PHR: Project Narrative: Children born to obese mothers are at increased risk of developing type 2 diabetes at a younger age and preclinical models demonstrate the presence of worsened pancreatic beta cell dysfunction in males when compared to female offspring, but the mechanistic pathways underlying this observation are unclear. The goal of this proposal is to delineate the role of Reg3g-mediated heparan sulfate polymerization as a mechanistic pathway amenable to treatment of sex-specific islet dysfunction in offspring of obese mice. This proposal will address a critical gap in our understanding of the developmental programming of offspring islet dysfunction induced by maternal obesity and has the potential to inform novel therapeutic strategies.

PI_NAMEs: KUA, KOK LIM  (contact)

PROGRAM_OFFICER_NAME: CLARK, DAVID

PROJECT_TERMS: Ablation;Adult;Age;analog;Beta Cell;Binding;Biology;burden of illness;career;Cell Line;Cell Physiology;Child;cytokine;Data;Development;Diabetes Mellitus;Diet;differential expression;Disaccharides;Disease;Environment;Exhibits;Exposure to;Failure;Female;Foundations;Functional disorder;Future;Glucose Intolerance;glucose tolerance;Glycobiology;glycosyltransferase;Goals;Health;Heparin Lyase;Heparitin Sulfate;high risk;Human;improved;in utero;in vivo;Inflammation;Inflammatory;inhibitor;Insulin;Insulin Resistance;insulin secretion;Interleukin-1 beta;Intervention;islet;Islets of Langerhans;K-Series Research Career Programs;Laboratories;Life;Ligands;Maintenance;male;MAPK3 gene;maternal obesity;Mediating;Metabolic;Modeling;Molecular;Molecular Target;Morbidity - disease rate;mouse model;Mus;neonatal period;Newborn Infant;Non-Insulin-Dependent Diabetes Mellitus;novel;novel therapeutic intervention;Obese Mice;obese mothers;Obesity;offspring;Pancreas;Pathway interactions;Phosphorylation;Physicians;Play;polymerization;Polymers;polysulfated glycosaminoglycan;postnatal;Pre-Clinical Model;preclinical study;preservation;Prevention;Principal Investigator;Process;Recombinants;Regenerating islet derived protein 3-Gamma;regeneration potential;Reporting;Research;response;Risk;Role;Scientist;Secondary to;Serum;sex;Sex Differences;Shapes;Signal Transduction;skills;societal costs;Structure of beta Cell of islet;sulfated polymer;Testing;Therapeutic;Training;United States;Up-Regulation;Work

PROJECT_TITLE: Investigating the Downstream Mechanisms Contributing to Beta Cell Failure in Offspring Exposed to Maternal Obesity

STUDY_SECTION: CHHD

STUDY_SECTION_NAME: Health, Behavior, and Context Study Section[CHHD-M]


ADMINISTERING_IC: AG

ARRA_FUNDED: N

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);American Indian or Alaska Native;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Neurodegenerative;Neurosciences;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: CAMBRIDGE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: NATIONAL BUREAU OF ECONOMIC RESEARCH

ORG_STATE: MA

PI_NAMEs: CUTLER, DAVID M (contact)

PROJECT_TERMS: Administrative Supplement;Adult;Aging;Alzheimer's Disease;Alzheimer's disease related dementia;Area;Attention;Award;caregiving;Caring;Characteristics;Collaborations;Communication;Data Analytics;data resource;Databases;Decision Making;Dementia;design;Development;Diagnosis;Diffusion;Economics;Ecosystem;Funding;Geography;Health;health determinants;health inequalities;health management;Health Policy;Health trends;Healthcare;improved;Incentives;Income;Information Technology;innovation;Institution;Insurance Coverage;International;Leadership;Life Expectancy;Machine Learning;Measurement;Medical;meetings;middle age;Morbidity - disease rate;mortality;Native Americans;Outcome;Pain;Personal Satisfaction;Persons;Pilot Projects;Process;Productivity;programs;Provider;Research;research and development;Research Personnel;Research Priority;Research Project Grants;Series;socioeconomics;Structure;symposium;System;Time;United States Agency for Healthcare Research and Quality;Universities;working group

PROJECT_TITLE: Core C. External Innovative Network Core


ADMINISTERING_IC: DA

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurosciences;Pediatric;Prevention;Social Determinants of Health;Substance Misuse;Substance Misuse Prevention

ORG_CITY: DETROIT

ORG_NAME: HENRY FORD HEALTH SYSTEM

ORG_STATE: MI

PHR: PROJECT NARRATIVE Problematic substance use during adolescence predicts morbidity and mortality across the lifespan, suggesting the urgent public health need to prevent the escalation of use during this developmental period. The proposed project will examine the feasibility and effectiveness of implementing a preventative intervention aimed at improving decision making processes among adolescents in a traditionally underserved community. Targeting mechanisms of problematic substance use using transportable and scalable methods will set the stage for future, large-scale prevention efforts among low-resource populations.

PI_NAMEs: FELTON, JULIA W (contact);YI, RICHARD

PROGRAM_OFFICER_NAME: ROMBERG, ALEXA RUTH

PROJECT_TERMS: active method;Adolescence;Adolescent;adolescent substance use;Adult;adverse childhood events;Aftercare;Age;Alcohol abuse;Alcohol consumption;Behavioral Mechanisms;Case Series;Childhood;childhood adversity;Choice Behavior;Clinical;community setting;computerized;Computers;cost;critical period;Data;Decision Making;design;Development;Disadvantaged;discounting;Disparity;dosage;drinking;Drug usage;E-learning;early adolescence;early life adversity;early-life disadvantage;Effectiveness;effectiveness evaluation;Effectiveness of Interventions;Enrollment;Environment;ethnic minority;Etiology;Event;evidence base;executive function;Exposure to;feasibility trial;follow-up;Future;Goals;Health behavior;high school;implementation trial;improved;Impulsivity;Individual;informant;insight;Intervention;Intervention Studies;Interview;Investigational Therapies;Leadership;Life;life span;Link;Literature;Low income;marijuana use;Measures;meetings;Methods;Michigan;middle age;Modeling;Morbidity - disease rate;mortality;National Institute of Drug Abuse;neighborhood disadvantage;Neighborhoods;Neurocognitive;Neurologic;Outcome;Parents;Pathway interactions;pilot trial;Population;post intervention;Poverty;Prediction of Response to Therapy;preference;prevent;Prevention;Prevention approach;Prevention Research;preventive intervention;Process;Public Health;racial minority;Randomized;Randomized, Controlled Trials;recruit;reduced substance use;Research;Research Personnel;Resource-limited setting;Resources;Rewards;Risk;Schools;Services;Short-Term Memory;sobriety;socioeconomic disparity;socioeconomics;substance misuse;substance misuse prevention;substance use;substance use prevention;Surveys;System;Taxes;Testing;therapy development;Time;Tobacco use;Training;Training Programs;underserved area;underserved community;Vulnerable Populations;Youth

PROJECT_TITLE: Improving Decision Making to Prevent Substance Misuse among Adolescents from Traditionally Underserved Communities

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


NIH_SPENDING_CATS: Aging

PI_NAMEs: CASE, ANNE  (contact)

PROJECT_TITLE: Core D. External Research Resources Support and Dissemination Core


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF MEDICINE

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

ORG_CITY: LA JOLLA

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Project Narrative The proposed research is relevant to public health as there is still a gap in understanding maternal-infant pharmacology. The UCSD MPRINT Center of Excellence in Therapeutics will bring together basic and data scientists, pharmacologists and clinical researchers in a highly collaborative fashion to understand the impact of infant exposure to maternal antibiotic treatment via breastmilk on the metabolism of the drugs, microbiome and immune function. The proposed research will help create a national resource for expertise in maternal and pediatric therapeutics and is relevant to NICHD’s mission by furthering the field of pediatric developmental pharmacology and in working towards ensuring that “all children have the chance to achieve their full potential for healthy and productive lives”.

PI_NAMEs: BODE, LARS ;CHAMBERS, CHRISTINA ;NIZET, VICTOR ;TREMOULET, ADRIANA H (contact);TSUNODA, SHIRLEY M

PROGRAM_OFFICER_NAME: REN, ZHAOXIA

PROJECT_TERMS: Address;Ampicillin;Analytical Chemistry;Antibiotic Prophylaxis;Antibiotic Therapy;Antibiotics;Basic Science;Biological Assay;Breast Feeding;Breastfed infant;Centers of Research Excellence;Child;Childhood;Clinical;Clinical Pharmacology;Clinical Sciences;cohort;Collection;Cytochrome P450;Data;Data Science;Data Scientist;Development;Drug Kinetics;drug metabolism;Education;Enrollment;Ensure;enzyme activity;Enzymes;experience;Exposure to;Face;Faculty;Fostering;fundamental research;Growth and Development function;Hepatic;High Pressure Liquid Chromatography;Human;Human Milk;human milk oligosaccharides;Immune;immune function;Immune response;Infant;infant monitoring;infant outcome;Infection;Infrastructure;innovation;Laboratories;Lead;Leadership;Mass Spectrum Analysis;Metabolic;metabolome;metabolomics;microbiome;Milk;Mission;Molecular;Mothers;mouse model;National Institute of Child Health and Human Development;Near-Infrared Spectroscopy;Neonatal;non-invasive monitor;novel;Nutritional;Oligosaccharides;operation;Outcome;pathogen;pediatric pharmacology;Performance;Pharmaceutical Preparations;Pharmacology;pharmacometrics;physiologic model;Physiological;Pilot Projects;Pneumococcal vaccine;Productivity;programs;Protocols documentation;Public Health;Research;Research Infrastructure;Research Methodology;Research Personnel;Research Project Grants;Resources;response;Role;Sampling;Serum;Skin;Source;Stress;Technical Expertise;Technology;Therapeutic;Therapeutic Research;Training;training opportunity;Validation

PROJECT_TITLE: Optimization of Antibiotics in Mothers and their Breastfed Infants Using Pharmacomicrobiomic and Metabolomic Analyses


NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Clinical Research;Microbiome;Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Women's Health Research

PI_NAMEs: CHAMBERS, CHRISTINA  (contact)

PROJECT_TERMS: 1 year old;Adult;Age;Amoxicillin;Amoxicillin-Potassium Clavulanate Combination;Analytical Chemistry;Antibiotic Therapy;Antibiotics;Azithromycin;biobank;Biological Assay;Biological Markers;Breast Feeding;Breastfed infant;California;Carbohydrates;Clavulanic Acids;Clinical;Collaborations;Collection;Data;Data Science;Development;Drug Kinetics;Drug Prescriptions;Enrollment;evidence base;Fatty acid glycerol esters;Feces;Female;follow-up;Growth;Growth and Development function;gut health;Health Personnel;Height;Home;Home environment;Human Milk;Immune response;Infant;Infant Development;infant gut microbiome;infant outcome;Infection;Infrastructure;Interdisciplinary Study;Interview;Knowledge;Lactation;Life;male;mastitis;Measures;Medical Records;metabolomics;microbiome;microbiota;Milk;Monitor;Mothers;Nitrofurantoin;Nutritional;Oligosaccharides;Participant;pharmacometrics;Population;Postpartum Period;Postpartum Women;prospective;Proteins;Public Health;Qualifying;Questionnaires;recruit;reproductive;Research;Sampling;Skin;stool sample;Swab;Testing;Time;transmission process;Universities;Upper Respiratory Infections;uptake;Urinary tract;Weight;Woman;Writing

PROJECT_TITLE: Antibiotic Treatment in Breastfeeding Mothers: Effects on Milk, Microbiome, and Infant Outcomes


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Fragile X Syndrome;Intellectual and Developmental Disabilities (IDD);Mental Health;Pediatric;Rare Diseases;Women's Health Research

ORG_CITY: MADISON

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PROJECT NARRATIVE The proposed project is relevant to public health because it contributes to a program of research focused on significantly improving the communication abilities of individuals with neurodevelopmental disorders, including females with idiopathic autism spectrum disorder (iASD) and females with fragile X syndrome (FXS). Through a rigorous, longitudinal design, the proposed study will examine both language and executive function using well validated measures including experimental tasks, standardized assessments, parent report, and naturalistic language sampling to successfully achieve our three specific aims. Given the prevalence of iASD (1 in 54 children), and the significant overlap between FXS and iASD, this project directly addresses the NIDCD's mission to improve the lives of individuals with communication disorders.

PI_NAMEs: STERLING, AUDRA MARIE (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: 12 year old;Academic achievement;Academic skills;Adaptive Behaviors;Address;Age;Area;Attention;autism spectrum disorder;autistic;behavioral phenotyping;Biological Models;Child;Clinical;clinical practice;Coffee;Cognition;Cognitive;cognitive ability;Communication;Communication impairment;Comparative Study;Complex;course development;Data;Development;Diagnosis;Disease;education planning;Educational Models;executive function;experience;Female;Foundations;Fragile X Syndrome;functional outcomes;Genes;Goals;Impairment;improved;Individual;individualized medicine;Inherited;Intellectual functioning disability;Intervention;Knowledge;Language;Language Development;language impairment;literacy;longitudinal design;male;Measures;Mission;National Institute on Deafness and Other Communication Disorders;Nature;Neurodevelopmental Disorder;non-verbal;Outcome;Parents;peer;Performance;Phenotype;Population;Prevalence;programs;psychiatric comorbidity;Public Health;recruit;Reporting;Research;Sampling;School-Age Population;Schools;Severities;skills;Specificity;Standardization;symptomatology;Symptoms;Syndrome;Testing;Time;Work

PROJECT_TITLE: Language and Executive Function in Females with ASD or FXS

STUDY_SECTION: CPDD

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Aphasia;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Machine Learning and Artificial Intelligence;Neurosciences;Rehabilitation

ORG_CITY: NEW YORK

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: COLUMBIA UNIV NEW YORK MORNINGSIDE

ORG_STATE: NY

PHR: Speech and language disorders are major health issues. Speech perception requires a listener to compute linguistic units from variable acoustic signals, and where and how these computations happen in the human auditory cortex remains speculative. Using invasive human electrophysiology, we propose to study the neural encoding and computational underpinnings of the acoustic and linguistic features that enable speech perception; investigating this process in various auditory areas at high resolution will extend our knowledge of human speech perception and produce new insights into the mechanisms of speech and language disorders.

PI_NAMEs: MESGARANI, NIMA  (contact)

PROGRAM_OFFICER_NAME: KOPF, LISA MARIE

PROJECT_TERMS: Acoustics;Address;Anatomy;Animal Model;Aphasia;Area;Auditory area;Auditory Perception;auditory processing;auditory stimulus;Brain;Categories;Characteristics;Communication impairment;Comprehension;Computer Models;convolutional neural network;cortex mapping;Dimensions;Discipline;Dyslexia;Electrocorticogram;Electroencephalography;Electrophysiology (science);Frequencies;Health;Human;Impairment;Implanted Electrodes;improved;innovation;insight;interest;Intuition;Joints;Knowledge;Language Development;Language Disorders;Linear Regressions;linear transformation;Linguistics;Maps;Measurement;Measures;Methodology;Methods;Modeling;National Institute on Deafness and Other Communication Disorders;Nature;neural;neural circuit;neural network;Neural Network Simulation;Neurobiology;neurophysiology;neurosurgery;neurotransmission;nonhuman primate;novel;Patients;Persons;Phonetics;phonology;predicting response;Process;Property;Prosthesis;receptive field;Regional Anatomy;Research;Resolution;response;Response Latencies;Semantics;Signal Transduction;Site;sound;Specific qualifier value;Specificity;Speech;Speech Acoustics;Speech Disorders;Speech Pathology;Speech Perception;speech processing;Stimulus;Superior temporal gyrus;Surface;Technology;temporal measurement;Time;Training;United States;Work

PROJECT_TITLE: Functional and computational characterization of the human auditory cortex

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Complementary and Integrative Health;Diabetes;Dietary Supplements;Genetics;Nutrition;Prevention

ORG_CITY: BALTIMORE

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: PROJECT NARRATIVE Development of new strategies to slow or prevent the progression of prediabetes to type 2 diabetes would have a significant health benefit to millions of individuals worldwide and would reduce related economic burden on healthcare systems. Zinc supplementation may represent an efficacious, safe, and inexpensive way to improve insulin action and reduce fasting glucose, hemoglobin A1c, and lipid levels in subjects with prediabetes. The proposed research will provide novel insights regarding the utility of zinc supplementation in those with prediabetes, prospectively characterize genetic variation that impacts zinc transport, and ultimately provide justification for future mechanistic studies and larger clinical trials of zinc supplementation to prevent or delay onset of type 2 diabetes.

PI_NAMEs: LEWIS, JOSHUA PATRICK (contact)

PROGRAM_OFFICER_NAME: GOROSPE, RAFAEL

PROJECT_TERMS: adverse outcome;Alleles;American;Anabolism;Behavioral;Blood Glucose;blood glucose regulation;Body Weight decreased;C-Peptide;Callback;Cardiovascular Diseases;Cholesterol;Chronic;Clinical;Clinical Trials;Data;design;Development;diabetes risk;Diet Modification;Dietary Supplementation;Disease;Double-Blind Method;double-blind placebo controlled trial;Dropout;Economic Burden;economic impact;Exercise;Family;fasting glucose;fasting plasma glucose;FDA approved;Future;Genes;Genetic;Genetic Determinism;Genetic Polymorphism;Genetic Variation;genome wide association study;Genomics;Genotype;global health;Glucose;Glucose tolerance test;glycemic control;Glycemic Index;Glycosylated hemoglobin A;Health;Health Benefit;Health Care Costs;Healthcare Systems;Homozygote;Hour;impaired glucose tolerance;improved;indexing;Individual;insight;Insulin;Insulin Resistance;insulin secretion;insulin sensitivity;intravenous glucose tolerance test;Investigation;islet;Islet Cell;Kidney Failure;LDL Cholesterol Lipoproteins;Life Style;Lipids;Measures;Medical;member;Metabolic;Minor;Morbidity - disease rate;mortality;Neuropathy;Non-Insulin-Dependent Diabetes Mellitus;Nonpharmacologic Therapy;novel;nutrition related genetics;OGTT;Participant;Patients;Peripheral;Pharmaceutical Preparations;placebo group;Placebos;Play;Prediabetes syndrome;prevent;Prevention;Probability;Proinsulin;prospective;Randomized;randomized, clinical trials;recruit;Research;Resistance;response;Retinal Diseases;Risk;Role;Sampling;side effect;solute;Structure of beta Cell of islet;therapeutic development;Tissues;trial comparing;Triglycerides;United States;Variant;Zinc;Zinc Acetate;Zinc supplementation;zinc-binding protein

PROJECT_TITLE: Clinical and Nutrigenetic Assessment of Zinc in Patients with Prediabetes

STUDY_SECTION: NMHD

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


NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Immunization;Infectious Diseases;Microbiome;Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention;Vaccine Related;Women's Health Research

PI_NAMEs: NIZET, VICTOR  (contact)

PROJECT_TERMS: Adverse effects;Affect;Age;Ampicillin;Antibacterial Response;Antibiotic Prophylaxis;Antibiotic Therapy;Antibiotics;antimicrobial;Area;Attention;Bacterial Infections;Bacterial Vaccines;Basic Science;Birth;Breast Feeding;Breastfed infant;Childhood;Clinical Pharmacology;Communicable Diseases;Development;Diagnosis;Disease;Drug Kinetics;early onset;Experimental Models;Guidelines;gut microbiome;gut microbiota;Helper-Inducer T-Lymphocyte;Hepatitis B Vaccines;Human;Human Milk;Immune;immune function;Immune response;Immune system;Immunology;improved;Incidence;Infant;infant gut microbiome;Infant Health;Infection;infection risk;innate immune pathways;insight;intrapartum;Investigation;Length;Leukocytes;Life;Measurable;metabolome;metabolomics;microbial;microbiome;Morbidity - disease rate;mortality;Mothers;mouse model;Mucous Membrane;Mus;Natural Immunity;Neonatal;neonatal infection;Newborn Infant;novel;Oligosaccharides;pathogen;pathogenic bacteria;Perinatal Infection;Pharmacology;Physicians;Placenta;polarized cell;Predisposition;Pregnancy;Pregnant Women;prevent;Prevention;promote resilience;Property;prophylactic;Prophylactic treatment;Recommendation;Research Personnel;response;Risk Reduction;Scientist;Sepsis;Serum;Shapes;Streptococcal Infections;Streptococcus Group B;Streptococcus pneumoniae;Testing;Therapeutic;Toxicology;Training;translational research program;Vaccination;vaccine response;Vaccines;vaccinology;Virulence Factors;Weaning

PROJECT_TITLE: The impact of ampicillin and breast milk oligosaccharides on the infant microbiome and immune functions


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Bioengineering;Biomedical Imaging;Cardiovascular;Heart Disease;Lung;Orphan Drug;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative Acute respiratory distress syndrome (ARDS) is common complication of acute lung injury that is associated with a high mortality. We propose a multimodality imaging approach for evaluation of activation of an enzyme in the lung that has been shown to play an important role in disease progression. We will use this same imaging approach to also assess a novel drug delivery system for local inhibition of this enzyme in the lung to prevent the progressive lung injury associated with ARDS.

PI_NAMEs: SINUSAS, ALBERT J (contact)

PROGRAM_OFFICER_NAME: SHENOY, SIDDHARTH KAUP

PROJECT_TERMS: Acute Lung Injury;Acute Respiratory Distress Syndrome;Alveolar;Anatomy;Angiography;Animal Model;Animals;Architecture;Autopsy;Biophysics;Blood;Blood Vessels;Bronchial Lavages;Cardiac;Cardiac Myocytes;Cardiopulmonary;Cardiopulmonary Physiology;Cardiovascular Diseases;Chemical Injury;clinical application;clinically relevant;Complement Activation;complement pathway;Complication;contrast enhanced computed tomography;Coupled;COVID-19 pandemic;COVID-19/ARDS;cytokine;Cytokine Activation;Detection;detection sensitivity;Diagnostic Imaging;diagnostic strategy;Diffuse;Disease;Disease Progression;Dose;Doxycycline;Drug Delivery Systems;Early Diagnosis;Elastin;Endothelium;Enzyme Activation;Enzyme Inhibition;Evaluation;experience;Extracellular Matrix;Extracellular Matrix Degradation;Family;Fibrillar Collagen;first-in-human;Formulation;Future;Heart;Human;Hybrids;Hydrogels;Image;imaging approach;imaging biomarker;imaging modality;Imaging technology;Impairment;improved;individual patient;Inflammation;Inflammatory;Inhibition of Matrix Metalloproteinases Pathway;inhibitor;Injury;Intensive Care Units;Interruption;Intervention;Intravenous;ischemic injury;Life;Lung;Lung Compliance;Lung Diseases;lung injury;Matrix Metalloproteinase Inhibitor;Matrix Metalloproteinases;Measurement;Medical;Molecular;molecular imaging;mortality;multidisciplinary;Multimodal Imaging;Myocardial dysfunction;myocardial injury;Myocardium;novel;novel diagnostics;novel therapeutic intervention;novel therapeutics;Outcome Study;Pathology;Pathway interactions;Patients;Peptide Hydrolases;Perfusion;Physicians;Play;porcine model;Positioning Attribute;pre-clinical;pressure;prevent;Proteolysis;pulmonary arterial hypertension;pulmonary arterial pressure;Pulmonary Circulation;pulmonary function;pulmonary vascular disorder;radiotracer;Recovery;Research Personnel;Resistance;Resources;respiratory;Respiratory Failure;Right Ventricular Dysfunction;right ventricular failure;Risk;Role;Scheme;Scientist;single photon emission computed tomography;Stress;Structure of parenchyma of lung;targeted treatment;Testing;Therapeutic;therapeutic evaluation;therapeutic target;Tissues;Treatment Efficacy;treatment strategy;validation studies;vascular injury;ventilation;Ventilator;Ventilator-induced lung injury;Ventricular;Visualization;X-Ray Computed Tomography

PROJECT_TITLE: Imaging and Targeting Lung Proteolysis in ARDS

STUDY_SECTION: EITA

STUDY_SECTION_NAME: Emerging Imaging Technologies and Applications Study Section[EITA]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics;Infectious Diseases

ORG_CITY: EAST LANSING

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: MICHIGAN STATE UNIVERSITY

PHR: Narrative The study of lactate racemase and its newly discovered nickel-pincer nucleotide (NPN) cofactor is highly relevant to public health because the enzyme is present in many microorganisms associated with the human microbiome and in numerous pathogens. The racemase enzyme produces D-lactate that is required for biosynthesis of the cell walls and responsible for vancomycin resistance in some microorganisms. This project will elucidate the steps of NPN cofactor synthesis and define its roles in metabolism beyond lactate racemization.

PI_NAMEs: HAUSINGER, ROBERT P (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Acids;adduct;Aerococcus;Anabolism;analog;anti-microbial drug;antimicrobial;Bacteria;Bacterial Genome;Binding;Binding Proteins;Biochemical;Bioinformatics;Biological;C-terminal;Carbon;Carbon Dioxide;carboxylate;Catalysis;Cell Wall;Cells;Coenzyme A;Coenzymes;cofactor;Complex;Cryoelectron Microscopy;Crystallography;cysteine desulfurase;dehydroalanine;Drug Targeting;enantiomer;enzyme structure;Enzymes;epimerase;Gene Cluster;Genes;Health;Homologous Gene;Human;Human Microbiome;human pathogen;Hydrolysis;Hydroxy Acids;In Vitro;in vivo;in vivo evaluation;interest;Investigation;Iron;Knowledge;Lactic acid;Lactobacillus plantarum;Ligand Binding;Link;Metabolic;Metabolism;microbiome;microorganism;N-terminal;Nickel;nicotinic acid adenine dinucleotide;novel;Nucleotides;Ornithine;pathogen;pathogenic bacteria;Pathogenicity;Pathway interactions;persulfides;Property;Protein Binding Domain;Proteins;Public Health;Racemases;racemization;Reaction;Recycling;Research;Role;Site;skills;Specificity;Spectrophotometry;Spectrum Analysis;Structure;Sulfides;Sulfur;System;Testing;Thermotoga maritima;Thioamides;Vancomycin Resistance;Variant;Work;Zinc

PROJECT_TITLE: Nickel-pincer nucleotide enzymes

STUDY_SECTION: MSFA

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Clinical Research;Genetics;Hematology;Rare Diseases;Women's Health Research

ORG_CITY: HERSHEY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

ORG_STATE: PA

PHR: Project Narrative Bleeding symptoms in female Hemophilia A carriers are underrecognized and poorly understood, leading to adverse health events and outcomes. Current methods of assessing bleeding risk in males with Hemophilia A are inadequate when applied to female Hemophilia A carriers, and no formal classification consistent with their bleeding risk exists. To improve the identification and risk stratification of this large group, we will develop and validate a multivariate risk prediction model, perform mechanistic studies to evaluate the underlying molecular basis for bleeding, and evaluate additional modifiers of hemostasis to further refine risk prediction.

PI_NAMEs: CYGAN, PETER H (contact)

PROGRAM_OFFICER_NAME: HILL-PRYOR, CRYSTAL DARLEANE-ROBIN

PROJECT_TERMS: Activated Partial Thromboplastin Time measurement;activated Protein C;Address;Adolescent;Adult;Adult women;adverse outcome;Advocate;Affect;Alleles;Anticoagulants;Antigens;Area;Award;Benign;biological adaptation to stress;Biological Assay;Biology;Biometry;Blood Coagulation Disorders;career;career development;Carrier State;Categories;Cell Culture System;Cell Line;Cells;Chromogenic Substrates;Classification;Clinical;Clinical Management;clinically relevant;clinically significant;Coagulation Process;cohort;Cultured Cells;Data;Desmopressin;Development;Diagnostic;Endothelial Cells;Ensure;Evaluation;Event;experience;Experimental Designs;F8 gene;Factor V;Factor VIII;Feedback;Female;Future;Generations;genetic variant;Goals;Health;Hematology;Hemophilia A;Hemorrhage;Hemostatic Agents;Hemostatic function;high risk;Impairment;improved;improved outcome;Individual;Injury;innovation;Institution;Investigation;K-Series Research Career Programs;Life;Link;Logistic Regressions;male;Measures;meetings;men;Mentors;Mentorship;Methods;Modeling;Molecular;Mosaicism;multidisciplinary;mutant;Mutation;novel strategies;Operative Surgical Procedures;Outcome;Pathway interactions;Pattern;Perinatal;Phenotype;Physiological;Plasma;Population;Postpartum Hemorrhage;Postpartum Period;Pregnancy;Process;programs;prospective;Recording of previous events;Research;Resistance;response;Risk;risk prediction;risk prediction model;risk stratification;Role;Sampling;Scientist;statistics;stressor;success;Symptoms;Testing;TFPI;Thrombin;Training;Training Programs;translational research program;treatment response;Validation;women's treatment;Work;X Chromosome;X Inactivation

PROJECT_TITLE: Abnormal Bleeding Risk in Female Hemophilia A Carriers

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(MA)]


NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Clinical Research;Microbiome;Nutrition;Pediatric;Prevention;Women's Health Research

PI_NAMEs: TSUNODA, SHIRLEY M (contact)

PROJECT_TERMS: Adult;Affect;Amoxicillin;Ampicillin;Analytical Chemistry;Animals;Antibiotics;Area;Asthma;Azithromycin;Basic Science;Blood;Blood Volume;Breast Feeding;Breastfed infant;Celiac Disease;Chronic;Clavulanate;Clinical;Clinical Research;Complement;Cytochrome P450;Data;Data Science;Dedications;Development;Diabetes Mellitus;Disease;Drug Monitoring;enzyme activity;Enzymes;experimental study;Exposure to;Health;Hepatic;Home environment;Human;human data;Human Milk;Hypersensitivity skin testing;Individual;Infant;infant monitoring;Infection;innovation;innovative technologies;insight;Intake;Intestines;Life;Liver;Mass Spectrum Analysis;Mediating;Metabolic;Metabolism;metabolome;metabolomics;Methods;Microbe;microbial;microbiome;microbiome alteration;microbiome analysis;microbiome composition;Microsomes;Milk;Molecular;Monitor;Mothers;Mus;Nature;Nitrofurantoin;non-invasive monitor;Obesity;Outcome;Pharmaceutical Preparations;pharmacometrics;Protein Isoforms;Regulation;research study;Role;Sampling;Series;Skin;stool sample;Swab;Therapeutic;Time

PROJECT_TITLE: Impact of Maternal Antibiotics on the Breastfeeding Infant Microbiome and Metabolome


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Patient Safety;Prevention;Social Determinants of Health

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Project Narrative/Public Health Relevance Statement There is an urgent need for effective diabetes self-management interventions that are convenient, scalable, sustainable, and able to meet the needs of diverse patient populations including those with limited health literacy. Designed with user feedback and sensitivity to patients' literacy levels and developed with the ability to integrate into a variety of electronic health records, the My Diabetes Care (MDC) patient portal intervention has demonstrated the potential to fill this critical gap. The overall objective of this proposal is to: (1) expand MDC's display of user's diabetes health data beyond hemoglobin A1C, blood pressure, cholesterol, and flu vaccination status to include microalbumin and BMI and enhance access by creating a Spanish-language version; (2) evaluate the effects of MDC on diabetes-related outcomes while demonstrating its scalability by integrating it into another health system and conducting a pragmatic randomized controlled trail in an ethnically and racially diverse patient population; and (3) examine how the effects of MDC arise by studying causal mediators.

PI_NAMEs: MARTINEZ, WILLIAM  (contact)

PROGRAM_OFFICER_NAME: LAWRENCE, JEAN M

PROJECT_TERMS: Academic Medical Centers;Address;Adherence;Adoption;Adult;Affect;Albumins;Attention;Behavior;Behavioral;behavioral outcome;Blood Pressure;Body mass index;Caring;Cholesterol;Clinical;Communities;cost;Data;Data Display;design;Diabetes Mellitus;diabetes self-management;Diet;dietary adherence;Disease;Education;Electronic Health Record;Ensure;ethnic diversity;ethnic minority;Exercise;experience;Fast Healthcare Interoperability Resources;Feedback;follow-up;Future;Glucose;glycemic control;Glycosylated hemoglobin A;Health;health data;health inequalities;health information technology;health literacy;Health system;Health Technology;Healthcare Systems;Hospitals;improved;improved outcome;Influenza vaccination;Institution;interoperability;Intervention;intervention effect;Knowledge;Language;literacy;Low-Density Lipoproteins;Maintenance;Measures;Mediating;Mediation;Mediator;Medical;Medical Care Team;Medical center;Methodology;Mobile Health Application;Modeling;Monitor;Motivation;Nature;Non-Insulin-Dependent Diabetes Mellitus;Notification;novel;Outcome;patient engagement;patient population;patient portal;Patients;Pharmaceutical Preparations;Premature Mortality;prevent;primary care clinic;primary outcome;psychosocial;public health relevance;racial diversity;racial minority;Randomized;Randomized, Controlled Trials;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Readiness;recruit;Research;routine care;Sampling;Self Care;Self Management;Site;skills;Spanish;Specific qualifier value;study population;System;Technology;Testing;therapy design;treatment as usual;uptake;usability;user centered design;Visualization;Woman;Work

PROJECT_TITLE: Effects of a Novel, Scalable, and Sustainable Patient Portal Intervention on Diabetes-Related Outcomes: A Pragmatic Randomized Controlled Trial

STUDY_SECTION: CIDH

STUDY_SECTION_NAME: Clinical Informatics and Digital Health Study Section[CIDH]


NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Microbiome;Nutrition;Pediatric;Prevention

PI_NAMEs: TREMOULET, ADRIANA H (contact)

PROJECT_TERMS: Administrator;Annual Reports;Antibiotic Therapy;Antibiotics;Biochemistry;Biology;Breastfed infant;Businesses;Childhood;Clinical Pharmacology;Collaborations;Communicable Diseases;Communication;Education;Effectiveness;Elements;Evaluation;experience;Fostering;Future;Goals;Health Sciences;Human Milk;Immunology;improved;Infant Health;interest;Knowledge;Lead;Leadership;Logistics;Maternal Health;Mentors;metabolomics;microbiome;microbiome research;Milk;Mission;Mothers;Neonatal;Occupational activity of managing finances;Outcome Assessment;outreach;pediatric pharmacology;pharmacometrics;Preparation;programs;Progress Reports;Publications;Recording of previous events;Records;Research;Research Activity;Research Project Grants;Research Training;Resources;Role;science teacher;Site;success;Therapeutic;timeline;Training

PROJECT_TITLE: Optimization of Antibiotics in Mothers and their Breastfed Infants Using Pharmacomicrobiomic and Metabolomic Analyses (mPRINT P50)


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_DEPT: PATHOLOGY

ORG_NAME: WAYNE STATE UNIVERSITY

PHR: The goal of this application is to test the therapeutic efficacy of novel therapeutic agents for AR protein degradation using autophagy-targeting chimera (AUTOTAC) in castrate-resistant prostate cancer.

PI_NAMEs: KIM, HYEONG-REH CHOI (contact)

PROGRAM_OFFICER_NAME: GREENBERG, WILLIAM A

PROJECT_TERMS: Agonist;Anabolism;Androgen Antagonists;androgen deprivation therapy;androgen independent prostate cancer;Androgen Receptor;androgen sensitive;Androgens;Animal Model;antagonist;Anti-androgen Therapy;Autophagocytosis;Autophagosome;Biochemical Pathway;Biogenesis;Biology;cancer cell;Cell Line;Cell model;Cells;Chimera organism;Clinical Research;clinically relevant;Complex;Cytoplasm;Data;deprivation;Development;dimer;Disease;Disease Progression;DNA Binding Domain;DNA Sequence Alteration;enzalutamide;Excision;gain of function;Gene Expression Profile;Goals;high risk;Histopathology;Human;In Vitro;in vivo;inhibitor;innovation;Knock-out;Knockout Mice;Length;Ligand Binding;Ligand Binding Domain;Ligands;Link;Literature;Lysosomes;Malignant neoplasm of prostate;malignant phenotype;Mediating;Membrane;men;Modeling;Molecular;mortality risk;mouse model;mutant;neoplastic cell;novel;novel therapeutics;Nuclear;Oncogenic;Pathway interactions;patient derived xenograft model;Patients;Pharmaceutical Preparations;Pharmacotherapy;Play;Production;programs;Prostate;prostate cancer cell;prostate cancer model;prostate cancer progression;Protac;protein complex;protein degradation;Proteins;PTEN gene;receptor;receptor binding;receptor function;Receptor Inhibition;Receptor Signaling;Resistance;response;RNA Splicing;Role;single-cell RNA sequencing;small molecule;standard of care;Stanolone;Technology;Testing;Testosterone;Therapeutic;Therapeutic Agents;therapeutic evaluation;therapeutic target;therapeutically effective;therapy resistant;Tissues;transcription factor;transcriptome;Treatment Efficacy;treatment response;tumor;tumor heterogeneity;tumor microenvironment;Ubiquitination;Variant

PROJECT_TITLE: A novel AR degrader in castrate-resistant prostate cancer


PI_NAMEs: BODE, LARS  (contact)

PROJECT_TERMS: Aliquot;Analytical Chemistry;analytical tool;Antibiotic Therapy;Antibiotics;assay development;Biological;Biological Assay;biological heterogeneity;Biomedical Research;Breast Feeding;Breastfed infant;California;Cells;Childhood;Clinical;Clinical Sciences;Collaborations;Collection;Communities;Complex;Coupled;cytokine;Data;Data Science;design;Detection;Disease;experience;feeding;Fluorescence;ghrelin;glucagon-like peptide 1;Goals;Growth Factor;High Pressure Liquid Chromatography;Hormones;Human Characteristics;Human Milk;human milk oligosaccharides;Immunoassay;improved;Infant;Infant Development;Infant Health;infant morbidity/mortality;Infant Mortality;Knowledge;Lactation;Lactose;Leukocyte L1 Antigen Complex;lipidomics;Lipids;macromolecule;Macronutrients Nutrition;Maternal and Child Health;Measurement;Measures;metabolomics;Microbe;microbiome;microbiome analysis;Micronutrients;Milk;milk fat globule;milk microbiome;Mothers;Mus;Mutation;Near-Infrared Spectroscopy;Oligosaccharides;operation;Outcome;Participant;Peptide Hydrolases;Peptides;Performance;pharmacometrics;Pregnancy;programs;Proteins;Protocols documentation;Research;Research Personnel;Research Project Grants;Resources;response;Risk Reduction;Role;Safety;sample collection;Sampling;Services;sialylation;skills;Technology;technology validation;Therapeutic;Therapeutic Agents;Universities;Validation;Woman

PROJECT_TITLE: Milk Analytics Core


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE TET DNA demethylases are essential for revising the DNA methylation patterns and are required for gene regulation and cell differentiation. TET enzymes are indispensable for human health, as TET mutations are frequently found in blood cancers and are associated with immunodeficiency and childhood cancers. Our proposed studies will provide critical mechanistic insights into how TET regulates gene expression and cell differentiation and identify potential therapeutic targets for treating immunodeficiency and cancers.

PI_NAMEs: LIO, JERRY CHAN-WANG (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Aberrant DNA Methylation;Acute;Animal Model;Biological Process;Cell Differentiation process;Chromatin;Cytosine;demethylation;Disease;DNA;DNA Methylation;DNA Modification Process;Elements;Enhancers;Ensure;Environment;Enzymes;Epigenetic Process;epigenome;epigenome editing;Family;Gene Activation;Gene Expression;Gene Expression Regulation;Genes;Genomic Instability;Germ Lines;Goals;Health;Hematologic Neoplasms;Hematopoietic Neoplasms;Histones;Human;Immunodeficiency and Cancer;insight;Link;Maintenance;Malignant Childhood Neoplasm;Malignant Neoplasms;Mammalian Cell;Maps;Mediating;Methods;Methylation;methylation pattern;methylome;Modification;Molecular;Monitor;Mutate;Mutation;novel;permissiveness;programs;Research;therapeutic target

PROJECT_TITLE: Molecular Mechanism of TET-mediated Gene Regulation

STUDY_SECTION: MRAA

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


ADMINISTERING_IC: AR

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Biomedical Imaging;Clinical Research;Clinical Trials and Supportive Activities;Duchenne/ Becker Muscular Dystrophy;Lung;Muscular Dystrophy;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: GAINESVILLE

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: This study addresses critical barriers in therapeutic development for muscular dystrophy, a genetic muscle wasting disease. We will develop and test new outcome measures that provide an unbiased assessments of muscle quality, without the need for muscle biopsies. We will also collect much needed natural history data.

PI_NAMEs: VANDENBORNE, KRISTA H (contact)

PROGRAM_OFFICER_NAME: CARIFI, EMILY FORAN

PROJECT_TERMS: 9 year old;Abdomen;Address;advanced disease;Age;Alleles;arm;arm function;Becker Muscular Dystrophy;Biological Markers;biomarker development;Biopsy;Cause of Death;Chest wall structure;chromosome X loss;Cine Magnetic Resonance Imaging;Clinical assessments;Clinical Trials;Clinical Trials Design;cohort;Communities;curative treatments;Data;data sharing;Disease;disease model;Disease Progression;Duchenne muscular dystrophy;Dystrophin;Enrollment;Europe;Exhibits;exon skipping;experience;Fatty acid glycerol esters;Funding;Future;Gene Delivery;Genes;Genetic;Goals;Histologic;Image;imaging biomarker;Impairment;in vivo monitoring;Individual;Infiltration;Inflammation;International;Leg;Lower Extremity;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Measures;Molecular;Monitor;Motor;Multi-Institutional Clinical Trial;Multicenter Studies;Muscle;Muscle Weakness;Muscular Atrophy;Muscular Dystrophies;Mutation;Natural History;next generation;novel;Outcome Measure;Patients;Pelvic Girdle;Pharmaceutical Preparations;Phenotype;Population;Positioning Attribute;predictive marker;primary endpoint;Production;Protocols documentation;pulmonary function;Reproducibility;Research;Research Design;respiratory;Respiratory Diaphragm;Respiratory Failure;Respiratory Muscles;Respiratory physiology;response;restoration;secondary endpoint;Site;Technology;Testing;therapeutic development;Upper Extremity;Wasting Syndrome;whole body imaging;Work

PROJECT_TITLE: Magnetic Resonance Imaging and Biomarkers for Muscular Dystrophy

STUDY_SECTION: SMEP

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


NIH_SPENDING_CATS: Breastfeeding, Lactation and Breast Milk;Clinical Research;Nutrition;Pediatric;Prevention;Women's Health Research

PI_NAMEs: MOMPER, JEREMIAH D (contact)

PROJECT_TERMS: Acceleration;Address;Analytical Chemistry;Animal Model;anti-microbial drug;Antibiotics;Basic Science;Biological Assay;Blood;Breast Feeding;Breastfed infant;Cerebrospinal Fluid;Clinical;cost effective;Coupled;Data;data integration;Data Science;Dedications;Development;Drug Kinetics;Dryness;Education and Outreach;Environment;experience;Goals;Hair shaft structure;High Pressure Liquid Chromatography;Human Milk;Infant;Infrastructure;innovation;instrumentation;Knowledge acquisition;Laboratories;laboratory facility;Leadership;Liquid Chromatography;Measures;Meconium;medical specialties;meetings;metabolomics;Milk;models and simulation;Mothers;multidisciplinary;novel;Parents;pediatric department;pediatric pharmacology;Pharmaceutical Preparations;pharmacokinetic model;Pharmacologic Substance;Pharmacology;pharmacometrics;Pharmacy Schools;physiologic model;Physiological;Plasma;pre-clinical;Productivity;programs;Qualifying;Research;Research Activity;Resources;Sampling;Science;Secure;Serum;Spottings;tandem mass spectrometry;Testing;Therapeutic Effect;Tissues;Training;Translational Research;Translations;Urine;Validation;Whole Blood

PROJECT_TITLE: Pharmacometrics and Analytical Chemistry Core


ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: The overarching goal of our Center proposal entitled “Translational Medicine and Mechanistic Studies of Brain Neurophysiology in Fragile X Syndrome” is to utilize highly interrelated research strategies with two primary aims, advancing translational medicine approaches (biomarker development, drug challenge studies, resolving illness heterogeneity) and expanding the mechanistic understanding of Fragile X syndrome (FXS) biology. The goal of this work is to foster the development of new, more effective therapies. We propose to pursue these aims through the establishment of integrated, interdependent research programs from patient-centered research to in vivo animal experiments to cellular sub-type specific and molecular models.

PI_NAMEs: ERICKSON, CRAIG  (contact)

PROGRAM_OFFICER_NAME: KAU, ALICE S

PROJECT_TERMS: Address;Animal Experiments;Animal Model;Back;Behavior;Behavioral;bench to bedside;Biological Markers;Biology;biomarker development;Brain;brain dysfunction;Cholecystokinin;Clinical;Clinical Research;Clinical Sciences;Clinical Trials;clinically relevant;Cognition;Collaborations;Data;design;Development;Disease;drug development;Drug Monitoring;effective therapy;Electroencephalography;Electrophysiology (science);endocannabinoid signaling;Endocannabinoids;endogenous cannabinoid system;Ensure;Environment;experience;Failure;FMR1 gene;Fostering;Fragile X Syndrome;Future;Gene Proteins;gene therapy;Glutamates;Goals;Heterogeneity;Human;human study;improved;in vivo;individualized medicine;insight;interest;Interneurons;Investigation;Knowledge;Link;Measures;Methodology;Mission;Modeling;Molecular;Molecular Analysis;molecular modeling;multi-electrode arrays;multidisciplinary;Mus;Neocortex;network models;neural circuit;neurobehavioral;Neurobiology;Neurons;neurophysiology;Neurosciences Research;neurotransmission;novel;novel therapeutics;Patient Monitoring;patient oriented;patient stratification;Patients;personalized medicine;Persons;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phenotype;Physiology;pre-clinical;pre-clinical research;preclinical study;predictive marker;Preparation;Principal Investigator;programs;protein expression;receptor;Research;response;Risk;Role;Science;Shapes;Slice;small molecule;Speed;Stimulus;success;Surface;Technology;Testing;Therapeutic Effect;therapy development;Time;translational medicine;translational potential;Translations;Work

PROJECT_TITLE: Translational medicine and mechanistic studies of brain neurophysiology in Fragile X Syndrome


NIH_SPENDING_CATS: Brain Disorders;Fragile X Syndrome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Orphan Drug;Pediatric;Precision Medicine;Rare Diseases

PROJECT_TERMS: Accountability;Achievement;Address;Advisory Committees;analytical tool;Animal Experiments;Animal Model;Area;Back;Behavior;behavior test;bench to bedside;Biological Markers;Biology;biomarker development;Brain;Clinical;Clinical Research;clinical training;Code;cognitive testing;Collaborations;Communication;Communities;Consultations;Data;Data Analyses;data archive;design;Development;disease model;drug development;drug discovery;Drug Monitoring;Education;effective therapy;Electrophysiology (science);Ensure;experience;Failure;Family;FMR1 gene;Fostering;Foundations;Fragile X Syndrome;Functional disorder;Future Generations;Goals;Guidelines;Heterogeneity;Housing;Human;Human Resources;human study;IACUC;in vivo;Institutional Review Boards;Methods;Mission;Modeling;molecular modeling;mouse model;Mus;National Institute of Mental Health;Neurons;neurophysiology;Neurosciences;Neurosciences Research;novel;novel therapeutics;patient biomarkers;Patient Monitoring;patient oriented;patient oriented research;patient stratification;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Policies;pre-clinical;predictive marker;Procedures;Productivity;programs;Provider;Recovery;Regulation;Research;research data dissemination;Resource Sharing;Resources;Risk;Rodent;Scientist;Services;Shapes;Signal Transduction;Site;Statistical Data Interpretation;statistics;Structure;Students;success;support network;synergism;Testing;therapy development;Training Support;Translating;translational medicine;translational scientist;Treatment outcome;United States National Institutes of Health;Universities;Voice;Work


NIH_SPENDING_CATS: Autism;Behavioral and Social Science;Brain Disorders;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Intellectual and Developmental Disabilities (IDD);Mental Health;Networking and Information Technology R&D (NITRD);Pediatric;Prevention;Rural Health;Social Determinants of Health;Telehealth

ORG_CITY: DAVIS

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative The goals of this project are to determine the developmental and clinical outcomes of infants with early parent concern for autism via telehealth, and to identify the material and psychosocial factors that support engagement and satisfaction with telehealth-mediated assessments. We propose to use a promising telehealth protocol for evaluating infants’ development, the TEDI, to prospectively follow 100 infants 6-12 months from diverse community settings through 36 months of age. Successful completion of these aims will increase the capacity to identify infants with elevated likelihood of autism and other neurodevelopmental disorders particularly in rural and low-resource areas, and will ultimately help to increase access to high-quality interventions and improve the developmental outcomes of many more underserved children with autism.

PI_NAMEs: TALBOTT, MEAGAN RUTH (contact)

PROJECT_TERMS: 4 year old;acceptability and feasibility;Address;Age;Age Months;Attention deficit hyperactivity disorder;autism spectrum disorder;autistic children;behavior measurement;caregiver education;Caregivers;Child;Clinical;Clinical Research;Communication;Communities;community partners;community setting;COVID-19 pandemic;Data;Development;Developmental Course;Developmental Process;Devices;Diagnosis;Diagnostic;digital assessment;digital health;Early identification;Early Intervention;Ensure;Equity;Evaluation;Family;family support;feasibility testing;Feedback;Future;General Population;Geographic Locations;Geography;Goals;health assessment;health care availability;Health Services Accessibility;Healthcare;improved;infancy;Infant;Infant Development;Infant Health;infant outcome;Intervention;Intervention Studies;Intervention Trial;Language;Life;Measures;Mediating;Methodology;Monitor;Motor Skills;Neurodevelopmental Disorder;Outcome;outreach;Parents;Participant;personalized strategies;Play;prospective;Protocols documentation;Provider;Psychosocial Factor;Race;recruit;Reporting;Research;Resource-limited setting;response;Rural;rurality;Sampling;satisfaction;screening;Screening procedure;service delivery;service intervention;Services;Siblings;skills;social media;Social support;Speech Delay;Strategic Planning;Stress;telehealth;Testing;tool;trait;United States;United States National Institutes of Health;Visit;Waiting Lists;Work

PROJECT_TITLE: Leveraging Telehealth to Identify Infants at Elevated Likelihood for Autism in the First Year of life

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


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Fragile X Syndrome;Intellectual and Developmental Disabilities (IDD);Neurosciences;Orphan Drug;Pediatric;Precision Medicine;Rare Diseases

PROJECT_TERMS: Acute;Adult;advanced analytics;Age;age related;analytical method;association cortex;Auditory;auditory stimulus;Award;Behavior;Behavioral;behavioral impairment;behavioral phenotyping;behavioral study;bench to bedside;Biological Markers;Blood;Brain;brain dysfunction;Childhood;Clinical;Clinical Markers;Clinical Trials;clinically significant;Cognition;Cognitive;cognitive process;Collaborations;connectome;Coupling;Cross-Sectional Studies;Development;disease heterogeneity;disease model;Dose;Double-Blind Method;drug development;drug discovery;drug response prediction;Electroencephalography;Electrophysiology (science);Ensure;experience;experimental study;Female;FMR1 gene;follow-up;Fragile X Syndrome;Frequencies;gamma-Aminobutyric Acid;Genetic;Glutamate Receptor;Glutamates;graph theory;habituation;Heterogeneity;Human;Impairment;improved;Individual;Intellectual impairment;Link;male;Memantine;Methylation;Modeling;molecular marker;mosaic;mouse model;Mus;Mutation;N-Methylaspartate;Nature;network models;neural;neural model;neuronal circuitry;neuronal excitability;neurophysiology;neurotransmission;new therapeutic target;novel;novel marker;Outcome;Participant;Patients;Peripheral;personalized care;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phase;Placebo Control;Placebos;pre-clinical;precision medicine;Process;programs;protein expression;Regulation;Reporting;Research;response;Rest;Sampling;Sensory;Severities;sex;Slice;small molecule;somatosensory;Speed;Symptoms;synergism;System;targeted biomarker;Techniques;Testing;Translating;translational medicine;Translational Research;Translations;Validation;Work;Youth

PROJECT_TITLE: Network Mechanisms, Biomarkers and Pharmacology of Fragile X Syndrome in Humans


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Cannabinoid Research;Endocannabinoid System Research;Fragile X Syndrome;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Orphan Drug;Rare Diseases;Therapeutic Cannabinoid Research

PI_NAMEs: BINDER, DEVIN K (contact)

PROJECT_TERMS: Acute;Adult;analysis pipeline;Auditory;auditory stimulus;awake;Behavior;behavior test;behavioral outcome;Biological Markers;Brain;Brain region;cell type;Chronic;Clinical;Clinical Trials Design;clinically relevant;CNR1 gene;cognitive process;Cortical Synchronization;Data;density;Development;Discrimination;Disease;Dose;drug testing;Drug Tolerance;Electrodes;Electroencephalography;Electrophysiology (science);Endocannabinoids;endogenous cannabinoid system;Equilibrium;FAAH inhibitor;Fragile X Syndrome;Functional disorder;Glutamates;Human;Impaired cognition;Impairment;improved;In Vitro;Individual;inhibitor;inhibitory neuron;Measures;Memantine;Metabolism;Molecular;mouse model;multi-electrode arrays;Mus;neural circuit;Neurodevelopmental Disorder;neurophysiology;novel marker;novel therapeutic intervention;Outcome;Outcome Measure;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phase;Phenotype;Physiological;Physiology;Preparation;Research;Research Personnel;response;Rest;Reversal Learning;rimonabant;Sensory;Sensory Process;Slice;social communication;sound;Symptoms;Synapses;targeted treatment;Technology;Testing;Time;Translating;translational medicine;Treatment Efficacy;United States National Institutes of Health

PROJECT_TITLE: Network Mechanisms of Neurophysiology and Behavior in mouse models of Fragile X Syndromeme


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Dementia;Genetics;Human Genome;Neurodegenerative;Neurosciences;Prevention

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative The majority of people with Alzheimer’s dementia confirmed at autopsy—around 80%—are found to have one or more additional brain pathologies, including Lewy bodies, vascular brain injury, and TDP-43. A complementary and necessary strategy conventional case-control Alzheimer’s disease (AD) genetic studies is to perform genome-wide association studies (GWAS) using data from autopsies and distinguishing between research participants exhibiting “pure AD” and those with mixed AD pathology. The overarching goal of this proposal is to address this knowledge gap and further scientific understanding of the genetic influences of these differences by integrating detailed autopsy-derived data together with state-of-the-art statistical approaches and variety of omics data.

PI_NAMEs: FARDO, DAVID WILLIAM;MUKHERJEE, SHUBHABRATA  (contact)

PROGRAM_OFFICER_NAME: FENG, LI REBEKAH

PROJECT_TERMS: Address;Aging;Alzheimer's Disease;Alzheimer's disease brain;Alzheimer's disease pathology;Alzheimer's disease related dementia;Atlases;Autopsy;biobank;Bioinformatics;Biological;brain cell;Brain Pathology;Brain region;case control;cell type;Cerebrovascular Trauma;Chromatin;Clinical;Clinical Data;clinical risk;Clinical Trials;Clinical Trials Design;Cognitive;Data;data resource;Dementia;Development;Disease Progression;disorder control;Drug Targeting;epidemiology study;Exhibits;follow-up;Future;gene network;Genetic;genetic analysis;genetic architecture;Genetic study;genome wide association study;genome-wide;Genomic Segment;Genotype;Goals;Hand;Heterogeneity;hippocampal sclerosis;Human;improved;Individual;Infarction;insight;Knowledge;Lead;Lewy Bodies;Machine Learning;Memory;Mendelian randomization;Molecular;Multiomic Data;neuropathology;novel;novel strategies;Participant;Pathology;Pathway Analysis;Pattern;Persons;Phenotype;pleiotropism;prevent;protein TDP-43;religious order study;Research;Resolution;Risk Factors;risk variant;Sample Size;single nucleus RNA-sequencing;Stratification;Tissue-Specific Gene Expression;trait;transcriptome;Variant

PROJECT_TITLE: Genetic Architecture of Pure Alzheimer's Disease and Mixed Pathology

STUDY_SECTION: NMBH

STUDY_SECTION_NAME: Neurological, Mental and Behavioral Health Study Section[NMBH]


NIH_SPENDING_CATS: Brain Disorders;Cannabinoid Research;Endocannabinoid System Research;Fragile X Syndrome;Genetics;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Rare Diseases

PI_NAMEs: HUBER, KIMBERLY M. (contact)

PROJECT_TERMS: Acute;Area;base;Behavior;behavioral phenotyping;Biochemical;Brain;cell type;Cholecystokinin;Clinical;CNR1 gene;Collaborations;Contralateral;Coupling;Cre driver;Data;Defect;Electroencephalography;Endocannabinoids;Environment;Excitatory Synapse;experience;experimental study;FMR1 gene;Fragile X Syndrome;Frequencies;Functional disorder;Genetic;genetic manipulation;Glutamates;hippocampal pyramidal neuron;Human;in vivo;inhibitory neuron;Knock-out;Link;loss of function;Measures;Mediating;Methods;Molecular;mouse model;Mus;neocortical;Neurons;neurophysiology;optogenetics;Outcome;Parvalbumins;pharmacologic;Phenotype;Positioning Attribute;postnatal;Process;Proteins;receptor;Regulation;Research Personnel;response;Rest;Ribosomes;RNA;Role;Sensory;sensory cortex;Slice;somatosensory;Somatosensory Cortex;sound;Synapses;targeted treatment;Testing;Thalamic structure;Touch sensation;transcriptome;transcriptome sequencing;Translating;translational medicine;translatome

PROJECT_TITLE: FMRP regulation of local and long-range neocortical circuits in the mouse:  Links with EEG phenotypes


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Precision Medicine;Urologic Diseases

ORG_CITY: BUFFALO

ORG_NAME: ROSWELL PARK CANCER INSTITUTE CORP

PHR: PROJECT NARRATIVE Bladder cancer is among the top ten most common and fatal cancers in the U.S, of which about 75% are non- muscle invasive bladder cancer (NMIBC) characterized by exceptionally high risks of recurrence and progression. The proposed study is seeking to identify molecular signatures of NMIBC, with a goal to develop and validate tools to address the two most urgent challenges in clinical management of NMIBC: identifying high-risk patients for early and aggressive treatment and identifying patients who will be unresponsive or intolerant to Bacillus Calmette-Guerin (BCG), the mainstay adjuvant treatment for NMIBC, in favor of other treatments. Given that our study will be using data and specimens from a population-based, prospective cohort of NMIBC patients diagnosed within a large U.S. health care system, we can rapidly translate the findings into clinical practice to help improve NMIBC patient outcomes.

PI_NAMEs: KWAN, MARILYN L;TANG, LI  (contact)

PROGRAM_OFFICER_NAME: FILIPSKI, KELLY

PROJECT_TERMS: Acceleration;Address;Adjuvant Therapy;Adverse effects;aggressive therapy;Bacillus Calmette-Guerin Therapy;BCG Live;Biological Assay;cancer care;cancer epidemiology;cancer heterogeneity;Cancer Patient;cancer recurrence;cancer subtypes;cancer therapy;Classification;Clinical;clinical care;Clinical Management;clinical practice;clinical translation;cohort;Consensus;cost;Data;Demographic Factors;Diagnosis;Disease;Early treatment;effective therapy;environmental chemical exposure;Ethnic Origin;Etiology;Event;Failure;follow-up;Generations;Genes;Goals;health care delivery;Healthcare Systems;Heterogeneity;high risk;Immune;immunogenic;improved;Individual;individualized medicine;intravesical;Intravesical Administration;Investigation;Knowledge;Life Style;Malignant neoplasm of urinary bladder;Malignant Neoplasms;meetings;Modeling;Molecular;molecular marker;Molecular Profiling;molecular subtypes;Muscle;nano-string;Nature;Newly Diagnosed;non-muscle invasive bladder cancer;Occupational;Outcome;Pathologic;Patient-Focused Outcomes;Patients;population based;predicting response;predictive modeling;predictive tools;prevent;primary outcome;prognostic;prognostic value;Prospective cohort;Race;Recurrence;Recurrent disease;Research;Research Priority;response;Risk;Risk Factors;risk prediction model;risk stratification;Sample Size;sex;Smoking;Specimen;Survival Rate;System;Taxonomy;Therapeutic;tool;transcriptome;transcriptomics;Translating;Translations;Treatment outcome;treatment response;tumor;tumor progression;Tumor Subtype;Validation

PROJECT_TITLE: Transcriptomic classification of non-muscle invasive bladder cancer and its clinical and prognostic implication

STUDY_SECTION: CHSA

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


NIH_SPENDING_CATS: Asthma;Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Lung;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: WORCESTER

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

PHR: PROJECT NARRATIVE Over 6 million children in the United States have asthma, causing more than 14 million missed school days and billions of dollars in healthcare costs annually, with most poorly controlled asthma symptoms attributable to difficulties taking a daily inhaler that helps to control asthma. The proposed research program will evaluate Asthma Link, a school-supervised asthma therapy intervention tailored for real-world settings, that ensures children receive their daily inhaler at school. This intervention fills an unmet need for the families, pediatric practices and schools that support children with poorly controlled asthma and has the potential to dramatically improve childhood asthma outcomes.

PI_NAMEs: TRIVEDI, MICHELLE  (contact)

PROGRAM_OFFICER_NAME: FREEMER, MICHELLE M

PROJECT_TERMS: 14 year old;Address;Adherence;adherence rate;Adopted;Adrenal Cortex Hormones;Affect;Asthma;asthma exacerbation;Black race;Caring;Child;Child Care;Child Health;Child Support;Childhood;Childhood Asthma;Chronic Disease;Cities;Clinic;Clinical;clinical practice;Communities;comparison intervention;Control Groups;cost;Data;disabling disease;Effectiveness;effectiveness evaluation;effectiveness testing;effectiveness trial;Eligibility Determination;Emergency department visit;Ensure;ethnic minority;experience;Family;feasibility trial;follow-up;Future;future implementation;Health;Health Care Costs;health disparity;Health Expenditures;Health Personnel;Health Promotion;high risk;Hispanic;Hospitalization;Human Resources;implementation trial;improved;Infrastructure;Inhalation;Inhalation Drug Administration;Inhalators;innovation;interest;Intervention;Latino;Leadership;Link;Low income;Massachusetts;Measures;Medicaid;Medical Records;medication compliance;medication nonadherence;Methods;minority children;Modeling;Morbidity - disease rate;multidisciplinary;Outcome;Parents;Patient Compliance;pediatrician;Performance;Pharmaceutical Preparations;Pharmacy facility;Physicians;pilot trial;Play;Policies;pragmatic trial;Prevention;Preventive;primary care practice;primary outcome;Principal Investigator;Process;Process Assessment;process evaluation;Proctor framework;programs;Protocols documentation;Public Health;Quality of life;Questionnaires;racial minority;Randomized, Controlled Trials;Recording of previous events;Regimen;Reporting;Reproducibility;Research;Research Personnel;Resource-limited setting;Resources;response;Risk;Role;routine practice;school health;School Nursing;School-Age Population;Schools;standard of care;Symptoms;System;Testing;Therapeutic Intervention;Time;treatment adherence;treatment as usual;United States;United States National Institutes of Health;Work

PROJECT_TITLE: Asthma Link: A Partnership between Pediatric Practices, Schools, and Families to Improve Medication Adherence and Health Outcomes in Children with Poorly Controlled Asthma

STUDY_SECTION: CMGC

STUDY_SECTION_NAME: Clinical Management in General Care Settings Study Section[CMGC]


ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: ZIP8 is a poorly understood transmembrane metal importer of iron, zinc, and manganese that appears to be important in multiple organ systems, including the lung, spleen, and placenta. We propose to study the functions of ZIP8 during bacterial and fungal lung infection, red blood cell recycling and iron processing by the spleen, and delivery of essential micronutrients to the developing fetus. Our findings will inform the clinical management of important public health issues, including infectious pneumonias, blood disorders, and pregnancy.

PI_NAMEs: KIM, AIRIE  (contact)

PROGRAM_OFFICER_NAME: ESPINOZA GRANDON, INGRID CECILIA

PROJECT_TERMS: Ablation;Acceleration;Alveolar;alveolar epithelium;Anemia;antioxidant enzyme;Attenuated;Biological Process;Blood;Body System;career;Cell membrane;Cell Physiology;Cells;Circulation;Clinical;clinical development;Clinical Management;Cytosol;Data;defined contribution;Diagnosis;differential expression;Disease;divalent metal;Embryo;Embryo Transfer;Embryonic Development;enzyme mechanism;Epithelium;Erythrocytes;Erythrophagocytosis;Erythropoiesis;fetal;Fetal Development;Future;genome wide association study;Gram-Negative Bacterial Infections;Health;Hematological Disease;Hematopoietic;Hemoglobinopathies;Hemolysis;Hemorrhage;Homeostasis;Human;Immune response;Immunity;In Vitro;in vitro Model;Infection;Inflammation;Inflammatory;Innate Immune Response;Iron;iron deficiency;Iron Overload;Knock-out;Knockout Mice;Lipopolysaccharides;Location;Lung;Lung infections;lung injury;Macrophage;Manganese;Mediating;Membrane;Metals;Micronutrients;mouse model;Mus;Mutation;novel;novel therapeutics;Nutrient;Nutritional Immunity;Nutritional Requirements;Other Genetics;Outcome;oxidative damage;pathogenic microbe;Pathologic;Pathologic Processes;Pathology;Patients;Phenotype;Physiological;Physiological Processes;Placenta;Pneumonia;Pregnancy;Proteins;Public Health;Pulmonary Inflammation;Radioactive;Radioactive metal;Recovery;Recycling;Regulation;Research;Research Personnel;Role;Serum;SOD2 gene;Spleen;Splenic Red Pulp;Stimulus;Stress;Syncytiotrophoblast;System;Tissues;tool;Trace metal;Tracer;transcription factor;trophoblast;Zinc;Zinc deficiency

PROJECT_TITLE: ZIP8: A Metal Transporter with Pathophysiologic Roles in the Lung, Spleen, and Placenta


ORG_CITY: IOWA CITY

ORG_DEPT: DERMATOLOGY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: PROJECT NARRATIVE Alopecia areata is an autoimmune disease with no FDA-approved treatments that carries a lifetime risk of approximately 2%. The goal of our research is to determine the mechanisms by which exogenous IL-27 prevents autoimmune attack of the hair follicle.

PI_NAMEs: JABBARI, ALI  (contact)

PROGRAM_OFFICER_NAME: UNDALE, ANITA H

PROJECT_TERMS: 20 year old;Ablation;Address;adenovirus mediated delivery;Adopted;Adoptive Transfer;Affect;Alopecia Areata;Anti-Inflammatory Agents;Antigen-Presenting Cells;Antiinflammatory Effect;Autoimmune;Autoimmune Diseases;autoimmune pathogenesis;Autoimmune Responses;Autoimmunity;Automobile Driving;autoreactive T cell;Blocking Antibodies;Bone Marrow;CD8-Positive T-Lymphocytes;CD8B1 gene;cell type;Cells;Cellular biology;Clinical;cytokine;Data;Dependovirus;Development;Disease;draining lymph node;effector T cell;Endothelial Cells;Epithelial Cells;Epithelium;Equilibrium;Familiarity;FDA approved;Gene Expression;Genetic;Goals;Hair;Hair follicle structure;Immune;Immune response;Immune system;Immune Targeting;immunoregulation;improved;in vivo;Infiltration;Inflammatory;Interleukin-10;interleukin-10 receptor;Knowledge;lifetime risk;Ligands;Ligation;Maintenance;Mediating;Medical;MHC Class I Genes;MHC Class II Genes;Modeling;Molecular;mortality;mouse model;Mus;new therapeutic target;novel strategies;novel therapeutic intervention;Organ;Outcome;overexpression;Participant;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;Phenotype;Population;preservation;prevent;Production;Proliferating;Property;psychosocial;Quality of life;receptor;Regulatory T-Lymphocyte;Research;restraint;Role;self esteem;side effect;Signal Pathway;Signal Transduction;Site;Skin;T cell differentiation;T cell response;T-Lymphocyte;Therapeutic Agents;Therapeutic Uses;Tissues;tool;transcriptomic profiling;tumor;United States;Up-Regulation;Work

PROJECT_TITLE: IL-27 and downstream mechanisms in Alopecia Areata

STUDY_SECTION: ACTS

STUDY_SECTION_NAME: Arthritis, Connective Tissue and Skin Study Section[ACTS]


ADMINISTERING_IC: MH

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: STONY BROOK

ORG_DEPT: NEUROSCIENCES

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: PROJECT NARRATIVE SAPAP3-deletion mouse models recapitulate the prevalent and debilitating neuropsychiatric condition, Obsessive Compulsive Disorder (OCD), by evidence of their shared striatal dysfunction, behavioral validity (anxiety and compulsive grooming), as well as treatment validity (serotonin reuptake inhibitor). Within the SAPAP3-lacking striatum, we home in on a newly characterized dysregulation of the crucial striatal neuromodulator, Acetylcholine (ACh), and the cholinergic interneurons (ChIs) which release ACh, as we test the functional determinants of ChI dysregulated output and the ability of ChI directed treatment to modify OCD- like behavior.

PI_NAMEs: BAEZ, ALEXANDER THEODOR (contact)

PROGRAM_OFFICER_NAME: PINARD, COURTNEY ROSE

PROJECT_TERMS: Acetylcholine;Acute;Age;Anxiety;Basal Ganglia;Behavior;Behavioral;behavioral phenotyping;Brain;Brain region;Cells;cholinergic;Cholinergic Receptors;Chronic;Compulsive Behavior;Corpus striatum structure;Data;density;Diagnosis;Disabling;Disease;Dopamine;Dorsal;early onset;Electrophysiology (science);Excitatory Synapse;Face;Functional disorder;Gene Expression;genome wide association study;Glutamate Receptor;Goals;Grooming;Home;Human;Immunohistochemistry;Interneuron function;Interneurons;Intrinsic drive;Investigation;Knock-in;Knockout Mice;Laser Scanning Microscopy;Link;Measures;Mediating;Membrane;men;Mental disorders;Modeling;Motor;motor behavior;mouse model;Movement;Mus;Mutation;N-Methyl-D-Aspartate Receptors;Neurodevelopmental Disorder;neuroimaging;Neuromodulator;neuronal cell body;Neurons;neuropsychiatric disorder;neuropsychiatry;neurotransmitter release;Neurotransmitters;Obsessive-Compulsive Disorder;optogenetics;Output;patch clamp;Pathologic;Pathology;Pattern;Phase;Phenotype;Physiological;Physiology;Population;postnatal;postsynaptic;postsynaptic density protein;Prediction of Response to Therapy;Prevalence;Process;Property;Proteins;response;Role;scaffold;Scaffolding Protein;Selective Serotonin Reuptake Inhibitor;sensor;Sensory;Shapes;Signal Transduction;Site;Slice;Source;Specificity;Substantia nigra structure;Synapses;targeted treatment;Testing;Thalamic structure;Transferase;Trichotillomania;two photon microscopy;two-photon;United States;Viral;Woman

PROJECT_TITLE: Functional study of the role of SAPAP3 postsynaptic density protein on dorsolateral striatal cholinergic interneurons


NIH_SPENDING_CATS: Behavioral and Social Science;Bioengineering;Cardiovascular;Clinical Research;Heart Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: PROJECT NARRATIVE In this study, we seek to develop a system that will learn from expert perfusionists in the cardiac operating room and will be integrated into the surgical workflow as an artificial intelligence (AI) teammate. This clinical decision support system will support perfusionists during critical decision-making and will be used to standardize gold standard patient care, mitigating errors and preventing patient harm.

PI_NAMEs: DIAS, ROGER DAGLIUS  (contact);GOMBOLAY, MATTHEW

PROGRAM_OFFICER_NAME: HSU, LI-YUEH

PROJECT_TERMS: Adopted;Adult;Adverse event;Algorithms;Anesthesia procedures;apprenticeship;Artificial Intelligence;Awareness;Belief;biomarker performance;Cardiac;Cardiac Surgery procedures;Cardiopulmonary Bypass;Childhood;Clinical;Clinical Decision Support Systems;clinical practice;Cognition;Cognitive;cognitive load;Communication;Complex;computational intelligence;Computers;Cues;Data;Decision Making;Decision Support Systems;Dedications;design;Deterioration;Digital biomarker;Discipline of Nursing;distraction;Electrocardiogram;Electroencephalography;Engineering;Environment;experience;Expert Systems;Fatigue;Future;Goals;Health Personnel;Heterogeneity;Hospitals;Hour;Human;human error;human-in-the-loop;Impairment;improved;Incidence;interoperability;Interruption;Intuition;Knowledge;knowledge base;Laboratories;Learning;Libraries;Literature;Measures;Medical;Medical Errors;medical schools;Modeling;non-verbal;novel;Nurses;open source;Operating Rooms;operation;Operative Surgical Procedures;Outcome;Patient Care;patient safety;Patients;Performance;Perfusion;Phase;Physiological;Policies;prevent;Probability;Procedures;Process;Protocols documentation;Provider;Reporting;Rewards;Risk;Robot;robot assistance;Robotics;Safety;Serious Adverse Event;simulation;skills;Standardization;standardized care;Stress;System;Techniques;Technology;Time;Training;Trust;Uncertainty;usability;Variant;Ventilator;verbal;virtual surgery;visual tracking;willingness;Work;Workload

PROJECT_TITLE: A ROBOT-ASSISTED PERFUSION SYSTEM TO IMPROVE PATIENT SAFETY IN THE CARDIAC OPERATING ROOM


FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

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

ORG_CITY: NEW YORK

ORG_NAME: CITY COLLEGE OF NEW YORK

PHR: Project Narrative Racial/ethnic minority (REM) researchers, who may be uniquely poised to address racial/ethnic disparities in mental and physical health, are underrepresented at all levels of the biomedical and behavioral sciences. Our Manhattan-Bridge program seeks to enhance the number of REM students in biomedical and behavioral sciences research by bridging the path from a minority-serving community college (Borough of Manhattan Community College) to a baccalaureate degree in a STEM field at a minority-serving senior college (The City College of New York). Manhattan-Bridge includes a coordinated system of faculty mentoring, peer mentoring, peer support, diversity training, STEM coursework, laboratory training, tutoring, and supplemental instruction to address and overcome the obstacles known to impede REM students from success in completing their baccalaureate degrees and launching careers in biomedical fields.

PI_NAMEs: GIZA, JOANNA ;MELARA, ROBERT  (contact);RUGLASS, LESIA MONIQUE

PROGRAM_OFFICER_NAME: STEPANEK, LAURIE ELIZABETH

PROJECT_TERMS: Academic advising;Address;Award;Bachelor's Degree;Behavioral Sciences;bridge program;bridge to the baccalaureate;career;Cities;Clinical Research;cohort;college;community college;Coping Skills;Data Analyses;Development;Educational Curriculum;Emotional;ethnic disparity;ethnic minority;experience;faculty mentor;Fellowship;Funding;journal article;laboratory experience;meetings;Mental Health;Mentors;Minority;minority investigator;minority student;Neurocognitive;New York;Outcome;Paper;peer;peer coaching;peer support;physical conditioning;posters;programs;psychologic;racial disparity;racial minority;Research;Research Methodology;Research Project Grants;Research Training;Self Efficacy;skills;Social Development;STEM field;Stress;Students;success;summer research;supplemental instruction;symposium;System;Training;Training and Education;Training Programs;transfer student;Travel;tutoring

PROJECT_TITLE: Bridges to the Baccalaureate Research Training Program (T34) for racial/ethnic minorities at the Borough of Manhattan Community College (BMCC) and the City College of New York (CCNY)

STUDY_SECTION: TWD

STUDY_SECTION_NAME: Training and Workforce Development Study Section - D[TWD-D]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Health Services;Rehabilitation;Social Determinants of Health

ORG_CITY: PORTLAND

ORG_NAME: PORTLAND VA RESEARCH FOUNDATION, INC.

ORG_STATE: OR

PHR: The purpose of this grant is to supplement the funding of three conferences (“Vestibular Disorders: From Cause to Cure”, “Post-pandemic Innovations in Connected Audiology”, and “Multi-Sensory Approaches to Auditory Rehabilitation”) to be hosted by the National Center for Rehabilitative Auditory Research between 2021 and 2025. The aim of these conferences is to improve auditory research and clinical practice by sharing the knowledge and perspectives of patients, clinicians, scientists and health policy stakeholders to alleviate the burden of auditory and vestibular deficits on function and quality of life. This conference is unique in its multidisciplinary, multiple stake holder approach to providing specialized training in clinical innovations, identification of the critical gaps in research, and appreciation of the health system barriers to advances in the field.

PI_NAMEs: KONRAD-MARTIN, DAWN L (contact)

PROGRAM_OFFICER_NAME: KING, KELLY ANNE

PROJECT_TERMS: Address;Affect;age group;Aging;Ally;American;Artificial Intelligence;Audiology;Auditory;auditory rehabilitation;Award;Basic Science;Bilateral;Caring;Case Study;cell regeneration;Clinical;clinical care;clinical decision-making;Clinical Management;clinical practice;Clinical Research;Collaborations;Communication;Communication Barriers;Communities;Compensation;Craniocerebral Trauma;Data;Development;Diagnosis;Diagnostic;Diagnostic tests;disability;Educational process of instructing;Electronic Mail;Environment;equilibration disorder;Equilibrium;ethnic minority population;Ethnic Origin;Evaluation;Event;evidence base;fall risk;falls;Feedback;Female;Functional disorder;Funding;Grant;Health;health care availability;Health Policy;Health system;Healthcare;Hearing;hearing impairment;Hearing problem;Impaired cognition;implantation;implementation strategy;improved;Individual;innovation;interdisciplinary approach;Journals;Knowledge;Laboratories;Learning;Lesion;Manuscripts;Medical Care Costs;medical specialties;meetings;member;Mental Depression;Mentors;Migraine;Modeling;multidisciplinary;multisensory;National Institute on Deafness and Other Communication Disorders;novel;Occupational;Oral;Outcome;Participant;Patient Care;Patient-Centered Care;Patient-Focused Outcomes;Patients;people of color;Physicians;Policy Maker;Population;Positioning Attribute;post-pandemic;posters;Prevention;Preventive measure;Price;Problem-Based Learning;Process;Professional Organizations;Psychometrics;Psychophysics;Publishing;Quality of life;Race;racial minority population;Recommendation;Recreation;Rehabilitation Centers;Rehabilitation therapy;Research;research and development;Research Personnel;Schedule;Scholarship;Science;Scientist;Series;Service delivery model;Shapes;Site;social;social media;Societies;socioeconomics;Strategic Planning;student mentoring;Students;symposium;Symptoms;Techniques;Technology;Testing;Therapeutic Intervention;Time;Training;translational scientist;Underrepresented Populations;Vestibular Diseases;Vestibular dysfunction;Vestibular function;Vestibular loss;Vestibular Neuronitis;vestibular system;Videotape;virtual reality;web site;Woman

PROJECT_TITLE: The Biennial VA NCRAR Scientific Conference Series

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


ORG_CITY: HOUSTON

ORG_DEPT: GENETICS

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: Overall project narrative: Repeating sequences of nucleotides in the Fragile X gene variably cause as set of human diseases (Fragile X Syndrome, Fragile X associated Tremor Ataxia Syndrome, and Fragile X primary ovarian insufficiency) for which we have no effective treatments. Our expert group will investigate the mechanisms by which this repeat causes disease in the broader context of its normal genomic functions while also identifying genes that modify the expressivity of Fragile X associated disorders. By using an integrative approach to understand how repeats work normally and how they elicit dysfunction, we hope to achieve a breakthrough in therapy development for Fragile X.

PI_NAMEs: NELSON, DAVID LOREN (contact);TODD, PETER K

PROJECT_TERMS: 5' Untranslated Regions;Age;Antisense Oligonucleotide Therapy;Antisense Oligonucleotides;Area;Base Sequence;Bioinformatics;Biological Models;CGG repeat;CGG repeat expansion;Clinical;Collection;Coupled;Data;Development;Disease;DNA;effective therapy;Epigenetic Process;Family;FMR1 gene;Fragile X Gene;Fragile X Premutation;Fragile X Syndrome;Functional disorder;FXTAS;gain of function;Gene Modified;Genetic;Genetic Transcription;genome wide screen;Genomics;Haplotypes;Human;human disease;Impairment;improved;Individual;insight;Mammals;Mediating;Modeling;multidisciplinary;Mutation;Nervous System Disorder;Neurodevelopmental Disorder;Neurons;novel;Onset of illness;Ovarian;Pathogenicity;Pathology;Patients;Penetrance;Pharmacologic Substance;primary ovarian insufficiency;Process;Production;Proteins;Reproductive Biology;reproductive system disorder;Research;Research Personnel;Resources;risk prediction;risk variant;RNA;Role;Running;Series;Severities;Site;Structure;Symptoms;targeted treatment;therapeutic development;therapeutic target;therapy development;tool;Toxic effect;Translations;Tremor/Ataxia Syndrome;Variant;Work

PROJECT_TITLE: Fragile X Premutations, Mechanisms and Modifiers


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Clinical Research;Dementia;Neurodegenerative;Neurosciences;Prevention

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: NARRATIVE The locus coeruleus is one of the first sites of abnormal forms of Alzheimer's disease-related tau proteins in the brain, and from there it is assumed to spread through brain connections, altering its ability to coordinate large- scale networks. The proposed study aims to characterize the patterns and genetic features underlying locus coeruleus-related functional networks that facilitate tau spreading and cognitive decline as well as those that provide resiliency in the face of pathology. This project has important public health implications and is relevant to part of the NIH's mission as it will provide insights into the selective vulnerability of the locus coeruleus in Alzheimer's disease and can provide new targets for treatment early in the disease trajectory.

PI_NAMEs: JACOBS, HEIDI IRMA (contact);SEPULCRE, JORGE

PROGRAM_OFFICER_NAME: GRAY, ERIN EMILY

PROJECT_TERMS: Address;Adult;Affect;Age;aging brain;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease risk;Alzheimer’s disease biomarker;Amyloid;Anatomy;apolipoprotein E-4;Atlases;Attention;Autopsy;autosomal dominant Alzheimer's disease;Biological;Biological Markers;Brain;Brain Injuries;Brain region;Brain Stem;Cells;Cognition;Cognitive;cognitive performance;cohort;Communication;Data;Data Set;Dedications;Deposition;Detection;Disease;Disease Marker;Disease Progression;Dorsal;Early Diagnosis;Early treatment;Electronic Medical Records and Genomics Network;Electrophysiology (science);Enrollment;entorhinal cortex;Female;Frequencies;Functional Magnetic Resonance Imaging;Funding;Gene Expression Profile;Genetic;Goals;Head;healthy aging;Human;hyperphosphorylated tau;Impaired cognition;improved;in vivo;Individual;innovation;insight;Learning;Life;life span;locus ceruleus structure;longitudinal dataset;Magnetic Resonance Imaging;Maintenance;Maps;Measures;Medial;medial temporal lobe;Memory;Methods;mild cognitive impairment;Mission;multimodality;multisensory;network architecture;Neural Pathways;Neurofibrillary Tangles;Neurons;novel;Older Population;pathological aging;Pathology;Pathway interactions;Patients;Pattern;Performance;Persons;Plasma;Positron-Emission Tomography;pre-clinical;Predisposition;Prevention trial;Primary Prevention;prodromal Alzheimer's disease;Public Health;Reporting;Research;resilience;Rest;Risk;Role;segregation;sex;Site;Structure;targeted treatment;tau aggregation;tau Proteins;tau-1;Time;trait;transcriptome;ultra high resolution;United States National Institutes of Health;Work;young adult

PROJECT_TITLE: Locus coeruleus network architecture of Alzheimer's disease vulnerability


NIH_SPENDING_CATS: Brain Disorders;Fragile X Syndrome;Intellectual and Developmental Disabilities (IDD);Neurosciences;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

PI_NAMEs: NELSON, DAVID LOREN (contact)

PROJECT_TERMS: Address;Basic Science;Beavers;CGG repeat;college;Committee Members;Communication;Communities;Development;Discipline of obstetrics;Disease;Ensure;FMR1 Premutation;FMR1 repeat;Fostering;Fragile X Premutation;Fragile X Syndrome;Functional disorder;FXTAS;General Population;Generations;Genetic;Goals;Hares;Institution;interest;Journals;Leadership;Literature;medical schools;Medicine;meetings;member;Michigan;Molecular;Mutation;Neurology;Neurosciences;novel;novel therapeutics;operation;Participant;Pediatrics;pre-clinical;primary ovarian insufficiency;Publishing;Recording of previous events;Research;Research Activity;Research Personnel;Resource Allocation;Resources;Role;Schedule;Scientist;Structure;success;symposium;Talents;Therapeutic;Training;Training and Education;United States National Institutes of Health;Universities;videoconference;Work

PROJECT_TITLE: Administrative Core


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Fragile X Syndrome;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

PI_NAMEs: TODD, PETER K (contact)

PROJECT_TERMS: 5' Untranslated Regions;age related neurodegeneration;Antisense Oligonucleotide Therapy;Antisense Oligonucleotides;autism spectrum disorder;Biological Assay;Biological Models;Cell Line;CGG repeat;CGG repeat expansion;CRISPR/Cas technology;cryptic protein;Data;Dendrites;Disease;Elements;FMR1 gene;FMR1 repeat;Fragile X Premutation;Fragile X Syndrome;FXTAS;Gene Expression Regulation;Genetic Transcription;genome-wide;Goals;Human;human disease;human embryonic stem cell;Human Genome;Impairment;improved;Inherited;Initiator Codon;innovation;Intellectual functioning disability;Knock-in Mouse;Learning;Long-Term Depression;Memory;Metabotropic Glutamate Receptors;Microsatellite Repeats;Modeling;mouse model;Mus;Nerve Degeneration;Nervous System Disorder;Neurobiology;Neuronal Plasticity;Neurons;novel strategies;novel therapeutics;Open Reading Frames;Pathogenesis;Pathway interactions;patient derived induced pluripotent stem cells;Patients;Phenotype;Phosphorylation;Physiologic pulse;Play;prevent;Process;Protein Biosynthesis;Proteins;Receptor Activation;Regulation;Repetitive Sequence;Reporter;response;Role;Series;Short Tandem Repeat;Site;Small Interfering RNA;synaptic function;Synaptic plasticity;System;Testing;therapeutic development;therapeutic target;tool;Translational Repression;Translations

PROJECT_TITLE: The FMR1 CGG repeat as functional element and therapeutic target in Fragile X associated disorders


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Fragile X Syndrome;Genetics;Intellectual and Developmental Disabilities (IDD);Neurodegenerative;Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

PROJECT_TERMS: Adult;Affect;Age;age effect;Age of Onset;age related;Alleles;Animal Model;Architecture;Behavioral;Biological Assay;Biological Models;Brain;Candidate Disease Gene;Cell model;Cell Physiology;Cerebellum;CGG repeat;Collection;college;Data;Disease;Dropout;Exhibits;fly;FMR1 gene;Fragile X Premutation;Fragile X Syndrome;FXTAS;gain of function;Gait Ataxia;Genes;Genetic;Genetic Polymorphism;Genetic Screening;genetic variant;Genome;Haplotypes;hnRNP A2;Human Genetics;human model;Impaired cognition;improved;Individual;Intention Tremor;Knockout Mice;Length;Link;male;Mammalian Cell;Mammals;Mediating;Medicine;Messenger RNA;Michigan;model organism;Modeling;Molecular;mouse model;Mus;mutant;Mutation;mutation carrier;Nervous System Disorder;Neurodegenerative Disorders;Neurons;neuropathology;Nuclear Inclusion;Parkinsonian Disorders;Pathogenesis;Pathogenicity;Patients;Penetrance;primary ovarian insufficiency;Production;protein expression;protein TDP-43;PURA gene;Reporter;RNA;RNA interference screen;RNA-Binding Proteins;RNASE3L gene;Role;Sequence Analysis;Symptoms;System;Targeted Resequencing;therapeutic candidate;therapeutic target;Toxic effect;Transgenic Organisms;Translations;Triplet Multiple Birth;Ubiquitin;Variant;whole genome;Woman;Work

PROJECT_TITLE: FXTAS: Mechanisms and Modifiers


NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Contraception/Reproduction;Fragile X Syndrome;Genetics;Human Genome;Infertility;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Osteoporosis;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Women's Health Research

PI_NAMEs: ALLEN, EMILY GRAVES (contact)

PROJECT_TERMS: 5' Untranslated Regions;Acceleration;Address;Age;Alleles;Animal Model;autism spectrum disorder;Binding Proteins;Biological;Body System;Bone Density;Candidate Disease Gene;candidate identification;cell type;Cells;CGG repeat;Child;Cholesterol;Clinical;clinically significant;cohort;combinatorial;Coronary heart disease;Data;Data Set;Defect;Development;Diagnosis;Disease;DNA;DNA Resequencing;early onset;effective intervention;Emotional Stress;Endothelium;Estrogen deficiency;Etiology;experience;Family;family building;Fertility;Fracture;Fragile X Premutation;Fragile X Syndrome;FXTAS;Genes;Genetic;genetic architecture;Genetic Carriers;genome sequencing;Genotype;Goals;granulosa cell;Health;Human;human model;Impairment;improved;induced pluripotent stem cell;innovation;insight;Intellectual functioning disability;Knowledge;Length;life span;Link;Medical History;Menstruation;Messenger RNA;Modeling;Molecular;mortality;mouse model;multidisciplinary;Mus;Mutation;novel;offspring;Oocytes;Osteoporosis;Outcome;Ovarian;ovarian dysfunction;Ovary;Pathogenicity;Pathway interactions;Penetrance;Phenotype;phenotypic data;polyglycine;polypeptide;Population;primary ovarian insufficiency;Records;reproductive;Reproductive History;Research Personnel;Resources;Risk;Risk Factors;RNA;Role;Series;Severities;single-cell RNA sequencing;steroid hormone;subfertility;SUMO1 gene;synergism;Targeted Resequencing;Testing;therapeutic target;Time;Tissue-Specific Gene Expression;tool;Toxic effect;Transcript;Translating;Translations;transmission process;whole genome;Woman;Work

PROJECT_TITLE: FXPOI: Mechanisms and Modifiers


ED_INST_TYPE: SCHOOLS OF PHARMACY

ORG_CITY: PHILADELPHIA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

PHR: PROJECT NARRATIVE Plasminogen activators are the only approved pharmacologic intervention for acute, life-threatening, thrombotic events, despite unfavorable pharmacokinetics resulting in a poor benefit/risk ratio. In order to solve this longstanding issue, this proposal will apply a novel, physiologically attractive strategy to prolong the circulation of plasminogen activators, namely coupling to albumin-binding ligands to co-opt the endosomal salvage pathway mediated by the neonatal Fc receptor. By delineating mechanisms underlying half-life extension, this research ultimately seeks to not only improve treatment strategies in acute thrombosis, but also guide rational development of pharmacokinetically-optimized protein therapeutics across a range of diseases.

PI_NAMEs: GLASSMAN, PATRICK MCKENNA (contact)

PROJECT_TERMS: Acute;Adverse effects;Affect;Affinity;Albumins;antibody engineering;Area;Binding;Biodistribution;Biological Response Modifier Therapy;biological systems;Biomedical Research;Blood Cells;Blood Circulation;blood fractionation;Catabolism;Charge;chemical conjugate;Circulation;Clinical;Coagulation Process;cost;Coupling;Cytolysis;Data;design;Development;Diffusion;Disease;Dose;Drug Delivery Systems;Drug Kinetics;Drug usage;Endosomes;Engineering;Erythrocytes;Event;Eye;Faculty;Fc Receptor;Filtration;Functional disorder;Genetic;Grant;Half-Life;Hemorrhage;Hemostatic Agents;Hemostatic function;Immunoglobulin G;improved;in silico;in vivo;Individual;Infusion procedures;inhibitor;Injections;insight;Intervention;Ischemic Stroke;Kidney;Kinetics;Knockout Mice;Knowledge;Label;Libraries;Life;Life Extension;Ligand Binding;Ligands;mathematical model;Mediating;member;Mentors;Modeling;Molecular Conformation;mouse model;Mus;mutant;Mutation;Myocardial Infarction;nanobodies;Nature;neonatal Fc receptor;novel;Pathologic;Pathway interactions;Patient Compliance;Patient-Focused Outcomes;Penetration;Pennsylvania;Pharmaceutical Preparations;Pharmacodynamics;pharmacologic;Pharmacological Treatment;Physiological;Plasma;Plasma Proteins;Plasminogen Activator;Polymers;predictive modeling;Property;prophylactic;Protein Engineering;Proteins;Pulmonary Embolism;receptor;Recycling;Research;Resources;Risk;risk/benefit ratio;Role;Safety;Serum Proteins;side effect;Structure;Testing;Therapeutic;therapeutic protein;Therapeutic Uses;Thrombin;thrombolysis;Thrombolytic Therapy;Thrombosis;thrombotic;Thrombus;Time;Tissues;Transcend;treatment strategy;Universities;uptake;Urokinase

PROJECT_TITLE: FcRn-enabling strategies for improved thrombolytic therapy

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS