ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Complementary and Integrative Health;Depression;Major Depressive Disorder;Mental Health;Mental Illness;Neurosciences;Serious Mental Illness

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF UTAH

PHR: Major depressive disorder (MDD), comorbid anxiety and cognitive dysfunction are linked to deficits in brain en- ergetic function. In an animal model of treatment-resistant depression, we will examine 3 bioenergetic com- pounds, creatine, cyclocreatine and acetyl-L-carnitine for their potential therapeutic use for depression, anxiety and cognitive dysfunction. Since bioenergetic deficits can cause inflammation and oxidative stress to promote onset of MDD, we will study the impact of these bioenergetic compounds on inflammation and oxidative stress, and then identify signaling pathways which may be involved.

PI_NAMEs: KANEKAR, SHAMI  (contact)

PROGRAM_OFFICER_NAME: STILL, PATRICK COLBY

PROJECT_TERMS: Adult;adult neurogenesis;Affect;Altitude;analog;Animal Model;Anti-Anxiety Agents;anti-depressive agents;Antioxidants;Anxiety;anxiety symptoms;arm;Behavioral;Behavioral Symptoms;Bioenergetics;Biological Markers;Biological Response Modifiers;Brain;Brain-Derived Neurotrophic Factor;Chronic;Cognitive deficits;cognitive function;comorbidity;Creatine;cytokine;Data;depression model;depressive symptoms;design;dietary supplements;disease model;Encephalitis;Estrous Cycle;Etiology;Evaluation;Exhibits;Female;FRAP1 gene;functional disability;Genetic;Goals;Guidelines;HIF1A gene;Hippocampus;Housing;Hypoxia;IL6 gene;Impaired cognition;improved;Inflammation;Inflammatory;inflammatory marker;inhibitor;innovation;Interleukin-1 beta;Levocarnitine Acetyl;Life Experience;Life Stress;Link;Major Depressive Disorder;Marble;Mediating;Mental Depression;Methods;Modeling;Molecular;monoamine;National Center for Complementary and Integrative Health;Neurobehavioral Manifestations;neurogenesis;NF-kappa B;novel marker;novel therapeutic intervention;novel therapeutics;Oxidative Stress;Pathway interactions;Patients;Persons;Pharmaceutical Preparations;PIK3CG gene;Pilot Projects;preference;Prosencephalon;protective factors;Radial;Rattus;Reactive Oxygen Species;reduce symptoms;Resistance;response;restraint stress;Rodent Model;Sea;Selective Serotonin Reuptake Inhibitor;sex;Sex Differences;Signal Pathway;Staging;Sucrose;Swimming;System;systemic inflammatory response;Testing;Therapeutic;therapeutic biomarker;Therapeutic Uses;TNF gene;transcription factor;treatment-resistant depression

PROJECT_TITLE: Evaluation of Bioenergetic Supplements in Treatment-Resistant Depression, Cognitive Dysfunction and Anxiety

STUDY_SECTION: BNRS

STUDY_SECTION_NAME: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS]


ADMINISTERING_IC: HD

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

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

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Contraception/Reproduction;Maternal Health;Prevention;Women's Health Research

ORG_CITY: SAN FRANCISCO

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OBSTETRICS & GYNECOLOGY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: PROJECT NARRATIVE Following the U.S. Supreme Court’s decision to overturn Roe v Wade, 14 states have banned abortion, and the consequences of this dramatic shift in legal abortion access are unknown. This study will apply a rigorous quasi- experimental design to examine the long-term health and economic consequences for people who obtained abortions despite or before imposition of a state ban and those for whom abortion is legally restricted. The study will document how people’s lives are affected by unwanted pregnancies in this new legal landscape, and the findings will be able to inform state policy decisions regarding abortion bans and the development of harm- reduction strategies for pregnant people living in states where legal abortion is no longer available.

PI_NAMEs: BERGLAS, NANCY ;FOSTER, DIANA GREENE (contact)

PROGRAM_OFFICER_NAME: POPKIN, RONNA

PROJECT_TERMS: abortion;Affect;Age;Automobile Driving;California;care seeking;Clinic;cohort;cost;court;Data;Data Analyses;Development;economic outcome;Economics;Effectiveness;effectiveness evaluation;evidence base;experience;Financial Hardship;follow-up;Funding;Harm Reduction;Health;health organization;Individual;innovation;Interview;Legal;Legal Abortion;Logistics;Long-Term Effects;Longitudinal Studies;Longitudinal Surveys;Longitudinal, observational study;Medical;Methods;Minor;Modeling;Motivation;multidisciplinary;nonbinary;Online Systems;Outcome;Participant;participant enrollment;Personal Satisfaction;Persons;Pharmaceutical Preparations;pill;Policies;poor health outcome;Population;Positioning Attribute;Pregnancy;Pregnancy Complications;Pregnancy Outcome;pregnant;Privatization;Quasi-experiment;recruit;Reporting;reproductive;Reproductive Health;Research;Research Design;Resources;response;San Francisco;Scientist;Self Administration;Self Management;Services;Source;success;Supreme Court Decisions;Surveys;System;Time;transgender men;Travel;Universities;Unwanted pregnancy;Vulnerable Populations;Woman;Women's cohort;Women's Health

PROJECT_TITLE: Health and economic consequences of changing federal and state policies on reproductive health.

STUDY_SECTION: SSPB

STUDY_SECTION_NAME: Social Sciences and Population Studies B Study Section[SSPB]


ADMINISTERING_IC: CA

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: RICHARDSON

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF TEXAS DALLAS

ORG_STATE: TX

PHR: Project Narrative  Solitary fibrous tumors (SFTs), historically sometimes called hemangiopericytomas (HPCs), are nonhereditary cancers which is a result of an environmental intrachromosomal gene fusion between NAB2 and STAT6 on chromosome 12. We propose to systematically evaluate the in vitro and in vivo efficacy and specificity of BET inhibitors against SFTs, and explore the underlying molecular mechanisms related to NAB2- STAT6 fusions.

PI_NAMEs: BLERIS, LEONIDAS  (contact);HAYENGA, HEATHER NAOMI;MARTIN-BROTO, JAVIER

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Adult;Adverse effects;Anatomy;Angiogenesis Inhibitors;Animal Model;antitumor effect;Area;Binding;Biological Assay;Biological Markers;Biomedical Engineering;Blood Vessels;bone;Bromodomain;Bromodomains and extra-terminal domain inhibitor;Cancer Biology;Cancer Center;Cell model;Central Nervous System;Characteristics;chemotherapy;Chemotherapy-Oncologic Procedure;Chimeric Proteins;Chromosome 12;Clinical;Clinical Research;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Data;Disease remission;DNA biosynthesis;DNA Damage;DNA Double Strand Break;DNA Repair;DNA Repair Pathway;Dose;Family member;Gamma-H2AX;Gene Fusion;Genes;Genetic;genome editing;Goals;Growth;Head;hemangiopericytoma;high throughput screening;high-throughput drug screening;Histopathology;In complete remission;In Vitro;in vivo;in vivo evaluation;Infant;inhibitor;Investigation;Investigational Drugs;Liver;Location;Lung;Malignant - descriptor;Malignant Neoplasms;malignant phenotype;Malignant Solitary Fibrous Tumor;Medical Oncologist;Meninges;Mesenchymal Cell Neoplasm;Modeling;Molecular;Neoplasm Metastasis;neoplastic cell;novel therapeutics;Oncologist;Operative Surgical Procedures;partial response;Pathologic;Pathologist;Pathway interactions;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phase;Phenotype;Poly(ADP-ribose) Polymerase Inhibitor;prevent;Prognosis;Proliferating;Radiation;Recurrence;repaired;Repression;Research;Research Personnel;Resected;response;Safety;Sarcoma;Secure;Soft tissue sarcoma;Solitary Fibrous Tumor;Spain;Specificity;Stable Disease;STAT6 gene;success;Systemic Therapy;targeted treatment;Testing;Tissue Sample;Travel;tumor;Tumor Cell Line;tumorigenesis;Tyrosine Kinase Inhibitor;Variant

PROJECT_TITLE: Bromodomain and extra-terminal motif (BET) inhibitors in Solitary fibrous tumor (SFT)

STUDY_SECTION: ATA

STUDY_SECTION_NAME:
Advancing Therapeutics A Study Section
[ATA]


ADMINISTERING_IC: MH

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_CITY: Boulder

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: Project Narrative PUBLIC HEALTH RELEVANCE: Anxiety-related processes are characterized by social avoidance and enhanced fear. While it is known that the ventral tegmental area (VTA) participates in the regulation of such motivated behaviors, the specific cell-types and circuits that govern these behaviors are unclear. This research program will determine the involvement of specific circuits and neurotransmitters released by cell-type specific VTA neurons that regulate behavioral outcomes that follow traumatic stress, which may provide new cellular- based intervention strategies for stress-related disorders.

PI_NAMEs: BARATTA, MICHAEL V;ROOT, DAVID H (contact)

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Address;Adverse event;Affect;Anxiety;anxiety-like behavior;Aversive Stimulus;Axon;Behavior;Behavior Control;Behavioral;behavioral outcome;Brain;cell type;Data;Development;Diagnostic;Disease;Dopamine;Etiology;Event;experience;Exposure to;Fiber;Freezing;Fright;gamma-Aminobutyric Acid;Genes;Glutamates;Habenula;Human;Individual;Individual Differences;insight;Intervention;knock-down;Lateral;Life;Link;Maintenance;Mediating;Mental disorders;Molecular;Monitor;motivated behavior;Mus;Neurons;neurotransmission;neurotransmitter release;Neurotransmitters;novel;Nucleus Accumbens;Optics;optogenetics;Outcome;Output;Pathway interactions;Photometry;Post-Traumatic Stress Disorders;postsynaptic;Process;programs;public health relevance;Regulation;Research;resilience;response;RNA Interference;Rodent;Role;social;Social Development;Specificity;Stimulus;Stress;stress related disorder;Stressful Event;stressor;System;Testing;tool;traumatic stress;Tyrosine 3-Monooxygenase;Ventral Tegmental Area;ventral visual stream;vesicular GABA transporter;vesicular glutamate transporter 2;Work

PROJECT_TITLE: Circuits and neurotransmitters involved in VTA glutamate neuron regulation of the consequences of stress

STUDY_SECTION: BRLE

STUDY_SECTION_NAME: Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]


PHR: Project Narrative Traumatic life events play a critical role in the etiology of a number of psychiatric conditions; however the outcome of a traumatic event can vary widely between individuals. Thus, an understanding of what factors produce resilience to the impact of a traumatic event, as well as the neural mechanisms that mediate these factors, is of clinical importance. The proposed research is directed at these issues.

PI_NAMEs: BARATTA, MICHAEL V (contact);MAIER, STEVEN F

PROJECT_TERMS: Adverse event;Behavior Control;Behavioral;behavioral outcome;Brain Stem;Clinical;Communication;Corpus striatum structure;Data;Desire for food;dorsal raphe nucleus;Elements;Etiology;Event;experience;Exposure to;Female;Future;generalized anxiety;Goals;Grant;Habits;Human;Immunization;Individual;information processing;Label;Lead;Learning;Life;Long-Term Effects;male;Medial;Mediating;Mental Depression;neural;neurochemistry;neuromechanism;Neurons;Organism;Outcome;Pathway interactions;Pattern;Play;Post-Traumatic Stress Disorders;Prefrontal Cortex;prevent;Process;protective effect;Research;resilience;Resistance;response;Rodent;Role;sex;social;Social Dominance;Stress;stress management;stress resilience;stressor;Structure;System;Thalamic structure;traumatic event;Work

PROJECT_TITLE: Stressor controllability: Prefrontal circuits that produce resilience and dominance

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


NIH_SPENDING_CATS: Autoimmune Disease;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Immunotherapy;Machine Learning and Artificial Intelligence;Precision Medicine;Skin Cancer

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Immune checkpoint inhibitors have transformed modern cancer medicine, however the severe toxicity rate is up to ~60% in melanoma patients treated with combination immunotherapy. Unfortunately, the pathophysiology underlying these severe immune-related toxicities remains unclear, and we have no way in clinical practice to forecast who will experience them. To address these issues, we will perform multi-modal high-dimensional profiling of melanoma peripheral blood to delineate cellular determinants of immunotherapy-related toxicities and to devise an assay for predicting both immunotherapy response and toxicity from pretreatment plasma cell-free DNA using genome-wide methylation sequencing.

PI_NAMEs: CHAUDHURI, AADEL  (contact);NEWMAN, AARON M

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: Address;anti-cancer treatment;anti-CTLA-4 therapy;anti-CTLA4;anti-PD-1;Autoimmune Diseases;autoreactivity;B-Lymphocytes;Benchmarking;Biological Assay;Biological Markers;Biology;Biopsy;Blood;blood treatment;BLR1 gene;Body System;CD4 Positive T Lymphocytes;cell free DNA;Cells;Cessation of life;Clinical;clinical decision-making;clinical practice;Clonal Expansion;cohort;Combination immunotherapy;Combined Modality Therapy;Computational Biology;Data;Decision Making;Dermal;Development;DNA Methylation;DNA methylation profiling;Ecosystem;experience;Flow Cytometry;Foundations;Frequencies;Functional disorder;Future;Genes;genetic signature;genome wide methylation;high dimensionality;Hospitalization;Human;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;immune-related adverse events;Immunotherapy;immunotherapy clinical trials;improved;Incidence;innovation;insight;Insulin-Dependent Diabetes Mellitus;Knowledge;learning strategy;Life;Link;liquid biopsy;Lupus;Lymphocyte;Machine Learning;machine learning method;Malignant Neoplasms;Measures;Mediating;Medicine;Melanoma;Melanoma patient;memory CD4 T lymphocyte;minimally invasive;Modernization;Morbidity - disease rate;mortality;multimodality;Nature;new technology;Organ;organ growth;Outcome;Patients;Peripheral;peripheral blood;Peripheral Blood Mononuclear Cell;personalized medicine;Plasma;Plasma Cells;Play;predictive signature;predictive test;Probability;profiles in patients;prospective;Publishing;response;response biomarker;Rheumatoid Arthritis;Risk;risk prediction;Sampling;single-cell RNA sequencing;Site;Skin;skin lesion;Sorting;T-Lymphocyte;Technology;Testing;Tissues;Toxic effect;Validation;Visceral

PROJECT_TITLE: Determinants of toxicity and response to immune checkpoint blockade through integrative profiling of T cell clonal dynamics and plasma cell- free DNA

STUDY_SECTION: TIO

STUDY_SECTION_NAME: Translational Immuno-oncology Study Section[TIO]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Biotechnology;Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Genetics;Human Genome;Pediatric

ORG_CITY: BERKELEY

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative: PUBLIC HEALTH RELEVANCE: The proposed research will provide fundamental knowledge about how genes control craniofacial development in vertebrates. This knowledge will help develop therapeutic targets and treatments for human craniofacial diseases. Since the majority of birth defects are craniofacial and dental abnormalities, this research will lead to improved diagnosis, treatment, and prevention of human birth defects.

PI_NAMEs: MARTIN, CHRISTOPHER HERBERT (contact)

PROGRAM_OFFICER_NAME: SAIFUDEEN, ZUBAIDA

PROJECT_TERMS: 3-Dimensional;Affect;Alleles;Bahamas;Binding Sites;Biological Models;Candidate Disease Gene;candidate identification;candidate validation;Caribbean region;causal variant;Chemicals;Clinical;Congenital Abnormality;craniofacial;Craniofacial Abnormalities;craniofacial bone;craniofacial development;craniofacial disorder;craniofacial structure;craniofacial tissue;CRISPR/Cas technology;Cyprinodons;Cyprinodontidae;Dental;Development;developmental genetics;Diagnosis;Disease;egg;Embryo;Environment;Evolution;Exhibits;experimental study;Fishes;forward genetics;Gene Expression;Genes;Genetic;Genetic study;Genome;genome editing;genome wide association study;Genomic Segment;Genomics;Human;human disease;Human Genetics;Human Pathology;improved;In Situ Hybridization;insight;Investigation;Island;Jaw;Knock-out;Knowledge;Laboratory Study;life history;malformation;Maps;Measures;Methods;Mexico;Modeling;Molecular;Morphology;mutant;Mutation;Natural experiment;novel;Oral;Organism;orofacial cleft;overexpression;Pathway interactions;Pattern;Phenocopy;phenomics;Phenotype;Population;Prevention;public health relevance;Quantitative Genetics;Quantitative Trait Loci;Radiation;Reaction;reference genome;Reporter Genes;Research;RNA;Role;Scanning;Shapes;skeletal;spatiotemporal;Specialist;success;System;Testing;therapeutic target;Tissues;trait;transcription factor;transcriptome sequencing;transcriptomics;Transgenic Organisms;Validation;Variant;Vertebrates;whole genome;Zebrafish

PROJECT_TITLE: Discovery and functional analysis of novel candidate genes and variants underlying craniofacial diversification in Cyprinodon pupfishes

STUDY_SECTION: SBDD

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


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Clinical Research;Conditions Affecting the Embryonic and Fetal Periods;Congenital Structural Anomalies;Fetal Alcohol Spectrum Disorders (FASD);Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention;Social Determinants of Health;Substance Misuse

ORG_CITY: LOS ANGELES

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative The primary focus of this project is the use of non-invasive neuroimaging and 3D facial photography to identify Fetal Alcohol Spectrum Disorder (FASD)-related brain abnormalities from birth to adolescence. Fetal exposure of the brain to alcohol can trigger brain abnormalities that unfold over a lifetime with severe consequences both for the affected individual and for society at large. To date, these abnormalities have mostly been studied starting in later childhood, with very few studies following the consequences of well documented alcohol exposure as they develop in the same individual in the early years and across time into adolescence.

PI_NAMEs: DONALD, KIRSTY ;JOSHI, SHANTANU H. (contact)

PROGRAM_OFFICER_NAME: EGLI, MARK

PROJECT_TERMS: 12 year old;2 year old;3-Dimensional;6 year old;Address;Adolescence;Adolescent;adolescent mental health;Affect;Age;Aging;alcohol exposure;Alcohols;Area;Attention;Behavior;Behavioral;behavioral outcome;Biological;Biological Markers;Birth;Brain;brain abnormalities;Brain imaging;Brain Mapping;brain morphology;Central Nervous System;Child;Child Health;Childhood;Chronic stress;clinically significant;Cognition;Cognitive;cohort;Cohort Studies;Communities;Computing Methodologies;Corpus striatum structure;Corticospinal Tracts;cost;Data;Data Collection;Decision Making;Detection;Development;diagnostic strategy;digital;Dysmorphology;early adolescence;early childhood;early detection biomarkers;Early Diagnosis;Early Intervention;Enrollment;Environment;Environmental Exposure;executive function;experience;Face;Fetal alcohol effects;Fetal Alcohol Exposure;Fetal Alcohol Spectrum Disorder;Fetal Alcohol Syndrome;flexibility;Funding;General Population;Goals;gray matter;Health;high risk;Image;Impulsivity;indexing;Individual;Infant;interest;intergenerational;Intervention;Joints;Knowledge;Life;Link;Liquid substance;Location;Longitudinal cohort;Malnutrition;Measurement;Measures;Mental Health;Methodology;Methods;Modeling;Morphology;Neonatal;neonate;neural;neurobehavioral;Neurobiology;neurodevelopment;Neurodevelopmental Disorder;neuroimaging;Neurologic;neuroregulation;novel;offspring;Outcome;Pathway interactions;Pattern;Phase;Photography;Population;predictive modeling;prenatal exposure;Prevalence;Property;prospective;psychosocial;Public Health;Publishing;Reporting;Research;resilience;Resource-limited setting;Risk;Sampling;Scanning;Shapes;social;Societies;South Africa;Specificity;statistics;Structure;substance use;Substance Use Disorder;success;sugar;Surface;Testing;Thalamic structure;Time;Toddler;tool;Variant;violence exposure;white matter;white matter change;Youth

PROJECT_TITLE: Longitudinal mapping of brain-face-behavior trajectories in prenatal alcohol exposure from birth through adolescence

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

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

ORG_CITY: SAN DIEGO

ORG_NAME: SCINTILLON INSTITUTE FOR PHOTOBIOLOGY

PHR: Project Narrative We recently identified dysfunction in the cerebellum of patients with an extreme excessive eating disorder and found that cerebellar-mediated reward processing potently regulates food intake in mice. This proposal will examine how cerebellar circuits interact with midbrain dopaminergic centers to influence food seeking and consumption. Using intersectional viral tools and single cell sequencing to anatomically and molecularly define the subcortical cerebellar output pathways and deep brain imaging of neural and dopamine activity in diet-induced obese mice, we will define the cerebellar-striatal control of food intake.

PI_NAMEs: BETLEY, JOHN NICHOLAS;CHEN, ALBERT  (contact)

PROGRAM_OFFICER_NAME: COOKE, BRAD

PROJECT_TERMS: Affective;Anatomy;Animals;Anterior;Appetite Disorder;Body Weight;Brain;Brain imaging;Calcium;Cell Nucleus;cell type;Cells;Cerebellar Nuclei;Cerebellum;conditioned place preference;Consumption;Corpus striatum structure;Cues;Data;Desire for food;detection of nutrient;Development;diet-induced obesity;Dopamine;DRD2 gene;Eating;Eating Disorders;experimental study;feeding;Food;Functional disorder;Gene Expression Profiling;Genetic Transcription;Goals;Human;Individual;Lateral;Link;Mediating;metabolic rate;Midbrain structure;Molecular;Molecular Profiling;molecular subtypes;Monitor;Motivation;Mus;neural;neural circuit;neural patterning;neuroimaging;Neurons;neurotransmission;novel;Nutrient;Obese Mice;Obesity;Output;Pathway interactions;Patients;pharmacologic;Phase;Phenocopy;Physiological;Population;Prader-Willi Syndrome;Psychological reinforcement;Publishing;Rabies;reduced food intake;Research;response;reward processing;Rewards;Rodent;Satiation;Signal Transduction;single cell sequencing;single nucleus RNA-sequencing;Source;Stomach;Substantia nigra structure;System;Testing;Thinness;tool;Transcript;Ventral Tegmental Area;Viral;Weight maintenance regimen;Work

PROJECT_TITLE: Cerebellar-striatal circuits for control of dopamine activity and food intake

STUDY_SECTION: POMD

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


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease

ORG_DEPT: BIOCHEMISTRY

PHR: PROJECT NARRATIVE Muscles (including the heart and fast and slow skeletal muscles) have an ability to change how they contract to meet the needs of changing environments, like exercise, hormones, or genetic disease. We propose to study how they make these adaptations with a particular emphasis on the motor proteins of muscle called myosins. Mutations in these motors cause a large number of diseases and our work should lead to novel therapies for these debilitating diseases.

PI_NAMEs: LEINWAND, LESLIE ANNE (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Address;Adult;Affect;Age;Animal Model;Animals;Arginine;Autophagocytosis;biological sex;Cardiac;Cardiac Myocytes;Cardiac Myosins;Cardiomyopathies;Cell Culture Techniques;cell type;Clinical;Contracts;Data;Deuterium Oxide;Development;Dilated Cardiomyopathy;Disease;Electron Microscopy;Embryo;Environment;Exercise;Family;Fiber;Genes;Genetic Diseases;Goals;Half-Life;Health;Heart;Heterogeneity;Homeostasis;Hormonal;Hormones;Hour;Human;Hypertrophic Cardiomyopathy;improved;in vivo;Individual;inhibitor;insight;Isotopes;Label;live cell imaging;Lysine;mass spectrometric imaging;Mass Spectrum Analysis;Measures;Metabolism;Methods;Modeling;Molecular Conformation;molecular imaging;Motor;mouse model;multicatalytic endopeptidase complex;Mus;Muscle;Muscle Cells;Muscle Fibers;Muscle function;muscle physiology;Muscle Proteins;Mutagens;mutant;Mutation;Myocardium;Myofibrils;Myopathy;Myosin ATPase;Myosin Rod;novel therapeutics;Organelles;Pathway interactions;Pattern;Phenotype;Physiology;Play;Process;Protein Analysis;protein degradation;Proteins;Proteomics;proteostasis;repaired;response;Rod;Role;Sarcomeres;Site;skeletal;Skeletal Muscle;small molecule;spatiotemporal;Stable Isotope Labeling;Stimulus;Striated Muscles;System;targeted treatment;Thyroid Gland;Thyroid Hormones;Tissues;Ubiquitin;Ubiquitination;Work

PROJECT_TITLE: Myosin Gene Diversity and Function

STUDY_SECTION: SMEP

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Lung;Pulmonary Hypertension;Rare Diseases

ORG_CITY: LA JOLLA

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE We have devised a simple blood test that has the capacity to screen patients for the presence of pulmonary arterial hypertension, as well as give a readout of disease progression over time, based on our studies of the NOTCH3 receptor in this disease. We will test the hypothesis that quantification of serum NOTCH3 ECD levels is a highly sensitive and specific method to diagnose and determine the severity of World Health Organization Group 1 (idiopathic) pulmonary arterial hypertension in all age groups, sexes, and racial/ethnic backgrounds, as well as elucidate the cellular interactions and mechanisms leading to NOTCH3 ECD release into the blood. This novel biomarker test will bring pulmonary arterial hypertension diagnostics into a more patient-friendly, less invasive, and less costly realm and serve as a useful adjunct to other currently used modalities to diagnose this disease.

PI_NAMEs: THISTLETHWAITE, PATRICIA A (contact)

PROGRAM_OFFICER_NAME: SUTLIFF, ROY L

PROJECT_TERMS: Age;age group;Apoptosis;Binding;Biological Assay;Biological Markers;Blocking Antibodies;Blood;Blood Tests;Cardiac Catheterization Procedures;Cell Nucleus;Cell Proliferation;Cells;Clinical;clinical practice;cohort;cost;Data;Diagnosis;Diagnostic;Disease;disease diagnosis;Disease Progression;Echocardiography;Endothelial Cells;Ethnic Origin;Ethnic Population;Event;experimental study;Extracellular Domain;Failure;Family suidae;Friends;Geography;Goals;Grant;Human;Hypoxia;Individual;jagged1 protein;Laboratories;Ligand Binding;Lung;Lung Diseases;Measurement;Measures;Membrane;Methods;Modality;Molecular;Monitor;Monoclonal Antibodies;Mus;noninvasive diagnosis;NOTCH3 gene;novel;novel marker;overexpression;Pathologic;patient population;patient screening;Patients;Peptide Fragments;peripheral blood;Pharmaceutical Preparations;Pilot Projects;Proliferating;pulmonary arterial hypertension;pulmonary arterial pressure;Pulmonary artery structure;Pulmonary Hypertension;Pulmonary Vascular Resistance;Race;racial population;Rattus;receptor;Regimen;Reproducibility;response;Right Ventricular Hypertrophy;Rodent;Sensitivity and Specificity;Serum;Severities;Severity of illness;sex;Signal Transduction;Smooth Muscle Myocytes;Specificity;SU 5416;Tertiary Protein Structure;Testing;Time;Translations;treatment response;Validation;Vascular Smooth Muscle;Ventilation Perfusion Scanning;Work;World Health Organization;X-Ray Computed Tomography

PROJECT_TITLE: NOTCH3 ECD as a Serum Biomarker for Pulmonary Arterial Hypertension

STUDY_SECTION: RIBT

STUDY_SECTION_NAME: Respiratory Integrative Biology and Translational Research Study Section[RIBT]


ADMINISTERING_IC: AG

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);Brain Disorders;Dementia;Genetics;Neurodegenerative;Neurosciences

ORG_CITY: Los Angeles

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE When our cells activate a gene, they make a disposable copy of it that can be used for various biological purposes. We will investigate whether mistakes are made when these copies are synthesized and determine how these mistakes affect human health. Ultimately, these experiments could provide new insight into the natural aging process and the origins of various human diseases, including Alzheimer’s disease, Parkinson’s disease and cancer.

PI_NAMEs: VERMULST, MARC  (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: adduct;Affect;age related;Age related pathologies;Aging;aging process;Alleles;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease patient;Amyloid;Amyloid Beta A4 Precursor Protein;amyloid peptide;Amyloid Proteins;Amyloidosis;Animals;Back;base;Behavior;Biochemical;biochemical tools;bioinformatics pipeline;Biological;Biology;biophysical techniques;biophysical tools;Brain;Cell Aging;Cells;Coupled;Cryoelectron Microscopy;Custom;Data;Databases;Development;Diabetes Mellitus;Disease;DNA;DNA Damage;DNA lesion;DNA Repair;DNA Repair Gene;Endemic Diseases;Event;experimental study;exposed human population;Exposure to;fluorescence imaging;Genes;Genetic;Genetic Transcription;Genome;Germ Lines;Germ-Line Mutation;Goals;Guanine;Health;Heart Diseases;Human;human disease;human stem cells;Impaired cognition;insight;Late Onset Alzheimer Disease;Lesion;Libraries;life span;Malignant Neoplasms;MGMT gene;Modern Medicine;Molecular;Monitor;mouse model;Mus;Mutagenesis;mutant;Mutation;Neurodegenerative Disorders;Neuronal Differentiation;Neurons;normal aging;Organoids;Parkinson Disease;Pathology;Patients;Plasmids;Play;presenilin-1;presenilin-2;prion-like;Process;protein aggregation;protein misfolding;Proteins;PrP;recruit;repaired;Research;Role;Senile Plaques;Shapes;single cell sequencing;Societies;Stream;System;Testing;Thinking;Time;Transcript;transcriptome;women patients;Work

PROJECT_TITLE: DNA-damage-induced transcription errors provide a constant stream of amyloid and prion-like proteins in human cells

STUDY_SECTION: CMAD

STUDY_SECTION_NAME: Cellular Mechanisms in Aging and Development Study Section[CMAD]


ORG_NAME: LA JOLLA INSTITUTE FOR IMMUNOLOGY

PHR: Project Narrative Hundreds to thousands of phosphorylation events in the T cell signaling pathway create dynamic biochemical networks that orchestrate essentially all functions needed for proper immune responses to malignant cells. We currently have no technology to functionally screen and identify individual phosphorylation sites that drive specific, distinct downstream phenotypes. Here, we propose combining DNA base editor-mediated mutations of phosphorylation sites, proteome-wide, coupled to phenotypic screens to discover novel signaling events that are associated with defects in T cell effector functions.

PI_NAMEs: MYERS, SAM ANTHONY (contact)

PROGRAM_OFFICER_NAME: AMIN, ANOWARUL

PROJECT_TERMS: Adoptive Cell Transfers;Age;Aging;Automobile Driving;base editing;base editor;Biochemical;Biology;cancer cell;CD8-Positive T-Lymphocytes;cell behavior;Cell Compartmentation;Cell membrane;Cell Physiology;Cell Proliferation;Cells;Cellular Assay;Clustered Regularly Interspaced Short Palindromic Repeats;Codon Nucleotides;Complex;computer framework;Coupled;CRISPR screen;cytotoxic;Data;Decision Making;Defect;Disease;DNA;drug development;effector T cell;Engineering;Event;exhaustion;experimental study;fighting;follow-up;functional genomics;Gene Expression;Gene Expression Profiling;Genes;Genetic Transcription;Genome;Genomic DNA;Genomics;Human;Immune;Immune response;immunosenescence;Individual;innovative technologies;insight;Knock-out;Laboratories;Link;Malignant Neoplasms;Maps;Mass Spectrum Analysis;Mediating;Methods;migration;molecular phenotype;mutant;Mutate;Mutation;Nerve Degeneration;new therapeutic target;NF-kappa B;novel;nuclear factors of activated T-cells;pathogen;Pathway interactions;Phenotype;phosphoproteomics;Phosphorylation;Phosphorylation Site;Physiological Processes;Post-Translational Modification Site;Post-Translational Protein Processing;programmed cell death protein 1;programs;Proliferating;Proteome;Reporter;response;screening;Signal Pathway;Signal Transduction;Signal Transduction Pathway;T-Cell Activation;T-Cell Proliferation;T-Cell Receptor;T-Lymphocyte;Techniques;Technology;Therapeutic;Time;Tissues;tool;Vaccines;Validation;Work

PROJECT_TITLE: Proteome-wide base editor screens to assess phosphorylation site functionality in immunosenescence

STUDY_SECTION: MCTA

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics A Study Section[MCTA]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Eye Disease and Disorders of Vision;Infectious Diseases;Wound Healing and Care

ORG_CITY: IRVINE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Narrative Pseudomonas aeruginosa is an important cause of blinding corneal infections in the USA and worldwide. Our studies have characterized the role of P. aeruginosa virulence factors and the immune response, especially neutrophils that control bacterial growth in infected corneas, but also causes corneal disease and visual impairment. Proposed studies will continue to examine the interactions of bacterial virulence factors with neutrophils at the molecular level, with the goal of understanding molecular pathways underlying these observations. Results from these studies will identify novel inhibitors of inflammatory cell activation that can be used to block the tissue damage and loss of vision.

PI_NAMEs: DUBYAK, GEORGE R;PEARLMAN, ERIC  (contact);RIETSCH, ARNE

PROGRAM_OFFICER_NAME: MCKIE, GEORGE ANN

PROJECT_TERMS: Adenosine Diphosphate Ribose;ADP ribosylation;Anti-Inflammatory Agents;Antibiotic Resistance;Antibodies;Area;Arginine;Bacteria;Bacterial exotoxin;Binding;Blindness;Caring;Cell Culture Techniques;Cell Death;Cells;Centrosome;Cessation of life;Clinical;Cornea;Corneal Diseases;corneal epithelium;Corneal Ulcer;Cryoelectron Microscopy;Cytosol;Data;Disease Outbreaks;Disease Progression;Drug resistant Pseudomonas aeruginosa;Early Endosome;Endosomes;Ensure;Epithelial Cells;Event;exoenzyme;Exotoxins;experience;experimental study;Eyedrops;Funding;Goals;Grant;Growth;HDAC6 gene;Human;Immune response;Immune Targeting;immunological intervention;In Vitro;Infection;Inflammasome;Inflammatory;inhibitor;Interleukin-1 beta;Keratitis;Length;lens;Licensing;Macrophage;Mediating;Modification;Molecular;Mus;mutant;Needles;neutrophil;novel;Pathogenesis;pathogenic bacteria;Pathway interactions;Patients;Peptide Elongation Factor 2;Phosphotransferases;Printing;Protein Secretion;protein structure;Proteins;Pseudomonas aeruginosa;Pseudomonas aeruginosa infection;Reporting;Ribosomes;Role;Signal Transduction;Site-Directed Mutagenesis;small molecule inhibitor;Stimulus;Stress;structural biology;Structure;System;tandem mass spectrometry;Testing;Therapeutic Intervention;Tissues;trafficking;trans-Golgi Network;Transferase;Translations;Type II Secretion System Pathway;Type III Secretion System Pathway;US State;Vesicle;Virulence;Virulence Factors;Visual impairment;Western Blotting

PROJECT_TITLE: Pathogenesis of Bacterial Keratitis

STUDY_SECTION_NAME: Pathophysiology of Eye Disease - 1 Study Section[PED1]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Clinical Research;Digestive Diseases;Urologic Diseases

ORG_CITY: PALO ALTO

ORG_NAME: PALO ALTO VETERANS INSTIT FOR RESEARCH

PHR: PROJECT NARRATIVE Lymphocytes migrate from the blood into the various tissues of the body where they provide immunity to infection and control cancer, but can also cause autoimmune and other inflammation associated diseases. The focus of this application is on newly discovered mechanisms that control lymphocyte access to some of the most clinically important organs in the body...including the lungs and airways, stomach, genitourinary tract and the pancreas. The proposed studies could lead to improved vaccine strategies and to novel preventative, therapeutic or curative treatment strategies for autoimmune, inflammatory, and neoplastic diseases.

PI_NAMEs: BUTCHER, EUGENE C (contact)

PROGRAM_OFFICER_NAME: JOFFE, AARON MICHAEL

PROJECT_TERMS: Address;Adhesions;Autoimmune;Autoimmune Diseases;autoimmune inflammation;B-Lymphocytes;Binding;Biological Assay;Blood;Bone Marrow;C-terminal;Cancer Control;CCL25 gene;CCR9 gene;Cells;chemokine;Chemotactic Factors;Chemotaxis;Chimera organism;Chronic;Clinical;CMKLR1 gene;Colon;curative treatments;cytokine;Data;design;Development;Disease;Environmental Risk Factor;Epithelial Cells;Epithelium;Flow Cytometry;fMet-Leu-Phe receptor;G-Protein-Coupled Receptors;Genitourinary system;Gland;Goals;GPR15 gene;GPR2 gene;high dimensionality;Homeostasis;Homing;Human;Immune;immune reconstitution;Immune response;Immune system;Immune Targeting;Immunity;imprint;improved;In Vitro;in vivo;Infection;Inflammation;Inflammatory;innovation;Intestinal Mucosa;Intestines;Invaded;Knowledge;Ligands;Lung;Lymphocyte;Lymphocyte Biology;lymphocyte trafficking;Lymphoid;Mediating;migration;Modeling;Mucosal Immune System;mucosal site;Mucous Membrane;Mus;mutant;Myeloid Cells;Nature;neoplastic;novel;novel strategies;Organ;Orphan;Pancreas;pathogen;Pathology;Pathway interactions;Peptides;Population;Population Study;primary lymphoid organ;Property;receptor;Receptor Activation;receptor binding;receptor expression;recruit;Regulation;response;Role;Salivary Glands;secondary lymphoid organ;selective expression;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Site;Skin;Small Intestines;Specificity;stem cells;Stomach;Structure;System;T-Cell Activation;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Therapeutic;therapy development;Thymus Gland;Tissues;tool;trafficking;Translating;treatment strategy;Upper digestive tract structure;urogenital tract;vaccine strategy;Variant;γδ T cells

PROJECT_TITLE: Novel Lymphocyte Chemoattractant Receptor and Ligand

STUDY_SECTION: CMIB

STUDY_SECTION_NAME: Cellular and Molecular Immunology - B Study Section[CMIB]


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Clinical Research;Genetics;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Mental Health;Mental Illness;Psychosis;Racial and Ethnic Minority Health Research;Schizophrenia;Serious Mental Illness

ORG_CITY: Newark

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: Project Narrative  African Ancestry and other minority populations have been poorly represented in large-scale genomic studies, and yet these populations have the largest disparities in health care and outcomes and have the potential to broaden our knowledge of human genetics. The African Ancestry-Genomic Psychiatry Cohort (AA-GPC) will combine the African Ancestry (AA) participants in this study, the VA-CSP study, and the NeuroGap-Psychosis study creating a study population over 100,000 AA participants. This analysis has the potential for significant novel discovery.

PI_NAMEs: BIGDELI, TIM BERNARD;FANOUS, AYMAN H;PATO, CARLOS N;PATO, MICHELE T (contact)

PROGRAM_OFFICER_NAME: PEVSNER, JONATHAN ABRAM

PROJECT_TERMS: Africa;African;African ancestry;Agreement;Benchmarking;Bipolar Disorder;cohort;Data;Data Set;Diagnosis;Disease;Enrollment;European;European ancestry;Event;Funding;Genetic;genetic association;Genetic Polymorphism;Genetic Recombination;Genetic Risk;Genome;genome wide association study;genome-wide;genome-wide analysis;Genomics;Goals;Haplotypes;health care disparity;Human;Human Genetics;improved;Individual;Knowledge;Linkage Disequilibrium;Maps;Mental disorders;Meta-Analysis;Minority Groups;National Institute of Mental Health;neuropsychiatry;non-genomic;novel;Outcome;Participant;Patients;Phase;Philanthropic Fund;polygenic risk score;Population;Population Heterogeneity;psychiatric genomics;Psychiatry;Psychoses;psychosis risk;Resolution;Sampling;Schizoaffective Disorders;Schizophrenia;screening;Signal Transduction;SNP genotyping;statistics;Strategic Planning;study population;training data;Variant;whole genome

PROJECT_TITLE: African Ancestry Genomic Psychiatry Cohort

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: DURHAM

ORG_NAME: DURHAM VA MEDICAL CENTER

ORG_STATE: NC

PI_NAMEs: MARX, CHRISTINE E. (contact)

PROJECT_TERMS: acylcarnitine;Address;Agreement;Authorization documentation;Biological Markers;Blood;Blood specimen;Brain;C-reactive protein;candidate marker;Chemical Agents;Clinical;clinical investigation;cohort;Conflict (Psychology);Consent Forms;Data;Development;efficacious intervention;Endocrine disruption;Enrollment;Environmental Exposure;Esters;Etiology;Feasibility Studies;follow-up;Follow-Up Studies;functional outcomes;Future;Guidelines;Gulf War;Gulf War veteran;Health;Inflammation;inflammatory marker;Institute of Medicine (U.S.);Intervention;Investigation;Magnetic Resonance Imaging;Malignant Neoplasms;Medical;Metabolism;Mitochondria;Neurobehavioral Manifestations;neuroimaging;neurosteroids;operation;Pain;Persian Gulf Syndrome;Pilot Projects;Process;protein biomarkers;Recommendation;Recontacts;Recording of previous events;Research;research study;Sampling;Secondary to;Serum;Signal Transduction;small molecule;Structure;symptomatology;Symptoms;therapeutic development;Therapeutic Intervention;therapeutically effective;Thick;Translating;translational medicine;Translational Research;Translations;treatment response;Validation;Veterans;Vitamin D

PROJECT_TITLE: Biomarker Candidates in Gulf War Veterans: A 10-year Follow-up Investigation

STUDY_SECTION: SPLD

STUDY_SECTION_NAME: Special Emphasis - Research on Gulf War Veterans' Illnesses[SPLD]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

NIH_SPENDING_CATS: Cancer;Genetics;Hematology

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE Germline ETV6 mutations are associated with familial thrombocytopenia and ~30% of carriers develop hematologic malignancies, but the pathophysiologic mechanisms of disease are poorly understood. Preliminary data we have gathered demonstrates that one of these mutations, Pro214Leu, creates a de novo nuclear export signal that leads to the cytoplasmic localization of ETV6. A preliminary bioinformatics approach suggests that creation of a de novo nuclear export signal by a missense mutation may be a generalized mechanism of human disease.

PI_NAMEs: MCCONVILLE, MICHAEL R (contact)

PROGRAM_OFFICER_NAME: GOLDBERG, ILANA GRACE

PROJECT_TERMS: Affect;Amino Acids;Animal Model;Binding;Bioinformatics;Biological Models;biophysical techniques;Blood Platelets;Cell Maintenance;Cell model;Cell Nucleus;Cells;Chemicals;Childhood Precursor B Lymphoblastic Leukemia;Chronic Myelomonocytic Leukemia;ClinVar;conditional knockout;Cytoplasm;Data;Development;Disease;DNA Binding;DNA Binding Domain;Dysmyelopoietic Syndromes;ETV6 gene;Exhibits;exportin 1 protein;Family;Functional disorder;Functional Imaging;gene repression;Genetic;genetic approach;Genetic Markers;Genetic Variation;Germ Lines;Germ-Line Mutation;Goals;Hematologic Neoplasms;Hematopoietic;Heterozygote;Hour;human disease;In Vitro;Induced Mutation;Inherited;inhibitor;Knockout Mice;leptomycin B;leukemia;Malignant Neoplasms;Mammalian Cell;Maps;Mediating;Megakaryocytes;meter;Missense Mutation;mouse model;mutant;Mutate;Mutation;mutation carrier;novel;novel marker;Nuclear;Nuclear Export;Penetrance;Peripheral;Platelet Count measurement;Point Mutation;Production;protein function;protein reconstitution;Proteins;public database;Recurrence;Risk;RUNX1 gene;Signal Transduction;Somatic Mutation;stem cells;Tertiary Protein Structure;Thrombocytopenia;Thrombopoiesis;tool;transcription factor;Transcription Repressor;Transgenic Mice;Variant;Work

PROJECT_TITLE: Unexpected mechanism underlying mislocalization of thrombocytopenia-associated ETV6 point mutation


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Osteoporosis;Women's Health Research

ORG_CITY: NEW HAVEN

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Narrative Characterizing the profile of anabolic clastokines induced by the soluble isoform of CSF1 in osteoclasts will provide important insights in the paracrine interaction between osteoblasts and osteoclasts and lead to n e w treatments for skeletal diseases including osteoporosis.

PI_NAMEs: INSOGNA, KARL LEONARD (contact)

PROGRAM_OFFICER_NAME: NICKS, KRISTY

PROJECT_TERMS: Affinity;Agonist;Anabolism;Animal Model;Animals;Attenuated;B-Lymphocytes;Binding;bone;bone loss;bone mass;Bone Resorption;C57BL/6 Mouse;Cells;Coculture Techniques;Colony-Stimulating Factors;CSF1 gene;CSF1R gene;Data;density;Dose;Enzymes;Estrogen deficiency;Event;experimental study;Exposure to;Immunophenotyping;Impairment;In Vitro;in vivo;in vivo Model;inhibitor;insight;Kinetics;Macrophage Colony-Stimulating Factor;Membrane;Modeling;Molecular;mouse model;Mus;new therapeutic target;novel;Osteoblasts;osteoclastogenesis;Osteoclasts;Osteogenesis;Osteoporosis;Ovariectomy;paracrine;Paracrine Communication;Patients;pharmacologic;Phospholipids;Population Study;Postmenopausal Osteoporosis;pre-clinical;Production;Protein Isoforms;receptor;Regimen;response;Role;Serum;Signal Transduction;skeletal;skeletal disorder;sphingosine 1-phosphate;sphingosine kinase;T-Lymphocyte;Testing;Therapeutic;Time;transcriptome;transcriptome sequencing;transcriptomic profiling;Treatment Efficacy;Treatment Protocols;Wild Type Mouse

PROJECT_TITLE: Different Roles for Colony Stimulating Factor 1 Isoforms in Anabolic Therapy for Low Bone Mass


PHR: Project Narrative The ability to escape from danger is a critical skill necessary for survival. The neural circuits that control escape, however, sometimes over-activate leading to intense feelings of fear and panic in the absence of threat – a process that is understudied. This proposal aims to elucidate escape circuits involving a genetically-defined cell population, cholecystokinin, within the lateral ventrolateral periaqueductal grey, a region of the brain highly implicated in panic, to provide novel avenues for understanding panic mechanisms.

PI_NAMEs: TOROSSIAN, ANITA  (contact)

PROGRAM_OFFICER_NAME: PINARD, COURTNEY ROSE

PROJECT_TERMS: Acceleration;Adult;Affect;Behavior;Behavioral;Behavioral Assay;Biological Assay;Brain region;Brain Stem;Breathing;Calcium;cell type;Cells;Cholecystokinin;Data;Electric Stimulation;Ethology;Experimental Designs;Exposure to;Feeling;Freezing;Fright;Genetic;Genetic Identity;genetic manipulation;Heart Rate;Human;Image;Impairment;in vivo calcium imaging;Injections;insight;Label;Lateral;Measures;Mediating;Methods;Microscope;midbrain central gray substance;miniaturize;Molecular Profiling;Mus;neural;neural circuit;neural network;neuromechanism;Neurons;Neuropeptides;Neurotransmitters;novel;Panic;Panic Attack;Panic Disorder;Pharmaceutical Preparations;Population;Positioning Attribute;Preparation;Process;Rattus;Resolution;Rodent;Role;skills;Slice;Testing;Training

PROJECT_TITLE: Dissecting Cell-Specific Brainstem Circuits Mediating Escape Behavior


ORG_CITY: ANN ARBOR

ORG_NAME: VETERANS HEALTH ADMINISTRATION

ORG_STATE: MI

PHR: Metastatic prostate cancer is likely to surge over the next decade as Vietnam Veterans age into their 70s. Black men and men exposed to Agent Orange have nearly twice the risk of metastatic diagnosis and death. Fortunately, new therapies have improved survival for men with metastatic prostate cancer, transforming guidelines and clinical practice. However, delivery of these new and complex treatments (i.e. treatment intensification) in men with multiple comorbid conditions raises equity and safety concerns. We aim to use a novel natural language processing tool developed in the VA to prospectively identify Veterans with incident metastatic prostate cancer and investigate patient, facility, and neighborhood factors that influence receipt of treatment intensification. We will also analyze real-world development of adverse events in this vulnerable population, and survey Veterans and physicians about their perception of barriers to care.

PI_NAMEs: CARAM, MEGAN ELIZABETH VERESH (contact)

PROJECT_TERMS: abiraterone;Address;advanced prostate cancer;Adverse event;Affect;Age;agent orange;androgen deprivation therapy;Androgens;Area;barrier to care;black men;cancer care;Cancer Etiology;Cardiovascular Diseases;care delivery;Caring;Cessation of life;clinical practice;Clinical Trials;cohort;comorbidity;Complex;Data;demographics;deprivation;Development;Diabetes Mellitus;Diagnosis;Disease;disparity elimination;docetaxel;Electronics;Emergency department visit;enzalutamide;Equity;Event;experience;Exposure to;Foundations;Frequencies;Future;Genus Mentha;Geography;Goals;Guidelines;Health;Healthcare Systems;high risk;Hospitalization;hospitalization rates;improved;Incidence;individual patient;Infrastructure;inhibitor;innovation;Institution;Intervention;Knowledge;Laboratories;Link;Logistic Regressions;Malignant neoplasm of prostate;Malignant Neoplasms;men;men's group;Mental Health;Metastatic Prostate Cancer;Methodology;military veteran;Modeling;Monitor;Natural Language Processing;neighborhood association;neighborhood disadvantage;Neighborhoods;Neoplasm Metastasis;Newly Diagnosed;novel;novel therapeutics;Outcome;Outpatients;Patient Outcomes Assessments;patient population;Patient Preferences;Patients;Perception;personalized medicine;Physicians;preference;prospective;Provider;Quality of Care;Quality of life;Records;Regression Analysis;Reporting;Research;Resources;Risk;Safety;safety assessment;Sampling;Shapes;side effect;Signal Transduction;Social support;socioeconomic disadvantage;standard of care;Strategic Planning;Support System;Surveys;Time;tool;treatment risk;trend;United States Department of Veterans Affairs;Veterans;Vietnam;Visit;Vulnerable Populations;Work

PROJECT_TITLE: Optimizing Advanced Prostate Cancer Care Among US Veterans

STUDY_SECTION_NAME: HSR-1 Health Care and Clinical Management[HSR1]


FUNDING_MECHANISM: OTHERS

ORG_CITY: BEDFORD

ORG_NAME: EDITH NOURSE  ROGERS MEMORIAL VETERANS HOSPITAL

ORG_STATE: MA

PHR: This Career Development Award seeks to support the efforts of Veterans Health Administration (VHA) to build the Whole Health (WH) system of care in which Veterans are empowered and equipped to pursue their best possible vision of health and well-being through self-care, conventional clinical care, and complementary and integrative health services. The objective of the CDA is to optimize the implementation of WH-Coaching, a key service in the WH system of care that provides extended, one-on-one support for setting and achieving personal health and well-being goals, for a specific chronic condition population – Veterans with chronic obstructive pulmonary disease (COPD). The proposed CDA will build on my strengths in qualitative research methods and implementation science, while simultaneously filling considerable gaps in my training related to theory-driven evaluation and complex systems approaches, quantitative research methods, co-design, implementation/hybrid trial design, and leadership/mentorship.

PI_NAMEs: ANDERSON, EKATERINA  (contact)

PROJECT_TERMS: Adoption;aspirate;care seeking;care systems;career;Caring;Chronic;Chronic Disease;Chronic Obstructive Pulmonary Disease;Clinical;clinical care;cohort;Complementary Health;Complex;complex chronic conditions;Data;design;Distress;effectiveness/implementation trial;empowerment;Enabling Factors;Enrollment;Ensure;Evaluation;experience;Face;Foundations;Goals;Health;health care service utilization;Health Services;Healthcare;Healthcare Systems;Hospitalization;Hybrids;implementation efforts;implementation science;improved;innovation;insight;Integrative Medicine;Intervention;Interview;K-Series Research Career Programs;Knowledge;Leadership;Longitudinal trends;Medical;Mentored Clinical Scientist Development Program;Mentors;Mentorship;Methodology;Methods;military veteran;Modeling;Modernization;Morphologic artifacts;National Heart, Lung, and Blood Institute;Outcome;patient oriented;Patient Outcomes Assessments;patient population;Patient-Centered Care;Patients;Personal Satisfaction;Persons;Play;Population;Positioning Attribute;programs;Promoting Action on Research Implementation in Health Services framework;psychologic;psychosocial;Publishing;pulmonary rehabilitation;Qualitative Research;Quality of Care;Quality of life;Rehabilitation therapy;Research;Research Methodology;Research Personnel;Role;Self Care;Services;Site;skills;smoking cessation;Strategic Planning;success;supportive environment;Surveys;System;Testing;theories;Tobacco;Training;Training Programs;treatment services;trial design;Veterans;Veterans Health Administration;Vision;whole health;Work

PROJECT_TITLE: Optimizing the Implementation of Whole Health Coaching for Veterans with COPD

STUDY_SECTION_NAME: Research Career Scientist[MRA0]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Precision Medicine;Prostate Cancer;Urologic Diseases

ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: This proposal aims to develop novel percutaneous robotic devices that will lead to a higher instrument placement accuracy and maneuverability, currently a major impediment to successful MRI-targeted interventions. The proposed research has relevance to public health because the devices will have a positive impact on the treatment of cancers in the pelvis. The work is also thematically aligned to the NIH precision medicine initiatives, as we propose to develop and apply precision treatment tools with the imaging phenotype for treatment guidance.

PI_NAMEs: HATA, NOBUHIKO  (contact);ZHANG, HAICHONG

PROGRAM_OFFICER_NAME: LIU, GUOYING

PROJECT_TERMS: Address;Adopted;anatomic imaging;Animals;Antibiotics;Area;Automobiles;Biopsy;Biopsy Specimen;cancer diagnosis;cancer therapy;Clinical;clinical practice;Clinical Research;clinically significant;Collection;Compensation;Data;design;Detection;detection method;Devices;Diagnosis;Diagnostic;Dose;editorial;Engineering;Ensure;Escherichia coli;Excision;experience;fluoroquinolone resistance;Functional Imaging;Future;Goals;Guidelines;Gynecologic Brachytherapy;Image;image guided;Image Guided Biopsy;image guided intervention;improved;individual patient;Infection;Information Systems;innovation;instrument;Intervention;Interventional Imaging;Knowledge;Learning;Lesion;Literature;Magnetic Resonance Imaging;Malignant neoplasm of prostate;Malignant Neoplasms;Manuals;Measurement;Measures;Medical Device;Methods;Modernization;Molecular;molecular imaging;Motion;Needle biopsy procedure;Needles;next generation;novel;Pathologic;Patients;Pelvis;Phenotype;Physicians;pre-clinical;Precision Medicine Initiative;Precision therapeutics;prevent;Procedures;programs;Prostate;prostate biopsy;Protocols documentation;Public Health;Radiology Specialty;Rectum;Reporting;Research;Research Methodology;Research Personnel;risk stratification;Robot;robot control;robotic device;Robotics;Safety;Sampling;Science;Site;Specific qualifier value;Techniques;Technology;technology development;technology platform;Testing;Time;Tissues;tool;Translating;Transrectal Ultrasound;Treatment Protocols;tumor;Ultrasonography;ultrasound;United States National Institutes of Health;Work

PROJECT_TITLE: Physician Assistance Technology in Image-guided Robotic Intervention of Prostate

STUDY_SECTION: IGIS

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


ADMINISTERING_IC: MD

IC_NAME: NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Patient Safety;Prevention;Primary Health Care;Social Determinants of Health

ORG_CITY: MEMPHIS

ORG_NAME: UNIVERSITY OF TENNESSEE HEALTH SCI CTR

ORG_STATE: TN

PHR: PROJECT NARRATIVE Medication nonadherence (i.e., not taking one’s prescribed medicine) is a major cause of death, higher rates of hospital readmission, and extra costs for low-income patients with multiple chronic conditions. Major barriers to medication adherence among low-income patients during transitioning from the hospital to home include inability to pay for medications, inability to pick up prescribed medications, and not being given all necessary medications prior to discharge. This study seeks to find out if interventions that directly address these barriers will improve medical adherence and reduce hospitalizations and emergency department visits and costs among these patients.

PI_NAMEs: SURBHI, SATYA  (contact)

PROGRAM_OFFICER_NAME: WHITE, DOLLY PENN

PROJECT_TERMS: Acute;Address;Adherence;Adopted;Adult;African American population;Aftercare;care coordination;Caring;Cause of Death;Certification;Chronic Disease;community setting;Computerized Medical Record;copayment;cost;cost comparison;Cost Savings;Data;Drug Prescriptions;Economically Deprived Population;Effectiveness;effectiveness evaluation;Effectiveness of Interventions;effectiveness testing;Emergency department visit;Ensure;experience;follow-up;future implementation;Goals;group intervention;Health;health care delivery;health care service utilization;Health system;Healthcare Systems;Home;hospital readmission;Hospitalization;Hospitals;improved;Incidence;informant;innovation;Inpatients;Intervention;intervention effect;Interview;Length of Stay;Low income;Low Income Population;Medicaid;Medical;medication compliance;Medication Management;medication nonadherence;Medicine;Modeling;mortality;multiple chronic conditions;Outcome;Participant;participant enrollment;Patients;Pharmaceutical Preparations;Pharmacy facility;pill;Pilot Projects;Policy Maker;Polypharmacy;Primary Care;primary outcome;Randomized;Randomized, Controlled Trials;readmission rates;Reporting;Research;response;secondary outcome;service coordination;Services;social health determinants;socioeconomic disadvantage;System;system-level barriers;Tennessee;Time Management;Training;Transportation;treatment as usual;Uninsured;United States National Institutes of Health;Vulnerable Populations

PROJECT_TITLE: Pharmacy-led Transitions of Care Intervention to Address System-Level Barriers and Improve Medication Adherence in Socioeconomically Disadvantaged Populations

STUDY_SECTION: HSQE

STUDY_SECTION_NAME: Health Services: Quality and Effectiveness Study Section[HSQE]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Clinical Research

ORG_CITY: CAMBRIDGE

ORG_NAME: HARVARD UNIVERSITY

PHR: Project Narrative Musculoskeletal simulations that quantify muscle forces generated during movements, rigorously validated in animal and human studies, have great potential to improve life-long mobility for many persons, but to date suffer from physiologically inaccurate muscle models, significantly limiting their ability to accurately predict the magnitude and time course of muscle force; thereby hampering their usefulness in the clinic. A fundamental underlying cause is that muscle tissue mass has been ignored in muscle models and simulations. This proposal tests the key hypothesis that inactive muscle mass, reflective of submaximal activities of daily living (ADL), significantly limits a muscle’s shortening velocity, work, efficiency, and power output, by examining the contractile properties of different-sized whole animal muscles versus small fiber bundles that will inform the design of mass-enhanced muscle models incorporated into computationally efficient musculoskeletal simulations of human movement across ADL and gait.

PI_NAMEs: BIEWENER, ANDREW A (contact)

PROGRAM_OFFICER_NAME: LINDHURST, MARJORIE JEAN

PROJECT_TERMS: Activities of Daily Living;Address;Adult;Affect;Animals;Architecture;Area;Behavior;Cerebral Palsy;Characteristics;Child;Clinic;Computer Models;Computers;Data;design;Disease;Elderly;Exhibits;Fatty acid glycerol esters;Fiber;Gait;Goals;Goat;Growth;Health;Human;Human Activities;Human body;improved;in silico;In Situ;In Vitro;intercalation;Intervention;kinematics;life span;Measures;Mechanics;Modeling;models and simulation;Motion;Motor;Movement;Mus;Muscle;Muscle Fibers;muscle form;Muscle function;Musculoskeletal;Output;Performance;Persons;Physiological;predictive modeling;Property;Publishing;Rattus;Recording of previous events;rehabilitation strategy;Research;Running;Shapes;simulation;Speed;Tendon structure;Testing;Time;virtual;Walking;Work

PROJECT_TITLE: Muscle Mass: a Critical but Missing Component in Muscle Modeling and Simulation

STUDY_SECTION: MRS

STUDY_SECTION_NAME: Musculoskeletal Rehabilitation Sciences Study Section[MRS]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Contraception/Reproduction;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Prevention;Social Determinants of Health;Women's Health Research

ORG_CITY: BLOOMINGTON

ORG_DEPT: SOCIAL SCIENCES

ORG_NAME: TRUSTEES OF INDIANA UNIVERSITY

ORG_STATE: IN

PHR: PROJECT NARRATIVE Unmet sexual and reproductive healthcare (SRH) needs can have deleterious consequences and are associated with poorer physical and emotional health outcomes both among women and their children. This study investigates women’s unmet SRH needs over the life course by specifying the connections between women’s experiences of SRH, the predisposing factors and enabling resources associated with unmet SRH needs, and disparities in unmet SRH needs over time. Findings may inform the development of public policy, public health programming, or clinical interventions to reduce unmet SRH needs and eliminate disparities by identifying the women most at risk and informing when and how to intervene most effectively.

PI_NAMEs: ANDERSON, ELIZABETH MARIE (contact)

PROGRAM_OFFICER_NAME: POPKIN, RONNA

PROJECT_TERMS: Acute;acute care;Address;Age;aged;Caring;Characteristics;Child;Classification;Clinical;Contraceptive Agents;Contraceptive methods;Data;Data Collection;Data Set;demographic disparity;Development;Diagnosis;Disparity;disparity elimination;Economics;Electronic Health Record;Elements;Emotional;Event;experience;Female;Future;geographic disparity;Guidelines;Health;health care availability;health care service utilization;health inequalities;Health Services Accessibility;Healthcare;Healthcare Systems;Household;improved;Inequality;innovation;intergenerational;Intervention;Interview;Life Cycle Stages;Link;Logistic Regressions;Maternal and Child Health;Measures;member;Methods;Modeling;Outcome;Participant;Patient Recruitments;Pattern;Patterns of Care;Perception;Personal Satisfaction;Persons;physical conditioning;predictive modeling;Predisposing Factor;Preventive care;Probability;Probability Samples;Public Health;Public Policy;racial disparity;racism;Recording of previous events;recruit;Reporting;reproductive;Research;Research Personnel;Resources;Respondent;Risk;Sampling;Sequence Analysis;sexual and reproductive health;social;social disparities;Social Environment;Social support;sociodemographic disparity;sociodemographics;socioeconomic disparity;Source;Specific qualifier value;Structure;Surveys;Time;time use;transmission process;Trust;Typology;United States;Woman

PROJECT_TITLE: Patterns in Women's Unmet Sexual and Reproductive Healthcare Needs Over the Life Course

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F18-L(20)L]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Chronic Pain;Genetics;Neurodegenerative;Neurosciences;Pain Research;Peripheral Neuropathy;Physical Injury - Accidents and Adverse Effects

ORG_DEPT: ANESTHESIOLOGY

PHR: Project Narrative The proposal will examine a role of recently identified dorsal root ganglion-specific long noncoding RNA (DS-lncRNA) in neuropathic pain. We propose that peripheral nerve injury-induced downregulation of DS- IncRNA may contribute to the development and maintenance of neuropathic pain through enhancement in the binding of RALY (a transcriptional co-factor) to RNA polymerase II and consequent promotion of the RALY/RNA polymerase II-triggered G9a expression in the injured dorsal root ganglion. The proposed study will identify a previously unknown regulatory mechanism for neuropathic pain as well as a novel and potential therapeutic target.

PI_NAMEs: HU, HUIJUAN  (contact);TAO, YUAN-XIANG

PROGRAM_OFFICER_NAME: GREENWELL, THOMAS

PROJECT_TERMS: Adverse effects;Attenuated;Binding;chemokine;Chronic;clinical application;Clinical Trials;Code;cofactor;cytokine;Data;Development;Disease;Disease Management;Distress;Down-Regulation;Enzymes;Gene Expression;gene therapy;Genes;Genetic Transcription;Human;Hypersensitivity;injured;Injury;Ion Channel;knock-down;Laboratories;Lead;Length;Ligation;Maintenance;Mediating;Messenger RNA;Mus;Names;nerve injury;Neurons;next generation;novel;novel strategies;Nucleotides;Opioid Receptor;overexpression;Pain;Pain management;pain symptom;painful neuropathy;Peripheral nerve injury;POU Domain;POU domain factors;promoter;Proteins;Public Health;receptor;Regulation;RNA I;RNA Polymerase II;Role;Spinal Ganglia;Spinal nerve structure;Testing;therapeutic target;Time;Transcription Coactivator;Transcription Factor 3;transcriptome sequencing;Untranslated RNA;Up-Regulation;Virus;Voltage-Gated Potassium Channel

PROJECT_TITLE: Identification of a novel DRG-specific long noncoding RNA and its role in neuropathic pain


ORG_CITY: La Jolla

ORG_NAME: SALK INSTITUTE FOR BIOLOGICAL STUDIES

PHR: PROJECT NARRATIVE – Overall As a largely refractory disease, a better understanding of the mechanisms underlying therapeutic resistance in pancreatic ductal adenocarcinoma is urgently needed for the rational development of new therapies. This program project will determine the interdependent contributions to therapeutic resistance of epigenetic programs (Project 1), paracrine signaling pathways (Project 2), and metabolic adaptations (Project 3) in both the tumor and stromal compartments. Supporting these Research Projects, three state-of-the-art Shared Resource Cores and an Administrative and Biostatistics Core will provide central expertise for mouse and organoid models, single-cell analyses, digital spatial profiling, and immune cell characterizations, as well as key biostatistical and informatic support.

PI_NAMEs: HUNTER, TONY R. (contact)

PROGRAM_OFFICER_NAME: BERA, TAPAN K

PROJECT_TERMS: Automobile Driving;Autophagocytosis;Biology;Biometry;Biostatistics Core;CA-19-9 Antigen;Cancer Etiology;Cell Communication;Cell Survival;cell type;Cells;Cessation of life;checkpoint inhibition;Chemoresistance;chemotherapy;Clinical;Coculture Techniques;combinatorial;Coupled;Cues;cytokine;Death Rate;Desmoplastic;Development;digital;DNA Damage;Drug Delivery Systems;Drug resistance;Epidermal Growth Factor Receptor;Epigenetic Process;epigenome;Fibroblasts;Genome;glycosylation;Goals;Growth;HDAC1 gene;Heterogeneity;Histone Deacetylase;Histone Deacetylase Inhibitor;Human;Hypoxia;Immune;Immune checkpoint inhibitor;immunogenic cell death;Immunotherapy;improved;Individual;Inflammatory;Informatics;inhibition of autophagy;inhibitor;innovation;interest;LIF gene;Macrophage;Macrophage Activation;Malignant neoplasm of pancreas;Malignant Neoplasms;Mediating;Metabolic;Metabolism;Modeling;mouse model;Mus;Mutation;nanoparticle drug;Nature;neoplastic cell;novel;novel therapeutics;Nutrient availability;Nutrient Depletion;Organoids;Outcome;Pancreatic Ductal Adenocarcinoma;paracrine;Paracrine Communication;Pathway interactions;Patients;Polysaccharides;Post-Translational Protein Processing;Production;programs;Refractory Disease;Regulation;Research Personnel;Research Project Grants;Research Support;Resistance;resistance factors;resistance mechanism;Resource Sharing;response;Role;Sampling;Signal Pathway;Signal Transduction;single cell analysis;Specimen;STAT3 gene;stem;Stress;Stromal Cells;support network;Survival Rate;synergism;System;targeted treatment;Testing;Therapeutic;therapy outcome;therapy resistant;Toxic effect;Treatment Efficacy;treatment response;treatment strategy;tumor;tumor growth;tumor microenvironment;Tumor Promotion;tumorigenic;Vascularization

PROJECT_TITLE: Overcoming mechanisms of therapeutic resistance in pancreatic ductal adenocarcinoma


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Immunotherapy;Orphan Drug;Pancreatic Cancer;Rare Diseases

PHR: PROJECT NARRATIVE – Project 1: Epigenetics Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest forms of cancer, displaying resistance to a broad range of therapeutics. Alterations of the epigenetic landscape, including aberrant histone acetylation, in both tumor and stromal cells integrate with metabolic and signaling adaptations to drive cancer cell growth, survival, and therapeutic resistance. We take pharmacological and genetic approaches to determine how targeted inhibition of Class I histone deacetylases can disrupt PDA therapeutic resistance programs in both tumor and stromal cells, leveraging these findings to sensitize PDA to existing and/or developing cancer drugs.

PI_NAMEs: EVANS, RONALD M (contact)

PROJECT_TERMS: Affect;anti-PD-1;anti-PD1 therapy;anti-tumor immune response;Antigen Presentation;Antineoplastic Agents;Autophagocytosis;Biopsy;Cancer Cell Growth;Cell Communication;Cell Compartmentation;Cell Death;cell growth;Cell Proliferation;cell type;Cells;checkpoint inhibition;Chemoresistance;Chromatin;Clinical;Clinical Trials;Collaborations;Complex;cytokine;Cytotoxic T-Lymphocytes;Data;digital;Disease;Disease Progression;DNA Damage;DNA Repair;Dose;Down-Regulation;Drug Delivery Systems;drug sensitivity;efficacy testing;Epigenetic Process;epigenome;epigenomics;Exhibits;experimental study;Extracellular Matrix;Fibroblasts;Gene Expression;Gene Expression Profile;Genes;Genetic;genetic approach;Genetic Transcription;HDAC1 gene;Heterogeneity;Histone Acetylation;Histone Deacetylase;Histone Deacetylase Inhibitor;Histones;Human;I-antigen;Immune;immunogenic;Immunologics;immunoregulation;Immunotherapy;improved;In Vitro;in vivo;Incidence;Induction of Apoptosis;Inflammatory;inhibition of autophagy;inhibitor;insight;Intercellular Fluid;Laboratory Finding;LIF gene;Malignant neoplasm of pancreas;Malignant Neoplasms;Maps;Mediating;Mediator;Metabolic;Molecular;mouse model;Mus;Mutation;nano-string;nanoparticle;nanoparticle delivery;neoplastic cell;novel;novel therapeutics;Organoids;Outcome;pancreatic cancer cells;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;Pathway interactions;Patient-Focused Outcomes;Patients;pharmacologic;Phenotype;Population;prevent;Production;Prognosis;programs;reconstitution;Refractory;Regulation;Resistance;response;Role;Signal Transduction;Stromal Cells;synergism;System;T-Lymphocyte;targeted treatment;Testing;Therapeutic;therapy resistant;Tissues;Toxic effect;transcriptional reprogramming;Treatment Efficacy;treatment response;treatment strategy;tumor;Tumor Burden;tumor growth;Tumor Immunity;tumor microenvironment;Tumor Promotion;tumorigenic;Work

PROJECT_TITLE: Project 1: Overcoming therapeutic resistance in pancreatic cancer through epigenetic reprogramming


NIH_SPENDING_CATS: Breast Cancer;Cancer;Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Heart Disease;Prevention;Women's Health Research

ORG_CITY: LITTLE ROCK

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: Cancer patients who have had long-term treatment with the drug doxorubicin often suffer from cardiotoxicity, caused by an enzyme, topoisomerase 2b (Top2b), which can be prevented by dexrazoxane, an FDA- approved drug that inhibits Top2b. However, dexrazoxane is not commonly used due to a concern for reducing the effectiveness of doxorubicin. This study will test a new strategy to resurrect the clinical use of dexrazoxane by giving it to patients eight hours before doxorubicin based on a different mechanism of action by dexrazoxane.

PI_NAMEs: CHANG, HUI-MING  (contact)

PROGRAM_OFFICER_NAME: DESVIGNE-NICKENS, PATRICE

PROJECT_TERMS: Adult;Animal Model;Anthracycline;ATPase Domain;Binding;Biological Markers;Blood;Breast Cancer Patient;Breast Cancer Treatment;cancer cell;Cancer Patient;Cancer Survivor;cancer therapy;cardiac magnetic resonance imaging;Cardiac Myocytes;cardioprotection;Cardiotoxicity;Cell Death;Cell division;chemotherapy;Chemotherapy-Oncologic Procedure;Childhood Leukemia;Clinical;cost effective;Data;Dexrazoxane;Disease-Free Survival;DNA;DNA Topoisomerases;Dose;Double-Blind Method;Doxorubicin;Effectiveness;Electron Transport;Enrollment;Enzymes;ERBB2 gene;Evaluation;FDA approved;Female Breast Carcinoma;gene repression;Generations;Genes;Genetic Transcription;Half-Life;Heart failure;Hour;Human Volunteers;inhibitor;Intravenous;Isoenzymes;Laboratories;Left Ventricular Ejection Fraction;Malignant Breast Neoplasm;Mediating;mitochondrial dysfunction;Monitor;Mus;Nonmetastatic;novel;novel strategies;Oncologist;Outcome;Patients;peripheral blood;Pharmaceutical Preparations;phase III trial;Placebo Control;Placebos;preservation;prevent;Prevention;primary endpoint;prospective;Proteins;Randomized;Recovery;Regimen;response;Sarcoma;secondary endpoint;Solid Neoplasm;Specific qualifier value;Testing;Time;Topoisomerase;tumor;ubiquitin mediated proteasome degradation

PROJECT_TITLE: Prevention of Heart Failure induced by Doxorubicin with Early Administration of Dexrazoxane

STUDY_SECTION: CICS

STUDY_SECTION_NAME: Clinical and Integrative Cardiovascular Sciences Study Section[CICS]


NIH_SPENDING_CATS: Aging;Cardiovascular;Genetics;Heart Disease;Human Genome;Lymphatic Research;Lymphedema;Nutrition;Obesity;Regenerative Medicine

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: PROJECT NARRATIVE Restoring function to the lymphatic system can alleviate lymphedema, heart disease, obesity, diabetes, and stroke. Consequently, our long-term goal is to uncover the molecular and cellular events governing lymphatic function in health and disease, with the hope of identifying new therapeutic targets to combat cardiovascular and metabolic diseases, which represent leading causes of morbidity and mortality, and remain highly-relevant to the mission of the NIH. In this project, we will investigate the pathophysiological role of the potential therapeutic target miR-22 in regulating lymphatic metabolic programming, signal transduction, and function.

PI_NAMEs: CHEN, HONG  (contact);DIXON, JAMES BRANDON;SRINIVASAN, RAJANARAYANAN S;WANG, DA-ZHI

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: Acceleration;Adaptor Signaling Protein;Adult;Affect;ATAC-seq;attenuation;Bioenergetics;Blood Vessels;Breeding;Cardiovascular Diseases;Cells;chromatin isolation by RNA purification sequencing;combat;Data;Development;Diabetes Mellitus;diabetic;Diabetic Angiopathies;diet-induced obesity;Disease;Edema;Epigenetic Process;epsin;Event;Fluid Balance;Fortification;Functional disorder;functional restoration;Funding;gain of function;Gene Expression;Genes;Genetic Models;Goals;Health;Heart Diseases;heart function;Heterozygote;Homeostasis;Human;Impairment;improved;In Vitro;in vivo;injured;innovation;Intestines;Knowledge;Link;Lipids;Literature;loss of function;Loss of Heterozygosity;Lymphangiogenesis;Lymphatic;lymphatic circulation;lymphatic development;lymphatic drainage;lymphatic dysfunction;Lymphatic Endothelial Cells;Lymphatic function;Lymphatic System;lymphatic vasculature;lymphatic vessel;Lymphedema;Metabolic;Metabolic Control;Metabolic Diseases;Metabolism;MicroRNAs;Mission;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;Myocardial Infarction;Natural regeneration;Near-infrared optical imaging;new therapeutic target;novel;Obesity;older adult;Operative Surgical Procedures;Outcome;Patient-Focused Outcomes;Patients;Play;Production;Recovery;regenerative;Regulation;Regulator Genes;Repression;Resolution;restoration;restraint;RNA;Role;Signal Induction;Signal Transduction;single-cell RNA sequencing;Skin wound healing;Stimulus;Stroke;System;Tail;targeted treatment;Testing;Therapeutic;therapeutic evaluation;therapeutic target;Tissue Sample;Tissues;transcription factor;treatment strategy;United States National Institutes of Health;uptake;Vascular Endothelial Growth Factor C;Vascular Endothelial Growth Factor Receptor-3;Vascular System;VEGFC gene

PROJECT_TITLE: Molecular Mechanisms Controlling Lymphatic Vascular Function in Health and Disease

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


ADMINISTERING_IC: DC

ED_INST_TYPE: SCHOOLS OF EDUCATION

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Behavioral and Social Science;Caregiving Research;Clinical Research;Clinical Trials and Supportive Activities;Pediatric;Prevention

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Project Narrative Over 1.4 million children in the US have diagnosed reading difficulties, and children with developmental language disorder (DLD) are highly susceptible. Caregiver-implemented interventions, such as the STAR intervention of focus in this study, are critical to accelerating the early-literacy growth of young children with DLD as early as possible in order to reduce risks for reading difficulties.

PI_NAMEs: BOSTER, JAMIE BETH;HUTTON, JOHN S.;JUSTICE, LAURA M. (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: 4 year old;Acceleration;Address;Adult;Affect;Audiotape;behavior change;blind;Buffers;Caregiver support;Caregivers;Child;Classification;Cognitive;design;Development;Diagnosis;disability;dosage;Dose;Early Intervention;Exhibits;experience;Exposure to;Family;first grade;Future;Growth;Home;implementation barriers;improved;Incidence;interest;Intervention;intervention effect;Intervention Studies;kindergarten;Knowledge;Language;Language Development Disorders;Learning;learning strategy;literacy;Low income;Manuals;Mediating;National Institute on Deafness and Other Communication Disorders;Outcome;Pattern;post intervention;Predisposition;Preschool Child;Printing;Randomized, Controlled Trials;Reader;Reading;reading difficulties;Research;Research Design;Rewards;Risk;Risk Reduction;Self Efficacy;skills;stressor;Time;Variant

PROJECT_TITLE: Promoting Caregiver Implementation of an Effective Early Learning Intervention

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


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Immunotherapy;Pancreatic Cancer;Rare Diseases

PHR: PROJECT NARRATIVE – Project 2: Signaling Pancreatic ductal adenocarcinoma is one of the deadliest common carcinomas due, in part, to both inherent and acquired therapeutic resistance engendered by the complex crosstalk between cancer cells and the surrounding microenvironment. We will utilize a combination of in vivo and organoid co-culture models to systematically map the intricate cellular signaling networks that promote PDA survival and treatment resistance. We will then leverage our understanding of paracrine signaling to intercept key hubs in this resistance network using genetic and pharmacologic perturbation.

PROJECT_TERMS: Acceleration;Affect;Antibodies;Automobile Driving;Autophagocytosis;biobank;Blocking Antibodies;CA-19-9 Antigen;cancer cell;Cell Compartmentation;Cell membrane;Cell Proliferation;cell type;Cells;checkpoint inhibition;Chemoresistance;chemotherapy;Clinical;Coculture Techniques;Combined Modality Therapy;Common Carcinoma;Complex;conventional therapy;cytokine;Cytokine Signaling;Data;Diagnosis;Disease;Disease Resistance;Epidermal Growth Factor Receptor;Epithelial Cells;Epithelium;Epitopes;experimental study;Family;Fibroblasts;Genes;Genetic;Genetically Engineered Mouse;glycosylation;Growth;Heterogeneity;Human;IL6 gene;Immune;Immune checkpoint inhibitor;in vivo;Intercept;Kinetics;KRAS2 gene;leukemia inhibitory factor receptor;LIF gene;loss of function;Malignant neoplasm of pancreas;Malignant Neoplasms;Maps;Mediating;Mediator;Methodology;Methods;Modeling;Molecular;mouse model;Mus;Mutation;neoplastic cell;novel;organoid transplantation;Organoids;Pancreas;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;pancreatic tumorigenesis;paracrine;Paracrine Communication;Pathway interactions;Patients;pharmacologic;Phenotype;Play;Polysaccharides;Post-Translational Protein Processing;preempt;Production;Proteins;Receptor Protein-Tyrosine Kinases;Refractory;Residual state;Resistance;Resistance development;Resolution;response;Role;Signal Pathway;Signal Transduction;Specimen;STAT3 gene;Stromal Cells;success;targeted treatment;Therapeutic;therapy resistant;Time;Tissues;TP53 gene;treatment response;treatment strategy;tumor;tumor growth;tumor microenvironment;Tumor Promotion;tumor-immune system interactions;tumorigenesis;Work

PROJECT_TITLE: Project 2: Targeting signaling networks to overcome therapeutic resistance in pancreatic cancer


NIH_SPENDING_CATS: Biotechnology;Genetics;Immunization;Immunotherapy;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Vaccine Related

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

ORG_STATE: NY

PHR: PROJECT NARRATIVE  CD8+ T cells regulate the adaptive response to infection, antitumor immunity, and autoimmunity through their remarkable ability to detect intracellular antigen and mediate potent cytotoxic functions. Further investigating mechanisms by which long-lasting immunological memory is generated remains of great significance to human health. Findings from this study will enhance our understanding of how the quality of T cell receptor signaling imprints a memory program in CD8+ T cells with important implications in the rational design of vaccine development and adoptive T cell transfer immunotherapies.

PI_NAMEs: GUILLEN, ERIK  (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: Antigens;Autoimmunity;Binding;Biological Assay;CD8-Positive T-Lymphocytes;Cells;Cellular biology;cellular transduction;Chromatin;Clonal Expansion;cytokine;cytotoxic;Data;design;differential expression;Empathy;engineered T cells;Epigenetic Process;Epitopes;Exhibits;experimental study;Flow Cytometry;Foundations;Gene Targeting;gene-editing approach;Genes;Genetic;Genetic Transcription;Genomics;Goals;Health;high dimensionality;Human;Immunize;Immunologic Memory;Immunotherapy;imprint;improved;Infection;innovation;IRF4 gene;Listeria monocytogenes;Longevity;Maintenance;Mediating;Memory;Mentorship;MHC Interaction;Modeling;mouse model;Mus;neoplastic cell;overexpression;Ovum;pathogen;Peptide/MHC Complex;Peptides;Phenotype;Physicians;Point Mutation;precursor cell;prevent;Productivity;programs;promoter;rational design;Receptor Signaling;Reporter;Research;response;Role;Scientist;self-renewal;Signal Transduction;stem cells;stemness;T cell differentiation;T cell therapy;T memory cell;T-Cell Activation;T-Cell Receptor;T-Lymphocyte;TCR Activation;Techniques;Testing;Training;transcription factor;Transgenic Organisms;Tumor Immunity;Vaccine Design;vaccine development;Vaccines;Variant;Work

PROJECT_TITLE: Impact of T cell receptor signaling on memory CD8+ T cell stemness

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F07B-U(20)]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Arthritis;Bioengineering;Biomedical Imaging;Clinical Research;Disability Research;Physical Rehabilitation;Rehabilitation

ORG_CITY: LEXINGTON

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: Project Narrative Strength deficits following transtibial amputation contribute to gait asymmetries resulting in increased risk of osteoarthritis development in the intact knee for the over 1 million individuals with limb loss in the United States. The underlying causes of muscle dysfunction leading to these negative secondary complications are poorly understood. We propose to characterize the relationships between muscle quality and strength of the quadriceps of the amputated side to resulting knee joint loading of the intact limb.

PI_NAMEs: OWEN, MEREDITH  (contact)

PROGRAM_OFFICER_NAME: NURMINSKAYA, MARIA

PROJECT_TERMS: Activities of Daily Living;Affect;Amputation;Anisotropy;Award;Biomechanics;Biomedical Engineering;career;career development;Clinical Research;clinically relevant;Collaborations;Computer Models;Data;Degenerative polyarthritis;design;Development;Devices;Diffusion Magnetic Resonance Imaging;Educational workshop;Environment;Evaluation;Event;Fellowship;Fiber;Fibrosis;Foundations;Functional disorder;functional improvement;functional outcomes;Future;Gait;Goals;Grant;Health;Image;image processing;Imaging Techniques;improved;Individual;Infiltration;Injury;insight;Institution;instrument;Intervention;Isometric Exercise;joint loading;Joints;kinematics;Kinetics;Knee;Knee joint;Length;Life;limb amputation;limb loss;Limb structure;long-term sequelae;loss of function;Lower Extremity;Magnetic Resonance Imaging;Maps;Measures;Mechanics;Medical Imaging;Mentors;Mentorship;Modeling;Morphology;Motion;Movement;Muscle;Muscle Fibers;Muscle function;muscle strength;Musculoskeletal;National Research Service Awards;novel;novel imaging technique;novel therapeutic intervention;Orthopedics;Outcome;Participant;Patient Self-Report;Postdoctoral Fellow;Property;prosthesis wearer;prosthetic socket;quadriceps muscle;Quality of life;Relaxation;research data dissemination;Research Personnel;residual limb;Risk;Scientist;Side;skill acquisition;skills;Statistical Data Interpretation;statistics;success;Surveys;Technical Expertise;Techniques;Testing;Thigh structure;Time;Tissues;Training;translational scientist;United States;Walking;Work;Writing

PROJECT_TITLE: Establishing the Relationship Between Muscle Quality and Joint Loading for Individuals with Transtibial Amputation


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Contraception/Reproduction;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Neurosciences;Patient Safety;Pediatric;Precision Medicine;Suicide

ORG_CITY: COLUMBUS

ORG_NAME: RESEARCH INST NATIONWIDE CHILDREN'S HOSP

PHR: Project Narrative This project aims to define the impact of pubertal suppression treatment in transgender youth on mental health trajectories and underlying neural systems. By comparing transgender youth who receive pubertal suppression treatment to those who do not, with repeated assessments over time, we seek to identify patterns of improvement and/or worsening in each group. The information gained from this project will inform the optimization of standard of care pubertal suppression treatment.

PI_NAMEs: CHEN, DIANE ;NELSON, ERIC E (contact);STRANG, JOHN

PROGRAM_OFFICER_NAME: MURPHY, ERIC ROUSSEAU

PROJECT_TERMS: Adolescence;Adolescent;Adolescent Development;Affective;Agonist;Amygdaloid structure;Anxiety;Attenuated;Behavior;behavioral response;Benefits and Risks;Birth;Brain;Brain region;Caring;Characteristics;Child;Cognitive;cognitive development;cohort;Data;Data Collection;Development;Dimensions;Distress;Early treatment;Emotional;Endocrine;Enrollment;Estrogens;executive function;Family;Feminization;gender dysphoria;Gender Identity;GNRH1 gene;GNRH2 gene;Gonadal Hormones;Gonadotropin Hormone Releasing Hormone;Health;health assessment;Health Benefit;high risk;Hospitals;improved;Link;Literature;Maps;Masculine;Measures;Medical Care Team;Mental Depression;Mental Health;Methods;multimodality;National Institute of Mental Health;neural;neural circuit;Neurocognitive;neurodevelopment;neuroimaging;Neuropsychology;neurotransmission;Operative Surgical Procedures;Outcome;Parents;Pattern;Pediatric Hospitals;personalized medicine;personalized predictions;Persons;Prefrontal Cortex;Process;Professional Organizations;psychologic;Puberty;puberty blocker;Quality of life;Recording of previous events;Reporting;Research Domain Criteria;response;Rewards;Risk;Sampling;secondary analysis;Severities;sex assigned;side effect;Site;social;social cognition;Societies;standard of care;Standardization;Structure of superior temporal sulcus;Substance abuse problem;substance use;suicidal;Suicide attempt;Symptoms;System;Task Performances;Testosterone;Time;transgender;treatment effect;treatment group;treatment optimization;Treatment Protocols;Ventral Striatum;Visit;Vulnerable Populations;white matter;young adult;Youth

PROJECT_TITLE: THE IMPACT OF PUBERTAL SUPPRESSION ON ADOLESCENT NEURAL AND MENTAL HEALTH TRAJECTORIES - Resubmission - 1

STUDY_SECTION: PDRP

STUDY_SECTION_NAME: Psychosocial Development, Risk and Prevention Study Section[PDRP]


FUNDING_MECHANISM: SBIR-STTR RPGS

ORG_NAME: PURACATH MEDICAL, INC.

PHR: Public Health Relevance For hospitals, including Intensive Care Units, operating rooms, emergency rooms, dialysis clinics, interventional radiology, vascular suites, and burn centers, the current Peripherally Inserted Central Catheter (PICC) connection disinfection process is a time-consuming process that relies upon strict nurse protocol and compliance for efficacy. Improper, or incomplete disinfection is a significant cause of catheter related blood stream infections (CRBSIs), which can result in sepsis and even death, as well as a costly event for the hospital or care facility since CMS will no longer reimburse hospitals for their treatment. This project proposes a therapeutic medical device to reduce CBSRIs in patients with PICCs, this reducing mortality, morbidity, and cost of care.

PI_NAMEs: FOURKAS, MICHAEL ;RASOOLY, JULIA  (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Accident and Emergency department;Adoption;Ambulatory Care Facilities;Bacteria;Blood;Blood Vessels;Burn Centers;care costs;Catheter-related bloodstream infection;Catheters;Cessation of life;Charge;Clinic;Clinical;clinical practice;Clinical Research;clinical research site;Clinical Trials;commercialization;commercialization readiness;Conduct Clinical Trials;Consumption;Contracts;cost;Data;design;Devices;Dialysis procedure;Disinfection;Distributed Systems;Educational Curriculum;Educational Materials;Effectiveness;Ensure;Equipment;Evaluation;Event;Fireflies;Funding;fungus;Goals;Grant;handheld equipment;Health care facility;Hospital Administration;Hospitals;improved;Infection;Infection Control;Intensive Care Units;Interventional radiology;Knowledge;manufacture;manufacturing systems;Medical;Medical Device;Methods;Microbe;Microbial Biofilms;Monitor;Morbidity - disease rate;mortality;Nursing Protocols;Operating Rooms;Outcome;Patients;Performance;Peripheral;Phase;prevent;printed circuit board;Process;process repeatability;Production;programs;public health relevance;Publications;Quality Control;Readiness;Reporting;Risk Reduction;Sales;sensor technology;Sepsis;Small Business Innovation Research Grant;software development;software systems;Source;ST14 gene;Stream;Surface;System;Therapeutic;Time;Training;Training and Education;ultraviolet;Ultraviolet Rays;United States National Institutes of Health;Validation

PROJECT_TITLE: Therapeutic UV Disinfection System to Prevent Catheter Related Bloodstream Infections (CRBSIs) in Patients with Peripherally Inserted Central Catheters (PICCs)


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Digestive Diseases;Genetics;Orphan Drug;Pancreatic Cancer;Rare Diseases

PHR: PROJECT NARRATIVE – Project 3: Autophagy Therapeutic resistance in pancreatic ductal adenocarcinoma (PDA) is driven, in part, by metabolic adaptations that support tumor cell survival, including the upregulation of autophagy. Here, we use a combination of genetic and pharmacological tools to define how activation of the AMPK autophagy pathway in both tumor and stromal compartments contributes to PDA development and drug responses. In addition, proposed experiments will determine the efficacy of new autophagy-selective inhibitors in treating PDA and in overcoming resistance to clinical therapeutics.

PI_NAMEs: SHAW, REUBEN  (contact)

PROJECT_TERMS: Address;Adenocarcinoma;Affect;Alanine;antagonist;Attenuated;Automobile Driving;Autophagocytosis;Autophagosome;Biochemical;Biological Availability;Cell Compartmentation;Cell Nucleus;Cell Physiology;Cell Survival;Cells;Characteristics;checkpoint inhibition;Chemoresistance;chemotherapy;Chloroquine;Clinic;Clinical;Collaborations;defined contribution;Desmoplastic;Development;Disease;Disease Progression;DNA Damage;Duct (organ) structure;effective therapy;efficacy evaluation;Enzymes;Epigenetic Process;epigenetic regulation;Epithelial Cells;Epithelium;experimental study;Fibroblasts;FRAP1 gene;Gene Expression;Genetic;Genetic Transcription;Genetically Engineered Mouse;Growth;HDAC3 gene;Histone Deacetylase;Human;in vivo;inhibition of autophagy;inhibitor;kinase inhibitor;Knowledge;KPC model;Lesion;Malignant neoplasm of pancreas;Malignant Neoplasms;Measures;Mediating;Mediator;MEK inhibition;MEKs;Metabolic;Metabolic stress;Metabolism;Modality;mouse model;mTOR inhibition;Mus;Mutation;Myelogenous;neoplastic cell;Normal Cell;novel;novel strategies;Nutrient;Nutrient availability;Organelles;Organoids;Pancreas Transplantation;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma model;pancreatic neoplasm;Paracrine Communication;Pathway interactions;Performance;Pharmaceutical Preparations;pharmacologic;Phenotype;Phosphorylation;Phosphotransferases;Population;programs;Proteins;Recycling;Regulation;Reporter;Reporting;Research;Resistance;response;Role;Signal Transduction;Source;Stress;Stromal Cells;synergism;targeted treatment;Therapeutic;therapeutic target;therapy resistant;tool;Toxic effect;transcriptional reprogramming;Translating;treatment response;treatment strategy;tumor;tumor growth;tumor microenvironment;tumor progression;Up-Regulation;Vascularization;Work;Xenograft procedure

PROJECT_TITLE: Project 3: The AMPK Autophagy Pathway as a Metabolic Liability in Pancratic Ductal Adenocarcinoma


NIH_SPENDING_CATS: Biotechnology;Brain Cancer;Brain Disorders;Cancer;Neurosciences;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: CHICAGO

ORG_NAME: LURIE CHILDREN'S HOSPITAL OF CHICAGO

ORG_STATE: IL

PHR: The success of our proposed study will have broad impact on pediatric CNS tumors, particularly glioblastoma, DIPG, medulloblastoma and ependymoma. Completion of our study will provide strong preclinical rationale to support the initiation of clinical trials of 6-10 drugs per year.

PI_NAMEs: LI, XIAONAN  (contact)

PROGRAM_OFFICER_NAME: OLKHANUD, PUREVDORJ BALJINNYAM

PROJECT_TERMS: animal facility;Animal Model;Animals;Autopsy;Biological Assay;Biological Models;Brain;Brain Neoplasms;Breeding;Cancer Etiology;Cancer Patient;cancer therapy;cell bank;cell killing;Cells;Central Nervous System Neoplasms;Childhood;Childhood Brain Neoplasm;childhood cancer mortality;Childhood Central Nervous System Neoplasm;Childhood Glioblastoma;Clinic;Clinical;Clinical Drug Development;Clinical Trials;clinically relevant;cohort;cost effective;Cryopreservation;data mining;Databases;Diagnosis;Diffuse intrinsic pontine glioma;DNA;DNA methylation profiling;Dose;drug action;drug candidate;Drug Screening;drug testing;efficacy evaluation;Ensure;Ependymoma;experience;Faculty;Funding Opportunities;Gene Expression;Glioblastoma;Glioma;Goals;Grant;Histopathology;Human;Implant;implantation;In Vitro;in vivo;in vivo evaluation;Injections;Institution;Investigational Drugs;Laboratories;Location;medical schools;Medulloblastoma;member;Modeling;Molecular;Molecular Abnormality;molecular modeling;molecular subtypes;Molecular Target;mouse model;Mus;neoplastic cell;New Agents;new therapeutic target;NOD/SCID mouse;novel;novel anticancer drug;novel therapeutics;Operative Surgical Procedures;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Positioning Attribute;pre-clinical;Preclinical Testing;Primary Neoplasm;programs;protein biomarkers;radioresistant;Recurrent tumor;Relapse;Resistance;response;RNA;SCID Mice;screening;Series;Serum-Free Culture Media;Specimen;success;System;Techniques;Testing;therapeutic evaluation;therapeutic target;Time;Transplantation;Treatment Efficacy;tumor;tumor xenograft;tumorigenic;Universities;Xenograft Model;Xenograft procedure

PROJECT_TITLE: In vivo Drug Testing of Pediatric CNS Tumors Using Patient Derived Orthotopic Xenograft Models