NIH_SPENDING_CATS: Atherosclerosis;Biomedical Imaging;Cardiovascular;Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Effects of Household Energy Combustion;Health Effects of Indoor Air Pollution;Heart Disease;Heart Disease - Coronary Heart Disease;Prevention;Social Determinants of Health

ORG_CITY: AMHERST

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: Project Narrative Air pollution remains a ubiquitous exposure worldwide and is an important potential risk for coronary heart disease, the leading cause of death worldwide, through which atherosclerosis is the most common pathway. The precise consequences of exposure to air pollution on coronary heart disease remain uncertain, the responsible air pollutants, and the mechanisms underlying the effects are largely unknown: long-term exposure to outdoor and indoor air pollutants may make susceptible patients with atherosclerosis more likely to develop and promote coronary atherosclerosis with thickening and calcification and cause rupture and thrombosis of vulnerable plaques, leading to coronary events. This project holds the promise to generate new knowledge about modifiable environmental factors that may contribute new approaches to developing effective prevention modalities.

PI_NAMEs: WANG, MENG  (contact)

PROGRAM_OFFICER_NAME: JOUBERT, BONNIE

PROJECT_TERMS: 12-HETE;Acceleration;Address;Age;Air;Air Pollutants;Air Pollution;Algorithms;ambient air pollution;American;Angiography;Arterial Fatty Streak;Atherosclerosis;attenuation;Biological;Biological Markers;Biological Process;Biometry;Blood;Blood Vessels;calcification;Carbon Black;cardiovascular health;Cardiovascular system;Caring;Cause of Death;Cessation of life;China;Clinic Visits;Clinical assessments;clinical biomarkers;Clinical Management;coarse particles;cohort;cooking;Coronary;Coronary Arteriosclerosis;coronary calcium scoring;coronary event;Coronary heart disease;Coronary Stenosis;critical period;Data;Development;Diameter;Disease;Disease Progression;Disparity;Environmental Exposure;Environmental Risk Factor;Epidemiology;evidence base;experience;Exposure to;Fatty acid glycerol esters;fine particles;Functional disorder;Health Benefit;Health Policy;Health protection;high risk;Imaging technology;improved;indexing;Individual;Indoor Air Pollution;indoor pollutant;Inflammation;inflammatory marker;insight;interest;Intervention;Joints;Knowledge;Lipid Peroxidation;Lipids;Longitudinal cohort study;Measures;Mediating;Modality;Modeling;Morbidity - disease rate;Morphology;mortality;multidisciplinary;Natural experiment;Nitrogen Oxides;Noise;novel;novel marker;novel strategies;Outcome;Oxidative Stress;Ozone;Participant;Particle Size;Particulate Matter;Pathway interactions;Patients;phenotypic data;Play;Policies;Pollution;Population;population based;Predisposition;Prevention;progression risk;Public Health;public health priorities;Public Policy;Qualifying;Regulation;response;Risk;Role;Rupture;Site;solid fuel;Source;specific biomarkers;Stenosis;stressor;Thrombosis;Time;Toxic effect;ultrafine particle;vascular inflammation;X-Ray Computed Tomography

PROJECT_TITLE: Air Pollution, Coronary Events and Atherosclerotic Progression in a Susceptible Population

STUDY_SECTION: CHSA

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology A Study Section[CHSA]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF PHARMACY

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: ANN ARBOR

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PHARMACOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: The goal of this proposal is to improve the delivery of agents (anti-sense oligonucleotides), which are capable to silencing neurogenerative disease-specific genes, to neurons without the need for invasive methods of administration. This research will involve conjugating anti-sense oligonucleotides to antibodies that penetrate the intact blood-brain barrier, target cell-surface neuronal proteins, and release their conjugated agents after antibody cellular internalization. Successful completion of this research would accelerate the development of therapeutics for treating diverse neurodegenerative disorders.

PI_NAMEs: TESSIER, PETER M (contact)

PROGRAM_OFFICER_NAME: RANGANATHAN, SRIKANTH

PROJECT_TERMS: Acceleration;Address;Aging;Amino Acid Transport System L;Antibodies;antibody conjugate;Antisense Oligonucleotides;Ataxia;Behavioral;Behavioral Assay;Binding;Biochemical;Biological Assay;Bispecific Antibodies;Blood - brain barrier anatomy;blood-brain barrier penetration;Brain;brain parenchyma;Cell Culture Techniques;Cell surface;Cell Surface Proteins;Cells;Cessation of life;comparative efficacy;Conjugating Agent;Data;Development;Disease;disease phenotype;Dose;Drug Kinetics;efficacy evaluation;fluorophore;Gene Silencing;Genes;Goals;GPM6A gene;high reward;high risk;Human;Immunoglobulin G;improved;In Vitro;in vivo evaluation;Inherited;Injections;interest;intravenous administration;Label;Laboratories;Machado-Joseph Disease;Maleimides;Mammals;Measures;Mediating;Membrane Proteins;Methods;MJD1 protein;Molecular;Motor;motor control;mouse model;Mus;mutant;Nerve Degeneration;Neurodegenerative Disorders;Neurons;novel therapeutics;Outcome;Penetration;Peptides;Peripheral;Pharmacodynamics;Phenotype;prevent;Proteins;radiotracer;Research;Route;Severity of illness;Sulfhydryl Compounds;Technology;Testing;Therapeutic;therapeutic development;Transgenic Mice

PROJECT_TITLE: Neuronal Silencing of ATXN3 Using Peripherally Administered Antibody/ASO Conjugates That Penetrate the Blood-Brain Barrier

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MDCN-M(91)]


ADMINISTERING_IC: GM

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology

ORG_CITY: MINNEAPOLIS

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Project Narrative This project will transformatively accelerate and streamline protein discovery and engineering via creation and implementation of a platform for high-throughput evaluation of protein developability (i.e. biophysical robustness to manufacture, storage, and use). The platform will eliminate molecular liabilities – that otherwise cause detrimental complications from use; expensive, time-consuming engineering; or wasteful termination of protein discovery campaigns – to improve therapeutics, diagnostics, and industrial reagents.

PI_NAMEs: HACKEL, BENJAMIN  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Engineering protein developability

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Epilepsy;Genetics;Neurodegenerative;Neurosciences;Pediatric;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: CHICAGO

ORG_DEPT: NEUROLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Narrative Epilepsy affects up to 1% of the population, causing disruptions in quality of life and even mortality due to sudden death. In pediatric epilepsy especially, changes in a single gene of an ion channel are recognized as a major contributor to infantile-onset seizures that can be very difficult to control with medications. This proposal will provide new insight into the way single gene changes lead to recurrent seizures by examining single neurons and animal models, allowing for new approaches to therapy.

PI_NAMEs: ADNEY, SCOTT K. (contact)

PROGRAM_OFFICER_NAME: REZAIZADEH, KAVON PAUL

PROJECT_TERMS: Affect;Animal Model;animal tissue;Animals;Area;autism spectrum disorder;Award;Benchmarking;Biological Markers;Biophysical Process;Brain;career;career development;causal variant;Cell Line;Childhood;childhood epilepsy;clinical phenotype;collaborative environment;Data;design;Development;Disease;disease model;Disparate;dravet syndrome;early onset;Electrodes;Electroencephalography;Electrophysiology (science);Epilepsy;epileptic encephalopathies;Equilibrium;excitatory neuron;Exhibits;Fostering;Foundations;Functional disorder;Funding;Future;gain of function;Genes;Genetic;genetic analysis;Genetic Diseases;Genetic Models;genetic variant;genome editing;Glutamates;Hippocampus;Human;human induced pluripotent stem cells;human stem cell-derived;human tissue;Impairment;Implant;in silico;in vivo;in vivo evaluation;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;infancy;inhibitory neuron;insight;interest;Interneurons;Intractable Epilepsy;Ion Channel;K-Series Research Career Programs;Link;loss of function;Mentors;Missense Mutation;Modeling;mortality;mouse model;multi-scale modeling;Mus;National Institute of Neurological Disorders and Stroke;network dysfunction;neural circuit;neurodevelopment;Neurodevelopmental Disorder;neuronal circuitry;Neuronal Dysfunction;neuronal excitability;Neurons;neurophysiology;novel strategies;Optics;Output;Pathogenicity;Patients;Pharmaceutical Preparations;Phenotype;Physicians;Population;Population Analysis;programs;Quality of life;Recurrence;Reporter;Research;research study;Scientist;SCN1A protein;SCN2A protein;Seizures;Severities;Signal Transduction;Slice;Sodium Channel;Sodium Channel Blockers;spatiotemporal;Sudden Death;Synapses;Teacher Professional Development;Training;United States;Variant;voltage

PROJECT_TITLE: Multi-scale disease modeling of SCN2A-related epilepsy due to gain-of-function variants

STUDY_SECTION: NST

STUDY_SECTION_NAME: NST-1 Study Section[NST-1]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON AGING

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);Bioengineering;Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: CORAL GABLES

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF MIAMI CORAL GABLES

ORG_STATE: FL

PHR: Narrative Blood flow is reduced in small brain blood vessels in patients and mouse models of Alzheimer’s disease, in part due to capillary obstruction that disrupts blood flow dynamics. We discovered that blood flow dynamics are normally sensed by force sensors such as Piezo1, but it is unknown whether these sensors are impaired during Alzheimer's disease. Here, we will use advanced imaging and electrophysiological techniques to study whether Piezo1 function changes during Alzheimer’s Disease and whether restoring its function reduces capillary obstructions and improves blood flow.

PI_NAMEs: BRACKO, OLIVER  (contact);HARRAZ, OSAMA F

PROGRAM_OFFICER_NAME: NEWMAN, ELIZABETH

PROJECT_TERMS: Age;Aging;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease model;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid beta-Protein;Architecture;Autopsy;Blood;Blood - brain barrier anatomy;Blood capillaries;Blood flow;Blood Vessels;blood-brain barrier permeabilization;capillary bed;Capillary Endothelial Cell;Cell Line;Cephalic;cerebral capillary;cerebrovascular;Cerebrovascular Circulation;Cerebrovascular Disorders;Cerebrovascular system;Cognitive deficits;constriction;Data;Disease;Disease Progression;Electrophysiology (science);Embryo;end of life;Endothelial Cells;endothelial dysfunction;Endothelium;Esthesia;Exposure to;flexibility;force sensor;Foundations;Functional disorder;Future;Genetic;Health;hemodynamics;Image;Impairment;improved;in vivo;in vivo imaging;innovation;insight;Ion Channel;Life;Link;Maintenance;Measures;mechanical force;Mechanics;mechanotransduction;Memory impairment;Metabolic;Metabolism;Molecular;Molecular Analysis;mouse model;Mus;Neurodegenerative Disorders;neuron loss;Neurons;novel;novel therapeutic intervention;Obstruction;patch clamp;Patients;Pericytes;pharmacologic;Piezo 1 ion channel;Play;Probability;Proteins;Regulation;Resolution;Risk Factors;Role;sensor;shear stress;Signal Transduction;Stimulus;Techniques;Testing;Three-Dimensional Image;Time;transcriptome sequencing;Translating;two photon microscopy;two-photon;vascular contributions;vascular inflammation;Western Blotting;Wild Type Mouse;Work

PROJECT_TITLE: Brain capillary Piezo1 ion channels and blood flow regulation in Alzheimer’s Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AN-Q(55)R]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: Project narrative Advances in sequencing technology have enabled millions of human genomes to be sequenced by short-read high-throughput sequencing (HTS), and thousands of genomes using single-molecule sequencing (SMS). To maximize utility in human genetics, we propose developing new software tools that detect complex genetic variation in SMS data, and can discover the population frequency of this variation by genotyping large HTS datasets.

PI_NAMEs: CHAISSON, MARK  (contact)

PROGRAM_OFFICER_NAME: WETTERSTRAND, KRIS A

PROJECT_TERMS: algorithm development;Algorithms;base;cohort;Complex;Computer software;contig;Copy Number Polymorphism;Darkness;Data;Data Set;Databases;Detection;Development;Diagnostic;Disease;DNA Sequence Rearrangement;Ecosystem;Frequencies;Genetic Predisposition to Disease;Genetic Variation;Genome;genome sequencing;Genotype;Goals;Haplotypes;Heritability;High-Throughput Nucleotide Sequencing;Human;human disease;Human Genetics;Human Genome;improved;Individual;innovation;insertion/deletion mutation;Knowledge;Length;light weight;Maps;Methods;Minisatellite Repeats;Minor;novel;Optics;pan-genome;Population;Process;Repetitive Sequence;Research;Resources;Role;Sensitivity and Specificity;Sequence Alignment;single molecule;Single Nucleotide Polymorphism;Software Tools;Structure;Technology;Testing;Trans-Omics for Precision Medicine;Variant;variant detection;Work

PROJECT_TITLE: Detection and genotyping complex human genetic variation using single-molecule sequencing

STUDY_SECTION: GCAT

STUDY_SECTION_NAME: Genomics, Computational Biology and Technology Study Section[GCAT]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Neurodegenerative;Neurosciences;Parkinson's Disease;Physical Rehabilitation;Rehabilitation

ORG_CITY: CHAPEL HILL

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: Project Narrative People with Parkinson's disease exhibit reduced walking ability that can be addressed by physical therapy. Learning how to improve walking represents a considerable challenge for patients and rehabilitation professionals. The proposed project will determine how to improve motor learning related to walking, through residual intact neural pathways for improved gait and long-term retention of functional benefits.

PI_NAMEs: DAYAN, ERAN ;LEWEK, MICHAEL D (contact)

PROGRAM_OFFICER_NAME: AJISAFE, TOYIN DELE

PROJECT_TERMS: Address;Adult;Affect;Attention;Auditory;Basal Ganglia;Behavioral;Biomechanics;Brain;Calibration;Cerebellum;clinical care;Compensation;Corpus striatum structure;Cues;Data;Deep Brain Stimulation;Dependence;Development;Diffusion Magnetic Resonance Imaging;Disease;Disease Progression;dopaminergic neuron;Educational Intervention;Effectiveness;Evaluation;Exhibits;follow-up;Freezing;Frequencies;Functional Magnetic Resonance Imaging;Gait;Gait abnormality;gait rehabilitation;Hippocampus;improved;Individual;insight;Intervention;Learning;Length;Long-Term Effects;Magnetic Resonance Imaging;motor impairment;motor learning;Motor Skills;motor symptom;Movement;multimodality;Nerve Degeneration;neural;neural circuit;Neural Pathways;Neuroanatomy;Neurodegenerative Disorders;neuroimaging;neurological rehabilitation;Outcome;Parkinson Disease;Participant;Patients;Periodicity;Persons;Pharmaceutical Preparations;pharmacologic;Phase;Physical Rehabilitation;physical therapist;Physical therapy;Positioning Attribute;Process;Psychological reinforcement;Randomized;randomized controlled design;Rehabilitation therapy;Residual state;Rest;Safety;Speed;Structure;Subconscious;Substantia nigra structure;Testing;Training;Walking;walking intervention

PROJECT_TITLE: Targeted Motor Learning to Improve Gait for Individuals with Parkinson's Disease

STUDY_SECTION: MFSR

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

PHR: PROJECT NARRATIVE (2-3 sentences) This proposal will test a hypothesis that communication between immune cell populations and pancreatic islets (the producers of insulin) is mediated by extracellular vesicles (EVs). EVs are known to mediate signals between cells and tissue in several diseases, however their role in type 1 diabetes (T1D) is still largely unknown. Here, we will examine the role of EVs from islet-infiltrating T cells and islets and evaluate their role in the T1D pathogenesis.

PI_NAMEs: KENT, SALLY CHOATE;REIJONEN, HELENA KRISTIINA (contact);VASAVADA, RUPANGI C

PROGRAM_OFFICER_NAME: BLONDEL, OLIVIER

PROJECT_TERMS: Address;Affect;Autoantibodies;Autoantigens;autocrine;Autoimmune;Autoimmune Diseases;Autologous;Beta Cell;Cardiovascular Pathology;Cardiovascular system;CD8B1 gene;Cell Communication;Cell Line;Cell Physiology;Cell Separation;cell type;Cells;Characteristics;Communication;cytokine;cytotoxic;cytotoxicity;Data;Dendritic Cells;Development;Diabetes Mellitus;diabetes pathogenesis;Disease;early detection biomarkers;Environment;extracellular vesicles;Family;Functional disorder;Goals;Hand;Health;Human;human tissue;Immune;immune cell infiltrate;Individual;Inflammation;Inflammatory;inflammatory milieu;Innate Immune System;insight;Insulin;Insulin-Dependent Diabetes Mellitus;intercellular communication;islet;islet cell antibody;Islets of Langerhans;Knowledge;Malignant Neoplasms;Mediating;Mediator;Membrane;Molecular;monocyte;National Institute of Diabetes and Digestive and Kidney Diseases;Nerve Degeneration;neurological pathology;Non-Insulin-Dependent Diabetes Mellitus;novel;Organ;Organ Donor;Pancreas;paracrine;Pathogenesis;Patients;Peripheral;Phenotype;Population;potential biomarker;Proteins;Research;Research Personnel;Resources;Role;Signal Transduction;Slice;Source;Spleen;STEM research;Stress;T cell infiltration;T cell response;T-Cell Activation;T-Lymphocyte;Techniques;Testing;therapeutic target;Tissue Donors;Tissue Sample;Tissues;Vesicle

PROJECT_TITLE: Extracellular Vesicle-mediated islet immune cross talk in Type 1 Diabetes pathogenesis


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

ORG_STATE: MA

PHR: NARRATIVE: (max 3 sentences) Individual cells of the human body continuously experience DNA damage and accumulate somatic mutations throughout life, and specific mutations may alter the phenotype of a cell through diverse mechanisms. Characterization of somatic mutations across diverse tissues from many individuals will immensely enhance our ability to understand the impact of somatic mutations and discover novel aspects of human biology. As a Genome Characterization Center (GCC) for the SMaHT program, we will contribute to the characterization, and creation of a resource catalog of somatic variation across human tissues at scale.

PI_NAMEs: ARDLIE, KRISTIN  (contact);LENNON, NIALL JOHN;NATARAJAN, PRADEEP

PROGRAM_OFFICER_NAME: LOSSIE, AMY C

PROJECT_TERMS: Affect;age related;Aging;Agreement;Anatomy;Benchmarking;Biological Assay;Blood;Cardiovascular Diseases;Catalogs;Cell Physiology;Cells;Chromosome abnormality;Chromosome Deletion;Chromosome Structures;Code;cohort;Collaborations;Communities;Computational Biology;computer framework;Data;Data Analyses;data harmonization;data resource;Data Set;data submission;design;Detection;Development;Disease;DNA;DNA Damage;DNA sequencing;Dryness;exome sequencing;experience;Exposure to;fitness;Frequencies;Gene Expression;Generations;Genetic;Genome;genome sequencing;Genomics;Genotype-Tissue Expression Project;Goals;Guidelines;Hematopoiesis;High Prevalence;high throughput screening;Human;Human Biology;Human body;Human Development;Human Genetics;human tissue;Individual;insight;Joints;Knowledge;Life;life history;life span;Malignant Neoplasms;Measures;Molecular;Mosaicism;multidisciplinary;Mutagenesis;Mutation;new technology;Normal tissue morphology;novel;Nucleic Acid Regulatory Sequences;Organ;Outcome;Pathogenesis;Pattern;Phenotype;Phylogenetic Analysis;preservation;Process;Production;programs;Proteins;Protocols documentation;Recording of previous events;Resolution;Resources;response;Role;Sampling;Science;Site;Somatic Mutation;Specimen;Standardization;Stretching;success;Technology;timeline;Tissue Banks;tissue processing;Tissue Procurements;Tissue Sample;Tissues;Trans-Omics for Precision Medicine;transcriptome sequencing;Trees;United States National Institutes of Health;Untranslated RNA;Variant;Work

PROJECT_TITLE: Whole Individual Comprehensive KnowlEDge: Somatic Mosaicism across Human Tissues (WICKed SMaHT)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CDB-K(70)R]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Gene Therapy;Genetics;Hematology;Machine Learning and Artificial Intelligence;Orphan Drug;Pain Research;Rare Diseases;Sickle Cell Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: BERKELEY

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative This U01 research project seeks to develop and analytically validate a robust, first-in-kind, potency assay for editing-based therapies for SCD. Rather than relying on a single diagnostic tool, the proposed assay will consist of an integrated suite of complementary functional RBC tests, the outputs of which will enable a trained machine learning to determine the fraction of RBCs in a differentiated edited cell product that have been effectively repaired.

PI_NAMEs: GIANNIKOPOULOS, PETROS  (contact);GURKAN, UMUT A.

PROGRAM_OFFICER_NAME: POON, BETTY

PROJECT_TERMS: Abnormal Hemoglobins;Abnormal Red Blood Cell;Address;Affect;algorithm training;American;assay development;autosome;base editing;biochip;Biological Assay;biophysical properties;Biophysics;Blood capillaries;cell preparation;Cells;Chemistry;Clinical;clinical development;Clinical Trials;clinically relevant;Code;cohort;Data;Development;Devices;Diagnostic;diagnostic assay;Diagnostic Equipment;diagnostic tool;differentiation in vitro;Disease;disease phenotype;DNA sequencing;Erythrocytes;Event;Exhibits;experience;FDA approved;Feedback;gene therapy;Genes;genome editing;Health;health assessment;Hematological Disease;Hematology;Hematopoietic stem cells;Hemoglobin;High Pressure Liquid Chromatography;Human;improved;in vivo;Individual;Inherited;innovation;Label;Laboratories;laboratory equipment;Life Expectancy;Linear Regressions;Machine Learning;machine learning model;manufacture;Measures;Methods;Microfluidics;Modality;Modeling;Modification;Molecular;Morbidity - disease rate;mortality;neural network;next generation;novel;Organ;Organ failure;Outcome;Output;Pain;Pathologic;Patients;Performance;personalized diagnostics;Pharmaceutical Preparations;Phenotype;polymerization;Polymers;Population;Positioning Attribute;primary endpoint;Property;Protocols documentation;Reference Standards;Regulation;repaired;Research Project Grants;Resolution;response;Sampling;Severities;Sickle Cell Anemia;simulation;Source;supervised learning;Testing;therapeutic genome editing;Training;Validation;Variant;vaso-occlusive pain

PROJECT_TITLE: A Modality-Agnostic Potency Assay Enabling Both Ex Vivo and In Vivo Genome Editing Therapeutics for Sickle Cell Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MGG-M(70)R]


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Digestive Diseases;Pediatric

ORG_CITY: SAINT LOUIS

ORG_DEPT: PEDIATRICS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE The digestive health of children influences the health of populations throughout the life span. Pathobiology beginning in childhood often has irreversible consequences (e.g., obesity, inflammatory bowel disease) in children, adolescents, adults, families and communities. We provide rigorous training to young scientists from diverse disciplines so they can prevent or cure these daunting problems.

PI_NAMEs: TARR, PHILLIP I (contact)

PROGRAM_OFFICER_NAME: SERRANO, KATRINA JANE

PROJECT_TITLE: Pediatric Gastroenterology Research Training Program


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Immunotherapy;Orphan Drug;Ovarian Cancer;Rare Diseases;Women's Health Research

ORG_CITY: Pittsburgh

ORG_NAME: MAGEE-WOMEN'S RES INST AND FOUNDATION

ORG_STATE: PA

PHR: Narrative We have developed novel ALDH1A inhibitors (ALDHi) which, via altered retinoic acid signaling, induce inflammatory death in cancer cells while promoting proliferation of CD8+ T cells. We will evaluate the mechanisms of ALDHi-induced inflammatory cell death, the impact of ALDHi on immune cells, and whether ALDHi can enhance anti-tumor immunotherapy.

PI_NAMEs: BUCKANOVICH, RONALD J (contact);CASCIO, SANDRA

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: aldehyde dehydrogenases;American;Anabolism;Binding;cancer cell;cancer immunotherapy;cancer initiation;Cancer Patient;cancer therapy;Cancer Vaccines;carcinogenesis;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Death;Cell Physiology;Cell Proliferation;cell type;Cells;Cellular biology;Cessation of life;checkpoint therapy;Clinical;cytokine;Data;Dendritic Cells;Disease;Down-Regulation;Enzyme Inhibitor Drugs;Enzymes;exhaustion;Family;Family member;FOXP3 gene;Generations;Genetic Transcription;Goals;Human;Immune;immune checkpoint blockade;Immune system;Immune Tolerance;Immunity;Immunobiology;Immunocompetent;Immunomodulators;Immunotherapeutic agent;Immunotherapy;In Vitro;in vivo;Incidence;Individual;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;inhibitor;Interleukin-12;knock-down;Knock-out;LacZ Genes;Link;Malignant neoplasm of ovary;Malignant Neoplasms;Mediating;Modeling;Molecular;mortality;MUC1 gene;Mucin 1 protein;Mus;Necrosis;neoplasm immunotherapy;neoplastic cell;new therapeutic target;novel;novel strategies;novel therapeutics;NR4A1 gene;Nuclear Receptors;ovarian neoplasm;Patients;Pattern;pharmacologic;Phenotype;Production;Proliferating;receptor;Regulatory T-Lymphocyte;Reporter;Resistance;response;Retinoic Acid Receptor;Role;RXR;Signal Transduction;stemness;T cell differentiation;T cell infiltration;T cell response;T-Cell Activation;T-Lymphocyte;Testing;Therapeutic;therapeutic target;therapy resistant;transcription factor;transcriptome sequencing;transdifferentiation;Transgenic Mice;Tretinoin;tumor;Tumor Antigens;Tumor Immunity;Tumor-Infiltrating Lymphocytes;Up-Regulation;Vaccines;Woman;Women's mortality

PROJECT_TITLE: ALDH Inhibition as Modulator of Tumor Immunobiology

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Machine Learning and Artificial Intelligence;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Neurosciences;Pediatric;Precision Medicine;Prevention

ORG_CITY: Boulder

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: Project Narrative Mood and anxiety disorders are highly prevalent, debilitating psychopathologies that commonly emerge in young adulthood, which in turn is a developmental period characterized by increased exposure to stressors related to the transition to independence. The proposed study takes a longitudinal, mechanistic approach to understand how distinct profiles of cognitive functioning (related to executive functioning and responsiveness to reward or threat) interact to confer general or specific vulnerability for internalizing symptoms (anhedonia, anxious arousal, and mania). By testing new interdisciplinary tools for predicting future psychiatric health, this research aims to provide information that may be translated to inform the delivery of preventive interventions to young adults.

PI_NAMEs: KAISER, ROSELINDE H (contact);SNYDER, HANNAH R.

PROGRAM_OFFICER_NAME: FERRANTE, MICHELE

PROJECT_TERMS: Address;Age;Anhedonia;Anxiety;Anxiety Disorders;anxious;approach behavior;Arousal;Behavior;behavior prediction;Behavioral;biobehavior;Clinical;clinical practice;clinical translation;clinically significant;Cognition;cognitive control;cognitive function;college;comorbidity;Complex;Counseling;Data Set;Development;Diagnosis;Diagnostic;diagnostic platform;diaries;Dimensions;Disease;Dropout;emerging adult;emerging adulthood;emotion regulation;Enrollment;Environment;Etiology;Evaluation;Event;executive function;experience;Exposure to;Future;Goals;Health;high reward;Impairment;in vivo;Incidence;Individual;Individual Differences;Intervention;Investigation;Life;Link;Longitudinal Studies;Machine Learning;maladaptive behavior;Manic;Measures;Mental Depression;Mental Health;Methodology;mobile application;Modeling;Mood Disorders;Negative Valence;Neurocognition;Neurocognitive;novel;Outcome;outcome prediction;Participant;Pathology;Pathway interactions;Patient Self-Report;Performance;Persons;Phenotype;Physiological;Physiology;Positive Valence;precision medicine;predictive modeling;predictive tools;preventive intervention;Psychopathology;Public Health;Recording of previous events;recruit;Research;Research Domain Criteria;response;Rewards;Risk;Risk Behaviors;Risk Factors;Risk Marker;Sample Size;Sampling;screening;sex;Sex Differences;social;Statistical Models;Stress;stressor;Students;Symptoms;Targeted Research;Techniques;Technology;Testing;Time;Translating;university student;Withdrawal;young adult

PROJECT_TITLE: Leveraging Latent Factors and Machine Learning to Forecast Internalizing Psychopathology in Emerging Adulthood

STUDY_SECTION: APDA

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


NIH_SPENDING_CATS: Genetics

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Emerging evidence from recent genome-wide studies has revealed that promoters across eukaryotes are commonly paired to drive bidirectional transcription. Work in yeast suggests bidirectional transcription could be the naïve or innate state of transcription initiation with directionality evolving due to the action of diverse pathways. Building on our initial success in developing a highly efficient in vitro reconstitution system of transcription initiation from highly purified yeast factors, we set out to further develop this system to solve the mechanism of divergent transcription through structural and biochemical dissection.

PI_NAMEs: MURAKAMI, KENJI  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: analytical ultracentrifugation;Base Pairing;Biochemical;Chemicals;Complex;crosslink;Cryo-electron tomography;Cryoelectron Microscopy;Dependence;dimer;Dimerization;Dissection;Dissociation;DNA;Elongation Factor;Employment;Eukaryota;Evolution;Funding;Gene Expression;Genes;genetic regulatory protein;Genetic study;Genetic Transcription;genome-wide analysis;Human;Impairment;In Vitro;in vivo;insight;Length;Mass Spectrum Analysis;Mediator;Modeling;Molecular;Molecular Conformation;mutant;novel;Nucleosomes;particle;Pathway interactions;Phosphotransferases;Polymerase;Positioning Attribute;promoter;Property;Proteins;reconstitution;recruit;Research;RNA;RNA Polymerase II;Role;Sedimentation process;Series;stoichiometry;Structure;success;System;Tail;Transcript;transcription factor;transcription factor TFIIH;Transcription Initiation;Transcriptional Activation;Transcriptional Regulation;transcriptome sequencing;Work;Yeasts

PROJECT_TITLE: Functional and structural studies of the transition from transcription initiation to elongation

STUDY_SECTION: MSFB

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


ADMINISTERING_IC: AA

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Assistive Technology;Bioengineering;Biotechnology;Clinical Research;Networking and Information Technology R&D (NITRD);Substance Misuse

ORG_CITY: THOUSAND OAKS

ORG_NAME: ACTIOX LLC

PHR: Public Health Relevance Excessive alcohol use is a leading preventable cause of death and disability, with an average of 95,158 alcohol- attributable deaths in the United States each year. Despite the high demands for a wearable sensor that can continuously monitor alcohol consumption in real-time, current devices lack the desired workability. In this SBIR Fast-Track application, we propose further development of ActioX, LLC biosensor system, a discreet, non- obtrusive, and calibration-free wearable integrated device capable of continuously measuring alcohol consumption in real-time.

PI_NAMEs: TEHRANI, FARSHAD  (contact)

PROGRAM_OFFICER_NAME: MURRAY, GARY

PROJECT_TERMS: Age;Alcohol consumption;alcohol measurement;alcohol monitoring;alcohol oxidase;alcohol related problem;alcohol response;alcohol use disorder;Alcohols;Algorithms;attributable mortality;Bacterial Artificial Chromosomes;Biological Assay;biomaterial compatibility;Biosensing Techniques;Biosensor;Blood;Blood alcohol level measurement;Body measure procedure;body sense;Calibration;Cause of Death;Centers for Disease Control and Prevention (U.S.);Cessation of life;Chemicals;Chemistry;Clinic;Clinical;Clinical Research;commercialization;cost;Coupled;Custom;cytotoxicity;Data;Data Display;design;Detection;Development;Devices;Diameter;disability;Dose;Drug Rehabilitation Centers;drug testing;Economic Factors;Electronics;enzyme activity;Enzymes;Ethnic Population;Face;Feasibility Studies;feasibility testing;Forensic Medicine;Gender;Goals;Government;Health;Heavy Drinking;Hospitals;Hour;Human;human subject;Hydrogen Peroxide;Immobilization;In Vitro;innovation;innovative technologies;Intercellular Fluid;interest;Laboratories;Life;Measurement;Measures;Mechanics;Methods;Microinjections;miniaturize;miniaturized device;Mission;mobile application;Modification;Molds;monitoring device;National Institute on Alcohol Abuse and Alcoholism;Needles;Noise;novel;operation;oxidation;Pain Free;Painless;Penetration;Performance;Phase;Polymers;Population Heterogeneity;printed circuit board;programs;prospective;prototype;public health relevance;racial population;real time monitoring;Reporting;Reproducibility;Research;research clinical testing;response;Secure;sensor;sensor technology;Series;Signal Transduction;Skin;Small Business Innovation Research Grant;Sterilization;Structure;System;Testing;Thick;Time;trial design;United States;Validation;vapor;Variant;Venous;Visualization;wearable data;wearable device;wearable sensor technology;wireless;Work;World Health Organization

PROJECT_TITLE: Discreet Wearable device for Continuous Real-time Monitoring of Alcohol


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Neurosciences;Patient Safety;Pediatric

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

PHR: Narrative Despite continuous advances, magnetic resonance imaging (MRI) remains largely inaccessible to patients who have electronic implants. The problem is worse in children, for whom MR-conditional devices are not readily available. Here we develop, validate, and deploy a novel MRI technology that allows ultra-fast and high- resolution MRI to be safely performed in children with conductive implants regardless of the implant location.

PI_NAMEs: GOLESTANI RAD, LALEH  (contact)

PROGRAM_OFFICER_NAME: WANG, SHUMIN

PROJECT_TERMS: 3-Dimensional;6 year old;absorption;Acceleration;Accounting;Adult;Age;Biophysics;Body Size;Brain imaging;Brain scan;Cardiac;cardiac implant;Cardiovascular system;case-by-case basis;Central Nervous System;Child;Childhood;Clinical;Coiled Bodies;Couples;design;Devices;electric field;Electrodes;Electronics;Engineering;Exclusion;FDA approved;Fever;flexibility;Head;heart imaging;Heating;Helmet;History of Medicine;Human;Human Biology;Human Pathology;Image;Implant;implantable device;improved;Individual;Industrialization;industry partner;Infant;Injury;innovation;instrumentation;interest;Intervention;Investments;Knowledge;Location;Magnetic Resonance Imaging;Manufacturer;Maps;Marketing;Mechanics;Methodology;Motion;multidisciplinary;Nervous System;novel;Pathology;patient safety;Patients;pediatric patients;Pediatric Radiology;Pediatric Surgical Procedures;Performance;Phase;radio frequency;Research;Resolution;Resources;Risk;Rotation;Safety;safety assessment;Scientific Inquiry;Severities;Slice;standard of care;System;Techniques;Technology;Tissues;transmission process;vagus nerve stimulation;Vendor;virtual;Vulnerable Populations;Work

PROJECT_TITLE: Novel MRI coil technology for safe imaging of children with implants

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: PITTSBURGH

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Current antiretroviral therapies dramatically reduced mortality in persons living with HIV (PWH), yet immune activation, inflammation and hypercoagulability persist in this population and are responsible for comorbidities, such as cardiovascular disease. Here we propose that excessive NETosis, a neutrophil dysfunction is a key determinant of persistent inflammation and of the hypercoagulation status in SIV/HIV infected individuals. We will directly target the neutrophil dysfunction through administration of an inhibitor of neutrophil extracellular traps (NETs). This project will improve our understanding of SIV/HIV pathogenesis, response to treatment and the mechanisms of SIV/HIV-related comorbidities, and thus may have a major impact on the clinical management and survival of the PWH. Our study may validate a drug that can be used to inhibit excessive NETosis. This approach could benefit multiple diseases, including infections with pandemic potential, such as COVID-19.

PI_NAMEs: VASILE PANDREA, IVONA  (contact)

PROGRAM_OFFICER_NAME: ZOU, SHIMIAN

PROJECT_TERMS: Acceleration;Acquired Immunodeficiency Syndrome;Address;Adjuvant;Age;Animal Model;antiretroviral therapy;antithrombin III-protease complex;Automobile Driving;Biological Markers;Blood Platelets;Cardiovascular Diseases;Cause of Death;CD4 Positive T Lymphocytes;Cells;Cessation of life;Chronic;chronic infection;Clinical Management;Coagulation Process;comorbidity;COVID-19;cytokine;Data;design;Development;Disease;Disease Progression;Environment;Experimental Designs;experimental study;extracellular;Fibrin fragment D;Frequencies;Functional disorder;Goals;gut health;HIV;HIV Infections;HIV/AIDS;Immune;immune activation;improved;in vivo;Individual;Infection;Inflammation;Inflammatory;inhibitor;innovation;Intervention;Intestines;Knowledge;Laboratories;Macaca;Macaca nemestrina;Modeling;Morbidity - disease rate;mortality;Mucous Membrane;Mus;Natural History;neutrophil;nonhuman primate;novel therapeutics;Organ;pandemic potential;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Platelet Count measurement;Population;Process;Production;Prognosis;Recovery;Reporting;Research;Residual state;response;restoration;Role;SIV;Testing;Thrombophilia;Thromboplastin;Thrombosis;Tissues;treatment response;Virus;Virus Replication

PROJECT_TITLE: Impact of NETosis on SIV Pathogenesis and Response to Treatment

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


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: SEATTLE

ORG_NAME: SEATTLE CHILDREN'S HOSPITAL

ORG_STATE: WA

PHR: PROJECT NARRATIVE Precision genomic medicine depends on a complete understanding of genetic variation in normal individuals, but current approaches fail to capture all the types of genetic variation, because they 1) do not measure genetic variation in so-called “unmappable” regions of the genome, and 2) assume the genomes of every cell in a single multicellular human are identical. The goal of our proposal “Mosaicism in Human Tissues, from Telomere to Telomere” is to characterize multiple types of human somatic variation across the entire human genome in a set of 10 tissues from 50 donors, and to work with other members of the network towards producing a framework for understanding somatic variation in post-mortem, non-pathological human tissues.

PI_NAMEs: BENNETT, JAMES T (contact);EICHLER, EVAN ;STERGACHIS, ANDREW BEN;WEI, CHIA-LIN

PROJECT_TERMS: Address;Alleles;Area;Autopsy;Benchmarking;Biology;Blood;Cancer cell line;Catalogs;Cell Line;Cells;Chromatin;Collaborations;Complex;cost;Data;Data Analyses;Data Set;design;Detection;Disease;DNA Sequence;DNA sequencing;Elements;Epigenetic Process;Genes;Genetic study;Genetic Transcription;genetic variant;Genetic Variation;Genome;genome-wide;genomic locus;Genomic Segment;Genomics;Goals;Haplotypes;Health;Hi-C;Human;human disease;Human Genetics;Human Genome;human reference genome;human tissue;improved;Individual;International;Knowledge;Large-Scale Sequencing;Length;Location;member;Methods;Methylation;Molecular Conformation;Mosaicism;Mutate;nanopore;Normal Cell;Nucleotides;Pattern;Phase;Play;precision genomic medicine;Principal Investigator;programs;reference genome;RNA;Role;Sampling;scaffold;single molecule;Somatic Mutation;Structure;telomere;Tissues;Transcript;transcription factor;transcriptome sequencing;Validation;Variant;Vision;whole genome;Work

PROJECT_TITLE: 'Mosaicism in Human Tissues, from Telomere to Telomere to RFA-22-013: "Somatic Mosaicism across Human Tissues Program: Genome Characterization Centers."


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Human Genome;Nutrition

ORG_CITY: CLEVELAND

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

ORG_STATE: OH

PHR: The overall goal of this proposal is to develop a mechanistic, transcriptome-wide understanding of translation regulation during osmoadaptation. We will generate the first predictive “code” for translation regulation with multiple parameters for any stress response. Our predicted models will provide molecular targets and biomarkers for therapeutics for diseases involving loss of osmotolerance such as dry eye syndrome.

PI_NAMEs: HATZOGLOU, MARIA  (contact);SCHAFFER, ASHLEIGH E

PROGRAM_OFFICER_NAME: MARUVADA, PADMA

PROJECT_TERMS: Address;Affect;Amino Acid Transporter;Amino Acids;balance testing;Binding;Binding Proteins;biological adaptation to stress;Biological Process;Cell Death;Cell Survival;cell type;Cell Volumes;Cells;Cellular Assay;Cellular biology;Cellular Stress;Code;corneal epithelium;Cytoplasmic Granules;Data;Defect;Dehydration;Diabetes Mellitus;Disease;Dry Eye Syndromes;environmental change;Epithelial Cells;experience;exposed human population;Exposure to;Eye;FRAP1 gene;Future;G3BP1 gene;Genetic Transcription;Goals;Homeostasis;Human;Hyperglycemia;Individual;Inflammatory;Inflammatory Bowel Diseases;insight;Ionic Strengths;Knowledge;Life;Link;link protein;Liquid substance;Malignant Neoplasms;Measurement;Measures;Messenger RNA;Modeling;Molecular;Molecular Biology Techniques;molecular marker;Molecular Target;mRNA Translation;novel;Nutrient;Organism;Osmolar Concentration;Osmotic Pressure;Pathologic;Pathology;Pattern;Phase;Physiological;predictive modeling;Process;programs;Protein Biosynthesis;Regulation;Reporter;Research;response;ribosome profiling;RNA;RNA Binding;RNA-Binding Proteins;Stress;Syndrome;System;Therapeutic;therapeutic development;Tissues;Transcript;transcriptome;transcriptome sequencing;transcriptomics;Translational Regulation;Translations;Water

PROJECT_TITLE: Translational control by nutrients

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Genetics;Huntington's Disease;Neurodegenerative;Neurosciences;Prevention;Rare Diseases

ORG_CITY: MOUNT PLEASANT

ORG_NAME: CENTRAL MICHIGAN UNIVERSITY

PHR: PROJECT NARRATIVE The BRAIN initiative has enabled the development of approaches for modulating specific microcircuits through genetically targeting discrete types of neurons; however, their application to disease models is lagging. In this collaboration between Huntington’s disease (HD) researchers and BRAIN tool developers we will utilize novel interventional tools for changing neural circuit dynamics at the early, pre-symptomatic stage for preventing or delaying and mitigating the behavioral deficits in a transgenic mouse model of HD. Our project will drive translational progress toward potential novel therapeutic purposes for HD as well as other neurodegenerative diseases that show circuit imbalances, while at the same time addressing basic questions of neural circuit function underlying behavior relevant to both NINDS and NIMH.

PI_NAMEs: HOCHGESCHWENDER, UTE H (contact);ROSSIGNOL, JULIEN

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: Address;Adenine;Affect;Behavior;Behavioral;Behavioral Research;Brain;Brain Diseases;BRAIN initiative;Cell Survival;Cellular Morphology;Chimeric Proteins;Cognition;Cognitive deficits;Collaborations;Communication;Compensation;Complex;Corpus striatum structure;Cytosine;Development;Disease;disease model;Disease Progression;DNA Sequence Alteration;Early Intervention;efficacious treatment;Electrophysiology (science);Event;Excitatory Synapse;Exons;Genes;Genetic;Goals;Guanine;hippocampal pyramidal neuron;Human;Huntington Disease;Huntington gene;Hyperactivity;Interneurons;Intervention;Ion Channel;Light;light emission;Link;Luciferases;luciferin;Mental Health;mouse model;Movement;Mus;National Institute of Mental Health;National Institute of Neurological Disorders and Stroke;Neocortex;neural;neural circuit;Neurodegenerative Disorders;neuronal circuitry;Neurons;neuropathology;novel;novel therapeutics;Opsin;optogenetics;Output;Parvalbumins;Pathogenesis;Pathologic;Patients;Peripheral;Persons;Phase;Physiological;Population;postsynaptic;postsynaptic neurons;preservation;presynaptic;prevent;Process;Regulation;Research;Research Personnel;sensor;Symptoms;Synapses;Synaptic Transmission;Target Populations;Testing;Therapeutic;Time;tool;tool development;Transgenes;Transgenic Mice;translational progress;Triplet Multiple Birth

PROJECT_TITLE: Targeted Circuit Manipulation for Ameliorating Huntington's Disease Pathogenesis

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: TR

IC_NAME: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Rural Health;Social Determinants of Health

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: Project Narrative The North Carolina Translational and Clinical Sciences Institute (TraCS) is the integrated hub of the NIH Clinical and Translation Science Award (CTSA) at the University of North Carolina at Chapel Hill and our partners. Over the next seven years, we will apply our expertise and infrastructure to catalyze development, testing, implementation, and dissemination of translational science and research to improve human health, with an explicit focus on advancing health equity.

PI_NAMEs: SHAHEEN, NICHOLAS J (contact)

PROGRAM_OFFICER_NAME: BOUGH, KRISTOPHER J

PROJECT_TERMS: Acceleration;Address;Attention;Automobile Driving;Basic Science;Breathing;career;Clinical;Clinical and Translational Science Awards;clinical care;Clinical Research;Clinical Sciences;Clinical Trials Design;Communities;computer science;Country;Data Science;design;Development;diagnostic strategy;Discipline;Dissemination and Implementation;Diverse Workforce;Economics;Emergency Situation;empowerment;Engineering;Ensure;Environment;Evaluation;Event;evidence base;flexibility;Fostering;Future;Goals;Harm Reduction;Health;health disparity;health equity;health equity promotion;Health equity research;health inequalities;Health Personnel;Health Policy;Healthcare Systems;Home;Human;implementation strategy;improved;Informatics;Infrastructure;innovation;Institution;Intervention;Laboratories;Lead;Leadership;Learning;Methods;multidisciplinary;NIH Program Announcements;North Carolina;novel;Outcome;pandemic disease;Participant;Patient Recruitments;Patients;Persons;Policies;Population;Population Heterogeneity;Prevention strategy;Process;programs;Public Health;Readiness;recruit;Reduce health disparities;Research;Research Infrastructure;Research Institute;Research Personnel;Research Support;research to practice;Resources;Rural Population;rural underserved;Services;social health determinants;Social Justice;Testing;Time;Training;Translating;translational goal;Translational Research;Translations;treatment strategy;Trust;United States National Institutes of Health;Universities;Veterinary Medicine;Veterinary Schools;Vision;Workforce Development

PROJECT_TITLE: North Carolina Translational and Clinical Sciences Institute (NC TraCS)


ADMINISTERING_IC: OD

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Cancer;Immunotherapy;Lung;Lung Cancer

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative While the immune system is the body’s first line of defense against cancer, tumor cells are known to develop mechanisms to alter the immune system’s response to support their growth and progression. In this proposal, I will establish animal models to 1) understand how tumors can exploit the immune response and 2) establish therapeutic strategies to reverse this process by focusing on the interaction between immune cells and tumor cells.

PI_NAMEs: WETTERSTEN, HIROMI INOUE (contact)

PROGRAM_OFFICER_NAME: TANDON, RITESH

PROJECT_TERMS: Acceleration;adhesion receptor;Advanced Malignant Neoplasm;Animal Model;anti-tumor immune response;Antibodies;cancer cell;carcinogenesis;Carcinoma;career;Cell Adhesion;Cells;Chemicals;Chronic;Communication;cytokine;Cytotoxic T-Lymphocytes;Data;Development;Drug resistance;Ectopic Expression;Environment;Epithelial Cells;epithelial to mesenchymal transition;Epithelium;Equipment;Foundations;Gene Modified;Goals;Growth;Human;Immune;Immune checkpoint inhibitor;Immune response;Immune system;Immunocompetent;Immunocompromised Host;Immunosuppression;Immunotherapeutic agent;In Vitro;Inflammation;Inflammation Mediators;Inflammatory;Integrin alphaVbeta3;Integrins;interest;Knock-out;Knockout Mice;Knowledge;KRAS2 gene;Laboratories;Link;Lung;lung cancer cell;lung carcinogenesis;Macrophage;Malignant neoplasm of lung;Malignant Neoplasms;Mature T-Lymphocyte;Mediating;Modeling;mouse model;Mus;Mutant Strains Mice;Neoplasm Metastasis;neoplastic cell;novel;novel therapeutic intervention;Nude Mice;Organ;Pharmaceutical Preparations;Phenotype;prevent;Process;Publishing;Pulmonary Inflammation;recruit;Reporting;Research Personnel;Risk Factors;success;Testing;Therapeutic;Training;tumor;tumor microenvironment;tumor progression;Tumor-associated macrophages;tumor-immune system interactions;Veterinarians;Work

PROJECT_TITLE: αvβ3-induced epithelial cancer progression via macrophage recruitment


NIH_SPENDING_CATS: Behavioral and Social Science;HIV/AIDS;Infectious Diseases;Mental Health;Prevention

PHR: NARRATIVE To date, the use of HIV molecular surveillance has not been linked to a reduction in HIV incidence. The proposed project will perform secondary analyses of coded and de-identified public health HIV surveillance data from the Los Angeles County (LAC) Health Department. The study team will engage key stakeholder populations and use regional estimates of HIV transmission and HIV program data to project the impact of alternative strategies for the optimal allocation of resources to LAC HIV prevention programs relevant to EHE targets.

PI_NAMEs: LITTLE, SUSAN JANET (contact);MARTIN, NATASHA

PROGRAM_OFFICER_NAME: POLLARD-BRANCHARD, SUZANNE LEE

PROJECT_TERMS: Acute;Affect;AIDS prevention;Area;Blood specimen;Code;Consensus;cost;cost effectiveness;County;Data;Data Analyses;data exchange;Decision Making;detection method;Economic Models;Economics;efficacy outcomes;Epidemic;Equity;Evaluation;evidence base;Feedback;Future;Geography;Goals;Health;health equity;Health Personnel;HIV;HIV Infections;HIV/STD;Human Resources;implementation strategy;improved;Incidence;Individual;Infection;Infrastructure;Intervention;Laboratories;Link;Los Angeles;Measures;Methods;Modeling;Molecular;Outcome;Pathway Analysis;Persons;Phylogenetic Analysis;Population;population based;Prevalence;Prevention;Prevention program;preventive intervention;Process;Program Evaluation;programs;prospective;Public Health;rapid detection;Reporting;Research Personnel;Resource Allocation;Resources;Risk;secondary analysis;Services;surveillance data;Surveillance Program;Testing;tool;transmission process;Universities;user-friendly;Viral

PROJECT_TITLE: Miami Dade County ASsessment of Phylogenetics to Improve Resource Equity: MD ASPIRE


ORG_CITY: CHICAGO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE Current studies in the non-human primate model led to surprising, important findings such as the possible dependence of the reservoir on myeloid cell infection and to the development of groundbreaking technologies for the investigation of the tissue reservoir. By leveraging these new insights and technologies, we will investigate the dynamics of the HIV reservoir with unprecedented, unbiased resolution, including dissecting the role of little known, tissue resident cell targets of HIV infection of myeloid origins.

PI_NAMEs: HOPE, THOMAS  (contact)

PROGRAM_OFFICER_NAME: NOVAK, LEIA KAYE

PROJECT_TERMS: acute infection;Animals;Anti-viral Response;Antibodies;Aquila;Area;Autopsy;Binding;Biological Assay;Blood;Blood Cells;Blood specimen;CCR5 gene;CD4 Positive T Lymphocytes;Cell Differentiation process;Cell Separation;cell type;Cells;Characteristics;Collaborations;critical period;Data;Dependence;Detection;Development;Disadvantaged;emerging virus;Goals;granulocyte;HIV;HIV Infections;Human;human tissue;humanized mouse;ImmunoPET;In Vitro;in vivo;Infection;innovation;insight;Interferons;Interruption;Investigation;Location;lymph nodes;Macaca mulatta;Macrophage;mast cell;Methods;Modeling;Mucous Membrane;Myelogenous;Myeloid Cells;nonhuman primate;nonhuman tissue;Outcome;Patients;PET/CT scan;Phase;Plasma;Play;Population;Population Dynamics;Positron-Emission Tomography;Predisposition;pressure;Process;Proteins;Residual state;Resolution;Resources;response;Role;Sampling;Scanning;Shapes;Signal Transduction;Site;SIV;Skin;Source;Stains;Stimulus;T-Lymphocyte;Techniques;Technology;Testing;text searching;therapy design;Time;Tissue Banks;Tissues;Tryptase;Viral;viral detection;viral rebound;Viremia;Virus;Virus Replication

PROJECT_TITLE: Unraveling the Mechanisms of HIV Persistence and Rebound


NIH_SPENDING_CATS: Aging;Atherosclerosis;Behavioral and Social Science;Cardiovascular;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Heart Disease;Heart Disease - Coronary Heart Disease;Kidney Disease;Palliative Care;Women's Health Research

ORG_CITY: CINCINNATI

ORG_NAME: UNIVERSITY OF CINCINNATI

PHR: PROJECT NARRATIVE The work from the proposal will identify disparities across sex in cardiovascular disease, build a novel sex- specific model for optimal revascularization strategy, and understand patient experiences on coronary artery disease treatment, among dialysis patients. With cardiovascular disease being the leading cause of death in dialysis patients and inadequate recruitment of women with end-stage kidney disease in the clinical trials, understanding the impact of sex on cardiovascular disease-related health status in dialysis patients becomes highly significant. The net effect will hopefully be an improvement in the quality of life, reduction in sex disparities in cardiovascular disease, and an overall increase in survival, among dialysis patients.

PI_NAMEs: SHAH, SILVI  (contact)

PROGRAM_OFFICER_NAME: SMITH, SHARON M

PROJECT_TERMS: Accounting;acute coronary syndrome;Address;Attitude;Biometry;Cardiovascular Diseases;cardiovascular health;Cardiovascular system;career;career development;Caring;Cause of Death;Cessation of life;Clinical;clinical epidemiology;Clinical Research;Clinical Trials;cohort;Cohort Studies;Congestive Heart Failure;Coronary;Coronary Arteriosclerosis;Coronary Artery Bypass;Coronary Vessels;Counseling;Data;Decision Analysis;Decision Making;Decision Modeling;Dedications;design;Development Plans;Dialysis patients;Dialysis procedure;Discipline;Disease Outcome;Disparity;End stage renal failure;Equilibrium;Event;Exclusion;experience;Focus Groups;Fostering;Frequencies;Funding;Future;General Population;Goals;Health Benefit;health disparity;health equity;Health Planning;Health Status;improved;improved outcome;Incidence;Information Systems;Infrastructure;innovation;Intervention;Ischemia;K-Series Research Career Programs;Kidney;Kidney Diseases;Knowledge;Link;Medicare claim;men;Mentors;Mentorship;Methodology;Methods;Modeling;mortality;mortality risk;Myocardial Infarction;novel;Observational epidemiology;Outcome;patient oriented;Patients;percutaneous coronary intervention;Performance;Policies;Population;Prevalence;Process;prospective;Qualitative Methods;Quality of life;recruit;Reduce health disparities;Reporting;Research;Research Methodology;Research Personnel;revascularization;Risk;sex;Sex Differences;sex disparity;skills;Stroke;Structure;support tools;surgical risk;tool;Training;Translational Research;treatment strategy;United States;Universities;Unstable angina;Woman;women versus men;Women's Health;Women's mortality;Work

PROJECT_TITLE: Sex Disparities in Cardiovascular Disease and Optimal Coronary Revascularization in Dialysis Patients

STUDY_SECTION: MPOR

STUDY_SECTION_NAME: NHLBI Mentored Patient-Oriented Research Study Section[MPOR(JA)]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Pediatric;Prevention;Serious Mental Illness;Women's Health Research

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

PHR: PROJECT NARRATIVE Offspring of depressed mothers are three-to-six times more likely to meet criteria for major depressive disorder (MDD) by early adulthood than are individuals in the general population; however, not all high risk (HR) youth develop MDD, suggesting factors that may exacerbate risk profiles. The current project combines measures of brain function, psychophysiology, and behavior across three time points during a developmental window of heightened MDD risk to study how deficits in negative emotion processing are implicated in both the development and course of depression among HR offspring. By exploring how biological sex and puberty interact with negative emotion processing styles to predict depression profiles in HR youth, findings from the current study have significant potential to inform novel prevention and intervention targets for specific populations of at-risk youth.

PI_NAMEs: BURKHOUSE, KATIE L (contact)

PROGRAM_OFFICER_NAME: KING, ERIN MICHELE

PROJECT_TERMS: Address;Affect;affective neuroscience;Age;Amygdaloid structure;Area;Behavior;Behavioral;biological sex;biomarker discovery;Brain;brain based;Child;child depression;clinical application;cognitive control;cost effective;Data;Depressed mood;depression prevention;depressive symptoms;Development;Diagnosis;disorder prevention;disorder risk;Early Diagnosis;Early identification;Economic Burden;emerging adult;Emotional;emotional stimulus;Emotions;Event-Related Potentials;Exhibits;Female;Functional disorder;Functional Magnetic Resonance Imaging;Future;General Population;Goals;high risk;High Risk Woman;Image;imaging study;improved;indexing;Individual;innovation;Insula of Reil;Intervention;Intervention Studies;Interview;Knowledge;Link;Longitudinal Studies;Major Depressive Disorder;maternal depression;Measures;Mental Depression;Mentored Patient-Oriented Research Career Development Award;Modeling;Mothers;multimodality;National Institute of Mental Health;Negative Valence;network dysfunction;novel;offspring;Onset of illness;Pathway interactions;Patient Self-Report;Performance;Physiological;Populations at Risk;Poverty;Prevention;Principal Investigator;Property;Psychophysiology;Puberty;Recording of previous events;recruit;Recurrence;Regulation;Research Personnel;response;Rest;Risk;Risk Marker;Role;Sample Size;Sampling;Series;sex;Sex Differences;social;Specificity;statistics;Stimulus;Strategic Planning;support network;Surveys;Symptoms;System;Telephone;Testing;theories;Time;Work;Youth

PROJECT_TITLE: Neurodevelopmental Mechanisms Underlying the Onset of Depression among At-Risk Youth: The Role of Dysregulation in the Negative Valence System

STUDY_SECTION: CPDD

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


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Clinical Research;Drug Abuse (NIDA only);HIV/AIDS;Health Services;Infectious Diseases;Machine Learning and Artificial Intelligence;Opioids;Patient Safety;Prevention;Substance Misuse

ORG_CITY: Newark

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PROJECT NARRATIVE People living with HIV (PLWH) commonly report chronic pain and are more likely to receive prescription opioids, placing them at elevated risk for adverse events. However, data are limited for a growing population of older PLWH 65+ years with multiple comorbidities, increasing polypharmacy, and increased risk for untoward drug- drug interactions. Using large-scale administrative claims data and machine learning approaches, this project will analyze prescription opioid use, risks, and outcomes in older PLWH, generating valuable new information and tools to support clinical decisions and more precisely target prevention and treatment interventions to improve health for older PLWH who use opioids.

PI_NAMEs: SHIAU, STEPHANIE  (contact)

PROGRAM_OFFICER_NAME: FITZ-RANDOLPH, MARCY ESTHER

PROJECT_TERMS: Accident and Emergency department;Address;Adverse event;adverse event risk;adverse outcome;Affect;Age;Age Years;Aging;Anti-Retroviral Agents;antiretroviral therapy;Area;Area Under Curve;beneficiary;Benzodiazepines;career development;chronic pain;clinical decision support;clinical practice;co-infection;comorbidity;Data;Data Set;Databases;Dementia;Development Plans;Disease;Dose;Drug Interactions;Drug Prescriptions;Drug usage;Drug Utilization;Environment;Epidemic;Epidemiology;experience;falls;Foundations;Fracture;General Population;Goals;Health;health care service utilization;high risk;HIV;HIV Infections;HIV risk;Hospitalization;human old age (65+);improved;infection risk;Injecting drug user;Inpatients;insight;Interdisciplinary Study;Intervention;life span;Machine Learning;machine learning method;Medicare;Medicare claim;Mental Health;Mentored Research Scientist Development Award;Mentors;Methods;Morbidity - disease rate;mortality;multidisciplinary;non-nucleoside reverse transcriptase inhibitors;novel;older adult;Older Population;Opioid;opioid use;Outcome;Outpatients;Pattern;Persons;Pharmaceutical Preparations;Pharmacoepidemiology;Polypharmacy;Population;Positioning Attribute;prescription opioid;Prevention;Prevention program;profiles in patients;programs;Protease Inhibitor;Quality of life;Reporting;Research;research and development;Research Infrastructure;Research Personnel;Research Priority;Research Support;Risk;Sampling;sedative;substance use;symposium;Techniques;tool;Training;treatment program;United States National Institutes of Health;Universities;Visit

PROJECT_TITLE: Leveraging large-scale administrative claims data to evaluate prescription opioid use, risks, and outcomes in older adults living with HIV

STUDY_SECTION: PPAH

STUDY_SECTION_NAME: Population and Public Health Approaches to HIV/AIDS Study Section[PPAH]


ADMINISTERING_IC: LM

FUNDING_MECHANISM: OTHERS

IC_NAME: NATIONAL LIBRARY OF MEDICINE

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Project Narrative The Spencer S. Eccles Health Sciences Library at the University of Utah, will implement a 5-year grant to bring quality health, public health, and biomedical information resources within easy reach of the public and all health and public health professionals, with emphasis on medically underserved communities. We will address this charge by improving access to quality health information in Region 4 (Arizona, Colorado, Idaho, Montana, New Mexico, North Dakota, South Dakota, Utah, and Wyoming) while collaborating with other Network of the National Library of Medicine Regional Medical Libraries, Offices, and Centers nationwide.

PI_NAMEs: SOEHNER, CATHERINE B (contact)

PROGRAM_OFFICER_NAME: YOON, SUNG SUG

PROJECT_TERMS: Area;Arizona;Awareness;Canada;Charge;Cities;Clinic;Collaborations;college;Colorado;Communication;Communities;community organizations;Data;demographics;design;Diverse Workforce;Education;Educational process of instructing;effectiveness evaluation;Evaluation;experience;Funding;Future;Grant;Health;health equity;health literacy;Health Personnel;Health Professional;Health Science Library;Health Status;Hospitals;Idaho;Impact evaluation;Improve Access;improved;Indian reservation;Individual;Information Resources;innovation;Internet;Learning;Libraries;Medical Libraries;medically underserved;Medicine;member;Mexico;Mission;Montana;New Mexico;North Dakota;outreach;Positioning Attribute;programs;Public Health;Research;Research Personnel;Resources;rural area;rural health clinic;Rural Hospitals;Schools;Services;South Dakota;Specialist;success;Training;tribal college;Trust;Underrepresented Populations;underserved community;Underserved Population;United States National Library of Medicine;Universities;Utah;vision development;Voice;Work;Wyoming

PROJECT_TITLE: Region 4, Regional Medical Library and Network of the National Library of Medicine Training Office


PROJECT_TERMS: Communities;community engagement;Data;demographics;design;Disasters;effectiveness evaluation;Emergency Situation;Evaluation;Foundations;Funding Opportunities;Health;Health Personnel;Health Professional;Health Science Library;Health Status;Impact evaluation;improved;Information Resources;innovation;Leadership;Medical Libraries;Mission;operation;programs;Public Health;Research Personnel;Training;training opportunity;United States National Library of Medicine;Universities;Utah;Work

PROJECT_TITLE: Region 4, Regional Medical Library Administrative Core


PROJECT_TERMS: Area;Communication;Communities;community engagement;community organizations;Data;data science resource;demographics;design;Development;Education;Evaluation;Funding;Funding Opportunities;Future;Health;health equity;Health Personnel;Health Professional;Health Science Library;Health Sciences;Health Status;Improve Access;improved;Information Resources;Information Sciences;innovation;Libraries;Medical Libraries;member;Mission;outreach;programs;Public Health;Research Personnel;Services;Training;training opportunity;Trust;United States National Library of Medicine;Universities;Utah;Voice;Work

PROJECT_TITLE: Region 4, Regional Medical Library Program Core


PI_NAMEs: VAN DER VOLGEN, JESSICA  (contact)

PROJECT_TERMS: Area;Award;Collaborations;Communities;Contracts;Country;course development;Data;design;Development;Education;Educational Curriculum;Educational Materials;Educational process of instructing;effectiveness evaluation;Ensure;Evaluation;evidence base;experience;foot;Foundations;Funding;Geography;Goals;Grant;Growth;Guidelines;Health;health equity;health literacy;Health Personnel;Health Professional;Health Science Library;high standard;Human Resources;Improve Access;improved;Information Resources;Infrastructure;innovation;Instruction;instructor;Knowledge;Leadership;Learning;Librarians;Libraries;Marketing;Medical Libraries;member;Methodology;Participant;Persons;Positioning Attribute;programs;Public Health;Qualifying;Quality Control;Research;Research Personnel;Resources;Services;skills;Solid;Technology;Training;Training Programs;United States National Library of Medicine;Universities;Utah;Vision;Work

PROJECT_TITLE: Network of the National Library of Medicine Training Office


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Genetics;Neurosciences;Substance Misuse

ORG_CITY: MERCED

ORG_NAME: UNIVERSITY OF CALIFORNIA, MERCED

PHR: PROJECT NARRATIVE Engrams hold the functional brain changes that define the addictive properties of drugs of abuse, including alcohol. Molecules that control plasticity in plasticity-relevant neurons and that are conserved in humans are candidates for therapies targeted at reversing the effects of alcohol.

PI_NAMEs: WOLF, FREDERICK W (contact)

PROGRAM_OFFICER_NAME: POWELL, ELIZABETH

PROJECT_TERMS: alcohol effect;alcohol exposure;alcohol response;alcohol use disorder;Alcohols;Anatomy;Automobile Driving;Behavior;Behavioral;Behavioral Paradigm;behavioral plasticity;Brain;Brain region;cell type;Chronic;Code;Complex;Detection;Development;diagnostic development;DNA cassette;Drosophila genus;drug of abuse;Early Gene Transcriptions;Enhancers;Ethanol;experience;Foundations;Future;gene conservation;Gene Expression;Gene Expression Regulation;gene function;Genes;Genetic Crosses;genetic manipulation;Genetic Transcription;Goals;Human;Immediate-Early Genes;Intake;Label;Location;Mammals;Measures;Memory;Methods;Modeling;Molecular;Neuroanatomy;Neurons;Nuclear;Orthologous Gene;Outcome;Pattern;Pharmaceutical Preparations;Property;Reporter;response;Risk Factors;Role;Sampling;Signal Transduction;spatiotemporal;Speed;Stimulus;System;targeted treatment;Techniques;Testing;Therapeutic;tool;transcription factor;transcriptomics;Transgenes;Translations;Validation;Work

PROJECT_TITLE: Engram encoding for ethanol tolerance in Drosophila

STUDY_SECTION: AA

STUDY_SECTION_NAME: Neuroscience and Behavior Study Section[AA-4]


NIH_SPENDING_CATS: Genetics;HIV/AIDS;Infectious Diseases

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE HIV post-treatment controllers (PTCs) are individuals who can maintain virologic suppression after interruption of antiretroviral therapy and represent a natural model of sustained HIV remission. However, our understanding of the virologic determinants of HIV remission remains incomplete, which is in part due to the scarcity of PTCs identified through any one research center or clinical trial, and in part because of the limited scope of viral reservoir studies that have been performed to date. The main goal of this proposal is to perform an in-depth virologic analysis of PTCs and our overarching hypotheses are that HIV reservoir characteristics can provide mechanistic insights behind their ability to achieve HIV remission.

PI_NAMEs: LI, JONATHAN  (contact)

PROGRAM_OFFICER_NAME: REFSLAND, ERIC WILLIAM

PROJECT_TERMS: Aftercare;Anti-Retroviral Agents;antiretroviral therapy;ATAC-seq;Biological Assay;Biological Markers;Characteristics;Chromatin;Clinical Trials;cohort;Complex;design;Disease remission;Distal;DNA;Ecology;Environment;experience;Gene Silencing;Genetic Transcription;Genome;Goals;HIV;holistic approach;Individual;insight;integration site;International;Interruption;Laboratories;Length;Location;Lymph Node Tissue;Measures;Modeling;Molecular;novel;Peripheral;peripheral blood;Peripheral Blood Mononuclear Cell;Persons;Pharmaceutical Preparations;Poly A;Polyadenylation;Proviruses;Reporting;Research;Research Personnel;RNA;RNA Splicing;T memory cell;T-Lymphocyte Subsets;Therapeutic Intervention;Tissues;Transcription Initiation;Transcriptional Regulation;transcriptome sequencing;transcriptomic profiling;Viral;viral rebound;Viral reservoir;Withholding Treatment

PROJECT_TITLE: HIV Reservoir Ecology of Viral Remission

STUDY_SECTION: HIVD

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


NIH_SPENDING_CATS: Infectious Diseases;Lung

ORG_CITY: RIVERSIDE

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: The optimal host response to mucosal infection relies on the critical balance between pathogen killing (immunity) and limiting immunopathology (tolerance) in the host. Host disease tolerance is especially important in infections with macroparasites such as helminths that cause significant tissue damage, therefore investigating these host disease tolerance mechanisms may be applicable to the treatment of tissue injury and inflammation of significant public health impact. This proposal will investigate how the secreted protein RELMa contributes to host disease tolerance to helminths through regulation of alternatively activated macrophage subsets, macrophage-helminth interactions and macrophage-lung stromal cell interactions.

PI_NAMEs: NAIR, MEERA GOH (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: 3-Dimensional;Acute;Address;Adoptive Cell Transfers;Adoptive Transfer;Air;airway epithelium;arginase;Back;Biological Assay;Biology;Blocking Antibodies;Bone Marrow;CD4 Positive T Lymphocytes;Cell Communication;Cell Separation;Cells;Chimera organism;Chimeric Proteins;Coculture Techniques;Communicable Diseases;Complement;Cre lox recombination system;cytokine;Data;design;Disease;eosinophil;Epithelial Cells;Equilibrium;experimental study;Gene Expression;genetic signature;healing;helminth infection;Helminths;Hematopoietic;Heterogeneity;Hookworm Infections;Hookworms;Human;Immune;Immune response;Immunity;immunopathology;Impairment;Infection;Inflammation;Inflammatory;inhibitor;Injury;insight;Integrins;Liquid substance;Lung;lung repair;Macrophage;Measures;Mediating;Mesenchymal Stem Cells;migration;Migration Assay;monocyte;mouse model;Mucous Membrane;Mus;new therapeutic target;Nippostrongylus;novel;Parasites;pathogen;pathogenic microbe;Pathogenicity;Pathologic;Pathology;Pathway interactions;Persons;Protein Secretion;Proteins;Public Health;public health relevance;Pulmonary Inflammation;Reagent;Recovery;Regulation;Reporter;resistin;Resolution;response;Rodent;scaffold;Signal Pathway;Signal Transduction;Signaling Molecule;Soil;Sorting;Stromal Cells;Structure of parenchyma of lung;Technology;Therapeutic;tissue injury;tissue repair;Tissues;transmission process;Visualization;wound healing

PROJECT_TITLE: RELMalpha-expressing macrophages mediate host disease tolerance in mucosal infection

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: LINCOLN

ORG_NAME: UNIVERSITY OF NEBRASKA LINCOLN

ORG_STATE: NE

PHR: PROJECT NARRATIVE This Administrative Supplement requests funding to support the research training and career development of the predoctoral candidate. The project's research outcomes will be instrumental in understanding the role and mechanism of Fe-S proteins in disease progression and designing new therapeutic strategies against diverse pathogens. The training provided to the candidate will have a positive impact on promoting students from underrepresented groups to pursue careers in biomedical sciences.

PI_NAMEs: ZHANG, LIMEI  (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Address;Administrative Supplement;Anabolism;Award;Bacterial Infections;biological adaptation to stress;career;career development;Cell Physiology;Cell Survival;cofactor;Collaborations;Communication;Communities;Crystallography;design;Diabetes Mellitus;Disease;Disease Progression;diversity and inclusion;Doctor of Philosophy;Environment;experience;Fellowship;Funding;Genetic Transcription;Genus Mycobacterium;Goals;Health;Homeostasis;Human;Iron;Iron-Sulfur Proteins;Leadership;Ligands;Link;Malignant Neoplasms;Mediating;Molecular;novel therapeutic intervention;Outcomes Research;Oxidation-Reduction;parent project;Parents;pathogen;Physiological;Play;Postdoctoral Fellow;pre-doctoral;Protein Biochemistry;Protein Family;Proteins;Regulation;repaired;Research;Research Personnel;Research Project Grants;Research Support;Research Training;Role;Science;skill acquisition;skills;Stress;Structural Biochemistry;structural biology;Structure;Sulfhydryl Compounds;Sulfur;System;Training;Training Activity;Transcriptional Regulation;undergraduate research;Underrepresented Populations;Underrepresented Students

PROJECT_TITLE: Structures and Mechanisms of Iron-Sulfur Proteins in Redox Control and Stress Response

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1(55)-R]


ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative During cell division, the cell must accurately segregate its chromosomes to its two daughter cells and any errors in this process can lead to birth defects and diseases such as cancer. The kinetochore is essential to ensuring that force is transmitted from spindle microtubules to move chromosomes, and here we ask how the kinetochore can do so under high forces without structural failure. This work will provide insight into the structural engineering principles underlying the kinetochore’s robust structure and function, and in the long run inform on possible failures linked to disease.

PI_NAMEs: DUMONT, SOPHIE  (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Aneuploidy;Architecture;Binding;Binding Proteins;Biochemical;Biophysics;Cell Cycle Progression;Cell Cycle Regulation;Cell division;Cells;Centromere;Chemicals;Chromosome Segregation;Chromosomes;Communication;Congenital Abnormality;daughter cell;Disease;Engineering;Ensure;Failure;Genetic;Goals;graduate student;Histones;imaging approach;In Vitro;in vivo;insight;Kinetochores;Lateral;Lead;Link;Macromolecular Complexes;Maintenance;Malignant Neoplasms;Measures;Mechanics;Mentorship;Microtubules;Molecular;molecular modeling;Movement;physical model;Process;Proteins;Proxy;Psychological reinforcement;Quantitative Microscopy;Research;Resolution;Role;Science;segregation;Shapes;Signal Transduction;Stretching;Structure;superresolution imaging;Testing;Time;Training;transmission process;Work

PROJECT_TITLE: Defining the physical and molecular basis of kinetochore structural maintenance under force


ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Project Narrative In this supplement application we will train a postbac student, Nathan Ho, on single molecule and biochemical approaches investigating how mammalian histone methylases (‘writers”) engage with the chromatin substrate. In the formation of repressive chromatin structures, these “writers” deposit repressive information and we aim to understand how their own reaction product, their oligomeric state, or the density of chromatin, influence “writer” association with chromatin. In the time Nathan is in the lab, we will address all the training goals he has articulated via his myIDP with structured and continuous mentoring, in-lab training, and opportunities to refine communication of science and incorporating relevant literature into his research.

PI_NAMEs: AL-SADY, BASSEM  (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Area;Articulation;Award;Binding;Biochemical;career development;Cells;Chemicals;Chromatin;Chromatin Structure;Communication;Contracts;Critical Thinking;Data Analyses;density;Deposition;design;Development;Development Plans;Distal;DNA Sequence;enzyme activity;Enzymes;Epigenetic Process;experience;Experimental Designs;falls;flexibility;Funding;Genes;Genome;genome integrity;Goals;graduate school;Grant;Heterochromatin;histone methyltransferase;Histones;Individual;Inosine Diphosphate;insight;Laboratories;laboratory development;laboratory experience;Literature;Mediating;Mentors;Methods;Microscopy;Mission;Molecular Machines;National Institute of General Medical Sciences;Nuclear Structure;parent grant;Pattern;Postbaccalaureate;Preparation;preservation;Process;Productivity;programs;Reaction;reconstitution;Research;Research Personnel;Science;Scientist;Shapes;single molecule;Site;skills;Specialist;Structure;Students;System;Time;Training;Ultraviolet Rays;Visualization;Work

PROJECT_TITLE: Tracking how molecular machines propagate epigenetic information in time and space


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

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

PHR: The focus of our work is to determine how mutations carbohydrate aggregates impact multiple neurological diseases and to translate this knowledge into therapies. Our proposal is built on our past discoveries and uses complementary approaches to advance our understanding of the intertwined events of cell metabolism, neurodegeneration, and neurological disease. Completion of this work will yield a better comprehension of these complex events and will allow us to translate our insights into disease mechanisms, diagnoses, and treatments.

PI_NAMEs: GENTRY, MATTHEW S. (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Adolescence;Affect;Alzheimer's Disease;Ataxia;autosome;Behavior;Biochemical;Biology;biomarker development;Brain;brain metabolism;Carbohydrates;Cell Physiology;Cellular Metabolic Process;Cessation of life;Cognition;Complex;Comprehension;Consumption;Data;Development;Diagnosis;Disease;Disease Progression;driving force;Event;Excision;flexibility;Freedom;Funding;Glucose;glucose metabolism;Glycogen;glycogen metabolism;Glycogen Storage Disease;Homeostasis;human disease;insight;Intractable Epilepsy;Knowledge;Lafora Disease;Memory;Metabolic;Metabolism;Modality;Modeling;Molecular;mouse model;Mutation;National Institute of Neurological Disorders and Stroke;Nerve Degeneration;Nervous System Disorder;novel therapeutics;Patients;Play;polyglucosan;pre-clinical;Research;Role;Seminal;sex;Signal Transduction;Symptoms;Therapeutic;therapy development;Tissues;tool;Translating;Vegetative States;Work

PROJECT_TITLE: Brain Glycogen-Metabolism,Mechanisms, and Therapeutic Potential


ADMINISTERING_IC: FD

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_CITY: TUCSON

ORG_NAME: CRITICAL PATH INSTITUTE

ORG_STATE: AZ

PHR: NARRATIVE Although multiple sclerosis (MS) has a significant impact on physical functioning and is a major cause of non- traumatic disability in younger adults in the U.S., traditional endpoint measures in clinical trials focus on mobility and overlook impacts on upper extremity and other aspects of physical function that are important to people with MS; therefore, it is important that MS clinical trials measure the full range of physical function and the impact of new MS treatments on physical function. The overall objective of this project is to prepare and submit a Full Qualification Package to support the qualification of the PROMISnq Short Form v2.0 - Physical Function - Multiple Sclerosis 15a for use as a patient-reported measure of physical function among individuals diagnosed with all forms of MS. The impact of this work will be the advancement of a publicly available, psychometrically sound measure of physical function that can be used in MS treatment trials to better assess and understand the impact of new treatments on physical function in individuals with MS.

PI_NAMEs: EREMENCO, SONYA  (contact);TEGEL, KAREN KAISER

PROGRAM_OFFICER_NAME: TOMITA, YORK

PROJECT_TITLE: Development of a Full Qualification Package (FQP) for the PROMISnq Short Form v2.0 - Physical Function - Multiple Sclerosis 15a (DDT COA #000123)

STUDY_SECTION_NAME: Special Emphasis Panel[ZFD1 CDER-S (12)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: DALLAS

ORG_DEPT: NEUROSURGERY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: Project Narrative We propose to study gene expression changes elicited by brain stimulation using tissue obtained from neurosurgical patients. First, we will compare gene expression profiles between stimulation and non-stimulated tissue from the lateral temporal cortex in vivo. Second, using neural tissue cultures of human cortex, we will examine gene expression changes elicited by ex vivo stimulation over six days, and connect stimulation-related changes in neural connectivity with gene expression data.

PI_NAMEs: KONOPKA, GENEVIEVE ;LEGA, BRADLEY C (contact)

PROGRAM_OFFICER_NAME: HWANG, GRACE MEI-HUA

PROJECT_TERMS: Address;Administrative Supplement;ATAC-seq;Brain;Brain Diseases;BRAIN initiative;Cell Nucleus;chromatin remodeling;Data;Data Correlations;data integration;Data Set;Development;Disease;expectation;experience;experimental study;Gene Expression;Gene Expression Profile;Gene Expression Profiling;Genes;genomic data;Genomics;Human;human data;human subject;in vivo;Individual;Knowledge;Lateral;Link;Measures;Memory;Methods;Multiomic Data;neural;neurophysiology;neurosurgery;parent project;Pathology;Patients;Physiology;programs;Publishing;Research;Series;single nucleus RNA-sequencing;Slice;Specimen;success;Temporal Lobe;Testing;tissue culture;Tissues;transcription factor

PROJECT_TITLE: Deciphering the genomic mechanisms underlying the physiology of human brain stimulation


ADMINISTERING_IC: IP

IC_NAME: NATIONAL CENTER FOR IMMUNIZATION AND RESPIRATORY DISEASES

ORG_CITY: PANAMA

ORG_COUNTRY: PANAMA

ORG_FIPS: PM

ORG_NAME: GORGAS MEMORIAL INSTITUTE OF HEALTH ST

PHR: Relevance to Public Health The proposed project strengthens surveillance of respiratory illness and influenza by building-on existing infrastructure, Regional partnerships and networks, and research projects. The public health significance of this project is to understand the impact of influenza and other respiratory virus on the psychomotor, cognitive, and behavioral development of small children in a large cohort. Outbreak investigation will be deployed if necessary. The in-depth understanding of respiratory illness and influenza in pediatrics population offer tremendous public health implications with repercussions at international levels. The proposed project will help generate surveillance and research protocols and public policies. This information will be most useful for future research and to determine the impact of respiratory illness during pregnancy on the development of the offspring. We anticipate that frequent and severe cases of influenza and other respiratory viral infections, during pregnancy and early life affect neurocognitive, psychomotor, and behavioral development in infants, this will assist clinicians and researchers in the following manner:  a. Prevention of influenza would be more proactive.  b. The innovative study will provide results that can be used and replicated globally.  c. Influenza vaccination during pregnancy will be promoted more actively. Another important contribution of the study is the analysis of demographic, social, and cultural factors that impact the onset of respiratory illnesses during pregnancy. As well as the use of the Bayley's III Test to evaluate the impact of cognitive, psychomotor, and language development. And, finally the innovative inclusion of behavioral analysis in the participants' follow-up will contribute immensely to universal knowledge and applied to public health policies and interventions. The study will provide enormous contributions to public health. The results will generate the tools and necessary information to promote influenza vaccination among pregnant women. This is a segment of the population, where vaccination was been low in many countries. If the results of the study prove positive to prevent influenza and furthermore the impact in their offspring development, this will generate compelling information to promote and educate the population at large and health care providers on the importance of vaccination against influenza and prevention of respiratory illness during pregnancy.

PI_NAMEs: GONZALEZ, ROSALBA DEL CARMEN (contact)

PROJECT_TITLE: RFA-IP-20-001 Psychomotor and cognitive development problems in a cohort of children after respiratory infection during pregnancy and/or early childhood


ADMINISTERING_IC: OH

IC_NAME: NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Repetitive manual lifting and lower back pain injuries impose a significant socioeconomic burden and substantial personal toll on health, prosperity and wellbeing. This proposal investigates if computer vision can more effectively evaluate worker exposure and assess the associated risk for injuries.

PI_NAMEs: KAPELLUSCH, JAY M;MERRYWEATHER, ANDREW STEVEN;RADWIN, ROBERT G (contact)

PROJECT_TITLE: A Computer Vision Lifting Monitor

STUDY_SECTION: SOH

STUDY_SECTION_NAME: Safety and Occupational Health Study Section[SOH]


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

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE The overall goal of this proposal is to identify new gene candidates that might cause familial glioma and to conduct functional validation using mouse models. We will use CRISPR gene editing technology to functionalize POT1 and other newly discovered mutations. This study will contribute to our understanding of gliomagenesis, and provide information on potential pathways or molecular events that lead to familial glioma.

PI_NAMEs: BAINBRIDGE, MATTHEW NEIL;BONDY, MELISSA L. (contact);DENEEN, BENJAMIN

PROGRAM_OFFICER_NAME: ROTUNNO, MELISSA

PROJECT_TERMS: Affect;Alleles;Animal Model;Biological;Biological Assay;Biology;Breast;Candidate Disease Gene;Case/Control Studies;Clustered Regularly Interspaced Short Palindromic Repeats;Code;cohort;Colorectal;Data;Data Sources;Development;Diagnosis;Disease;disorder risk;Early Diagnosis;Etiology;European;Event;Family;Family history of;Family member;Family Study;Future;Gender;gene discovery;gene editing technology;Gene Mutation;General Population;Genes;Genetic;Genetic Predisposition to Disease;Genetic study;genetic testing;Genome;genome sequencing;Germ Lines;Glioma;Gliomagenesis;Goals;Hereditary Malignant Neoplasm;high risk;In Vitro;in vivo;Incidence;Individual;Inherited;innovation;inquiry-based learning;insertion/deletion mutation;insight;interest;International;Knowledge;Length;Malignant Glioma;Malignant Neoplasms;Mendelian disorder;Molecular;mouse model;Mus;Mutation;NF1 gene;novel;Pathway interactions;Patients;Penetrance;Play;Population;Predisposition;proband;rare cancer;rare condition;rare variant;Recording of previous events;recruit;Reporting;Research;Resources;Risk;Role;Sample Size;Sampling;screening;stem cells;success;Susceptibility Gene;Syndrome;targeted treatment;telomere;Testing;TP53 gene;tumor;Tumor Subtype;Tumor Suppressor Proteins;tumorigenesis;Untranslated RNA;Validation;Variant;whole genome;Work

PROJECT_TITLE: Discovery, Biology and Risk of Inherited Variants in Glioma

STUDY_SECTION: CHSB

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology B Study Section[CHSB]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA CITY VA MEDICAL CENTER

ORG_STATE: OK

PHR: To date there are no effective therapeutic treatments for preventing age-related loss of muscle mass and function, or to enhance recovery of muscle following atrophy and injury. The studies outlined in this proposal will test the effectiveness of dietary supplementation with fish oil to prevent the loss of muscle mass and function with age and enhance the recovery of muscle mass and function following disuse-induced atrophy in a rat model that has high translatability. This research is relevant to the Veteran’s Administration since a significant number of patients in the system will require rehabilitation to recover skeletal muscle mass following atrophy induced by bed rest, immobilization, or neural trauma. The aging population represents a growing medical and monetary concern for the VA, since the elderly will suffer greater consequences of atrophy due to poor recovery. The development of effective therapies for the enhancement of muscle recovery following atrophy in the elderly is an unmet clinical need, and is the long-term goal of our research.

PI_NAMEs: BODINE, SUE C (contact)

PROJECT_TERMS: Acceleration;Acute;Address;Age;Age Months;age related;age-related muscle loss;Aging;aging population;aging process;Animal Model;animal old age;Atrophic;Attenuated;Bed rest;Clinical;cohort;Cues;Data;Denervation;Development;Diet;dietary;Dietary Supplementation;Disuse Atrophy;Dose;effective therapy;effectiveness testing;Elderly;Euthanasia;Event;falls;fatty acid supplementation;Female;Fish Oils;frailty;functional loss;Gene Expression;Genetic Transcription;Goals;Growth;Hindlimb Suspension;Human;Hybrids;Immobilization;impaired capacity;Impairment;improved;Individual;Injury;insight;Length of Stay;Life Style;Limb structure;Long term disability;male;mechanical load;Medical;middle age;Mobility decline;Modeling;Molecular;Monitor;Motor;Muscle;Muscle Fibers;muscle form;Muscle function;muscle strength;Muscular Atrophy;Nerve;neural;Neuromuscular Junction;Norway;older adult;Older Population;Omega-3 Fatty Acids;Output;Pathway interactions;Patients;Persons;Pharmacologic Substance;prevent;programs;Rattus;Recovery;Recovery of Function;Rehabilitation therapy;Research;resistance exercise;Rodent;sarcopenia;Skeletal Muscle;skeletal muscle wasting;Supplementation;System;Testing;therapeutically effective;Time;translational applications;Trauma;Traumatic injury;United States Department of Veterans Affairs;Veterans;Weight-Bearing state

PROJECT_TITLE: Sarcopenia and recovery from Disuse-Induced Atrophy


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: PROJECT NARRATIVE The BRCA1-BARD1 protein complex acts to eliminate highly toxic DNA double-strand breaks, to ensure the faithful propagation of our genetic blueprint, and to suppress cancer development. However, there is little information regarding the intricate roles fulfilled by BRCA1-BARD1 in these processes, or how loss of specific BRCA1-BARD1 functions leads to tumorigenesis. Elucidating the DNA and RAD51 interaction interfaces of BRCA1-BARD1 and their function in DNA damage repair and DNA replication fork preservation will help illuminate the functional consequence of cancer mutations in BRCA1-BARD1 and lay the foundation for developing therapeutic strategies to target tumors deficient in DNA repair.

PI_NAMEs: JASPER, ANGELA MARY (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: BARD1 gene;Binding;Biochemical;Biochemistry;Biological;BRCA1 gene;Breast;Cancer Biology;career;Cause of Death;Cells;Cessation of life;Chromosomal Rearrangement;Clinical;clinically relevant;Complex;Defect;design;Development;Disease;DNA;DNA Binding;DNA Binding Domain;DNA Damage;DNA Double Strand Break;DNA lesion;DNA Repair;DNA Repair Gene;DNA Repair Pathway;DNA Replication Damage;DNA replication fork;Double Strand Break Repair;Ensure;Excision;Exposure to;Fanconi's Anemia;Fellowship;Filament;Foundations;Future;Generations;Genes;Genetic;Genome;Genome Stability;Genomic Instability;Hereditary Breast and Ovarian Cancer Syndrome;homologous recombination;Impairment;insertion/deletion mutation;Invaded;Knowledge;Label;Laboratories;Lead;Location;Maintenance;Malignant Neoplasms;Maps;Mediating;mutant;Mutation;Neoplastic Cell Transformation;Nonhomologous DNA End Joining;novel therapeutics;Nucleoproteins;Ovarian;p53-binding protein 1;Pathway interactions;Physicians;preservation;presynaptic;Process;protective pathway;protein complex;Proteins;Rad51 recombinase;reconstitution;repaired;Research Personnel;restoration;Role;Scientist;Single-Stranded DNA;Sister Chromatid;Site-Directed Mutagenesis;Stress;Syndrome;synergism;System;Tail;Tertiary Protein Structure;Testing;Therapeutic;therapeutic development;tool;Training;tumor;Tumor Suppressor Proteins;tumorigenesis;Work

PROJECT_TITLE: The Mechanistic Role of BRCA1-BARD1 DNA and RAD51 Binding in DNA Double-Strand Break Repair