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

ORG_CITY: ANN ARBOR

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE The Research Domain Criteria (RDoC) initiative is a prominent research effort to identify differences in brain functions that place people at risk for mental disorders, but many of these functions are difficult to define and measure, have ambiguous links to neurobiology, and do not have selective relationships with specific disorders. The proposed project seeks to evaluate whether efficiency of evidence accumulation (EEA), a precisely defined brain process that has been well-characterized in computational modeling and neurophysiological research, can move the RDoC initiative forward by improving measurement of complex brain functioning and better explaining its relationship with a wide array of mental disorders. Insights from this project could be used to accelerate neuroscience research into the causes and treatments of psychological disorders and refine diagnostic criteria in mental health care.

PI_NAMEs: WEIGARD, ALEXANDER  (contact)

PROGRAM_OFFICER_NAME: FERRANTE, MICHELE

PROJECT_TERMS: Acceleration;Affect;Age;Arousal;Attention;Attention deficit hyperactivity disorder;Behavior;Biological;Brain;clinical phenotype;Cognition;Cognitive;cognitive ability;cognitive control;Cognitive deficits;cognitive performance;cognitive system;cognitive task;Complex;computer framework;Computer Models;contextual factors;Data;Data Collection;Decision Making;design;Diagnostic;diagnostic criteria;Dimensions;Disease;disease classification;Disinhibition;Emotional;Etiology;experimental study;Human;Impairment;improved;Individual;Individual Differences;individual variation;Informal Social Control;insight;Intervention;Level of Evidence;Link;Mathematics;Measurement;Measures;Memory impairment;Mental disorders;Mental Health Services;Methods;Modeling;negative affect;neurobehavioral;neurobiological mechanism;Neurobiology;neurophysiology;Neurosciences;Neurosciences Research;Participant;Performance;Persons;Populations at Risk;Process;programs;Properdin;Property;psychologic;Psychometrics;Psychopathology;Research;Research Domain Criteria;response;Risk;Risk Factors;Role;Schizophrenia;Short-Term Memory;Sleep;Sleep disturbances;sleep regulation;smartphone application;Stress;stressor;Structure;substance use;Symptoms;Testing;theories;tool;trait;Variant;Work

PROJECT_TITLE: Efficiency of evidence accumulation (EEA) as a higher-order, computationally defined RDoc construct

STUDY_SECTION: NPAS

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: GRADUATE SCHOOLS

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: CAMBRIDGE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: CHEMISTRY

ORG_FIPS: US

ORG_NAME: HARVARD UNIVERSITY

ORG_STATE: MA

PHR: Project Narrative The research proposed here is directed towards understanding the protein machinery responsible for the biogenesis of the cell envelopes of Gram-negative bacteria and mycobacterium tuberculosis. These multi- layered envelopes are essential for survival and provide intrinsic drug resistance. A better understanding of the lipid transporters that assemble the cell envelope may lead to the discovery of inhibitors that could ultimately be developed for therapeutic uses to treat drug-resistant infections.

PI_NAMEs: KAHNE, DANIEL  (contact);KRUSE, ANDREW

PROGRAM_OFFICER_NAME: ROBINSON, RICHARD THOMAS

PROJECT_TERMS: Acinetobacter baumannii;Address;Affinity;Amino Acids;Amino Acyl-tRNA Synthetases;Antibiotics;ATP-Binding Cassette Transporters;Bacteria;Biochemical;Biochemistry;Biogenesis;Biological Assay;Biology;Carrier Proteins;cell assembly;cell envelope;Cell surface;Cells;Cellular Structures;Collaborations;Complex;Cytoplasm;Data;Development;Disaccharides;Drug resistance;Escherichia coli;Face;Family;Genus Mycobacterium;Glycolipids;Gram-Negative Bacteria;Health;Human;Impairment;improved;Infection;inhibitor;Lipid A;Lipid Binding;Lipids;Lipopolysaccharides;Maps;Membrane;Methods;Molecular Conformation;Monitor;multidisciplinary;muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol;Mycobacterium tuberculosis;Mycolic Acid;novel;novel strategies;novel therapeutics;Organism;Pathway interactions;Penetration;Peptidoglycan;periplasm;Permeability;Pharmaceutical Preparations;Polymers;Polysaccharides;Process;Proteins;Public Health;Pump;Research;Resistance;resistance frequency;Role;Side;small molecule;structural biology;Structure;sugar;Surface;therapeutic development;Therapeutic Uses;tool;Toxic effect;Transmembrane Transport;transport inhibitor;Trehalose;tuberculosis treatment;Variant;Work

PROJECT_TITLE: Targeting Membrane Transport Steps in Cell Envelope Assembly

STUDY_SECTION: MSFA

STUDY_SECTION_NAME: Macromolecular Structure and Function A Study Section[MSFA]


ADMINISTERING_IC: DK

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Kidney Disease;Organ Transplantation;Transplantation

ORG_CITY: Aurora

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Low serum bicarbonate levels, even within the normal laboratory range, are strongly associated with increased risks of endothelial dysfunction, cardiovascular disease, worsening kidney disease and death. The current proposal will investigate whether bicarbonate administration in patients who have received a kidney transplant will improve the health and function of arteries and the transplanted kidney. Overall, the proposed research will provide important new scientific evidence upon which physicians can base recommendations to kidney transplant recipients to decrease the risk of developing cardiovascular disease and worsening kidney disease.

PI_NAMEs: KENDRICK, JESSICA B (contact);THURMAN, JOSHUA M

PROGRAM_OFFICER_NAME: ABBOTT, KEVIN C

PROJECT_TERMS: Acids;Alkalies;Allografting;Alternative Complement Pathway;Ammonium;Aorta;arterial stiffness;Arteries;Atrophic;base;Bicarbonates;Blood Vessels;brachial artery;Calcineurin inhibitor;Cardiovascular Diseases;cardiovascular risk factor;Cardiovascular system;cardiovascular transplantation;Cause of Death;Cessation of life;Chronic Kidney Failure;clinical practice;Clinical Trials;Collagen;comparison control;Complement;Complement Activation;Controlled Clinical Trials;Data;Deposition;Development;dietary;Double-Blind Method;Elasticity;endothelial dysfunction;Endothelium;Equilibrium;Event;Excretory function;experience;Feasibility Studies;Fibrosis;General Population;Glomerular Filtration Rate;graft function;Health;Histology;improved;Inflammation;Inflammatory;interstitial;Intervention Trial;Kidney;kidney allograft;kidney biopsy;Kidney Diseases;Kidney Transplantation;Laboratories;Measures;Mediating;Metabolic acidosis;mortality;Nephrons;novel;novel therapeutics;Observational Study;Oral;Patients;Pharmaceutical Preparations;Physicians;Physiologic pulse;Placebo Control;Placebos;Plasma;preservation;prospective;Proteinuria;Randomized;randomized trial;Recommendation;Renal tubular acidosis;Reporting;Research;Risk;safety and feasibility;Serum;Sodium Bicarbonate;soluble complement C5b-9;Surrogate Markers;Testing;Time;Tissues;Transplant Recipients;Transplantation;trend;Tubular formation;urinary;Urine;Vascular Diseases;Vascular Endothelium;Vascular Graft

PROJECT_TITLE: Effect of Alkali Therapy on Vascular and Graft Function in Kidney Transplant Recipients

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


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

PHR: PROJECT NARRATIVE: Inactive lifestyle leads to a variety of diseases, including metabolic disorders, cardiovascular dysfunctions, and mental illness, and the sedentary behavior caused by diseases exacerbates pathogenesis. Irisin was identified as an exercise-induced hormone that benefits multiple tissues/organs. Elucidating the molecular basis of irisin- mediated effects via its integrin receptor may reveal a novel mechanism of hormone-induced integrin signaling, and therapeutically, it will assist drug and antibody development to treat sedentary individuals to prevent disease progression.

PI_NAMEs: A, MU  (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Adipocytes;Adipose tissue;Affect;Affinity;Affinity Chromatography;age-related disease;Amino Acids;Animals;Antibodies;Binding;Biochemical;Biochemistry;Biological;biophysical properties;Biophysics;Blood;bone;Bone remodeling;Brain;Bypass;Cardiovascular Diseases;Cardiovascular system;Cell Culture Techniques;Cell surface;Cells;Cellular biology;Cellular Metabolic Process;cofactor;Cognitive deficits;Complex;Cultured Cells;Data;Degenerative Disorder;Development;disability;Disease;Disease Progression;endurance exercise;Equilibrium;Exercise;Exhibits;Fatty acid glycerol esters;Fibronectins;Fluorescence Microscopy;Functional disorder;glycosylation;Half-Life;Heart;Heat-Shock Response;Hormones;Human;improved;in vivo;Individual;Integrin alphaV;Integrin Binding;Integrins;Life Style;Ligand Binding;Ligands;Liver;Malignant Neoplasms;Mammalian Cell;Maps;Measures;Mediating;Membrane Proteins;Mental disorders;Metabolic Diseases;Metabolism;Molecular;molecular modeling;Morbid Obesity;Mus;Muscle;Muscle Cells;Muscle Fibers;Muslim religion;mutant;myogenesis;N-terminal;Nature;neuropathology;Non-Insulin-Dependent Diabetes Mellitus;novel;Nuclear;obese patients;Organ;Pathogenesis;Pathway interactions;Pattern;Persons;Pharmaceutical Preparations;Physical activity;physical inactivity;Physiology;Plasma;polypeptide;PPAR gamma;prevent;protein purification;Proteins;Publishing;receptor;receptor binding;Recombinant Proteins;Recombinants;Research;Resources;RGD (sequence);Role;Scientist;sedentary;sedentary lifestyle;Signal Transduction;Site;Skeletal Muscle;Structure;subcutaneous;Symptoms;Technology;Testing;Therapeutic;Tissues;Training;Transcription Coactivator;Work

PROJECT_TITLE: Elucidating novel molecular mechanisms of irisin-mediated effects via integrin


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Cerebral Palsy;Clinical Research;Clinical Trials and Supportive Activities;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rehabilitation

ORG_CITY: CHICAGO

ORG_NAME: REHABILITATION INSTITUTE OF CHICAGO D/B/A SHIRLEY RYAN ABILITYLAB

ORG_STATE: IL

PHR: Project Narrative: The goal of the proposed study is to examine the neuromuscular mechanisms underlying the therapeutic effect of hippotherapy and determine whether repeated exposure to a pelvic perturbation force would be effective in improving trunk postural control and gait of children with cerebral palsy (CP). The results from this study will lead to innovative clinical therapies aimed at improving trunk postural control and locomotor function in children with CP. We anticipate that this paradigm will be extremely useful for improving trunk postural control and locomotor function in children with CP through robotic hippotherapy.

PI_NAMEs: WU, MING  (contact)

PROGRAM_OFFICER_NAME: CHEN, DAOFEN

PROJECT_TERMS: Agonist;antagonist;Articular Range of Motion;autistic children;Cerebral Palsy;Chest;Child;Childhood;Clinical;conventional therapy;Data;effective intervention;Equilibrium;Exhibits;Exposure to;Extensor;Flexor;Foundations;Frequencies;Functional disorder;functional gain;functional improvement;Gait;gait rehabilitation;Goals;Head;Impairment;improved;Incidence;Infant;innovation;Intervention;Kyphosis deformity of spine;Live Birth;Locomotion;Lordosis;Measures;Motor;motor control;Movement;Muscle;muscle strength;Musculoskeletal;Musculoskeletal Equilibrium;Neck;neural;neuromuscular;neuromuscular examination;Neuronal Plasticity;novel;Pathway interactions;patient population;peer;Pelvis;physically handicapped;Postural response;Psychological reinforcement;response;robotic system;Robotics;skills;Specificity;Synapses;Therapeutic Effect;Training;Walking;Work

PROJECT_TITLE: Neuromuscular mechanisms of specific trunk interventions in children with cerebral palsy

STUDY_SECTION: MRS

STUDY_SECTION_NAME: Musculoskeletal Rehabilitation Sciences Study Section[MRS]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Narrative  Abdominal aortic aneurysm (AAA) rupture can be a deadly disease. We introduce, develop, and evaluate a novel approach to imaging AAA biology, and translate it for AAA imaging in humans. This may ultimately, help identify patients who are at risk for rupture and reduce AAA mortality.

PI_NAMEs: GROPLER, ROBERT J.;SADEGHI, MEHRAN M (contact)

PROGRAM_OFFICER_NAME: SERRA, MONICA CHRISTINE

PROJECT_TERMS: Abdominal Aortic Aneurysm;Address;Affect;aged;Aneurysm;Aorta;Aortic Aneurysm;Autoradiography;Binding;Biodistribution;Biological;Biological Process;Biology;Blood;Blood Vessels;Cell Density;Cessation of life;Characteristics;Clinical;Clinical Research;clinical translation;comorbidity;DCNU;Detection;Diameter;Disease;Dissection;Donor person;drug development;Drug Kinetics;Elastin;Elastin Fiber;Elderly;Evaluation;Evolution;Extracellular Matrix Degradation;Extracellular Matrix Proteins;Family;first-in-human;fluorodeoxyglucose positron emission tomography;Funding;Half-Life;high risk;Histologic;Hour;Human;Image;imaging modality;imaging study;improved;In Vitro;in vivo;Inflammation;Isotope Labeling;Link;Matrix Metalloproteinases;Measurement;Medical;medical schools;men;Methods;microPET/CT;microSPECT;molecular imaging;Monitor;Morbidity - disease rate;mortality;mouse model;Multicenter Trials;Multimodal Imaging;Mus;National Institute of Biomedical Imaging and Bioengineering;Non-Invasive Detection;novel;novel strategies;Operative Surgical Procedures;Pathogenesis;patient stratification;patient subsets;Patients;Performance;Play;Positron-Emission Tomography;Practice Guidelines;Predictive Value;Production;Property;Proteins;Radioisotopes;Radiometry;radiotracer;Recommendation;repaired;Research Personnel;Resources;Risk;Risk Factors;risk stratification;Rupture;Ruptured Abdominal Aortic Aneurysm;Safety;screening;Shipping;Signal Transduction;single photon emission computed tomography;Site;Smoker;Smooth Muscle Myocytes;Species Specificity;Specificity;Specimen;targeted imaging;Technology;temporal measurement;therapeutic effectiveness;Tissues;tool;Tracer;Translating;ultrasound;Universities;uptake;Vascular remodeling;Vascular Smooth Muscle;volunteer;Washington;X-Ray Computed Tomography

PROJECT_TITLE: PET Imaging of MMP Activation in AAA: First in-Human Evaluation

STUDY_SECTION: IPCA

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


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Complementary and Integrative Health;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Nutrition;Obesity;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Women's Health Research

ORG_CITY: TAMPA

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

ORG_STATE: FL

PHR: PUBLIC HEALTH RELEVANCE: Obesity is a significant public health concern that is disproportionately represented among adult black females. Current obesity treatment strategies among this population produce suboptimal weight loss outcomes. This project will determine whether addressing stress management among a group of adult black females with obesity and elevated stress will lead to greater weight loss than standard behavioral weight loss programs.

PI_NAMEs: CARSON, TIFFANY LASHAUN (contact)

PROGRAM_OFFICER_NAME: EVANS, MARY

PROJECT_TERMS: 2 arm randomized control trial;Address;Adult;Affect;Behavioral;Behavioral Mechanisms;Biological Markers;Black Populations;black women;Blood Glucose;Body Weight;Body Weight Changes;Body Weight decreased;Chronic;Chronic Disease;Chronic stress;Clinical;combat;comparison intervention;Coping Skills;diabetes prevention program;diabetes risk;Disparate;disparity reduction;Effectiveness;effectiveness testing;Energy Intake;Energy Metabolism;evidence base;experience;follow-up;Gender;group intervention;Health;high body mass index;High Prevalence;high risk;Hydrocortisone;improved;improved outcome;Individual;intersectionality;Intervention;intervention effect;lifestyle intervention;lifetime risk;Link;Literature;Malignant Neoplasms;Measures;Mediating;Mediation;member;Modality;Modeling;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;Obesity;Obesity Epidemic;obesity risk;obesity treatment;Outcome;Outcome Study;Overweight;Paper;Participant;perceived stress;Persons;Physical activity;Population;Prevalence;primary outcome;Process Assessment;Process Measure;Psychological Stress;Public Health;public health relevance;Publishing;Race;racial difference;Randomized;Randomized, Controlled Trials;Reporting;Risk;Risk Factors;Role;Salivary;secondary outcome;sex;Site;Stress;stress management;stress reduction;Surveys;systematic review;Testing;Time;Training;treatment adherence;treatment strategy;trend;United States;Weight;Weight Gain;weight loss intervention;weight loss program;Weight maintenance regimen;White Women;Work

PROJECT_TITLE: Improving weight loss outcomes of black women using a culturally relevant, stress management enhancement behavioral weight loss intervention

STUDY_SECTION: PRDP

STUDY_SECTION_NAME: Psychosocial Risk and Disease Prevention Study Section[PRDP]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Aging;Atherosclerosis;Bioengineering;Biomedical Imaging;Cardiovascular;Heart Disease;Heart Disease - Coronary Heart Disease;Precision Medicine;Prevention

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: The most prevalent type of heart disease is caused by atherosclerosis, the thickening of the vessel wall and creation of atherosclerotic plaque. In this project, we will develop an imaging tool for the compre- hensive assessment of atherosclerotic plaque composition and vulnerability, with a clear pathway for translation into the clinical environment to enable the determination of the optimal treatment strategy in individual patients.

PI_NAMEs: URIBE-PATARROYO, NESTOR  (contact)

PROGRAM_OFFICER_NAME: ANDERSON, AFROUZ AZARI

PROJECT_TERMS: Address;Angiography;Arterial Fatty Streak;Atherosclerosis;biomechanical test;Biomechanics;Cadaver;Cardiac;Catheterization;Catheters;Cause of Death;Cessation of life;Chemicals;Clinical;Clinical Research;Consumption;Coronary Arteriosclerosis;Coronary artery;Coronary heart disease;coronary plaque;Development;Disease;Distal;elastography;Elements;Environment;Event;Family suidae;Funding;Future;Goals;Heart;Heart Diseases;Human;human subject;Image;Imaging Device;imaging platform;Imaging technology;improved outcome;individual patient;instrumentation;Intervention;Lasers;Lateral;Lesion;Link;Measures;Mechanics;meter;Methods;Modeling;Molecular;Myocardial Infarction;Near-Infrared Spectroscopy;novel;Obstruction;Optical Coherence Tomography;optical imaging;Optics;optimal treatments;Pathology;Pathway interactions;Patients;percutaneous coronary intervention;preventive intervention;Procedures;Property;Research;Resolution;response;Risk;Robotics;Rupture;signal processing;Source;Specificity;Speed;Stents;Structure;System;Techniques;Technology;technology development;technology validation;Testing;Thinness;Time;tool;Translations;treatment strategy;Validation

PROJECT_TITLE: Intravascular microstructural, chemical and biomechanical characterization of coronary plaques

STUDY_SECTION: IGIS

STUDY_SECTION_NAME: Imaging Guided Interventions and Surgery Study Section[IGIS]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Cardiovascular

ORG_CITY: HOUSTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: The ion channel protein, TRPV2 is important for regulation of cardiovascular health, and has been implicated in cancer, diabetes, muscular dystrophy and other diseases. This project aims to understand the structural basis for its regulation as a prerequisite for structure-based design of new therapies.

PI_NAMEs: WENSEL, THEODORE G (contact)

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Agonist;Animal Model;antagonist;Binding;Biological Assay;Cardiac Myocytes;Cardiovascular Agents;cardiovascular health;Cardiovascular Physiology;Cardiovascular system;Cations;Cellular Membrane;Clinical;Clinical Research;Cryoelectron Microscopy;Cultured Cells;Cytoplasm;Defect;design;Development;Diabetes Mellitus;Disease;Drug Targeting;Dyes;Electrophysiology (science);Engineering;Enzymes;experimental study;extracellular;Face;Family;Future;Goals;inhibitor;Ion Channel;Ion Channel Protein;Knock-out;Ligands;Lipids;Malignant Neoplasms;Measures;mechanical stimulus;Mechanical Stress;Mediating;Membrane;Monitor;Muscular Dystrophies;Mutagenesis;mutant;Mutation;nanodisk;novel therapeutics;patch clamp;Pathologic;Pharmaceutical Preparations;Phenotype;Phosphatidylinositol 4,5-Diphosphate;Phosphatidylinositols;Phosphoric Monoester Hydrolases;Phosphotransferases;Physiology;Play;Process;Property;protein reconstitution;Proteins;Recombinants;reconstitution;Regulation;Reporting;response;Role;Specificity;Structure;Symptoms;Testing;Therapeutic;TRPV channel;Vesicle;voltage

PROJECT_TITLE: Cardiovascular drug target, TRPV2

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-TDPS-R(01)]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Breastfeeding, Lactation and Breast Milk;Childhood Obesity;Clinical Research;Eating Disorders;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurosciences;Nutrition;Obesity;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: LOS ANGELES

ORG_NAME: CHILDREN'S HOSPITAL OF LOS ANGELES

ORG_STATE: CA

PHR: Project Narrative  Deficits in brain processes associated with executive functioning (i.e., decision-making) are postulated to contribute to appetite dysregulation and subsequent obesity. Theoretical models propose explanations for these associations, but it is unknown if: A) underlying differences in brain regions associated with executive function cause weight gain, and/or, if: B) diet-induced neuroinflammation causes changes to brain structure in regions associated with executive function, particularly during developmental periods (e.g., childhood, adolescence) when the brain is undergoing changes in executive function and appetite regulation. During periods of critical physical growth and brain maturation (e.g., birth to adolescence), the current proposal will investigate the temporal and directional cause vs. consequence associations between executive function and obesity development, while also examining potential moderating and attenuating effects of factors know to increase obesity risk and executive functioning development, such as sex, puberty, social and economic disparities, and infant nutrition.

PI_NAMEs: ADISE, SHANA  (contact)

PROGRAM_OFFICER_NAME: CUMMINGS, DIANA M

PROJECT_TERMS: 6 year old;Abdomen;Address;Adolescence;Adolescent;Adolescent obesity;Affect;Age;Appetite Regulation;Attenuated;Award;Behavioral;Biological Markers;Birth;Body Composition;Body fat;Bottle feeding;Brain;Brain region;career;career development;Cattle;Child;Child Development;Child Health;Childhood;cognitive development;cognitive neuroscience;cohort;Complex;computational neuroscience;critical developmental period;critical period;Data;Data Analyses;Data Set;Decision Making;Desire for food;Development;Development Plans;Diabetes Mellitus;Diet;Dietary Sugars;early-life nutrition;eating in absence of hunger;economic disparity;Endocrinology;Environment;environmental disparity;executive function;experience;Exposure to;Faculty;Feeding behaviors;Foundations;Functional Magnetic Resonance Imaging;Funding;Future;Goals;Grain;Grant;Growth;Health;healthy weight;high body mass index;Hospitals;Human Milk;Hyperphagia;Infant;infant nutrition;innovation;insight;Intake;Intervention Studies;Laboratories;Latino;Life;Link;Los Angeles;Machine Learning;Magnetic Resonance Imaging;Measures;Mediating;Mentored Research Scientist Development Award;Mentors;Mentorship;Metabolism;Milk;Modeling;Mothers;National Institute of Diabetes and Digestive and Kidney Diseases;Neighborhoods;Neuroanatomy;Neurocognitive;neurodevelopment;neuroimaging;neuroinflammation;Neurologic;novel;nutrition;Obesity;obesity development;obesity in children;obesity risk;Outcome;pediatric department;Pediatric Hospitals;Pediatric Research;Performance;Phenotype;Population;population based;Postdoctoral Fellow;Prefrontal Cortex;Process;programs;prospective;Protocols documentation;Puberty;Publications;recruit;Research;Research Personnel;Research Support;Resources;Rewards;Scientist;sex;Short-Term Memory;Site;skills;social disparities;social influence;Solid;Source;Statistical Data Interpretation;statistics;Structure;sugar;Theoretical model;Thinness;Time;tool;Training;treatment program;United States National Institutes of Health;Variant;Ventral Striatum;Weight;Weight Gain;Youth

PROJECT_TITLE: Neurodevelopment of executive function, appetite regulation, and obesity in children and adolescents

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Clinical Research;Comparative Effectiveness Research;Patient Safety;Physical Injury - Accidents and Adverse Effects

ORG_CITY: BALTIMORE

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: NARRATIVE Minimally displaced femoral neck fractures have traditionally been treated with internal fixation, however, preliminary data suggests treating these fractures with arthroplasty may yield better outcomes. While promising, data supporting the use of arthroplasty is limited, and clinical practice would benefit from a definitive trial that clearly defines the optimal surgical treatment for patients with a minimally displaced femoral neck fracture. We propose an 18-month planning period to finalize the patient-centered trial protocol, establish trial infrastructure, and prepare clinical sites for initiation for a multi-center randomized controlled trial designed to address this need.

PI_NAMEs: O'HARA, NATHAN NOEL;SLOBOGEAN, GERARD  (contact)

PROGRAM_OFFICER_NAME: WASHABAUGH, CHARLES H

PROJECT_TERMS: Address;Adopted;Adult;Caring;Clinical;clinical care;clinical practice;clinical research site;clinical trial protocol;Complication;Consensus;Contracts;Data;Data Management Resources;design;Devices;Dissection;Elderly;Ensure;experience;Failure;Femoral Neck Fractures;Fracture;Funding;Grant;Health;Hip Fractures;hip replacement arthroplasty;Hospitals;Implant;improved;improved mobility;In Situ;Individual;Infrastructure;Injury;Institutional Review Boards;Institutionalization;Modeling;mortality;mortality risk;Multicenter Trials;National Institute of Arthritis, and Musculoskeletal, and Skin Diseases;novel;Operative Surgical Procedures;Orthopedics;Outcome;patient oriented;Patient-Focused Outcomes;Patients;Pattern;Phase;Principal Investigator;Process;Protocols documentation;Qualifying;Randomized;randomized, clinical trials;Randomized, Controlled Trials;recruit;Repeat Surgery;Replacement Arthroplasty;Research;Risk;Risk Reduction;sample fixation;Selection Criteria;Site;standard care;Statistical Data Interpretation;success;Surgeon;Target Populations;Testing;Training;Trauma;treatment choice;trial comparing;trial design;Work

PROJECT_TITLE: A Planning Grant for a Multicenter Randomized Clinical Trial Comparing Hip Arthroplasty to Internal Fixation for Minimally Displaced Femoral Neck Fractures

STUDY_SECTION: AMSC

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


NIH_SPENDING_CATS: Aging;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Diabetes;Health Services;Heart Disease;Precision Medicine

ORG_CITY: Canton

ORG_NAME: HARVARD PILGRIM HEALTH CARE, INC.

PHR: PROJECT NARRATIVE While newer antihyperglycemic agents have reported cardiovascular benefits, little is known about how to choose among an expanded range of medication choices for older patients. The proposed research aims to understand the comparative effectiveness and safety of these agents in older adults in routine care while applying, developing, and disseminating state-of-the-art analytical and causal inference methods. The findings will improve the evidence base for decision-making available for clinicians treating older patients, promote effective and safe drug therapy, and ultimately improve the care of older patients.

PI_NAMEs: LI, XIAOJUAN  (contact)

PROGRAM_OFFICER_NAME: SALIVE, MARCEL

PROJECT_TERMS: Accounting;Address;Adult;Agonist;Agreement;analytical method;Area;Benchmarking;Cardiac;Cardiovascular Diseases;Cardiovascular system;career;career development;Caring;Cause of Death;Cessation of life;Characteristics;Clinical;clinical care;Clinical Data;clinical practice;Clinical Research;comparative effectiveness;comparative safety;Complex;Data;Data Set;Decision Making;design;Diabetes Mellitus;Doctor of Philosophy;Effectiveness;effectiveness outcome;EFRAC;Elderly;electronic health database;Eligibility Determination;Environment;Event;evidence base;Exclusion;experience;Feedback;follow-up;Fracture;frailty;Funding;Future;Geriatrics;GLP-I receptor;Glucose;Goals;Head;head-to-head comparison;Health Care Costs;Healthcare;Heart failure;Heterogeneity;high dimensionality;Hospitalization;human old age (65+);Hypoglycemia;Hypoglycemic Agents;improved;Individual;inhibitor;instructor;Laboratories;limb amputation;Link;Long-Term Effects;Lower Extremity;Machine Learning;Measures;Medical;medical schools;Medicine;Mentors;Methods;Mission;Modernization;mortality;National Institute on Aging;New Agents;Non-Insulin-Dependent Diabetes Mellitus;novel;novel strategies;Observational Study;older adult;older patient;Older Population;Outcome;Patients;personalized medicine;Pharmaceutical Preparations;Pharmacoepidemiology;Pharmacotherapy;Placebo Control;Placebos;Population;Positioning Attribute;preservation;prevent;Productivity;Publishing;Randomized, Controlled Trials;Reporting;Research;Research Methodology;Research Scientist Award;response;revascularization;Risk;routine care;Safety;safety outcomes;Sample Size;semiparametric;skills;Sodium;symporter;Test Result;Time;tool;Training;treatment comparison;treatment effect;treatment strategy;Urinary tract infection;Work

PROJECT_TITLE: Optimizing care for older adults in the new treatment era for type 2 diabetes and heart failure: Strengthening causal inference through novel approaches and evidence triangulation

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development For Early Career Investigators Study Section [AGCD-2]


ADMINISTERING_IC: HL

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: Newark

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF DELAWARE

ORG_STATE: DE

PHR: PROJECT NARRATIVE The proposed research is highly relevant to public health because pulmonary arterial hypertension (PAH) is a progressive vascular disease with high morbidity and mortality. The proposed studies will define the role of vacuolar protein sorting (Vps34) in regulating increased proliferation and survival of pulmonary vascular smooth muscle cells in PAH; will provide insights into the molecular mechanisms that are important in the pathogenesis of PAH; and will explore whether Vps34 could serve as a target pathway for pulmonary vascular remodeling- focused therapeutic interventions.

PI_NAMEs: SHEN, YUANJUN  (contact)

PROGRAM_OFFICER_NAME: SUTLIFF, ROY L

PROJECT_TERMS: alpha Actin;Apoptosis;Applications Grants;Area;Attenuated;Binding;Biological;Blood Vessels;cancer cell;Cell Proliferation;Cell Survival;Cells;Cessation of life;Co-Immunoprecipitations;Complex;Data;Development;Disease;Enzyme-Linked Immunosorbent Assay;Experimental Models;FRAP1 gene;Future;Growth;Heart failure;hemodynamics;Human;Hypoxia;Immunoblot Analysis;improved;in vivo;Induction of Apoptosis;inhibitor;insight;Lung;Malignant Neoplasms;Medial;Methods;Microscopy;Modeling;Molecular;molecular targeted therapies;Morbidity - disease rate;Morphology;mortality;Mus;novel;Pathogenesis;Pathway interactions;Patients;pharmacologic;phosphatidylinositol 3-phosphate;Phosphorylation;Physiologic intraventricular pressure;PIK3CG gene;pre-clinical;pressure;Production;Proliferating;Protein Dephosphorylation;Proteins;Public Health;Publishing;pulmonary arterial hypertension;Pulmonary arterial remodeling;Pulmonary artery structure;Pulmonary Hypertension;pulmonary vascular remodeling;Regulation;Research;Right Ventricular Hypertrophy;RNA Interference;Rodent;Rodent Model;Role;Signal Transduction;Small Interfering RNA;Smooth Muscle;Smooth Muscle Myocytes;SU 5416;Systolic Pressure;Technology;Testing;Therapeutic Intervention;Thick;TSC1 gene;TSC1/2 gene;TSC2 gene;Vacuolar Protein Sorting;Vascular Diseases;Vascular Smooth Muscle;vascular smooth muscle cell proliferation;Ventricular;ventricular hypertrophy

PROJECT_TITLE: Vascular Smooth Muscle Vps34 in Pulmonary Arterial Hypertension

STUDY_SECTION: MTI

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


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Brain Disorders;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Depression;Genetics;Mental Health;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: Los Angeles

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE Craniosynostosis is a congenital craniofacial disorder caused by genetic mutations and environmental insults such as antidepressant drugs. This proposal investigates how gene mutations interplay with maternal usage of antidepressant drugs, leading to craniosynostosis, and whether MSC implantation can rescue related skull and neurocognitive defects. The knowledge gained from this study will improve our understanding of gene- environment interaction in craniosynostosis and guide our therapeutic efforts in MSC-mediated tissue regeneration in treating craniosynostosis.

PI_NAMEs: CHAI, YANG ;CHEN, JIANFU  (contact)

PROGRAM_OFFICER_NAME: SAIFUDEEN, ZUBAIDA

PROJECT_TERMS: Address;Affect;Animal Model;anti-depressive agents;Behavior;Behavioral;bone;Brain;brain dysfunction;brain volume;Calvaria;Cells;Citalopram;clinically relevant;Cognitive;Complex;Congenital Abnormality;Congenital Disorders;Coupled;Craniofacial Abnormalities;craniofacial disorder;Craniosynostosis;cranium;Defect;Deformity;Depressed mood;Disease;DNA Sequence Alteration;Dura Mater;Dysmorphology;Environment;Environmental Risk Factor;Exposure to;fighting;Functional disorder;gene environment interaction;Gene Mutation;Genes;Goals;Hormones;Human;Implant;implantation;improved;in utero;Individual;Infant;innovation;Intellectual functioning disability;Intracranial Hypertension;Intracranial Pressure;Joint structure of suture of skull;Knowledge;Legal patent;Life;Link;Maternal Exposure;Mediating;Meninges;Mental Depression;Mesenchymal Stem Cells;Modeling;Molecular;Morphology;mouse model;Mus;Mutant Strains Mice;Mutation;Natural regeneration;neglect;Neurocognitive;Neurocognitive Deficit;Neurologic;Neurotransmitters;Operative Surgical Procedures;Patients;Penetration;Pharmaceutical Preparations;Phenotype;pregnant;premature;prenatal exposure;programs;Quality of life;recruit;Repeat Surgery;restoration;scaffold;Selective Serotonin Reuptake Inhibitor;Serotonin;Severities;skull base;stem cell exhaustion;stem cell therapy;stem cells;Structure;Surgical sutures;Testing;Therapeutic;Therapeutic Studies;tissue regeneration;transcription factor;TWIST1 gene;United States;WNT Signaling Pathway;Woman

PROJECT_TITLE: Mechanisms and rescue of craniosynostosis associated with gene-environment interaction

STUDY_SECTION: SBDD

STUDY_SECTION_NAME: Skeletal Biology Development and Disease Study Section[SBDD]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Clinical Research;Comparative Effectiveness Research;Cost Effectiveness Research;Genetic Testing;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Human Genome;Pediatric;Precision Medicine;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases;Social Determinants of Health

PHR: PROJECT NARRATIVE With hundreds of genetic tests becoming available for clinical use, adding genomic sequencing for all newborns at birth to predict and prevent future diseases is becoming a possibility. Our research aims to extend the Precision Medicine Policy and Treatment (PreEMPT) Model – a sophisticated computer model capable of simulating short- and long-term clinical benefits and estimating the cost-effectiveness of integrating different genomic sequencing strategies into clinical care for newborns for a wide variety of heritable conditions – to evaluate outcomes through adulthood and testing of siblings of newborns with mutations. We will also evaluate targeted strategies for newborn genomic sequencing with the goal of reducing race-based medical care disparities.

PI_NAMEs: CHRISTENSEN, KURT DEREK (contact)

PROGRAM_OFFICER_NAME: PARISI, MELISSA

PROJECT_TERMS: Accounting;Address;Adoption;Adult;Age;Area;Benefits and Risks;Biotinidase Deficiency;Birth;Cardiovascular system;Caring;cascade genetic testing;Cessation of life;Child;Childhood;Clinical;clinical care;Clinical Data;clinically actionable;cohort;Computer Models;Computers;Conscious;cost;cost effective;cost effectiveness;cost estimate;cost-effectiveness evaluation;Costs and Benefits;Data;Diagnostic;Disease;Disease Outcome;Disparity;Early Diagnosis;economic value;Economics;epidemiologic data;Epidemiology;Ethnic Origin;Evaluation;Event;expectation;Family member;Foundations;Funding;Future;Genetic Diseases;Genetic Screening;genetic testing;Genomic medicine;Genomics;Glycogen storage disease type II;Goals;Health;Health Benefit;health disparity;health economics;Health Policy;Health system;Heart Diseases;Heritability;high risk population;improved;Infant Care;Informatics;Inherited;innovation;insight;Knowledge;Life Cycle Stages;Logic;Long-Term Effects;Malignant Childhood Neoplasm;Malignant hyperpyrexia due to anesthesia;Measurement;Medical;Metabolic Diseases;Methods;Modeling;models and simulation;Morbidity - disease rate;mortality;Mutation;Neonatal Screening;Newborn Infant;Onset of illness;Other Genetics;Outcome;Pathogenicity;Pediatrics;Policies;Population;population based;precision medicine;predictive modeling;prevent;Progress Reports;Public Health;Race;racial disparity;randomized trial;Research;Research Personnel;Research Priority;research study;Risk;Scientific Advances and Accomplishments;screening;Siblings;simulation;Solid;standard of care;systems research;Technology;Testing;tool;translational genomics;treatment as usual;Uncertainty;Underrepresented Populations;United States;uptake;Variant

PROJECT_TITLE: Precision Medicine Policy and Treatment (PreEMPT) Model II


NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: NEW YORK

ORG_DEPT: NEUROLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Immune cells are instrumental in the fatal neurological disease, amyotrophic lateral sclerosis (ALS), but how and why remain to be established. Herein, we propose to use a state-of-the-art technology to elucidate the characteristics of immune cells in ALS. If successful, the generated information will have far-reaching implications for the development of biomarkers and treatments for ALS and related conditions.

PI_NAMEs: PRZEDBORSKI, SERGE E (contact)

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Adult;ALS pathology;ALS patients;Amyotrophic Lateral Sclerosis;amyotrophic lateral sclerosis therapy;Anatomy;Anti-Inflammatory Agents;Autopsy;Axon;axon injury;axonal degeneration;Biological Markers;biomarker development;biomarker identification;Cells;Central Nervous System;Characteristics;Chronic;Confocal Microscopy;Cost of Illness;Data;Data Set;Databases;Disease;disease model;Environment;Exhibits;Future;genomic signature;glial activation;Goals;Heterogeneity;Hippocampus;Human;Immune;Immune response;Immune system;Immunofluorescence Microscopy;immunological diversity;In Situ;Infiltration;Inflammatory Response;innovation;Investigation;Knowledge;Macrophage;Microglia;Modeling;Molecular;monocyte;Motor;motor neuron degeneration;Motor Neuron Disease;Motor Neurons;mouse model;Mus;mutant;Myeloid Cells;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;neuroinflammation;Neuromuscular Junction;neuropathology;novel;Paralysed;Pathogenesis;Pathogenicity;Patients;Peripheral Nerves;Peripheral Nervous System;Phenotype;Play;Predisposition;Process;Research;Resistance;Resolution;response;Role;Sampling;sciatic nerve;Signal Transduction;single-cell RNA sequencing;Spinal Cord;spinal cord mapping;superoxide dismutase 1;Surface;T cell infiltration;Technology;Testing;Therapeutic;Therapeutic Intervention;therapeutically effective;Time;Tissues;transcriptome;Transgenic Organisms

PROJECT_TITLE: Defining Immune Cell Heterogeneity in Human ALS and Mouse Model of the Disease

STUDY_SECTION: CDIN

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


ORG_DEPT: PATHOLOGY

PHR: PROJECT NARRATIVE Cell migration is a fundamental property of most cells and contributes to development, wound healing, immune responses and a host of other processes. This project focuses on two poorly understood processes in cell migration: nuclear positioning and endocytic recycling of integrin adhesion receptors. Deciphering the contribution of these processes to cell migration will provide new basic information to understand cell migration and may help identify new strategies for intervention in cases where cell migration becomes unregulated, such as cancer metastasis and inflammation.

PI_NAMEs: GUNDERSEN, GREGG G (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: adhesion receptor;Adhesions;Attention;cell motility;Cell Nucleus;Cells;Complex;Cytoskeleton;Defect;Development;Exocytosis;graduate student;Immune response;Inflammation;Integrins;Intervention;Knowledge;Laboratories;Lead;Measures;Mechanics;Microfilaments;Microtubules;Molecular Conformation;Movement;National Institute of General Medical Sciences;Neoplasm Metastasis;non-healing wounds;Nuclear;Organ;Pathologic Processes;Physiological Processes;Positioning Attribute;Postdoctoral Fellow;Process;Property;Recycling;sensor;Signal Transduction;Site;System;Testing;tissue regeneration;Tissues;trafficking;Training;Travel;wound healing

PROJECT_TITLE: Cytoskeleton, Nucleus and Integrin Recycling in Cell Migration

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


ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE One in two women and one in five men will suffer an osteoporotic fracture after age 50, causing pain, diminished quality of life, and costing $20 billion/year in the United States. Physical loading of the skeleton and weight-bearing exercise can increase bone density, but is not as effective in older people and animals. This project will address this issue by testing new drugs that can potentially work together with exercise to increase bone density and strengthen osteoporotic bones.

PI_NAMEs: SILVA, MATTHEW J (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: Address;Adult;Age;Aging;Anabolism;animal old age;Antibodies;Antibody Therapy;arm;Binding;Biomechanics;bone;bone cell;Bone Density;bone loss;bone mass;bone strength;C57BL/6 Mouse;Cells;Compensation;cost;Data;dentin matrix protein 1;Development;early onset;effectiveness evaluation;Exercise;extracellular;Funding;gain of function mutation;Gene Expression;hallmarks of aging;Health;Human;human model;Immature Bone;Impairment;In Vitro;in vivo;inhibitor;Intervention;Lead;Ligand Binding;Ligands;Link;loss of function mutation;Mature Bone;mechanical load;men;microCT;Modeling;mouse model;Mus;Mutant Strains Mice;Mutation;novel;novel therapeutics;old mice;Older Population;Osteoblasts;Osteocytes;Osteogenesis;Osteoporosis;osteoporosis with pathological fracture;osteoporosis-pseudoglioma syndrome;Osteoporotic;osteoporotic bone;Pain;Pathway interactions;personalized approach;Persons;Phenotype;Pilot Projects;Quality of life;receptor;response;Role;Signal Transduction;skeletal;Skeleton;synergism;Testing;Therapeutic;United States;Up-Regulation;Weight-Bearing state;WNT Signaling Pathway;WNT1 gene;Woman;Work;young adult

PROJECT_TITLE: Response of the Osteoporotic Skeleton to Mechanical Loading

STUDY_SECTION: SBSR

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


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

NIH_SPENDING_CATS: Diabetes

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE The purpose of this Training Grant is to prepare qualified postdoctoral trainees in Endocrinology, Diabetes and Metabolism for scientific research careers that significantly impact on the health-related research needs of the United States. This training program will utilize Stanford University’s world-class faculty and resources in the fields of basic, translational and population health research in endocrinology with a primary focus on diabetes. Trainees who graduate from this program will be well-prepared to independently lead (within an academic or industrial setting), create and apply new scientific discoveries that enhance public health in areas of diabetes, obesity, bone health and hormone-dependent cancer.

PI_NAMEs: ANNES, JUSTIN PIERCE (contact);MAAHS, DAVID MATTHEW

PROJECT_TITLE: Diabetes, Endocrinology and Metabolism Training Grant

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


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Kidney Disease;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: AUSTIN

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF TEXAS AT AUSTIN

PHR: Glomerular filtration rate (GFR) is the clinical standard assay for the assessment of kidney function, however existing estimation techniques are imperfect. The goal of this work is to therefore develop, validate and evaluate novel, non-ionizing, non-contrast renal functional MRI markers of blood flow, blood oxygen and GFR using advanced modeling, data acquisitions and image reconstruction approaches. We will evaluate our techniques in a large population of African Americans as a first step towards demonstrating efficacy in all patients with kidney disease.

PI_NAMEs: BUSH, ADAM M (contact);TAMIR, JONATHAN ISAAC

PROGRAM_OFFICER_NAME: BARRY, ROBERT LEO II

PROJECT_TERMS: 3-Dimensional;Abdomen;Adoption;Adult;Affect;African American;African American population;Agreement;American;Anemia;APOL1 gene;arterial spin labeling;bioaccumulation;Biological Assay;Biological Markers;Black American;Blood;Blood flow;blood oxygen level dependent;Blood Pressure;Bolus Infusion;Brain;cerebral hemodynamics;Chronic Kidney Failure;Clinical;clinical imaging;Clinical Trials;Collection;Complex;Consumption;Contrast Media;Creatinine;data acquisition;data modeling;deoxyhemoglobin;Development;Diabetes Mellitus;Diagnosis;Diet;Dimensions;Disease;Diuresis;Drug usage;Economic Factors;End stage renal failure;Environmental Pollution;Estimation Techniques;Evaluation;Filtration;Foundations;Functional Magnetic Resonance Imaging;Gadolinium;Gases;Genetic;Glomerular Filtration Rate;Glycosylated hemoglobin A;Goals;Healthcare;hemodynamics;human old age (65+);Image;image reconstruction;Imaging Techniques;improved;indexing;Individual;Inequity;Infusion procedures;Inhalation;Injections;Kidney;Kidney Diseases;kinetic model;Life Style;Link;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Maps;Medical;Methods;Modality;Modeling;Motion;motion sensitivity;Near-Infrared Spectroscopy;nephrotoxicity;next generation;Nitrogen;novel;Operative Surgical Procedures;Organ;Outcome;Oxygen;Oxygen saturation measurement;Patients;Perfusion;perfusion imaging;Persons;Phase;Physics;physiologic model;Physiological;Plasma;Policies;Population Heterogeneity;Predisposition;prevent;Product Packaging;Protocols documentation;Race;Radial;Radiation;radiation risk;recruit;Renal function;Renal Plasma Flow;Research Methodology;Resolution;Rest;Risk;Safety;Scanning;Screening procedure;Serum;Sickle Cell Trait;Slice;social factors;spatiotemporal;success;Techniques;temporal measurement;Testing;Time;tissue oxygenation;Tissues;Toxic effect;Tubular formation;Underserved Population;Urine;Validation;Vendor;Water;Work

PROJECT_TITLE: Robust, Contrast-Free Functional Renal MRI


NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: This grant will study Zonula Occludens and Vinculin proteins that are important in cardiomyocyte cellular junctions. We will use genetically manipulated mouse models, along with tissue and cells derived from them, to examine how these proteins affect cardiac conduction and contractile function. The mechanistic data obtained will advance the field and could lead to future novel therapies for a range of heart diseases.

PI_NAMEs: GOLDHABER, JOSHUA I;ROSS, ROBERT SCOTT (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Abbreviations;Adult;Affect;Arrhythmia;atrioventricular node;base;Binding;Biochemical;Black race;Cardiac;Cardiac conduction system;cardiac muscle disease;Cardiac Myocytes;Cardiomyopathies;Categories;Cell Communication;Cell-Cell Adhesion;Cells;Classification;Complex;Confocal Microscopy;Connexins;Coupling;Data;Defect;Dilated Cardiomyopathy;Elements;Etiology;Evaluation;Functional disorder;Future;Genetic;genetic manipulation;Genetic Predisposition to Disease;Genetic Screening;Genetic Transcription;Giant Cells;Grant;Hand;Heart;Heart Atrium;Heart Diseases;Heart failure;heart function;heart preservation;heart rhythm;hemodynamics;human disease;Hypertension;Intercalated disc;intercellular connection;Intercellular Junctions;Ion Channel;Ischemia;Knowledge;Lateral;Link;Location;Maps;Mechanics;Membrane;Membrane Proteins;Microscopic;Modeling;Molecular;molecular phenotype;Morbidity - disease rate;mortality;mouse model;Mus;Myocardium;non-genetic;novel strategies;novel therapeutics;Optics;patch clamp;Patients;Perinatal;Physiological;Positioning Attribute;postnatal;Property;Proteins;Proteomics;Resolution;Role;screening;Severities;sex;Sex Differences;Sinoatrial Node;Stress;sudden cardiac death;Sudden Death;Symptoms;System;Systemic disease;Testing;Tight Junctions;Tissues;transcriptomics;Ventricular;Ventricular Arrhythmia;Vinculin;voltage;Work

PROJECT_TITLE: Cardiac Myocyte Protein Partners in Heart Function

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: SANTA CRUZ

ORG_NAME: UNIVERSITY OF CALIFORNIA SANTA CRUZ

PHR: Project Narrative The complexity of splicing, a key step in the expression of nearly all human genes, remains daunting, and yet intervention in splicing for treatment of diseases is already bearing fruit. Recent success repairing splicing to treat spinal muscular atrophy and awareness that cancer mutations in splicing factor genes influence tumor progression has exposed new opportunities for basic research on the spliceosome as a pathway to treatments. Given the fundamental conservation of the splicing machinery, this work promises to stimulate new approaches to engineering splicing that will improve human health.

PI_NAMEs: ARES, MANUEL  (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Address;Alternative Splicing;Antibiotics;Area;Awareness;Bacteria;Basic Science;Biochemical;cancer recurrence;Candidate Disease Gene;cell growth;Cell Physiology;Cells;Complex;Defect;Disease;Drosophila genus;Engineering;Eukaryota;Evolution;experimental study;Fruit;Gene Expression Regulation;Gene Proteins;Genes;Genetic Transcription;Health;Human;improved;in vivo;Individual;innovation;Intervention;Introns;Investigation;Knowledge;Lethal Genes;Malignant Neoplasms;Measures;Mediating;mRNA Precursor;Mutation;Nature;Noise;novel;novel strategies;Output;Pathway interactions;predictive modeling;Process;Reaction;Regulation;repaired;Reporter;RNA Polymerase II;RNA Splicing;RNA-Binding Proteins;Role;sex;Site;Spinal Muscular Atrophy;Spliceosome Assembly Pathway;Spliceosomes;Structure;success;synthetic biology;System;Testing;Time;transcriptome sequencing;Translating;tumor progression;U2 Small Nuclear Ribonucleoprotein;Variant;Work;Yeasts

PROJECT_TITLE: Structure, regulation, and evolution of the splicing machinery

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Childhood Injury;Clinical Research;Depression;Mental Health;Mental Illness;Pediatric;Prevention;Suicide;Suicide Prevention

ORG_DEPT: PSYCHOLOGY

ORG_NAME: COLUMBIA UNIVERSITY TEACHERS COLLEGE

PHR: 8. Project Narrative PROJECT NARRATIVE This proposed R21 explores how specific aspects of positive future thinking may be counterintuitively harmful among suicidal adolescents. Findings will help achieve a more comprehensive, nuanced, and ecologically valid understanding of this potential intervention target during adolescence. This is relevant to public health because it could inform more precise intervention strategies to reduce suicide risk early in life.

PI_NAMEs: CHA, CHRISTINE B. (contact)

PROGRAM_OFFICER_NAME: MURPHY, ERIC ROUSSEAU

PROJECT_TERMS: Adolescence;Adolescent;Adolescent and Young Adult;Adult;age group;Cause of Death;Characteristics;Child;Clinical;clinical risk;Cognition;cognitive process;Complex;depressive symptoms;Development;Distress;Ecological momentary assessment;Event;experience;Feeling suicidal;follow-up;Future;Goals;innovation;Intervention;Investigation;Laboratories;Learning;Life;life span;Measures;Mediating;Motivation;motivational processes;Nature;novel;Outcome;Outcome Measure;outcome prediction;Pattern;Personal Satisfaction;Persons;phenomenological models;Positive Valence;prevent;Process;prospective;protective factors;Psyche structure;psychologic;Psychotherapy;Public Health;Recording of previous events;recruit;reducing suicide;Research;Research Design;Risk;Risk Factors;Role;Sampling;simulation;standard care;suicidal;suicidal adolescent;suicidal behavior;suicidal individual;suicidal risk;Suicide;Task Performances;Teenagers;Testing;therapy adverse effect;Thinking;Time;United States;Work

PROJECT_TITLE: Positive future thinking among suicidal adolescents

STUDY_SECTION: CPDD

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


NIH_SPENDING_CATS: Behavioral and Social Science;Biomedical Imaging;Bipolar Disorder;Brain Disorders;Clinical Research;Mental Health;Mental Illness;Neurosciences;Serious Mental Illness

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: Project Narrative This project uses sophisticated mathematical models to measure deficits in a core dimension of cognition in a large population with bipolar disorder. We then use neuroimaging to link these deficits to changes in structural and functional networks in the brain. This work will shed light on brain mechanisms of cognitive dysfunction in bipolar disorder, which in turn can lead to better diagnosis and improved interventions.

PI_NAMEs: SRIPADA, CHANDRA SEKHAR (contact)

PROGRAM_OFFICER_NAME: WIJTENBURG, SARAH ANDREA

PROJECT_TERMS: Address;Adult;Affect;Affective;Age;Architecture;Bayesian Analysis;Behavioral;Bipolar Disorder;Brain;brain based;Chronic;Clinical;clinical imaging;Cognition;Cognitive;cognitive ability;cognitive training;Computer Models;connectome;Data;Development;Diagnosis;Diffusion;Dimensions;disability;Disease;Etiology;flexibility;follow-up;Fostering;Foundations;Functional Magnetic Resonance Imaging;Genetic;imaging study;Impaired cognition;Impairment;improved;Impulsivity;Individual;Individual Differences;interest;Intervention;Knowledge;large datasets;Link;longitudinal course;Longitudinal Studies;mathematical model;Measures;Mediating;Mediation;Mental disorders;Methodology;Methods;Michigan;Modeling;multimodal fusion;Multimodal Imaging;multimodality;network architecture;Neurocognitive;Neurocognitive Deficit;neuroimaging;neuromechanism;Neurosciences;Neurosciences Research;novel;Participant;Pattern;Performance;Pilot Projects;Population;predictive modeling;programs;Psychiatry;Psychopathology;Publishing;Regulation;response;Rest;Sampling;Severity of illness;Stimulus;success;Symptoms;Task Performances;Testing;Time;trait;trait impulsivity;Translations;Work

PROJECT_TITLE: Establishing Network Neuroscience Mechanisms of Efficiency of Evidence Accumulation in a Well-Characterized Sample with Bipolar Disorder: A Multi-Modal Clinical Imaging Study

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


NIH_SPENDING_CATS: Behavioral and Social Science;Child Abuse and Neglect Research;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Mental Health;Pediatric;Primary Health Care;Rural Health;Social Determinants of Health;Violence Research;Youth Violence

ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative  Improving access to evidence-based mental health treatment is critical to improving outcomes for children who experience maltreatment. This study will develop and pilot strategies to improve multidisciplinary team functioning and facilitate implementation of a mental health screening and referral protocol in in rural Child Advocacy Centers. The proposed training and research will prepare the investigator to advance NIMH Strategic Objective 4.2 – “establish research-practice partnerships to improve dissemination, implementation, and continuous improvement of evidence-based mental health services” – and has the potential to positively impact public health by improving the capacity of systems in rural areas to meet the mental health needs of vulnerable children.

PI_NAMEs: MCGUIER, ELIZABETH ANN (contact)

PROGRAM_OFFICER_NAME: SWEENEY, MARY MARGARET

PROJECT_TERMS: Adoption;Advisory Committees;Advocate;Affect;Affective;Behavior;Behavioral;Behavioral Sciences;Businesses;California;Caregivers;Caring;Child;Child Abuse and Neglect;Child Advocacy;Child Mental Health;Child Welfare;Clinical;Clinical Sciences;cognitive process;cohesion;Committee Members;Communication;community based research;community partners;Competence;Conflict (Psychology);Data;Development;Education;effectiveness/implementation hybrid;Eligibility Determination;Ensure;evidence base;Evidence based practice;Evidence based treatment;experience;Goals;health care settings;Health Personnel;hybrid type 2 trial;Hybrids;Impairment;implementation efforts;implementation facilitation;implementation outcomes;implementation process;implementation science;implementation strategy;implementation/effectiveness;Improve Access;improved;improved outcome;Intervention;intervention mapping;Interview;Law Enforcement;maltreatment;member;Mental Health;Mental Health Services;Mentors;Mentorship;Methods;Modeling;multidisciplinary;National Institute of Mental Health;Outcome;Partnership Practice;patient safety;Pediatrics;peer;Penetration;Pennsylvania;Performance;pilot trial;Play;Positioning Attribute;post implementation;Primary Care;Process;professor;Protocols documentation;Psychiatry;Psychology;Public Health;Randomized;Recommendation;Replicating Effective Programs;Research;Research Personnel;Resources;response;Rewards;Rice;Risk;Role;routine practice;Rural;rural area;Rural Health Services;Schools;screening;Screening procedure;Service setting;skill acquisition;skills;Speed;Standardization;stress symptom;Structure;suicidal;Suicide;suicide rate;Surveys;System;team-based care;Testing;theories;tool;Training;Translational Research;traumatic stress;Universities;Utah;Vulnerable Populations;Washington;Youth

PROJECT_TITLE: Improving access to mental health services for rural youth: Leveraging multidisciplinary teams to enhance implementation of a screening and referral protocol in rural Child Advocacy Centers

STUDY_SECTION: SERV

STUDY_SECTION_NAME: Mental Health Services Study Section[SERV]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: Chicago

ORG_DEPT: PHYSICS

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: Gene expression is regulated by both chromatin structure and chromatin-binding proteins. We will develop a novel assay to probe both aspects at the single cell level with unprecedented resolution and complexity. The resulting multi- dimensional datasets will be of tremendous value for our understanding of chromatin structure-function relationships in human health and disease.

PI_NAMEs: SPILLE, JAN-HENDRIK  (contact)

PROGRAM_OFFICER_NAME: BECKER, STEVEN

PROJECT_TERMS: 3-Dimensional;Acceleration;Alleles;Antibody Repertoire;Architecture;Binding;Binding Proteins;Binding Sites;Biological Assay;Boundary Elements;Cell Culture Techniques;Cell Nucleus;Cell Reprogramming;Cells;Cellular Assay;Cellular biology;ChIP-seq;Chromatin;chromatin immunoprecipitation;chromatin protein;Chromatin Structure;chromosome conformation capture;Chromosome Territory;Chromosomes;color detection;combinatorial;Data;Data Set;Detection;detection limit;Development;Disease;DNA Sequence;Elements;Enhancers;Epigenetic Process;Frequencies;Gene Expression;Genes;Genetic Transcription;Genome;genomic locus;Genomics;Health;Hi-C;high risk;histone modification;Human;Image;Immune system;Individual;innovation;insight;instrumentation;interest;Interphase;Knowledge;Length;Link;Maps;Measurement;Methods;Molecular;Molecular Conformation;multidimensional data;nanometer;Nature;novel;Nuclear;Nuclear Proteins;Nucleosomes;Optics;Outcome;parallelization;Performance;Population;Post-Translational Protein Processing;Process;promoter;Property;Proteins;Protocols documentation;Reading;reconstruction;Regulatory Element;Resolution;Sampling;segregation;Signaling Protein;single molecule;stem cell population;stem cells;Stretching;Structure;Structure-Activity Relationship;superresolution microscopy;Technology;Time;timeline;transcription factor;ultra high resolution;Variant;Visualization

PROJECT_TITLE: Mapping protein signatures to single allele chromatin topologies at genomic resolution

STUDY_SECTION: GCAT

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


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Caregiving Research;Maternal Health;Mental Health;Neurosciences;Pediatric;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: RICHARDSON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF TEXAS DALLAS

PHR: PROJECT NARRATIVE Human parental care is compromised under conditions of adversity and/or chronic stress, which in turn compromises neurobehavioral development, including the expression of later life maternal behavior, in the female offspring. Little is known about the neural mechanisms contributing to early adversity-induced disruptions in mother-infant attachment, including how these are transmitted across generations. This application will examine the impact of early life adversity (i.e., induced by resource depletion in rat dam’s nesting environment) on maternal behaviors and mesolimbic dopamine function in the adult female offspring and test a mechanistic role for the stress hormone corticosterone by employing an integrated approach (e.g. environmental perturbation, behavior, pharmacology, in vivo electrophysiology) in order to provide the initial insights into the dopaminergic mechanisms contributing to environmentally-driven alterations in mother-infant attachment, which may facilitate better treatments for improving functional deficits in maternal care during/following adversity exposure.

PI_NAMEs: RINCON CORTES, MILLIE  (contact)

PROGRAM_OFFICER_NAME: MILLER, BRETT

PROJECT_TERMS: Adult;Adult women;Affective;Attenuated;attenuation;Beds;Behavior;Behavioral;Birth;Brain;Breeding;Caregivers;caregiving;Caring;Chronic;Chronic stress;Clinical Data;Clinical Research;Corticosterone;Data;Development;Discipline of Nursing;Dopamine;dopamine system;dopaminergic neuron;Down-Regulation;early experience;early life adversity;early life exposure;early life stress;Electrophysiology (science);Emotional;Environment;Exhibits;experience;Exposure to;Female;Functional disorder;Generations;Goals;Health;Hormonal;Hormones;Human;hypothalamic-pituitary-adrenal axis;Impairment;improved;in vivo;Induced Neurons;Infant;insight;intergenerational;late life;Life;Long-Term Effects;maltreatment;Maternal Behavior;Mediator;mesolimbic system;Metyrapone;Modeling;Moods;motherhood;Mothers;Motivation;neglect;neural;neurobehavioral;neuromechanism;neurotransmission;Nipples;offspring;Outcome;Ovarian;Pathway interactions;Pattern;Pharmacology;Play;Postdoctoral Fellow;Postpartum Depression;Postpartum Period;Poverty;pre-clinical;pre-clinical research;prevent;Process;pup;Quality of Care;Rattus;Recording of previous events;Regulation;Research;Resource-limited setting;Resources;response;Retrieval;Rewards;Risk Factors;Rodent;Role;Signal Transduction;Stress;Testing;transmission process;Ventral Tegmental Area;Woman;Work

PROJECT_TITLE: Impact of early life adversity on caregiving behaviors and reward-related brain function: testing a mechanistic role for corticosterone

STUDY_SECTION: CHHD

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


NIH_SPENDING_CATS: Autism;Brain Disorders;Genetics;Human Genome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: PROJECT NARRATIVE There is an urgent need to gain a greater understanding of basic biological mechanisms in autism spectrum disorders (ASDs) as a path to discover new therapeutic targets. We propose to use cutting-edge genomic technologies to investigate how loss of function of two top ASD risk genes affects protein synthesis and specific neural cell types in the developing brain. Our central goal is to advance our knowledge of novel targetable pathways downstream of ASD genes with potential therapeutic implications.

PI_NAMEs: HOFFMAN, ELLEN J (contact)

PROGRAM_OFFICER_NAME: LEINWAND, SARAH GOLDBERG

PROJECT_TERMS: Affect;Affinity Chromatography;autism spectrum disorder;Behavioral;Biological;Brain;Cell Physiology;cell type;Communication;Data;Development;differential expression;Disparate;FMR1 gene;Functional disorder;gene discovery;Gene Expression Regulation;gene function;Gene set enrichment analysis;Genes;Genetic Models;Genomics;gliogenesis;Goals;in vivo;innovation;insight;Knowledge;Lead;loss of function;Mammals;Messenger RNA;model of autism spectrum disorder;Molecular;mutant;neural;neurogenesis;Neuroglia;Neurons;new therapeutic target;novel;Orthologous Gene;Outcome;Outcomes Research;Pathway interactions;Phenotype;Process;Proliferating;Protein Biosynthesis;Research;Ribosomes;RiboTag;Risk;risk variant;Role;single-cell RNA sequencing;Technology;Testing;Therapeutic;transcriptome sequencing;Transgenic Organisms;Translating;translating ribosome affinity purification and RNA-sequencing;Translational Regulation;Translations;translatome;Zebrafish

PROJECT_TITLE: Investigating the Translatome in Genetic Models of Autism

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MDCN-P(57)]


NIH_SPENDING_CATS: Antimicrobial Resistance;Clinical Research;Immunotherapy;Infectious Diseases;Physical Injury - Accidents and Adverse Effects;Wound Healing and Care

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Narrative Severely burned patients are highly susceptible to developing life-threatening nosocomial infections due to a significantly weakened immune system, exposure to pathogens during prolonged hospitalization, and emergence of antibiotic resistant pathogens. The information gained in this project will advance current knowledge on the mechanisms by which TLR agonists trigger innate immune memory leading to enhanced antimicrobial responses and resistance to infection. New understandings may be harnessed to develop immunotherapies which enhance immunity and broadly protect severely burned patients.

PI_NAMEs: BOHANNON, JULIA K. (contact)

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Agonist;antimicrobial;Burn injury;burn model;Cause of Death;Cells;clinical application;clinical development;clinically relevant;drug resistant pathogen;Drug Targeting;efficacy evaluation;Exposure to;Functional disorder;Genetic;Goals;High Prevalence;Hospitalization;Human;Immune;Immune response;Immune system;Immune System Diseases;Immunity;Immunologic Memory;immunomodulatory therapies;immunoregulation;Immunotherapeutic agent;Immunotherapy;Impairment;improved;Infection;Infection prevention;Knowledge;Leukocytes;Life;Macrophage;Mediating;Metabolic;Mitochondria;Modification;Molecular;Mus;Myeloid Cells;Nosocomial Infections;Oxidative Stress;pathogen;Patients;Predisposition;programs;Research;Resistance;Resistance to infection;response;severe burns;Signal Pathway;Signal Transduction;Stimulus;Techniques;Therapeutic;therapeutic target;Tissue-Specific Gene Expression;TLR4 gene;Toll-like receptors;Training

PROJECT_TITLE: Protection Against Nosocomial Infections After Severe Burn Injury Through Trained Immunity

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


NIH_SPENDING_CATS: Aging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Colorectal Cancer;Digestive Diseases;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE Although previous randomized controlled trials (RCT)s demonstrate that low-dose aspirin (LDA, 81-100mg/day) reduces the risk of colorectal cancer (CRC), a recent RCT reported that initiating LDA late in life had no benefit on CRC incidence and was potentially detrimental for mortality. Taken together with our compelling preclinical data that aging and age-related processes, such as inflammaging, promote a decrease in the colonic intestinal stem cell (cISC) pool that is normally sensitive to aspirin chemoprevention, we propose to examine the impact of LDA at single cell resolution on colonic epithelium, patient-derived organoids, and urinary PGs in an RCT of older adults and in novel in vivo experimental models to dissect the role of inflammaging on PG signaling in cISCs and colon tumor incidence and progression. These studies could have a significant influence in shaping population guidelines for LDA in chronic disease prevention and the development of precision biomarkers to optimize the risk-benefit profile of LDA.

PI_NAMEs: CHAN, ANDREW T (contact);STAPPENBECK, THADDEUS S;YILMAZ, OMER

PROGRAM_OFFICER_NAME: UMAR, ASAD

PROJECT_TERMS: Address;Adult;Age;age effect;age related;age related changes;aged;Aging;aging related;anti-cancer;APC gene;Aspirin;Benefits and Risks;Biological;Biological Assay;Biological Markers;biomarker development;Biopsy;cancer biomarkers;Cancer Model;Cell Count;Cell Culture Techniques;Cell Physiology;Cells;Chemoprevention;Chemopreventive Agent;Chemoprotective Agent;Chronic Disease;Clinical;Colon;Colon Carcinoma;Colonic Neoplasms;Colorectal Cancer;colorectal cancer prevention;colorectal cancer risk;Data;Depreciation;Development;Dinoprostone;disorder prevention;Dose;Double-Blind Method;Elderly;Endowment;Enrollment;Epithelial Cells;epithelial stem cell;Epithelium;Etiology;Experimental Models;fetal;Gene Expression Profile;Genetic;Guidelines;Human;human old age (65+);in vitro Model;in vivo;Incidence;Individual;Inflammaging;Inflammation;Inflammatory;Intervention;Intestinal Cancer;intestinal epithelium;Intestines;late life;LGR5 gene;Life;Measures;Mediating;Methods;Modeling;mortality;mouse model;Mucous Membrane;Mus;Mutation;Non-Steroidal Anti-Inflammatory Agents;novel;old mice;older adult;Older Population;Oncogenic;Organoids;Pathway interactions;Patients;pharmacologic;Placebo Control;Population;pre-clinical;Pre-Clinical Model;premalignant;Process;Prostaglandin Inhibition;Prostaglandins;Randomized, Controlled Trials;receptor;Recommendation;regenerative;Reporter;Reporting;Resistance;Resolution;Risk Reduction;Role;Secondary to;Shapes;Signal Transduction;single-cell RNA sequencing;Small Intestines;stem cell function;stem cells;Testing;tumor;tumor initiation;tumor progression;tumorigenesis;tumorigenic;United States Preventative Services Task Force;urinary;young adult

PROJECT_TITLE: Effects of inflammaging on intestinal epithelial cells and aspirin chemoprevention.

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


NIH_SPENDING_CATS: Natural Products

ORG_CITY: CHAMPAIGN

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

PHR: PI, White, M.C. R35 GM 122525 Project Narrative  This program is discovering catalytic reactions that selectively perform the atomistic change of C(sp3)– H to C–O, C–N, and C–C in complex molecules, which has been demonstrated to alter their biological function and efficacy as therapeutics. Using these reactions, we are pioneering the area of late-stage functionalization where atomistic changes are made directly on drugs and natural products, circumventing lengthy, individual de novo syntheses, which present a significant technological challenge to drug discovery. To broaden the application of late-stage functionalization, we are inventing catalysts that have a higher tolerance for pre- existing reactive functionality and effect novel site-selectivity; control over three-dimensional outcomes; and C(sp3)–H cross-couplings with O- , N- , and C-containing complex fragments.

PI_NAMEs: WHITE, MARIA CHRISTINA  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TITLE: Selective C(sp3)-H Oxidations and Functionalizations with Tunable Metal Catalysts for Synthesis

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Mental Health;Mental Illness;Neurosciences

ORG_CITY: COLD SPRING HARBOR

ORG_NAME: COLD SPRING HARBOR LABORATORY

PHR: Project Narrative The proposed studies aim to reveal subtype-specific molecular elements of N-methyl-D-aspartate receptor (NMDAR) ion channels, which play a major role in brain function and development. These studies are relevant to public health because dysfunctional NMDARs are implicated in neurological disorders such as depression, and schizophrenia, as well as Alzheimer’s diseases. Understanding the mechanisms by which subtype-specific reagents bind and regulate functions of NMDARs will support the development of therapeutic strategies for these neurological disorders and diseases.

PI_NAMEs: FURUKAWA, HIROYASU  (contact)

PROGRAM_OFFICER_NAME: NADLER, LAURIE SUE

PROJECT_TERMS: Achievement;Active Sites;Affect;Agonist;Allosteric Regulation;Alzheimer's Disease;antagonist;Antibodies;antibody engineering;Anxiety Disorders;aspartate receptor;Autoantibodies;Autoimmune;Binding;Binding Sites;biophysical tools;Brain;Cells;Cerebellum;channel blockers;Chemosensitization;clinical research site;clinically relevant;Complex;Coupled;Cryoelectron Microscopy;Crystallography;Cycloserine;desensitization;Development;Disease;Electrophysiology (science);Elements;Encephalitis;Engineering;Epilepsy;excitatory neuron;Exhibits;experimental study;Family;Glutamate Receptor;Glutamates;Glycine;Goals;Grant;IgG Receptors;improved;Insecta;insight;Ion Channel;Ion Channel Gating;Kainic Acid Receptors;Ketamine;Kinetics;Lead;Libraries;Ligand Binding Domain;Ligands;Measures;Mediating;Memantine;Membrane Proteins;Mental Depression;mental health related disorder;Methods;Molecular;Molecular Conformation;Movement;Mutagenesis;N-Methyl-D-Aspartate Receptors;N-Methylaspartate;nanobodies;Nervous System Disorder;Neurotransmitters;NMDA receptor A1;novel;particle;patch clamp;Patients;Pattern;pharmacologic;Pharmacology;Phencyclidine;Play;Property;protein complex;Psychoses;Public Health;Reagent;receptor function;Recombinants;Regulation;Research;Resolution;RNA Splicing;Roentgen Rays;Role;Schizophrenia;screening;Series;Serine;Site;Site-Directed Mutagenesis;spatiotemporal;Specificity;stoichiometry;Stroke;Structure;Surface Plasmon Resonance;Synaptic Transmission;Technology;Therapeutic;therapeutic development;Time;Transmembrane Domain;Variant;X-Ray Crystallography;Yeasts;Zinc

PROJECT_TITLE: Structures and reagents of NMDA receptors

STUDY_SECTION: BPNS

STUDY_SECTION_NAME: Biophysics of Neural Systems Study Section[BPNS-M]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cannabinoid Research;Chronic Pain;Neurodegenerative;Neurosciences;Opioids;Pain Research;Peripheral Neuropathy;Therapeutic Cannabinoid Research

ORG_DEPT: ANESTHESIOLOGY

PHR: Public Health Relevance Statement  To address the current opioid crisis, a new class of potent non-opioid analgesics has been developed in the investigators’ laboratories. These future drug candidates are designed to target brain circuits involving a family of proteins called glycine receptors. The proposed investigations aim to elucidate the dual roles of the α3 subtype of glycine receptors in alleviating chronic pain and at the same time inhibiting the reward circuits in the brain, thereby reducing the risk of drug dependence and abuse potential.

PI_NAMEs: XU, YAN  (contact)

PROGRAM_OFFICER_NAME: MOHAPATRA, DURGA PRASANNA

PROJECT_TERMS: Absence of pain sensation;abuse liability;Acute;Address;American;Analgesics;antinociception;Behavior;behavior test;Binding;Binding Sites;Brain;Brain region;Cannabidiol;Cannabinoids;cellular targeting;Chemosensitization;chronic constriction injury;chronic pain;chronic pain management;Collaborations;Complement;conditioned place preference;coping;Coupling;cross reactivity;Data;design;dopaminergic neuron;dorsal horn;Dose;Drug abuse;Drug Addiction;Drug Binding Site;drug candidate;drug seeking behavior;Drug Targeting;drug-like compound;Electrophysiology (science);Equilibrium;experience;Formalin;Foundations;Future;Genetic;Glycine Receptors;Human;Hypersensitivity;in silico;In Situ Hybridization;In Vitro;in vivo;Inflammatory;inflammatory pain;Investigation;Knock-out;knockout animal;Knockout Mice;Knowledge;Laboratories;Lead;Legal patent;Marijuana;Mechanics;Mediating;Microinjections;Midbrain structure;Molecular;Molecular Target;Morphine;morphine administration;Motivation;Mus;Names;Neurons;Neuropathy;neurotransmission;Nociception;non-opioid analgesic;novel therapeutics;Nucleus Accumbens;Operant Conditioning;Opioid;opioid epidemic;Opioid Receptor;Pain;Pain management;pain model;pain perception;pain processing;pain signal;painful neuropathy;Pathway interactions;Peripheral;Persistent pain;Pharmaceutical Preparations;pharmacologic;Play;Population;positive allosteric modulator;Process;Protein Family;public health relevance;Rattus;receptor;reconstitution;Regulation;Research Personnel;Rewards;Risk;Risk Reduction;Rodent;Role;scaffold;screening;Self Administration;side effect;Signal Pathway;Signal Transduction;Site;Specificity;Spinal;Spinal Cord;Spinal cord posterior horn;structural biology;Substantia nigra structure;Testing;Time;tool;Transmembrane Domain;transmission process;Tyrosine 3-Monooxygenase;United States National Institutes of Health;Ventral Tegmental Area

PROJECT_TITLE: Peripheral and Central Pathways of α3 Glycine Receptors as Non-Opioid Molecular Targets to Treat Pain

STUDY_SECTION: SAT

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


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Hematology;Microbiome;Orphan Drug;Prevention;Rare Diseases;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: PROJECT NARRATIVE An important and often lethal complication after allogeneic hematopoietic cell transplantation (allo-HCT) is graft-vs-host disease (GVHD), in which the donor immune system attacks the patient's tissue. We propose to evaluate a rationally designed oral-ecobiotic capsule that delivers a defined composition of pure bacterial strains, which aims to reduce GVHD and offers advantages of predictable and reproducible pharmacology and would be immediately scalable in future studies. Findings will inform future research not only for the reduction of transplant-related complications including GVHD, but also for other conditions in which GI injury occurs such as chemotherapy and/or radiation-induced toxicity and nonmalignant inflammatory GI conditions.

PI_NAMEs: PONCE, DORIS  (contact);VAN DEN BRINK, MARCEL R M

PROGRAM_OFFICER_NAME: WELNIAK, LISBETH A

PROJECT_TERMS: Allogenic;Antibiotic Resistance;Bacteria;capsule;Cells;Cessation of life;Chemotherapy and/or radiation;Clinical;Complication;curative treatments;Data;dysbiosis;Ecosystem;Enterococcus;fecal transplantation;first-in-human;Functional disorder;Funding;Future;gastrointestinal;gastrointestinal function;Gastrointestinal Injury;Gastrointestinal tract structure;graft vs host disease;gut microbiome;gut microbiota;Health;Hematocrit procedure;Hematologic Neoplasms;Hematopoietic Stem Cell Transplantation;human study;Immune;immune reconstitution;Immune system;Immunity;Immunologics;improved;Infection;Infectious Agent;Inflammatory;innovation;insight;Intervention;Intestines;Knowledge;Malignant Neoplasms;member;metabolomics;microbial colonization;microbial community;microbiome;microbiome analysis;microbiota;mortality;Multicenter Studies;Mus;Non-Malignant;novel;novel strategies;Oral;Outcome;pathobiont;Pathogenicity;Patient-Focused Outcomes;Patients;Pharmacology;Phase;phase 3 study;Phase Ib Trial;Placebo Control;placebo controlled trial;Population;post-transplant;Pre-Clinical Model;preservation;prevent;Prevention;Production;Prophylactic treatment;prospective;rational design;reconstitution;Reporting;Reproducibility;Research Personnel;resistance gene;restoration;Risk;Sampling;scale up;Stem cell transplant;therapeutic evaluation;Therapeutic immunosuppression;Tissues;Toxic effect;translational study;transmission process;transplant centers;Transplant Recipients;Transplantation;Treatment Protocols;tumor;Volatile Fatty Acids

PROJECT_TITLE: Intestinal microbiome restoration in allogeneic stem cell transplantation

STUDY_SECTION: TTT

STUDY_SECTION_NAME: Transplantation, Tolerance, and Tumor Immunology Study Section[TTT]


NIH_SPENDING_CATS: Antimicrobial Resistance;Infectious Diseases;Natural Products

ORG_CITY: COLLEGE STATION

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: TEXAS ENGINEERING EXPERIMENT STATION

PHR: PROJECT NARRATIVE  Combination therapy has shown great promise in addressing the rapid emergence of drug resistance, but the development of effective drug cocktails is lagging due to the challenges in both design and production processes. We propose to address these challenges by identifying drug cocktails produced by individual biosynthetic pathways of microbial origin and overproducing these naturally evolved cocktails using a metabolic division of labor strategy.

PI_NAMEs: ZHU, XUEJUN  (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Address;Anabolism;Binding;Biological;Collection;combinatorial;Combined Modality Therapy;design;Development;drug development;Drug resistance;drug resistant microorganism;experience;fighting;Grant;improved;Individual;insight;Metabolic;Methods;Microbe;microbial;microbial genome;multidrug resistance inhibition therapy;natural antimicrobial;Natural Products;Natural Selections;Nature;Pathway interactions;Pharmaceutical Preparations;Pharmacologic Substance;Population;Process;process optimization;Production;Recipe;Research;Resistance;synergism;System;Therapeutic

PROJECT_TITLE: Discovery and development of drug cocktails evolved by Nature


ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: There has been growing interest in developing composite outcomes for use in trials where a single outcome may not fully capture the effect of an intervention. The proposal will do secondary analyses of the data from the EXCITE trial, available from the NICHD Data and Specimen Hub (DASH), to gain insight into the characteristics of individual outcomes that combine into a relevant composite outcome.

PI_NAMEs: CONAWAY, MARK R (contact);STEVENSON, RICHARD D

PROGRAM_OFFICER_NAME: NITKIN, RALPH M

PROJECT_TERMS: Affect;Agreement;arm;Authorization documentation;base;Blinded;Characteristics;Clinical Trials;clinically relevant;Consensus;Contracts;Data;data access;Data Analyses;data hub;data resource;Data Set;Evaluation;Formulation;Funding;Future;Grant;Heterogeneity;improved;Individual;insight;interest;Intervention;intervention effect;Investigation;Ischemia;longitudinal design;Measures;Methods;National Institute of Child Health and Human Development;Outcome;Paper;Participant;Patients;Performance;primary endpoint;primary outcome;Property;randomized, clinical trials;repository;response;Role;secondary analysis;secondary endpoint;Specimen;Statistical Methods;Structure;Testing;Therapeutic Intervention;trial design;Universities;Upper Extremity;Virginia;Work

PROJECT_TITLE: An evaluation of composite endpoints using data from the EXCITE trial

STUDY_SECTION_NAME: Function, Integration, and Rehabilitation Sciences Study Section[CHHD-K]


NIH_SPENDING_CATS: Biotechnology;Digestive Diseases;Genetics;Human Genome;Liver Disease;Physical Injury - Accidents and Adverse Effects

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because cholangiopathies, which often affect extrahepatic bile ducts, are poorly understood and, therefore, have no effective treatment options. This project will unveil cellular and molecular mechanisms underlying extrahepatic bile duct responses to injury and inform potential strategies for treatment of cholangiopathies and prevention of their complications. Thus, the proposed research is relevant to the NIH mission that pertains to improvement of people’s health and quality of life.

PI_NAMEs: RAZUMILAVA, NATALIYA  (contact)

PROGRAM_OFFICER_NAME: SASLOWSKY, DAVID E

PROJECT_TERMS: Acute;Affect;Agonist;Alleles;Archives;Automobile Driving;bile duct;Biliary;biliary tract;Binding Sites;candidate identification;Cell Culture Techniques;Cell Separation;Cells;chemokine;Chemotactic Factors;Cholangiocarcinoma;cholangiocyte;Chromatin;Cleavage Under Targets and Release Using Nuclease;Complex;CXCL1 gene;cytokine;Data;Dependence;Disease;effective therapy;Epithelial Cell Proliferation;Epithelium;Erinaceidae;Extrahepatic Bile Ducts;Fibroblasts;Flow Cytometry;FOSL1 gene;Functional disorder;Gene Expression;Genes;Genetic;Genetic Transcription;GLI gene;Health;Hour;Human;Immunohistochemistry;improved;improved outcome;In Situ Hybridization;In Vitro;in vivo;Inflammation;Inflammation Mediators;Inflammatory;inhibitor;injured;Injury;Interleukin-1 beta;Ligands;Ligation;Link;LoxP-flanked allele;Maps;Mediating;Mission;Mitogen-Activated Protein Kinases;Modeling;Molecular;morphogens;mouse model;Mus;neutrophil;Neutrophil Infiltration;novel;novel therapeutic intervention;Organoids;overexpression;Pathogenicity;Patient-Focused Outcomes;Patients;Persons;pharmacologic;prevent;Prevention;Primary Cell Cultures;Process;Proliferating;Public Health;Publishing;Quality of life;Quantitative Reverse Transcriptase PCR;receptor;Regenerative Medicine;Regulation;repaired;Reporter;Research;response;response to injury;Role;severe injury;Signal Induction;Signal Pathway;Signal Transduction;single-cell RNA sequencing;smoothened signaling pathway;Sorting;Stromal Cells;Testing;Therapeutic;tissue injury;tissue repair;Tissues;tool;transcription factor;Transcription Factor AP-1;Transcriptional Activation;transcriptome sequencing;treatment strategy;United States National Institutes of Health;Wild Type Mouse

PROJECT_TITLE: Cellular crosstalk regulating cholangiocyte proliferation following extrahepatic bile duct injury

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

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

ORG_DEPT: OTOLARYNGOLOGY

PHR: Project Narrative The auditory system is remarkably plastic and can flexibly response to acoustic cues depending on task demands and context allowing for many auditory behaviors such as communication, language acquisition, and learning. This proposal aims to investigate the neural basis of flexible auditory learning using in vivo electrophysiology, behavior, and optogenetics to understand how the auditory system flexibly gates the behavioral relevance of sounds in dynamic environments. The results from the proposed experiments will provide critical insights into improved diagnosis and treatment of hearing deficits caused by disease or injury and will inform targeted therapies for central auditory processing disorders.

PI_NAMEs: INSANALLY, MICHELE  (contact)

PROGRAM_OFFICER_NAME: POREMBA, AMY

PROJECT_TERMS: Acoustics;Adult;Animals;Area;Auditory;Auditory area;Auditory Perception;auditory processing;Auditory system;auditory thalamus;Behavior;Behavioral;Brain;Brain region;Cells;Central Auditory Processing Disorder;Communication;computerized tools;Cues;deaf;density;Development;developmental disease;Devices;Diagnosis;Dimensions;Disease;Electrophysiology (science);Environment;Exclusion;expectation;experience;experimental study;flexibility;Frequencies;Goals;hearing impairment;Hearing problem;hearing restoration;improved;in vivo;Injury;insight;Language Development;Language Disorders;Learning;Learning Disorders;learning outcome;Measures;Motor Cortex;Mus;neural;neural circuit;Neurons;neuroprosthesis;new therapeutic target;next generation;novel;optogenetics;Pathway interactions;Patients;Pattern;Perception;Perceptual learning;Phase;Physiological;Prevalence;Process;Property;Publishing;recruit;Reporting;response;Reversal Learning;Rewards;Role;Sensory;sensory gating;sensory input;Shapes;sound;Stimulus;Synapses;Synaptic plasticity;targeted treatment;Task Performances;Techniques;Testing;Thalamic structure;Work

PROJECT_TITLE: The significance of nominally non-responsive neural dynamics in auditory perception and behavior


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Cardiovascular;Contraception/Reproduction;Hypertension;Maternal Health;Maternal Morbidity and Mortality;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Women's Health Research

ORG_CITY: LAS CRUCES

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: NEW MEXICO STATE UNIVERSITY LAS CRUCES

ORG_STATE: NM

PHR: Impaired placental function is the root cause of preeclampsia, intrauterine growth restriction, and fetal morbidity and mortality, but the underlying causes of placental dysfunction are not well characterized. Improper signaling of the chemokine CXCL12 (L12) leads to placental dysfunction, but the mechanisms leading to and the potential consequences of altered L12-dependent signaling remain unclear. This proposal will advance the comprehension of L12-induced actions in early placental development to improve pregnancy success and elucidate novel therapies to treat pregnancy complications.

PI_NAMEs: ASHLEY, RYAN LYNN (contact)

PROGRAM_OFFICER_NAME: BERNAL, FEDERICO

PROJECT_TERMS: Abruptio Placentae;Adult;AMD3100;Amniotic Fluid;Animal Model;Autophagocytosis;Biological;Blood Pressure;Cardiovascular Diseases;cell motility;Cell Survival;Cells;chemokine;Comprehension;CRISPR/Cas technology;CXCR;CXCR4 gene;cytokine;Dangerousness;Data;Dissection;Endometrial;Environment;Etiology;Event;Excretory function;fetal;Fetal Growth;Fetal Growth Retardation;Fetal health;Foundations;Functional disorder;Funding;Generations;Growth;Growth Factor;Health;high risk;Human;Hypertension;Immune;Impairment;implantation;improved;In Vitro;in vivo Model;Inflammatory;inhibitor;innovation;insight;Insulin Resistance;Invaded;KDR gene;Knowledge;Maternal-Fetal Exchange;Measures;Mediating;Methods;migration;Modeling;Molecular;Morbidity - disease rate;mortality;natural Blastocyst Implantation;neonatal morbidity;Neonatal Mortality;Non-Insulin-Dependent Diabetes Mellitus;novel therapeutics;Obesity;offspring;Outcome;Pathogenesis;Pathologic;Pathology;Perfusion;PGF gene;Pharmacological Treatment;Phenotype;Placenta;Placental Biology;Placental Insufficiency;Placentation;Plasma;Play;Positioning Attribute;potential biomarker;Pre-Eclampsia;Pregnancy;Pregnancy Complications;Process;Production;Productivity;Proliferating;Proteome;Publications;Publishing;receptor;recruit;Regulation;Research;response;Role;Signal Induction;Signal Transduction;skills;Solid;Source;stillbirth;Stimulation of Cell Proliferation;Stroke;Stromal Cell-Derived Factor 1;success;Testing;trophoblast;United States National Institutes of Health;Uterus;Vascularization

PROJECT_TITLE: CXCL12 regulation of placental development and fetal health


NIH_SPENDING_CATS: Genetics;Muscular Dystrophy;Myotonic Dystrophy;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: ALBANY

ORG_DEPT: BIOLOGY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT ALBANY

PHR: Project Narrative This proposal uses in vitro, in cellulo and in vivo strategies to understand the mechanism of action of a new class of small molecules, modified polycyclic compounds (MPCs), to address the unmet need for therapeutics for Myotonic Dystrophy (DM), the most common cause of muscular dystrophy. A design-model-test cycle will be used to understand the mechanism(s) of action of these new compounds, systematically refine their efficacy and test their therapeutic potential in patient-derived DM cells lines and animal models. The successful completion of this project will provide a new class of small molecules, a better understanding of their mechanism of action and in vivo data from multiple animal models supporting their future therapeutic potential – all critical steps towards future clinical studies for this complex and devastating disease.

PI_NAMEs: BERGLUND, ANDREW  (contact);NAKAMORI, MASAYUKI ;REDDY, KAALAK

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: ABCB1 gene;Address;Affinity;Alleles;Animal Model;benzimidazole;Binding;Biological Assay;Biological Availability;Biology;Brain;Calorimetry;candidate identification;candidate selection;Cell Line;Cell model;Cell Survival;Clinical Research;Complex;CUG repeat;Dactinomycin;Data;design;Diamidine;Disease;DNA;DNA Maintenance;drug candidate;efficacy study;Elements;Event;Exons;Family;Future;gain of function;Genetic Transcription;Goals;Hand Strength;Hela Cells;Histopathology;improved;In Vitro;in vivo;in vivo evaluation;inhibitor;Lead;lead candidate;Longitudinal Studies;Measures;Mediating;melting;Microtubules;model design;Modeling;Modification;Molecular;molecular modeling;monolayer;mouse model;Muscle;Muscular Dystrophies;Myotonia;Myotonic Dystrophy;nanomolar;Nerve Degeneration;neuromuscular;novel therapeutics;Organ;Pathogenesis;Pathology;Pathway interactions;Patients;Poison;Polycyclic Compounds;preclinical study;Property;Proteins;Reverse Transcriptase Polymerase Chain Reaction;RNA;RNA Processing;RNA Splicing;RNA-Binding Proteins;Series;Side;small molecule;small molecule therapeutics;Solubility;System;Testing;Therapeutic;Toxic effect;Transcript;transcriptome sequencing;transcriptomics;uptake;water solubility;Weight

PROJECT_TITLE: Design, Synthesis and Efficacy of New Small Molecule Therapeutics to Impede Myotonic Dystrophy

STUDY_SECTION: SMEP

STUDY_SECTION_NAME: Skeletal Muscle and Exercise Physiology Study Section[SMEP]