NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: AUSTIN

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: Project Narrative The goals of this proposal are to shed light on the nature, sources, and behavioral consequences of the large neural variability of sensory cortical neurons, the contribution of internal state fluctuations to this variability, and to generate cortical circuit models that account for the observed neural variability. Our three laboratories have developed a computational and experimental strategy leveraging our ability to perform whole-cell intracellular recordings in awake, behaving animals performing well-controlled and demanding visual tasks. Novel datasets will be used to provide critical constraints on cortical circuit models that mediate sensation.

PI_NAMEs: PRIEBE, NICHOLAS J;SEIDEMANN, EYAL J (contact);TAILLEFUMIER, THIBAUD O.

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Accounting;Address;Affect;Anesthesia procedures;Animals;area striata;Attention;awake;Behavior;Behavior Control;Behavioral;behavioral response;Biophysics;Cells;Cerebral cortex;computational platform;Computer Models;Data Set;Detection;Esthesia;Event;expectation;experimental study;Facial Expression;Future;Goals;Grant;individual response;insight;Laboratories;Macaca;Measurement;Measures;Mediating;Membrane;Membrane Potentials;millimeter;Modeling;Monitor;Monkeys;Motivation;Nature;neural;neural circuit;neural model;Neurons;Noise;novel;originality;Output;Photic Stimulation;Physiological;Population;Primates;Property;Pupil;Recurrence;recurrent neural network;Research;response;Role;sample fixation;Sensory;sensory cortex;Shapes;Signal Transduction;Source;Stimulus;Synapses;Techniques;Testing;Time;V1 neuron;Variant;Vision;Visual;visual control;Visual Perception;visual stimulus;Whole-Cell Recordings

PROJECT_TITLE: Cortical mechanisms mediating visual function and behavior

STUDY_SECTION: NBVP

STUDY_SECTION_NAME: Neuroscience of Basic Visual Processes Study Section[NBVP]


ADMINISTERING_IC: HD

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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

NIH_SPENDING_CATS: Genetics;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: FAYETTEVILLE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: BIOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF ARKANSAS AT FAYETTEVILLE

ORG_STATE: AR

PHR: PROJECT NARRATIVE Mitochondria play a critical role in the life of the cell as they control metabolic rates, energy production and cell death. Many devastating diseases arise from insults to the mitochondrial genome. This project will explore how insults to the mitochondrial genome alter mitochondrial dynamics and impacts bioenergetic function; ultimately regulating cellular function, multiple organ failure and disease severity.

PI_NAMEs: IYER, SHILPA  (contact)

PROGRAM_OFFICER_NAME: SAMEDY BATES, LESLY

PROJECT_TERMS: Address;Affect;Age;Biochemistry;Bioenergetics;biological adaptation to stress;Biological Markers;Brain;Cardiac Myocytes;Categories;Cell Culture Techniques;Cell Death;Cell Differentiation process;Cell model;Cell Physiology;cell type;Cells;Child;Childhood;Chronic;Clinical;Communities;comparison control;Complex;current pandemic;Data;Defect;Diagnosis;Disease;DNA;DNA Sequence Alteration;Event;Exhibits;Experimental Designs;Fibroblasts;fighting;Frequencies;Functional disorder;Gastrointestinal tract structure;Generations;Genetic;Genomics;Health;Heart;Human;human induced pluripotent stem cells;Impairment;improved;in vivo Model;indexing;Injury;interest;Intervention;Kidney;Life;Link;Medical Genetics;Membrane Potentials;Metabolic;Metabolic Control;Metabolic Diseases;metabolic rate;Metabolic stress;Metabolism;metabolomics;Mission;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;mitochondrial dysfunction;mitochondrial genome;mitochondrial membrane;Morphology;mortality;mouse model;Multiple Organ Failure;Muscle;NADH;Neurons;next generation sequencing;novel;Nuclear;Organ;Organ failure;Outcome;Oxidation-Reduction;Oxidative Stress;Pathogenicity;Pathway interactions;Patients;personalized medicine;personalized strategies;Phenotype;Physiology;Play;podocyte;Polyamines;polycation;pre-clinical;Process;Production;Putrescine;Regulation;Research;Respiration;Respiratory Chain;response;Role;Severities;Severity of illness;Skin;skin disorder;stem cell biology;stem cells;Stress;stressor;Symptoms;Testing;Therapeutic;therapeutic candidate;Tissues;Toxic effect;United States National Institutes of Health;Variant;Virus Diseases

PROJECT_TITLE: Metabolic regulation of MODS in pediatric mitochondrial disorders

STUDY_SECTION: SAT

STUDY_SECTION_NAME: Surgery, Anesthesiology and Trauma Study Section[SAT]


ADMINISTERING_IC: GM

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cardiovascular;Neurosciences;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BOSTON

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: NORTHEASTERN UNIVERSITY

ORG_STATE: MA

PHR: NARRATIVE This proposal will produce innovative technologies to assemble human in vitro platforms of the cardiovascular system towards providing better platforms for toxicity assays for therapeutic compound testing. This work will illuminate the importance of 3D cell culture and the inclusion of the autonomic nervous system. The resultant platforms leverage previously established fabrication methods that have been validated to support innervation and real-time functional measures.

PI_NAMEs: KOPPES, RYAN ALAN (contact)

PROGRAM_OFFICER_NAME: SALVADOR MORALES, CAROLINA

PROJECT_TERMS: 3-Dimensional;Acceleration;Address;Adrenal Glands;Adrenal Medulla;Animal Model;Automobile Driving;Autonomic nervous system;Award;Biocompatible Materials;bioelectricity;bioelectronics;Biological Assay;Biomedical Research;Blood Vessels;Cardiac;Cardiac Myocytes;Cardiovascular Models;Cardiovascular system;Cell Communication;Cells;Chromaffin Cells;Clinical;Clinical Trials;design;Development;Endothelium;Engineering;Equilibrium;Equipment;fabrication;Goals;Healthcare;Human;improved;In Vitro;innovation;innovative technologies;instrument;instrumentation;Lasers;lithography;Measures;Methods;Microfabrication;Microfluidics;microphysiology system;Modeling;Myocardium;nerve supply;neural;Neurons;Organ;Oxygen;pharmacologic;Physiological;Plumbing;polydimethylsiloxane;response;Scientific Advances and Accomplishments;screening;sex;Smooth Muscle;Statistical Models;stem cell differentiation;Structure;System;Techniques;Testing;Therapeutic;three dimensional cell culture;Time;Tissues;tool;Toxic effect;Toxicity Tests;Work

PROJECT_TITLE: Engineering multifaceted 3D human organ platforms for toxicity testing

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


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Infectious Diseases

ORG_CITY: CARSON

ORG_DEPT: CHEMISTRY

ORG_NAME: CALIFORNIA STATE UNIV-DOMINGUEZ HILLS

ORG_STATE: CA

PHR: Project Narrative Glycosaminoglycans (GAGs) are expressed ubiquitously on mammalian cell surfaces and interact with a wide variety of biological molecules to modulate processes, including immune response, regulation of cell growth and blood-stream clotting. Disruption of GAG-binding has the potential to prevent infection by viruses, such as HIV-1, and to reduce inflammation caused by autoimmune disorders. This project will utilize recently developed synthetic GAG libraries and NMR-based structural models to develop a pipeline to identify key interactions between heparan sulfate and heparan sulfate binding proteins, which can be used as a basis for development of drugs to target and disrupt GAG-protein binding.

PI_NAMEs: PEDERSON, KARI JOANNE (contact)

PROGRAM_OFFICER_NAME: REVILLEZA, MARIA

PROJECT_TERMS: Autoimmune Diseases;Binding;Binding Proteins;Biological;Biological Process;Blood Circulation;Blood Coagulation Factor;California;Calorimetry;Carbohydrates;Catalysis;Categories;CCL2 gene;Cell Adhesion;Cell Adhesion Molecules;Cell Communication;Cell Culture Techniques;cell growth regulation;Cell surface;Cells;Characteristics;chemokine;Coagulation Process;Collaborations;Complex;Core Protein;CXCL10 gene;cytokine;Data;Disaccharides;Disease Progression;Docking;drug development;Drug Targeting;Early identification;experimental analysis;extracellular;Extracellular Matrix;Foundations;Funding;Future;Glycosaminoglycans;Goals;Growth Factor;Heparitin Sulfate;Hispanic-serving Institution;HIV-1;Human;IL8 gene;Immune response;Infection;Infection prevention;Inflammation;institutional capacity;Isotope Labeling;Libraries;Life Cycle Stages;Ligands;Mammalian Cell;Membrane Proteins;Methodology;Modeling;Molecular;Molecular Conformation;Nuclear Magnetic Resonance;nuclear transfer;Process;programs;protein complex;Proteins;Proteoglycan;RANTES;receptor;Research;Role;screening;Signal Transduction;Spectrum Analysis;Stromal Cell-Derived Factor 1;Structural Models;Structural Protein;Structure;sugar;Surface Plasmon Resonance;Testing;tissue repair;Titrations;Training;undergraduate student;Universities;viral entry inhibitor;virtual;Virus;Virus Diseases

PROJECT_TITLE: Identifying Key Structural Interactions in Heparan Sulfate-Protein Complexes


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: We will test whether the extracellular milieu of the brain is altered by glial scarring after brain injury. One component of this milieu, the extracellular concentration of chloride ions, is a critical component of the brain’s endogenous anticonvulsant system. Changes to this component are not effectively compensated by anticonvulsant treatment, but could be prevented by short-term treatment with stabilizers of the extracellular milieu immediately after injury.

PI_NAMEs: STALEY, KEVIN J. (contact)

PROGRAM_OFFICER_NAME: CHURN, SEVERN BORDEN

PROJECT_TERMS: Acute;animal facility;Animals;Anticonvulsants;Antiepileptogenic;Area;Automobile Driving;Behavior;Brain;Brain Injuries;brain remodeling;brain tissue;Chloride Ion;Chlorides;Chondroitinases;Chronic;Cicatrix;Compensation;cost;Data;Disinhibition;driving force;Electroencephalography;Elements;Epilepsy;Epileptogenesis;Etiology;experimental study;extracellular;Extracellular Matrix;Extracellular Space;Family suidae;fluorescence lifetime imaging;Functional disorder;Funding;gamma-Aminobutyric Acid;Gliosis;Goals;high throughput screening;Human;Image;imaging facilities;in vitro Model;in vivo;in vivo calcium imaging;injured;Injury;Intractable Epilepsy;Investigation;Kinetics;Matrix Metalloproteinase Inhibitor;Measures;Mediating;Medical;Membrane;Microscope;Microscopy;Miniature Swine;Modeling;multiphoton imaging;Neocortex;neocortical;Neurons;novel;pharmacologic;Phase;Photons;Post-Traumatic Epilepsy;preservation;prevent;programs;prophylactic;Proteoglycan;receptor;reconstruction;Research;Research Personnel;Research Support;Resected;Resolution;screening program;Seizures;Signal Transduction;Structure;Sulfate;System;Testing;Time;tool;Translational trial;Trauma;two-photon

PROJECT_TITLE: Changes in the Ionic Basis of GABAergic Inhibition that Contribute to Post-Traumatic Epilepsy


PROJECT_TERMS: Address;Administrative Coordination;Administrator;Animals;archive data;Authorship;Biomedical Engineering;Boston;Brain Injuries;Budgets;career;cohort;Communication;Communities;Consultations;cost;Data;Data Analyses;data archive;Data Collection;data exchange;data management;Data Storage and Retrieval;Discrimination;Documentation;Education;Enrollment;Epileptogenesis;experimental study;Feedback;Funding;Goals;Grant;harassment;Human Resources;Institutional Policy;Intellectual Property;International;lectures;Manuscripts;Mathematics;Measures;medical schools;meetings;Microscopy;Monitor;neocortical;Neurology;neuropathology;Neurosciences;Operating Rooms;Persons;Phase;Policies;Post-Traumatic Epilepsy;Preparation;Professional Organizations;programs;Progress Reports;Publications;Research;Research Personnel;Research Project Grants;Review Committee;Schedule;Scientific Misconduct;Scientist;Series;statistics;Structure;Testing;Time;tool development;United States National Institutes of Health;Universities;Vendor;virtual;Visit

PROJECT_TITLE: Administrative Core


PI_NAMEs: COSTINE-BARTELL, BETH A (contact)

PROJECT_TITLE: Large Animal Core (Core 1)


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Dementia;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Neurodegenerative;Neurosciences;Prevention;Social Determinants of Health

ORG_CITY: CHICAGO

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Impoverished social relationships have been linked to poor cognitive functioning and Alzheimer's and related dementias (ADRD) in older adults, but the relative contribution of loneliness and social isolation to cognitive decline and dementia across the adult life span are not well understood. This project investigates social asymmetry or the degree of overlap or discordance between subjective feelings of loneliness and objective social network size, its consequences for established indicators of cognitive morbidity and decline, and the extent to which these associations are amplified during the COVID-19 pandemic. We will utilize 11 existing longitudinal data sets to address these aims using coordinated integrative data analysis (IDA), thereby enhancing the rigor, reproducibility, and replicability of our results.

PI_NAMEs: GRAHAM, EILEEN KRANZ (contact)

PROGRAM_OFFICER_NAME: HOOKER, EMILY DIANE

PROJECT_TERMS: Acceleration;Address;Adult;Aging;Alzheimer's disease related dementia;Alzheimer's disease risk;cigarette smoking;Cognitive;Cognitive aging;cognitive function;cognitive testing;cohort;COVID-19;COVID-19 pandemic;Data;Data Analyses;Data Collection;data harmonization;Data Set;Dementia;dementia risk;effectiveness evaluation;Episodic memory;Evaluation;evidence base;experience;Feeling;follow-up;Goals;Growth;Health;Heterogeneity;human old age (65+);Impaired cognition;Individual Differences;insight;interest;Investigation;life span;Link;Loneliness;long term COVID-19 pandemic impacts;Longitudinal cohort study;longitudinal dataset;Longitudinal Studies;Measurement;Measures;Methodology;Methods;middle age;Modeling;Morbidity - disease rate;mortality;novel;novel strategies;Obesity;older adult;Outcome;Pattern;Perception;Personality;Persons;Population;post-COVID-19;Poverty;Predisposition;prevent;Process;processing speed;prospective;Protocols documentation;psychosocial;Reaction Time;Reproducibility;Research Personnel;response;Risk Factors;Role;Sampling;Short-Term Memory;social;social contact;social disparities;Social Distance;social factors;Social isolation;Social Network;social relationships;social vulnerability;Source;Testing;Time;Twin Multiple Birth;United States National Institutes of Health;Work

PROJECT_TITLE: Advancing the Study of Social Isolation, Loneliness, and Cognitive Functioning in Older Adults Through the Use of Integrative Data Analysis

STUDY_SECTION: SPIP

STUDY_SECTION_NAME: Social Psychology, Personality and Interpersonal Processes Study Section[SPIP]


NIH_SPENDING_CATS: Genetics;Neurodegenerative

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

ORG_STATE: PA

PHR: Project Narrative Liquid–liquid phase separation of proteins and nucleic acids drives the biogenesis of diverse membraneless organelles with important biological functions. Dysregulated phase separation of RNA-binding proteins leads to the formation of toxic fibrils, which is a pathological hallmark in multiple fatal neurodegenerative diseases. Elucidating molecular mechanisms of phase separation regulation and developing strategies to reverse aberrant phase transition and fibrillization will lay the foundation for advances in novel therapeutic strategies to combat these fatal diseases.

PI_NAMEs: GUO, LIN  (contact)

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Biogenesis;Biological;Biological Process;biophysical techniques;Cells;combat;Disease;driving force;Fluorescence;Foundations;Goals;Health;innovation;Knowledge;Link;Liquid substance;Membrane;Molecular;Nerve Degeneration;Neurodegenerative Disorders;novel therapeutic intervention;Nuclear Import;Nucleic Acids;Oligonucleotides;Organelles;Pathologic;Phase;Phase Transition;programs;protein aggregation;Proteins;proteotoxicity;receptor;Regulation;Research;RNA;RNA-Binding Proteins;single molecule;Specificity;Therapeutic;Work

PROJECT_TITLE: Elucidating the Mechanism in the Regulation of RNA-binding Protein Phase Separation

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


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Brain Disorders;Epilepsy;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

PI_NAMEs: LILLIS, KYLE PATRICK (contact)

PROJECT_TERMS: adeno-associated viral vector;Algorithms;Animals;Biophysics;Brain;Calcium;Calibration;Chlorides;Chronic;cost;cost effective;Custom;Data;Data Collection;data standards;Dedications;design;Development;Devices;digital;Dyes;Epileptogenesis;Experimental Designs;extracellular;Family suidae;flexibility;Fluorescence;fluorescence lifetime imaging;Fluorescence Microscopy;fluorophore;Funding;Image;image archival system;image registration;Imaging Device;imaging modality;in vivo;in vivo imaging;in vivo two-photon imaging;Injections;instrument;instrumentation;Ions;Measurement;Measures;Microscope;Microscopic;Microscopy;Modeling;Molecular;Morphologic artifacts;Motion;multi-photon;multimodal data;novel;Phase;Post-Traumatic Epilepsy;Procedures;programs;Research;Resolution;Resources;Rodent;serial imaging;Silicon;Speed;Technical Expertise;Technology;tool;tool development;Traumatic Brain Injury;Trephine hole;two-photon

PROJECT_TITLE: Multiphoton In Vivo Microscopy (Core 2)


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Neurosciences;Nutrition;Obesity

ORG_CITY: NEW YORK

ORG_DEPT: PHYSIOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: To understand the etiology of metabolic disorders and motivated behavior it is essential that we gain better insight into the neuronal mechanisms that regulate metabolism and behavior. We propose studies that will assess and define the role of lipid metabolism in the arcuate melanocortin neurons in the regulation of feeding behavior and energy metabolism. The proposed studies are a logical continuation of our ongoing studies and, if successful, their completion will unmask a novel mechanistic principle in central regulation of feeding and systemic metabolism.

PI_NAMEs: DIANO, SABRINA  (contact)

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: Acute;Affect;Anabolism;Appetite Stimulants;Behavior;Catabolic Process;Catabolism;Ceramides;Chimeric Proteins;Chronic;Data;Development;diet-induced obesity;Disinhibition;Down-Regulation;Eating;Elements;Endoplasmic Reticulum;Energy Metabolism;Enzymes;Etiology;Fasting;fatty acid metabolism;Fatty Acids;feeding;Feeding behaviors;Food deprivation (experimental);Generations;Genes;High Fat Diet;Hypothalamic structure;in vivo calcium imaging;insight;Link;lipid metabolism;Lipids;long chain fatty acid;Mediating;member;Messenger RNA;Metabolic;Metabolic Diseases;Metabolic Pathway;Metabolism;Mitochondria;motivated behavior;Neurons;novel;Obese Mice;oxidation;parabrachial nucleus;Pathway interactions;Phenotype;Physiological Processes;Play;Production;Protein Family;Proteins;Regulation;Role;RTN4 gene;Signal Transduction;Site;Sphingolipids;sphingosine 1-phosphate;Sphingosine-1-Phosphate Receptor;Structure of nucleus infundibularis hypothalami;Testing;Up-Regulation

PROJECT_TITLE: Hypothalamic lipid signaling in metabolism regulation

STUDY_SECTION: POMD

STUDY_SECTION_NAME: Pathophysiology of Obesity and Metabolic Disease Study Section[POMD]


NIH_SPENDING_CATS: Brain Disorders;Epilepsy;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

PROJECT_TERMS: Affect;Algorithms;Animal Model;Animals;anti-epileptic agents;base;Behavior;Bilateral;Biological Markers;biomarker identification;black hole;Blood - brain barrier anatomy;Brain;Categories;Cells;cellular imaging;Chronic;Complex;Contusions;Convulsions;Development;Electroencephalography;Epilepsy;Epileptogenesis;Extracellular Matrix;Family suidae;field study;Frequencies;Functional disorder;Goals;healing;Human;Imaging technology;Immune;Inflammation;Injury;injury and repair;innovation;insight;Investigation;Label;Lesion;Machine Learning;machine learning pipeline;Mediating;Methods;Modeling;Morbidity - disease rate;neocortical;neuroblast;Neuroglia;neurovascular unit;new therapeutic target;Noise;Pathogenesis;Peripheral;Phase;Plasma;porcine model;Post-Traumatic Epilepsy;prevent;Refractory;Rodent;Seizures;Serum;Signal Transduction;Site;specific biomarkers;Synapses;targeted treatment;TBI Patients;Technology;Testing;Therapeutic;therapy development;tool;Training;Traumatic Brain Injury;Traumatic Brain Injury recovery

PROJECT_TITLE: A Biofidelic Model of PTE (Project 1)


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Neurosciences;Sleep Research

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE The proposed studies will provide new insights into how sleep uniquely contributes to long-term memory formation. This work has the potential to lead to targeted interventions for cognitive dysfunction induced by sleep loss, and interventions for psychiatric disorders where both sleep and cognition are adversely affected, including schizophrenia, depression, autism, and dementia. PHS 398/2590 (Rev. 06/09) Page 1 Continuation Format Page

PI_NAMEs: ATON, SARA J (contact)

PROGRAM_OFFICER_NAME: DAVID, KAREN KATE

PROJECT_TERMS: Address;Affect;Affinity Chromatography;Anatomy;Animal Model;Architecture;autism spectrum disorder;Behavioral;Behavioral Paradigm;Biochemical;Biological Models;Brain;cell type;Cells;Cellular biology;Cognition;cognitive process;conditioned fear;Data;Dementia;experience;experimental study;fear memory;Genetic;Genetic Transcription;Hippocampus;Hour;human subject;Impaired cognition;Information Storage;insight;Interneurons;Intervention;Label;Learning;Link;long term memory;Measures;Mediating;Memory;memory consolidation;memory process;Mental Depression;Mental disorders;Messenger RNA;Morphology;Mus;neuronal circuitry;Neurons;non rapid eye movement;novel;optogenetics;Parvalbumins;Pattern;Pharmacogenetics;Phosphorylation;Population;Process;Proteins;Pyramidal Cells;rapid eye movement;Regulation;Reporting;Ribosomes;Role;Schizophrenia;Sleep;Sleep Deprivation;Sleep disturbances;Somatostatin;Structure;Synapses;Synaptic plasticity;Testing;tool;Translating;Translations;Work

PROJECT_TITLE: Linking interneuron-mediated circuit regulation with sleep-dependent plasticity and memory storage in the hippocampus


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Pediatric;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative. The goal of this project is to use human induced pluripotent stem cells, micropatterned culture, synthetic biomaterial scaffolds, and microfluidics, to recreate the dynamic microenvironmental cues that coax tissue self- assembly and maturation. We anticipate that this holistic approach will enhance our understanding of multi- germ layer communication in lineage specification, as well as the role of mechanical and chemical cues in directing stem cell fate. Collectively, these approaches will build a framework for elucidating the mechanisms of human development and improve stem cell models of morphogenesis and disease.

PI_NAMEs: SMITH, QUINTON  (contact)

PROGRAM_OFFICER_NAME: SALAZAR, DESIREE LYNN

PROJECT_TERMS: bioscaffold;Cells;Chemicals;Clinical;Communication;Cues;Developmental Biology;developmental disease;Disease;Embryo;Extracellular Matrix;gastrulation;Germ Layers;Goals;holistic approach;Human Development;human induced pluripotent stem cells;improved;induced pluripotent stem cell;Investigation;matrigel;mechanical signal;Mechanics;Metabolic Diseases;Microfluidics;Modeling;Morphogenesis;Organ;Organoids;paracrine;Patients;Pattern;Population;Process;regenerative approach;Regenerative Medicine;Role;self assembly;self organization;self-renewal;Specific qualifier value;stem cell fate;stem cell model;stem cell niche;Technology;Tissue Engineering;Tissues;tool;Variant

PROJECT_TITLE: Physicochemical control of multilineage emergence

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


NIH_SPENDING_CATS: Bioengineering;Brain Disorders;Epilepsy;Neurodegenerative;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

PROJECT_TITLE: Epileptogenic Changes in Local Network Structure Following Injury (Project 2)


ORG_DEPT: PHARMACOLOGY

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE  We anticipate that retinoic acid receptor (RAR) β agonists will be useful in diminishing the severity of nephropathy in several murine models of chronic kidney disease. Data from this study could lead to new molecular targets for the treatment of various kidney disorders.

PI_NAMEs: GUDAS, LORRAINE J (contact)

PROGRAM_OFFICER_NAME: NIHALANI, DEEPAK

PROJECT_TERMS: Acute;Adult;Advanced Development;Affect;Agonist;Agriculture;All-Trans-Retinol;American;Area;Binding;Biochemical;Bioinformatics;Biology;Body System;Cardiovascular system;cell type;Cells;Chronic Kidney Failure;Data;Development;Diabetes Mellitus;Diet;Disease;disease model;Drops;efficacy testing;experience;Food Interactions;Funding;Gene Targeting;Genes;Genetic;genetic approach;Genetic Transcription;global health;Glomerulonephritis;Grant;Health;Human;Hypertension;Injury;Injury to Kidney;Kidney;kidney cell;Kidney Diseases;kidney fibrosis;Laboratories;Lead;Life;Manuscripts;Measurement;medical schools;Medicine;Methods;Micronutrients;Modeling;Molecular;molecular targeted therapies;Mothers;mouse model;Mus;nephrogenesis;Nephrolithiasis;Nephrons;New York City;novel;novel therapeutic intervention;novel therapeutics;nutrition;Obesity;Pathologic;Pathologist;Pathology;pharmacologic;Pharmacology;Play;Polycystic Kidney Diseases;Population;Positioning Attribute;Postdoctoral Fellow;Pregnancy;Prevalence;pup;RARB gene;Receptor Signaling;Renal Carcinoma;Renal function;Research;Research Personnel;Retinoic Acid Receptor;retinoic acid receptor alpha;retinoic acid receptor gamma;Retinoids;Role;Severities;Signal Transduction;Specialist;success;Syndrome;Testing;Therapeutic;tool;toxicant;Tretinoin;Vitamin A;Vitamin A Deficiency;Vitamins

PROJECT_TITLE: Gene Nutrient Interactions in Kidney Function

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DKUS-W(05)]


NIH_SPENDING_CATS: Bioengineering;Nanotechnology

ORG_CITY: NORMAN

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF OKLAHOMA

ORG_STATE: OK

PHR: Project Narrative The long-term goal of the proposed research program is to establish a novel framework for nanomedicine development, which will enable safer and more effective applications of nanotechnology in medicine. The proposed research will impact the therapeutic uses of nanomedicine across multiple areas of medicine in line with the mission of the National Institute of General Medical Sciences (NIGMS).

PI_NAMEs: WILHELM, STEFAN  (contact)

PROGRAM_OFFICER_NAME: KODURI, SAILAJA

PROJECT_TERMS: Area;bioimaging;biological systems;Cells;Development;Diagnostic;Effectiveness;Goals;in vivo;Kinetics;Medicine;Methods;Mission;Muscle Fibers;Myopathy;nanomedicine;nanoparticle;nanoparticle delivery;nanoscale;Nanotechnology;National Institute of General Medical Sciences;novel;Nucleic Acids;Organ;Pharmaceutical Preparations;programs;Research;Safety;Skeletal Muscle;small molecule;spatiotemporal;Therapeutic;Therapeutic Uses;Tissues;ultra high resolution

PROJECT_TITLE: A novel framework for nanomedicine development


ADMINISTERING_IC: CA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: OVERALL NARRATIVE The University of California and University of Texas Southwestern Diversity Patient-Derived Xenograft Development and Trial Center takes advantage of the collective strengths of six NCI-Comprehensive Cancer Centers to create minority patient cancer models and characterize targeted treatment responses to stomach and lung tumors. The impact of this collaborative is to understand the biological processes involved in cancer health disparities and to develop new effective treatments in patient-derived models to translate into clinical trials.

PI_NAMEs: CARVAJAL CARMONA, LUIS GUILLERMO (contact);RIESS, JONATHAN W

PROGRAM_OFFICER_NAME: WALLACE, TIFFANY A

PROJECT_TERMS: Advanced Malignant Neoplasm;Affect;Asian ancestry;Asian population;Asian Women;Bioinformatics;Biological;Biological Process;California;Cancer Biology;Cancer Center;cancer health disparity;Cancer Model;cancer subtypes;Cancer Therapy Evaluation Program;Catchment Area;Cause of Death;Cell Cycle;Cells;Clinical;Clinical Trials;Collection;Combination Drug Therapy;Combined Modality Therapy;comparative;Complex;Comprehensive Cancer Center;Data;Decision Making;Development;Digit structure;Disease;Disparity;Drug Combinations;effective therapy;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;ethnic diversity;ethnic minority;expectation;Family;FDA approved;FRAP1 gene;Frequencies;Genetic;Genome;Genomics;Goals;Grant;Health Disparities Research;health equity;Implant;Indigenous American;Infrastructure;Latina Population;Latino;Latino Population;Light;Los Angeles;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;malignant stomach neoplasm;member;Minority;Minority Groups;minority patient;Modeling;Molecular;Molecular Abnormality;molecular subtypes;mortality;mortality disparity;multidisciplinary;mutant;Mutate;Mutation;never smoker;new therapeutic target;novel;Oncogenes;Pathway interactions;patient derived xenograft model;Patient Isolation;Patients;people of color;Pharmaceutical Preparations;Phosphotransferases;PI3K/AKT;Pilot Projects;Population;Population Heterogeneity;Pre-Clinical Model;Precision Health;precision oncology;Precision therapeutics;Preclinical Drug Development;Preclinical Testing;Process;Productivity;Publishing;racial diversity;racial minority;Regimen;Research;Research Personnel;Research Project Grants;Resistance;resistance mechanism;Resources;response;response biomarker;Risk Factors;Role;San Francisco;Signal Transduction;Site;Smoking;Smoking History;Solid;Stomach;Stomach Neoplasms;targeted cancer therapy;targeted treatment;Testing;Texas;therapeutically effective;Time;Translating;treatment response;tumor;tumor diagnosis;tumorigenesis;Underrepresented Minority;Universities;women patients;women's diagnosis;Work

PROJECT_TITLE: University of California and UT Southwestern D-PDTC


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Lung Cancer;Racial and Ethnic Minority Health Research;Social Determinants of Health

PHR: ADMINISTRATIVE CORE NARRATIVE The University of California and University of Texas Southwestern Diversity Patient-Derived Xenograft Development and Trial Center leverages the collective strengths of six NCI- Comprehensive Cancer Centers to create minority patient cancer models and characterize targeted treatment responses to stomach and lung tumors. The responsibility of the Administrative Core is to create an efficient infrastructure to a) coordinate specimen collection and data exchange, b) manage scientific progress and fiscal responsibilities, c) sustain quality assurance and quality control procedures, d) maintain communication with key stakeholders, and e) centralize standard operating procedures. Through UCaTS activities, we expect to extend our large repository to facilitate the discover of new therapies that could impact vulnerable racial and ethnic minority cancer patients.

PI_NAMEs: CARVAJAL CARMONA, LUIS GUILLERMO (contact)

PROJECT_TERMS: Academic Medical Centers;Accountability;Administrator;Animals;anti-cancer research;Benchmarking;Bioinformatics;Budgets;California;Cancer Center;cancer health disparity;Cancer health equity;Cancer Model;Cancer Patient;cancer type;Catchment Area;Certification;Clinical Research;Collaborations;Collection;Communication;Complex;Comprehensive Cancer Center;Data Commons;data exchange;data sharing;Decision Making;Deposition;Development;Doctor of Philosophy;Documentation;Ensure;ethnic diversity;ethnic minority;ethnic minority population;expectation;experimental study;Family;Funding;Generations;Genetic;Genomics;Goals;Grant;Health;Health Disparities Research;human subject;Infrastructure;Institution;International;Interruption;Laboratories;Leadership;Los Angeles;Lung;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;malignant stomach neoplasm;Maps;meetings;member;Minority;minority patient;Modeling;Monitor;novel therapeutics;Pathway interactions;patient derived xenograft model;Patients;Pre-Clinical Model;pre-clinical research;precision oncology;Procedures;Productivity;programs;quality assurance;Quality Control;racial diversity;racial minority;racial minority population;Recommendation;repository;Research;Research Activity;Research Personnel;Research Project Grants;Resources;Role;sample collection;San Francisco;Site;Specimen;Stomach;Stomach Neoplasms;success;targeted treatment;Texas;timeline;treatment response;Universities;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Admin Core


NIH_SPENDING_CATS: Behavioral and Social Science;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Effects of Indoor Air Pollution;Health Services;Pediatric;Prevention;Primary Health Care;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: Project Narrative Racial and ethnic minority groups and those from low socioeconomic groups suffer disproportionately from the effects of tobacco marketing, have less access to evidence-based treatments for tobacco use, and report needing more support for cessation efforts. Pediatricians are uniquely positioned to help medically underserved families to address smoking and protect children from secondhand smoke (SHS) exposure, but a major barrier to protecting children from SHS exposure and extending tobacco use treatment to underserved adults who smoke is identifying an effective and scalable method to engage all household members who smoke, not just parents who present to the pediatric clinic with the child. To address this barrier, we will conduct a pragmatic trial through a large, urban pediatric network to evaluate a novel, proactive intervention that uses population health and clinical informatics implementation strategies to increase the reach, effectiveness, and health equity of tobacco use treatments for underserved families.

PI_NAMEs: JENSSEN, BRIAN P. (contact)

PROGRAM_OFFICER_NAME: LEE, YOUN OK

PROJECT_TERMS: Address;Adult;arm;Behavior Therapy;Caregivers;Characteristics;Child;Child health care;Childhood;Clinic;Clinic Visits;Clinical;Clinical Decision Support Systems;Clinical Informatics;Communities;compare effectiveness;Control Groups;Cotinine;Data;Decision Support Systems;Effectiveness;effectiveness/implementation design;Electronic Health Record;Enrollment;environmental tobacco smoke;environmental tobacco smoke exposure;ethnic minority population;evidence base;Evidence based treatment;Exposure to;Family;Funding;health care settings;health equity;Healthcare;Home;Household;implementation intervention;implementation strategy;Individual;informatics tool;innovation;Interdisciplinary Study;Intervention;Low income;Measures;Medicaid;medically underserved;member;Methods;nicotine replacement;novel;Office Visits;Outcome;Parents;Patients;pediatric patients;pediatrician;Persons;population based;population health;Positioning Attribute;Pragmatic clinical trial;pragmatic trial;Primary Care;Public Health Informatics;quitline;racial minority;Randomized, Controlled Trials;Recommendation;Reporting;Research Proposals;Respondent;Smoke;Smoking;socioeconomics;Source;Surgeon;Surveys;System;Testing;Tobacco;tobacco advertising;Tobacco use;treatment as usual;underserved community;Underserved Population;United States Dept. of Health and Human Services;United States Preventative Services Task Force;Visit;Work

PROJECT_TITLE: Refer 2 Quit: Proactive Promotion of Tobacco Use Treatment for Underserved Household Members Who Smoke through Pediatric Primary Care

STUDY_SECTION: IPTA

STUDY_SECTION_NAME: Interventions to Prevent and Treat Addictions Study Section[IPTA]


NIH_SPENDING_CATS: Biotechnology;Cancer;Digestive Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Lung Cancer;Orphan Drug;Racial and Ethnic Minority Health Research;Rare Diseases;Social Determinants of Health;Stomach Cancer

PHR: PDX CORE NARRATIVE The University of California and University of Texas Southwestern Diversity Patient-Derived Xenograft (PDX) Development and Trial Center leverages the collective strengths of six NCI- Comprehensive Cancer Centers to create minority patient cancer models and characterize targeted treatment responses to stomach and lung tumors. The PDX Core will establish, maintain, characterize, store, and distribute lung and stomach cancer minority PDX models adhering to applicable guidelines, standards, quality control procedures, and ongoing surveillance procedures for animal and human pathogens. Through UCaTS activities, we expect to extend our large repository to facilitate the discover of new therapies that could impact vulnerable racial and ethnic minority cancer patients.

PI_NAMEs: LLOYD, KC KENT (contact)

PROJECT_TERMS: Alaska Native;American Indians;animal care;animal colony;Animals;anti-cancer research;Antineoplastic Agents;Asian Americans;Asian population;biobank;Bioinformatics;Biology;Budgets;California;Cancer Center;cancer health disparity;Cancer Model;Cancer Patient;cancer therapy;Catchment Area;Charge;Clinical;clinical development;Clinical Trials;cohort;Collection;Color;Communities;Comprehensive Cancer Center;cost;Country;Cryopreservation;Data;Death Rate;Dedications;Deposition;Development;Diagnosis;Disparity;distributed model;Drug Combinations;drug efficacy;drug testing;Early Diagnosis;Ensure;Environment;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;ethnic minority;Ethnic Origin;Evaluation;experience;Failure;genomic data;Goals;Grant;Guidelines;Harvest;Healthcare;Human;human pathogen;Human Resources;immunodeficiency;Implant;implantation;Implantation procedure;improved;Incidence;Individual;Infrastructure;Institution;Intervention;Laboratories;Latino;Latino Population;Lead;Light;Los Angeles;Lung Neoplasms;Lymphoma;Malignant neoplasm of lung;Malignant Neoplasms;malignant stomach neoplasm;member;Methods;Minority;minority patient;Modeling;Molecular;Morphology;mortality;Mus;mutant;Mutation;Native Hawaiian;novel therapeutics;Oncogenes;operation;Operative Surgical Procedures;Organoids;Pacific Islander;pathogen;patient derived xenograft model;Patient Isolation;Patients;personalized medicine;Pharmaceutical Preparations;Pharmacotherapy;precision oncology;Preclinical Testing;Prevention;Procedures;programs;Qualifying;Quality Control;Race;racial minority;repository;Research;Research Personnel;Research Project Grants;Research Support;Resistance;Resource Sharing;Resources;response;rituximab;San Francisco;Service delivery model;Site;Smoking History;Standardization;Stomach Neoplasms;success;System;targeted treatment;Testing;Texas;treatment response;tumor;tumor xenograft;Universities;Validation;Work

PROJECT_TITLE: PDX Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Digestive Diseases;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Lung;Lung Cancer;Orphan Drug;Precision Medicine;Racial and Ethnic Minority Health Research;Rare Diseases;Stomach Cancer

PHR: BIOINFORMATICS CORE NARRATIVE The University of California and University of Texas Southwestern Diversity Patient-Derived Xenograft (PDX) Development and Trial Center leverages the collective strengths of six NCI- Comprehensive Cancer Centers to create minority patient cancer models and characterize targeted treatment responses to stomach and lung tumors. The goal of the UCaTS’ Bioinformatics Core is to provide extensive dataanalytic support for PDX studies at multiple stages including study design, PDXs molecular characterization, target selection, and statistical correlation and modeling of drug responses. Through UCaTS activities, we expect to extend our large repository to facilitate the discover of new therapies that could impact vulnerable racial and ethnic minority cancer patients.

PI_NAMEs: TEPPER, CLIFFORD G (contact)

PROJECT_TERMS: analysis pipeline;Antineoplastic Agents;Asian Americans;biobank;Biochemical;Bioinformatics;Biological;Biometry;Biostatistics Shared Resource;California;Cancer Model;Cancer Patient;Characteristics;Clinical;Collaborations;Comprehensive Cancer Center;Conduct Clinical Trials;Correlation Studies;Data;Data Analyses;Data Analytics;data integration;data repository;Data Set;data sharing;Dedications;design;Development;Drug Combinations;Drug Modelings;drug testing;efficacy testing;Epidermal Growth Factor Receptor;ethnic minority;exome sequencing;Frequencies;Gene Expression Profile;Gene Mutation;Genes;Genetic;genetic variant;genomic data;Genomics;Goals;high throughput analysis;Human Resources;improved;In Vitro;Individual;individual patient;Infrastructure;Latino Population;Light;Link;Lung;Lung Adenocarcinoma;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;malignant stomach neoplasm;Methods;Minority;minority patient;Modeling;Molecular;molecular marker;mutant;Mutation;Native Hawaiian or Other Pacific Islander;never smoker;next generation sequencing;Non-Small-Cell Lung Carcinoma;novel;novel therapeutics;patient derived xenograft model;Patients;Performance;Pharmaceutical Preparations;Pilot Projects;Population;pre-clinical;precision oncology;Property;racial minority;Regimen;relational database;repository;Research Design;Research Personnel;Research Project Grants;Resistance;response;Sampling;Services;Smoker;Statistical Models;Stomach;Stomach Neoplasms;targeted treatment;Testing;Texas;Therapeutic;Therapeutic Agents;therapeutic target;Transcript;transcriptome sequencing;Treatment Efficacy;treatment response;treatment strategy;tumor;tumor heterogeneity;Tumor Subtype;tumor xenograft;Universities

PROJECT_TITLE: Bioinformatics Core


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

ORG_DEPT: OPHTHALMOLOGY

PHR: Project Narrative Vision is a unique process, depending upon both the eye and the brain. This Core Facilities grant will support work on basic and clinical aspects of vision research, such as understanding how the eye and the visual brain develop, the brain mechanisms that underlie visual behavior, the treatment of diseases like macular degeneration, glaucoma, and myopia and the behavior of patients with ocular disease. By providing technical support, the Core modules will enable its participants to work effectively on problems related to the causes and treatment of blindness.

PI_NAMEs: GOLDBERG, MICHAEL E. (contact)

PROGRAM_OFFICER_NAME: GOVER, TONY DOUGLAS

PROJECT_TERMS: Animals;Behavior;Biochemical;Blindness;Brain;Center Core Grants;Clinical;clinical database;Collaborations;Communities;Computer Hardware;Computer software;Computers;Core Facility;Core Grant;Custom;Data;Data Analyses;data integration;Data Storage and Retrieval;database design;Databases;Dedications;design;Development;Diagnostic;Disease;Drosophila genus;Educational process of instructing;Electronics;Emergency Situation;Equipment;Eye;Eye Development;Eye diseases;fabrication;fluorescence microscope;Fluorescence Microscopy;Functional disorder;Funding;Funding Mechanisms;Genetic;genetic analysis;Genetic study;Genomics;Glaucoma;Grant;Health Insurance Portability and Accountability Act;Histologic;Histology;Human;Image;improved;in vivo;in vivo imaging;Individual;instrument;instrumentation;Laboratories;Light;light microscopy;Macular degeneration;Maintenance;member;Microscopic;Microscopy;Modification;Mus;Myopia;National Eye Institute;neurophysiology;Neurosciences;new technology;ocular angiogenesis;oculomotor behavior;Oryctolagus cuniculus;Participant;Patients;Postdoctoral Fellow;Privatization;Process;programs;Qualifying;repaired;Research;Research Personnel;Research Project Grants;Research Support;Resources;Retina;Retinal Diseases;Retinitis Pigmentosa;Rodent;Scientist;Security;Sequence Analysis;Services;student training;System;Techniques;Technology;Time;tissue culture;tissue preparation;Training;United States National Institutes of Health;Universities;Vision;Vision research;vision science;Visual;Work

PROJECT_TITLE: Core Facilities for Vision Research


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Bioengineering;Eye Disease and Disorders of Vision;Neurosciences

PI_NAMEs: SILVERMAN, RONALD H (contact)

PROJECT_TITLE: Instrumentation, Fabrication, and Design Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Digestive Diseases;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Orphan Drug;Precision Medicine;Racial and Ethnic Minority Health Research;Rare Diseases;Stomach Cancer

PHR: PROJECT 1 NARRATIVE The University of California and University of Texas Southwestern Diversity Patient-Derived Xenograft (PDX) Development and Trial Center leverages the collective strengths of six NCI- Comprehensive Cancer Centers to create minority patient cancer models and characterize targeted treatment responses to stomach and lung tumors.Thisprojectaddressesagastriccancer disparity-focusedresearchproblemusingPDXmodels. Through UCaTS activities, we expect to extend our large repository to facilitate the discover of new therapies that could impact vulnerable racial and ethnic minority cancer patients.

PROJECT_TERMS: Address;African American;Biological Assay;California;Cancer Burden;Cancer Etiology;cancer genome;cancer genomics;cancer health disparity;Cancer Model;Cancer Patient;cancer therapy;Cancer Therapy Evaluation Program;cancer type;candidate identification;candidate marker;Cell Cycle;chemotherapy;Chemotherapy-Oncologic Procedure;Clinical Research;Clinical Trials;Collection;Complex;Comprehensive Cancer Center;Data;Death Rate;Development;Diagnosis;Disparity;Drug Combinations;Drug Modelings;ethnic minority;Ethnic Origin;Ethnic Population;European;exome sequencing;FDA approved;FRAP1 gene;Frequencies;Funding;Generations;Genes;Genetic;Genome;genomic data;Genomics;Goals;High Prevalence;high risk;In Vitro;in vivo;Incidence;Indigenous American;Infrastructure;inhibitor;kinase inhibitor;Knowledge;Latina Population;Latino;Latino Population;Lung Neoplasms;male;Malignant Neoplasms;malignant stomach neoplasm;Medicine;men;Minority;Minority Groups;minority patient;Modeling;molecular subtypes;Molecular Target;mortality;mortality disparity;mutant;Mutate;Mutation;novel drug combination;novel therapeutics;Organoids;Pathway interactions;patient derived xenograft model;Patients;Pattern;Pharmaceutical Preparations;Phosphotransferases;PI3K/AKT;PIK3CA gene;PIK3CG gene;Population;pre-clinical;precision medicine;precision oncology;Race;racial minority;racial population;Receptor Protein-Tyrosine Kinases;repository;Research;Research Personnel;Resistance;response;Signal Pathway;Somatic Mutation;Stomach Neoplasms;survival disparity;targeted cancer therapy;targeted therapy trials;targeted treatment;Testing;Texas;The Cancer Genome Atlas;Translating;Translational Research;treatment response;tumor;tumor growth;Universities;White Women;Work

PROJECT_TITLE: Advancing gastric cancer precision medicine in Latinos through patient-derived modeling


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Networking and Information Technology R&D (NITRD);Neurosciences

PI_NAMEs: ALLIKMETS, RANDO L (contact)

PROJECT_TERMS: Animal Behavior;Area;arm movement;Behavior;Brain;Clinical;Clinical Data;Collaborations;Computer Interface;Computer software;Computers;Control Animal;Core Facility;Core Grant;cost;Creativeness;Data;Data Analyses;data integration;data management;Data Set;Data Storage and Retrieval;Database Management Systems;Databases;design;Development;Emergency Situation;Eye;Eye Movements;Fostering;Genetic;Genetic Databases;Genomics;Goals;Grant;Health Insurance Portability and Accountability Act;Health protection;Image;Individual;innovation;instrument;Laboratories;Maintenance;Measures;Mind;Mission;Modernization;molecular sequence database;Neurons;Neurosciences;Operating System;Patients;Physiological;Process;programs;Research;Research Institute;Research Personnel;Research Project Grants;Resources;Role;Scientist;Security;Services;Site;Speed;Structure;System;Technology;Time;Universities;Vision;Vision research;vision science;Visual System

PROJECT_TITLE: Computer Core


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Biotechnology;Drug Abuse (NIDA only);Genetics;Methamphetamine;Neurosciences;Stimulant Use and Misuse;Substance Misuse;Tobacco

ORG_CITY: PROVIDENCE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: PROJECT NARRATIVE: Psychoactive substances have disruptive and compounding eﬀects on memory circuit function. However, the mechanisms through which these substances alter gene expression to aﬀect circuit plasticity and behavioral choice are not well understood. We propose to discover the gene regulatory networks altered by the synergistic eﬀects of polystimulant use that drive escalation in drug self-administration.

PI_NAMEs: KAUN, KARLA R. (contact);LARSCHAN, ERICA NICOLE;O'CONNOR-GILES, KATHALEEN M

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: Affect;alcohol consequences;Alcohol consumption;Alcohols;Animals;approach behavior;Behavior;Behavioral;Behavioral Assay;Biological Assay;Brain;causal variant;Cells;Chromatin;cocaine use;Coupled;CREB1 gene;Cues;Drosophila genus;Drosophila melanogaster;drug of abuse;drug seeking behavior;Ethanol;experimental study;fly;Functional Imaging;gene discovery;Gene Expression;Gene Expression Regulation;gene regulatory network;Genes;Genetic Transcription;Goals;individual variation;innovation;Investigation;Learning;Legal;Memory;Methamphetamine;methamphetamine exposure;methamphetamine use;Molecular;Mushroom Bodies;neural;neurogenetics;Neuronal Plasticity;Neurons;Nicotine;nicotine seeking behavior;nicotine self-administration;nicotine use;Odors;opioid use;Pathway interactions;Pharmaceutical Preparations;polysubstance use;preference;Process;Psychological reinforcement;psychostimulant;response;RNA;Role;Self Administration;Signal Pathway;stimulant use;synaptic function;System;Testing;tool;Transcriptional Regulation;Volatilization;Work;Youth

PROJECT_TITLE: Gene Regulation in Memory Circuits as a Consequence of Polysubstance Use


NIH_SPENDING_CATS: Diabetes;Nutrition;Obesity

ORG_CITY: DUARTE

ORG_NAME: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE

PHR: Project Narrative  Obesity is the most important risk factor for diabetes. Dysfunctional adipocytes play a critical role in insulin resistance and obesity associated comorbidities. Studies laid out here will dissect the contribution of uridine biosynthesis in adipocytes in obesity and diabetes progression, which will provide new insights into the underlying pathophysiology of insulin resistance and shed light on novel therapeutic approaches.

PI_NAMEs: DENG, YINGFENG  (contact)

PROGRAM_OFFICER_NAME: GUPTA, DHANANJAY

PROJECT_TERMS: Acute;Adipocytes;adipokines;Adipose tissue;Agonist;Anabolism;antagonist;Attenuated;Beta Cell;Cell Line;Cells;Characteristics;Chronic;Circulation;combat;comorbidity;Couples;Data;design;Development;Diabetes Mellitus;diet-induced obesity;dietary;driving force;endoplasmic reticulum stress;Enzymes;Epidemic;Etiology;experimental study;Fasting;feeding;Functional disorder;gain of function;glucose uptake;glycemic control;High Fat Diet;Homeostasis;Human;Hyperinsulinism;Impairment;In Vitro;in vivo evaluation;insight;Insulin;Insulin Resistance;insulin secretagogues;insulin secretion;insulin sensitivity;Insulin Signaling Pathway;Intake;islet;Islet Cell;Leptin;Link;lipid biosynthesis;Liver;loss of function;Mammals;Mediating;Modeling;Molecular;mouse model;Mus;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutic intervention;Nucleosides;Nutrient;Obese Mice;Obesity;Organ;Osmosis;partial response;Pathologic;Pathway interactions;Plasma;Play;Post-Translational Protein Processing;Prediabetes syndrome;Production;Proteins;Pump;Regulation;response;Risk Factors;Role;Scientist;Structure of beta Cell of islet;Testing;therapeutically effective;Transducers;Uridine;XBP1 gene

PROJECT_TITLE: The Role of Adipocyte Uridine Biosynthesis in Obesity and Diabetes Progression

STUDY_SECTION: IPOD

STUDY_SECTION_NAME: Integrative Physiology of Obesity and Diabetes Study Section[IPOD]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Behavioral and Social Science;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Emergency Care;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Hematology;Pain Research;Pediatric;Rare Diseases;Sickle Cell Disease;Social Determinants of Health

ORG_CITY: WILMINGTON

ORG_NAME: NEMOURS CHILDREN'S HOSPITAL, DELAWARE

ORG_STATE: DE

PHR: PROJECT NARRATIVE Our proposal will institute a care pathway across seven emergency departments with the goal of improving guideline adherent care for children with sickle cell disease presenting with an acute vaso-occlusive pain crisis. If successful, this work will improve pain, decrease hospitalizations and improve the quality of life of children with sickle cell disease and acute vaso-occlusive pain crisis.

PI_NAMEs: BROUSSEAU, DAVID C (contact)

PROGRAM_OFFICER_NAME: KINDZELSKI, ANDREI L

PROJECT_TERMS: Abnormal Hemoglobins;Accident and Emergency department;Accounting;Acute;Acute Pain;Adherence;Adoption;Affect;American Society of Hematology;analytical method;Applied Research;Black race;Caring;Categories;Child;Child Care;Chronic;Clinical;Collaborations;combat;Data;data tools;design;Discipline of Nursing;Disease;Dissemination and Implementation;Dose;Education;Effectiveness;effectiveness/implementation trial;Emergency Care;Emergency department visit;Emergency Medicine;Engineering;Erythrocytes;evidence base;evidence based guidelines;Family;Feedback;Foundations;Funding;Goals;Grant;group intervention;Guideline Adherence;Guidelines;Health;Hematological Disease;Hospitalization;hospitalization rates;implementation facilitation;implementation outcomes;implementation research;implementation science;implementation strategy;improved;Inherited;Institution;Intervention;Interview;Journals;Medicine;Modification;multidisciplinary;National Heart, Lung, and Blood Institute;New England;Opioid;Outcome;Pain;Pain management;pain score;Pathway interactions;Patients;pediatric emergency;Persons;Protocols documentation;Quality of Care;Quality of life;Randomized;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recurrence;Registries;Reporting;Research Methodology;Sickle Cell;Sickle Cell Anemia;sickling;Site;Stress;Structural Racism;Structure;Testing;Theoretical Domains framework;Time;treatment adherence;treatment guidelines;United States;United States National Academy of Sciences;Universities;vaso-occlusive crisis;vaso-occlusive pain;Visit;Vulnerable Populations;Washington;Work

PROJECT_TITLE: Sickle Cell Improvement: ENhancing Care in the Emergency Department (SCIENCE)


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Eye Disease and Disorders of Vision;Neurosciences

PI_NAMEs: SPARROW, JANET RUTHE (contact)

PROJECT_TERMS: 3D Print;Achievement;Adult;Angiography;Animal Disease Models;Animal Experimentation;animal facility;Animal Model;Animals;Area;Brain;brain pathway;Buffers;Clinical;clinical application;Clinical Research;Collaborations;Color;Computer software;Core Facility;Core Grant;Cornea;cost;cryostat;Dedications;Development;Diagnostic;Diagnostic tests;Disease;Doctor of Philosophy;Electroretinography;Embryo;Ensure;Equipment;equipment acquisition;Equipment and Supplies;experience;Eye;Faculty;Film;Fixatives;Floor;Funding;Fundus;fundus imaging;Glaucoma;Goals;graduate student;Histologic;Histological Techniques;Histology;Human Resources;Human Subject Research;Image;Imaging Device;in vivo;in vivo imaging;Individual;instrument;instrumentation;Investigation;Knowledge;Laboratory Technicians;Lasers;Learning;lens;Letters;Light;Maintenance;Microscopic;Microtome - medical device;Mission;Modality;Molds;Monkeys;multimodality;Mus;Neonatal;Nursing Faculty;Ophthalmology;Ophthalmoscopes;Optical Coherence Tomography;Oryctolagus cuniculus;Paraffin;pathogen;Pathology;Patients;Pattern;Photoreceptors;Postdoctoral Fellow;postnatal;Preparation;Procedures;Productivity;programs;Protocols documentation;Qualifying;Rattus;recruit;repaired;Research;research faculty;Research Personnel;Resolution;Resources;Retina;Retinal Ganglion Cells;Retirement;Rodent;Role;Scanning;Schedule;Scientist;Services;skills;Sparrows;Specialist;Stains;Structure;Structure of retinal pigment epithelium;student training;Students;Study Section;System;Techniques;Testing;Thick;Thinness;time use;tissue preparation;tissue processing;Tissues;tool;Training;Translational Research;translational study;transmission process;United States National Institutes of Health;Universities;Vision;Vision research;Water;Work

PROJECT_TITLE: Imaging, Histology and Functional Diagnostics Core


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Mental Health;Neurodegenerative;Neurosciences;Nutrition;Post-Traumatic Stress Disorder (PTSD)

ORG_CITY: BIRMINGHAM

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: Older adults with PTSD are at an increased risk for age-related cognitive decline and Alzheimer’s disease. Increased inflammation is known to associate with PTSD, age-related cognitive decline, and Alzheimer’s disease, and central to the neural circuitry underlying these disorders are medial temporal lobe structures such as the basolateral amygdala. The proposed research is relevant to the aging population because it seeks to identify both neurobiological mechanisms at the core of these disorders and a feasible therapeutic intervention, and furthermore, this contribution will be significant because identifying neural mechanisms of fear-based neuropsychiatric disorder in aging will reveal targets for interventions to promote improved quality of life outcomes across the lifespan.

PI_NAMEs: HERNANDEZ, CAESAR MIGUEL (contact)

PROGRAM_OFFICER_NAME: SUTTERER, MATTHEW

PROJECT_TERMS: Acceleration;Address;Age;Age-associated memory impairment;age-related disease;aged;Aging;aging population;Alzheimer's Disease;Alzheimer's disease model;Amygdaloid structure;Anatomy;anti-epileptic agents;Anti-Inflammatory Agents;Antiinflammatory Effect;Autopsy;Award;Behavioral;Biochemical;career;chemokine;Cognitive aging;combat;comorbidity;conditioned fear;cytokine;Data;Dedications;Dementia;Diet;Dietary Intervention;Disease;Electrophysiology (science);Elements;Esters;Extinction;extracellular;fear memory;Fiber;Foundations;Fright;Functional disorder;functional improvement;Hippocampus;Human;Hyperactivity;Impairment;improved;In Vitro;in vivo;Individual;Inflammation;Inflammatory;innovation;Intervention;ketogenic diet;ketogentic;Ketones;Knowledge;Learning;life span;Lifestyle-related condition;Link;Measures;medial temporal lobe;Mediator;Membrane;Modeling;neural circuit;neurobiological mechanism;Neurodegenerative Disorders;neuroinflammation;neuromechanism;Neurons;neurophysiology;neuropsychiatric disorder;Neurosciences;neurotransmission;normal aging;older adult;optogenetics;Outcome;patch clamp;Pathologic Processes;Pathology;Phase;Photometry;Physiological;Physiology;Post-Traumatic Stress Disorders;postsynaptic;Prefrontal Cortex;Process;programs;Property;Protocols documentation;Quality of life;Rattus;remediation;Research;Risk;Rodent;Role;Scientist;Sensory;Signal Transduction;skills;Structure;success;suicide rate;Synapses;Techniques;Testing;Therapeutic Intervention;Tissues;Training;translational approach;Work

PROJECT_TITLE: The Impact of Normative Aging and Alzheimers Disease on Fear based Disorders and Amygdala Dysfunction

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Biotechnology;Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Lung Cancer;Precision Medicine;Racial and Ethnic Minority Health Research

PHR: PROJECT 2 NARRATIVE The University of California and University of Texas Southwestern Diversity Patient-Derived Xenograft (PDX) Development and Trial Center leverages the collective strengths of six NCI-Comprehensive Cancer Centers to create minority patient cancer models and characterize targeted treatment responses to lung tumors. This project focuses on the epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer, which is a tumor driving gene that occurs with a higher frequency in Asian Americans, Native Hawaiians, Pacific Islanders (AANHPI ~50%), and Latinos (~38%). Through UCaTS activities, we expect to extend our repository of minority PDXs focused on EGFR mutant lung cancer and to facilitate the discovery of new therapies that could impact vulnerable racial and ethnic minority cancer patients.

PI_NAMEs: RIESS, JONATHAN W (contact)

PROJECT_TERMS: Address;Apoptotic;Asian Americans;Asian ancestry;Asian population;Automobile Driving;BCL1 Oncogene;BCL2 gene;BCL2L1 gene;Biological;Biosensor;Bypass;California;Cancer Model;Cancer Patient;cancer subtypes;Cancer Therapy Evaluation Program;Cell model;Cells;Clinical;Clinical Trials;Collaborations;Combined Modality Therapy;Comprehensive Cancer Center;Data;Development;Drug Combinations;drug development;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Equity;ethnic minority;Ethnic Origin;experience;Family;FDA approved;Frequencies;Gender;Generations;Genes;Genetic;genomic biomarker;Genomics;high risk;imaging platform;in vivo;Indigenous American;Individual;inhibitor;inhibitor therapy;Latino;Latino Population;live cell imaging;Lung Adenocarcinoma;Lung Neoplasms;machine learning method;Malignant neoplasm of lung;Mediating;Minority;minority patient;Modeling;mutant;Mutation;Native Hawaiian;Non-Small-Cell Lung Carcinoma;novel therapeutic intervention;novel therapeutics;Oncogenes;Pacific Islander;patient derived xenograft model;Patients;Pattern;Pharmaceutical Preparations;Phosphotransferases;Population;Proto-Oncogene Proteins c-akt;Race;racial minority;Receptor Inhibition;Receptor Protein-Tyrosine Kinases;Receptor Signaling;repository;Research;research and development;Resistance;resistance mechanism;Resolution;response;Role;Signal Pathway;Signal Transduction;Smoking;Smoking Status;targeted treatment;Testing;Texas;The Jackson Laboratory;Translating;Translations;treatment optimization;treatment response;tumor;tumor progression;Universities;Variant;Woman;Work

PROJECT_TITLE: Characterizing treatment responses for common lung cancer (LC) subtypes in Latinos and Asians


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular

ORG_CITY: COLLEGE STATION

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

ORG_STATE: TX

PHR: Project Narrative Recently a gut microbe derived metabolite, Trimethylamine-N-oxide (TMAO), was identified as a novel risk factor for cardiovascular diseases, however, the mechanism by which it causes cardiovascular injury is unclear. In this application, we have proposed innovative studies that will delineate TMAO’s role in producing both inflammation and injury to cells which lead to hardening of the arteries and ultimately cause heart or blood vessel diseases. We believe that knowledge derived from these studies will help understand the molecular basis of TMAO induced cardiovascular injury and will provide novel therapeutic targets for the treatment of these diseases.

PI_NAMEs: KOKA, SAI SUDHA (contact)

PROGRAM_OFFICER_NAME: HASAN, AHMED A  K

PROJECT_TERMS: Abbreviations;Acceleration;acid sphingomyelinase;Address;Adhesions;Amines;Applications Grants;Arterial Fatty Streak;Arteries;atherogenesis;Atherosclerosis;Blood Vessels;Cardiovascular Diseases;cardiovascular injury;cardiovascular risk factor;Cardiovascular system;Carnitine;Carotid Arteries;CASP1 gene;Caspase Inhibitor;Cathepsins B;cell injury;Cells;Ceramides;Cessation of life;Choline;Circulation;clinical development;clinically relevant;Developed Countries;dietary;Disease;Disease Progression;Endothelial Cells;endothelial dysfunction;endothelial regeneration;endothelial stem cell;Endothelium;exosome;Exposure to;Fluorochrome;gut microbes;Health;Heart;High Mobility Group Proteins;HMGB1 gene;Homing;Human;IL18 gene;Impairment;In Vitro;in vivo;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;innovation;insight;Interleukins;Intestines;Knockout Mice;Knowledge;Lecithin;Lysosomes;Macrophage;marenostrin;Mediating;Membrane;Metabolic;metabolomics;microbial;Molecular;monocyte;Morbidity - disease rate;mortality;Multivesicular Body;Mus;NADPH Oxidase;new therapeutic target;Nitric Oxide;novel;novel therapeutic intervention;Nucleotides;Oxides;Pathogenesis;Pathogenicity;Patients;Pattern;Permeability;Plasma;Process;Production;Proteins;receptor;recruit;repaired;response;Risk Factors;Rodent;Rodent Model;Role;Sclerosis;Series;Signal Pathway;Signal Transduction;Sphingolipids;Sphingosine;sphingosine 1-phosphate;Superoxides;T-Lymphocyte;Testing;Tight Junctions;trafficking;Transmission Electron Microscopy;vascular inflammation;vascular injury;Vasodilation;Work

PROJECT_TITLE: Role of Trimethylamine-N-oxide in endothelial dysfunction

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


NIH_SPENDING_CATS: Aging;Clinical Research;Eye Disease and Disorders of Vision

ORG_CITY: STONY BROOK

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: Project Narrative The World Health Organization identified cataract as the leading cause of blindness. In the US, cataract extraction is the most common Medicare surgery, adding a financial burden to healthcare of more than $6.8 billion annually. Better knowledge of the biological mechanisms that regulate lens transport, and how their failure contribute to its age-related decline will suggest new therapeutic strategies to prevent or postpone the progression of cataract, thereby alleviating the need for surgical intervention, and possibly save billions in Medicare expenditures.

PI_NAMEs: WHITE, THOMAS W (contact)

PROGRAM_OFFICER_NAME: ARAJ, HOUMAM H

PROJECT_TERMS: Acceleration;Age;age related;age related changes;age related decline;aging process;Biological;Biometry;Blindness;Carrier Proteins;Cataract;Cataract Extraction;Cell Physiology;Ciliary Muscle;Clinical;cohort;cycloplegic;Development;efficacy evaluation;Elderly;electric impedance;Excision;Expenditure;Eye;Failure;Feedback;Financial Hardship;Funding;Future;Gap Junctions;genetic manipulation;Geometry;Healthcare;Homeostasis;Human;human subject;Human Volunteers;Hydrostatic Pressure;Image;Impairment;in vivo;insight;Ion Channel;Ion Transport;Ions;Knowledge;lens;Liquid substance;Longitudinal Studies;Magnetic Resonance Imaging;Maintenance;Maps;Measurement;Measures;Mechanics;Mediating;Medicare;Microcirculation;middle age;Modeling;Monitor;mouse model;Mus;Muscle relaxation phase;new therapeutic target;normal aging;novel therapeutic intervention;Nuclear;Nutrient;Operative Surgical Procedures;Optics;Oxygen;Pathology;Patients;pharmacologic;Presbyopia;prevent;Property;Proteins;Protocols documentation;Refractive Errors;Refractive Indices;Scanning;Schedule;Shapes;Signal Pathway;Stimulus;Structure;Surface;System;Testing;Time;tool;Transgenic Mice;Translating;Tropicamide;Visit;Vitrectomy;Water;World Health Organization

PROJECT_TITLE: Age related changes in lens transport and cataract

STUDY_SECTION: BDE

STUDY_SECTION_NAME: Biology and Development of the Eye Study Section[BDE]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

ORG_CITY: INDIANAPOLIS

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: PROJECT NARRATIVE The proposed research is relevant to public health since it is likely to contribute a mechanistic understanding for novel drug-drug interactions that contribute to treatment-limiting toxicities during immune checkpoint inhibi- tor therapy. This knowledge will be clinically impactful since it is likely to inform clinical strategies to identify pa- tients at highest risk for immune checkpoint inhibitor-related drug interactions and to prevent these drug inter- actions. The long-term goal of this translational research is to identify clinical strategies to enhance the safety, and thereby the clinical benefit, of immune checkpoint inhibitors.

PI_NAMEs: SHUGG, TYLER A (contact)

PROGRAM_OFFICER_NAME: PAUL, MOUSHUMI

PROJECT_TERMS: Adverse event;adverse event risk;Affect;Biological Assay;Cancer Patient;cancer therapy;career;checkpoint therapy;Citalopram;Clinical;clinical development;Clinical Management;clinical practice;Clinical Research;clinical risk;Clinical Trials;clinically relevant;Collaborations;comorbidity;CYP1A2 gene;CYP2B6 gene;CYP2C19 gene;CYP2C9 gene;CYP2D6 gene;CYP3A4 gene;Cytochrome P450;cytokine;Data;Development;Drug Interactions;drug metabolism;Enzymes;Family;Fentanyl;Funding;Future;Goals;Hepatic;high risk;Immune;Immune checkpoint inhibitor;immune-related adverse events;Inflammatory;Interleukin-6;Investigation;Knowledge;Lead;Malignant Neoplasms;Measures;Mediating;member;Mentored Patient-Oriented Research Career Development Award;Mentors;Metabolic;Metabolic Pathway;Metabolism;Methodology;Methods;models and simulation;Monoclonal Antibodies;novel therapeutics;Opioid Analgesics;Outcome;Patients;Pharmaceutical Preparations;pharmacokinetic model;Phase;Physiological;Positioning Attribute;post-market;prevent;Production;programs;prospective;Public Health;Regulation;Research;Research Technics;Risk;Safety;Serious Adverse Event;stem;Study models;Supportive care;T-Cell Activation;Therapeutic;Toxic effect;Tramadol;translational approach;translational goal;Translational Research;Tyrosine Kinase Inhibitor

PROJECT_TITLE: Investigation of the Immune-Mediated Drug-Drug Interaction Potential of Immune Checkpoint Inhibitors


NIH_SPENDING_CATS: Genetics;Hematology;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Stem Cell Research - Umbilical Cord Blood/ Placenta;Stem Cell Research - Umbilical Cord Blood/ Placenta - Human;Stem Cell Research - Umbilical Cord Blood/ Placenta - Non-Human

ORG_CITY: WORCESTER

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: Project narrative Erythropoiesis is the life-long process by which red cells are formed in the bone marrow, and its failure leads to anemia. This project investigates a stage of erythropoiesis when erythroid precursors replicate unusually fast, a situation that might lead to errors in genome replication and genomic instability. The proposal will determine whether genomic instability does in fact take place in fast-cycling red cell precursors, or whether they are somehow equipped to handle fast cycling without compromising genomic integrity.

PI_NAMEs: SCULLY, RALPH ;SOCOLOVSKY, MERAV  (contact)

PROGRAM_OFFICER_NAME: ROY, CINDY

PROJECT_TERMS: Affect;Anemia;Biochemical;Bone Marrow;Bone Marrow Cells;Cell Cycle;Cell division;Cell Survival;Cells;CFU-E;Chromatids;Copy Number Polymorphism;cost;Coupled;Data;Development;Developmental Biology;disability;Disease;DNA biosynthesis;DNA Damage;DNA Interstrand Crosslinking;DNA Repair;DNA replication fork;Erythroblasts;Erythrocytes;Erythroid;Erythroid Cells;Erythropoiesis;Erythropoietin Receptor;Event;Failure;Fanconi Anemia pathway;Fanconi's Anemia;gene induction;Genes;Genetic Transcription;Genome;genome integrity;genome sequencing;Genomic Instability;Goals;homologous recombination;in vivo;indexing;inhibitor;Life;Measures;Mitomycin C;Modality;mouse model;Mus;novel;Oncogenes;Pathway interactions;Physiological;Process;progenitor;programs;repaired;replication stress;Reporter;Resistance;response;S phase;self-renewal;Site;Speed;Stress;stress reduction;Study models;System;Testing;whole genome;Wild Type Mouse

PROJECT_TITLE: The DNA damage response of fast-cycling erythroblasts

STUDY_SECTION: HTBT

STUDY_SECTION_NAME: Hemostasis, Thrombosis, Blood Cells and Transfusion Study Section[HTBT]


NIH_SPENDING_CATS: Biotechnology;Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Lung Cancer;Racial and Ethnic Minority Health Research;Social Determinants of Health

PHR: PILOT PROJECTS AND TRANS-NETWORK ACTIVITIES CORE NARRATIVE The University of California and University of Texas Southwestern Diversity Patient-Derived Xenograft (PDX) Development and Trial Center leverages the collective strengths of six NCI- Comprehensive Cancer Centers to create minority patient cancer models and characterize targeted treatment responses to stomach and lung tumors. The Pilot Projects and Trans-Network Activities Core will administer NCI-funded pilot project opportunities to facilitate interactions among UCaTS, the PDXNet Consortium, and non-PDXNet investigators. Additionally, this Core will coordinate the development of standard operating procedures and develop methods of experimental validation and reproducibility that will be shared within the Trans-Network and in collaboration with non-Network projects. Through UCaTS activities, we expect to extend our large repository to facilitate the discover of new therapies that could impact vulnerable racial and ethnic minority cancer patients.

PI_NAMEs: CHEN, MOON SHAO-CHUANG (contact)

PROJECT_TERMS: Achievement;Administrator;Affect;African American;American;Asian Americans;Basic Cancer Research;California;Cancer Center;cancer health disparity;Cancer Model;Cancer Patient;Cells;chemotherapy;Collaborations;Collection;community engagement;Comprehensive Cancer Center;Conduct Clinical Trials;Data Commons;Decision Making;design;Development;Discipline;Disparity;Doctor of Philosophy;Drug Combinations;drug testing;efficacy validation;Ensure;ethnic minority;ethnic minority population;Evaluation;experience;Fostering;Funding;Goals;Grant;Health Disparities Research;Human Resources;innovative technologies;International;Latino;Latino Population;Lead;Los Angeles;Lung Neoplasms;Malignant neoplasm of lung;Malignant Neoplasms;malignant stomach neoplasm;meetings;Methods;Minority Groups;minority patient;Monitor;Moon;Native Hawaiian;novel;novel therapeutics;Pacific Islander;Pathology;patient derived xenograft model;people of color;Pharmaceutical Preparations;Phase;Pilot Projects;pre-clinical;precision oncology;preclinical study;Preclinical Testing;Procedures;programs;racial minority;racial minority population;repository;Reproducibility;Research;Research Personnel;San Francisco;Site;Stomach Neoplasms;symposium;System;targeted treatment;Technology;Testing;Texas;treatment response;tumor;Universities;Validation;Woman;Xenograft procedure


PHR: PROJECT NARRATIVE Phenylketonuria (PKU), hereditary tyrosinemia type 1 (HT1), and mucopolysaccharidosis type 1 (MPSI) are inherited disorders of metabolism that cause debilitating and even life-threatening medical problems as early as birth. We seek to use a type of CRISPR gene editing technology, called base editing, to directly and permanently correct gene mutations or otherwise alter genes at the DNA level in the liver, either after or before birth—a “one- and-done” treatment strategy that could substantially improve the long-term health of patients with these diseases .

PI_NAMEs: MUSUNURU, KIRAN ;PERANTEAU, WILLIAM H. (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Address;Adenine;adeno-associated viral vector;Anaphylaxis;ANGPTL3 gene;Animal Model;animal resource;Animals;Antibodies;Area;Bacteria;base editing;base editor;Biodistribution;Birth;cancer immunotherapy;chimeric antigen receptor T cells;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR/Cas technology;Dependovirus;Development;Disease;disease-causing mutation;DNA;Dose;Drug Kinetics;efficacy testing;enzyme replacement therapy;Enzymes;fetal;Funding;gene correction;gene editing technology;Gene Mutation;Genes;Genetic Diseases;genome editing;Goals;Guide RNA;Health;Heart;Hematopoietic Stem Cell Transplantation;Hemoglobinopathies;Hepatocyte;Hereditary Disease;Human;human model;humanized mouse;improved;in utero;in vivo;Injectable;Intravenous;Joints;Lead;lead optimization;Life;lipid nanoparticle;Liver;Lung;Medical;meetings;Metabolic;Metabolic Diseases;Modality;Modeling;Morbidity - disease rate;mortality;mortality risk;Mucopolysaccharidoses;Mus;Mutation;Neurologic;non-compliance;nonhuman primate;novel;novel therapeutics;nuclease;Nucleotides;Organ;Outcome;Pathogenicity;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacology and Toxicology;Phase I/II Clinical Trial;Phenotype;Phenylketonurias;postnatal;pre-Investigational New Drug meeting;preclinical study;prenatal;Primates;prime editing;Process;programs;Publishing;Research Activity;Research Project Grants;Resources;response;Sheep;somatic cell gene editing;success;targeted treatment;Therapeutic;therapeutic genome editing;Time;timeline;Tissue Sample;tool;Treatment Efficacy;treatment strategy;Tyrosinemias;Variant;Writing

PROJECT_TITLE: Postnatal and Prenatal Therapeutic Base Editing for Metabolic Diseases

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


PI_NAMEs: MUSUNURU, KIRAN  (contact)

PROJECT_TERMS: Advisory Committees;base editing;Budgets;Clinical Trials;cloud based;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Communication;Computer software;conflict resolution;Creativeness;Data;Documentation;Dose;Ensure;experience;Failure;Fostering;Generations;Grant;Human Resources;Individual;Infrastructure;Interdisciplinary Study;Laboratories;Lead;Learning;meetings;member;Metabolic Diseases;multidisciplinary;New Zealand;organizational structure;Patients;Pharmaceutical Preparations;Phase I Clinical Trials;Play;Positioning Attribute;postnatal;preclinical study;prenatal;Preparation;Principal Investigator;Problem Solving;programs;Progress Reports;Protocols documentation;Recurrence;Registries;Research;research and development;Research Personnel;Research Project Grants;Resources;Role;Scientist;Secure;Site;somatic cell gene editing;Strategic Planning;success;synergism;Therapeutic;Time;tool;Training and Education;United States National Institutes of Health

PROJECT_TITLE: ADMINISTRATIVE CORE

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MGG-G]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Digestive Diseases;Gene Therapy;Genetics;Human Genome;Liver Disease;Mucopolysaccharidoses (MPS);Orphan Drug;Pediatric;Rare Diseases

PI_NAMEs: WANG, XIAO  (contact)

PROJECT_TERMS: Address;adeno-associated viral vector;base editing;Biochemical;Bioinformatics;Biological;Biological Assay;candidate identification;case-by-case basis;Cell model;cell type;Center for Translational Science Activities;Chromosomal Rearrangement;delivery vehicle;design;Development;Disease;disease-causing mutation;Dose;Elements;Evaluation;Event;Frequencies;Gene Expression;gene therapy;Genetic Variation;genome editing;genome integrity;genome-wide analysis;genotoxicity;Growth;Hepatocyte;high risk;Human;Human Genetics;Human Genome;Hybrids;in silico;Industry;Insertional Mutagenesis;Laboratories;Lead;Location;Maps;Metabolic Diseases;Methodology;Methods;Modeling;Mucopolysaccharidosis I;New Zealand;novel strategies;off-target site;Optics;Patients;Pennsylvania;Phenylketonurias;postnatal;preclinical development;preclinical safety;preclinical study;prenatal;Program Development;Recommendation;Research;Research Design;Research Personnel;Research Project Grants;Resources;Risk;safety assessment;Services;Site;Therapeutic;Time;tool;Tyrosinemias;United States Food and Drug Administration;Universities;Variant;Work;Writing

PROJECT_TITLE: OFF-TARGET RESOURCE CORE


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: NORTHAMPTON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: SMITH COLLEGE

PHR: Project Narrative Training scientists in principles of rigorous experimental methods is essential to maintain the high quality of our biomedical research. In this grant we will work collaboratively to develop engaging and effective training materials to achieve improved training in rigor and reproducibility.

PI_NAMEs: HARRINGTON, MARY E (contact)

PROGRAM_OFFICER_NAME: CRAWFORD, DEVON CHRISTINE

PROJECT_TERMS: Address;Area;Biomedical Research;Brain;career;Case Study;college;Communities;Computer software;Data Analyses;Data Set;data sharing;demographics;design;Education;Educational process of instructing;equity, diversity, and inclusion;Exercise;experience;Experimental Designs;experimental study;Female;Goals;graduate student;Grant;Human;human disease;improved;Individual;instructor;Laboratory Scientists;Learning;Methods;Nervous System Disorder;Neurosciences;Neurosciences Research;open data;Participant;pedagogy;programs;Property;racism;Recovery;Reporting;Reproducibility;Research;Research Personnel;Resources;Sampling;Science;Scientist;simulation;skills;Stroke;Structure;Students;Testing;Training;Training Activity;undergraduate student;Voice;Woman;Work

PROJECT_TITLE: Developing Training Materials for Experimental Rigor in Neuroscience


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Digestive Diseases;Gene Therapy;Genetics;Liver Disease;Mucopolysaccharidoses (MPS);Nanotechnology;Orphan Drug;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Rare Diseases;Women's Health Research

PI_NAMEs: FLAKE, ALAN W. (contact)

PROJECT_TERMS: Animal Model;animal resource;Animals;base editing;base editor;Biodistribution;Birth;Cell Therapy;cisterna magna;Clinical Research;Data;delivery vehicle;design;Disease;Dose;Early treatment;effective therapy;efficacy evaluation;experience;fetal;Fetal safety;Fetal Sheep;Fetus;Future;gene editing technology;gene therapy;Genes;genome editing;Growth;Harvest;hepatic vein;Human;Immune response;Immune system;in utero;in vivo;information gathering;Injections;Knowledge;Lead;Letters;lipid nanoparticle;Liver;Macaca fascicularis;maternal safety;maternal serum;maternal wellbeing;Mendelian disorder;Metabolic Diseases;Modeling;Morbidity - disease rate;mortality;Mothers;mouse model;Mucopolysaccharidosis I;Mus;nanoparticle delivery;nonhuman primate;Onset of illness;Organ;Pathology;Personal Satisfaction;postnatal;preclinical study;Pregnancy;prenatal;Preparation;Procedures;Property;Proteins;Publishing;Research Personnel;Resources;Safety;Services;Sheep;sheep model;stem cells;Structure of omphalomesenteric vein;Technical Expertise;Techniques;Technology;Therapeutic;therapeutic genome editing;Time;Tissue Harvesting;Tissues;Toxic effect;Tyrosinemias;ultrasound;Umbilical vein;Weight

PROJECT_TITLE: IN UTERO SMALL AND LARGE ANIMAL RESOURCE CORE


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Disorders;Gene Therapy;Genetics;Intellectual and Developmental Disabilities (IDD);Nanotechnology;Neurosciences;Nutrition;Orphan Drug;Pediatric;Rare Diseases

PROJECT_TERMS: Address;Adenine;amino acid metabolism;Anaphylaxis;Animal Model;autosome;base editing;base editor;Biodistribution;Blood;causal variant;Classical phenylketonuria;cofactor;cognitive development;curative treatments;Defect;Diet;Dietary Intervention;Disease;Dose;Drug Kinetics;Drug Packaging;enzyme therapy;Enzymes;Europe;Felis catus;Funding;gallium arsenide;Genes;genome editing;Goals;Guide RNA;Hepatocyte;High Prevalence;Human;humanized mouse;Hyperphenylalaninaemias;Impaired cognition;Impairment;Inherited;Injectable;Investigational Drugs;Investigational New Drug Application;Lead;lead optimization;Link;lipid nanoparticle;Liver;Mediating;Medical;Metabolic;Metabolic Diseases;Middle East;Modeling;Mus;Mutation;mutation correction;neuropsychiatry;neurotoxic;neurotoxicity;nonhuman primate;Oral;Outcome;Pathogenicity;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacology and Toxicology;Phase I/II Clinical Trial;Phenotype;Phenylalanine;Phenylalanine Hydroxylase;Phenylketonurias;Population;postnatal;pre-Investigational New Drug meeting;prenatal;prime editing;prime editor;response;Risk;Russia;Therapeutic;therapeutic genome editing;Toxic effect;transition mutation;United States Food and Drug Administration;Variant;Work

PROJECT_TITLE: LEAD PROJECT 1: PHENYLKETONURIA (PKU)


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Digestive Diseases;Gene Therapy;Genetics;Liver Disease;Nanotechnology;Nutrition;Orphan Drug;Pediatric;Rare Diseases

PI_NAMEs: PERANTEAU, WILLIAM H. (contact)

PROJECT_TERMS: Adenine;Adherence;autosome;base editing;base editor;Biodistribution;Birth;Cause of Death;Cell Line;Clinical Trials;Coagulation Process;Cytosine;dietary;dietary restriction;Dioxygenases;Disease;disease model;Dose;Drug Kinetics;Early treatment;Enzymes;fetal;Fumarylacetoacetase;Funding;Genes;genome editing;Germ-Line Mutation;Goals;Guide RNA;Hepatocyte;Herbicides;high risk;Human;Impairment;in utero;in vivo;Lead;Life;lipid nanoparticle;Liver;Liver diseases;Liver Failure;liver transplantation;Medical;meetings;Messenger RNA;Metabolic;Metabolic Diseases;Mus;Mutation;nanoparticle delivery;Neonatal;neonatal period;Neurologic;non-compliance;Nonsense Mutation;novel strategies;Outcome;Pathogenicity;Pathology;Pathway interactions;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacology and Toxicology;Phenotype;Phenylalanine;postnatal;pre-Investigational New Drug meeting;preclinical study;prenatal;Primary carcinoma of the liver cells;Prior Therapy;Proteins;Proximal Kidney Tubules;renal tubular dysfunction;response;Risk;RNA Splicing;Safety;Sheep;Site;somatic cell gene editing;standard of care;succinylacetone;Therapeutic;therapeutic genome editing;Tyrosine;Tyrosinemias;United States Food and Drug Administration

PROJECT_TITLE: PROJECT 2: HEREDITARY TYROSINEMIA TYPE 1 (HT1)


ADMINISTERING_IC: AI

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: CHAMPAIGN

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

PHR: A subset of Immunoglobulin (Ig) heavy chain classes, including IgA and IgM, assemble into polymeric (p) antibodies, which are delivered to the mucosa where they play crucial roles mediating interactions with commensal microbes and eliminating pathogens such as Clostridium difficile. Building upon cryoelectron microscopy structures of secretory IgA, recenty published by our group and others, we aim to investigate pIg assembly mechanisms, determine unknown structures, and engineer IgAs that can bind and neutralize human mucosal pathogens including C. difficile. These studies will expand knowledge of mucosal immunity and host- microbe interactions while also delivering the ability to modify pIg structure for therapeutic benefit.

PI_NAMEs: STADTMUELLER, BETH M. (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Antibodies;Antigens;Binding;Binding Sites;Biochemical;Biological Assay;Biological Models;biophysical techniques;Birds;Cells;Clostridium difficile;commensal microbes;Complex;crosslink;Cryoelectron Microscopy;Data;dimer;Electrons;Engineering;Experimental Models;experimental study;Fab Immunoglobulins;Family suidae;flexibility;Foundations;functional outcomes;Heavy-Chain Immunoglobulins;host-microbe interactions;Human;Immune response;Immunity;Immunoglobulin A;Immunoglobulin M;Immunoglobulins;Immunologics;Immunology;improved;In Vitro;insight;Investigation;Knowledge;Ligand Binding;Ligands;Mammals;Mediating;Methods;microbial;Modeling;Modification;Molecular;Molecular Conformation;monomer;Mucosal Immunity;Mucous Membrane;Mus;Mutation;Outcome;pathogen;pathogenic bacteria;Pathogenicity;Play;polymeric IgA;Polymeric Immunoglobulin Receptors;polymerization;Polymers;porcine model;Positioning Attribute;Predictive Factor;preservation;Process;programs;Publishing;receptor;receptor binding;Reporting;Reptiles;Research;Role;Salmonella enterica;Secretory Component;Secretory Immunoglobulin A;Side;Solvents;Spectrum Analysis;Structure;Structure-Activity Relationship;Surface Plasmon Resonance;teleost;teleost fish;Testing;Therapeutic;Vertebrates;Wing;Work;X-Ray Crystallography

PROJECT_TITLE: Investigating polymeric antibody assembly, structure, function and therapeutic potential

STUDY_SECTION: CMIA

STUDY_SECTION_NAME: Cellular and Molecular Immunology - A Study Section[CMIA]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Genetics;Neurosciences;Physical Injury - Accidents and Adverse Effects;Regenerative Medicine

ORG_CITY: COLUMBIA

ORG_NAME: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA

ORG_STATE: SC

PHR: PROJECT NARRATIVE There is a pressing clinical need to develop new strategies to both encourage and accelerate axon regeneration in the peripheral and central nervous systems; however, we need to understand the molecular mechanisms underlying what restricts rates of axon regeneration to the 1-2 mm/day seen for peripheral nerves. Translation of mRNAs in axons has been shown to promote axon regeneration; this proposal focuses how levels of those mRNAs are regulated to sustain localized protein synthesis and promote regeneration.

PI_NAMEs: TWISS, JEFFERY L (contact)

PROGRAM_OFFICER_NAME: TYLER, WILLIAM A

PROJECT_TERMS: Acceleration;Adult;Affect;Affinity;Alleles;Appearance;Axon;axon growth;axon injury;axon regeneration;Behavior;Binding;Binding Proteins;Bioinformatics;Biotinylation;Central Nervous System;Clinical;cohort;Collaborations;Complex;Cytoplasm;Data;Dendrites;Development;Elements;Environment;exosome;extracellular;Family;FMR1 gene;Funding;Growth;Heterogeneous-Nuclear Ribonucleoproteins;Hippocampus;HuD antigen;Human;Impairment;In Vitro;in vivo;Injury;Knockout Mice;Knowledge;Link;link protein;Mediating;memory consolidation;Memory impairment;Messenger RNA;MicroRNAs;Molecular;mRNA Stability;mRNA Transcript Degradation;mRNA Translation;Mus;Natural regeneration;Nerve;Nerve Regeneration;Nervous System;neuron loss;neuronal cell body;neuronal growth;Neurons;neurotransmission;Nuclear;particle;Peripheral nerve injury;peripheral nerve regeneration;Peripheral Nerves;Peripheral Nervous System;Physiological;posttranscriptional;Prefrontal Cortex;presynaptic;Protein Binding Domain;Protein Biosynthesis;protein complex;Proteins;Proteome;Recovery of Function;Regenerative capacity;Regulation;Regulon;response;response to injury;Ribonucleoproteins;RNA;RNA analysis;RNA-Binding Proteins;RNA-Protein Interaction;Rodent;Role;Seizures;Stimulus;stoichiometry;Testing;transcriptome;Translating;translational impact;Translational Regulation;Translations;Up-Regulation;Work

PROJECT_TITLE: Destabilization of axonal mRNAs by KHSRP complexes during axon regeneration

STUDY_SECTION: NDPR

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


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Digestive Diseases;Gene Therapy;Genetics;Intellectual and Developmental Disabilities (IDD);Liver Disease;Mucopolysaccharidoses (MPS);Orphan Drug;Pediatric;Rare Diseases;Regenerative Medicine;Transplantation

ORG_CITY: PHILADELPHIA

PI_NAMEs: DAVIDSON, BEVERLY L. (contact)

PROJECT_TERMS: 10 year old;2 year old;Address;Adenine;Adult;Age Months;autosome;base editing;base editor;Biochemical;Biodistribution;Birth;causal variant;Child;Clinical Trials;conditioning;Congenital musculoskeletal anomalies;cost;Dependovirus;Disease;disease phenotype;Dose;Drug Kinetics;enzyme replacement therapy;Enzymes;Exhibits;fetal;Fibroblasts;Funding;gallium arsenide;Genes;genome editing;Genotype;Glycosaminoglycans;Goals;Guide RNA;Heart Diseases;Hematopoietic Stem Cell Transplantation;Hepatocyte;Hepatosplenomegaly;Hernia;Heterozygote;Human;immunogenic;improved;in utero;in vivo;Incidence;ineffective therapies;Infant;L-Iduronidase;Lead;Liver;Lysosomal Storage Diseases;meetings;Metabolic;Metabolic Diseases;mouse model;Mucopolysaccharidosis I;Mucopolysaccharidosis I H;Mus;Musculoskeletal Diseases;Mutation;mutation correction;Neurocognitive;novel strategies;Organ;Outcome;Pathology;Patients;Pharmaceutical Preparations;pharmacologic;Pharmacology and Toxicology;Phenotype;postnatal;pre-Investigational New Drug meeting;preclinical study;prenatal;prevent;Prior Therapy;Property;response;Retina;Route;Safety;Sheep;Therapeutic;therapeutic genome editing;Transplantation;United States Food and Drug Administration

PROJECT_TITLE: PROJECT 3: MUCOPOLYSACCHARIDOSIS TYPE 1 (MPS1)


FUNDING_MECHANISM: SBIR-STTR RPGS

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Liver Disease;Nutrition;Orphan Drug;Prevention;Rare Diseases

ORG_CITY: CAMBRIDGE

ORG_NAME: REVEAL PHARMA

PHR: Project Narrative Liver fibrogenesis is the active scarring of liver tissue that occurs in chronic liver diseases like nonalcoholic steatohepatitis (NASH). If left unattended liver fibrosis can progress to liver failure, cirrhosis, or primary liver cancer. There are no methods to noninvasively detect and quantify fibrogenesis. The goal of this project is to develop a magnetic resonance imaging (MRI) probe that can detect fibrogenesis, monitor disease progression and drug treatment response, and is safe for human use.

PI_NAMEs: HOFFMAN, VERA  (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: Adult;Affect;Affinity;Age;Alcoholic steatohepatitis;Aldehydes;analog;Animal Model;Benign;bile duct;Binding;Binding Proteins;biomarker panel;Biopsy;Blood;Cardiotoxicity;chelation;Cholestasis;chronic liver disease;Cicatrix;Cirrhosis;clinical development;Clinical Trials;Collagen;Complex;Contrast Media;cost effective;crosslink;Detection;Development;Diagnosis;Diet;dietary;Disease;Disease Progression;Dissociation;Dose;Drug Kinetics;early detection biomarkers;Early Diagnosis;Excretory function;Extracellular Protein;Fatty Liver;fibrogenesis;Fibrosis;Gadolinium;genotoxicity;Goals;Health Care Costs;Healthcare;Hepatic Fibrogenesis;Hepatocyte;Histologic;Human;Image;imaging probe;Immune;In Vitro;in vivo;Inflammation;Kinetics;lead candidate;lead optimization;Left;Libraries;lifestyle intervention;Ligation;Link;lipophilicity;Liver;Liver diseases;Liver Failure;Liver Fibrosis;Magnetic Resonance;Magnetic Resonance Elastography;Magnetic Resonance Imaging;Manganese;Maximum Tolerated Dose;Metabolism;Methods;Microsomes;Modeling;molecular modeling;Molecular Target;Monitor;Monkeys;mouse model;Mus;Muscle;Noise;non-alcoholic fatty liver disease;Non-Invasive Detection;non-invasive imaging;nonalcoholic steatohepatitis;Onset of illness;Patients;Pharmacotherapy;Phase;preclinical development;predictive marker;Prevalence;Primary carcinoma of the liver cells;Primary Malignant Neoplasm of Liver;primary sclerosing cholangitis;Process;Proteins;Rattus;Reporter;Resolution;Safety;Sampling;screening;Series;Serum;Structure-Activity Relationship;Techniques;Technology;Tissues;Toxic effect;Toxicokinetics;Toxicology;Treatment Efficacy;treatment response;ultrasound;uptake;Western World

PROJECT_TITLE: Fibrogenesis Targeted Manganese Based MRI Contrast Agent