NIH_SPENDING_CATS: Cancer

ORG_CITY: STANFORD

ORG_DEPT: PHARMACOLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Kinases have been implicated in almost all cellular processes and are attractive targets in the development of cancer therapeutics, with most drugs depending on kinase inhibition to achieve their therapeutic effect. This grant aims to expand on our previous efforts towards a novel mode of action for protein modulation – Targeted Protein Degradation – which induces complete elimination of the target protein from the cancer cell and thereby not only targets kinase catalytic activity but also important scaffolding functions. To accomplish this, we will develop novel small molecule degrader scaffolds and compound libraries in addition to elevating our compound characterization efforts to increase coverage of the degradable kinome and our understanding of degrading and non-degrading complexes, and we will further introduce the development of non-degrading glue molecules as new drugs for the modulation of (pseudo)kinase activity.

PI_NAMEs: FISCHER, ERIC SEBASTIAN;GRAY, NATHANAEL SCHIANDER (contact)

PROGRAM_OFFICER_NAME: FU, YALI

PROJECT_TERMS: Applications Grants;Automobile Driving;Biochemical;Bioinformatics;Biological Assay;Biology;Bypass;cancer cell;Cancer Model;cancer therapy;cancer type;cell growth;Cell Lineage;Cell Physiology;Chemicals;chemoproteomics;Clinical;Communities;community engagement;Complex;Credentialing;crowdsourcing;Data;Data Set;Databases;design;Development;Drug Modulation;Epidermal Growth Factor Receptor;ERBB2 gene;ERBB3 gene;FRAP1 gene;Funding;Geometry;Glues;Goals;Grant;Heterodimerization;improved;Induced Mutation;inhibitor;interest;IRAK4 gene;kinase inhibitor;Libraries;Ligands;Ligase;Malignant Neoplasms;MDM2 gene;Mediating;Meta-Analysis;Methods;Molecular;multicatalytic endopeptidase complex;Natural Products;neoplastic cell;novel;novel therapeutic intervention;novel therapeutics;Oncogenic;open source;Pathway interactions;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phosphotransferases;protein complex;protein degradation;Protein Degradation Induction;Protein Kinase;protein protein interaction;Proteins;Proteomics;prototype;public database;rational design;recruit;Reporting;Research;Resistance;Resources;response;scaffold;Series;Signal Pathway;Signal Transduction;Sirolimus;Site;small molecule;small molecule inhibitor;Therapeutic;Therapeutic Effect;tool;treatment response;tumor;Ubiquitin;ubiquitin-protein ligase;Ubiquitination;Update;Work

PROJECT_TITLE: Degrading therapeutically important kinases using small molecules

STUDY_SECTION: DMPC

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology C Study Section[DMPC]


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

ORG_CITY: PHILADELPHIA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_FIPS: US

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: Project Narrative Malaria remains a major health problem in the world with over 230 million cases and 627,000 deaths each year. Antimalarial drugs are the mainstay for controlling malaria and the mitochondrion of the malaria parasite is a validated target for existing drugs as well as those in development. This project aims to derive a deeper understanding of mitochondrial functions in malaria parasites to identify additional vulnerable targets for novel antimalarial compounds.

PI_NAMEs: VAIDYA, AKHIL B (contact)

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: Address;Adoption;Anabolism;Anti-malarials;asexual;ATP phosphohydrolase;Award;Biochemical;Biogenesis;Blood;Bypass;Cessation of life;Collaborations;Complex;Cryo-electron tomography;Cryoelectron Microscopy;Cryptosporidium;Development;Electron Transport;Electron Transport Complex III;Eukaryota;Event;Evolution;Family;Fluorescence;Funding;Gene Modified;Genes;Genetic;Genetic Complementation Test;genetic manipulation;Genome;Grant;Growth;Health;Human;Image;In Situ;Insecta;insight;interest;Investigation;Ions;knock-down;Laboratories;Life Cycle Stages;Malaria;Metabolic;Metabolism;metabolomics;Mitochondria;Mitochondrial DNA;Mitochondrial Proteins;mung bean;Mutagenesis;Nature;novel;novel strategies;Nuclear;Organelles;Organism;Orthologous Gene;Paramecium;Parasites;pathogen;Pennsylvania;Peptide Hydrolases;Personal Satisfaction;Pharmaceutical Preparations;Physiology;Planet Earth;Plasmodium;Plasmodium falciparum;Probability;Proteins;Proteomics;Pyrimidine;Regulation;Research Personnel;Ribosomal RNA;Role;Structure;System;Testing;Toxoplasma;Universities;Work

PROJECT_TITLE: Mitochondrial Functions in Malaria Parasites

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


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Cancer;Colorectal Cancer;Digestive Diseases;Infectious Diseases

ORG_CITY: COLLEGE STATION

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

ORG_STATE: TX

PHR: PROJECT NARRATIVE  Streptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic human pathogen that is implicated in life-threatening diseases including bacteremia, infective endocarditis, and colorectal cancer. This proposal aims to investigate a novel and critical virulence mechanism to gain a better understanding of how Sgg causes diseases.

PI_NAMEs: XU, YI  (contact)

PROGRAM_OFFICER_NAME: UPADHYAY, MEENU MISHRA

PROJECT_TERMS: Animal Model;Animals;Bacteremia;Binding;Biological;Biological Markers;biotypes;Cancerous;Cardiovascular system;cell behavior;Cell Culture Techniques;Cell Physiology;Cell Proliferation;Cell surface;Cell Surface Receptors;Characteristics;Clinical;Colon;Colon Carcinoma;Colonic Neoplasms;Colorectal Cancer;comorbidity;Data;Development;Disease;Epidermal Growth Factor Receptor;Epithelial Cell Proliferation;Epithelial Cells;Epithelium;Exposure to;Extracellular Domain;Genbank;Genome;Goals;Growth Factor Receptors;Homeostasis;human disease;human pathogen;In Vitro;Infection;Infective endocarditis;Inflammatory;innovation;Intestinal permeability;Intestines;Invaded;Knowledge;Lead;Life;Ligands;Maintenance;Malignant Neoplasms;Mediating;microbial;Modeling;monolayer;mutant;novel;Outcome;pathobiont;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;Phenotype;Play;Pre-Clinical Model;Proteins;Receptor Cell;Recombinant Proteins;Recombinants;Regulation;Role;Signal Transduction;Sorting;Stimulation of Cell Proliferation;Streptococcus;Streptococcus bovis;System;Therapeutic;Tissues;trait;tumor;Tumor Burden;tumor growth;Virulence;Virulence Factors;Work

PROJECT_TITLE: Type VII secretion in Streptococcus gallolyticus pathogenesis

STUDY_SECTION: BV

STUDY_SECTION_NAME: Bacterial Virulence Study Section [BV]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Neurosciences;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Stroke

ORG_CITY: NEW YORK

ORG_DEPT: NEUROLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative: Stroke is the leading cause of adult disability in the US with the greatest burden on communities of color. It is increasingly clear that disparities in Social Determinants of Health (SDOH), produced by structural racism and discrimination, are major drivers of stroke outcomes disparities. Demonstrating improved stroke outcomes with our equity-trained SDOH Homecare Intervention Focus Team (SHIFT), in addition to showing the impact of SHIFT on a more equity-centered provider practice model, may result in a paradigm shift in the approach to treating underserved minority stroke populations and close the gap in health disparities in this and other medical conditions.

PI_NAMEs: MARSHALL, RANDOLPH S;WILLIAMS, OLAJIDE  (contact)

PROGRAM_OFFICER_NAME: SANKAR, CHERYSE A

PROJECT_TERMS: acute stroke;Address;Adult;Adverse effects;African American;African American population;African American Women;Age;aged;allostatic load;Automobile Driving;Biological;Biological Markers;Biological Models;Blood Pressure;blood pressure control;care coordination;Clinical;Clinical Trials;Cognition;Cognitive;Color;Communities;community building;Community Health Aides;Community Healthcare;community organizations;Conscious;Consolidated Framework for Implementation Research;Data;design;disability;Discipline of Nursing;Discrimination;Disparity;disparity reduction;DNA Methylation;Dose;economic disparity;Effectiveness;effectiveness/implementation design;Electronic Health Record;Epigenetic Process;Equity;Ethnic Population;food insecurity;functional outcomes;Goals;Guidelines;Health;health disparity;health inequalities;health literacy;health related quality of life;Health system;Healthcare;Healthcare Systems;Hispanic;Hospital Records;Hospitals;Housing;Human Resources;Hybrids;improved;Incidence;Individual;Institution;interest;Intervention;intervention effect;Knowledge;Length;lens;Link;Location;Measures;Mediating;Medical;men;Methods;Minority;Minority Groups;minority patient;Modeling;Morbidity - disease rate;mortality;multidisciplinary;Neighborhoods;Nurses;Occupational;Organizational Affiliation;Outcome;outcome disparities;patient home care;Patient Triage;Patient-Focused Outcomes;Patients;Physicians;Physiological;Population;post stroke;Prevention approach;preventive intervention;primary outcome;Process;process evaluation;Protocols documentation;Provider;Public Health;Race;racial disparity;Racial Equity;racial population;racism;Randomized;randomized, clinical trials;Randomized, Controlled Trials;readmission rates;Reporting;Research;Risk Factors;Risk Reduction;Role;scale up;Scientific Advances and Accomplishments;secondary outcome;Services;social;social health determinants;Social Workers;Standardization;Stroke;stroke intervention;stroke outcome;stroke patient;Stroke prevention;stroke recovery;stroke risk;stroke therapy;Structural Racism;System;telomere;Testing;Training;Transportation;treatment as usual;Trust;underserved minority;usual care arm;Work

PROJECT_TITLE: The SDOH-Homecare Intervention Focus Team (SHIFT) trial to mitigate SDOH in stroke outcomes and build community capacity

STUDY_SECTION: HSQE

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Hematology;Orphan Drug;Rare Diseases;Women's Health Research

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative Proteasome inhibitor drugs revolutionized the treatment of multiple myeloma and mantle cell lymphoma. However, the current proteasome inhibitor drugs have little efficacy in solid tumor treatment. We propose to develop novel proteasome inhibitor drugs that overcome the shortcomings and expand the anticancer spectrum of the current proteasome inhibitor drugs from hematological malignancies to solid tumors.

PI_NAMEs: LIN, GANG  (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Adverse effects;Amyloid;Animal Model;anti-cancer;anticancer activity;Antineoplastic Agents;Apoptotic;B-Lymphocytes;Biological Availability;Bortezomib;Breast Cancer Cell;Breast Cancer cell line;cancer diagnosis;Cancer Etiology;cancer therapy;Cardiovascular system;Cells;Clinical;clinical development;Clinical Trials;clinically relevant;Complex;cytotoxic;cytotoxicity;design;Development;Dose;drug candidate;Drug Kinetics;efficacy study;efficacy testing;Enzymes;Hematologic Neoplasms;Human;Hydrophobicity;improved;In Vitro;in vivo;inhibitor;inhibitor therapy;Kidney;Lactams;Lactones;lead optimization;Malignant - descriptor;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant Neoplasms;Mantle Cell Lymphoma;Mitochondria;mortality;mouse model;multicatalytic endopeptidase complex;Multiple Myeloma;Natural Products;neoplastic cell;neuroblastoma cell;Neuropathy;novel;Patients;Penetration;Peptide Hydrolases;Peptides;Peripheral Blood Mononuclear Cell;Pharmaceutical Preparations;Pharmacodynamics;Pharmacologic Substance;Plasma Cells;preference;primary amyloidosis of light chain type;Property;Proteasome Inhibition;Proteasome Inhibitor;Quality of life;Rare Diseases;Reporting;Resistance;Serine Protease;Solid Neoplasm;Specificity;stem;Stress;Structure;Structure-Activity Relationship;success;Sulfhydryl Compounds;targeted treatment;Testing;Therapeutic Index;Toxic effect;transcription factor;Transcriptional Activation;triple-negative invasive breast carcinoma;United States Food and Drug Administration;Waldenstrom Macroglobulinemia;Work;Xenograft procedure

PROJECT_TITLE: Novel proteasome inhibitors targeting both beta5 and beta2 subunits for treatment of triple negative breast cancer


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Back Pain;Biomedical Imaging;Biotechnology;Chronic Pain;Genetics;Human Genome;Neurosciences;Pain Research;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

ORG_STATE: CA

PHR: PROJECT NARRATIVE Low back pain has complex mechanism and involves multiple tissues including the spine, spinal cord and the brain. In this study we will use an in vitro model for a low back pain and in vivo bioassay, focusing on what makes one degenerative disc painful and another not. Here will utilize the human IVD tissues for single cell analysis and will to establish the mechanisms that drives specifically discogenic pain in degenerated IVDs.

PI_NAMEs: SHEYN, DMITRIY  (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: 3-Dimensional;Adult;Affect;Afferent Neurons;Age;aged;Analgesics;Anti-Inflammatory Agents;Attenuated;Axon;Behavioral;biobehavior;Biochemical;Biological Assay;Brain;Cadaver;Categories;Cell Separation;Cell surface;Cell Therapy;Cells;Coculture Techniques;Complex;cytokine;Cytoprotection;Data;Databases;Development;disability;discogenic pain;Fibrosis;Future;Goals;Growth;Hand;Height;Histology;Human;human model;human RNA sequencing;Hydrogels;IL8 gene;In Vitro;in vitro Model;in vivo;in vivo Bioassay;in vivo evaluation;induced pluripotent stem cell;Inflammation;Inflammatory;inflammatory marker;Injections;Interleukin-1 beta;Intervention;Intervertebral disc structure;intervertebral disk degeneration;Low Back Pain;Magnetic Resonance Imaging;Magnetism;Measurement;Measures;Mediating;MicroRNAs;MMP3 gene;Modeling;Molecular;Molecular Profiling;Morbidity - disease rate;Needles;Neuronal Differentiation;new therapeutic target;Nociception;Nociceptors;novel;nucleus pulposus;Operative Surgical Procedures;Opioid;overexpression;Pain;pain behavior;Pain management;pain outcome;Pain Research;Painless;Pathologic;Pathway interactions;Patients;Phenotype;Population;Population Characteristics;porcine model;prevent;Process;Property;protective effect;Publishing;Puncture procedure;radiological imaging;Rattus;regenerative;response;restoration;Role;Severities;sex;single cell analysis;single-cell RNA sequencing;Sorting;Spinal Cord;standard of care;Stress;Surface;System;targeted treatment;Testing;Therapeutic;Therapeutic Effect;therapeutic target;Tissues;transcriptome sequencing;transcriptomics;Vertebral column

PROJECT_TITLE: Studying the mechanism of discogenic low back pain induction.

STUDY_SECTION: SBSR

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


ORG_CITY: CHICAGO

ORG_DEPT: UROLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE  EZH2 is a well-known histone lysine methyltransferase and an oncogene upregulated in many types of cancer, including prostate cancer. In this project, we will investigate the novel noncanonical, Polycomb- repressive complex-independent role for EZH2 in A-to-I RNA editing via ADAR. Successful completion of this project will provide novel mechanistic insights EZH2’s novel functions beyond its lysine methyltransferase and transcription repressor activities.

PI_NAMEs: CAO, QI  (contact);CHEN, KAIFU

PROGRAM_OFFICER_NAME: MAAS, STEFAN

PROJECT_TERMS: Adenosine;adenosine deaminase;advanced prostate cancer;Affect;Area;Benign;Biological Markers;Biotechnology;BMI1 gene;cancer cell;cancer initiation;Cancer Patient;cancer type;Cancerous;cell growth;ChIP-seq;Clinical;Combined Modality Therapy;Complex;Data;Data Set;demethylation;design;Development;DNA;DNA Methylation;Enhancers;Enzymes;Epigenetic Process;epigenetic regulation;Epithelial Cells;Event;Future;gain of function;Gene Expression;Gene Silencing;Genes;Genetic;Genetically Engineered Mouse;Growth;histone methyltransferase;histone modification;Histone-Lysine N-Methyltransferase;Histones;Homologous Gene;Immunoblot Analysis;Immunoprecipitation;In Vitro;in vivo Model;inhibitor;Inosine;insight;Invaded;Investigation;knock-down;Lysine;Malignant neoplasm of prostate;Malignant Neoplasms;men;Messenger RNA;Metastatic Prostate Cancer;Methyltransferase;MicroRNAs;migration;Modification;mutant;Mutation;Neoplasm Metastasis;new therapeutic target;novel;novel therapeutics;Oncogenes;Oncogenic;Outcome;patient derived xenograft model;Patients;Pharmaceutical Preparations;Pharmacologic Substance;Play;Polycomb;Property;Prostate;prostate cancer cell;prostate cancer progression;Prostate carcinoma;Proteins;Regulation;Relapse;Reporting;Research Design;Resistance development;RNA;RNA Editing;RNA methylation;RNA Splicing;RNA Stability;Role;Sampling;Site;Solid;Solid Neoplasm;targeted treatment;Testing;The Cancer Genome Atlas;Therapeutic;therapeutic target;therapy development;therapy resistant;Time;TOP2A gene;Transcript;Transcription Repressor;transcriptome sequencing;Translations;Treatment Efficacy;tumor;tumor growth;Untranslated RNA;Variant;Work

PROJECT_TITLE: A novel role for EZH2 in A-to-I RNA editing in prostate cancer

STUDY_SECTION: GRIC

STUDY_SECTION_NAME: Gene Regulation in Cancer Study Section[GRIC]


NIH_SPENDING_CATS: Neurosciences;Regenerative Medicine

ORG_CITY: WHITE PLAINS

ORG_NAME: WINIFRED MASTERSON BURKE MED RES INST

PI_NAMEs: SAHNI, VIBHU VINODCHANDRA (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: Ablation;Adult;Affect;Amyotrophic Lateral Sclerosis;Astrocytes;Axon;axon growth;axon guidance;axon regeneration;Axotomy;CD2 gene;Cells;Central Nervous System;central nervous system injury;Cerebral Palsy;Cervical;Chest;Cicatrix;Corticospinal Tracts;Development;Environment;Event;Fostering;Foundations;gain of function;Gene Expression;gene repression;Goals;Growth;Injections;Investigation;Knowledge;Lesion;Life;loss of function;LoxP-flanked allele;Mediating;Microsurgery;Modeling;Molecular;Motor Neurons;Movement;Mus;myelination;Natural regeneration;Neocortex;Neonatal;neonatal injury;neonatal mice;Nerve Degeneration;neural;Neuronal Differentiation;Neurons;Neurosciences;novel;novel strategies;Nuclear;Outcome;overexpression;Paralysed;Play;postnatal;prevent;Process;RE1-silencing transcription factor;Recovery;regenerative;Regenerative capacity;Regulation;Research;response;Role;spasticity;Spinal;Spinal Cord;Spinal cord injury;Stroke;Testing;Time;timeline;Transcription Repressor;transcriptomics;Work

PROJECT_TITLE: Molecular regulation over the decline in long-distance corticospinal axon regenerative ability during development

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Brain Disorders;Clinical Research;Genetics;Human Genome;Neurosciences;Rare Diseases;Regenerative Medicine

ORG_DEPT: OTOLARYNGOLOGY

PHR: Narrative: Degeneration of sensory hair cells causes vestibular hypofunction. While the mammalian cochlea lacks the ability to regenerate, the vestibular organs regenerate to a limited degree. The proposed research aims to reveal the effects of ATOH1-enhanced mouse and human vestibular hair cell regeneration.

PI_NAMEs: CHENG, ALAN GI-LUN (contact)

PROGRAM_OFFICER_NAME: FREEMAN, NANCY

PROJECT_TERMS: Ablation;Acceleration;Acoustic Neuroma;Adult;Aftercare;Animal Model;Atlases;Autopsy;Bioinformatics;Biological Response Modifier Therapy;Cell Maturation;Cell Physiology;cell regeneration;Cells;Chickens;Cochlea;cohort;Cytomegalovirus;Data;Data Set;Dependovirus;Development;differential expression;Dimensions;Disease;Dizziness;Down-Regulation;Electrophysiology (science);Equilibrium;experimental study;Fetal Tissues;Functional disorder;gain of function;gene therapy;Genes;genetic signature;Glial Fibrillary Acidic Protein;Hair;hair cell regeneration;Hair Cells;Histologic;Histology;Human;Immunohistochemistry;In Situ;In Situ Hybridization;In Vitro;in vivo;in vivo Model;insight;Knowledge;Label;Maps;Mechanoreceptor Cell;Modeling;Molecular;Morphology;mouse model;Mus;Natural regeneration;Operative Surgical Procedures;Organ;Organ Donor;organ regeneration;overexpression;Patients;Preclinical Testing;promoter;Property;Proteins;Research;restoration;Sensory;Sensory Hair;single-cell RNA sequencing;Supporting Cell;Synapses;Technology;Temporal bone structure;Testing;transcription factor;transcriptome;transcriptomics;Transgenic Mice;Transgenic Organisms;Translations;Type II Hair Cell;Utricle structure;Vertebrates;Vertigo;vesicular release;Vestibular function;Vestibular Hair Cells;Vestibular inner ear;vestibular system;Work;Zebrafish

PROJECT_TITLE: Mouse and human vestibular regeneration and function

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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;Neurosciences

ORG_CITY: IRVINE

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: Project Narrative This project will investigate a topic of significance in advancing research on everyday spoken language communication in children and adults: the ability to navigate across-talker variability in human speech sounds. Although the past 40 years of research have shown that the human comprehension capacity flexibly adapts to characteristics of the input, we do not yet know what perceptual, cognitive, and neural mechanisms underlie this adaptivity. Through contrasting three major proposals and testing their predictions in large-scale perceptual experiments, our project will be the first to identify what mechanism(s) support our adaptive speech perception – knowledge critical to understanding when/why healthy perception can break down.

PI_NAMEs: KURUMADA, CHIGUSA ;XIE, XIN  (contact)

PROGRAM_OFFICER_NAME: SALO, VIRGINIA CHARLOTTE

PROJECT_TITLE: Identifying the mechanisms of adaptive speech perception

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Cancer;Data Science;Genetics;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention;Prostate Cancer;Urologic Diseases

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Prostate cancer is a leading cause of cancer death in American men, but up to 60% of patients who receive treatment may not require it as they would eventually succumb to a different health problem. The focus of this research is to investigate new methods for more accurately detecting cancer and assessing its aggression us- ing medical imaging data, histology data, genetic data, and other risk factors towards reducing overdiagnosis and overtreatment, thus preventing patients from receiving unnecessary treatment and incurring associated negative functional outcomes.

PI_NAMEs: ARNOLD, COREY WELLS (contact)

PROGRAM_OFFICER_NAME: KOHAAR, INDU

PROJECT_TERMS: Accounting;Address;Aggressive behavior;algorithm development;American;Benign;Biochemical;Biological Markers;Biopsy;Biopsy Specimen;Cancer Detection;cancer diagnosis;Cancer Etiology;cancer genetics;Cancer Patient;cancer risk;Cessation of life;Clinical;clinical biomarkers;Clinical Data;clinical decision-making;Clinical Treatment;cohort;Computational Technique;convolutional neural network;Core Biopsy;cost;Data;Data Set;Decision Making;Diagnosis;Diagnostic;digital;Disease;DNA;Evaluation;Functional Imaging;functional outcomes;Genetic;Genetic Risk;Genomics;Germ Lines;Goals;Graph;graph neural network;Health;Hematoxylin and Eosin Staining Method;Histology;Image;Image Analysis;Individual;Indolent;Institution;Intervention;large datasets;Learning;Link;Local Therapy;Magnetic Resonance Imaging;Malignant - descriptor;Malignant neoplasm of prostate;Malignant Neoplasms;Measures;Medical Imaging;men;Methods;Modeling;Monitor;Morbidity - disease rate;multi-scale modeling;multimodal data;multimodal modeling;multimodality;National Cancer Institute;network models;Nomograms;novel;novel marker;Operative Surgical Procedures;Outcome;overtreatment;patient subsets;Patients;Performance;Phenotype;Physicians;predict clinical outcome;prevent;Probability;Process;Prostate;prostate cancer model;Prostate specific antigen measurement;Prostate-Specific Antigen;Prostatectomy;Radiation therapy;Radical Prostatectomy;Rectum;Recurrence;Research;research and development;Resolution;Resources;Risk;Risk Factors;risk stratification;Sampling;screening;Screening for Prostate Cancer;Serum;serum PSA;Signal Transduction;Source;Specificity;Specimen;Stains;Testing;Tissues;tool;Training;tumor;Universities;unnecessary treatment;Washington;Work

PROJECT_TITLE: Computational Feature Profiling and Modeling for Prostate Cancer Detection and Risk Stratification

STUDY_SECTION: CDMA

STUDY_SECTION_NAME: Clinical Data Management and Analysis Study Section[CDMA]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CHICAGO

PHR: PROJECT NARRATIVE The combination of unsurpassed genetic tractability, the stereotyped organization of the tissue, and the fundamental conservation of developmental mechanisms, makes the Drosophila retina an ideal model system in which to elucidate the mechanisms that establish and maintain pattern and form during tissue morphogenesis. The discoveries resulting from our investigations will improve understanding of both normal developmental mechanisms and of how disease-associated cellular defects in a complex organ can disrupt tissue-level patterns and organ morphology.

PI_NAMEs: REBAY, ILARIA  (contact)

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TITLE: Cell-Cell Signaling In Embryonic and Retinal Development-Revised Renewal

STUDY_SECTION: BDE

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


ADMINISTERING_IC: VA

FUNDING_MECHANISM: RESEARCH CENTERS

IC_NAME: Veterans Affairs

ORG_CITY: WEST HAVEN

ORG_NAME: VA CONNECTICUT HEALTHCARE SYSTEM

ORG_STATE: CT

PHR: Approximately 60% of US Veterans with spinal cord injuries (SCI) experience clinically significant spasticity, which can disrupt rehabilitation and negatively impact quality-of-life, e.g., mobility, personal hygiene, intimate relationships. Previously, we have found that intraperitoneal (IP) injection of the FDA approved compound Romidepsin (a PAK1 inhibitor) suppresses the H-reflex in mice SCIs. In this project we will determine whether intrathecal (IT) route administration of Romidepsin reduces H-reflex hyperexcitability following SCI, as well as dendritic spine dysgenesis. [To compare safety, efficacy, and side effects of IT delivery of Romidepsin to that of IV delivery of Romidepsin (standard clinical delivery method for T-cell lymphoma in humans).] Results from this project will allow us to determine the safety and efficacy of IT administration for translational studies of Romidepsin for treatment of spasticity following SCI.

PI_NAMEs: KAUER, SIERRA DAWN (contact)

PROJECT_TERMS: Acute;Address;Afferent Neurons;Area;blood-brain barrier crossing;Catheters;Central Nervous System Diseases;central nervous system injury;Chronic;Chronic Disease;Clinical;clinically relevant;clinically significant;comparative;Data;Dendritic Spines;Development;Dose;drug action;drug candidate;Drug Delivery Systems;Effectiveness;experience;FDA approved;flexibility;Goals;H-Reflex;Health;Human;Hygiene;Inflammatory;Infusion procedures;inhibitor;Injectable;intraperitoneal;Intraperitoneal Injections;Intravenous infusion procedures;Investigational New Drug Application;Lateral;Mental Depression;Methods;Modeling;Motor Neurons;Mus;Nociception;novel therapeutics;Outcome;Outcome Measure;Pathology;Pharmaceutical Preparations;primary outcome;Quality of life;Rehabilitation therapy;Risk Reduction;Route;Safety;side effect;spasticity;Spinal;Spinal Cord;Spinal cord injury;System;T-Cell Lymphoma;Tail;translational approach;translational study;Veins;Veterans;Work

PROJECT_TITLE: Development of Long-term Intrathecal Romidepsin: A New Drug Candidate for SCI-Induced Spasticity

STUDY_SECTION: RRDS

STUDY_SECTION_NAME: Rehabilitation Research and Development SPiRE Program[RRDS]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: BOSTON

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: HARVARD MEDICAL SCHOOL

ORG_STATE: MA

PHR: Project Narrative Normal human development and survival is contingent upon rapid and accurate gene control in response to environmental and developmental signals. The proposed work will elucidate how the Integrator complex regulates signal-responsive gene expression at a mechanistic level. The importance of this knowledge is underscored by the numerous human diseased states associated with Integrator mutation and dysfunction such as cancer, neuronal and blood disorders and developmental abnormalities.

PI_NAMEs: ADELMAN, KAREN L (contact);WAGNER, ERIC J

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Acute;Address;Affect;Attenuated;Automobile Driving;Binding;Biochemical;Biochemistry;Biological Models;Biology;blocking factor;cell growth;Cell Line;Cells;Cementation;ChIP-seq;Chromatin;ciliopathy;Code;Complex;controlled release;Cues;Data;Development;developmental disease;Disease;Dissociation;DNA;Drosophila genus;Elongation Factor;endonuclease;Endoribonucleases;Enhancers;Excision;experience;experimental study;FGF3 gene;Functional disorder;functional genomics;Funding;Gene Activation;Gene Expression;Gene Expression Regulation;gene induction;gene repression;Genes;Genetic;Genetic Transcription;Genomic approach;Growth;Heavy Metals;Hematological Disease;Hematopoietic Neoplasms;Homeostasis;Human Development;human disease;Immune;improved;Inflammation;insight;Joints;Knowledge;Laboratories;Malignant neoplasm of liver;Malignant Neoplasms;malignant stomach neoplasm;Mass Spectrum Analysis;Mediating;member;Messenger RNA;migration;Modeling;Mutation;negative elongation factor;Neurodevelopmental Disorder;Neurons;Normal Cell;oxidation;Oxidative Stress;Pathway interactions;phosphoproteomics;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Positive Transcriptional Elongation Factor B;premature;Productivity;promoter;Promoter Regions;Property;protein complex;protein expression;Protein phosphatase;Proteins;Proteomics;recruit;Regulation;Repression;Research;response;RNA;RNA chemical synthesis;RNA Polymerase II;Role;Scaffolding Protein;Series;Signal Transduction;Small Nuclear RNA;Specificity;stem;Stress;stressor;synergism;System;Testing;transcription factor;transcription termination;Transcriptional Regulation;transcriptomics;Untranslated RNA;Work;Zinc Fingers

PROJECT_TITLE: Probing the specificity and activity of the metazoan Integrator complex

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

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

ORG_DEPT: NEUROSCIENCES

PHR: NARRATIVE Social memory, the process by which an individual recognizes and remembers encounters with others, is a key component of social behavior. Impairments in social memory are important contributing factors to neuropsychiatric disorders. Here we focus on the neural circuits through which the CA2 region of the hippocampus, an area critically important for social memory that has been implicated in neuropsychiatric disorders, receives social information and contributes to socially relevant learning.

PI_NAMEs: SIEGELBAUM, STEVEN A (contact)

PROGRAM_OFFICER_NAME: RANGEL GOMEZ, MAURICIO

PROJECT_TERMS: Address;Age;Animals;Area;Association Learning;base;Behavior;Behavioral;Calcium;Cholecystokinin;Classification;Code;cohort;Complex;Cues;dentate gyrus;Detection;Discrimination;Disease;Dorsal;entorhinal cortex;Epilepsy;examination questions;experience;Familiarity;Functional disorder;Genetic Diseases;Grant;Head;hippocampal pyramidal neuron;Hippocampus;Human;human disease;human model;Image;Impairment;Individual;information processing;Inherited;inhibitory neuron;insight;Interneurons;Laboratories;Lateral;Learning;Long-Term Depression;Mammals;Mediating;member;Memory;memory encoding;Memory impairment;memory recognition;mouse model;Mus;Nature;neural;neural circuit;neuromechanism;Neurons;neuropsychiatric disorder;new therapeutic target;novel;odor discrimination;Odors;optogenetics;Parvalbumins;Play;Population;Process;Property;psychiatric symptom;recruit;response;Rewards;Role;Schizophrenia;Sensory;sensory input;sex;social;Social Behavior;social deficits;Social Identification;Social Interaction;Social isolation;Source;spatial memory;Stimulus;Synapses;System;Testing;Thinness;Training;two-photon;Urine;Water

PROJECT_TITLE: Control of CA2 by its cortico-hippocampal inputs and local inhibition in social information processing and learning

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ICN-A (02)]


FUNDING_MECHANISM: OTHERS

ORG_CITY: White River Junction

ORG_NAME: WHITE RIVER JUNCTION VA MEDICAL CENTER

ORG_STATE: VT

PHR: While the VA has made considerable progress in predicting and preventing suicide for patients at the highest risk—including those who previously attempted suicide, were recently released from inpatient mental health treatment, or use opioids—no comparable achievements have been made for patients in lower-risk tiers. Indeed, even though they constitute the vast majority of VA suicide deaths, very little is known about VA patients who die by suicide but are not identified as being at high-risk by existing programs. The proposed study is highly relevant to Veterans’ health because it will advance epidemiological understanding and targeted prediction and prevention resources for these non-high-risk suicide decedents. This work would be highly scalable and could have a large positive impact on Veterans’ health by preventing suicide in patients whose risk otherwise would go undetected. The proposed research is highly relevant to the VA’s top clinical priority, aiding development of accurate and effective suicide prevention services that reach deeper into the risk pool.

PI_NAMEs: LEVIS, MAXWELL ELI JOSHUA (contact)

PROJECT_TERMS: Accounting;Achievement;Adult;Age;Area;associated symptom;Award;Big Data;Big Data Methods;career;career development;Cessation of life;Classification;classification algorithm;Clinical;Clinical Research;Clinical Sciences;Data;Data Set;data warehouse;deep learning;demographics;Development;dexterity;Education;Electronic Health Record;Epidemiology;Evaluation;evidence base;Exclusion;experience;Feeling suicidal;Future;Goals;Health;high risk;improved;Individual;innovation;Inpatients;Intervention;Investigator-Initiated Research;K-Series Research Career Programs;Location;Machine Learning;machine learning classification;machine learning method;Mental Health;Mentors;Mentorship;Modeling;Natural Language Processing;opioid use;Patients;Pharmacotherapy;Population;population based;prediction algorithm;predictive modeling;Prevention;Prevention Research;prevention service;Prevention strategy;Preventive measure;Preventive service;programs;Psychotherapy;public education;reducing suicide;Research;research and development;Research Personnel;Research Proposals;Research Support;Resources;response;Risk;Risk Factors;risk prediction model;Sampling;Services;sex;skill acquisition;skills;Societies;statistics;Structure;suicidal morbidity;suicidal patient;suicidal risk;Suicide;Suicide attempt;Suicide prevention;suicide rate;Symptoms;Testing;Text;Time;time use;Training;Treatment Efficacy;Treatment Factor;United States;United States Department of Veterans Affairs;unstructured data;Veterans;Work

PROJECT_TITLE: Using big data to develop universal and selective suicide prevention strategies

STUDY_SECTION_NAME: Special Emphasis Panel[ZRD1 MHBC-F (01)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Hematology;Nutrition

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: Project Narrative The proposed research holds significant relevance to public health because the vitamin K cycle supports blood coagulation and calcium homeostasis in vascular systems and bones, and through ferroptosis regulation, involves in cardiovascular diseases and suppresses cancers. This cycle is the target of the most commonly prescribed oral anticoagulants that are used to treat and prevent deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction. Understanding the structural and cellular mechanisms of this cycle will lead to new therapeutic strategies for treating and preventing thromboembolic disorders, bone disorders, cardiovascular diseases and cancers.

PI_NAMEs: LI, WEIKAI  (contact)

PROGRAM_OFFICER_NAME: WARREN, RONALD Q

PROJECT_TERMS: antagonist;Anticoagulants;Anticoagulation;Atherosclerosis;Basic Science;Binding;Binding Sites;Biochemical;Biology;Blood coagulation;Blood Coagulation Factor;Blood Vessels;bone;Bone Diseases;Calcium;carboxylation;Cardiovascular Diseases;Catalysis;Cells;Coagulation Process;Conus genus;Couples;Cryoelectron Microscopy;Data;Deep Vein Thrombosis;Disease;Docking;dosage;Endoplasmic Reticulum;enol;Enzymes;Foundations;Functional disorder;Glutathione;Goals;Heart failure;Hemophilia B;Hemorrhage;Homeostasis;Human;Hydroquinones;improved;in vivo;inhibitor;innovation;Knowledge;Link;Lipid Peroxidation;Lipids;Malignant Neoplasms;Mass Spectrum Analysis;Membrane;Membrane Proteins;Methods;Molecular;Molecular Conformation;molecular site;mouse model;Mutagenesis;mutant;Mutation;Myocardial Infarction;NADH dehydrogenase (ubiquinone);Natural regeneration;novel;novel therapeutic intervention;Oral;Overdose;Oxidation-Reduction;paralogous gene;Pathway interactions;Patients;pharmacologic;Physiologic calcification;Physiological Processes;Post-Translational Protein Processing;prevent;Process;Proteins;Public Health;Pulmonary Embolism;Reaction;Reduced Glutathione;reduced vitamin K;Regulation;Research;research study;Resistance;Resolution;Role;Series;Stroke;Structure;System;tautomer;Testing;Therapeutic;Vascular System;Vitamin K;vitamin K epoxide reductase;Vitamin K Reductase;Warfarin

PROJECT_TITLE: Structural and Functional Basis of the Vitamin K Cycle

STUDY_SECTION: HTBT

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Emerging Infectious Diseases;Infectious Diseases;Lung;Natural Products;Orphan Drug;Rare Diseases;Valley Fever

ORG_CITY: Boulder

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF COLORADO

ORG_STATE: CO

PHR: PROJECT NARRATIVE. Valley fever is a systemic fungal infection caused by the inhalation of the arthroconidia of two closely related dimorphic Coccidioides fungi. This project aims to develop next-generation small molecule anti-coccidioidomycosis agents, which by targeting the HOG pathway will eradicate the infection.

PI_NAMEs: WALCZAK, MACIEJ  (contact)

PROGRAM_OFFICER_NAME: LIU, BAOYING

PROJECT_TERMS: Address;Affect;analog;anti-fungal agents;Area;Arizona;Azoles;Binding;C-glycoside;Carbohydrates;Chemicals;Chronic;Clinic;Clinical;Coccidioides;Coccidioides immitis;Coccidioides posadasii;Coccidioidomycosis;Collaborations;Collection;cytotoxicity;Data;desert fever;design;drug discovery;Drug Kinetics;effective therapy;efficacy validation;Engineering;Fermentation;functional group;fungicide;fungus;Future;Generations;Glycerol;Goals;Health;Homology Modeling;Human;Hybrids;Hydro-Lyases;hydrophilicity;Hydrophobicity;improved;in silico;In Vitro;in vivo Model;Industrialization;Infection;Inhalation;inhibitor;Knock-out;Laboratories;Lead;lead candidate;Literature;Lung infections;Medical;member;Methods;Mitogen-Activated Protein Kinases;Modeling;Modification;Molecular Target;Morphogenesis;mouse model;Mus;Mycoses;Myxococcales;Natural Compound;Natural Products;next generation;novel;novel therapeutics;Oklahoma;Oral Administration;Organic Synthesis;Osmolar Concentration;Oxidative Stress;pathogenic fungus;Pathway interactions;Persons;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacokinetics and pharmacodynamics;pharmacophore;Pharmacy Schools;Phosphotransferases;Pneumonia;polyketide synthase;polyketides;pre-clinical;preclinical development;Predisposition;Preparation;programs;Property;protein-histidine kinase;Protocols documentation;Publishing;rational design;response;scale up;sensor;Site;small molecule;Soil;Solubility;Structure;tool;Toxic effect;United States;Universities;Virulence;Work

PROJECT_TITLE: Novel antifungal agents against coccidioidomycosis

STUDY_SECTION: DMPA

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology A Study Section [DMPA]


NIH_SPENDING_CATS: Arthritis;Biomedical Imaging;Osteoarthritis;Physical Injury - Accidents and Adverse Effects;Prevention

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Posttraumatic osteoarthritis is a common occurrence after joint injury such as anterior cruciate ligament rupture. Early events after joint injury response (apoptosis and inflammatory) have a synergistic crosstalk that can tip the healing response to injury into a vicious cycle of perpetuating joint damage. In this proposal we will use a novel multimodal imaging approach that allows to measure apoptosis and inflammation simultaneously on the same animal to test a novel combinatorial treatment targeting apoptosis and inflammation to reinstate joint homeostasis af ter injury.

PI_NAMEs: RUIZ GARZON, MARIA AMPARO  (contact)

PROGRAM_OFFICER_NAME: ZHENG, XINCHENG

PROJECT_TERMS: Age;Animal Model;Animals;anterior cruciate ligament rupture;Apoptosis;Apoptotic;articular cartilage;Cartilage;Cell Death;cell injury;Cells;Chondrocytes;Clinic;Clinical;Clinical Trials;combinatorial;Consensus;Contrast Media;Data;Diagnosis;Drug usage;Early Intervention;efficacy evaluation;Event;experimental study;Exposure to;Fibroblasts;folate-binding protein;Functional disorder;Future;Genes;genetic technology;healing;Histologic;Histology;Homeostasis;Human;Image;imaging approach;imaging study;In Vitro;in vivo;Inflammation;Inflammatory;Inflammatory Response;Inhibition of Apoptosis;Injury;innovation;joint injury;Joints;Knee Injuries;Knee joint;knee replacement arthroplasty;Macrophage;Magnetic Resonance Imaging;Measures;mechanical load;Mediator;Modeling;Molecular;molecular imaging;Multimodal Imaging;multimodality;novel;novel strategies;optical imaging;paracrine;Paracrine Communication;Pathologic;Pathway Analysis;Pathway interactions;Play;Population;Positron-Emission Tomography;prevent;Process;Production;Proteomics;Research;Research Design;response to injury;Role;Signal Transduction;Stimulus;Synovial Cell;Synovial Fluid;Synovial Membrane;targeted agent;Testing;Therapeutic;therapeutic development;therapeutic target;Time;Tissue-Specific Gene Expression;Tissues;tool;Tracer;transcriptome;transcriptomics;Translating;Translations;Trauma;Traumatic Arthropathy;Treatment Efficacy

PROJECT_TITLE: Imaging and therapeutic targeting of tissue crosstalk in the injured knee


ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative How excitatory and inhibitory circuits mediate neural computation in the cerebral cortex is central to understanding vision, and brain function more generally. Disruptions of the precise balance between excitation and inhibition in the cerebral cortex can lead to a variety of neurological disorders. Thus, understanding how excitatory and inhibitory circuits drive sensory perception should help reveal the underlying causes of certain neurological diseases.

PI_NAMEs: ADESNIK, HILLEL  (contact)

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TERMS: Architecture;area striata;awake;Brain;Calcium;Cells;Cerebral cortex;D Cells;Data;Dependence;Detection;Electrophysiology (science);Equilibrium;Exhibits;experimental study;extrastriate visual cortex;Feedback;Fire - disasters;flexibility;Goals;Holography;Image;imaging Segmentation;in vivo;insight;Interneurons;Knowledge;Lateral;Link;Location;Maps;Measures;Mediating;model building;Modeling;Mus;Nervous System Disorder;neural;neural circuit;Neurons;novel;object recognition;optogenetics;orientation selectivity;patch clamp;Pattern;Perception;Play;Population;postsynaptic;presynaptic;prevent;Probability;Process;Property;Pyramidal Cells;receptive field;Recurrence;response;Role;segregation;Sensory;Somatostatin;Stimulus;Synapses;Testing;two-photon;V1 neuron;Vision;Visual;Visual Cortex;visual excitation;Visual Fields;Visual Perception;visual stimulus;Work

PROJECT_TITLE: Excitation and Inhibition in Neural Circuits of the Visual Cortex

STUDY_SECTION: NBVP

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


NIH_SPENDING_CATS: Aging;Aphasia;Behavioral and Social Science;Bioengineering;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Neurosciences;Physical Rehabilitation;Rehabilitation;Stroke

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative Transcranial Magnetic Stimulation (TMS), sometimes in conjunction with Speech-Language Therapy, has been demonstrated to improve language function in subjects with chronic aphasia. We will use electrical field modeling to optimize TMS stimulation intensity in a double-blind study of continuous Theta Burst Stimulation combined with modified Constraint Induced Language Therapy as compared to sham stimulation and modified Constraint Induced Language Therapy in subjects with subacute aphasia. Additional aims are to identify anatomic, behavioral and genetic predictors of response to treatment and to identify the mechanisms underlying the beneficial effect of using network neuroscience imaging techniques.

PI_NAMEs: COSLETT, H BRANCH (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: Acquired Language Disorders;Address;Aftercare;American;Anatomy;Animals;Aphasia;behavior prediction;Behavioral;behavioral neurology;Brain;Chronic;Chronic Phase;Clinical;Cognitive;Cognitive deficits;conventional dosing;cost;Data;Data Set;disability;Double-Blind Method;efficacious treatment;electric field;Ensure;Evaluation;follow-up;Functional Magnetic Resonance Imaging;genetic predictors;Healthcare;Human;Image;Imaging Techniques;improved;Individual;insight;Intervention;Investigation;Language;Language Disorders;language outcome;Language Therapy;Left;Lesion;Location;Measures;Meta-Analysis;Middle Inferior Frontal Convolution;Modeling;MRI Scans;National Institute of Neurological Disorders and Stroke;neural;Neuroanatomy;Neurobiology;Neuronal Plasticity;neuroregulation;Neurosciences;Outcome Measure;Pathway interactions;Performance;Persons;Phase II Clinical Trials;post stroke;predicting response;Prediction of Response to Therapy;primary outcome;Probability;psychologic;Randomized;Recovery;Rehabilitation therapy;Resolution;Resources;response;Rest;Role;Site;Social isolation;Speech;Stroke;stroke-induced aphasia;Therapeutic Effect;Time;Transcranial magnetic stimulation;treatment duration;treatment effect;treatment response;United States National Institutes of Health;white matter;Work

PROJECT_TITLE: Electrical Field Guided TMS and Constraint Induced Language Therapy to TreatPost-Stroke Aphasia in the Subacute Stage


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Physical Activity;Prevention;Women's Health Research

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: In this project we propose to examine the role of longitudinal changes in physical activity (PA) diurnal patterns in the prevention of cardiovascular disease (CVD). To this end we will conduct a comprehensive analysis on longitudinal data from the Women’s Health Initiative Strong & Healthy (WHISH) accelerometry substudy with a novel functional data analysis approach based on Riemann manifold model.

PI_NAMEs: ZOU, JINGJING  (contact)

PROGRAM_OFFICER_NAME: HONG, YULING

PROJECT_TERMS: Accelerometer;Advanced Development;American;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular risk factor;Cause of Death;Cessation of life;Clinical Trials;Complex;Computer software;Data;Data Analyses;Dependence;design;Development;Dimensions;effective intervention;effectiveness evaluation;Environment;epidemiology study;Foundations;Frequencies;Goals;Guidelines;Habits;Health;Hour;Incidence;insight;Knowledge;large scale data;Link;longitudinal analysis;Longitudinal Studies;Measurement;Measures;Methodology;Methods;Modeling;novel;novel strategies;Outcome;Participant;Pattern;Physical activity;physical conditioning;physical inactivity;preservation;prevent;Public Health;Publishing;Records;Research;Research Personnel;Risk;Role;sedentary lifestyle;Source Code;statistical and machine learning;Testing;Time;tool;United States;Visit;Visualization;Women's Health

PROJECT_TITLE: Examining Longitudinal Changes in Accelerometer-Measured Physical Activity in Preventing Cardiovascular Disease with Novel Function Data Analysis Approaches

STUDY_SECTION: LHB

STUDY_SECTION_NAME: Lifestyle and Health Behaviors Study Section[LHB]


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

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Intracerebral hemorrhage is complex, has long-term significant cognitive and functional impairment, and has no proven treatment, resulting in a disproportionate disability rate and lifetime cost among stroke survivors. By employing novel cognitive outcomes methodology and neuroimaging analysis to study long-term outcomes in ICH with enhanced retention, we may accelerate understanding of the causes of cognitive impairment after ICH. In the REpeated ASSEssment of SurvivorS in IntraCerebral Hemorrhage study (REASSESS ICH), we will determine whether reduction of ICH volume with minimally invasive surgery is a critical target to reducing the risk of progressive cognitive decline, targets for residual hematoma volume and whether cerebral small vessel disease and inflammatory pathways in particular predict patients with cognitive impairment independent of gene risk scores for dementia and surgical status.

PI_NAMEs: FLAHERTY, MATTHEW ;ZIAI, WENDY C (contact)

PROGRAM_OFFICER_NAME: JANIS, SCOTT

PROJECT_TERMS: Acceleration;Acute;Address;Age;aging brain;Alzheimer's disease related dementia;Ancillary Study;Area;Atrophic;Biological Markers;Blinded;Blood Vessels;brain magnetic resonance imaging;burden of illness;Cerebral Amyloid Angiopathy;Cerebral hemisphere hemorrhage;cerebral microbleeds;Cerebral small vessel disease;Cerebrovascular system;Chronic;Clinical;Clinical Trials;Coagulation Process;Cognition;Cognitive;cognitive function;comparative;Complement;Complex;Data;Decision Making;Dementia;design;disability;Enrollment;follow-up;Functional disorder;Functional impairment;functional independence;functional outcomes;Funding;Gene Expression;Genes;Genotype;Hematoma;Hemorrhage;high risk;hypertension treatment;imaging biomarker;Impaired cognition;improved;Incidence;Inflammation;Inflammatory;Injury;insight;Intervention;Lacunar Infarctions;Lesion;Leukoaraiosis;life time cost;Longitudinal Studies;Longterm Follow-up;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Measurement;Measures;mental state;Methodology;minimally invasive;Modification;mortality;National Institute of Neurological Disorders and Stroke;neuroimaging;novel;Operative Surgical Procedures;Outcome;Parents;Participant;Pathogenesis;Pathway interactions;Patients;personalized decision;Persons;Population;Prevention;prospective;Protocols documentation;Randomized, Controlled Trials;recruit;Research;Residual state;Risk Factors;Risk Reduction;risk variant;Screening procedure;Severities;sex;Siderosis;standard of care;Standardization;stroke patient;stroke survivor;Supratentorial;Survivors;Testing;Time;tool;Validation;Vascular Dementia;Visit;White Matter Hyperintensity

PROJECT_TITLE: REpeated ASseSsmEnt of SurvivorS in ICH (REASSESS ICH)

STUDY_SECTION: ANIE

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Project Narrative The proposed work aims to identify the role of mitochondria dysfunction in the progression of chronic kidney disease. These findings will help to develop new treatments for the prevention and reversion of chronic kidney disease progression.

PI_NAMEs: LI, CHANGWEI  (contact)

PROGRAM_OFFICER_NAME: PARSA, AFSHIN

PROJECT_TERMS: Albuminuria;Base Pairing;Biological Markers;Blood;Blood Pressure;Blood specimen;Cardiovascular Diseases;Cells;Chronic Kidney Failure;Chronic Kidney Insufficiency;Clinical;clinical biomarkers;cohort;Cohort Studies;Cox Proportional Hazards Models;Data;Development;Disease Progression;DNA copy number;End stage renal failure;epidemiology study;Etiology;Event;evidence base;Fibrosis;follow-up;Frequencies;Functional disorder;Genome;hazard;Health;Hematopoiesis;heteroplasmy;Human;improved;Incidence;Inflammation;Injury to Kidney;innovation;Kidney;Life Style;Link;Lipids;Longitudinal Studies;Measurement;Measures;Mediating;Mendelian randomization;Metabolic;Methods;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Modeling;Molecular;molecular marker;mutant;Mutate;Mutation;Nature;new therapeutic target;novel;novel therapeutics;Organ;Outcome;Participant;Patients;Pharmaceutical Preparations;Play;prevent;Prevention;programs;prospective;prospective test;Proteinuria;Public Health;Publications;Publishing;Renal function;Research;Resources;Risk;Risk Factors;Role;Sample Size;Testing;therapeutic target;Time;Trans-Omics for Precision Medicine;Variant;Work

PROJECT_TITLE: The quality and quantity of mitochondrial DNA in chronic kidney disease progression

STUDY_SECTION: KEDD

STUDY_SECTION_NAME: Kidney Endocrine and Digestive Disorders Study Section[KEDD]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Cancer Genomics;Genetics;Human Genome;Neurosciences;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: Project Narrative The unique mental abilities of humans are rooted in the immensely expanded and folded neocortex, which reflects the expansion of neural progenitor/stem cells. Abnormal size or folding of the human neocortex can cause intellectual disability and other neurological disorders. By defining the mechanisms regulating neural progenitor/stem cell expansion, the proposed research will help us to understand the mechanisms underlying such disorders that are caused by genetic and other factors, including controlled substances and certain viruses.

PI_NAMEs: HAN, YOUNG-GOO  (contact)

PROGRAM_OFFICER_NAME: RIDDLE, ROBERT D

PROJECT_TERMS: Affect;ATRX gene;Automobile Driving;Autosomal recessive primary microcephaly;Behavior;Brain;Brain Neoplasms;CDK2 gene;Cell Cycle;Cell Cycle Progression;Cerebrum;Childhood;Childhood Glioma;Childhood Malignant Brain Tumor;Chromatin;Chromatin Structure;Cognition;cognitive ability;cognitive process;Complex;cyclin-dependent kinase 6;Data;Development;differential expression;Disease;epigenetic regulation;Evolution;Ferrets;fetal;Funding;Genes;Genetic;Genetic Transcription;Glial Fibrillary Acidic Protein;Glioma;Goals;Growth;Histone H3;histone modification;Histones;Human;human pluripotent stem cell;In Situ;in vivo;insight;Intellectual functioning disability;Knowledge;loss of function mutation;Mediating;Methods;Microcephaly;Modeling;Molecular;Motor;mouse model;Mus;mutant;Mutate;Mutation;Neocortex;neocortical;nerve stem cell;Nervous System Disorder;Neurodevelopmental Disorder;Neuroglia;Neurons;novel;Oncogenic;Organoids;Output;Pathway interactions;Phenotype;Phosphotransferases;Play;Process;Production;progenitor;programs;Property;Psyche structure;Radial;Recurrence;Regulation;Research;Resolution;Role;self-renewal;Sensory;SHH gene;smoothened signaling pathway;stem cell expansion;stem cell model;stem cells;Structure;Testing;TP53 gene;Transcriptional Regulation;transcriptome;transcriptomics;Tumor Suppressor Proteins;Ventricular;Virus;Wild Type Mouse

PROJECT_TITLE: Sonic Hedgehog Signaling in Neocortical Growth and Folding

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Behavioral and Social Science;Digestive Diseases;Liver Disease;Nutrition;Substance Misuse

ORG_CITY: ATLANTA

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Narrative: The project aims at understanding the pathophysiology of alcoholic ketoacidosis, a metabolic complication seen in people with alcohol use disorder. The project uses a novel mouse model for alcoholic ketoacidosis. The project also tests a pH-mediated strategy to reduce the risk of this metabolic complication.

PI_NAMEs: CHOI, INYEONG  (contact)

PROGRAM_OFFICER_NAME: MURRAY, GARY

PROJECT_TERMS: Abdominal Pain;Acidosis;Address;Admission activity;Agitation;Alcohol consumption;Alcohol dependence;alcohol reward;alcohol sensitivity;alcohol use disorder;Alcoholic Hepatitis;Alcoholic Liver Diseases;Alcohols;Animal Model;animal model development;Animals;Anion Gap;Attenuated;Behavior;beta-Hydroxybutyrate;Bicarbonates;binge drinker;Biochemical;Blood;Blood Glucose;Brain;Brain region;Cessation of life;Chronic;chronic alcohol ingestion;clinically relevant;Complication;Data;Dehydration;Development;Diagnosis;Diarrhea;Down-Regulation;Equilibrium;Exhibits;experience;Fasting;Fatty Acids;Feedback;feeding;Foundations;Functional disorder;Generations;Gluconeogenesis;Glucose;Glycogen;Goals;Heavy Drinking;Hormones;Hospitals;Human;Impairment;Inflammation;Intervention;ketogenesis;ketogenic diet;Ketone Bodies;Ketones;knock-down;Knowledge;Liver;Measures;Mediating;Metabolic;Metabolic acidosis;Metabolic Diseases;Metabolism;Modeling;Molecular Analysis;mouse model;Mus;Names;Nausea and Vomiting;Nonesterified Fatty Acids;novel;nutrition;Pathogenesis;Patients;Persons;Positioning Attribute;Predisposition;Prevention;problem drinker;Process;Production;Property;protective effect;Proteins;Protocols documentation;Reporting;Research;Rewards;Risk;Risk Reduction;Role;Sedation procedure;Sodium Bicarbonate;stressor;Tachycardia;Testing;Work

PROJECT_TITLE: Study of alcoholic ketoacidosis in mice

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Machine Learning and Artificial Intelligence

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE Using current approaches, determining the best treatments for patients with type B aortic dissection (TBAD) remains a clinical challenge. Our initial work suggests that measuring aorta blood flow with 4D flow MRI may better identify high-risk TBAD patients, and, in this proposal, we will develop more efficient imaging and data-analysis techniques to further test how 4D flow improves TBAD risk- assessment. Our overarching goal is to better understand the role of blood flow assessment in TBAD and make these techniques more broadly available in standard clinical practice.

PI_NAMEs: ALLEN, BRADLEY DAVID (contact)

PROGRAM_OFFICER_NAME: HALLER, JOHN WAYNE

PROJECT_TERMS: 4D MRI;Acceleration;Acute;Address;adverse outcome;Age;Algorithms;analysis pipeline;Angiography;Aorta;Artificial Intelligence;automated analysis;Biological Markers;Blood flow;Cessation of life;Chest;Chronic;Classification;Clinical;clinical biomarkers;clinical care;clinical decision-making;clinical practice;clinical translation;clinically relevant;cohort;convolutional neural network;cost;Data;Data Analyses;Data Set;Dedications;Development;Diameter;Dissection;Early Intervention;EFRAC;Evaluation;follow-up;Functional disorder;Gender;Genetic;genetic risk factor;Goals;Growth;hemodynamics;high risk;Hypertension;Image;imaging biomarker;Imaging Techniques;improved;in vivo;in vivo evaluation;insight;Intervention;Kinetics;Linear Regressions;Link;Location;Magnetic Resonance Imaging;Manuals;Measurement;Measures;Medical;Modeling;Morphology;Multicenter Studies;non-invasive imaging;novel;Outcome;Outcome Measure;outcome prediction;Patient Selection;patient subsets;Patient-Focused Outcomes;Patients;Physiologic pulse;Pilot Projects;pressure;prospective;Protocols documentation;Race;reconstruction;recruit;repaired;Reproducibility;Risk;Risk Assessment;Risk Factors;risk stratification;ROC Curve;Role;Rupture;Scanning;Smoking;social;standard of care;Stents;Techniques;Testing;Thrombus;Time;tool;Training;transfer learning;Translating;treatment choice;Uncertainty;Work

PROJECT_TITLE: Linking in vivo hemodynamics with outcomes in Type B aortic dissection using 4D flow MRI

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Women's Health Research

ORG_CITY: INDIANAPOLIS

ORG_DEPT: SURGERY

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: This proposal will examine a previously uncharacterized variability in biospecimen collection that impacts measurement of biomarkers in preclinical and clinical research. We recently reported that exposing biospecimens to ambient air, even for a short duration, impacts levels of key signaling molecules associated with stemness and therapeutic response compared to biospecimens that are maintained at physiologic oxygen levels of 3-5% levels (closely mimicking the in vivo oxygen tension). This study will investigate the impact of oxygen exposure on the detection and quantification of clinically relevant biomarkers such as pEGFR, pPDGFRb, and pAKT in primary breast tumor tissues and biospecimens collected from malignant ascites and pleural effusions.

PI_NAMEs: MILLER, KATHY D.;NAKSHATRI, HARIKRISHNA  (contact)

PROGRAM_OFFICER_NAME: AGRAWAL, LOKESH

PROJECT_TERMS: Address;Affect;Air;Aliquot;alpelisib;Alternative Splicing;Attention;beta catenin;Biological Assay;Biological Markers;Biology;biomarker driven;Biopsy;Breast;Breast biopsy;Breast Cancer Model;Calibration;cancer cell;Cells;Characteristics;Clinic;Clinical;clinical biomarkers;Clinical Research;clinical translation;Clinical Trials;clinically relevant;Collection;comparative;Data;Decision Making;demethylation;Detection;Development;Devices;differential expression;Disseminated Malignant Neoplasm;DNA;DNA Methylation;DNMT3a;drug discovery;drug efficacy;Drug Targeting;Engraftment;Enhancers;Ensure;Epidermal Growth Factor Receptor;epigenetic therapy;epigenome;ERBB2 gene;Evaluation;evidence base;Experimental Designs;Exposure to;Failure;Funding;Gene Expression;Hematopoietic stem cells;Human Biology;Immunohistochemistry;improved;In Situ;in vivo;inhibitor;Institution;lapatinib;LGR5 gene;malignant ascites;Malignant neoplasm of ovary;Malignant Neoplasms;Mammary Gland Parenchyma;Mammary Neoplasms;Measurement;Mediating;Messenger RNA;Methods;methylome;Non-Malignant;Normal tissue morphology;Organ;Outcome;Oxygen;Patients;Peritoneal Fluid;Pharmaceutical Preparations;Physiological;PIK3CA gene;Pilot Projects;Pleural effusion disorder;portability;pre-clinical;Pre-Clinical Model;pre-clinical research;preclinical study;preservation;Primary Neoplasm;Procedures;Process;progenitor;Proto-Oncogene Proteins c-akt;Reporting;repository;Reproducibility;Research;Research Support;Resources;response;Sampling;Science;screening;Seminal;Shock;Signal Induction;Signal Pathway;Signal Transduction;Signaling Molecule;Source;Standardization;stem cell differentiation;stemness;Stress;TACSTD1 gene;targeted treatment;Testing;Time;Tissue Banks;tissue processing;Tissues;transcriptome;transcriptomic profiling;Transgenic Mice;Transgenic Model;Transgenic Organisms;Translations;treatment response;tumor;Tumor Tissue;Tumor-Associated Process;Western Blotting;Woman;Work

PROJECT_TITLE: The impact of oxygen exposure on clinical biomarkers - an underrecognized source of pre-analytic variability

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 TCRB-J (O1)]


NIH_SPENDING_CATS: Biotechnology

PHR: Project Narrative: The Chaperone-Assisted Structure Determination (CSAD) pipeline provides novel classes of antibody-based reagents to further objectives in structural biology and membrane protein research. Membrane proteins are the principle drug targets in the pharmaceutical industry because they modulate myriad critical biological functions. The reagents produced are considerably more powerful than traditional antibodies because they can be targeted to specific sites on proteins and protein complexes and can be endowed with biological function. The CASD collaborates and services a large cohort of scientists whose interests span across multiple areas of high biomedical importance. These collaborations and the reagents that are produced are likely to lead to development of antibody-like leads that have significant therapeutic value.

PI_NAMEs: KOSSIAKOFF, ANTHONY A (contact)

PROGRAM_OFFICER_NAME: FLICKER, PAULA F

PROJECT_TERMS: Affect;Antibodies;Area;Base Sequence;Binding;Biological Assay;Biological Process;Biology;Characteristics;Charge;cohort;Collaborations;Communities;conformational conversion;Creativeness;Cryoelectron Microscopy;Crystallization;design;Development;dimer;Disease;drug development;Drug Industry;Drug Targeting;Elements;Endowment;Engineering;Epitopes;Family;Funding;Generations;Goals;Immunoglobulin Fragments;Infrastructure;insight;Integral Membrane Protein;interest;Ion Channel;Ligand Binding;Link;Maps;Measures;Membrane Proteins;method development;Methodology;Methods;Molecular;Molecular Chaperones;Molecular Conformation;Molecular Machines;Nature;novel;Parents;particle;Performance;Phage Display;Pilot Projects;Play;Productivity;Property;protein complex;Protein Dynamics;protein function;protein structure;Proteins;Reagent;receptor;Research;Research Personnel;Resistance;Resolution;RNA;RNA Recognition Motif;Scientist;Services;Site;structural biology;Structure;success;synthetic antibodies;System;Techniques;Technology;technology platform;Testing;Therapeutic;tool;virtual

PROJECT_TITLE: Chaperone-Assisted Structure Determination of Membrane Proteins

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MBBC-W (02)]


NIH_SPENDING_CATS: Cancer;Clinical Research;Genetics;Hematology;Infectious Diseases;Lymphatic Research;Lymphoma;Pediatric;Pediatric Cancer;Prevention;Rare Diseases

PHR: PROJECT NARRATIVE Disease progression associated with diagnostic delays reduces curability of endemic Burkitt Lymphoma. Earlier recognition of eBL may be facilitated by detection of EBV in blood and/or saliva, but poor specificity reduces the utility of EBV DNA as an early diagnostic marker. We propose to study a variety of specimen preparation techniques that enrich for tumor-derived EBV DNA to improve sensitivity and specificity of cell-free EBV DNA detection as an early diagnostic marker for eBL. 1

PI_NAMEs: AMBINDER, RICHARD FREDERICK (contact);XIAN, RENA

PROJECT_TERMS: Abdomen;Abdominal Mass;Affect;Africa;African;African Burkitt's lymphoma;Age;antimicrobial;Biological Assay;Biopsy;Blood;Body Fluids;Buffers;Bulky Disease;cell free DNA;Cells;Central Nervous System Diseases;Centrifugation;Characteristics;chemotherapy;Child;Clinical;Cold Chains;Collection;Communities;Country;Cyst;Cytolysis;dental abscess;Detection;Development;Diagnosis;Diagnostic;diagnostic accuracy;diagnostic assay;diagnostic biomarker;Diagnostic Specificity;diagnostic value;Disease;Disease Progression;DNA;DNA Methylation;early detection biomarkers;Early Diagnosis;Edetic Acid;Enrollment;Epithelial Cells;Epithelium;Epstein Barr Virus associated tumor;Epstein-Barr Virus latency;Epstein-Barr Virus-Related Malignant Neoplasm;Exclusion;experience;Extravasation;Future;Glycocalyx;Histologic;Histopathology;Hour;Human Herpesvirus 4;improved;Income;Individual;Inferior;innovation;Investigation;Jaw;Lymphocyte;Malaria;Malignant Childhood Neoplasm;Malignant Neoplasms;Measurement;Measures;Methods;Methylation;Monitor;Mumps;Non-Malignant;oral cavity epithelium;Outcome;Parasitic infection;Patients;Performance;Peripheral Blood Mononuclear Cell;Plasma;Preparation;Procedures;Process;Recovery;Saliva;salivary assay;Science;Screening for cancer;Sensitivity and Specificity;seropositive;sex;Specificity;Specimen;Specimen Handling;Splenomegaly;Sterility;Swelling;Symptoms;Techniques;Temperature;Testing;Time;Translating;Transportation;Transudate;Treatment Failure;Tube;tumor;tumor DNA;Tumor Lysis Syndrome;Tumor Tissue;Tumor-Derived;Uganda;viral DNA;Virion;Virus;Whole Blood

PROJECT_TITLE: Enrichment for Tumor-derived Cell-free EBV DNA: Towards a Diagnostic Assay for Endemic Burkitt Lymphoma


NIH_SPENDING_CATS: Chronic Pain;Pain Research;Prevention

ORG_CITY: PHILADELPHIA

ORG_DEPT: ORTHOPEDICS

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: Project narrative: The major risk factor associated with chronic low back and neck pain is the degenerative status of the intervertebral disc (IVD) and dystrophic mineralization significantly contributes to this pathology. Extracellular pyrophosphate, citrate and phosphocitrate are endogenous low molecular weight compounds that potently inhibit mineralization. Herein, we propose to decipher how the extracellular homeostasis of these small molecules is regulated and to explore if these endogenous compounds can be exploited therapeutically to prevent mineralization of the IVD.

PI_NAMEs: RISBUD, MAKARAND V;VAN DE WETERING, KOEN  (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Address;Affect;Aging;Animal Model;Anions;Apatites;Area;Attention;Autoimmune Diseases;Back Pain;Biological Availability;calcification;Calcium;Calcium Binding;calcium phosphate;calcium phosphate precipitation;Cardiovascular system;Cell membrane;Cells;Chronic low back pain;Circulation;Citrates;Citric Acid Cycle;Clinical;Collaborations;Connective and Soft Tissue;Connective Tissue;Data;Deposition;Diabetes Mellitus;Diphosphates;effective therapy;Environment;extracellular;Extracellular Protein;Fractionation;Genes;Goals;Health;Hepatic;High Prevalence;Homeostasis;Hydroxyapatites;In Vitro;in vivo;Individual;inhibitor;inorganic phosphate;insight;Intervertebral disc structure;intervertebral disk degeneration;Joints;Kidney Calculi;Laboratories;Ligaments;Link;Location;Malignant Neoplasms;matrix Gla protein;Mediating;Membrane Proteins;Metabolism;mineralization;Minerals;Molecular Weight;Morbidity - disease rate;mortality;Motion;mouse model;Mus;Neck Pain;nucleus pulposus;Oral;osteopontin;Pain;Pathologic;Pathology;Pathway interactions;Persons;Physiological;Plasma;Play;Positioning Attribute;prevent;Prevention;Process;Production;Proteins;Proteomics;Regulation;Research;Risk Factors;Role;Shotguns;Site;Skeleton;Skin;small molecule;socioeconomics;soft tissue;Source;Spinal;System;Techniques;Therapeutic;Therapeutic Uses;Tissues;Tooth structure;Transmembrane Transport;Trauma;Urine;Vertebral column;Vertebrates;Work;α-Fetoproteins

PROJECT_TITLE: The role of endogenous low molecular weight mineralization inhibitors in spine health

STUDY_SECTION: SBDD

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Genetics;Lung;Lung Cancer;Orphan Drug;Precision Medicine;Rare Diseases

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

PHR: PROJECT NARRATIVE KRAS-driven non-small cell lung cancer (NSCLC) remains one of the most aggressive and lethal solid tumors. Therapeutic options and outcomes for NSCLC have remained virtually unchanged over the past thirty years. Using novel CRISPR/Cas9-based genome-engineering technologies we have established a unique and rapid research program to functionally characterize lung cancer mutations and identify genotype-specific metabolic vulnerabilities that can lead to novel therapeutic approaches in KRAS-driven lung cancer.

PI_NAMEs: PAPAGIANNAKOPOULOS, THALES  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Acceleration;Affect;antagonist;Antioxidants;Biochemical;Bioenergetics;Cancer Etiology;Cancer Patient;cancer subtypes;Carbon;Carboxylesterase 1;Cells;Cessation of life;Clinical Data;Clinical Oncology;Clinical Trials;clinically relevant;CRISPR/Cas technology;Dependence;Enzymes;Genetic;genetic approach;Genetic Screening;Genetic Transcription;Genetically Engineered Mouse;Genome engineering;Genotype;Glutaminase;Glutamine;Goals;Growth;Human;Immunotherapy;inhibitor;K-ras mouse model;KRAS2 gene;KRASG12D;loss of function;loss of function mutation;Lung Adenocarcinoma;Lung Neoplasms;Malignant neoplasm of lung;Metabolic;Metabolic Pathway;Metabolism;Modeling;Molecular;Mus;mutant;Mutation;Neoplasm Metastasis;Nitrogen;Non-Essential Amino Acid;Non-Small-Cell Lung Carcinoma;novel;novel therapeutic intervention;Nutrient availability;Outcome;Pathway interactions;patient derived xenograft model;patient stratification;Patients;pharmacologic;pre-clinical;Pre-Clinical Model;precision medicine;Prodrugs;Prognosis;programs;Property;Radiation;Regulation;Research;Resistance;resistance mechanism;response;response biomarker;Role;Sampling;screening;Solid Neoplasm;standard of care;Stratification;targeted treatment;Technology;Therapeutic;treatment responders;treatment response;tumor;tumor growth;tumor microenvironment;Tumor Suppression;United States;uptake;virtual

PROJECT_TITLE: Investigating the therapeutic potential of a novel glutamine antagonist in KEAP1 mutant lung cancer

STUDY_SECTION: MCTA

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


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Bioengineering;Brain Disorders;Cerebrovascular;Neurosciences;Physical Rehabilitation;Rehabilitation;Stroke

ORG_CITY: KANSAS CITY

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because brain injuries, such as occur in stroke, leave many people with chronic motor disabilities, requiring long-term medical and institutional care. This project seeks to develop a greater understanding of the plasticity process that occurs after brain injury, specifically in the compensatory functional connections that form in uninjured regions of the brain. Information gained from this project will inform the development of new therapies, such as rehabilitative approaches designed to maximize functional recovery after brain injury.

PI_NAMEs: NUDO, RANDOLPH J. (contact)

PROGRAM_OFFICER_NAME: DOPERALSKI, ADELE ELIZABETH

PROJECT_TERMS: Activities of Daily Living;Acute;Address;Animals;Area;Behavioral;Biological Markers;Brain Injuries;Brain region;Caring;Cerebral cortex;Chronic;Clinical;Clinical Research;clinically relevant;cohort;Communication;Compensation;Complex;constraint induced movement therapy;Cross-Sectional Studies;Data;design;Development;Experimental Designs;extracellular;Functional Magnetic Resonance Imaging;functional restoration;Goals;Heterogeneity;Implant;improved;improved outcome;Individual;Infarction;Injury;innovation;Institution;Internal Capsule;Intervention;kinematics;Learning;Lesion;Limb structure;longitudinal design;Longitudinal Studies;Maps;Medical;Microelectrodes;Modeling;Molecular;Monkeys;Motivation;Motor;Motor Cortex;Motor disability;motor function recovery;motor impairment;motor recovery;Motor Skills;Movement;multi-electrode arrays;Necrosis;nerve injury;neural;Neuroanatomy;Neuronal Plasticity;Neurons;neurophysiology;nonhuman primate;novel;novel strategies;novel therapeutics;Pattern;Persons;Phase;Population;post stroke;pre-clinical;preclinical study;Procedures;Process;Protocols documentation;Public Health;Recovery;Recovery of Function;Rehabilitation therapy;Research;Research Design;response;restoration;Sensorimotor functions;Shapes;signal processing;Site;skills;software development;somatosensory;Somatosensory Cortex;Specificity;stem;Stimulus;Stratification;Stroke;stroke model;stroke rehabilitation;stroke-like episode;Structure;Subcortical Infarctions;Synaptic plasticity;Task Performances;Techniques;temporal measurement;Thalamic structure;Time;tractography;Training;United States

PROJECT_TITLE: Impact of post-stroke rehabilitation on neurophysiological dynamics


ORG_CITY: PALO ALTO

ORG_NAME: VETERANS ADMIN PALO ALTO HEALTH CARE SYS

PHR: Veterans with long-COVID experience debilitating symptoms that wax and wane over time. This results in poorer health, impaired occupational function, and reduced quality of life. Providers face increasing demands for treatment of long-COVID, yet treatment options are limited with no guidelines for optimal management of this group. Successful management of long-COVID should include a multi-modal health program that incorporates physical medicine and rehabilitation as well as mental health components. Combined aquatic exercise and cognitive training programs improve cognition, cardiorespiratory function, and mental health in older Veterans with cognitive impairment. Given this increased demand for effective treatments and the success of combined programs in healthy Veterans, it is critical to evaluate if the beneficial effects of these combined treatments extend to those suffering with long-COVID.

PI_NAMEs: FAIRCHILD, JENNIFER KACI (contact)

PROJECT_TERMS: 2019-nCoV;Address;Adherence;Adult;Adverse event;Aftercare;Age;Area;Attention;Biological;brain fog;brain health;Brain-Derived Neurotrophic Factor;Caring;Clinical Trials;clinically relevant;Cognition;Cognitive;cognitive function;cognitive training;cohort;Combined Modality Therapy;Consensus;COVID-19;COVID-19 pandemic;COVID-19 survivors;Data;debilitating symptom;Development;Educational Intervention;Educational Materials;effective intervention;effective therapy;Effectiveness;effectiveness evaluation;efficacy evaluation;Event;Exclusion Criteria;executive function;Exercise;exercise program;exercise training;experience;Face;Fatigue;Future;Genetic;Genotype;Guidelines;Health;Healthcare Systems;Impaired cognition;Impairment;improved;inclusion criteria;Infection;inflammatory marker;innovation;Intervention;Long COVID;long term consequences of COVID-19;Measurement;Measures;Mediator;Memory;Memory impairment;Mental Health;mild cognitive impairment;Minority;Modeling;multi-component intervention;multimodality;Neurologic;Neurologic Symptoms;Neuropsychology;Occupational;older adult;Outcome;Outcome Measure;Participant;Patients;Persons;Phase;Physical Exercise;Physical Fitness;Physical Medicine;Physical Rehabilitation;Physiological;Pilot Projects;pilot trial;Plasma;Population;predicting response;processing speed;programs;Provider;Quality of life;Randomized;Randomized, Controlled Trials;Recovery;recruit;Reporting;Research;retention rate;Sampling;Short-Term Memory;Signal Transduction;Single-Blind Study;Structure;success;Supervision;Symptoms;Techniques;Testing;Time;Training;Training Programs;Treadmill Tests;treatment as usual;treatment response;Veterans;Virus;VO2max;Vulnerable Populations;Walking;Water;Waxes;Work

PROJECT_TITLE: Water-based Activity to Enhance Recovery in Long COVID

STUDY_SECTION_NAME: Rehabilitation Research and Development SPiRE Program[RRDS]


NIH_SPENDING_CATS: Aging;Behavioral and Social Science;Cancer;Cancer Genomics;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Human Genome;Pediatric;Pediatric Cancer;Physical Activity;Prevention;Racial and Ethnic Minority Health Research;Rare Diseases;Rehabilitation;Sleep Research;Social Determinants of Health;Telehealth

PHR: RELEVANCE Survivors of childhood cancer experience accelerated aging with high burden of chronic health conditions (CHC) and premature mortality, hence it is critical to conduct proposed clinical aging research in this vulnerable population to improve survivorship care and quality of life for these individuals. In the current proposal, we will leverage preexisting epigenetic profiling data, and also generate additional epigenetic profiling data from stored biospecimens collected during the longitudinal follow-up of our well-established cohort of childhood cancer survivors, as well as from samples collected during two ongoing health promoting behavioral intervention trials. We will investigate how social determinants of health and health behaviors will affect the change of epigenetic age acceleration (EAA) among survivors of childhood cancer, and how the change in EAA will subsequently influence long-term health outcomes, and explore the effect of health promoting behavioral interventions on EAA and if the change pattern of EAA portends the improvement of targeted health outcomes.

PI_NAMEs: WANG, ZHAOMING  (contact)

PROGRAM_OFFICER_NAME: GALLICCHIO, LISA M

PROJECT_TERMS: accelerated epigenetic aging;Address;Adult;Aerobic;Affect;Age;age acceleration;age related;age related chronic disease;Aging;aging biomarker;anti aging;attentional control;bead chip;Behavior assessment;Behavior Therapy;Biological Aging;Black race;cancer therapy;Caring;Characteristics;childhood cancer survivor;Childhood Cancer Survivor Study;Chronic;Chronology;Clinical;Clinical assessments;clinical practice;clinical translation;Clinical Trials;Clinical Trials Design;Cognitive Therapy;cohort;Cohort Studies;Collecting Cell;Comorbid Insomnia;Control Groups;Data;Development;early onset;eHealth;Epigenetic age;epigenetic aging;Epigenetic Process;epigenetic profiling;Evaluation;exercise intolerance;experience;fitness;follow-up;Functional disorder;Funding;Future;Generations;Genetic;genome-wide;genomic locus;Germ Lines;Goals;group intervention;Health;health assessment;Health behavior;Health Promotion;healthspan;high risk;Hispanic;Home;improved;Individual;insight;Internet;internet delivery;Intervention;Intervention Trial;Late Effects;Life Cycle Stages;life span;Long-Term Survivors;Malignant Childhood Neoplasm;Malignant Neoplasms;Measures;Mediating;molecular marker;Morbidity - disease rate;mortality;Neurocognitive;Not Hispanic or Latino;novel;Outcome;Patient Care;Patient Education;Pattern;Peripheral Blood Mononuclear Cell;Phenotype;Physical Fitness;Population;Population Heterogeneity;Premature Mortality;Prevalence;prevent;programs;Quality of life;racial disparity;Randomized;rate of change;Recording of previous events;remediation;Reporting;Research;Residual state;Resources;Risk;Risk Factors;Saint Jude Children's Research Hospital;Sampling;Severities;Sleep;sleep quality;Sleeplessness;social health determinants;Survivors;survivorship;telehealth;Time;Translating;United States National Institutes of Health;Vulnerable Populations

PROJECT_TITLE: Trajectory of epigenetic aging and health outcomes in childhood cancer survivors

STUDY_SECTION: AIMR

STUDY_SECTION_NAME:
Aging, Injury, Musculoskeletal, and Rheumatologic Disorders Study
Section[AIMR]


NIH_SPENDING_CATS: Genetics;Hematology;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: Mutations in proteins that process ribonucleic acids (RNA) are highly prevalent in myelodysplastic syndromes (MDS), a chronic blood disorder that causes anemia, bleeding and risk of transforming to leukemia. This proposal seeks to understand basic mechanisms by which these mutant proteins dysregulate cellular function. This will help us develop better targeted therapies for these disorders.

PI_NAMEs: NEUGEBAUER, KARLA M;PILLAI, MANOJ M. (contact)

PROGRAM_OFFICER_NAME: GILLASPY, ALLISON

PROJECT_TERMS: Achievement;Address;Affect;Aging;Alternative Splicing;Anemia;Binding;Binding Proteins;Biogenesis;Biological Models;Biology;CD34 gene;Cell Physiology;cell type;Cells;Chromatin;Chronic;Complex;Coupling;Custom;Data;Defect;discount;Disease;disease phenotype;DNA;DNA metabolism;driver mutation;Dysmyelopoietic Syndromes;Epigenetic Process;Event;Excision;Exons;expectation;FarGo;Gene Expression;Gene Expression Process;Gene Expression Profiling;Gene Expression Regulation;Genes;Genetic Models;Genetic Transcription;Genomic Instability;Goals;Hematological Disease;Hematopoiesis;Hematopoietic;Hemorrhage;Heterozygote;Histone Deacetylase;Histones;human disease;insight;Introns;Kinetics;knock-down;Knowledge;Label;Lead;Learning;Length;Lesion;leukemia;Libraries;Life;Ligation;Mediating;Messenger RNA;Metabolic;Metabolism;Methods;Modification;Molecular;mouse model;mRNA Decay;mRNA Export;mRNA Precursor;mRNA Stability;multiplexed imaging;Mus;mutant;Mutate;Mutation;Myelogenous;Neoplasms;nonsynonymous mutation;novel;Organizational Change;Outcome;Pathogenesis;Pathway interactions;Patients;Pattern;Play;polyadenylated messenger RNA;Polyadenylation;Polymerase;Prevalence;Process;protein function;Proteins;Recurrence;replication stress;response;Reverse Transcription;Risk;RNA;RNA Polymerase II;RNA Splicing;Role;S Phase Arrest;Sampling;small hairpin RNA;Spliceosomes;SRSF2 gene;Structure;Syndrome;Tail;targeted treatment;Therapeutic;therapeutic target;Transcript;Transcription Elongation;Transcriptional Regulation;transcriptome;Translations;U2 Small Nuclear Ribonucleoprotein

PROJECT_TITLE: Altered RNA fates due to an MDS driver mutation in SF3B1


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Clinical Research;Emerging Infectious Diseases;Genetics;Infectious Diseases;Nanotechnology

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: PROJECT NARRATIVE Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE) represent a serious public health threat because they are resistant to many beta-lactam antibiotics and have spread rapidly worldwide. Predicting antibiotic resistance using whole genome sequencing-based methods may enable early identification of effective treatment options for multidrug-resistant bacteria, but accurate prediction models for antibiotics that could be used to treat ESBL-PE are currently lacking. Taking advantage of nanopore whole genome sequencing technology to comprehensively characterize bacterial genomes, this study seeks to delineate the role that mobile genetic elements (MGEs) harboring ESBL genes play in determining antibiotic resistance and whether accounting for MGEs in genomic prediction models improves detection of antibiotic resistance in ESBL-PE.

PI_NAMEs: GOMEZ-SIMMONDS, ANGELA  (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Accounting;Affect;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;Bacterial Genome;Bacterial Infections;beta-Lactam Resistance;beta-Lactamase;beta-Lactams;Biometry;carbapenem resistance;carbapenem resistant Enterobacterales;Carbapenems;Categories;Cefepime;Cefoxitin;Cells;Cephamycins;classification trees;Clinical;clinical outcome assessment;Collection;common treatment;Communicable Diseases;Complex;Data;Detection;Development;Diagnostic Procedure;diagnostic strategy;DNA Insertion Elements;Early Diagnosis;Early identification;effective therapy;Ensure;Environment;Enzymes;Escherichia coli;Extended Spectrum Beta lactamase producing Enterobacterales;Extended-spectrum β-lactamase;Gene Combinations;Gene Dosage;Gene Expression;Gene Mutation;Genes;Genetic;genetic resistance;Genome;genome sequencing;genomic predictors;Genomic Segment;Genomics;Genotype;Goals;Gram-Negative Bacteria;improved;In Vitro;Infection;Infectious Disease Epidemiology;inhibitor;Interdisciplinary Study;Least-Squares Analysis;Linear Regressions;Location;Machine Learning;Measures;Methods;Minimum Inhibitory Concentration measurement;Mobile Genetic Elements;Modeling;Molecular Biology;Multi-Drug Resistance;Multiple Bacterial Drug Resistance;nanopore;Other Genetics;pathogen;Patients;Phenotype;Piperacillin;Plasmids;Play;Population;predictive modeling;Predisposition;Proliferating;promoter;prospective;Public Health;Rapid diagnostics;Recommendation;Regimen;regression trees;Research;Research Priority;Resistance;resistance mechanism;Role;structural determinants;Structure;Tazobactam;Technology;Testing;Training;Treatment Efficacy;treatment guidelines;Urinary tract infection;Urine;VDAC1 gene;whole genome;Work

PROJECT_TITLE: Genetic factors associated with phenotypic beta-lactam resistance in extended-spectrum beta-lactamase-producing Enterobacterales

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 AIRT-J (01)]


ADMINISTERING_IC: ES

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Climate-Related Exposures and Conditions;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: COLLEGE STATION

ORG_NAME: TEXAS A&M TRANSPORTATION INSTITUTE

PHR: PROJECT NARRATIVE Concerns about adverse health effects of shipping emissions have been rising globally. The overall objective of the proposed study is to evaluate the impact of a policy/regulatory intervention to reduce shipping emissions on air quality and public health (i.e., total and cause-specific mortality and hospital admissions) using innovative Bayesian spatial multivariate receptor modeling, a causal inference method based on the concept of counterfactual outcomes and a strong study design that addresses issues of bias resulting from spatial misalignment and unmeasured confounding due to non-marine sources. We will also evaluate potential differences in the impact of the intervention among groups based on race/ethnicity, neighborhood disadvantage, sex, and age.

PI_NAMEs: PARK, EUN SUG  (contact);SYMANSKI, ELAINE

PROGRAM_OFFICER_NAME: JOUBERT, BONNIE

PROJECT_TERMS: Address;Age;Air;Air Pollution;American;Area;Cities;Climate;comparison group;Control Groups;County;Data;design;Development;disorder risk;Environmental Exposure;Ethnic Origin;Ethnic Population;expectation;fine particles;Fuel Oils;Future;General Population;Goals;Health;Health Benefit;health data;Home;Hospitalization;Hot Spot;innovation;International;Interruption;Intervention;intervention effect;Investigation;Location;Maps;marine;meetings;Methods;Mission;Modeling;Monitor;Morbidity - disease rate;mortality;National Institute of Environmental Health Sciences;neighborhood disadvantage;Nitrogen Oxides;Non-accidental;Outcome;Ozone;Particulate Matter;Persons;Play;Policies;pollutant;Pollution;Public Health;Race;racial population;receptor;Research;Research Design;Risk;Risk Estimate;Role;Scientific Advances and Accomplishments;Series;sex;Shipping;Site;Source;Sulfur;Sulfur Dioxide;Sulfur Oxides;Surface;Texas;Time;Transportation;Uncertainty;United States;United States Environmental Protection Agency;Visualization

PROJECT_TITLE: Effects of an Intervention on Shipping-Related Air Pollution and Health

STUDY_SECTION: SEDH

STUDY_SECTION_NAME: Social and Environmental Determinants of Health Study Section[SEDH]


NIH_SPENDING_CATS: Cardiovascular;Genetics;Heart Disease;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: HOUSTON

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE Cardiac conduction system (CCS) dysfunction leads to cardiac arrhythmias, a leading cause of death worldwide. With the goal to develop novel therapeutics and regenerative medicine for human patients with CCS dysfunction, we will decipher the molecular regulation mechanisms of the CCS homeostasis and repair at a single-cell level.

PI_NAMEs: WANG, JUN  (contact)

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Ablation;Adult;Arrhythmia;Biology;Cardiac;Cardiac conduction system;Cardiac Myocytes;Cardiac pacemaker;cardiogenesis;Cause of Death;Cell Cycle;Cell Death;Cell secretion;Cell Survival;Cells;Cessation of life;Characteristics;conditional knockout;Cre driver;Cytoprotection;Data;Data Set;Defect;Development;diphtheria toxin fragment A;Dissection;fetal;Fibroblasts;Fibrosis;Functional disorder;Future;Genes;Genetic;Genetic Transcription;Goals;Heart;heart function;heart rhythm;Homeostasis;Human;human embryonic stem cell;Hypoxia;Impairment;ImProv;improved;inducible Cre;Injury;innovation;insight;Ligands;Mediating;Medical;Modeling;Molecular;Morbidity - disease rate;mouse model;Multiomic Data;Mus;Mutate;Myocardial Infarction;Names;Natural regeneration;nodal myocyte;novel;novel strategies;novel therapeutics;Patients;PC4 Gene;Periodicity;Phosphorylation Site;Phosphotransferases;Play;prevent;progenitor;programs;Proliferating;Publishing;Regenerative Medicine;Regulation;repaired;Reporting;response;restoration;Role;Signal Pathway;Signal Transduction;Sinoatrial Node;Smooth Muscle;stem cell model;Structure;System;Tamoxifen;Testing;Therapeutic;therapeutic target;Tissues;Toxic effect;Transcription Coactivator;transcription factor;Transforming Growth Factor beta

PROJECT_TITLE: Genetic dissection of Cardiac Conduction System homeostasis and Repair

STUDY_SECTION: MPPA

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]


NIH_SPENDING_CATS: Cardiovascular;Diabetes;Digestive Diseases;Genetics;Heart Disease;Human Genome;Microbiome;Nutrition;Obesity;Prevention

PHR: PROJECT NARRATIVE Weight loss surgery can effectively reduce the risk of cardiovascular disease and type 2 diabetes, leading causes of illness and death in the US, but it is invasive and produces variable results. This project seeks to identify the biomarkers and pathways responsible for better cardiometabolic health after weight loss surgery. The findings may be used to develop nonsurgical methods to improve cardiometabolic health.

PI_NAMEs: THAKER, VIDHU V. (contact)

PROGRAM_OFFICER_NAME: CASTLE, ARTHUR

PROJECT_TERMS: Acids;Alternative Therapies;Amines;Aminoisobutyric Acids;Anatomy;Animals;Atherosclerosis;bariatric surgery;Behavioral;Bile Acids;Biological;Biological Markers;biomarker identification;Blood;Body Weight;Body Weight Changes;Body Weight decreased;Brain;Branched-Chain Amino Acids;Cardiometabolic Disease;cardiometabolism;Cardiovascular Diseases;cardiovascular disorder risk;Cessation of life;circulating biomarkers;Circulation;Clinical Data;cohort;Coupled;Data;Diet;differential expression;Disease;Disease remission;disorder risk;Eating;effective therapy;energy balance;Environmental Exposure;Environmental Risk Factor;Epigenetic Process;Ethnic Population;Etiology;Future;Gastrectomy;Gastric Bypass;Genes;Genetic;genetic association;Genetic Predisposition to Disease;genome wide association study;Genomics;Goals;gut microbiota;Health;high risk population;Hormones;Human;improved;Incidence;Individual;intestine surgery;Joints;Kynurenine;Lecithin;Link;Lipids;Liquid Chromatography;Literature;Mass Fragmentography;Measures;Mediating;Mediation;Mediator;Medical;Mendelian randomization;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Methods;microbiome;Modeling;Molecular;Monounsaturated Fatty Acids;Morbidity - disease rate;mortality;National Institute of Diabetes and Digestive and Kidney Diseases;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;obesity treatment;Operative Surgical Procedures;Organ;Oxides;Participant;Pathway Analysis;Pathway interactions;phenotypic data;Physiological;population based;predictive signature;Prevalence;Prevention strategy;Proteomics;Public Health;Regulation;Resolution;Risk;Risk Marker;Risk Reduction;Role;Sample Size;Sampling;Signal Pathway;Signal Transduction;small molecule;success;Testing;therapeutic target;Tissues;transcriptome;transcriptomics;Validation;Variant;Weight;Xenobiotics

PROJECT_TITLE: Defining the pathways of cardiometabolic health after weight loss


NIH_SPENDING_CATS: Congenital Structural Anomalies;Pediatric;Rare Diseases

ORG_NAME: SLOAN-KETTERING INST CAN RESEARCH

PHR: Narratives Centrosome and cilia dysfunction is prevalent in a wide range of diseases collectively called ciliopathy, including e.g. Bardet-Biedl syndrome, Joubert syndrome, Meckel-Gruber syndrome, polycystic kidney disease, and primary ciliary dyskinesia. However, how these cellular organelles form error-free from protein components scattered in the cell and what their physiological roles in most tissues remain elusive. A thorough understanding of the molecular pathways vertebrate cells employ to form and maintain the centrosome-cilium complex will allow for the development of therapeutic manipulations for some of these diseases.

PI_NAMEs: TSOU, MENG-FU BRYAN (contact)

PROGRAM_OFFICER_NAME: AINSZTEIN, ALEXANDRA M

PROJECT_TERMS: Address;Adopted;Alstrom syndrome;Amino Acids;Anabolism;appendage;Bardet-Biedl Syndrome;Biochemical;Biogenesis;Biological;Cell Cycle;Cell Extracts;Cell fusion;Cell Line;Cell Physiology;Cells;Centrioles;Centrosome;Chemicals;Cilia;ciliopathy;Complex;Cytoplasm;Defect;Disease;DNA;Evolution;fitness;Functional disorder;Genetic;genetic analysis;Genome;Higher Order Chromatin Structure;Human;human disease;Image;Individual;Information Systems;Investigation;Joubert syndrome;Lead;Left;Life;Link;Meckel-Gruber syndrome;Mitosis;Modeling;Molds;Molecular;mutant;Mutation;Nature;novel;Nucleic Acids;Organelles;Pathway interactions;Physiological;Polycystic Kidney Diseases;premature;Primary Ciliary Dyskinesias;Procentriole;Production;Protein Biosynthesis;Proteins;reconstitution;Reproducibility;restoration;RNA;Role;S phase;scaffold;self assembly;Series;Shapes;Structure;System;Testing;therapeutic development;Time;Tissues;transmission process

PROJECT_TITLE: Template-based replication of the centriole organelle

STUDY_SECTION_NAME: Cell Structure and Function 1 Study Section[CSF1]