting;epithelial stem cell;Excision;experience;experimental study;Gene Expression;General Population;Genes;Genetic;Growth;high risk;Hospitals;Human;human RNA sequencing;human tissue;improved;in vivo;in vivo Model;innovation;Invaded;Libraries;Link;liquid biopsy;Localized Malignant Neoplasm;Lung;Lung Adenocarcinoma;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;Metastatic malignant neoplasm to brain;metastatic process;Metastatic/Recurrent;Methods;migration;Modeling;Molecular;Molecular Target;mouse model;Neoplasm Circulating Cells;Neoplasm Metastasis;neoplastic cell;new therapeutic target;Non-Small-Cell Lung Carcinoma;novel;Oncogenes;Oncogenic;Operative Surgical Procedures;Organ;Organoids;Outcome;Outcome Study;Paclitaxel;Pathway interactions;patient derived xenograft model;patient prognosis;Patients;Pattern;personalized medicine;Pharmaceutical Preparations;Phenotype;Physicians;Population;Positioning Attribute;pre-clinical;Pre-Clinical Model;prevent;Primary Neoplasm;Prognosis;Proliferating;Public Domains;Publishing;Recurrence;Recurrent tumor;Reproducibility;Research;Resistance;Resistance development;response;risk stratification;Role;Scientist;self renewing cell;single cell analysis;single cell sequencing;single-cell RNA sequencing;Squamous Cell Lung Carcinoma;standard of care;stem cells;Surgeon;System;Techniques;Testing;therapeutic target;Thoracic Surgeon;three dimensional cell culture;Time;Tissues;transdifferentiation;translational cancer research;Translations;treatment strategy;tumor;tumor growth;tumor heterogeneity;tumor initiation;tumor progression;Tumor Tissue;Tumorigenicity;Type II Epithelial Receptor Cell;Validation;Veterans

PROJECT_TITLE: Alveolar epithelial cell type 2 populations and single cell gene expressions in non-small cell lung cancer progression and drug resistance

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ONCB-A (01)]


ORG_CITY: BIRMINGHAM

ORG_NAME: BIRMINGHAM VA MEDICAL CENTER

ORG_STATE: AL

PHR: Amyotrophic lateral sclerosis (ALS) is a fatal degenerative disease of motor neurons and neither the location of disease onset nor the determinants of disease progression are well-characterized. This proposal will investigate the contribution of peripheral muscle-based signaling molecules (Smads) and their downstream effector molecules to ALS disease pathogenesis and progression. It will assess the utility of the components of Smad signaling in the clinical assessment of ALS patients. Thus, the proposal has the potential for uncovering novel directions for the development of ALS therapies and enhancing the clinical management of patients.

PI_NAMEs: KING, PETER H (contact)

PROJECT_TERMS: Acceleration;Affect;ALS patients;Amyotrophic Lateral Sclerosis;amyotrophic lateral sclerosis therapy;Basic Science;bench to bedside;Biological Assay;Biological Markers;Biopsy;BMP4;Cell Culture Techniques;Cells;Cessation of life;Clinic;Clinical;Clinical assessments;clinical biomarkers;Clinical Management;clinical phenotype;Coupled;cytokine;Data;Degenerative Disorder;Development;Diagnosis;Disease;disease prognosis;Disease Progression;effective therapy;Elements;Fibrosis;Functional disorder;Gene Silencing;Generations;Growth Factor;Health;Homeostasis;Human;IGF1 gene;immune activation;immune cell infiltrate;Impairment;in silico;Infiltration;Inflammation;Inflammatory;insight;Knock-out;Knowledge;Ligands;Link;Location;Macrophage;mast cell;Measures;Messenger RNA;MicroRNAs;miRNA expression profiling;mitochondrial dysfunction;Molecular;Monitor;Motor Neuron Disease;Motor Neurons;mouse model;Mus;Muscle;Muscle Cells;Muscle Fibers;muscle regeneration;Muscle satellite cell;Muscle Weakness;Muscular Atrophy;Myeloid Cells;neuromuscular;Neuromuscular Junction;neuromuscular system;neurotrophin 4;neutrophil;novel;novel therapeutics;Onset of illness;Organ;paracrine;Pathogenesis;Pathogenicity;Pathologic;Pathology;Pathway interactions;Patients;Peripheral;Peripheral Nerves;Phenotype;Plasma;Play;Population;pre-clinical;Process;Production;Prognosis;programs;Regulation;reinnervation;Research Priority;Role;Sampling;Signal Pathway;Signal Transduction;Signaling Molecule;Skeletal Muscle;Symptoms;System;targeted biomarker;Techniques;Testing;therapeutic biomarker;therapeutic target;Tissues;transcriptome;transcriptome sequencing;Transforming Growth Factor beta;Up-Regulation;Veterans;Work

PROJECT_TITLE: Sustained Smad signaling in ALS muscle promotes disease progression through a dysregulated miRNA transcriptome

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURE-E (01)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Emergency Care;Hematology;Neurosciences;Orphan Drug;Pain Research;Rare Diseases;Sickle Cell Disease

ORG_CITY: MONTROSE

ORG_NAME: HILLHURST BIOPHARMACEUTICALS, INC.

ORG_STATE: CA

PHR: This application aims to investigate and develop HBI-201, an oral nitrous oxide (N2O) therapeutic, for the treatment of acute pain associated with vaso-occlusive crises (VOC) in sickle cell disease (SCD) patients. This project will evaluate whether HBI-201 has an appropriate preclinical efficacy and toxicologic profile for further development in SCD, and also evaluate the clinical safety, tolerability, pharmacokinetic and pharmacodynamic profile of HBI-201 in normal healthy volunteers. If successful, this research will provide critical safety, dosing, and preclinical efficacy information for advancing HBI-201 into a Phase 2 clinical trial in SCD patients, with the ultimate objective being to provide a non-opioid therapeutic for home use to treat the severely painful VOC episodes of SCD patients, thus reducing the pain experienced by patients, the need for opioid-based therapy, and the need for patients to present to emergency departments and hospitals.

PI_NAMEs: BELCHER, JOHN D;GOMPERTS, EDWARD  (contact);SIMONE, DONALD

PROGRAM_OFFICER_NAME: RICE, MATTHEW WARNER

PROJECT_TERMS: Abdominal colic;Absence of pain sensation;absorption;Accident and Emergency department;Acute;Acute Pain;Address;Analgesics;Anesthetics;Animal Model;Anti-Anxiety Agents;aqueous;Basic Science;Biological Markers;Blood Vessels;Burn injury;Cannulas;Cell Degranulation;Cell membrane;Chemistry;Clinical;Clinical Research;Clinical Sciences;Clinical Trials;Coupled;Cyclic GMP;Data;Dependence;Development;Disease;Dose;drug development;Drug Kinetics;efficacy study;Environment;Equipment;Erythrocytes;Evaluation;experience;FDA approved;Formulation;Fracture;France;Gases;Gastrointestinal tract structure;Geography;Glutamine;Goals;healthy volunteer;Home;Hospitals;hydroxyurea;Hyperalgesia;Impairment;Inflammation;Inhalation;innovation;innovative technologies;Intestinal Absorption;Laboratories;Lung;manufacturability;manufacture;manufacturing process development;Masks;mast cell;Medical;Methods;Modality;mouse model;Mus;Nitrous Oxide;non-opioid analgesic;novel;novel therapeutics;Obstetric Labor;Obstruction;Opioid;opioid use;Oral;Oral Administration;Organ;Oxygen;Pain;Pain management;pain model;pain reduction;Pathology;Patients;pediatric emergency;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;Phase;Phase II Clinical Trials;preclinical efficacy;Preparation;prevent;Procedures;Property;Rattus;Recurrence;Reperfusion Injury;Research;Research Personnel;Resistance;Risk;Safety;Sickle Cell Anemia;Sickle Hemoglobin;Sterile coverings;Technology;Testing;Therapeutic;Tissues;Toxicology;vaso-occlusive crisis;vaso-occlusive pain;ventilation

PROJECT_TITLE: Oral N2O Therapy in Treating Acute Vaso-Occlusive Pain in Sickle Cell Disease


ADMINISTERING_IC: AR

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Emerging Infectious Diseases;Health Services;Infectious Diseases;Microbiome;Women's Health Research

ORG_CITY: PHILADELPHIA

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Project Narrative Acne is responsible for a greater global burden of disease than psoriasis, cellulitis, and melanoma. While antibiotics are the most often used oral treatment for women with acne, use of antibiotics may contribute to bacterial resistance, pharyngitis, inflammatory bowel disease, and colon and breast cancer. We will conduct a double-blind randomized controlled non-inferiority comparative effectiveness study of spironolactone versus doxycycline for women with acne. This study will address a critical research gap regarding whether spironolactone, which targets the hormonal factors underlying acne, is a safe and effective alternative to oral antibiotics for women with acne, as well as the impact of spironolactone versus doxycycline treatment on the microbiome.

PI_NAMEs: MARGOLIS, DAVID  (contact)

PROGRAM_OFFICER_NAME: UNDALE, ANITA H

PROJECT_TERMS: Acne;Adolescent;Adult;Adverse event;adverse outcome;Affect;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;Antimicrobial Resistance;Area;Attention;Bacterial Antibiotic Resistance;bacterial resistance;beta diversity;Blood Vessels;burden of illness;Cardiovascular Diseases;Caring;Cellulitis;Centers for Disease Control and Prevention (U.S.);Clinical;Clinical Trials;cohort;Collagen;Colon Carcinoma;comparative effectiveness;Comparative Effectiveness Research;comparative effectiveness study;compare effectiveness;Consensus;Dermatologist;Dermatology;Development;Disease;Diuretics;Double-Blind Method;Doxycycline;Drug Prescriptions;Effectiveness;Evaluation;evidence base;Expert Opinion;Guidelines;gut microbiome;Healthcare;Hormonal;improved;indexing;Inflammatory;Inflammatory Bowel Diseases;innovation;insight;Institute of Medicine (U.S.);interest;International;Interview;Isotretinoin;Lesion;Malignant Breast Neoplasm;Measures;medical specialties;Medicine;meetings;Melanoma;microbial;microbiome;off-label use;Oral;Outcome;Outpatients;participant enrollment;Pathogenesis;Patient-Focused Outcomes;Patients;Pharmaceutical Preparations;Pharyngitis;Policies;Potassium;primary outcome;Provider;Psoriasis;Quality of life;Questionnaires;Randomized;randomized trial;randomized, clinical trials;Recommendation;Research;Research Personnel;Retrospective Studies;Safety;Sampling;skin microbiome;Spironolactone;Taxonomy;Tetracyclines;Therapeutic;therapy duration;trial comparing;trial design;Vascular Diseases;Woman;women's treatment;Work

PROJECT_TITLE: A randomized, double-blind, multi-center comparative effectiveness study of spironolactone versus doxycycline hyclate for the treatment of acne in women

STUDY_SECTION: AMSC

STUDY_SECTION_NAME: Arthritis and Musculoskeletal and Skin Diseases Clinical Trials Study Section [AMSC]


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);Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Health Services;Neurodegenerative;Neurosciences;Sleep Research

ORG_CITY: MINNEAPOLIS

ORG_NAME: INNOVATIVE DESIGN LABS, INC.

ORG_STATE: MN

PHR: Project Narrative A review of sleep disturbance prevalence among persons with dementia reported that on average 1 in 3 residents suffer nighttime disturbances such as insomnia and disruption of sleep, wandering, day/night confusion, repeatedly leaving bed, nightmares, and hallucinations. These disturbances often lead to reduced health and lower quality of life for persons with AD/ADRD while causing tremendous stress among long-term care staff. A practical system capable of monitoring sleep quality in individuals with AD/ADRD in long-term care would allow staff and clinicians to better detect, document, tailor treatments, and monitor sleep, towards improved quality of care and quality of life.

PI_NAMEs: KABLAN, JOHN  (contact)

PROGRAM_OFFICER_NAME: LUO, YUAN

PROJECT_TERMS: Acoustics;Adherence;Admission activity;Aging;Algorithms;Alzheimer's Disease;Alzheimer's disease diagnosis;Alzheimer's disease patient;Alzheimer's disease related dementia;American;Beds;Body measure procedure;care providers;Caregivers;Caring;Clinic;Clinical;Clinical Trials;Clothing;Collaborations;Computer software;Confusion;Consult;Consumption;cost;Custom;Data;Databases;Dementia;Dementia caregivers;design;Development;Devices;Documentation;Education;efficacy evaluation;Electronics;Environmental Monitoring;Environmental Risk Factor;Event;experience;Faculty;Feedback;Hallucinations;Health;Health care facility;Health Insurance Portability and Accountability Act;Health Personnel;improved;Indiana;Individual;individualized medicine;innovation;Institution;Institutionalization;interest;Internet;Intervention;Intervention Studies;Lead;Light;Long-Term Care;Mattresses;Measures;Mechanics;medical schools;Medicine;Methods;millimeter;Minnesota;mobile application;Monitor;Movement;Neurology;Nightmare;Nonpharmacologic Therapy;Participant;Patients;Persons;Phase;Phase Transition;Physiologic pulse;Polysomnography;Population;Positioning Attribute;Prevalence;Production;programs;prototype;Provider;Public Health;Quality of Care;Quality of life;Radar;remote monitoring;Reporting;Research;Risk;Safety;Scientist;sensor;signal processing;Signal Transduction;Skin;Sleep;Sleep Disorders;Sleep disturbances;sleep quality;Sleeplessness;Small Business Innovation Research Grant;Stress;success;System;Technology;Telephone;Temperature;Testing;Time;transmission process;trend;United States National Institutes of Health;Universities;Update;web app;web based interface;wireless fidelity

PROJECT_TITLE: Automated, Assistive, Non-Contact Sleep Quality Monitor for Individuals with Alzheimer Disease


ORG_CITY: DALLAS

ORG_NAME: VA NORTH TEXAS HEALTH CARE SYSTEM

ORG_STATE: TX

PHR: Veterans with Chronic Kidney Disease (CKD) suffer accelerated cardiovascular disease, accelerated loss of bone, and premature mortality despite adequate control of blood pressure and blood chemistries. CKD incidence and prevalence are risking, with estimates of cost to the VA in excess of $19 billion. The causes and clinical manifestations of kidney disease are highly variable, yet clinicians have been approaching all patients uniformly. Development of clinical tools that could both identify Veterans at high risk for bone and cardiovascular complications and recommend personalized therapies for them would be of great clinical benefit. The modeling system to be implemented in this proposal addresses the complex aspects of the clinical manifestations and the multi-drug therapies required to achieve clinically relevant outcomes including preservation of bone mineral and decreased cardiovascular risk.

PI_NAMEs: LEDERER, ELEANOR D (contact)

PROJECT_TERMS: Acceleration;Address;Artificial Intelligence;Biochemical;Biological Assay;Biological Models;Blood;Blood Chemical Analysis;blood pressure control;bone;Bone Diseases;bone loss;bone preservation;bone turnover;calcification;Calcium;Cardiovascular Diseases;cardiovascular health;cardiovascular risk factor;Cardiovascular system;Chronic Kidney Failure;Clinical;clinical development;Clinical Trials;clinically relevant;Complex;computerized tools;cost estimate;cytokine;Data;Databases;Diabetes Mellitus;Dialysis patients;Disease;Dose;electronic medical record system;Funding;General Population;Goals;Guidelines;Heterogeneity;high risk;human data;Hypertension;Immunosuppression;improved;in silico;Incidence;Individual;individual response;Inflammatory;innovation;inorganic phosphate;Kidney Diseases;Knowledge;Learning;Measurable;Measures;Medical;Metabolism;military veteran;Minerals;Minority;Modeling;Morbidity - disease rate;mortality;Outcome;Patients;personalized medicine;personalized therapeutic;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Physicians;Population;predictive modeling;Premature Mortality;Prevalence;Process;Provider;Psychological reinforcement;PTH gene;Radiology Specialty;Recommendation;recruit;Research;Serum;soft tissue;standard of care;success;Systems Biology;Techniques;Testing;Therapeutic;tool;Translating;translational approach;Treatment Protocols;treatment response;United States Department of Veterans Affairs;uptake;Urine;Vascular calcification;Vascular Smooth Muscle;Veterans;Work

PROJECT_TITLE: Systems Biology Approach to the Management of Chronic Kidney Disease-Mineral Bone Disorder

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ENDB-E (01)]


ORG_CITY: TUCSON

ORG_NAME: SOUTHERN ARIZONA VA HEALTH CARE SYSTEM

ORG_STATE: AZ

PHR: Mild traumatic brain injury (mTBI) is the most common traumatic brain injury affecting military personnel. mTBI may become a long-term debilitating condition associated with inflammation in the central nervous system (CNS), manifesting as headache, diffuse pain, cognitive impairment, and sleep disturbance. Opioids are a poor option for managing mTBI and other chronic pain conditions because of significant side effects, paradoxical pain, and misuse potential. We have shown that green light therapy (GLED) is effective in several pain conditions, including mTBI. GLED is mediated through the visual system, which projects to the periaqueductal gray (PAG), one of the primary control centers for pain modulation. This proposal seeks to elucidate the role of GLED in modulating the pain descending-facilitatory pathway starting from the PAG using a validated mTBI model. This knowledge will facilitate the development of an innovative regenerative medicine application using GLED to address the consequences of mTBI.

PI_NAMEs: IBRAHIM, MOHAB M (contact)

PROJECT_TERMS: active duty;Acute Pain;Address;Affect;Afghanistan;Age;Anti-Inflammatory Agents;antinociception;associated symptom;Astrocytes;Attenuated;Behavior;Brain;Cause of Death;Cells;Central Nervous System;Cerebrospinal Fluid;Chronic;chronic pain;chronic painful condition;clinical implementation;clinical translation;Clinical Trials;comorbidity;Coupled;cytokine;Development;Diffuse;Drops;Environment;experimental study;Exposure to;Female;Fibromyalgia;Freedom;Headache;high risk;Human;Human Resources;Hypersensitivity;Immunohistochemistry;Impaired cognition;improved;Individual;Inflammation;Inflammatory;innovation;Interleukin-10;Interleukin-6;Iraq;Knowledge;Lateral;Lateral Geniculate Body;Lidocaine;Light;male;Mechanics;Mediating;Medical;Methods;Microglia;midbrain central gray substance;Migraine;mild traumatic brain injury;Military Personnel;military veteran;minimally invasive;Modeling;Morphine;mouse model;Mus;Neuroglia;neuroinflammation;Neurologic Symptoms;neuronal circuitry;Neurons;North America;operation;Opiate Addiction;Opioid;opioid epidemic;opioid use;Pain;Pain Clinics;Pain management;Pathway interactions;Patients;Pharmaceutical Preparations;Photic Stimulation;Phototherapy;Plasma;Rattus;Recommendation;Recovery;regenerative;Regenerative Medicine;Reporting;response;Retina;Risk;Rodent;Role;Sedation procedure;sex;side effect;Sleep disturbances;Source;Spinal Cord;substance misuse;Symptoms;TNF gene;translational potential;Traumatic Brain Injury;Veterans;Visual;Visual System;Weight

PROJECT_TITLE: Identifying the Role of the Periaqueductal Gray in Mediating Traumatic Brain Injury Induced Thermal and Mechanical Hypersensitivity Reduction After Green Light Exposure

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURP-N (01)]


ORG_CITY: WEST HAVEN

ORG_NAME: VA CONNECTICUT HEALTHCARE SYSTEM

ORG_STATE: CT

PHR: Using a state-of-the art isotopic techniques, lipidomic and molecular analyses, the investigators will assess how fructose derived lipids adversely affect adipose tissue function, whether the addition of dietary fat further compounds fructose mediated adipose function and how hepatic fructose metabolism may augment aspects of liver insulin action. These studies will provide new insights into how inhibition of ketohexokinase, the first enzyme of fructose metabolism, may alter glucose and lipid metabolism to improve insulin sensitivity.

PI_NAMEs: SAMUEL, VARMAN T (contact)

PROJECT_TERMS: Accounting;ADD-1 protein;Adipocytes;Adipose tissue;Affect;Alanine;Antisense Oligonucleotides;Biological;Calories;Cardiovascular Diseases;Cell membrane;Chylomicrons;Consumption;Data;design;Diacylglycerol Kinase;Diet;dietary;Dietary Fats;Diglycerides;Dihydroxyacetone Phosphate;Disease;Dose;Enzymes;Esterification;Etiology;Exposure to;Fat-Restricted Diet;Fatty acid glycerol esters;Fructose;Functional disorder;Glucokinase;Glucose;Glucose Clamp;glucose metabolism;glucose uptake;Glycerol;Glycogen;Hepatic;High Fat Diet;Human;Hydroxysteroid Dehydrogenases;Hyperinsulinism;Impairment;improved;In Vitro;in vivo;Inflammation;inhibitor;insight;Insulin;Insulin Receptor;Insulin Resistance;insulin sensitivity;insulin signaling;Intestines;Isotopes;Ketohexokinase;Kidney;Leucine;Link;lipid biosynthesis;lipid metabolism;lipidomics;Lipids;Lipolysis;Liver;Liver Glycogen;liver metabolism;Mediating;Metabolic Diseases;Metabolism;Metformin;Molecular Analysis;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;novel;Nutrient;obesogenic;Oral;Pathway interactions;Pharmacologic Substance;Phosphorylation;Phosphotransferases;prevent;Production;Protein Isoforms;protein kinase C epsilon;Rattus;recruit;Research Personnel;Rodent;Role;Signal Transduction;Sucrose;sugar;Techniques;Testing;Tissues;Triglycerides;uptake;Very low density lipoprotein;very low density lipoprotein triglyceride

PROJECT_TITLE: Exploring the mechanisms by which dietary fructose primarily impairs white adipose, not hepatic, function: insights from a novel ketohexokinase antisense oligonucleotide

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ENDA-L (01)]


ORG_CITY: OMAHA

ORG_NAME: OMAHA VA  MEDICAL CENTER

ORG_STATE: NE

PHR: Inflammatory bowel disease (IBD) is a conglomerate of debilitating auto-immune disorders of the gastrointestinal tract, which significantly affect one’s lifestyle including active-duty army personnel and the Veterans. Studies for the Department of Veterans Affairs however found that the incidence of IBD among Veterans has recently increased 2-3 folds. An improved understanding of the causal regulation of this increase in IBD in Veterans can open novel therapeutic opportunities. In this proposal, we will perform “Proof-of-Concept” and mechanistic research to understand the causal role of Gut Microbiota associated with Post-Traumatic Stress Disorder (PTSD) in the Veterans in promoting IBD risk and severity. Critical concepts that will be evaluated include whether PTSD- associated Gut Dysbiosis promotes IBD risk by synergizing with gut barrier dysfunctions. Anticipated outcome from the proposed studies will have significant impact upon the clinical management of IBD, the quality of life of the Veterans IBD patients, and in reducing the economic burden of the VA-hospital system.

PI_NAMEs: SINGH, AMAR B (contact)

PROJECT_TERMS: active duty;Address;Affect;antimicrobial;Anxiety;Army Personnel;Autoimmune Diseases;Award;Behavior;biological adaptation to stress;Biological Response Modifier Therapy;Chronic stress;Clinical Management;Colitis;Collaborations;collaborative approach;Data;Defect;Dependence;Development;diarrheal disease;Digestive System Disorders;Disease;disease model;disease prognosis;disorder risk;dysbiosis;Economic Burden;Epithelium;Functional disorder;Funding;Gastroenterology;Gastrointestinal Diseases;Gene Modified;gut dysbiosis;gut microbiome;gut microbiota;Gut Mucosa;Health;Healthcare Systems;high risk;Hospitals;Human;humanized mouse;improved;in vivo;in vivo Model;Incidence;Inflammatory;Inflammatory Bowel Diseases;injury and repair;intestinal epithelium;Knowledge;Leaky Gut;Life Style;Link;Liver diseases;meetings;Metagenomics;microbiome;microbiota;Modality;Modeling;Molecular;mouse model;Mus;novel;novel strategies;novel therapeutics;Organoids;Outcome;Pathway interactions;Patients;Persian Gulf Syndrome;Pilot Projects;Play;Post-Traumatic Stress Disorders;Pre-Clinical Model;Predisposition;proctolin;Proteins;Publishing;Quality of life;Regulation;Reporting;Research;Resource Sharing;Risk;Role;Services;Severity of illness;Signal Transduction;Specimen;Stress;Study models;Symptoms;synergism;System;Technology;Testing;transcriptome sequencing;translational impact;United States Department of Veterans Affairs;Validation;Veterans

PROJECT_TITLE: Role of PTSD associated gut dysbiosis and barrier dysfunctions in promoting IBD in Veterans

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 GAST-L (01)]


ORG_CITY: BOSTON

ORG_NAME: VA BOSTON HEALTH CARE SYSTEM

ORG_STATE: MA

PHR: Prostate cancer is the most common non-skin cancer among Veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that healthcare providers screen male Veterans for prostate cancer.

PI_NAMEs: VASSY, JASON L (contact)

PROJECT_TERMS: aged;arm;black men;cancer diagnosis;Cancer Etiology;cancer therapy;Caring;Cessation of life;Classification;Clinical;clinical diagnosis;clinical practice;clinical predictors;Clinical Trials;clinically significant;Cohort Studies;cost;Diagnosis;Disease;disorder prevention;Enrollment;Equity;ethnic minority population;Ethnic Origin;Event;expectation;Family;follow-up;Genetic;Genetic Risk;genetic testing;genetic variant;Genetic Variation;Genotype;Germ Lines;Guidelines;Harm Reduction;Health Promotion;health related quality of life;high risk;high risk men;improved;Incidence;Individual;Intervention;Magnetic Resonance Imaging;Malignant neoplasm of prostate;Malignant Neoplasms;men;Metastatic Prostate Cancer;Morbidity - disease rate;National Comprehensive Cancer Network;Outcome;overtreatment;Participant;Patient Self-Report;Patients;personalized screening;Phase;Policies;polygenic risk score;Population;pragmatic trial;Predisposition;preference;primary care provider;programs;Prostate;prostate biopsy;prostate cancer metastasis;PSA screening;Race;racial minority population;randomized, clinical trials;rare variant;Recording of previous events;Risk;Risk Factors;risk stratification;screening;Screening for Prostate Cancer;screening guidelines;Specific qualifier value;Standardization;Subgroup;Testing;Time;treatment as usual;trial comparing;United States Preventative Services Task Force;Unnecessary Procedures;unnecessary treatment;usual care arm;Variant;Veterans;Veterans Health Administration

PROJECT_TITLE: The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS): A pragmatic trial of precision prostate cancer screening

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 ONCA-S (01)]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Eye Disease and Disorders of Vision;Networking and Information Technology R&D (NITRD);Neurosciences;Pediatric

ORG_DEPT: BIOLOGY

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: Project Narrative In humans and in monkeys neurological findings, functional magnetic resonance imaging (fMRI), and electrophysiology have all converged to show that the object recognition part of the visual pathway is divided up into domains specialized for processing specific object categories, such as faces, text, places, and body parts; these domains underlie complex social behavior, and astonishing skills like fluent reading. The project goal is to probe the circuitry underlying the remarkable selectivity of neurons in these domains by introducing specific manipulations of early visual experience. Early life experiences clearly can have long lasting consequences, and treating these consequences requires an understanding of how some kinds of experience, or the deprivation thereof, can permanently change how the brain processes visual information.

PI_NAMEs: LIVINGSTONE, MARGARET S (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: Acute;Adolescent;Adult;Age;Amblyopia;Animal Testing;Animals;Area;Augmented Reality;Behavior;Behavioral;Birth;Blinking;Body part;Brain;Categories;Cells;Chronic;Cognitive;Color;Complex;contrast imaging;Coupled;cytochrome c oxidase;Darkness;deprivation;Development;Devices;early experience;Electrophysiology (science);Equilibrium;Exclusion;experience;extrastriate visual cortex;Eye;Eye Movements;Face;Felis catus;Functional Magnetic Resonance Imaging;generative adversarial network;Goals;Goggles;Helmet;Histocytochemistry;Human;Image;Individual;Infant;inferotemporal cortex;Left;lens;Life Experience;Light;light weight;Lighting;liquid crystal;luminance;Macaca;Microcomputers;Monkeys;monocular;neural;Neurological observations;Neurons;novel;object perception;object recognition;Ocular Dominance;Optics;orientation selectivity;Pattern;Positioning Attribute;Primates;Reading;Research;Sensory;Shapes;Site;skills;Social Behavior;Spottings;statistics;Strabismus;System;Temporal Lobe;Testing;Tetrodotoxin;Text;Vision;Visual;visual information;Visual Pathways;visual processing;Visualization;wearable device;White Spots;Work

PROJECT_TITLE: Effects of abnormal early experience on IT circuitry


NIH_SPENDING_CATS: Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Chronic Pain;Neurosciences;Pain Research

ORG_CITY: NEW YORK

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

ORG_STATE: NY

PHR: PROJECT NARRATIVE Incomplete understanding of central mechanisms of pain has contributed to the dual public health crises of pain under-treatment and opioid overuse/misuse. The proposed research seeks to provide a novel predictive coding model for pain, based on multi-scale neural activities in the primary somatosensory cortex, anterior cingulate cortex, and the prefrontal cortex. Our new conceptual model indicates that dynamic integration of cortical circuits encode the perception of pain and has translational implications for pain diagnosis and treatment.

PI_NAMEs: CHEN, ZHE SAGE;WANG, JING  (contact)

PROGRAM_OFFICER_NAME: DAVID, KAREN KATE

PROJECT_TERMS: Acute Pain;Address;Affective;Algorithms;Anatomy;Anterior;Area;awake;Behavior;Brain;brain computer interface;Cells;central pain;chronic pain;cingulate cortex;Code;Cognitive;Complex;computer framework;Coupling;Data;design;Detection;Device Designs;Diagnosis;Emotional;Engineering;experience;Freund's Adjuvant;Human;Impairment;Location;machine learning method;Measures;millisecond;Modeling;Motor;Neocortex;nerve injury;neural;neuroimaging;Neuronal Plasticity;neurotransmission;Nociception;novel;novel diagnostics;novel therapeutic intervention;opioid overuse;optogenetics;Output;Pain;pain behavior;Pain Measurement;pain model;pain perception;pain signal;Peripheral;Prefrontal Cortex;Process;Public Health;Rattus;Regulation;Research;Resolution;response;Rodent;Rodent Model;Role;Scheme;Sensory;sensory cortex;sensory input;sensory integration;sensory neuroscience;Shapes;Signal Transduction;Somatosensory Cortex;spared nerve;spatiotemporal;Specificity;Statistical Data Interpretation;Statistical Methods;Stimulus;Testing;theories;Time;tool;Translating;Withdrawal

PROJECT_TITLE: Cortical information integration as a model for pain perception and behavior


ORG_CITY: IOWA CITY

ORG_NAME: IOWA CITY VA MEDICAL CENTER

ORG_STATE: IA

PHR: In the last 20 years over 3 million US military personnel have been deployed overseas and emerging evidence suggests that deployed personnel have a much greater risk of developing asthma. One potential explanation is that deployed U.S. military personnel experience elevated exposures to particulate matter and other inhalational exposures including desert dust, burn pit combustion, and industrial and military sources. In particular deployed troops are exposed to diesel fuel which is extensively used in ground equipment and tracked and wheeled vehicles. Diesel Exhaust Particles are the main component of exhaust particulate matter and exposure to increases oxidative stress, TH2 cytokine production and airway hyperreactivity. In this study, we will identify the mechanism by which TREM-1 regulates T cell function in lung to exacerbate allergic airway inflammation following inhalational exposures. Characterization of these pathways may identify novel therapeutics targets to treat and potentially prevent asthma.

PI_NAMEs: KLESNEY-TAIT, JULIA A (contact)

PROJECT_TERMS: Adoptive Transfer;Afghanistan;airborne allergen;airway hyperresponsiveness;airway inflammation;Allergens;Allergic;allergic airway disease;allergic airway inflammation;Asia;Asthma;asthmatic;atopy;Biological Process;Biological Response Modifiers;Biology;burden of illness;burn pit;CD4 Positive T Lymphocytes;Cell Physiology;Cells;chemokine;Coculture Techniques;Cohort Studies;combat;cytokine;Data;Data Reporting;Department of Defense;Development;Diesel Exhaust;Diesel Fuels;Disease;Dust;Economic Burden;effectiveness evaluation;Enterobacteria phage P1 Cre recombinase;Environmental Exposure;epidemiologic data;Equipment;Event;exhaust;experience;experimental study;Exposure to;Extrinsic asthma;Flow Cytometry;Foundations;Generations;Genetic;Goals;hazard;Health;Human;human disease;Human Resources;Immune;Immune response;improved;In Vitro;in vivo;Incidence;Individual;Industrialization;Inflammation;Inhalation;Inhalation Exposure;Investigation;Iraq;Licensing;Link;Literature;Lung;Measures;Mediating;Medical;Middle East;migration;Military Personnel;Modeling;Molecular;monocyte;Morbidity - disease rate;mortality;mouse model;Mus;Myeloid Cells;neutrophil;new therapeutic target;novel;novel therapeutic intervention;Outcome;Oxidation-Reduction;Oxidative Stress;Oxides;particle;Particulate Matter;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Pattern;permissiveness;Phenotype;Play;Positioning Attribute;Precipitation;Prevalence;prevent;Production;Reactive Oxygen Species;receptor;reconstitution;recruit;Regulation;Reporting;Research;Respiratory Disease;Respiratory Signs and Symptoms;response;Risk;Role;Sampling;service member;Severities;Signal Transduction;Source;Superoxides;synergism;System;T cell regulation;T cell response;T-Cell Activation;T-cell inflamed;T-Lymphocyte;Toll-like receptors;tumor-immune system interactions;United States;United States Department of Veterans Affairs;Veterans

PROJECT_TITLE: The Role of TREM-1 in the Regulation of Allergic Airway Inflammation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 PULM-N (01)]


ORG_CITY: SAN FRANCISCO

ORG_NAME: VETERANS AFFAIRS MED CTR SAN FRANCISCO

PHR: As veterans age, their skin increasingly develops eczema, dry skin, itch and increased susceptibility to contact dermatitis/infections. These diagnoses are an increasingly large proportion of aged veteran patient visits. In a survey of aged veterans, 38% reported itch. Similar skin problems are seen in younger patients with premature extrinsic skin aging due to particulate skin pollution, a problem made more relevant by newly described disease in veterans exposed to burn pit fumes. Decreases in the plasma membrane calcium receptor are to blame for many of these defects, particularly in veterans in the 70-90 age range. We aim to figure out why the plasma membrane calcium receptor is decreased in aged veteran skin and skin cells. We will use agents that stimulate this receptor to fix age-related growth and barrier defects. We will test these agents and find optimal treatments to improve skin dryness, itch and susceptibility to contact dermatitis. The overall goal here is to normalize age-related epidermal defects, thereby relieving age-related skin conditions common to veterans.

PI_NAMEs: MAURO, THEODORA M (contact)

PROJECT_TERMS: Age;age related;aged;Aging;Agonist;Aryl Hydrocarbon Receptor;Bacterial Infections;Binding;burn pit;Calcium;Calcium Oscillations;Calcium Signaling;Calcium-Sensing Receptors;Cell membrane;Cells;Ceramides;Contact Dermatitis;cost;Cutaneous;cytokine;Data;Defect;Diagnosis;Disease;Dryness;E-Cadherin;Eczema;Elderly;Epidermis;Epigenetic Process;epigenetic regulation;Exposure to;Functional disorder;Gene Expression;Genetic;Genetic Transcription;Goals;Growth;Health;Homeostasis;Impairment;improved;in vitro Model;in vivo;Infection;Infectious Skin Diseases;Inflammatory;innovation;insight;Intrinsic drive;keratinocyte;keratinocyte differentiation;Lasers;Link;Lipids;Long-Term Effects;Mediating;Metabolism;migration;Morbidity - disease rate;Motility;mouth squamous cell carcinoma;Mus;Mycoses;old mice;optimal treatments;Particulate;pathological aging;Pathway interactions;Patients;Pollution;Population;Predisposition;premature;Process;Proliferating;promoter;Pruritus;Published Comment;receptor;receptor expression;receptor for advanced glycation endproducts;receptor function;Receptor Signaling;Reporting;response;Risk;Serum;side effect;Signaling Protein;Skin;Skin Aging;skin barrier;skin damage;skin disorder;Source;sphingosine 1-phosphate;Structural Protein;Surveys;systemic inflammatory response;Testing;Therapeutic;therapy development;Thinness;Topical agent;Topical application;Topical Corticosteroids;Transcriptional Regulation;Veterans;Visit;Vitamin D;Vitamin D3 Receptor

PROJECT_TITLE: Optimizing Keratinocyte Calcium Signaling Enhances Differentiation in Aged Epidermis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 IMMA-G (01)]


FUNDING_MECHANISM: OTHERS

ORG_CITY: LOS ANGELES

ORG_NAME: VA GREATER LOS ANGELES HEALTHCARE SYSTEM

PHR: Influenza and pneumonia account for one in twenty deaths in the United States, placing a particularly high burden on older adults. Effective vaccination is key to mitigating this burden, however frailty and associated immune system aging, or immunosenesence, may limit the benefits from vaccination among older adults at the highest risk. This work will clarify the role of frailty in outcomes following influenza vaccination among older Veterans in the community and in long-term care within the VA Healthcare System. This will also pilot research to uncover the links among frailty, immunosenescence, and vaccine outcomes. This proposed research will inform vaccine policy within and outside the VA and lay the basis for work that will guide the development of future vaccines.

PI_NAMEs: SELIGMAN, BENJAMIN JOSEPH (contact)

PROJECT_TERMS: Acceleration;Address;Adjuvant;adverse outcome;Affect;aged;Aging;Award;Biological Markers;Biology;Blood;career development;Cessation of life;Clinical Assessment Tool;clinical outcome assessment;cohort;Cohort Studies;Communicable Diseases;Communities;community living;community setting;Data;Data Collection;Data Set;design;Development;Effectiveness;Electronic Health Record;Feasibility Studies;feasibility testing;Formulation;frailty;functional status;Future;Geriatrics;Goals;Grant;Health Status;Healthcare Systems;high risk;Hospitalization;Human;Immune system;immunosenescence;Impairment;improved;indexing;Infection;Influenza;influenza infection;Influenza prevention;Influenza vaccination;influenza virus vaccine;Integrated Health Care Systems;Link;Long-Term Care;Los Angeles;Measures;Mediating;Mediator;Mentors;Morbidity - disease rate;mortality;novel vaccines;older adult;Outcome;Pathway interactions;Physiological;Pneumonia;Policies;Population Heterogeneity;prevent;Prevention;programs;prospective;Prospective Studies;Recommendation;Recovery;Research;Research Personnel;Respiratory Tract Infections;Risk;Role;Sampling;seasonal influenza;Source;Streptococcus pneumoniae;stressor;Syndrome;T-Lymphocyte Subsets;Testing;United States;United States Department of Veterans Affairs;Vaccinated;Vaccination;vaccination outcome;vaccination strategy;vaccine development;vaccine effectiveness;vaccine response;Vaccines;Variant;Veterans;Veterans Health Administration;Work

PROJECT_TITLE: Frailty and Influenza Vaccination Among Older Adults

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 INFA-K (01)]


NIH_SPENDING_CATS: Assistive Technology;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Mental Health;Mental Illness;Neurosciences;Rehabilitation

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: We will apply highly specific stimulation and network-level electrical recording in rats to map which brain structures/pathways mediate the cognitive effects of deep brain stimulation (DBS) of the ventral internal capsule and striatum (VCVS). VCVS DBS has been proposed as a treatment for severe depression, obsessive-compulsive disorder, and even addiction. Results from this study could help us understand how VCVS DBS works and thus how to more effectively apply it in individual patients.

PI_NAMEs: WIDGE, ALIK S. (contact)

PROGRAM_OFFICER_NAME: HWANG, GRACE MEI-HUA

PROJECT_TERMS: addiction;Address;Animal Model;Animals;Axon;Behavior;behavior change;Behavioral;Biological;Biological Assay;Biological Markers;Biological Models;Brain;Cell Nucleus;Clinical;clinical efficacy;Clinical Trials;Cognition;Cognitive;cognitive control;cognitive function;cohort;Companions;Corpus striatum structure;Data;Deep Brain Stimulation;Dorsal;Dose;electric field;Electric Stimulation;Electrical Stimulation of the Brain;Elements;Entropy;executive function;experimental study;Feasibility Studies;Fiber;Frequencies;Functional disorder;Goals;gray matter;Homologous Gene;Human;human disease;improved;Individual;individual patient;Internal Capsule;lens;Lesion;Location;Long-Evans Rats;Maps;Measurement;Measures;Medial;Mediating;Mental Depression;Mental disorders;Methods;Modeling;National Institute of Mental Health;neural;Neurons;Obsessive-Compulsive Disorder;Opsin;Optics;optogenetics;Pathway interactions;Patients;Pattern;Performance;Physiological;Physiology;Population;Prefrontal Cortex;programs;psychiatric symptom;Psychiatrist;Psychiatry;Rattus;Reaction Time;Research Domain Criteria;response;Rodent;Role;Running;Site;Speed;Structure;success;symptomatic improvement;Symptoms;Technology;Testing;theories;Titrations;Transfection;Translating;translational model;Ventral Striatum;white matter;Work

PROJECT_TITLE: Circuit and Cognitive Mechanisms of Striatal Deep Brain Stimulation


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cerebrovascular;Dementia;Genetics;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: Los Angeles

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Microvascular injuries are commonly found in different forms of Alzheimer’s disease and related dementia, as well as in head injuries including traumatic brain injury and stroke. We have identified a common molecular signature in the brain endothelial cells between traumatic brain injury and aging at single-cell transcriptomic level, and validated it in stroke and Alzheimer models. By studying this common microvascular endophenotype between TBI, aging and Alzheimer’s disease, we hope to define a novel molecular signature for microvascular injuries.

PI_NAMEs: ZHAO, ZHEN  (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: adeno-associated viral vector;Age;age group;age related;Aging;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease related dementia;Anatomy;Antisense Oligonucleotides;Astrocytes;behavior test;Bioinformatics;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood Vessels;Brain;brain endothelial cell;Caspase;Cell Death;Cells;cerebrovascular;Cerebrovascular Disorders;Cerebrovascular system;Circulation;cognitive function;Collaborations;Craniocerebral Trauma;CRISPR/Cas technology;Data;Data Set;Development;Edema;Electron Microscopy;endophenotype;Endoplasmic Reticulum;Endothelial Cells;endothelial dysfunction;Endothelium;Event;Extravasation;Functional disorder;Gender;Gene Delivery;Goals;Homeostasis;Human;Hypoxia;Impaired cognition;Impairment;improved;in silico;In Vitro;in vivo;insight;Integral Membrane Protein;Intercellular Junctions;Intervention;Knockout Mice;Link;Magnetic Resonance Imaging;Membrane;Metabolic;Metabolic stress;mild traumatic brain injury;Mitochondria;Modeling;Molecular;Molecular Profiling;Molecular Target;multimodality;multiple datasets;Mus;Mutation;Nervous System Disorder;Neurologic;Neurological Models;Neuronal Dysfunction;Neurons;neuropathology;normal aging;novel;Nutrient;Pathogenesis;Pathologic;Pathway interactions;Phenotype;Physiological;Plasma Proteins;Poison;prevent;Proteins;Role;Sampling;seal;single cell analysis;single-cell RNA sequencing;small molecule inhibitor;Stress;Stroke;stroke model;Structure;System;Testing;Tg2576;Therapeutic Intervention;tool;transcriptomics;Traumatic Brain Injury;Up-Regulation;Validation;Vascular Diseases;vascular injury;wasting

PROJECT_TITLE: A TIMEM252-dependent Microvascular Endophenotype in  Alzheimer’s Disease

STUDY_SECTION: BINP

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


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

ORG_CITY: MEMPHIS

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF TENNESSEE HEALTH SCI CTR

ORG_STATE: TN

PHR: Narrative White matter damage has increasingly been recognized as an important contributing factor to neurodegeneration and the two most severe types of dementia: Alzheimer’s disease and vascular cognitive impaired dementia. The work proposed here will address a novel pericyte mediated signaling pathway as the underlying molecular and cellular mechanisms for white matter pathology induced by chronic hypoperfusion which may have therapeutic implication.

PI_NAMEs: LIAO, FRANCESCA-FANG  (contact);ZHOU, FU-MING

PROJECT_TERMS: Action Potentials;Age;Alzheimer's Disease;Alzheimer's disease patient;antagonist;Architecture;Area;astrogliosis;Axon;Blood - brain barrier anatomy;Blood Vessels;blood-brain barrier disruption;blood-brain barrier function;BMP4;Bone Morphogenetic Proteins;Brain;Cell Communication;Cell Separation;cell type;Cells;Cerebral Amyloid Angiopathy;Cerebral cortex;cerebral hypoperfusion;Chronic;Clinical;cohort;Corpus Callosum;demented;Dementia;Electrophysiology (science);Ensure;Event;Extravasation;Functional disorder;functional loss;Gene Mutation;gray matter;Health;Hemorrhage;hippocampal pyramidal neuron;Hippocampus;Histologic;Histology;Human;human old age (65+);hypoperfusion;Image;Immunohistochemistry;Impaired cognition;Impairment;In Vitro;in vivo;Infusion procedures;Label;Mediating;Membrane;Methods;Microvascular Dysfunction;middle age;Modeling;Molecular;mouse model;Mus;Myelin;neocortical;Nerve Degeneration;neural circuit;Neurodegenerative Disorders;neuroinflammation;neuronal circuitry;Neurons;neurophysiology;neurotransmitter release;neurovascular unit;NOS3 gene;novel;old mice;Oligodendroglia;Optics;Outcome;paracrine;patch clamp;Pathogenesis;Pathologic;Pathology;Patients;Peptide Initiation Factors;Pericytes;Play;preservation;Presynaptic Terminals;prevent;Property;Proteins;Regulation;Reporter;Role;Sampling;Signal Pathway;Signal Transduction;Slice;System;Techniques;Testing;theories;Therapeutic;therapeutic target;Tissues;transcriptome sequencing;Up-Regulation;Vascular Cognitive Impairment;Vascular Dementia;white matter;white matter change;white matter damage;White Matter Disease;Work

PROJECT_TITLE: Blood-brain-barrier and white matter mechanisms underlying dementia

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ORG_CITY: AUGUSTA

ORG_NAME: CHARLIE NORWOOD VA MEDICAL CENTER

ORG_STATE: GA

PHR: This exploratory study will help develop new methods of rehabiliting Veterans with vision loss. In this study, we will take advantage of the brain’s innate ability to compensate for vision loss by using hands as “seeing eyes”. Every aspect of the proposed research is geared toward ultimately helping our Veterans: We will exclusively recruit Veterans as study subjects, so that the outcomes are directly applicable to Veterans. Moreover, we will focus on Veterans with an eye disease called age-related macular degeneration, which is one of the most common causes of visual impairment in Veterans older than 50 years of age. We will use state-of- the-art methodologies to carry out the study and to assess the study outcomes. Successful completion of the study will build on the strengths of the existing treatments and will help develop the next generation of novel, more effective rehabilitative treatments for vision loss in Veterans.

PI_NAMEs: HEGDE, JAY  (contact)

PROJECT_TERMS: 3D Print;age group;Age related macular degeneration;Age Years;Basic Science;behavioral outcome;bench-to-bedside translation;blind;Blindness;braille;Brain;Brain Diseases;Brain imaging;Compensation;Control Groups;Custom;design;Development;Diameter;Disease;Effectiveness;effectiveness evaluation;effectiveness measure;evidence base;experience;Eye;Eye diseases;Feasibility Studies;Feeling;Foundations;Functional Magnetic Resonance Imaging;Funding;Future;Goals;Government;Government Agencies;Hand;Hand functions;haptics;Healthcare;Impairment;Implant;improved;innovation;insight;Intuition;Left;Lighting;Location;Measures;Medical;Medicine;Methodology;Methods;Modality;multisensory;neural;neural correlate;next generation;novel;novel strategies;object recognition;Outcome;Outcome Measure;Outcome Study;Patients;Periodicals;Physical Medicine;Procedures;Randomized;Randomized, Controlled Trials;recruit;Rehabilitation Centers;Rehabilitation therapy;Reporting;Research;Resort;Sensory;Sensory impairment;sensory integration;Solid;Source;Standardization;Stimulus;Study Subject;Testing;Time;tool;Touch sensation;Training;treatment group;trial design;United States National Institutes of Health;Veterans;Vision;Visual;Visual impairment;visual information

PROJECT_TITLE: Development of New Approaches to Rehabilitating Vision Loss in Veterans With Age-Related Macular Degeneration

STUDY_SECTION: RRDS

STUDY_SECTION_NAME: Rehabilitation Research and Development SPiRE Program[RRDS]


ORG_CITY: PROVIDENCE

ORG_NAME: PROVIDENCE VA  MEDICAL CENTER

ORG_STATE: RI

PHR: We will study whether the drug tadalafil improves shortness of breath in 126 Veterans with Chronic Obstructive Pulmonary Disease (COPD) and high blood pressure in the lungs. We will also assess whether tadalafil improves quality of life, home daily physical activity, exercise endurance, the frequency of acute flares of COPD, blood pressure in the lungs, and lung function. Veterans who enroll in the trial will be allocated by chance to either active tadalafil or an inactive identical capsule (placebo). Neither the Veteran nor the investigator will know whether the Veteran is taking tadalafil or placebo. Veterans will be followed closely in clinic or by telephone at 1, 2, 3, 4, 5, and 6 months, with attention to side effects and safety. At 1,3, and 6 months we will repeat the questionnaires and testing of blood pressures in the lung and lung function. We anticipate that the results of this study will determine whether tadalafil improves shortness of breath when added to usual medications for COPD.

PI_NAMEs: GOLDSTEIN, RONALD HOWARD;ROUNDS, SHARON IRENE SMITH (contact)

PROJECT_TERMS: Activities of Daily Living;Acute;airway obstruction;Aorta;Attention;Biological Availability;Blood Pressure;Blood Tests;Blood Vessels;California;capsule;Cardiac;Cardiopulmonary;Categories;Cause of Death;Chronic;Chronic Obstructive Pulmonary Disease;Clinic;Clinical;clinical care;Complication;Controlled Clinical Trials;debilitating symptom;Deterioration;Diameter;Dose;Double-Blind Method;Dyspnea;Echocardiography;effective therapy;effectiveness evaluation;Endothelium;endurance exercise;Enrollment;exercise capacity;experience;Fibrosis;Flare;Fluid overload;Frequencies;Funding;health care service utilization;health related quality of life;hemodynamics;Home;Hypertension;Hypoxia;improved;inhibitor;inhibitor therapy;Injury;low dose computed tomography;Lung;Measures;mortality;Nitric Oxide;novel strategies;novel therapeutics;Obstruction;Oral;Outcome;Participant;Pathogenesis;Pathologic;Patients;Pharmaceutical Preparations;phosphoric diester hydrolase;Physical activity;Physical Exercise;Physiological;Placebo Control;placebo group;Placebos;Polycythemia;primary outcome;prospective;pulmonary arterial hypertension;Pulmonary artery structure;Pulmonary Emphysema;pulmonary function;Pulmonary Function Test/Forced Expiratory Volume 1;Pulmonary Hypertension;pulmonary rehabilitation;Quality of life;Questionnaires;Randomized;randomized placebo controlled trial;Reporting;Research;Research Personnel;respiratory;Respiratory Signs and Symptoms;Safety;Sample Size;secondary outcome;Severities;Shortness of Breath;side effect;Signal Transduction;standard of care;Systolic Pressure;tadalafil;Telephone;therapy duration;Time;treatment group;United States Department of Veterans Affairs;Universities;Vasodilator Agents;Veterans;Walking;X-Ray Computed Tomography

PROJECT_TITLE: Effect of PDE5 inhibitor on respiratory symptoms in COPD complicated by pulmonaryhypertension


ORG_CITY: St. Louis

ORG_NAME: ST. LOUIS VA MEDICAL CENTER

PHR: Dengue disease is a global health emergency with half the world’s population at risk. Hundreds of veterans were hospitalized with dengue in Florida and Puerto Rico in a recent outbreak. There are 4 dengue viruses, infection with a 2nd virus 2+ years after the first infection has the highest risk for severe disease. Many recent deployments including to Somalia, Iraq, and Afghanistan were in dengue endemic areas; veterans who served in these areas are potentially at risk for severe dengue disease if exposed again. A dengue vaccine, TDV/TAK003, has recently shown good safety and protection in 4.5 years of followup. However the mechanisms of protection are not yet fully understood. Using samples already collected from vaccinees and U.S. veterans as part of our ongoing study, and collaborations which will provide us with samples from people who have had multiple dengue infections and are therefore protected, we will define the durability of immunity provided by the TDV/TAK003 vaccine. We will determine the specificity and durability of antibodies, memory B cells, and other potentially protective antibody mediated functions. We will determine if a recently described T cell phenotype is able to kill dengue infected cells in the lab. Finally, we will use a mouse model to determine if immune cells and antibodies can mediate durable protection in a mouse model. There studies will improve understanding of how this vaccine mediates protection, which is significant as TDV/TAK003 could soon be approved for use in the U.S.

PI_NAMEs: GEORGE, SARAH  (contact)

PROJECT_TERMS: adaptive immunity;Adoptive Transfer;Aedes;Afghanistan;Antibodies;Antibody titer measurement;antibody-dependent cell cytotoxicity;Antigen-Presenting Cells;Area;Attenuated;B-Lymphocyte Epitopes;B-Lymphocytes;Binding;Biological Assay;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cells;Cessation of life;Collaborations;Colombia;cross reactivity;cytotoxic;Cytotoxic T-Lymphocytes;Data;Dendritic Cells;Dengue;Dengue Fever;Dengue Infection;Dengue Vaccine;Dengue Virus;Dengvaxia;design;Development;Disease;Disease Outbreaks;Dose;Epitopes;Exanthema;Exposure to;Fever;Florida;follow-up;Follow-Up Studies;Formulation;Generations;global health emergency;Head;Headache;Hemorrhage;high risk;Hospitalization;Human;Humanities;Immune;Immunity;Immunoglobulin-Secreting Cells;improved;Indonesia;Infection;Iraq;Knowledge;Macrophage;Mediating;Memory B-Lymphocyte;Military Personnel;Modeling;monocyte;mouse model;Myalgia;neutralizing antibody;pandemic disease;Peripheral Blood Mononuclear Cell;Persons;phase III trial;Phenotype;Population;Populations at Risk;protective efficacy;Puerto Rico;receptor;Recombinants;Reporting;Research Design;Risk;Safety;Sampling;seropositive;Serotyping;Serum;severe dengue;Shock;Signal Transduction;Somalia;Specificity;T cell response;T-Lymphocyte;T-Lymphocyte Epitopes;Time;Vaccinated;Vaccination;Vaccinee;Vaccines;vector mosquito;Veterans;Viremia;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Durability and mechanisms of dengue vaccine and infection mediated immunity


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: Nashville

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: VANDERBILT UNIVERSITY

PHR: Project Narrative There are a growing number of children being identified with mutations in the mitochondrial fission protein Dynamin-related Protein 1 (DRP1), leading to severe neurodevelopmental symptoms including severe epilepsies. This study aims to address gaps in knowledge about interactions between mutant DRP1 and mitochondria-associated organelles such as actin and the endoplasmic reticulum during neurodevelopment. Successful completion of this project could improve our understanding of the role of mitochondrial fission during early brain development and how unique DRP1 mutations result in varied pathological mechanisms.

PI_NAMEs: BAUM, TIERNEY  (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Actins;Address;Adopted;Affect;Apoptosis;axon growth;Binding;Brain;Calcium;Cell Line;Cell model;cell type;Cells;Child;Complex;constriction;de novo mutation;Defect;Development;Developmental Delay Disorders;Dynamin;early childhood;Endoplasmic Reticulum;Epilepsy;epileptic encephalopathies;Event;Exhibits;exome sequencing;F-Actin;Feedback;Fibroblasts;Functional disorder;Guanosine Triphosphate;Guanosine Triphosphate Phosphohydrolases;Heterozygote;Human;Hydrolysis;Immunoprecipitation;Impairment;improved;induced pluripotent stem cell;insight;Investigation;Knowledge;Lead;loss of function mutation;Membrane;Metabolic;Microcephaly;Microscopy;Mitochondria;Mitochondrial Diseases;mitochondrial fitness;mitochondrial membrane;mitochondrial therapeutics;Modeling;Molecular;Morphology;Motility;mutant;Mutation;Nature;nerve stem cell;Neurites;neurodevelopment;Neurodevelopmental Deficit;Neurodevelopmental Disorder;neurogenesis;neuron development;Neuronal Differentiation;Neurons;novel;Optic Atrophy;Organelles;Outcome;Pathogenicity;Pathologic;Pathology;patient derived induced pluripotent stem cells;patient variability;Patients;personalized therapeutic;Phenotype;Process;Proteins;receptor;Resolution;Role;Seizures;Site;stem cell fate;stem cells;Symptoms;Synapses;synaptogenesis;Testing;Total Internal Reflection Fluorescent;trafficking;ultra high resolution

PROJECT_TITLE: Understanding the effects of mitochondrial fission disruption during early cortical development


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Assistive Technology;Bioengineering;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dementia;Hydrocephalus;Neurodegenerative;Neurosciences;Patient Safety;Rare Diseases

ORG_CITY: BALTIMORE

ORG_DEPT: NEUROSURGERY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: This trial aims to provide strong evidence of the effectiveness of shunting excess fluid from the brain for the surgical treatment of Idiopathic Normal Pressure Hydrocephalus (iNPH), a potentially reversible form of dementia and imbalance in the elderly. In addition, this study evaluates patient features to accurately identify people who may benefit. With this evidence, there can be an increase in the number of the 300-700,000 patients in the US with iNPH that can be treated and live more independent lives.

PI_NAMEs: HOLUBKOV, RICHARD ;LUCIANO, MARK GREGORY (contact)

PROGRAM_OFFICER_NAME: HARDY, KRISTINA KOREN

PROJECT_TERMS: active method;Adult;Affect;Age Years;aging population;Algorithms;Alzheimer's Disease;Amyloid beta-42;Anatomy;Biological Markers;biomarker identification;Bladder Control;Blinded;Blood Vessels;brain surgery;Cephalic;Cerebrospinal fluid shunts procedure;Clinical;Clinical effectiveness;clinical outcome measures;Cognition;Cognitive;Collaborations;comparison group;Controlled Clinical Trials;cost;Creation of ventriculo-peritoneal shunt;Data;Data Collection;Dementia;Devices;Diagnosis;disability;Disease;early experience;effective therapy;Effectiveness;Elderly;Enrollment;Equilibrium;Excision;FDA approved;fluid flow;Future;Gait;Gait abnormality;Goals;Guidelines;Health;health care service;Health Expenditures;Hydrocephalus;Image;imaging biomarker;Impaired cognition;Impairment;implantation;improved;Liquid substance;Magnetic Resonance Imaging;Measures;Medical;Methods;micturition urgency;Morbidity - disease rate;neurodegenerative dementia;Neurologist;Neurology;Neuropsychological Tests;Neuropsychology;Neurosurgeon;Normal Pressure Hydrocephalus;older patient;Operative Surgical Procedures;Outcome;Outcome Assessment;Outcome Measure;Participant;patient biomarkers;Patient Selection;Patients;Pattern;Persons;Physiological;Placebo Control;placebo controlled study;placebo controlled trial;Placebo Effect;placebo group;Placebos;Population;Prevalence;primary endpoint;primary outcome;prospective;Randomized;randomized placebo-controlled clinical trial;randomized, clinical trials;recruit;Reporting;Research;Research Proposals;response;Risk;Running;secondary analysis;secondary outcome;Shunt Device;Site;Subgroup;success;Surveys;Symptoms;System;tau Proteins;Testing;treatment effect;Treatment Effectiveness;Uncertainty;Uncontrolled Study;Urinary Incontinence;Ventricular;virtual;Work

PROJECT_TITLE: A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial


ADMINISTERING_IC: FD

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: HOUSTON

ORG_NAME: MARKER THERAPEUTICS, INC.

PHR: NARRATIVE Marker proposes a novel therapy, whereby white blood cells are trained in the laboratory to recognize and kill cancer cells via multiple surface markers expressed by the tumor cells but not healthy cells. To date, more than 150 patients have been treated in clinical studies with this therapy with no significant side effects. This application will advance the development of this novel treatment for acute myeloid leukemia (AML), a type of blood cancer afflicting a small number of patients with minimal treatment options and low survival rates, in order to benefit AML patients.

PI_NAMEs: VERA, JUAN FERNANDO (contact)

PROGRAM_OFFICER_NAME: KAPOOR, SHELLY

PROJECT_TITLE: Efficacy of a Multi-Tumor-Associated Antigen-Specific T Cell Therapy in AML Patients following Allogeneic Stem Cell Transplant with Minimal Residual Disease


ORG_CITY: Tampa

ORG_NAME: JAEB CENTER FOR HEALTH RESEARCH, INC.

ORG_STATE: FL

PHR: Project Narrative for Gyrate Atrophy: Ocular and Systemic Natural History Study (GYROS) Gyrate atrophy is a rare inherited chorioretinal degeneration that is associated with hyperornithinemia caused by autosomal recessive mutations in the ornithine aminotransferase (OAT) gene, leads to severe loss of vision, and for which the current standard of care treatment is a highly burdensome arginine-restricted diet (ARD) fraught with management complications. The principal investigators are currently developing a gene augmentation therapy, a potential treatment strategy that may preserve or improve vision while avoiding or reducing the need for ARD. The proposed natural history study will inform and facilitate the future interventional clinical trial design and implementation by characterizing the natural history and variability of OAT-related ocular and systemic disease progression, establishing sensitive endpoints, and identifying criteria for candidates most likely to benefit from intervention.

PI_NAMEs: AYALA, ALLISON RENEE (contact);SINGH, MANDEEP ;VALLE, DAVID

PROGRAM_OFFICER_NAME: MUELLER, CHRISTINE

PROJECT_TITLE: Gyrate Atrophy Ocular and Systemic Study (GYROS)


ORG_CITY: NASHVILLE

ORG_NAME: VETERANS HEALTH ADMINISTRATION

PHR: Narrative Lung cancer screening with low-dose chest computed tomography (CT) is currently recommended for high-risk individuals who are 50 to 80 years old, have smoked cigarettes for at least 20 pack-years, and currently smoke or quit smoking within the past 15 years. In a prospective cohort at Nashville, Denver and Louisville Veteran Affairs medical centers, we will evaluate the detection of lung cancer using new lung cancer screening eligibility criteria based on Veterans' personal and service-related exposures compared to standard of care criteria. Screening a larger population will increase the number of lung nodules needing clinical management and these nodules may or may not be cancer. In a population of Veterans with positive screenings at Nashville, we will also validate a combination biomarker-based approach to manage screen-detected lung nodules to reduce time to lung cancer diagnosis in nodules that are cancer and use of invasive procedures in nodules that are not cancer.

PI_NAMEs: LEWIS, JENNIFER A (contact)

PROJECT_TERMS: Address;Age;Age Years;aged;agent orange;Algorithms;artificial intelligence model;Asbestos;Benign;Biological Assay;Biological Markers;biomarker driven;burn pit;cancer biomarkers;Cancer Detection;cancer diagnosis;Cancer Etiology;cancer risk;candidate marker;chest computed tomography;Chronic Obstructive Pulmonary Disease;cigarette smoke;cigarette smoking;Classification;Clinical;Clinical Management;cohort;Communities;computed tomography screening;convolutional neural network;cooperative study;Cytokeratin;Data;design;Detection;Development;Diagnosis;Discrimination;Dose;Early Diagnosis;Eligibility Determination;Evaluation;Family history of;Hazardous Substances;High Prevalence;high risk;high risk population;imaging biomarker;improved;Individual;innovation;Ionizing radiation;Lead;low dose computed tomography;Lung;lung basal segment;lung cancer screening;Lung nodule;Malignant - descriptor;Malignant neoplasm of lung;Malignant Neoplasms;Medical center;meetings;Military Personnel;military service;military veteran;Modeling;mortality;Nodule;Non-Invasive Detection;oncology program;personalized screening;Policies;Population;precision oncology;Procedures;programs;Prospective cohort;Randomized;randomized, clinical trials;Randomized, Controlled Trials;Recommendation;Recording of previous events;Research;Risk;Risk Factors;screening;Screening for cancer;screening guidelines;screening program;Screening Result;Serum Proteins;Services;Smoke;Smoking;smoking cessation;Smoking History;standard of care;Testing;Time;Tobacco smoking behavior;Tobacco-Related Carcinoma;United States;United States Department of Veterans Affairs;United States Preventative Services Task Force;Veterans

PROJECT_TITLE: Personalizing Veterans' Lung Cancer Screening and Diagnosis


ORG_CITY: MIAMI

ORG_NAME: MIAMI VA HEALTH CARE SYSTEM

PHR: Gulf War Veterans’ illnesses (GWVI) is a multisystem disease estimated to affect 25% of Gulf War Era veterans. Neuroinflammation and neurodegeneration as a basis of GWI symptom development has been suggested by numerous human and animal studies. In this proposal, we apply a comprehensive neurosensory testing protocol in individuals with GWVI and appropriate controls, with the goal of forwarding knowledge regarding GWVI pathophysiology and heterogeneity. These data are needed in order to develop clinic-based tests that sub-group individuals based on underlying mechanisms, an important first step toward the development of targeted therapies that are greatly needed for this complex disease.

PI_NAMEs: GALOR, ANAT  (contact)

PROJECT_TERMS: Affect;Anesthetics;Animals;Area;Basal Ganglia;Bilateral;Blood;blood oxygen level dependent;Brain;Brain-Derived Neurotrophic Factor;Categories;Cerebrospinal Fluid;chronic pain;Clinic;Clinical;Cognition Disorders;Cognitive;comparison control;Complex;Cornea;cytokine;Darkness;Data;design;Development;Disease;Drops;Environmental Wind;Etiology;Event;Eye;Fatigue;Forearm;Forehead;Functional disorder;Functional Magnetic Resonance Imaging;gastrointestinal;Glutamates;Goals;Gulf War;Gulf War veteran;Health;Heterogeneity;Human;imaging program;Immune;improved;Individual;Inferior;Inflammation;Inflammatory;inflammatory marker;Infrastructure;Insula of Reil;Investigation;Knowledge;Light;Literature;Lobule;Measures;Medial;Methodology;Methods;Modeling;Mood Disorders;Motor;multidisciplinary;Musculoskeletal Diseases;Nerve Degeneration;neural;neural circuit;neuroimaging;neuroinflammation;Neurologic;neuromechanism;neurosensory;Nociception;ocular pain;ocular surface;Pain;Pain Measurement;pain processing;pain sensitivity;Parietal;Participant;Pathology;Pathway interactions;Patient Self-Report;Pattern;Peripheral;Persian Gulf Syndrome;Phenotype;Photophobia;Population;Protocols documentation;Reporting;respiratory;response;Sensory;Serum;Serum Markers;Severities;Signal Transduction;Signs and Symptoms;Site;Skin Manifestations;Sleep;somatosensory;Somatosensory Cortex;Stimulus;Stratification;Structure of trigeminal ganglion;Subgroup;symptom cluster;symptomatology;Symptoms;System;targeted treatment;Technology;Testing;Thalamic structure;tool;Trigeminal Nuclei;Trigeminal Pain;Trigeminal System;Veterans;Work

PROJECT_TITLE: Eye Pain and Photophobia: Ocular Signs and Symptoms As Markers of Central Abnormalities in Gulf War Illness

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 SPLD-T (01)]


ORG_CITY: MADISON

ORG_NAME: WM S. MIDDLETON MEMORIAL VETERANS HOSP

ORG_STATE: WI

PHR: Traumatic brain injury (TBI) is a major health problem in veterans of all ages. Every year, thousands of service personnel suffer TBI and there are >300,000 surviving veterans with post-TBI long-term consequences. The costs of post-TBI acute care, long-term rehabilitation and loss of productive years are hundreds of millions yearly. The negative impact of this devastating condition on veterans will increase enormously unless new therapies that can minimize the secondary brain damage during acute phase after TBI are tested in preclinical animal models and propagated to clinical trials. Vitamin C (ascorbate) is an FDA-approved and safe compound for human use which is shown to promote neuroprotection by modifying epigenetics. Hence, we will test the long-term effects of ascorbate therapy in rodents of both sexes subjected to TBI. The overall goal is to establish ascorbate as a TBI therapeutic.

PI_NAMEs: VEMUGANTI, RAGHU  (contact)

PROJECT_TERMS: Acute;Acute Brain Injuries;acute care;Adult;Age;Animal Model;animal old age;Antioxidants;ascorbate;Ascorbic Acid;Brain;Brain Injuries;Cause of Death;Cell Survival;Cerebrum;chromatin immunoprecipitation;Chronic;Clinical;Clinical Trials;Cognitive;controlled cortical impact;cost;Cytosine;Data;derepression;disability;Disease;DNA;DNA Methylation;Dose;drug action;efficacious treatment;Enzymes;Epigenetic Process;Family;FDA approved;Female;Functional disorder;functional outcomes;Funding;Gene Expression;Genes;Genetic Transcription;Genomics;Goals;Grant Review;Health;Human;Human Resources;Injury;interest;Ischemia;knock-down;Long-Term Effects;long-term rehabilitation;male;Maps;Massive Parallel Sequencing;mature animal;Mediating;Methylation;Mission;Mixed Function Oxygenases;Modeling;Modification;Motor;Mus;Neurodegenerative Disorders;Neurologic Deficit;Neurologic Dysfunctions;neuroprotection;neuropsychiatry;novel therapeutics;Organ;Outcome;Oxidative Stress;Pathologic;Patient Care;Pharmaceutical Preparations;Phase;post stroke;pre-clinical;Preclinical Testing;prevent;productivity loss;Quality of life;Recovery of Function;Rodent;Secondary to;Services;sex;Site;Societies;Stroke;Testing;Therapeutic;transcriptome sequencing;Translating;translocase;Traumatic Brain Injury;Traumatic Brain Injury recovery;Veterans;Work

PROJECT_TITLE: Ascorbate protects brain after TBI by epigenetic modulation of 5-hydroxymethylation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURC-C (01)]


ORG_CITY: ANN ARBOR

ORG_STATE: MI

PHR: The proposed research is relevant to health care in that heart failure with preserved ejection fraction (HFpEF), a major cause of morbidity and mortality in the U.S, has an exponentially increasing prevalence. We made significant advances in this area by identifying the role of bioactive lipid signaling in the development of HFpEF and designing much-needed therapies to prevent the progression of HFpEF. The proposed research is relevant to the Veterans Affairs’s mission pertaining to developing and applying fundamental knowledge to protect and improve the health of veterans and the public

PI_NAMEs: ABDEL-LATIF, AHMED  (contact);JOHNSON, RUDOLPH C

PROJECT_TERMS: Adipocytes;Adipose tissue;Affect;Aging;Animal Model;Animals;Antibodies;Area;Basic Science;Biological;Biological Markers;Cardiac;Clinical;clinical practice;clinical prognosis;Clinical Research;clinically relevant;cohort;Complex;coronary fibrosis;Cytometry;Data;design;Development;Diagnosis;diet-induced obesity;Disease;Disease Management;Disease Progression;Early Diagnosis;Early Intervention;EFRAC;Epidemic;experience;Fibrosis;Foundations;Functional disorder;Future;Genetic;genetic variant;Genomics;Goals;Health;Healthcare;Healthcare Systems;Heart;Heart failure;heart failure with reduced ejection fraction;Heritability;high risk;Human;Immune;Immune signaling;immunoregulation;improved;improved outcome;Individual;Infiltration;Inflammation;Inflammatory;innovation;insight;Ischemia;Knowledge;Lipids;lysophosphatidic acid;Lysophosphatidylcholines;Macrophage;Mediating;Metabolism;Michigan;military veteran;Mission;Modeling;Modernization;Morbidity - disease rate;mortality;mouse model;mRNA Expression;Myeloid Cells;Myocarditis;Myocardium;novel;obese patients;obese person;Obesity;Overweight;Pathologic;Pathway interactions;Patients;Plasma;Play;Population;preservation;Prevalence;prevent;Process;Prognosis;Publishing;Reporting;Research;Risk;Role;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Source;Specimen;Survival Rate;System;systemic inflammatory response;Techniques;Therapeutic;Therapeutic Studies;therapeutic target;therapeutically effective;Thinness;Tissues;transcriptome sequencing;Translational Research;United States;United States Department of Veterans Affairs;Veterans

PROJECT_TITLE: Lysophosphatidic acid mediates cardiac inflammation and heart failure with preserved ejection fraction

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 CARA-R (01)]


ORG_CITY: RICHMOND

ORG_NAME: VA VETERANS ADMINISTRATION HOSPITAL

ORG_STATE: VA

PHR: Project Narrative Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem affecting more than 30% of the USA population. The burden of NAFLD among veterans is substantial. Our preliminary studies have identified a novel function of ubiquitin-like protein 5 (UBL5) in suppression of lipid accumulation and a regulatory/signaling mechanism to control UBL5 protein stability and activity by ER stress. In this project, we will explore the roles of UBL5 in lipid metabolism and its dysfunction in connecting chronic ER stress to NAFLD.

PI_NAMEs: FANG, XIANJUN  (contact)

PROJECT_TERMS: Affect;arm;Attenuated;Automobile Driving;Binding;Biological;Biological Process;Caenorhabditis elegans;Catabolic Process;Cell Line;Cells;Cessation of life;Chronic;Communication;conditional knockout;Data;Development;Disease Management;Disease Progression;Down-Regulation;Endoplasmic Reticulum;endoplasmic reticulum stress;Fatty acid glycerol esters;fatty acid oxidation;Fatty Acids;Fatty Liver;Functional disorder;Genes;Genetic Transcription;High Fat Diet;Human;In Vitro;in vivo;Inflammatory;insight;knock-down;Link;lipid biosynthesis;lipid metabolism;Lipids;Liver;liver biopsy;liver development;liver injury;Location;Mammalian Cell;Mediating;Mediator;Messenger RNA;Metabolic Diseases;Metabolic Pathway;Mitochondria;Modeling;Molecular;mouse model;multicatalytic endopeptidase complex;Mus;non-alcoholic fatty liver disease;nonalcoholic steatohepatitis;novel;oxidation;Pathogenesis;Pathway interactions;Patients;pharmacologic;Phenotype;Phosphotransferases;Phylogeny;Population;Prevention;Process;programs;protein function;Proteins;Proteolysis;proteostasis;Public Health;Recurrence;response;RNA Splicing;Role;Signal Pathway;Signal Transduction;Specimen;Spliceosomes;Stress;stressor;Students;System;Testing;Tissues;transcriptome sequencing;Transgenic Mice;Transgenic Model;Triglycerides;Tunicamycin;Ubiquitin;Ubiquitin Like Proteins;Veterans;Wild Type Mouse;Yeasts

PROJECT_TITLE: Novel Function of Ubiquitin-Like Protein 5 As a Fat Suppressor


ORG_CITY: BUFFALO

ORG_NAME: VA WESTERN NEW YORK HEALTHCARE SYSTEM

PHR: The cornea functions as a lens on the front of the eye and its clarity is maintained by the corneal endothelium, a delicate layer of cells on the back of the cornea. Because these cells do not divide, when they are lost from disease or trauma, there is loss of vision. The corneal endothelium can tolerate a fair amount of injury before the cornea opacifies. However, insults are cumulative. Injuries from explosions are the most common source of eye injury in our military personnel and blast injuries cause permanent damage to the corneal endothelium. History of eye trauma and age predispose Veterans to cataracts and glaucoma. Cataract and glaucoma surgery cause additional injury to the corneal endothelium which can destroy enough corneal endothelial cells to result in vision loss. Finding ways to prevent loss of corneal endothelial cells from blast-induced and surgery-induced trauma is an important endeavor to prevent corneal vision loss in our Veterans.

PI_NAMEs: PATEL, SANGITA  (contact)

PROJECT_TERMS: Acetylcysteine;Acoustics;Actins;active duty;Acute;Affect;Age;Autopsy;Back;Biological Assay;Blast Cell;blast exposure;Blast Injuries;blast trauma;Blindness;Cataract;Cataract Extraction;Cell Death;Cell Density;cell injury;Cell membrane;Cell Proliferation;Cells;Cellular Structures;Cessation of life;comparison control;Complex;Cornea;Corneal Endothelium;Corneal Injury;Cytoskeleton;Data;decubitus ulcer;Devices;Disease;effectiveness evaluation;efficacy testing;Endothelial Cells;endothelial dysfunction;Explosion;Exposure to;Eye;Eye Injuries;Fuchs' Endothelial Dystrophy;Glaucoma;glaucoma surgery;healing;Heterogeneity;High Prevalence;Human;Iatrogenesis;Injury;Intervention;Keratoplasty;kinase inhibitor;Knowledge;Laceration;lens;Life;Lipid Peroxidation;Mechanics;Metabolic;metabolic phenotype;Metabolism;Methods;Military Personnel;military veteran;Mitochondria;mitochondrial metabolism;Molecular Profiling;monolayer;Nonpenetrating Wounds;Operative Surgical Procedures;Organ Culture Techniques;oxidative damage;oxidative DNA damage;Oxidative Stress;Phacoemulsification;Pharmaceutical Preparations;pharmacologic;Pharmacological Treatment;Phase;Physiological;pressure;prevent;primary outcome;Proliferating;protein expression;Recording of previous events;Reducing Agents;response;Rho-associated kinase;Sampling;Shock;Shunt Device;Source;Stains;Stress;Testing;Therapeutic;Tight Junctions;translational potential;Transplantation;Trauma;treatment response;Trypan Blue;Tube;ubiquinol;Ultrasonic Therapy;United States;Veterans;Vision;wound healing

PROJECT_TITLE: Injuries of the Corneal Endothelium

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 NURF-C (01)]


ORG_CITY: SYRACUSE

ORG_NAME: SYRACUSE VA  MEDICAL CENTER

PHR: Tobacco smoking, obesity and exposure to organic solvents, heavy metals, herbicides, and petrochemi- cals are all play a major role in development of kidney cancer. Members of the military are exposed to hazardous environments due to the nature of their service and deployments and thus are at risk of devel- oping kidney cancer. Traditional radiation and chemotherapies are ineffective in patients with kidney can- cer and ~50% of patients develop metastatic disease, for whom the 5-year survival rate is only ~10%. Such grim statistics point to an urgent need for developing better therapeutic strategies. This goal of this project is to decipher the mechanism of metabolic deregulation in kidney cancer which is essential for their sur- vival. This proposal also aims at using a novel therapeutic approach by targeting an enzyme responsible for this metabolic process in kidney cancer. The ultimate goal of this proposal is to develop novel strategies that can be translated into the clinic to successfully treat Veterans with kidney cancer.

PI_NAMEs: MOLLAPOUR, MEHDI  (contact)

PROJECT_TERMS: Acids;Active Sites;aerobic glycolysis;Apoptosis;Binding;Biochemical;Biological Assay;Biology;Biophysics;Cancer Biology;Cancer cell line;Cells;Chemotherapy and/or radiation;Clear cell renal cell carcinoma;Clinic;Clinical;Data;Department of Defense;design;Development;Disease;Disease Progression;Dissociation;Environment;Environmental Exposure;enzyme activity;Enzymes;experience;Exposure to;Family;flexibility;Folliculin;Glucose;glucose uptake;Glycolysis;Goals;Half-Life;Hand;Health Policy;Heavy Metals;Herbicides;Homeostasis;Human Resources;Hyperactivity;improved outcome;In Vitro;Incidence;ineffective therapies;inhibitor;kidney cell;Kidney Neoplasms;Knowledge;lactate dehydrogenase A;Lead;Malignant Epithelial Cell;Malignant Neoplasms;Mediating;Metabolic;Metabolic Diseases;Metabolism;military family;Military Personnel;military veteran;Mitogen-Activated Protein Kinases;Molecular;mortality;Movement;Mus;Nature;nephrogenesis;Normal Cell;novel strategies;novel therapeutic intervention;novel therapeutics;Obesity;operation;organic acid;Organic solvent product;Outcomes Research;Oxygen;Pathway interactions;patient derived xenograft model;Patient-Focused Outcomes;Patients;Peptide Hydrolases;Peptides;Periodicity;Persons;Phosphorylation;Play;prevent;Price;Process;Production;Protein Isoforms;Publishing;Pyruvate;Renal Carcinoma;Renal Cell Carcinoma;Reporting;Resistance;Risk;Risk Factors;Role;service member;Services;Signal Pathway;Signal Transduction;Smoking;Speed;statistics;Stress;Survival Rate;targeted treatment;Testing;Therapeutic;Tissue Microarray;Tobacco;Tobacco smoking behavior;Tobacco use;Translating;tumor growth;Tumor Suppressor Proteins;tumor xenograft;unpublished works;Veterans;Vietnam;Warburg Effect;women versus men;Work;Xenograft Model

PROJECT_TITLE: Targeting the Warburg Effect in Kidney Cancer


ORG_CITY: Aurora

ORG_NAME: VA EASTERN COLORADO HEALTH CARE SYSTEM

ORG_STATE: CO

PHR: Many veterans and their families are at elevated risk for severe illness, long term disability, or death from COVID-19. The cells in our bodies make diverse interferons (IFNs), which are proteins that function as central orchestrators of front-line (“innate”) immunity. They activate genes for numerous other antiviral proteins in cells. The IFNs have varying levels of activity against SARS-CoV-2. We found that SARS-CoV-2 variants that appeared later in the pandemic developed resistance to human IFNs. Understanding how they and future variants resist this fundamental antiviral system will provide insights into SARS-CoV-2 transmission and illness. The science to be done is important for pushing the field forward by helping us understand early stages of human immune defense against SAR-CoV-2, and how that impacts development of later “adaptive” immune responses such as antibodies and T cells. In addition, IFNs have potential use as therapeutic agents. The work that will be done using this grant funding may help design of novel treatment approaches against COVID19.

PI_NAMEs: POESCHLA, ERIC M. (contact)

PROJECT_TERMS: 2019-nCoV;A549;Acute;acute COVID-19;adaptive immune response;Adrenal Cortex Hormones;Alveolar;Animal Model;Animals;antagonist;Antibodies;arm;Attention;Automobile Driving;breakthrough infection;CD4 Positive T Lymphocytes;Cell Line;Cells;cellular targeting;Cessation of life;Chronic;Clinical Trials;Collaborations;comparative;Coronavirus;COVID-19;COVID-19 mortality;COVID-19 pandemic;COVID-19 patient;current pandemic;Data;design;Development;Early treatment;emerging virus;Employee;Epidemiology;Epithelial Cells;Evolution;experience;Family;follow-up;Funding;Future;Genes;Genetic;Grant;HIV-1;Hospitalization;Human;Human Genome;IFNAR1 gene;Immune;Immune Evasion;Immune system;Immunity;In Vitro;Infection;Inflammation;Innate Immune Response;insight;Interferon alpha;Interferon Type I;Interferon Type II;Interferons;Investigation;Laboratories;Link;Long term disability;Lower respiratory tract structure;Lung;Marketing;Mediating;Medical;Modeling;mucosal HIV infection;Mucous Membrane;Mutation;Natural Immunity;neutralizing antibody;novel;novel coronavirus;Nucleocapsid;overexpression;pandemic disease;pandemic potential;pandemic virus;Pathogenesis;Persons;Phase;Phenotype;Physiological;Probability;Process;protein function;Proteins;Publishing;receptor;Records;Research Personnel;Resistance;Resistance development;resistance mechanism;response;reverse genetics;Risk;Role;Route;Sampling;Sarbecovirus;SARS-CoV-2 B.1.1.529;SARS-CoV-2 B.1.1.7;SARS-CoV-2 B.1.351;SARS-CoV-2 B.1.617.2;SARS-CoV-2 inhibitor;SARS-CoV-2 transmission;SARS-CoV-2 variant;Science;severe COVID-19;Signal Transduction;spillover event;Structure of parenchyma of lung;System;T-Lymphocyte;Testing;Therapeutic;Therapeutic Agents;therapy development;Time;tissue culture;transcriptome;transmission process;Upper respiratory tract;Vaccinee;Vaccines;Variant;variants of concern;Veterans;Viral;Viral Drug Resistance;Viral Genes;Viral Load result;Viral Physiology;Viral Proteins;Virus;virus host interaction;Virus Replication;Work;Writing

PROJECT_TITLE: SARS-CoV-2 and Innate Immunity: Mechanisms of Resistance to Human Interferons