ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Biomedical Imaging;Clinical Research;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences;Nutrition;Pediatric;Prevention

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative Patients with long-chain-3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency develop a unique retinal degeneration that progresses over the lifespan leading to significant vision loss and decreased quality of life. There are currently no treatments for this genetic retinal disorder and the underlying etiology is not fully understood. We propose conducting a detailed prospective natural history study among 44 subjects with LCHAD/TFP to help elucidate retinal pathology, describe the clinical and environmental factors associated with vision loss and estimate the time course and rate of retinal decline across various ages.

PI_NAMEs: GILLINGHAM, MELANIE B (contact)

PROGRAM_OFFICER_NAME: PARISI, MELISSA

PROJECT_TERMS: 3-Hydroxyacyl-CoA dehydrogenase;Acute;acylcarnitine;Address;Affect;Age;age stratification;Alleles;Angiography;Atrophic;Blindness;Blood;Cardiomyopathies;Cell Culture Techniques;Cessation of life;Child;Clinical;Coenzyme A;cohort;Complication;Data;Development;Diagnosis;Diet therapy;Disease;DNA Sequence Alteration;Dropout;Early Diagnosis;Early treatment;Enrollment;Environmental Risk Factor;Etiology;fatty acid oxidation;Fatty Acids;FDA approved;Frequencies;Functional disorder;Future;gene therapy;Genetic;Genotype;Germ Cells;Goals;Histopathology;Hospitalization;human old age (65+);Hypoglycemia;Image;Imaging Techniques;in vivo;Infant;infant morbidity/mortality;Infant Mortality;Institution;Lactic Acidosis;Leber's amaurosis;life span;loss of function;mathematical model;Measures;Mediating;Metabolic;Metabolic Control;Mitochondria;Molecular;Multimodal Imaging;Mutation;Natural History;Neonatal Screening;Neural Retina;novel;Optical Coherence Tomography;Oxidoreductase;Pathology;Patient Outcomes Assessments;Patients;Perimetry;Phenotype;photoreceptor degeneration;Photoreceptors;Physiological;Plasma;preservation;prevent;Prevention;Production;prospective;Protein Deficiency;Quality of life;rate of change;Reporting;Retina;retinal damage;Retinal Degeneration;Retinal Diseases;Retinal gene therapy;retinal imaging;RPE65 protein;Secondary to;Structure;Structure of retinal pigment epithelium;Time;treatment trial;Vision;Visual Acuity

PROJECT_TITLE: The Natural History of LCHAD Retinopathy

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-GGG-P(02)M]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: SAN FRANCISCO

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PEDIATRICS

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE We combine proteomic and functional studies in vitro and in vivo to identify novel vulnerabilities for oncogenic KRAS. Preliminary data supports a synthetic effect of loss of RhoA and RAP1GDS1 in KRAS driven lung cancer. Here we will use proteomics, cell biology, biochemistry and in vivo studies in PDX and GEM models to understand the interaction of these two proteins and why they are required in cells carrying oncogenic KRAS mutations.

PI_NAMEs: JACKSON, PETER KENT;SWEET-CORDERO, ERIC ALEJANDRO (contact)

PROGRAM_OFFICER_NAME: GHOSH-JANJIGIAN, SHARMISTHA

PROJECT_TERMS: 3-Dimensional;Adenocarcinoma;Affinity Chromatography;AGFG1 gene;Apical;Apoptosis;Automobile Driving;Binding;Biochemical;Biochemistry;Biological Models;Biophysics;bronchial epithelium;Cancer Etiology;candidate validation;cell growth;Cell Line;Cell membrane;Cell Proliferation;Cells;Cellular biology;Cessation of life;Collaborations;combinatorial;Complex;Coupled;CRISPR/Cas technology;Data;Dependence;design;drug discovery;Endosomes;Epithelial Cells;Exons;experience;experimental study;Family;Family member;Frequencies;functional genomics;Funding;gene interaction;Genes;Genetic;genetic analysis;genetic approach;Genetically Engineered Mouse;Genomics;Genotype;Goals;Grant;Growth;Guanosine Triphosphate;Guanosine Triphosphate Phosphohydrolases;Human;human model;In Vitro;in vivo;inhibitor;innovation;Knock-out;knockout gene;KRAS oncogenesis;KRAS2 gene;Laboratories;Libraries;Link;Lung Adenocarcinoma;Malignant neoplasm of lung;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;Membrane;Modeling;Molecular;Molecular Chaperones;Monomeric GTP-Binding Proteins;mouse model;Mus;mutant;Mutate;Mutation;National Cancer Institute;Non-Small-Cell Lung Carcinoma;novel;novel therapeutic intervention;Oncogenic;overexpression;Pathway interactions;patient derived xenograft model;Phenotype;Physicians;Pre-Clinical Model;prenylation;Principal Investigator;Proliferating;Protein Analysis;Protein Family;Protein Isoforms;protein protein interaction;Proteins;Proteomics;rab GTP-Binding Proteins;RAS genes;recruit;Regulation;rho;Role;Scientist;Series;Shotguns;Signal Pathway;Signal Transduction;Specificity;Testing;Therapeutic;Therapeutic Effect;therapeutically effective;Tissues;Xenograft procedure

PROJECT_TITLE: Identifying and Targeting Mechanisms for Membrane Signaling in Human Cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OBT-K(02)M]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Pediatric;Social Determinants of Health

ORG_CITY: EAST LANSING

ORG_DEPT: PSYCHOLOGY

ORG_NAME: MICHIGAN STATE UNIVERSITY

ORG_STATE: MI

PHR: Project Narrative Neighborhood disadvantage (e.g., poverty and exposure to violence) is a robust indicator of youth adjustment difficulties across most domains of development, yet there are youth who thrive despite significant neighborhood adversity. This project investigates: (1) how resilience changes as youth reach important developmental milestones and freely explore their environments, (2) whether these developmental changes differ by resilience domain (psychiatric, social, emotional, academic), and (3) how warm and involved parenting as well as neighborhood protective factors might shape their development. In doing so, the proposed project can identify specific and modifiable protective factors that promote resilience to chronic neighborhood risk.

PI_NAMEs: SHEWARK, ELIZABETH  (contact)

PROGRAM_OFFICER_NAME: ESPOSITO, LAYLA E

PROJECT_TERMS: Adolescence;Adolescent Behavior;Adolescent Development;Adult;Area;Award;career;Characteristics;Child;Child Development;Child Rearing;Childhood;Chronic;Church;cognitive ability;cognitive reappraisal;Competence;Data;Development;developmental psychology;early childhood;emerging adulthood;Emotional;Environment;Exclusion;Family;family influence;Goals;Green space;Growth;improved;Informal Social Control;Interdisciplinary Study;intervention program;Knowledge;Lead;life span;Link;Literature;Maintenance;Measurement;Methodology;Methods;middle childhood;Modeling;Nature;neighborhood disadvantage;Neighborhoods;Outcome;Pathway interactions;Personal Satisfaction;Pharmacy facility;Phase;physical conditioning;Play;Populations at Risk;Positioning Attribute;Poverty;promote resilience;protective factors;Research;Research Personnel;resilience;Resources;Risk;Role;Scholars Program;Schools;Science;Shapes;skills;social;social skills;System;Techniques;Testing;Time;Training;Transportation;violence exposure;Work;Youth

PROJECT_TITLE: The Development of Youth Resilience to Neighborhood Disadvantage

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Biobehavioral and Behavioral Sciences Study Section[CHHD-H]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Autism;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric;Rare Diseases

ORG_CITY: Charlestown

ORG_NAME: MGH INSTITUTE OF HEALTH PROFESSIONS

ORG_STATE: MA

PHR: Comorbid Childhood Apraxia of Speech (CAS), a motor speech disorder affecting speech movement planning, may be one factor limiting the ability of some minimally verbal children with autism to acquire spoken language. This project aims to identify a cohort of minimally verbal children who meet criteria for autism and CAS and, using kinematic analysis of speech, to quantify how CAS affects speech movement consistency and precision. The relationship of speech movement parameters, intelligibility, and signs of CAS will be investigated in order to identify movements that are both disordered and intelligibility-reducing. These procedures will be used to create a set of mono- and bisyllabic stimuli, unique to each participant, that can reveal whether CAS-specific treatment, appropriately modified for minimally verbal children with autism, improves their speech.

PI_NAMEs: CHENAUSKY, KAREN V (contact)

PROGRAM_OFFICER_NAME: KOPF, LISA MARIE

PROJECT_TERMS: Acoustics;Address;Affect;Age;Aggressive behavior;Area;Auditory;autism spectrum disorder;autistic children;Characteristics;Child;Clinical;clinical practice;Clinical Research;clinical translation;cohort;comorbidity;Cues;Data;Development;Developmental apraxia;Diagnosis;Disease;effectiveness evaluation;experimental study;Face;Goals;Impairment;improved;innovation;Intervention;Investigation;kinematics;Language;language outcome;Leadership;Mentorship;Methods;minimally verbal;Motor;motor control;motor learning;Movement;movement analysis;Movement Disorders;neuromuscular;novel;Outcome Measure;Output;Participant;phonology;Population;Procedures;Production;Research;Self-Injurious Behavior;Series;Severities;Speech;Speech Disorders;Speech Intelligibility;Stimulus;System;Tactile;Target Populations;targeted treatment;Testing;Training;Work

PROJECT_TITLE: Identifying and Treating Childhood Apraxia of Speech in Minimally Verbal Children with Autism

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


NIH_SPENDING_CATS: Cancer;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetics;Precision Medicine;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: WISTAR INSTITUTE

ORG_STATE: PA

PHR: Project Narrative Individuals with DNA mismatch repair (MMR) gene inactivation have up to three orders of magnitude of increased risk of developing colorectal cancer and other malignancies with microsatellite instability (MSI). However, the genetic basis and underlying mechanisms that determine the rate of disease penetrance is poorly understood. This project will identify the mechanism by which MSI-derived target gene mutation drives CRC tumorigenesis and progression through the centrosome pathway and potentially identify new target to predict and/or treat MSI-associated malignancies.

PI_NAMEs: LIANG, CHENGYU  (contact)

PROGRAM_OFFICER_NAME: OKANO, PAUL

PROJECT_TERMS: Address;Adjuvant Chemotherapy;Animal Model;Appearance;Autophagocytosis;Behavior;Biochemistry;Biological Assay;Cancer Etiology;cancer genetics;Cancer Patient;carcinogenesis;Cell division;cell motility;cell transformation;Cells;Centrosome;Centrosome Pathway;Clinic;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Collaborations;Colon;colon cancer patients;colon carcinogenesis;Colorectal Cancer;colorectal cancer treatment;Development;Disease;DNA;Dominant-Negative Mutation;Down-Regulation;early onset colorectal cancer;effectiveness evaluation;Epithelium;Evolution;Failure;Fluorouracil;Frameshift Mutation;Gene Mutation;Genes;Genetic;Goals;Hereditary Nonpolyposis Colorectal Neoplasms;Human;Image;in vivo;in vivo evaluation;Individual;Induced Mutation;inhibition of autophagy;innovation;Invaded;Knock-in;Knowledge;Lesion;Link;live cell imaging;Lymphocytic Infiltrate;Malignant - descriptor;Malignant Neoplasms;Mediating;Microsatellite Instability;Microsatellite Repeats;Mismatch Repair;Mismatch Repair Deficiency;Mismatch Repair Gene Inactivation;Modeling;Modification;Molecular;Molecular Biology;mortality;Mucinous Differentiation;multidisciplinary;Mus;Mutagenesis;mutant;mutant mouse model;Mutation;Mutation Detection;novel;Oncogenes;Organoids;Pathogenesis;Pathologist;Pathway interactions;Patients;Penetrance;personalized medicine;Pharmaceutical Preparations;Phenotype;Physiological;Play;predictive marker;Productivity;Prognostic Marker;Proteins;Qualifying;Recurrence;Research Personnel;Risk;Risk Marker;Role;single molecule;Structure;System;therapeutic target;three dimensional cell culture;Translations;tumor;tumor initiation;tumor progression;Tumor Suppressor Proteins;Tumor-Associated Process;tumorigenesis;Validation

PROJECT_TITLE: A cancer-derived truncating mutation in disease penetrance and progression of MSI CRC

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: STANFORD

ORG_DEPT: BIOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative  Spinal cord projecting neurons in the Rostral Ventromedial Medulla (RVMSC) plays active roles in chronic pain, but its underlying circuitry and molecular mechanisms are largely unknown. We propose to identify monosynaptic inputs and molecular changes that engage RVMSC neurons in chronic mechanical pain. Our proposed studies will help identify novel targets for non-opioid treatment of chronic pain.

PI_NAMEs: CHEN, XIAOKE  (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Adult;Affect;American;Analgesics;Automobile Driving;Brain;Brain Stem;Calcium;Cell Nucleus;Cells;cellular targeting;Chronic;chronic pain;chronic pain management;Classification;Cognitive;Dependovirus;Development;Enterobacteria phage P1 Cre recombinase;experimental study;Genes;Genetic;global health;Individual;Infusion procedures;Injury;interest;knock-down;Knock-in Mouse;Lateral;Maintenance;mechanical allodynia;mechanical drive;Mechanics;Molecular;Moods;Morphine;Mus;mutant;nerve injury;Neural Pathways;Neurons;Neuropeptides;Nociception;Nociceptive Stimulus;non-opioid analgesic;novel;Opioid;opioid epidemic;Opioid Receptor;Overdose;Pain;painful neuropathy;Pathway interactions;Persistent pain;Play;prevent;rabies viral tracing;Rabies virus;receptor;recruit;response;RiboTag;Role;spared nerve;Spinal Cord;superior colliculus Corpora quadrigemina;Testing;Therapeutic;tissue injury;tool;transmission process;Viral

PROJECT_TITLE: Circuitry and Molecular Mechanisms for Descending Pain Facilitation

STUDY_SECTION: NPI

STUDY_SECTION_NAME: Neurobiology of Pain and Itch Study Section [NPI]


ADMINISTERING_IC: AR

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Biomedical Imaging;Physical Injury - Accidents and Adverse Effects;Physical Rehabilitation;Regenerative Medicine;Rehabilitation

ORG_CITY: EUGENE

ORG_NAME: UNIVERSITY OF OREGON

PHR: PROJECT NARRATIVE Complex musculoskeletal extremity trauma is associated with high complication rates and poor rates of functional recovery. The proposed work is significant because effective integration of local regenerative treatment strategies and rehabilitation protocols has the potential to reduce surgical revision procedures and may be essential to achieve full restoration of limb function following severe musculoskeletal trauma.

PI_NAMEs: GULDBERG, ROBERT E (contact)

PROGRAM_OFFICER_NAME: MARQUITZ, ARON

PROJECT_TERMS: Acceleration;Accidents;Area;Biocompatible Materials;Biological;Biological Markers;Biological Response Modifier Therapy;biomarker identification;biomechanical test;Biomechanics;Blood Vessels;bone;Bone Regeneration;clinical practice;cohort;Cohort Studies;combat;Complex;Complication;Coupled;Coupling;Data;Defect;design;disability;Dose;Elements;Environment;evidence base;Experimental Designs;Feedback;Femur;functional improvement;functional outcomes;Functional Regeneration;functional restoration;Funding;Gait;gait examination;Goals;healing;Histology;implanted sensor;improved;Individual;Injury;instrument;Interdisciplinary Study;Knowledge;limb injury;Limb structure;Lower Extremity;male;Maps;Measurement;Measures;mechanical signal;mechanical stimulus;Mechanics;Methodology;microCT;Modeling;Multivariate Analysis;Muscle;muscle regeneration;Musculoskeletal;musculoskeletal injury;Natural regeneration;new technology;non-invasive monitor;novel;Outcome;Pain;Patients;Physical Rehabilitation;Physicians;Physiological Processes;Pre-Clinical Model;predictive marker;predictive modeling;Procedures;prospective;Prospective Studies;Protocols documentation;quadriceps muscle;radiological imaging;Rattus;Recovery of Function;regeneration model;regenerative;regenerative rehabilitation;regenerative treatment;Regimen;Rehabilitation therapy;repaired;response;response biomarker;restoration;sample fixation;Second Look Surgery;sensor;Severities;sex;skeletal;skills;Testing;Time;tissue regeneration;Tissues;Translating;Trauma patient;Treatment outcome;Treatment Protocols;treatment strategy;Variant;Weight-Bearing state;wireless;wireless implant;Women's cohort;Work;X-Ray Computed Tomography

PROJECT_TITLE: Regenerative Rehabilitation of Complex Musculoskeletal Injuries

STUDY_SECTION: SBSR

STUDY_SECTION_NAME: Skeletal Biology Structure and Regeneration Study Section[SBSR]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: WEST LAFAYETTE

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: The proposal is to optimize a newly developed large-scale deep-brain neurophotonic interface platform. A key advance of this platform is that it can enable ~1000x tissue access volume than existing imaging modalities for deep brain imaging. Through further optimization and engineering innovation, we will make the platform broadly useful for neuroscience studies of mammalian brain.

PI_NAMEs: CUI, MENG  (contact);YANG, GUANG

PROGRAM_OFFICER_NAME: TALLEY, EDMUND M

PROJECT_TERMS: Action Potentials;Address;Adopted;Animals;Area;Behavior;Benchmarking;Blood capillaries;Brain;Brain imaging;Brain region;brain tissue;Calcium;Calcium Signaling;Calibration;Cells;Complement;Complex;Computer software;design;Development;Diameter;Electrodes;Engineering;experimental study;fabrication;Fiber;Freedom;Genetic;Glass;Goals;Head;Image;imaging modality;imaging probe;imaging system;Imaging Techniques;in vivo;innovation;Light;light weight;Liquid substance;Location;Mammals;Measurement;Mechanics;meter;Methods;millimeter;Miniaturization;miniaturize;miniaturized device;Modeling;Molecular;multiphoton microscopy;Mus;neural;neural circuit;Neurons;Neurosciences;Noise;operation;Operative Surgical Procedures;optical fiber;optical imaging;Optics;optogenetics;Performance;Photometry;Procedures;Publications;Refractive Indices;Resolution;Sampling;Side;Signal Transduction;Structure;success;Surface;symposium;System;Techniques;Technology;technology development;Thinness;Tissues;Translating;two-photon;web site;Work

PROJECT_TITLE: Optimization of Clear Optically Matched Panoramic Access Channel Technique (COMPACT) for large-scale deep-brain neurophotonic interface


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Brain Disorders;Huntington's Disease;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE Inflammation is linked to several CNS diseases, including Huntington’s disease (HD), and cyclooxygenases (COX) play a key role in the inflammatory process, most notably the isoform COX-2. Despite the fact that genetic testing is available to diagnose HD, there remains a critical need to visualize early-stage biological changes in the living brain that occur at disease onset. A COX-2-selective radiotracer for use in positron emission tomography will enable study of disease mechanisms at the molecular level and provide an objective clinical marker to measure therapeutic efficacy in the living HD brain.

PI_NAMEs: HOOKER, JACOB M. (contact);STEVENS, BETH ANN

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: Acceleration;Acute;Affect;Affinity;Automobile Driving;Autopsy;Autoradiography;autosome;Basal Ganglia;Binding;Binding Proteins;Biochemical;Biochemistry;Biological;Biological Assay;blood-brain barrier penetration;Brain;Brain Diseases;brain tissue;Carbon;Cells;Central Nervous System Diseases;Cessation of life;Clinical Markers;Coxibs;cyclooxygenase 1;cyclooxygenase 2;cytokine;Data;Degenerative Disorder;density;design;Development;Diagnosis;Diagnostic tests;Disease;disease mechanisms study;disease model;Disease Progression;Drug Kinetics;Early Intervention;Enzymes;Event;Evoked Potentials;Exhibits;Fluorine;Functional disorder;Generations;Genes;genetic testing;glial activation;Globus Pallidus;Goals;Grant;Human;Huntington Disease;Huntington gene;Image;image translation;imaging agent;Imaging Device;Immune;immune activation;Immunohistochemistry;Impaired cognition;improved;In Vitro;in vivo;in vivo imaging;in vivo Model;Inflammation;Inflammatory;Inherited;insight;Interdisciplinary Study;Involuntary Movements;Kinetics;Lead;Ligands;Link;Measurement;Measures;Mediating;Microglia;Molecular;Monitor;motor disorder;mouse model;nanomolar;Neurobehavioral Manifestations;Neurodegenerative Disorders;neuroinflammation;neuron loss;neuropathology;novel;novel therapeutics;Onset of illness;paralogous gene;Pathogenesis;Pathologic;Pathology;Pathway interactions;Patients;pharmacologic;Play;Positron-Emission Tomography;Pre-Clinical Model;prevent;Process;Prognosis;Prostaglandin-Endoperoxide Synthase;Prostaglandins;Protein Isoforms;Proteins;psychiatric symptom;radiochemical;Radiolabeled;radiotracer;Research;response;Rodent;Role;Signal Transduction;success;Symptoms;Synapses;synaptic pruning;therapeutically effective;Tissues;tool;Treatment Efficacy;treatment strategy;Up-Regulation;uptake;Visualization

PROJECT_TITLE: COX-2-Selective PET Imaging as an Onset Marker of Huntington's Disease

STUDY_SECTION: IPCA

STUDY_SECTION_NAME: Imaging Probes and Contrast Agents Study Section[IPCA]


ORG_CITY: CHICAGO

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative: We propose to develop and validate Drosophila and mouse models of PNPO deficiency. These studies will help to predict treatment outcomes for epilepsy due to PNPO deficiency, and elucidate the underlying biochemical and neural mechanisms.

PI_NAMEs: ZHUANG, XIAOXI  (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: Adult;Affect;Alleles;Anatomy;Animal Model;anti-epileptic agents;Biochemical;Biological Assay;Birth;Blood - brain barrier anatomy;Brain;cell type;Chemicals;Child;Coenzymes;cofactor;cost effective;Data;Defect;Development;Diet;dietary;Dominant-Negative Mutation;Dopamine;Drosophila genus;early onset;Environment;Environmental Risk Factor;Enzymes;Epilepsy;epileptic encephalopathies;Essential Genes;fly;Functional impairment;gamma-Aminobutyric Acid;gene interaction;Genes;Genetic;genetic manipulation;Histamine;Homologous Gene;Human;human disease;in vivo;International;knock-down;Knock-in;Knock-in Mouse;Knock-out;Larva;life span;Liver Cirrhosis;loss of function mutation;Malnutrition;Modeling;mouse model;Mus;mutant;Mutation;Neonatal;neural circuit;neurochemistry;neuromechanism;Neurons;Neurotransmitters;Newborn Infant;Other Genetics;Patients;Phenotype;Point Mutation;Prediction of Response to Therapy;Proteins;Pupa;Pyridoxal Phosphate;Pyridoxamine;Pyridoxine 5 Phosphate Oxidase;Reporting;Role;Seizures;Serotonin;Severities;System;Testing;transgene expression;Treatment outcome;Vitamin B 6 Deficiency;Vitamin B6

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Clinical Research;Dental, Oral, and Craniofacial Disease;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Rehabilitation

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: NORTHEASTERN UNIVERSITY

PHR: PROJECT NARRATIVE Emerging retrospective data are available linking neonatal sucking to subsequent communication development; however, more prospective and quantitative studies are needed to elucidate the details of this relationship in more detail. The goals of the proposed research are: to establish typical patterns of NNS across infants born full-term (> 37 weeks’ gestation) and moderate to late preterm (born at 32-37 weeks’ gestation) in the first year of life (Aim 1), and to determine the ability of NNS, sampled in infancy, to predict subsequent speech development across patient populations until age three (Aim 2). This study provides an unprecedented level of power in identifying the connection between neonatal sucking and subsequent speech emergence, and results generated will create a paradigm shift in how clinicians approach feeding and speech therapies.

PI_NAMEs: ZIMMERMAN, EMILY  (contact)

PROJECT_TERMS: 37 weeks gestation;Acoustics;Address;Age;Age Months;Area;Articulation;Assessment tool;Behavior;Central Nervous System;Characteristics;Child;Childhood;clinically relevant;Communication;computerized data processing;critical period;Custom;Data;Data Analyses;Data Collection;Development;Developmental Delay Disorders;Devices;Diagnostic;Disease;early childhood;Environment;Equipment and supply inventories;experience;feeding;Feeding Patterns;Frequencies;Future;Gestational Age;Goals;Home;infancy;Infant;innovation;Jaw;jaw movement;kinematics;Language;Life;Link;Lip structure;Longitudinal Studies;Measures;Methods;Motion;Motor;motor control;Neonatal;Neonatal Brain Injury;neonatal period;Nervous System Physiology;neural;non-nutritive sucking;Nutrient;Optics;oral motor;Outcome;patient population;Pattern;Physiology;portability;Premature Infant;Production;prospective;Reporting;Research;Resources;Risk;Sampling;Shapes;Signal Transduction;skills;spatiotemporal;Speech;Speech Development;Speech Therapy;Standardization;sucking;Testing;Time;timeline;tool;Visualization;Voice

PROJECT_TITLE: Using Infant Non-Nutritive Suck as a Diagnostic Measure of Future Speech Function

STUDY_SECTION: MFSR

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Chronic Obstructive Pulmonary Disease;Lung;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Tobacco;Tobacco Smoke and Health

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: NARRATIVE Chronic obstructive pulmonary disease (COPD), a major public health burden, can result from defective lung repair/renewal. The primary goal of this project is to define the molecular mechanisms by which FAM13A, a well-replicated gene associated with COPD in genome-wide association studies (GWAS) and enriched in lung epithelial progenitors, responds to extracellular growth factor cues and transduces the signal to intrinsic metabolic controls on the repair capacity of lung epithelial progenitors. This novel concept may shed fresh insights into the biological mechanisms on COPD and pinpoint to new treatment targeting metabolic controls on lung epithelial progenitors.

PI_NAMEs: ZHOU, ANNY XIAOBO (contact)

PROGRAM_OFFICER_NAME: LU, QING

PROJECT_TERMS: 5'-AMP-activated protein kinase;Address;airway obstruction;Alveolar;alveolar epithelium;beta catenin;Binding;Biochemical;Biological;Biological Assay;Cause of Death;Cell Differentiation process;cell growth;Cell Line;cell preparation;Cell Proliferation;Cell Separation;Cells;Chronic Obstructive Pulmonary Disease;cigarette smoking;Clustered Regularly Interspaced Short Palindromic Repeats;Coculture Techniques;Coupled;Couples;Coupling;Cues;Data;design;Development;Energy Supply;Epithelial Cells;epithelial stem cell;Exposure to;extracellular;Family;Fatty Acids;Funding;Genes;Genetic;Genetic Determinism;genome editing;genome wide association study;Glycolysis;Goals;Growth;Growth Factor;Hematopoietic stem cells;Homeostasis;Human;improved;In Vitro;in vivo;inhibitor;injury and repair;insight;Intestines;Knock-in Mouse;Knock-out;Label;lipid metabolism;Lung;Lung Capacity;Lung Diseases;lung injury;lung regeneration;lung repair;Mediating;meetings;member;Metabolic;Metabolic Control;Metabolism;Mitochondria;Modeling;Molecular;mouse model;multicatalytic endopeptidase complex;Mus;Natural regeneration;nerve stem cell;novel;Organ;Organoids;overexpression;Pathway interactions;Patients;Pharmacological Treatment;Phenotype;Phosphorylation;Phosphorylation Inhibition;Predisposition;Process;Production;Proliferating;Proteins;Public Health;Publishing;Pulmonary Emphysema;Regulation;repaired;Repression;Resistance;risk variant;sensor;Signal Pathway;Signal Transduction;Smoke;smoking exposure;Sorting;Spirometry;stem cells;stemness;Tamoxifen;Testing;Therapeutic;tissue stem cells;treatment strategy;ubiquitin-protein ligase;Ubiquitination;WNT Signaling Pathway;Work

PROJECT_TITLE: Metabolic Control of Stemness in lung epithelial progenitors by FAM13A

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Clinical Research;Disability Research;Multiple Sclerosis;Neurodegenerative;Neurosciences

ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: Project Narrative With the exception of head trauma, diseases of myelin are the major cause of permanent neurological disability in young adults. Myelin insulates nerve fibers and facilitates fast communication between nerve cells. Myelin also provides support that is essential for nerve fiber survival. Neurological disability in myelin disease results from nerve fiber death. This proposal investigates how nerve fibers die as a result of myelin disease. Our studies will identify new ways to treat diseases of myelin and reduce the progression of neurological disability in individuals with myelin disease.

PI_NAMEs: TRAPP, BRUCE D (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Affect;Alzheimer's Disease;Amyotrophic Lateral Sclerosis;Animal Model;autism spectrum disorder;Axon;axonal degeneration;axoplasm;Brain;Central Nervous System;Cessation of life;Communication;Communities;Coupling;Craniocerebral Trauma;Data;Demyelinating Diseases;Demyelinations;Development;Disease;Funding;Gene Expression;Gene Proteins;Hereditary Disease;human disease;Immune;Individual;Inflammatory;Inherited;Laboratories;Mediating;Mental Depression;Metabolic;Mitochondria;Multiple Sclerosis;Myelin;Myelin Proteins;National Institute of Neurological Disorders and Stroke;Nerve Degeneration;Nerve Fibers;Neurological disability;Neurons;neuroprotection;new therapeutic target;novel therapeutics;Pathogenesis;Pathology;Play;prevent;Property;remyelination;Research;Risk Factors;risk variant;Role;Schizophrenia;Structure;Synapses;white matter;young adult

PROJECT_TITLE: Pathogenesis of Neurological Disability in Primary Diseases of Myelin


NIH_SPENDING_CATS: Antimicrobial Resistance;Biotechnology;Cystic Fibrosis;Genetics;Infectious Diseases;Lung;Orphan Drug;Pneumonia;Pneumonia and Influenza;Rare Diseases

ORG_CITY: HANOVER

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: PROJECT NARRATIVE Our research, aimed at understanding how let-7b inhibits bacterial growth and biofilm formation, may lead to the identification of new therapeutic targets that can be manipulated to eliminate chronic P. aeruginosa lung infections in people with cystic fibrosis, chronic obstructive pulmonary disease, and pneumonia.

PI_NAMEs: STANTON, BRUCE A. (contact)

PROGRAM_OFFICER_NAME: LU, JINING

PROJECT_TERMS: Acute;Acute Respiratory Distress Syndrome;Adult;Aftercare;American;Anti-Inflammatory Agents;Antibiotic Resistance;Antibiotics;Bacterial Infections;Bacterial Pneumonia;beta-Lactamase;beta-Lactams;bioinformatics tool;Biological Assay;bronchial epithelium;Bronchiectasis;Cause of Death;Cell secretion;Chronic;Chronic Obstructive Pulmonary Disease;Clinical;Clinical Trials;Coculture Techniques;Code;Cystic Fibrosis;cystic fibrosis infection;cystic fibrosis patients;Data;Development;Diabetes Mellitus;Disease Management;efflux pump;Epithelial Cells;Event;extracellular vesicles;Family;Film;Fluoroquinolones;Gene Expression;Genes;Goals;Growth;Human;Immune response;improved;Individual;Inflammation;Inflammatory;inflammatory milieu;Liquid substance;Lung;Lung infections;Mass Spectrum Analysis;member;Messenger RNA;Microbe;Microbial Biofilms;MicroRNAs;Modeling;new therapeutic target;novel;novel strategies;Nucleotides;Obesity;opportunistic pathogen;Partner in relationship;pathogen;Patient-Focused Outcomes;Patients;Persons;Pharmaceutical Preparations;Pneumonia;Predisposition;Proteins;Pseudomonas;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Pulmonary Cystic Fibrosis;Research;resistant strain;RNA analysis;Techniques;Testing;transcriptome sequencing;uptake;Western Blotting;Work

PROJECT_TITLE: Let-7b in Extracellular Vesicles Secreted by Bronchial Epithelial Cells Increases the Antibiotic Sensitivity of Pseudomonas

STUDY_SECTION: LCMI

STUDY_SECTION_NAME: Lung Cellular, Molecular, and Immunobiology Study Section[LCMI]


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Lung;Orphan Drug;Patient Safety;Pediatric;Pulmonary Hypertension;Rare Diseases

ORG_CITY: DURHAM

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Pulmonary Arterial Hypertension (PAH) contributes to high morbidity and death in children with different types of heart, lung or systemic diseases. Despite advances in the development of PAH-targeted drug therapies in adults, there have been very few studies in children regarding safety, effectiveness and the optimal strategies for using these drugs in infants and children with PAH. Using a highly interactive and well-established network of experienced pulmonary hypertension specialists at multiple academic sites, we propose to determine whether early treatment with a combination of medicines will cause greater and more sustained clinical improvement in children with PAH when compared with monotherapy with sildenafil alone.

PI_NAMEs: CHAKRABORTY, HRISHIKESH  (contact);YENOKYAN, GAYANE ;ZIMMERMAN, KANECIA OBIE

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: 18 year old;Address;Adherence;Adult;Age;bosentan;Caring;Case Series;Cessation of life;Child;Child Care;Childhood;Clinical;clinical care;Clinical Management;clinical practice;Clinical Research;Clinical Trials;Clinical Trials Data Monitoring Committees;Collaborations;Combination Drug Therapy;Combined Modality Therapy;Communication;Communities;Data;Data Collection;Data Coordinating Center;data dissemination;data management;Data Set;Decision Making;design;Development;Diagnosis;Disease;Disease Progression;Drug usage;Early treatment;Effectiveness;efficacy evaluation;electronic data capture system;Electronics;Endothelin Receptor Antagonist;Ensure;Evaluation;evidence base;Exercise Tolerance;experience;follow-up;functional outcomes;functional status;health management;Heart Diseases;hemodynamics;improved;Infant;Informed Consent;Infrastructure;inhibitor;Leadership;Lung;Lung Diseases;Manuscripts;Measures;Medicine;meetings;Modernization;Monitor;Morbidity - disease rate;mortality;multidisciplinary;Nature;Newly Diagnosed;novel;novel therapeutics;Online Systems;operation;optimal treatments;Oral;Outcome;patient privacy;Patients;Pharmacotherapy;Phosphodiesterase Inhibitors;phosphodiesterase V;predictive modeling;Preparation;primary endpoint;programs;Protocols documentation;Public Health;Publications;pulmonary arterial hypertension;Pulmonary Heart Disease;Pulmonary Hypertension;Pulmonary Vascular Resistance;Quality of life;Randomized;randomized, clinical trials;Randomized, Controlled Trials;Reporting;Reproducibility;Research;Research Institute;right ventricular failure;Risk;Role;Safety;Scheme;secondary endpoint;Services;sildenafil;Site;Specialist;standard of care;Statistical Data Interpretation;success;Systemic disease;targeted treatment;Testing;Therapeutic;Time;treatment strategy;Universities;web site;Work;World Health Organization

PROJECT_TITLE: 2/2 Kids MoD PAH Trial:  Mono- vs. Duo-Therapy for Pediatric Pulmonary Arterial Hypertension-DCC


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Drug Abuse (NIDA only);Mental Health;Methamphetamine;Neurosciences;Opioids;Prevention;Stimulant Use and Misuse;Substance Misuse

ORG_CITY: GAINESVILLE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE    The  public  health  relevance  of  the  proposed  research  is  two- fold:  (1)  The  work  is  expected  to  identify  novel  therapeutic targets for the prevention of substance abuse relapse triggered by drug- associated memory that may  also  be  applicable  to  other  forms  of  aberrant  amygdala- dependent  memory,  such  as  post- traumatic  stress  disorder.  (2)  This  work  is  further  expected  to  profoundly  impact  our  fundamental  understanding  of  the  mechanisms  governing  amygdala  plasticity.  Taken  together,  this  will  significantly  contribute  to  the  missions  of  both NIDA and NIMH.

PI_NAMEs: MILLER, COURTNEY A (contact);RUMBAUGH, GAVIN R

PROGRAM_OFFICER_NAME: SATTERLEE, JOHN S

PROJECT_TERMS: Actins;Address;Amphetamines;Amygdaloid structure;AODD relapse;Association Learning;Behavior;Behavior Therapy;Brain;Brain region;cell cortex;Cell Culture Techniques;Clinical;Cocaine;Cytoskeletal Modeling;Cytoskeleton;Data;Dendritic Spines;depolymerization;Development;Dopamine;drug abuse vulnerability;drug of abuse;Drug usage;fear memory;Food;Funding;Genetic;Heroin;Hippocampus;Image;in vivo;Individual;inhibitor;innovation;Investigation;Knowledge;Learning;Literature;Memory;Memory impairment;Mental disorders;Methamphetamine;methamphetamine effect;Methamphetamine use disorder;methamphetamine user;Mission;Morphine;Motility;Motivation;Myosin ATPase;Myosin Type II;National Institute of Drug Abuse;National Institute of Mental Health;Nature;neural circuit;Neuromodulator;Neuromodulator Receptors;Neurons;new therapeutic target;Nicotine;non-muscle myosin;novel therapeutics;Opioid;opioid use;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;polymerization;Polymers;polysubstance use;Population;Post-Traumatic Stress Disorders;postsynaptic;Predisposition;Preparation;prevent;Proteins;public health relevance;recruit;Regulation;Relapse;relapse risk;Research;response;Retrieval;Rewards;Risk Factors;Role;Self Administration;Signal Transduction;Slice;Smoke;Specificity;Stimulant;stimulant abuse;Structure;substance abuse prevention;Synapses;Synaptic plasticity;Therapeutic;therapeutic target;Time;Tissues;Training;two-photon;United States National Institutes of Health;Vertebral column;Work

PROJECT_TITLE: Myosin II regulation of actin dynamics and the selective vulnerability of methamphetamine- and opioid-associated memory

STUDY_SECTION: MNPS

STUDY_SECTION_NAME: Molecular Neuropharmacology and Signaling Study Section[MNPS-M]


ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: This research is relevant to public health because it will analyze how a potent cellular regulator of gene expression controls molecular pathways and networks that contribute to epileptogenesis, the process turning a healthy brain into an epileptic brain. The identification and functional analysis of the protein networks that are regulated by the RNA-induced silencing complex after an epilepsy-precipitating event is aligned with NIH’s mission because it will increase fundamental knowledge of the molecular mechanisms underlying epileptogenesis, which, ultimately, could lead to the development of novel more potent therapeutic strategies for epilepsy.

PI_NAMEs: GROSS, CHRISTINA  (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: acquired epilepsy;Affect;Biological Assay;Brain;cell type;Cells;Chronic;Complex;Core Facility;Data;Development;Disease;Drug resistance;Epilepsy;Epileptogenesis;Event;excitotoxicity;Frequencies;Future;Gene Expression;gene network;Genes;Genetic;Goals;Immunoprecipitation;Impairment;improved;Induced Neurons;innovation;knock-down;Knowledge;Lead;Mediating;Messenger RNA;MicroRNAs;Mission;Modeling;Molecular;Molecular Target;mouse model;Mus;Nature;neuron loss;neuronal excitability;neuronal survival;neuroprotection;novel;Pathway Analysis;Pathway interactions;Pharmaceutical Preparations;Predisposition;prevent;Process;Protein Analysis;protein expression;Proteins;Public Health;recruit;Recurrence;Regulation;Regulator Genes;Research;Research Personnel;Ribosomes;RNA;RNA-Induced Silencing Complex;Rodent;Rodent Model;Role;Seizures;skills;Status Epilepticus;Testing;Therapeutic;therapeutic candidate;therapeutic miRNA;therapeutic target;transcriptome sequencing;Translating;Translations;translatome;treatment strategy;United States National Institutes of Health;Work

PROJECT_TITLE: Functional analysis of the microRNA-induced silencing complex in epilepsy

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: The relevance of this research to public health: This proposed research will provide insights into how the fungal pathogen Cryptococcus neoformans forms biofilms and coordinates their community behaviors. Despite the prevalence of microbial biofilms and their well-documented involvement in the majority of infectious diseases, little is known about biofilm formation in basidiomycetous fungi, including the major human fungal pathogen C. neoformans. Thus, findings from this exploratory research will fill an important gap of knowledge and provide a foundation for future investigation of the impact of biofilm regulation on fungal pathogenesis.

PI_NAMEs: LIN, XIAORONG  (contact)

PROGRAM_OFFICER_NAME: LOVE, DONA

PROJECT_TERMS: Adhesions;Affect;Ascomycota;Bacterial Adhesins;Basidiomycota;Behavior;Candida;Cell surface;Clinical;Communicable Diseases;Communication;Communities;Complex;congenic;Coupling;Cryptococcus;Cryptococcus neoformans;Environment;Farnesol;fast protein liquid chromatography;Foundations;fungus;Future;Gene Deletion;gene discovery;Gene Expression;Gene Targeting;Genes;Genetic;Goals;HIV/AIDS;Homologous Gene;Human;in vivo;insight;intercellular communication;Intercellular Communication Process;Investigation;Knowledge;Laboratories;Mass Spectrum Analysis;Mating Types;Meningoencephalitis;Microbe;Microbial Biofilms;microbial community;Microbiology;Modeling;Mutagenesis;mutant;Mutation;Nature;novel;Opportunistic Infections;overexpression;Partner in relationship;Pathogenesis;pathogenic fungus;Pathway interactions;Peptides;Persons;Pheromone;Prevalence;prevent;Process;Production;Proteins;Public Health;quorum sensing;Regulation;Research;response;Role;Saccharomyces;Signal Induction;Signal Transduction;Signaling Molecule;Signaling Protein;Specificity;Structural Protein;Structure;System;T-DNA;transcription factor;Transcription Repressor;transcriptome;Work

PROJECT_TITLE: Investigating a signaling molecule that cooperates with quorum sensing to induce biofilm formation in C. neoformans

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Dietary Supplements;Neurosciences;Nutrition;Pediatric;Prevention;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: PROVIDENCE

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: PROJECT NARRATIVE The proposed research is relevant to public health, as we will conduct pre-clinical studies of mechanism-based treatments for a new neurogenetic metabolic disorder. The disease mechanisms being studied also have broad relevance to the health of long-projecting neurons, such as those involved in a variety of neurological diseases.

PI_NAMEs: MORROW, ERIC M (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: Affect;Aging;Alanine;alpha ketoglutarate;Amino Acids;amino group;Animals;Axon;axon growth;axonopathy;Back;Brain;Brain Diseases;cancer cell;cell growth;Child;Childhood;Citric Acid Cycle;Clinical Trials;Consumption;Data;Defect;deprivation;Development;Diet;dietary;dietary restriction;dietary supplements;Disease;Early Intervention;efficacy study;Enzymes;Essential Amino Acids;Experimental Models;Fostering;Genetic;Germ Lines;Glutamates;Growth;Health;Hindlimb;Human;human stem cells;Impairment;In Vitro;in vivo;innovation;Intervention;Knockout Mice;Length;lens;loss of function mutation;macromolecule;Maintenance;Mediating;Metabolic;Metabolic Diseases;Metabolism;Mitochondria;mitochondrial metabolism;Motor;Motor disability;motor disorder;Motor Neurons;multidisciplinary;Mus;Mutation;Nervous System Disorder;Nervous System Trauma;neurogenetics;Neuroglia;neuron development;Neuronal Differentiation;neuronal growth;Neurons;Neurosciences;novel;null mutation;patient derived induced pluripotent stem cells;patient oriented research;Patients;Phenotype;Play;postnatal;pre-clinical;preclinical study;Prevention;Process;Protein Biosynthesis;Public Health;Pyruvate;Regulation;Research;Resources;Role;Spastic Paraplegia;stem cells;Supplementation;Testing;Therapeutic;Therapeutic Effect;therapy development;Transaminases;Translating;translational approach;treatment strategy;treatment trial

PROJECT_TITLE: Mechanisms of Disease and Treatment in Novel Metabolic Developmental Brain Disorders

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Brain Disorders;Cardiovascular;Epilepsy;Heart Disease;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Pediatric;Prevention;Rare Diseases

ORG_CITY: Columbus

ORG_DEPT: PHARMACOLOGY

ORG_NAME: OHIO STATE UNIVERSITY

PHR: Project Narrative Sudden, unexpected death in epilepsy (SUDEP) is a fatal complication, occurring in patients with epilepsy, who were otherwise healthy. Dravet syndrome, which results from a loss of function of the neuronal sodium channel, is associated with a particularly high risk of SUDEP. This proposal seeks to gain new insights into how regulation of sodium channels inside the heart regulates calcium cycling and underlie heart rhythm disorders and information gleaned from these studies will be used to develop new therapeutic approaches to treat sudden death in Dravet syndrome.

PI_NAMEs: RADWANSKI, PRZEMYSLAW  (contact)

PROJECT_TERMS: Address;Anti-Arrhythmia Agents;Apnea;Arrhythmia;Biochemical;Brain;Calcium;Cardiac;Cardiac Electrophysiologic Techniques;Cardiac Myocytes;Cardiovascular system;Cells;Cessation of life;clinically relevant;Complication;confocal imaging;Data;Defect;design;Disease;dravet syndrome;efficacy evaluation;Electrocardiogram;Electroencephalography;Electrophysiology (science);Ensure;Epilepsy;Functional disorder;Genetic;genetic approach;Glean;Heart;Heart Abnormalities;Heart Diseases;heart rhythm;high risk;humanized mouse;in vivo;Individual;Inherited;innovation;insight;Knock-out;Knowledge;Life;Link;loss of function;Mediating;Modeling;Molecular;mortality;mouse model;Mus;Muscle Cells;mutant;nano;nanoscale;neural;Neurons;novel;novel strategies;novel therapeutic intervention;patch clamp;Pathologic;Patients;pharmacologic;Phenotype;Physiological;prevent;Prevention;programs;Protein Isoforms;Proteins;Regulation;Research;Role;Ryanodine Receptor Calcium Release Channel;Safety;SCN1A protein;SCN8A gene;Seizures;Signal Transduction;Sodium Channel;Sodium-Calcium Exchanger;sudden cardiac death;Sudden Death;sudden unexpected death in epilepsy;superresolution microscopy;Testing;Tissues;Work

PROJECT_TITLE: Defining Novel Mechanisms of Sudden Death in Dravet Syndrome: Dysregulation of Sodium Channels in the Heart


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Kidney Disease;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

ORG_STATE: NY

PHR: PROJECT NARRATIVE. Mutations in a specific gene (Apolipoprotein L1 or APOL1) seen only in people of African ancestry (African Americans or Hispanic Americans) is linked to high rates of kidney disease, with only some of the individuals with these mutations developing kidney disease, indicating that other genetic or environmental factors are involved. We will explore these factors including other genes and common environmental exposures like air pollution/neighborhood environment, and heavy metal exposure. We will understand what additional risk factors contribute to kidney disease in individuals with this mutation, which will lead to preventative efforts to address the persistent racial and ethnic disparities in kidney disease.

PI_NAMEs: NADKARNI, GIRISH NITIN (contact)

PROGRAM_OFFICER_NAME: PARSA, AFSHIN

PROJECT_TERMS: Address;Affect;African American population;African ancestry;African Caribbean;Air Pollution;Apolipoproteins;Arsenic;biobank;Biological Assay;Cadmium;career development;case control;Case/Control Studies;cell type;Chromosome 22;Chronic Kidney Failure;Clinical;Clinical Data;clinical risk;cohort;Communities;Data;deprivation;design;Disease;Disease Outcome;disorder risk;Disparity;Early treatment;End stage renal failure;Ensure;Environment;Environmental Exposure;Environmental Risk Factor;ethnic disparity;ethnic minority;Evaluation;experience;Exposure to;Face;fine particles;Frequencies;Genes;Genetic;genetic association;Genetic Risk;genetic risk factor;Genetic study;genetic testing;Genotype;Geography;Goals;Grant;Heavy Metals;high risk;Hispanic Americans;HIV;improved;Individual;Inflammatory;inflammatory marker;innovation;insight;Investigation;Jackson Heart Study;Kidney;Kidney Diseases;large datasets;Link;Machine Learning;Maps;Measures;Mercury;Metabolic;Metal exposure;Metals;meter;Methods;minority communities;Minority Groups;Minority Health Research;minority patient;Modification;multidisciplinary;Mutation;Neighborhoods;nephrotoxicity;non-genetic;novel;Other Genetics;Outcome;Particulate Matter;Penetrance;Persons;podocyte;Positioning Attribute;Poverty;Preventive;racial determinant;racial disparity;racial minority;Reasons for Geographic And Racial Differences in Stroke;Reporting;Research;Research Personnel;Resources;Risk;Risk Factors;risk stratification;risk variant;Role;Sample Size;Single Nucleotide Polymorphism;socioeconomics;targeted treatment;Testing;Therapeutic;Time;Transplantation;Underrepresented Minority;urinary;Urine;Urokinase Plasminogen Activator Receptor;US State;Variant;walkability

PROJECT_TITLE: Elucidating Genetic and Environmental Second Hits in Racial and Ethnic Minorities with APOL1 High-Risk Genotypes

STUDY_SECTION: KNOD

STUDY_SECTION_NAME: Kidney, Nutrition, Obesity and Diabetes Study Section[KNOD]


ORG_CITY: BROOKLYN

ORG_NAME: SUNY DOWNSTATE MEDICAL CENTER

PHR: This project addresses our current limitations in the understanding of pulmonary surfactant lipid in idiopathic pulmonary fibrosis and it bridges lipid science and respiratory physiology. Pulmonary surfactant is an absolute requirement for lung function as it decreases alveolar surface tension, but the mechanisms for surfactant regulation are not completely understood and therefore not targeted during adult pathologies. By investigating novel mechanisms of surfactant lipid regulation, in the long term this project can enable identification of therapeutic targets to mitigate the decay of pulmonary function during chronic disease.

PI_NAMEs: GARCIA-ARCOS, ITSASO  (contact)

PROGRAM_OFFICER_NAME: PUNTURIERI, ANTONELLO

PROJECT_TERMS: A549;ABCA3 gene;Acute;Address;adipocyte differentiation;Adipose tissue;Adult;Agonist;Air;Alveolar;alveolar epithelium;alveolar lamellar body;Anti-Inflammatory Agents;Apical;Area;ATP binding cassette transporter 1;Bleomycin;Bronchoalveolar Lavage;Cell Culture System;Cell Differentiation process;Cell Line;Cell Physiology;Cells;Cholesterol;Cholesterol Esters;Chronic Disease;Chronic lung disease;Chronic Obstructive Pulmonary Disease;Coculture Techniques;Collagen;Complex;cytokine;Data;Defect;Deposition;Development;Diagnosis;Disease;Down-Regulation;Electron Microscopy;Ensure;Epithelium;Event;extracellular;Fibroblasts;Fibrosis;Foundations;Gene Expression;Genetic;Genetic Models;Genetic Transcription;Hepatic;Homeostasis;Human;Hydrolysis;idiopathic pulmonary fibrosis;In Vitro;in vivo;in vivo Model;Inflammation;Inflammatory;innovation;intercellular communication;Interleukin-1 beta;Intervention;knock-down;Knock-out;Knockout Mice;Knowledge;LDL-Receptor Related Protein 1;Lecithin;lipid biosynthesis;lipid mediator;lipid metabolism;lipidomics;Lipids;Lipoprotein (a);Lipoprotein Receptor;Lipoproteins;Liquid substance;Low Density Lipoprotein Receptor;Lung;Lung Diseases;Macrophage;Measures;Mediating;Membrane;Mesenchymal;Metabolic;Metabolic Pathway;Metabolism;Molecular;Morphology;mRNA Expression;Mus;novel;novel therapeutic intervention;novel therapeutics;old mice;Outcome;Pathology;Pathway Analysis;Pathway interactions;Patients;Peptide Hydrolases;Phenotype;Phospholipids;PPAR gamma;prevent;Process;Proteins;Proteomics;pulmonary arterial hypertension;Pulmonary Fibrosis;pulmonary function;Pulmonary Pathology;Pulmonary Surfactants;Pulmonology;receptor;Regulation;Research;Respiratory physiology;response;restoration;Role;Science;Serpins;Signal Transduction;single-cell RNA sequencing;small hairpin RNA;Smooth Muscle Myocytes;Source;Surface Tension;surfactant;surfactant deficiency;surfactant production;surfactant replacement therapy;Surfactant therapy;synthetic enzyme;Tamoxifen;Techniques;Testing;therapeutic target;Tissues;Tracer;transcriptome sequencing;transcriptomics;Transfection;uptake;Vital capacity;Work of Breathing

PROJECT_TITLE: Regulation of lipid metabolism in pulmonary Type 2 cells


NIH_SPENDING_CATS: Digestive Diseases;Liver Disease

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: The ATP-Binding Cassette (ABC) transporters comprise a large family of proteins that use energy from ATP to pump substrates across membranes. We identified an ABC transporter (referred to in this application as G5G8) that is essential for the excretion and homeostasis of cholesterol: people with genetic defects in G5G8 can suffer heart attacks in childhood. In this application we will determine the molecular basis for sterol transport by G5G8, as well as by another sterol transporter G1.

PI_NAMEs: HOBBS, HELEN HASKELL (contact)

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: absorption;Address;Antibodies;Applications Grants;ATP Hydrolysis;ATP phosphohydrolase;ATP-Binding Cassette Transporters;Bile fluid;Binding;Binding Sites;Biochemical;Biological;Biological Assay;Cell membrane;Cells;Cellular biology;Childhood;Cholelithiasis;Cholesterol;Cholesterol Homeostasis;Circulation;Complex;Coronary Arteriosclerosis;Coupling;Cryoelectron Microscopy;design;Development;Diet;Dietary Sterol;Disease;Ensure;Enterocytes;Epitopes;Equilibrium;Excretory function;Failure;Family;Family member;Funding;Gene Modified;Glean;Goals;Hepatocyte;Hydrolysis;In Vitro;in vivo;insight;Intestines;Laboratories;Lipid Bilayers;Lipids;Liver;marine;member;Membrane;Membrane Proteins;Metabolism;Missense Mutation;Modeling;Molecular;Molecular Conformation;Molecular Genetics;Mus;Mutagenesis;mutant;Mutation;Myocardial Infarction;Nucleotides;Organism;particle;Peripheral;Persons;Phospholipids;Physiology;Plants;preference;premature atherosclerosis;prevent;programs;Property;Protein Family;Proteins;Protocols documentation;Pump;rare mendelian disorder;Reagent;reconstitution;Research;Resolution;Role;Sitosterolemia;Sitosterols;Specificity;Sphingomyelins;sterol homeostasis;Sterols;structural biology;Structure;Substrate Specificity;Tissues;tool;Vertebrates;X-Ray Crystallography

PROJECT_TITLE: Role of ABCG1, ABCG5 and ABCG8 in Sterol Metabolism

STUDY_SECTION: NMHD

STUDY_SECTION_NAME: Nutrition and Metabolism in Health and Disease Study Section[NMHD]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Cost Effectiveness Research;Diabetes;Disability Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Nutrition;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

ORG_STATE: WI

PHR: Diabetes affects 13% of US adults and African Americans have higher prevalence of diabetes, higher diabetes related cost, higher risk of complications, and higher risk of early death compared to non-Hispanic Whites and a key factor that is emerging as a significant contributor to poor health outcomes for African Americans is structural racism. A promising intervention that may address the underlying poverty related chronic stress of structural racism and living in inner city environments for African Americans with type 2 diabetes is Cash Transfer, which can be conditional or unconditional. This study will test the preliminary efficacy of diabetes- tailored CCT (DM-CCT), which will be conditional on participating in biweekly (every two weeks), nurse-led, virtual diabetes education/skills training and stress/coping intervention compared to UCT (with no requirement for participation) on clinical outcomes, self-care behaviors, and psychological health in 100 inner city African Americans with poorly controlled type 2 diabetes using an RCT design.

PI_NAMEs: CAMPBELL, JENNIFER ANNETTE (contact)

PROGRAM_OFFICER_NAME: RAJAPAKSE, NISHADI

PROJECT_TERMS: Address;Adult;Affect;African American population;Attention;Behavior;Case/Control Studies;Cessation of life;Chronic Disease;Chronic stress;Clinical;Communities;comparison intervention;coping;cost;Cost Effectiveness Analysis;cost estimate;design;Developing Countries;diabetes education;Diabetes Mellitus;Diet;disability;Discrimination;Education;Environment;Exercise;food insecurity;Fostering;functional status;Funding;Future;glycemic control;Glycosylated hemoglobin A;Health;health disparity;Health education;High Prevalence;high risk;housing instability;human capital;Imprisonment;improved;Income;Individual;Inequity;inner city;intergenerational;Intervention;Lived experience;medication compliance;Mental disability;Mental Health;Morbidity - disease rate;mortality;Neighborhoods;Non-Insulin-Dependent Diabetes Mellitus;Not Hispanic or Latino;Nurses;Outcome;physically handicapped;poor health outcome;Poverty;poverty alleviation;Preparation;Preventive care;Productivity;Quality of life;racial health disparity;Randomized;Recommendation;residential segregation;Resources;Self Care;SF-12;skills training;Social Environment;Societies;Stress;Stress and Coping;Structural Racism;System;Testing;United States;urban area;Violence;virtual;Work

PROJECT_TITLE: Conditional Cash Transfer Intervention to Improve Health Outcomes among Inner-City African Americans with T2DM

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Cerebrovascular;Clinical Research;Dementia;Genetics;Neurodegenerative;Neurosciences;Rare Diseases;Rehabilitation;Stroke;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CINCINNATI

PHR: Program Director/Principal Investigator (Last, First, Middle): Woo, Daniel 4. Project Narrative  We have identified a population in which the rate of development of dementia is extraordinarily high. Survivors of brain hemorrhage, also called intracerebral hemorrhage, develop progressive dementia at a rate of approximately 40% within several years of the hemorrhage. We seek to evaluate if this high risk is due to the underlying causes or to inflammation from the hemorrhage. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

PI_NAMEs: WOO, DANIEL  (contact)

PROGRAM_OFFICER_NAME: YIN, XILING

PROJECT_TERMS: Acute;Address;Affect;African American population;Age;Ancillary Study;Atrophic;Behavioral;Biological Markers;Blinded;Blood Vessels;Brain hemorrhage;Budgets;CASP2 gene;Cerebral Amyloid Angiopathy;Cerebral hemisphere hemorrhage;Cerebral small vessel disease;Chronic;Clinical assessments;Cognitive;cohort;Contralateral;Data;Deferoxamine;Dementia;dementia risk;Deterioration;Development;Diffusion Magnetic Resonance Imaging;disability;disabled;DNA;Enrollment;Evaluation;follow-up;Funding;Gene Expression;Hemorrhage;Hemosiderin;high risk;Hypertension;Image;Impaired cognition;Incidence;Inflammation;Inflammatory;inflammatory marker;Inflammatory Response;Interleukin-8;Iron Chelating Agents;Lacunar Infarctions;Leukocytes;Longterm Follow-up;Magnetic Resonance Imaging;Measurement;Measures;Mediation;Microvascular Dysfunction;Minority;Molecular Genetics;Motor;multidisciplinary;neuroimaging;neuroimaging marker;novel;Outcome;patient population;Patients;Phenotype;Population;Prevention;Principal Investigator;programs;Prospective Studies;Recording of previous events;Recovery;recruit;Reporting;Risk;Risk Factors;RNA;Role;Sampling;Serum;Siderosis;Statistical Data Interpretation;Stroke;stroke recovery;Supratentorial;Survivors;tractography;transcriptome sequencing;United States National Institutes of Health;Variant;White Matter Disease

PROJECT_TITLE: Recovery of StrokE - Longitudinal Assessment With Neuroimaging (ROSE LAWN)

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


ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE Defects in mitochondria can lead to devastating neurological diseases, including subacute brain neurodegeneration, for which we have no approved medicines. Work in this grant application will provide mechanistic insight into mitochondrial neurodegeneration, while also helping to pioneer new therapeutic approaches. Because mild mitochondrial dysfunction accompanies virtually all age-associated diseases, our work may have implications for more common forms of neurodegeneration.

PI_NAMEs: MOOTHA, VAMSI KRISHNA (contact)

PROJECT_TERMS: Address;advanced disease;Age;age-related disease;Air;Altitude;Anemia;Applications Grants;Basal Ganglia;base editing;Basic Science;Bilateral;Biology;Brain;Brain Diseases;Brain Pathology;Brain Stem;Breathing;Buffers;Carbon Monoxide;Cells;Cessation of life;Childhood;Chronic;Collection;Dedications;Defect;Development;Disease;DNA;drug efficacy;efficacy testing;end stage disease;Engineering;Event;Exhibits;Foundations;Future;Genes;Genetic Heterogeneity;genomic profiling;Grant;gray matter;Growth;Human;Hyperoxia;Hypoxia;Image;Impairment;improved;in vivo;Inborn Errors of Metabolism;insight;Intervention;Knockout Mice;Laboratories;Leigh Disease;life span;Medicine;Mitochondria;Mitochondrial Diseases;Mitochondrial DNA;mitochondrial dysfunction;mitochondrial genome;Modeling;Molecular;mouse model;Mus;natural hypothermia;Necrosis;Necrotic Lesion;Nerve Degeneration;Nerve Regeneration;Nervous System Disorder;Neurites;neurogenesis;neuroinflammation;Neurologic;neuron loss;Neurons;neurovascular;novel therapeutic intervention;Nuclear;Orphan;Oxygen;Pathology;Patients;Pharmaceutical Preparations;Physiology;pre-clinical;preclinical efficacy;Preclinical Testing;prevent;Prevention;Proteomics;Reporting;single cell genomics;Site;small molecule;Stress;Technology;Therapeutic;Translations;virtual;wasting;Work

PROJECT_TITLE: Preventing and Reversing Mitochondrial Leigh Syndrome with Hypoxia

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


NIH_SPENDING_CATS: Cerebrovascular;Clinical Research;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: HERSHEY

ORG_DEPT: NEUROSURGERY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

PHR: PROJECT NARRATIVE Iron is required for multiple functions in cells including oxygen transport and its utilization for energy production. Thus iron must be delivered to the brain in a timely manner and in sufficient amounts during development and to maintain optimal function in adults. We conducted investigations to establish the then novel concept that brain iron uptake is regulated at the level of endothelial cells in the blood-brain barrier (BBB) which is in marked contrast to the formally held notion that endothelial cells simply serve as passive conduits for iron transport into the brain. Moreover, in addition to the established role for transferrin, we have identified H-ferritin as a significant iron delivery protein to the brain. The gap in our knowledge addressed in this application is how brain iron uptake is regulated. For these studies we will utilize a combination of animal models and a BBB model derived from induced pluripotent stem cells. The data generated can be expected to impact clinical and therapeutic strategies on management of iron deficiency and its effect on neurological function.

PI_NAMEs: CONNOR, JAMES ROBERT (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Address;Adult;Affect;Age;Alzheimer's Disease;Animal Model;Astrocytes;Biological;Blood;Blood - brain barrier anatomy;Brain;brain endothelial cell;brain iron;Carrier Proteins;Cell Culture Techniques;Cell model;Cells;Cerebrospinal Fluid;Clinical;clinically relevant;Cognitive;cognitive performance;Data;Development;Endothelial Cells;experimental study;Extracellular Fluid;Ferritin;Genotype;H ferritin;Health;hearing impairment;Human;human induced pluripotent stem cells;improved;In Vitro;in vivo;in vivo Model;indexing;induced pluripotent stem cell;Injections;Intervention;Intravenous;Investigation;Iron;iron deficiency;iron supplementation;Knowledge;Metabolic;Modeling;Mus;myelination;Nervous System Disorder;Nervous System Physiology;Neurodegenerative Disorders;Neurologic;Neurologic Process;Neurotransmitters;novel;Oral;Organ;Oxidative Stress;Oxygen;oxygen transport;Parkinson Disease;Physiological;pluripotent stem cell differentiation;pre-clinical;Production;Proteins;Public Health;Publishing;receptor;Regulation;response;Restless Legs Syndrome;Role;sex;Side;Signal Transduction;stem;Surface;System;Testing;Therapeutic;transcytosis;Transferrin;Translations;uptake;Work

PROJECT_TITLE: Mechanisms and Regulation of Brain Iron Uptake


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Genetics;Neurosciences;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: PHILADELPHIA

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Glioblastoma (GBM) is among the most lethal of human malignancies with a current median survival of about 14 months. The goals of this project are to understand the mechanism of tumor therapy resistance and to develop new therapy for treating GBM.

PI_NAMEs: FAN, YI  (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: angiogenesis;Angiogenesis Inhibitors;Angiogenic Factor;Area;beta catenin;bevacizumab;Blood Vessels;C10 chemokine;cancer therapy;Cell Lineage;cell motility;Cell Proliferation;Cell Therapy;Cells;Chemoresistance;chemotherapy;Chemotherapy and/or radiation;Combined Modality Therapy;coronary fibrosis;cytotoxic;Cytotoxic Chemotherapy;Data;Development;driving force;Embryonic Development;Endothelial Cells;Endothelium;Failure;Fibroblasts;Functional disorder;Genes;Genetic;genetic signature;Genetically Engineered Mouse;Glioblastoma;Glioma;Goals;Grant;Human;In Vitro;in vivo;insight;Investigational Therapies;Kaposi Sarcoma;KDR gene;kidney fibrosis;knock-down;Knockout Mice;Liver Fibrosis;Malignant - descriptor;Malignant Neoplasms;Mediating;Melanoma;Mesenchymal;Mesenchymal Stem Cells;Modeling;Molecular;Monitor;mouse model;Mus;Myositis;Neoplasm Metastasis;novel;novel therapeutic intervention;novel therapeutics;Nutrient;Oxygen;paracrine;Pathologic;pharmacologic;Phenotype;Phosphorylation;Physiologic Ossification;Play;pre-clinical;Primary Brain Neoplasms;Radio;Refractory;Resistance;response;Role;Science;Signal Transduction;single-cell RNA sequencing;Solid Neoplasm;Specimen;stem-like cell;stemness;System;temozolomide;Testing;Therapeutic;Therapeutic Effect;therapy resistant;transcriptome;transcriptome sequencing;trend;tumor;tumor eradication;tumor growth;tumor microenvironment;tumor progression;tumorigenesis;vascular abnormality;Vascular Endothelial Growth Factors;Vascularization;Work

PROJECT_TITLE: Endothelial plasticity in glioma vascularization and therapy resistance

STUDY_SECTION: TME

STUDY_SECTION_NAME: Tumor Microenvironment Study Section[TME]


ADMINISTERING_IC: OD

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

ORG_CITY: DAVIS

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: PROJECT NARRATIVE Veterinarians are trained as comparative biologists with an understanding of all living species and ideally suited to solve the complex problems presented by current and future medicine in humans and animals. The goal of the UC Davis Comparative Medical Scientist T32 Training Program is to provide an outstanding environment in biomedical research training at the nation's top-ranked School of Veterinary Medicine and to prepare our students with DVM-PhD degrees to become compassionate and exceptional clinician-scientists engaged in basic and translational research to advance the health of people and animals, in the context of their changing environment. This program addresses a national shortage of research-trained veterinarians who will conduct independent research utilizing animal model systems of human diseases as well as steward appropriate care and use of laboratory animals.

PI_NAMEs: SAEIJ, JEROEN ;THOMASY, SARA MICHELLE (contact)

PROGRAM_OFFICER_NAME: TANDON, RITESH

PROJECT_TITLE: Comparative Medical Science Training Program


NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Rare Diseases;Tuberculosis;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: RONDEBOSCH

ORG_COUNTRY: SOUTH AFRICA

ORG_FIPS: SF

ORG_NAME: UNIVERSITY OF CAPE TOWN

PHR: PROJECT NARRATIVE The University of Cape Town Clinical Trials Unit (UCTCTU) based at the Desmond Tutu HIV Centre, University of Cape Town has six unique, expert and integrated clinical research sites which are ready and willing to contribute to the research priorities of the 4 NIH funded clinical trial Networks namely the ACTG, IMPAACT, HPTN and HVTN. Collaboratively this Clinical trials consortium will utilise the experience and expertise of the core and it’s sites to efficiently and effectively promote the research and development of new innovations in treatment, prevention and management of HIV, tuberculosis and related conditions.

PI_NAMEs: BEKKER, LINDA-GAIL GAIL (contact)

PROGRAM_OFFICER_NAME: GREENFIELD, TERI L

PROJECT_TERMS: Africa;Africa South of the Sahara;AIDS clinical trial group;Area;clinical diagnostics;Clinical Practice Guideline;Clinical Research;clinical research site;Clinical Trials;Clinical Trials Network;Clinical Trials Unit;clinically relevant;cohesion;Communication;Communities;community engagement;Competence;Conduct Clinical Trials;Contracts;Cost Control;Country;Data;Development;Disease;Elements;Ensure;epidemic response;Ethics;Evaluation;experience;Face;Faculty;Feedback;Funding;Goals;Good Clinical Practice;good laboratory practice;Health Sciences;high standard;HIV;HIV Vaccine Trials Network;HIV/AIDS;HIV/TB;Information Dissemination;Infrastructure;innovation;Institution;International Maternal Pediatric Adolescent AIDS Clinical Trials;Intervention;Investments;Labor Forces;Laboratories;Lead;Leadership;Legal;Location;Mentorship;Methods;Monitor;novel strategies;participant safety;Performance;Persons;Pharmacy facility;Population;Prevention;Productivity;Protocols documentation;Province;quality assurance;recruit;Regulation;Reporting;Research;Research Activity;research and development;Research Infrastructure;Research Priority;Resource Sharing;Resources;Rights;Running;Series;Site;skills;South Africa;Southern Africa;Specialist;Structure;synergism;Technical Expertise;Training;Tuberculosis;United States National Institutes of Health;Universities

PROJECT_TITLE: HIV/AIDS Clinical Trials Units University of Cape Town CTU 2020 to 2027


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Chronic Pain;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Complementary and Integrative Health;Disability Research;Headaches;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Migraine;Networking and Information Technology R&D (NITRD);Neurosciences;Pain Research;Rehabilitation;Social Determinants of Health;Telehealth

ORG_CITY: ANN ARBOR

ORG_DEPT: ANESTHESIOLOGY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project Narrative Chronic migraines (CM) are among the most common, costly, and disabling conditions in the United States, and there is a significant need for comprehensive, biopsychosocially-informed approaches to management of CM. The current project proposes to test the efficacy of a 2-hour, single-session, telehealth-based behavioral intervention (Empowered Relief) against a health education control condition in addressing CM frequency, intensity, and associated disability. The proposed intervention has the potential to improve the quality of CM management by providing a brief, disseminable, evidence-based treatment for individuals at risk for poor CM-related outcomes.

PI_NAMEs: STURGEON, JOHN ANDREW (contact)

PROGRAM_OFFICER_NAME: OSHINSKY, MICHAEL L

PROJECT_TERMS: Absenteeism at work;Address;Aftercare;Analgesics;Anxiety;Area;arm;base;Behavior;Behavior Therapy;Behavioral;behavioral clinical trial;behavioral response;biopsychosocial;cancer surgery;career development;Caring;Chronic;Chronic low back pain;chronic pain;Clinic;Clinical;clinical pain;Clinical Trials;Clinical Trials Design;Cognitive;Cognitive Therapy;comparative efficacy;Complement;Complex;cost;Data;Development;diaries;digital;disability;Disabling condition;Economic Burden;effective therapy;efficacy testing;efficacy trial;empowerment;evidence base;Evidence based treatment;Expenditure;experience;follow-up;Frequencies;Funding;Future;Goals;Health education;Health Services Accessibility;Hour;Impairment;Improve Access;improved;Individual;interdisciplinary approach;Intervention;intervention effect;Length;Low Back Pain;Low income;Malignant Breast Neoplasm;Measures;Mediating;Medical;medical specialties;Meditation;Mental Depression;Mentorship;Methodology;Methods;Migraine;Migraine disability;migraine treatment;mindfulness meditation;Neurologic;Neurosciences;novel;opioid use;Outcome;Pain;pain catastrophizing;Pain intensity;Pain management;pain reduction;Patients;Pattern;Persons;Pharmaceutical Preparations;pharmacologic;Population;Populations at Risk;primary endpoint;primary outcome;Protocols documentation;Psychological adjustment;psychological distress;Psychological Factors;Psychologist;psychosocial;psychosocial adjustment;psychosocial outcome;Public Health;Randomized;randomized trial;randomized, clinical trials;remote delivery;Reporting;Research;Research Personnel;Resources;response;Retrospective Studies;Risk;Role;Sampling;secondary endpoint;secondary outcome;Self Management;Severities;skills;Sleep disturbances;Source;Statistical Models;statistics;Symptom Burden;Symptoms;telehealth;Testing;Time;Time Series Analysis;Training;treatment trial;trial comparing;United States;United States National Institutes of Health;Woman;Work

PROJECT_TITLE: Efficacy of a Single-Session Telehealth-Based Behavioral Intervention for Chronic Migraines

STUDY_SECTION: NST

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


ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: PROJECT NARRATIVE HIV-1 remains a substantial global health burden: antiretroviral therapy (ART) is capable of suppressing virus, but not curing infected individuals. Although broadly neutralizing antibodies (bNAbs) are a highly promising approach for cure, even the most potent molecules are currently only effective for a limited time period. Our goal in this project is to develop an in vivo delivery approach that reprograms B cells to express bNAbs and similar molecules for the lifetime of an individual, enabling long-term HIV-1 remission in the absence of ART.

PI_NAMEs: PETERSON, CHRISTOPHER W (contact)

PROGRAM_OFFICER_NAME: POON, BETTY

PROJECT_TERMS: 2019-nCoV;Address;adeno-associated viral vector;Anatomy;Animals;Antibodies;Antibody Therapy;Antigens;antiretroviral therapy;Autoimmune Diseases;B-Lymphocytes;Biological Assay;Capsid;Cells;chimeric antigen receptor T cells;Clinical;clinical application;Clinical Research;Communicable Diseases;CRISPR/Cas technology;Data;delivery vehicle;Dependovirus;Disease remission;Dose;Engineering;Experimental Designs;experimental study;Failure;fighting;gene editing technology;gene therapy;Gene Transduction Agent;gene-editing approach;Genes;Genetic;genetic information;global health;Goals;HIV;HIV Antibodies;HIV-1;HIV/AIDS;Human;humanized mouse;IGH@ gene cluster;Immune response;Immune system;Immunocompetent;Immunodeficient Mouse;immunogenic;immunogenicity;Immunoglobulin G;in vivo;Individual;Infection;Injections;innovation;Knock-in;Libraries;Link;Lymphocyte;Macaca mulatta;Malignant Neoplasms;Measures;Methodology;Methods;Modality;Modeling;Monoclonal Antibodies;Monoclonal Antibody Therapy;Mus;Nature;neutralizing antibody;nonhuman primate;novel;Pathology;Peripheral Blood Mononuclear Cell;Pharmaceutical Preparations;Phenotype;preclinical study;programs;Proteins;Publications;Publishing;Regimen;Resource-limited setting;screening;Secondary to;Serum;simian human immunodeficiency virus;Site;Specificity;success;Technology;Testing;Therapeutic;Therapeutic antibodies;Therapeutic Effect;Time;Tissues;tool;trafficking;transduction efficiency;Transgenes;Tropism;Variant;vector;vector biodistribution;Viral;Viral Antigens;viral rebound;Viremia;Virus;Virus Replication;Withdrawal

PROJECT_TITLE: In Vivo Gene Editing of B cells with NICE-AAV Vectors


NIH_SPENDING_CATS: Aging;Atherosclerosis;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Nutrition;Obesity;Prevention

ORG_DEPT: PATHOLOGY

PHR: PUBLIC HEALTH RELEVANCE STATEMENT (PROJECT NARRATIVE) Genetic and population studies have identified the association between 2 distinct mutations (epsilon2 and epsilon4) in the APOE gene with increased risk and severity of coronary and peripheral vascular disease. This project will establish unique mechanisms by which the expression of the polymorphic apoE2 and apoE4 in myeloid cells and adipocytes contributes to atherosclerosis progression. Completion of this project will yield novel information that can be harnessed to design personalized intervention strategies based on APOE genotype to reduce vascular diseases.

PI_NAMEs: HUI, DAVID YIU-KWAN (contact);JAESCHKE, ANJA

PROJECT_TERMS: Acceleration;Adipocytes;Adipose tissue;Adrenal Glands;Agonist;Alleles;Alzheimer's Disease;Apolipoprotein E;apolipoprotein E-3;apolipoprotein E-4;Area;Arterial Fatty Streak;atherogenesis;Atherosclerosis;Biomedical Research;Blood Vessels;Bone Marrow Cells;Bone Marrow Transplantation;Brain;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular risk factor;Carotid Arteries;Carotid Atherosclerotic Disease;Cause of Death;Cell Death;cell type;Cells;CETP gene;Cholesterol;Coronary Arteriosclerosis;coronary vascular disease;cytokine;Data;design;Diabetes Mellitus;Diet;Disease;E protein;effectiveness testing;endoplasmic reticulum stress;Experimental Animal Model;Extrahepatic;Follow-Up Studies;Functional disorder;gene replacement;Genes;Genetic Polymorphism;genetic risk factor;Genetic study;Genotype;Goals;Hepatic;Hepatic Tissue;Hepatocyte;Heterozygote;Homeostasis;Human;Hyperlipoproteinemia Type III;Immune;Impairment;improved;Inflammasome;Inflammation;Inflammatory;Inflammatory Response;Intervention;Knock-out;Lesion;lipid metabolism;Lipids;Lipoproteins;Liver;Macrophage;Metabolic dysfunction;Metabolic stress;Mus;Mutation;Myelogenous;Myeloid Cells;Myelopoiesis;Necrosis;non-diabetic;novel;novel therapeutic intervention;Obesity;overexpression;Oxidative Stress;Oxidative Stress Induction;Pathogenesis;Peripheral Vascular Diseases;personalized intervention;Phase;Plasma;Population;Population Study;Property;public health relevance;recruit;Risk;Risk Factors;Role;Severities;Signal Transduction;single nucleus RNA-sequencing;single-cell RNA sequencing;Smooth Muscle;Smooth Muscle Myocytes;sphingomyelin synthase;Testing;Time;Tissues;Transplantation;Triglycerides;Tunica Adventitia;Variant;Vascular Diseases;western diet

PROJECT_TITLE: Polymorphic ApoE at the crossroad of lipid metabolism and inflammation in atherosclerosis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


NIH_SPENDING_CATS: Cardiovascular

ORG_DEPT: SURGERY

PHR: PROJECT NARRATIVE Surgeon-scientists in training have competing clinical responsibilities but must compete for contentious funding lines, which means that state-of-the art training is critical for producing the best surgeon-scientists. With the aging of the population, the number of patients with cardiovascular disease is markedly increasing. The proposed program, with its overarching focus on vascular biology and three distinct tracks including (1) basic/translational, (2) health sciences and (3) biomedical engineering, under multi-disciplinary preceptor guidance, will produce the next generation of surgeon-scientist leaders who will pave the way to new discoveries in human health.

PI_NAMEs: GALLAGHER, KATHERINE ANN;HENKE, PETER K (contact)

PROGRAM_OFFICER_NAME: NEILSON, KAREN MARY

PROJECT_TERMS: Cardiovascular system;Research Training;Science;Translational Research

PROJECT_TITLE: Translational research training in cardiovascular science

STUDY_SECTION: NITM

STUDY_SECTION_NAME: NHLBI Institutional Training Mechanism Study Section[NITM(OA)]


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Lung;Mental Health;Mental Illness;Post-Traumatic Stress Disorder (PTSD);Prevention;Rare Diseases

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Mental health morbidity is presently an untreated major complication in survivors of acute respiratory failure. In this application, we will explore the feasibility of an intervention aimed at minimizing the psychological distress of intubated patients and will refine the intervention based on stakeholder feedback. We will then study the efficacy of the intervention on short- and long-term mental health and cognitive function of patients who have experienced acute respiratory failure.

PI_NAMEs: KARNATOVSKAIA, LIOUDMILA  (contact)

PROGRAM_OFFICER_NAME: KALANTARI, ROYA

PROJECT_TERMS: Acute respiratory failure;acute stress;Address;Affect;American;Analgesics;Anxiety;anxiety symptoms;Behavior Therapy;career;Chest;Chronic;Clinical;Cognitive;cognitive function;Collaborations;Communication;comparative efficacy;Complication;Conscious;cost;Critical Illness;Data;Delirium;design;effectiveness testing;efficacy study;Elements;Emotional;emotional experience;Evaluation;experience;Family;Feasibility Studies;Feedback;follow-up;Foundations;Fright;Funding;Goals;Grant;Health Care Costs;Health Personnel;Hospitals;Hungary;Impairment;improved;improved outcome;Inpatients;instrument;Intensive Care;Intensive Care Units;interest;Intervention;intervention refinement;Intervention Studies;Interview;Intubation;K-Series Research Career Programs;Measures;Mechanical ventilation;Medical;Memory;Mental Depression;Mental Health;Mentors;Mission;modifiable risk;Morbidity - disease rate;National Heart, Lung, and Blood Institute;Nurses;Outcome;patient oriented research;Patients;Persons;Physical Rehabilitation;Physicians;Pilot Projects;Population;Positioning Attribute;Post-Traumatic Stress Disorders;prevent;Prevention;Process;professor;Provider;psychologic;psychological distress;Psychologist;Psychology;Psychotherapy;Quality of life;Randomized;Randomized, Controlled Trials;readmission rates;reduce symptoms;Research;Research Design;Research Personnel;Risk Factors;sedative;semantic processing;Services;skills;Societies;Standardization;Structure;Suggestion;Survivors;survivorship;Syndrome;Testing;Therapeutic;Thinking;Time;Training;traumatic event;treatment as usual;Treatment Efficacy;Universities;ventilation;Weaning;Woman;Work

PROJECT_TITLE: Psychological support based on positive suggestions in acute respiratory failure patients

STUDY_SECTION: MPOR

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


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Infant Mortality;Lung;Neonatal Respiratory Distress;Neurosciences;Patient Safety;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Rare Diseases

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Non-InVasive Neurally Adjusted Ventilatory Assist (NIV-NAVA) is an FDA approved technology that consistently synchronizes non-invasive respiratory support with infant respiratory drive. We propose a Data Coordinating Center (DCC) to support a pragmatic, unblinded, phase III randomized controlled trial (RCT) in preterm infants 240/7-276/7 weeks gestation in respiratory failure to determine if NIV-NAVA, compared with non- synchronized nasal intermittent positive pressure ventilation (NIPPV), prevents extubation failure within 5 days of extubation from mechanical ventilation.

PI_NAMEs: RATCLIFFE, SARAH J (contact)

PROGRAM_OFFICER_NAME: SOOD, BEENA G

PROJECT_TERMS: Address;Alveolar;Biometry;Bronchopulmonary Dysplasia;Case Report Form;Chest wall structure;Childhood;Chronic lung disease;clinical research site;Clinical Trials;clinically relevant;Collaborations;Continuous Positive Airway Pressure;Cost Savings;Data;Data Coordinating Center;data infrastructure;data integration;data management;Data Security;data sharing;data structure;Development;Documentation;Ensure;evidence base;Exposure to;extreme prematurity;Extubation failure;Failure;FAIR principles;Familiarity;FDA approved;Funding;Gestational Age;Goals;Health Care Costs;Hour;Human;improved;Incidence;Infant;Injury;Intermittent Positive-Pressure Ventilation;Intubation;long-term sequelae;Lung;Mechanical ventilation;Meta-Analysis;Methodology;Methods;Morbidity - disease rate;Multi-Institutional Clinical Trial;neural;neurotransmission;Nose;novel;operation;Outcome;Oxygen;patient population;Phase;Phase III Clinical Trials;Physiological;Positioning Attribute;Pregnancy;premature;Premature Birth;Premature Infant;premature lungs;pressure;prevent;quality assurance;Quality Control;randomized trial;Randomized, Controlled Trials;recruit;Reproducibility of Results;Research;Research Design;respiratory;Respiratory Diaphragm;Respiratory Failure;Security;Statistical Data Interpretation;Technology;Testing;Tidal Volume;United States;United States National Institutes of Health;ventilation;Ventilator-induced lung injury;years of life lost

PROJECT_TITLE: 2/2 The Diaphragmatic Initiated Ventilatory Assist (DIVA) Trial

STUDY_SECTION: CLTR

STUDY_SECTION_NAME: Clinical Trials Review Study Section[CLTR(JA)]


NIH_SPENDING_CATS: Asthma;Clinical Research;Lung

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

ORG_STATE: CA

PHR: PROJECT NARRATIVE Asthma remains an important source of morbidity and health care costs in the U.S. The overall goals of this project are to use a combination of mouse models and human populations to understand the important cells that contribute to the pathogenesis and exacerbation in allergic asthma.

PI_NAMEs: AKBARI, OMID  (contact)

PROGRAM_OFFICER_NAME: LIU, QIAN

PROJECT_TERMS: adaptive immunity;Affect;Airway Disease;airway hyperresponsiveness;airway inflammation;Allergic Disease;Anti-Inflammatory Agents;Anti-Tumor Necrosis Factor Therapy;Asthma;asthmatic;asthmatic patient;ATAC-seq;Automobile Driving;Biology;Blood;Bronchodilator Agents;Cell Separation;Cell Survival;Cells;Clinical;cohort;Complement;cytokine;Data;design;Development;Disease;Effector Cell;Epithelial Cells;experience;Extrinsic asthma;fatty acid oxidation;Flow Cytometry;Generations;Glycolysis;Goals;Health Care Costs;Homeostasis;Human;Hypersensitivity;Immune;immunoregulation;Immunosuppressive Agents;Interleukin-10;Interleukin-13;Interleukin-5;Knowledge;Laboratories;lipidomics;Lung;Lymphoid Cell;Metabolic;Metabolic Pathway;Metabolism;Monitor;Morbidity - disease rate;mouse model;Mus;novel therapeutics;Oxidative Phosphorylation;Pathogenesis;Pathway interactions;Phenotype;Population;Pre-Clinical Model;Prevalence;Production;Pulmonary Inflammation;Pulmonology;Receptors, Tumor Necrosis Factor, Type II;Reporting;Research;Respiratory Therapy;response;Role;side effect;Signal Transduction;single cell genomics;single-cell RNA sequencing;Source;standard of care;Stimulus;systemic toxicity;Therapeutic;TNF gene;TNFRSF1A gene;TNFRSF1B gene;transcription factor;transcriptome;transcriptomics;Translating;Tumor Necrosis Factor Receptor;Widespread Disease;Work

PROJECT_TITLE: Role of TNF receptor 2 on Pulmonary Group 2 Innate Lymphoid Cells


ORG_CITY: HANOVER

ORG_NAME: DARTMOUTH COLLEGE

PHR: Project Narrative The human respiratory system and skin are the body’s largest interface exposed to ambient air and environmental particles, allergens, and microbes. This grant aims to identify homologous human and mouse mononuclear phagocytes in lung, skin and lymph nodes based on functional and transcriptional profiles. Identifying and characterizing mononuclear phagocytes cross-species homologies and the key genes conserved across species that are involved in their function, permits both basic and translational advances, including a more accurate picture of which mononuclear phagocyte subtypes to pursue in a given human application, how to identify these cell types in humans, and which specific genes or proteins to target in treatment development.

PI_NAMEs: JAKUBZICK, CLAUDIA V (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: adaptive immune response;adaptive immunity;Air;Allergens;Alveolar Macrophages;Antigens;Bacterial Infections;Bioinformatics;Biological Assay;Biological Models;Categories;cell type;conditional knockout;Dendritic Cells;Disease;draining lymph node;Exposure to;falls;gene conservation;Gene Expression;Gene Expression Profile;Genes;Genetic;Genetic Markers;Grant;Heart;Heterogeneity;Human;Immune response;in vitro Model;in vivo;interstitial;Knockout Mice;Langerhans cell;Liver;Lung;lymph nodes;Macrophage;Microbe;Microscopy;monocyte;Mononuclear;Morphology;mouse model;Mus;Mycoses;Natural Immunity;Organ;particle;Phagocytes;Play;Prevention strategy;Proteins;Respiratory System;Role;single-cell RNA sequencing;Skin;System;therapy development;Tissues;trafficking;transcriptome;transcriptome sequencing;transcriptomic profiling;Transgenic Organisms;treatment strategy;Validation;virtual;Virus Diseases

PROJECT_TITLE: Human and mouse transcriptome profiling identifies cross-species homology of mononuclear phagocytes


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Biotechnology;Gene Therapy;Genetics;Regenerative Medicine

ORG_DEPT: PEDIATRICS

PHR: PROJECT NARRATIVE There is a critical need for investigators to have access to a dedicated resource for evaluating new regenerative medicine and gene therapy/somatic cell genome editing approaches with nonhuman primates for the treatment of human diseases. The overarching goals of this application are to provide models, tools, and technologies to address safe and effective treatments across age groups, and ensure opportunities are available to obtain preclinical data that will lead to human clinical trials.

PI_NAMEs: TARANTAL, ALICE F (contact)

PROGRAM_OFFICER_NAME: MIROCHNITCHENKO, OLEG

PROJECT_TERMS: adaptive immune response;Address;Adverse event;Advisory Committees;Age;age group;Animal Model;Animals;Applications Grants;Biological;Biological Models;Bioluminescence;Body System;Brain;CD34 gene;Cells;Clinical Trials;Communities;conditioning;Data;Dedications;Dependovirus;Development;Disease;effective therapy;Engraftment;Ensure;Female;Gene Expression;gene therapy;Gene Transfer;Genes;Genetic Diseases;genome editing;Goals;Heart;Hematopoietic;Hereditary Disease;Human;human disease;imaging modality;Imaging technology;Immune response;Immune system;immunogenicity;improved;in utero transplantation;in vivo evaluation;in vivo imaging;individualized medicine;Infrastructure;innovation;insight;interest;Investigation;Investigational Drugs;Kidney;life span;Liver;Lung;Macaca mulatta;male;meetings;Methods;Modeling;Monitor;Monkeys;Musculoskeletal;National Heart, Lung, and Blood Institute;National Institute of Allergy and Infectious Disease;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;National Institute of Child Health and Human Development;National Institute of Diabetes and Digestive and Kidney Diseases;National Institute of Neurological Disorders and Stroke;nonhuman primate;novel strategies;novel therapeutics;Organ;Outcome;Patients;Physiology;Positron-Emission Tomography;postnatal;pre-clinical;Primates;prime editor;Process;programs;Protocols documentation;prototype;Rare Diseases;real time monitoring;Regenerative Medicine;Research;Research Personnel;Resources;response;Rhesus;Safety;safety assessment;Serotyping;somatic cell gene editing;Specificity;Technology;technology/technique;Testing;therapeutic evaluation;Tissues;tool;translational approach;translational pipeline;Translational Research;Umbilical Cord Blood;United States National Institutes of Health;Validation;validation studies;Xenograft Model

PROJECT_TITLE: Translational Nonhuman Primate Regenerative Medicine and Gene Therapy/Genome Editing Resource Program


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;Immunization;Infectious Diseases;Prevention;Vaccine Related

ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: Infectious diseases are a major cause of human suffering and mortality in the US and worldwide. The Vaccine and Treatment Evaluation Unit at Baylor College of Medicine offers a cadre of experts in clinical research who will perform clinical vaccine development research against a variety of pathogens, and studies in patients with respiratory, gastrointestinal and sexually transmitted infections. Results from these studies will improve the scientific community's understanding of these diseases and inform public health policies.

PI_NAMEs: EL SAHLY, HANA M (contact)

PROGRAM_OFFICER_NAME: HALL, CYNDA GAY

PROJECT_TERMS: Address;Administrator;Area;Clinical;clinical application;Clinical Research;Clinical Trials;college;Communicable Diseases;Communication;Communities;Data Analyses;Data Reporting;design;Development;Disease;Emerging Communicable Diseases;Enteral;epidemiology study;Evaluation;experience;gastrointestinal;Geography;Good Clinical Practice;Health Policy;Human;Human Resources;improved;Infection;Influenza;Infrastructure;interest;Laboratory Technicians;Leadership;Medicine;Mentors;mortality;National Institute of Allergy and Infectious Disease;Nurses;pathogen;Patients;Pharmacists;Phase;Physician Assistants;Policies;Population Heterogeneity;prevent;Process;Protocols documentation;Public Health;public health emergency;Publications;Qualifying;Regulation;Research;research and development;Research Personnel;Research Priority;respiratory;response;Role;Sexually Transmitted Diseases;Site;Therapeutic;vaccine development;vaccine evaluation;Vaccines;Virus

PROJECT_TITLE: Vaccine and Treatment Evaluation Units (VTEU)


ORG_CITY: CLEVELAND

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: CASE WESTERN RESERVE UNIVERSITY

PHR: NARRATIVE Many patients with epilepsy have seizures that cannot be treated by drugs or surgery and current stimulation methods do not provide significant relief. We propose to develop a novel stimulation method that relies on the stimulation of the corpus callosum, a fiber tract that connects the two sides of the brain to suppress cortical seizures. This methods is based on a previous method we have developed to treat seizures arising in the limbic system. 1

PI_NAMEs: DURAND, DOMINIQUE M (contact)

PROGRAM_OFFICER_NAME: CHURN, SEVERN BORDEN

PROJECT_TERMS: 4-Aminopyridine;Acute;Animal Model;Animals;Anterior;Auras;Bilateral;Brain;Cell Nucleus;Chronic;clinical translation;Collaborations;commercialization;Commissure;comparative efficacy;Corpus Callosum;Deep Brain Stimulation;Development;Electric Stimulation;Electrodes;Engineering;Epilepsy;Excision;experience;Fiber;Focal Seizure;Frequencies;Generalized seizures;gray matter;Hippocampus;improved;In Vitro;in vivo;Injections;Intractable Epilepsy;Kainic Acid;Limbic System;Location;medial temporal lobe;Methods;Modality;Modeling;Monitor;Motor Cortex;Nervous System Disorder;Neurons;novel;Operative Surgical Procedures;Partial Epilepsies;Patients;Pharmaceutical Preparations;Pharmacology;Phase I Clinical Trials;phase II trial;Preparation;prevent;Procedures;Protocols documentation;Published Comment;Quality of life;Recurrence;Resected;Rest;Scientist;Seizures;Side;Site;Slice;Symptoms;Technology;Temporal Lobe Epilepsy;Testing;Tetanus Toxin;Thalamic structure;Therapeutic;Therapeutic Agents;Thick;Translating;Unconscious State;voltage;Work

PROJECT_TITLE: Low-frequency stimulation of fiber tracts to control seizures

STUDY_SECTION: ANIE

STUDY_SECTION_NAME: Acute Neural Injury and Epilepsy Study Section[ANIE]