NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Prevention;Prostate Cancer;Urologic Diseases

ORG_DEPT: UROLOGY

PHR: Prostate cancer is the most common cancer in men and the second leading cause of cancer death. Men with clinically insignificant prostate cancer are placed on active surveillance which consists or repeat laboratory analysis, imaging, and prostate biopsy until patients progress to clinically significant prostate at which point they need treatment. The objective of this proposal is to explore the use of Prostate Specific Membrane Antigen Positron Emission Tomography- Computed Tomography (PSMA-PET CT) in detecting clinically significant prostate cancer in patients on active surveillance.

PI_NAMEs: MCCLURE, TIMOTHY  (contact);NAGAR, HIMANSHU

PROGRAM_OFFICER_NAME: TANDON, PUSHPA

PROJECT_TERMS: Aging;Amalgam;Area;arm;Biological Markers;biomarker identification;Biopsy;Biopsy Specimen;Cancer Etiology;Cancer Patient;cancer risk;Cessation of life;Clinical;clinically significant;Consensus;cost;Detection;Development;Diagnosis;Diagnostic;diagnostic accuracy;diagnostic value;Emission-Computed Tomography;Enrollment;Ensure;Evaluation;Extraprostatic;FOLH1 gene;Frequencies;Genomics;Health;Heterogeneity;Histologic;Image;improved;Individual;Indolent;Infection;Intervention;Laboratories;Lesion;Localized Disease;machine learning model;Magnetic Resonance Imaging;Malignant neoplasm of prostate;Malignant Neoplasms;Measurable;Measures;men;Metastatic Prostate Cancer;Molecular;Monitor;Morbidity - disease rate;Multi-Institutional Clinical Trial;Newly Diagnosed;novel;Operative Surgical Procedures;Outcome;Pain;Pathology;patient subsets;Patients;PET/CT scan;Population;Positron-Emission Tomography;Predictive Value;prospective;Prostate;prostate biopsy;prostate cancer risk;Prostate specific antigen measurement;Protocols documentation;Radiation therapy;radiologist;radiomics;Research Personnel;Risk;Sampling;standard of care;Symptoms;Techniques;Testing;Time;tool;transcriptomics;Treatment-related toxicity;uptake;urinary;Urinary Retention;Urologist;Validation;X-Ray Computed Tomography

PROJECT_TITLE: ESCAPE - Evaluation of Prostate Specific Membrane Antigen Positron Emission Tomography-Computed Tomography in Active Surveillance for Prostate Cancer

STUDY_SECTION: IGIS

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


ADMINISTERING_IC: DK

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Aging;Infectious Diseases;Kidney Disease;Urologic Diseases

ORG_CITY: AMHERST

ORG_COUNTRY: UNITED STATES

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_FIPS: US

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

ORG_STATE: NY

PHR: Project Narrative Urinary tract infections (UTI) are among the most common healthcare-associated infections worldwide, and the urothelium is the initial site of host-microbe interactions in the urinary tract. Glycosaminoglycans (GAGs) are an important barrier against bacterial infection of the urothelium, but some common pathogens have enzymes to degrade GAGs. The proposed research is relevant to NIH’s mission to enhance health, lengthen life, and reduce illness as we will determine the contribution of GAGs and microbial GAGases to infection, urosepsis, and mortality.

PI_NAMEs: ARMBRUSTER, CHELSIE ELIZABETH (contact)

PROGRAM_OFFICER_NAME: MULLINS, CHRISTOPHER V

PROJECT_TERMS: 3-Dimensional;Age;age difference;age effect;anti-microbial drug;Antibiotics;Apical;apical membrane;Architecture;Bacteria;Bacterial Infections;Bacteriuria;Binding;Biological Assay;Bladder;Bladder mucosa;Carbon;catheter associated UTI;Catheterization;Catheters;Cells;Cellular biology;Cessation of life;Chondroitin;chondroitin sulfate glycosaminoglycan;Chondroitin Sulfates;Chondroitinases;co-infection;constitutive expression;Data;Death Rate;Disease;Enterococcus faecalis;Enzyme Kinetics;Enzymes;expression vector;Female;fitness;Future;Glycocalyx;Glycoconjugates;Glycolipids;Glycoproteins;Glycosaminoglycan Degradation Pathway;Glycosaminoglycans;Growth;Health;Health Expenditures;healthcare-associated infections;heparanase;Heparin;Heparitin Sulfate;high risk;host-microbe interactions;Human;Hyaluronic Acid;Hyaluronidase;Immune;Immune response;Immunologic Surveillance;immunoregulation;improved;Individual;Infection;Innate Immune Response;innovation;insight;Interstitial Cystitis;Intervention;Invaded;Investigation;Kidney;kidney infection;Knowledge;Life;life span;Lyase;male;Measures;Membrane;Microbe;microbial;Mission;Modeling;Monitor;Morbidity - disease rate;mortality;mouse model;multi-drug resistant pathogen;Mus;mutant;older adult;Older Population;Organ;Organism;pathogen;Pathogenesis;patient population;Patients;potential biomarker;Predisposition;prevent;Prevention;Proteoglycan;Proteus mirabilis;Publishing;receptor;recurrent infection;renal damage;Reporter;Research;Resistance;Risk;Role;Severities;Severity of illness;sex;Site;Source;Specimen;Stratum Basale;Substrate Specificity;Sulfatases;Surface;Testing;Thick;Tight Junctions;Tissues;United States National Institutes of Health;urinary;Urinary tract;Urinary tract infection;Urine;Uropathogen;Uropathogenic E. coli;Urothelium

PROJECT_TITLE: The urothelial glycosaminoglycan layer: composition and contribution to pathogen fitness during catheter-associated urinary tract infection

STUDY_SECTION: KUFD

STUDY_SECTION_NAME: Kidney and Urological Systems Function and Dysfunction Study Section[KUFD]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Congenital Structural Anomalies;Eye Disease and Disorders of Vision;Genetics;Neurosciences;Pediatric;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: SALT LAKE CITY

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Proper formation of the eye relies on an enigmatic cell-cell communication circuit called the Hedgehog pathway that is deployed repeatedly in different contexts throughout eye development, and whose malfunction results in a spectrum of human developmental eye disorders. The proposed research will teach us how the Hedgehog pathway transmits signals during eye development, laying the groundwork for new strategy to activate Hedgehog signaling in ways that are more selective and specific than existing agents. The project is relevant to the mission of the National Eye Institute because it will define the signaling pathways that direct formation of multiple eye structures, including the optic cup and retina, reveal the molecular etiology of uveal colobomas and other birth defects affecting the visual system, and advance regenerative efforts aimed at directing ocular cell types toward specific lineage decisions for targeted cell replacement therapies.

PI_NAMEs: KWAN, KRISTEN M;MYERS, BENJAMIN  (contact);TAYLOR, SUSAN S.;WAHLIN, KARL J

PROGRAM_OFFICER_NAME: WRIGHT, CHARLES BAKER

PROJECT_TERMS: 3-Dimensional;Affect;Animal Model;Animals;Binding;Biochemical;Biological;Biophysics;Catalytic Domain;Cell Communication;Cell Culture System;Cell Differentiation process;Cell Nucleus;cell replacement therapy;Cell surface;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Coloboma;Communication;Complex;Congenital Abnormality;Coupling;Cryoelectron Microscopy;Cyclic AMP-Dependent Protein Kinases;Defect;Development;Disease;drug development;Educational process of instructing;effective therapy;Erinaceidae;Etiology;Event;Eye;Eye Development;Eye diseases;eye formation;Fostering;Future;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;ganglion cell;Generations;Genes;Genetic;Genetic study;Genetic Transcription;Glean;GTP-Binding Proteins;hedgehog signal transduction;Heterotrimeric GTP-Binding Proteins;Holoprosencephaly;Human;Image;in vivo;Knowledge;Learning;Link;Microscopy;Mission;Modeling;Molecular;Morphogenesis;Muscle Development;National Eye Institute;novel;optic cup;Optic vesicle;Optics;Organoids;Output;Pathway interactions;Pattern;pharmacologic;Phosphorylation;Process;Production;protein structure;regenerative;Regenerative Medicine;Reporter;Research;Resolution;Retina;Retinal Dystrophy;Retinal Ganglion Cells;Route;Second Messenger Systems;Signal Pathway;Signal Transduction;Site;smoothened signaling pathway;spatiotemporal;Specific qualifier value;Structure;System;Therapeutic;therapeutic development;therapeutic target;transcription factor;transcriptome sequencing;transmission process;Vertebrates;Visual Fields;Visual System;Work;X-Ray Crystallography;Zebrafish

PROJECT_TITLE: Morphogenetic signaling from the cell surface to the nucleus during vertebrate eye development

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 CDB-F (02)]


ADMINISTERING_IC: HG

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

ORG_STATE: MA

PHR: NARRATIVE During development, cells are arranged into intricately structured organs that carry out the many functions of the human body. To uncover the individual roles of cells in tissue function, and to determine how cells become dysfunctional in disease, we need technologies that can measure cell states within intact tissues. This proposal will develop a technology called Slide-tags that will enable detailed measurements of cells across entire human organs, shedding light on tissue function in both normal and disease conditions.

PI_NAMEs: CHEN, FEI  (contact);MACOSKO, EVAN Z

PROGRAM_OFFICER_NAME: NOVA, IAN CURTIS

PROJECT_TERMS: Architecture;Area;Brain;Cell Nucleus;cell type;Cells;Chromatin;Clinical;Communication;Complex;Development;Disease;Dissociation;DNA Methylation;DNA Sequence;Epigenetic Process;epigenome;epigenomics;frontal lobe;Functional disorder;Gene Expression;Genetic Transcription;Genome;genomic tools;Genomics;Histopathology;Human;Human body;human disease;human tissue;imaging modality;improved;In Situ;Individual;innovation;invention;Length;Lewy Bodies;Light;Maps;Measurement;Measures;Methodology;Microscopy;Modality;Modeling;Molecular;Morphology;multimodality;multiple omics;new technology;Normal tissue morphology;Organ;Paraffin Embedding;Pathology;Pattern;Positioning Attribute;preservation;Process;Proteins;Protocols documentation;reconstruction;Recovery;Regulation;Resolution;Role;Sampling;Signal Transduction;single cell genomics;single cell technology;Slide;Somatic Mutation;Specimen;Structure;Substantia nigra structure;Surface;Surveys;Suspensions;Technology;technology platform;Tissue Embedding;Tissue imaging;Tissues;tool;transcriptome;Variant;Work

PROJECT_TITLE: A platform for scalable spatial single cell genomics

STUDY_SECTION: GCAT

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Clinical Research;Cystic Fibrosis;Lung;Orphan Drug;Rare Diseases

ORG_CITY: SAINT LOUIS

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE (RELEVANCE): We identified calcium-activated chloride channel regulator 1 (CLCA1) protein as a specific potentiator of the calcium-activated chloride channel TMEM16A, however, this channel and modulator play an underappreciated role in human airway biology, in part due to the challenges of studying the system in the setting of broader airway channel activity. Cystic fibrosis represents an ideal context to study the CLCA1-TMEM16A system in human airway disease, allowing for both the unmasked investigation of TMEM16A channel activity (in the absence of CFTR) and the opportunity to evaluate a unique potential therapeutic angle for patients unresponsive to CFTR modulator therapy. In this proposal we investigate the cellular and tissue expression patterns of TMEM16A in human disease, the potential beneficial impact of CLCA1 on TMEM16A-mediated airway function, and determine the molecular features of the CLCA1-TMEM16A interaction in order to produce the molecular framework needed to develop new therapeutics for diseases hallmarked by mucus obstruction, such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).

PI_NAMEs: ALEXANDER-BRETT, JENNIFER ;BRETT, THOMAS JOHN (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: 3-Dimensional;Address;Air;Airway Disease;Anions;antimicrobial;Asthma;Bicarbonates;Biological Assay;Biological Models;Biology;biophysical properties;Calcium;Cell Line;Cell model;Cell Nucleus;Cells;Chemosensitization;Chloride Channels;Chlorides;Chronic Obstructive Pulmonary Disease;Coculture Techniques;Compensation;Complement;Complex;Cryoelectron Microscopy;Cystic Fibrosis;cystic fibrosis airway;Cystic Fibrosis Transmembrane Conductance Regulator;Data;Development;Disease;Epithelium;Exhibits;experimental study;Family member;Fluorescent in Situ Hybridization;Functional disorder;Human;human disease;human model;Hydration status;Image;Impairment;In Vitro;insight;Integral Membrane Protein;interest;Investigation;Ion Channel;Knowledge;Limes;Liquid substance;loss of function mutation;Lung;Mediating;Modeling;Molecular;Molecular Structure;Mucociliary Clearance;Mucous body substance;multidisciplinary;National Heart, Lung, and Blood Institute;new therapeutic target;novel;novel therapeutics;Obstruction;particle;patch clamp;Patients;Pattern;Play;Population;Property;protein function;Protein Isoforms;Protein Secretion;Protein Subunits;Proteins;Regulation;Research;respiratory health;RNA Splicing;Role;Series;single nucleus RNA-sequencing;Slice;Specimen;Structure;System;targeted treatment;Testing;Therapeutic;therapeutic target;therapy development;Tissue Model;Tissues;tool;transcriptome sequencing;transcriptomics;Work

PROJECT_TITLE: TMEM16A in human airway disease

STUDY_SECTION: LCMI

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


ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Overproduction of aldosterone causes high blood pressure in ~80M people and is among the most challenging forms of high blood pressure to treat. We recently discovered three pathways that can lower aldosterone levels suggesting they may represent potential targets of future therapies. Defining the pathways that govern aldosterone regulation will provide critical insight into the mechanisms causing high BP and lead to new targeted therapies for these high-risk patients.

PI_NAMEs: BREAULT, DAVID T (contact)

PROGRAM_OFFICER_NAME: MALOZOWSKI, SAUL N

PROJECT_TERMS: Actomyosin;Adherens Junction;Adrenal Cortex;Adrenal Glands;adrenal hypertension;Affect;Aldosterone;Alleles;alpha catenin;Angiotensin II;Atomic Force Microscopy;beta catenin;blebbistatin;Cells;Complex;Cues;Data;Data Set;Development;Disease;Event;FGFR2 gene;Fibroblast Growth Factor;Fibroblast Growth Factor Receptors;Fluorescence Resonance Energy Transfer;Future;gain of function;gain of function mutation;Genes;genome wide association study;Heterozygote;High Prevalence;high risk;Homeostasis;Human;Hyperaldosteronism;Hyperplasia;Hypertension;Hypoaldosteronism;In Vitro;in vivo;inhibitor;insight;Ligands;loss of function;Maintenance;Mediating;Mediator;Metabolic;Modeling;Molecular;Morphogenesis;mouse model;Mus;new therapeutic target;novel;novel therapeutic intervention;Pathway interactions;Patients;Persons;pharmacologic;Physiological;postnatal;postnatal development;Process;Production;Proteomics;receptor;Recombinants;Regulation;Reporter;Resolution;response;Risk;risk variant;Role;Signal Pathway;Signal Transduction;Slice;Structure;Testing;therapeutic target;transcriptomics;transdifferentiation;Untranslated RNA;Up-Regulation;Variant;Western Blotting;WNT2B gene;Zona Fasciculata;Zona Glomerulosa

PROJECT_TITLE: Rosettes in Adrenal Development, Maintenance and Disease

STUDY_SECTION: ICER

STUDY_SECTION_NAME: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Clinical Trials and Supportive Activities;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE The application of machine learning to randomized clinical trials (RCTs) represents a novel avenue for developing tools to enhance precision cardiovascular care. To realize the potential of care personalization algorithms derived from RCTs to improve outcomes, the proposed investigations will develop an end-to-end strategy for model evaluation and adaption to electronic health records to facilitate real-world, pragmatic validation and implementation. This will be achieved through an empirical approach to evaluating personalized effect estimates derived from RCTs and addressing information streams in RCTs concurrently with real-world data in the electronic health record to enhance translation.

PI_NAMEs: KHERA, ROHAN  (contact)

PROGRAM_OFFICER_NAME: SHIROMA, ERIC JITSUO

PROJECT_TERMS: Address;Algorithms;Benchmarking;candidate selection;Cardiovascular system;Caring;Characteristics;Clinical;clinical care;Clinical Trials;Complex;Coronary Arteriosclerosis;Data;data modeling;Data Set;data sharing;Data Sources;design;Development;digital twin;electronic health data;Electronic Health Record;Evaluation;follow-up;Funding;generative adversarial network;generative models;Goals;Health system;Heart failure;Hospitals;Hypertension;improved;improved outcome;in silico;individual patient;individualized medicine;innovation;interoperability;Intervention;Investigation;Investigational Therapies;Learning;Machine Learning;machine learning method;Maps;Medical;Methodology;Methods;model development;model generalizability;Modeling;Natural Language Processing;novel;novel strategies;open data;Outcome;Participant;Pathway interactions;patient response;Patient-Focused Outcomes;Patients;Performance;personalized care;Persons;Phenotype;Population;pragmatic study;pragmatic trial;Process;prospective;Prospective Studies;randomized, clinical trials;Readiness;Resources;response;Stream;Testing;tool;Training;Translating;Translations;treatment effect;United States National Institutes of Health;Validation;validation studies;Work

PROJECT_TITLE: Translating Personalized Inference from Randomized Clinical Trials to Real-World Cardiovascular Care

STUDY_SECTION: CDMA

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


NIH_SPENDING_CATS: Dietary Supplements;Kidney Disease;Nutrition;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Prevention

ORG_CITY: CHARLOTTESVILLE

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE The goal of this work is to understand the role of the vitamin D pathway in the developing kidney and the mechanisms that connect vitamin D deficiency to chronic kidney disease in preterm neonates as a key component to preventing kidney disease. We will investigate the vitamin D pathway and how this pathway influences kidney development, focusing on a key cell in the kidney, the podocyte. Our findings will build the foundation for a clinical trial in preterm babies that optimizes environmental and maternal factors to reduce chronic kidney disease development in preterm babies.

PI_NAMEs: CHARLTON, JENNIFER R (contact);REIDY, KIMBERLY JEAN;SUZUKI, MASAKO

PROGRAM_OFFICER_NAME: BRUNSKILL, ERIC WAYNE

PROJECT_TERMS: Adult;Affect;Albuminuria;Animals;antagonist;Archives;Binding;Birth;Blood Pressure;Bolus Infusion;Cell Differentiation process;Cells;Chronic Kidney Failure;Clinical;clinical practice;Clinical Trials;CYP27B1 gene;density;Development;Diet;Disease;Dose;early onset;Exposure to;extreme prematurity;Face;Fatty acid glycerol esters;Formulation;Foundations;Functional disorder;Future;gastrointestinal;Gene Expression;Genetic Transcription;glomerular filtration;Goals;Health;high risk;Human;Impairment;improved;In Vitro;in vivo;Individual;Injury;Kidney;Kidney Diseases;Lung;Measures;Metabolism;Micronutrients;Modeling;Modification;Molecular;Mothers;mouse model;Mus;neonatal mice;neonate;nephrin;nephrogenesis;novel;Nuclear;Nutritional;offspring;Organ;Outcome;Pathogenesis;Pathway interactions;Perinatal;Phenotype;Placenta;placental transfer;podocyte;Pregnancy;Premature Birth;Premature Infant;preterm newborn;prevent;primary outcome;pup;Renal function;Renal glomerular disease;Reporting;Research;Resolution;Retina;Risk;risk mitigation;Role;Safety;Sampling;secondary outcome;Serum;Source;Testing;Therapeutic;transcriptome sequencing;transcriptomics;Underserved Population;United States;urinary;Vitamin D;Vitamin D Deficiency;Vitamin D supplementation;Vitamin D3 Receptor;Vitamins;Work

PROJECT_TITLE: Investigating the effect of dysregulated vitamin D metabolism on kidney development following preterm birth


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Lung;Precision Medicine;Prevention

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

ORG_STATE: PA

PHR: Interstitial lung disease (ILD), lung inflammation and or scarring, can be a mild or severe consequence of autoimmune myositis but physicians lack tools to predict myositis-ILD progression resulting in under- or overtreatment. This research project aims to develop new tools for predicting progressive myositis-ILD to aid therapeutic decision making and reduce poor outcomes.

PI_NAMEs: JOHNSON, CHEILONDA  (contact)

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: aggressive therapy;Alleles;Antibodies;Asia;Asthma;Autoimmune;Behavior;biobank;biological heterogeneity;Biological Markers;biomedical referral center;Chicago;Chronic;Chronic Obstructive Pulmonary Disease;Cicatrix;Classification;Clinical;clinical application;clinical care;Clinical Data;clinical heterogeneity;clinical predictive model;clinical predictors;clinical remission;clinically relevant;Cluster Analysis;cohort;Complication;Data;Decision Making;Disease;Disease Clusterings;disease model;Disease Outcome;Disease Progression;Disease susceptibility;disorder risk;disorder subtype;Far East;genomic data;Genomics;Genotype;Goals;Haplotypes;Heterogeneity;HLA Antigens;immunomodulatory therapies;improved;indexing;Individual;Institution;Interstitial Lung Diseases;Interstitial Myositis;Intervention;Modeling;mortality;Myositis;North America;novel;novel marker;Outcome;overtreatment;Patient Care;patient population;Patients;Pennsylvania;Performance;Phenotype;Physicians;Population;Precision therapeutics;predictive marker;predictive modeling;predictive tools;Predictive Value of Tests;prognostic model;prognostication;Progression-Free Survivals;Progressive Disease;Pulmonary Inflammation;Research Project Grants;Risk;risk prediction;risk prediction model;Sampling;Serology;Therapeutic;tool;treatment response;United States;Universities;Validation;Work

PROJECT_TITLE: Myositis-ILD Risk Prediction Models and Endotypes

STUDY_SECTION: CRD

STUDY_SECTION_NAME: Cardiovascular and Respiratory Diseases Study Section[CRD]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: LOS ANGELES

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: The proposed study (EMERGE: Early Markers of Expressive and Receptive (language) Growth in Ethnically diverse autistic toddlers) aims to follow low-income children with autism who have no words at 18 months to 30 months to determine language growth. Results of this study will inform which children, and based on changes in which measures (brain, language, or their combination) are associated with trajectories of language development in a population and developmental period we currently have little information.

PI_NAMEs: BOYD, BRIAN ANTONIO;KASARI, CONNIE L. (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: 5 year old;Address;African American;Age;Age Months;Attention;autism spectrum disorder;autism symptoms;autistic;autistic children;Behavior;behavior measurement;Behavioral;Behavioral Mechanisms;Black race;Brain;Characteristics;Child;Child Development;Child Language;Cognition;Cognitive;cognitive ability;Communities;community setting;Data;Development;Diagnosis;Disabled Children;Disadvantaged;Early Intervention;economic disparity;effective intervention;Electroencephalography;Environment;ethnic diversity;Ethnic Origin;Exhibits;Family;Frequencies;Goals;Growth;Heterogeneity;high risk;Home;Impairment;improved;Income;Individual;joint attention;Knowledge;Language;Language Delays;Language Development;language outcome;Learning;Life;Longitudinal Studies;Low income;marginalized population;Measures;minimally verbal;Minority Groups;Motor;neural;neuromechanism;non-verbal;novel;Outcome;Parents;Participant;Pathway interactions;Phenotype;Physicians;Play;Population;portability;predictive modeling;Race;racial diversity;Reporting;Research Design;research study;Risk;Sampling;School-Age Population;segregation;Sensory;Severities;skills;Social Characteristics;social communication;sociodemographics;Source;Spanish;standardize measure;Stress;System;Time;Toddler;United States National Institutes of Health;verbal

STUDY_SECTION: CPDD

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


PHR: Most common diseases and medically important traits are influenced by a combination of many genes; one of these, obesity, is a pressing public health problem for which there are still few long-term effective and safe treatments. Discovering and understanding the genetic variation that influences the risk of obesity would provide new biological clues to guide better treatments. We plan to (1) use and expand our successful studies of the genetics of human height, a model trait, to chart out the best path to expand our studies of the genetics of obesity, (2) expand our already world-leading genetic studies of obesity and height to include more diverse and informative types of genetic variation studied in larger, more diverse sets of people, and (3) use new, innovative methods that combine genetic and other large data sets to better understand the biology that is implicated by these genetic studies.

PI_NAMEs: HIRSCHHORN, JOEL N (contact)

PROGRAM_OFFICER_NAME: PAWLIKOWSKA, LUDMILA SYLWIA

PROJECT_TERMS: Acceleration;Address;Adipose tissue;Adult;Alleles;Awareness;Benchmarking;biobank;Biological;Biological Assay;Biological Factors;Biology;Body mass index;Cardiovascular Diseases;causal variant;cell type;Cessation of life;Childhood;Clinical;Code;cohort;Collaborations;Computer Analysis;computerized tools;Computing Methodologies;cost;Data;Data Set;design;Destinations;Developmental Process;Diabetes Mellitus;Disease;Disease susceptibility;Drug Targeting;effective therapy;Epidemic;exome;Frequencies;functional genomics;Funding;Genes;Genetic;genetic analysis;genetic architecture;genetic association;Genetic Enhancement;genetic resource;genetic risk factor;Genetic study;genetic variant;Genetic Variation;Genome;genome wide association study;genomic data;Genomic Segment;Genotype;Goals;Growth;Height;Heritability;Human;Human Biology;human disease;Human Genetics;improved;Individual;innovation;insight;Intervention;Investigation;Knowledge;large datasets;Letters;Linkage Disequilibrium;Malignant Neoplasms;Maps;Measures;Mediating;Medical;Metabolic;Methods;Modeling;Natural experiment;Neurons;novel;novel strategies;Obesity;obesity biomarkers;obesity genetics;obesity risk;obesity treatment;Pathway interactions;Persons;Pharmaceutical Preparations;Phenotype;phenotypic data;polygenic risk score;Polygenic Traits;Population Heterogeneity;Predisposition;Public Health;rare variant;Regulatory Element;Resistance;Resources;Risk;Risk Factors;Role;Sample Size;Sex Differences;Signal Transduction;skeletal;Surveys;Testing;Therapeutic;Tissues;tool;trait;Translating;Untranslated RNA;Variant;Waist-Hip Ratio;whole genome;Work

PROJECT_TITLE: Biological Insights from Genetic Investigation of ANthropometric Traits (GIANT) Across the Allelic Spectrum

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Genetics;Neurosciences;Rare Diseases;Sleep Research

ORG_CITY: STORRS-MANSFIELD

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

PHR: PROJECT NARRATIVE Hypocretin/orexin (H/OX) neurons in the mammalian hypothalamus are critical for coordinating fundamental behavioral states such as arousal, stress, and motivation, and their dysfunction is implicated in devastating neurological and sleep disorders, notably narcolepsy with cataplexy. This proposal will use new and innovative molecular, cellular, and behavioral techniques to dissect the synaptic signaling pathways through which H/OX neurons shape physiology and behavior. In so doing, we hope to identify targets for therapeutic intervention in treating and improving the quality of life of patients suffering from neurological and sleep disorders.

PI_NAMEs: JACKSON, ALEXANDER CHOI (contact);MARTINELLI, DAVID CHRISTOPHER

PROGRAM_OFFICER_NAME: HE, JANET

PROJECT_TERMS: Address;Adhesions;Animal Model;Architecture;Arousal;Axon;Behavior;Behavior Control;Behavioral;behavioral phenotyping;Binding;Biochemical;Biological Assay;Biology;Brain;Cataplexy;Cell-Cell Adhesion;Cells;Central Nervous System;Chronic;chronic neurologic disease;Complement;Complement 1q;Complex;conditional knockout;Data;density;design;Development;Disease;Electroencephalography;Electrophysiology (science);Epitopes;Excitatory Synapse;Fiber;Functional disorder;G-Protein-Coupled Receptors;Genetic Epistasis;Glutamates;Goals;Human;hypocretin;Hypothalamic structure;improved;In Vitro;in vivo;innovation;insight;Investigation;Knock-in Mouse;Knockout Mice;Knowledge;Lateral Hypothalamic Area;Light;Maintenance;Mediating;Messenger RNA;Metabolic;Molecular;Molecular Genetics;motivated behavior;Motivation;Muscular Atrophy;Narcolepsy;Nature;Nervous System Disorder;Neuroanatomy;neuronal pentraxin;Neurons;Neuropeptides;neuropsychiatric disorder;novel;novel marker;Nucleic Acid Regulatory Sequences;optogenetics;overexpression;paralogous gene;Pathway interactions;Patients;Phenotype;Physiological;Physiology;pointed protein;postsynaptic;presynaptic;presynaptic neurons;Presynaptic Terminals;Proteins;Publishing;Quality of life;Role;Shapes;Signal Pathway;Signal Transduction;Sleep;Sleep Disorders;Sleep disturbances;sleep regulation;Slice;Stress;Structure;superresolution microscopy;Symptoms;Synapses;Synaptic Cleft;synaptic function;Synaptic Transmission;System;targeted treatment;Techniques;Testing;Therapeutic;Therapeutic Intervention;tool;transcriptomics;Vertebrates;vigilance;Viral;Visualization;Wakefulness;Work

PROJECT_TITLE: A novel trans-synaptic adhesion complex as a regulator of hypocretin/orexin control of arousal

STUDY_SECTION: BNRS

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


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Bioengineering;Wound Healing and Care

ORG_DEPT: CHEMISTRY

ORG_NAME: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)

PHR: PROJECT NARRATIVE Hypertrophic scars arise in over 50% of all surgical procedures and 90% of burn injuries, and are physically uncomfortable and painful, as well as inflict psychological damage due to their negative cosmetic appearances. Current treatment options are limited in their scope and efficacy, as they do not target the underlying cause of scar development: a dysregulated wound healing response. Here, the sustained and localized delivery of the natural antifibrotic peptide hormone, relaxin-2, via a hydrogel, is described as a novel solution to treat both the underlying etiology and symptomatic presentation of hypertrophic scars.

PI_NAMEs: GRINSTAFF, MARK W. (contact);SCHAER, THOMAS P

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: 3-Dimensional;Actins;Address;Adrenal Cortex Hormones;Affect;analog;angiogenesis;Animals;Appearance;Biochemical;Biodistribution;Biological Assay;Biological Markers;biomaterial compatibility;Biopsy;Birth;Burn injury;burn model;C-terminal;Chemistry;Cicatrix;Clinical;Clinical Chemistry;Cold Therapy;Collaborations;Collagen;Collagen Fiber;Collagen Fibril;Cosmetics;Crosslinker;cytokine;Cytotoxic agent;cytotoxicity;Data;Deposition;Dermal;Dermis;design;Development;Drug Kinetics;Ethylenes;Etiology;Exhibits;Experimental Designs;Extracellular Matrix;Extracellular Matrix Proteins;Family suidae;Fibroblasts;fibrogenesis;Fibronectins;Fibrosis;flexibility;Fluorouracil;Formulation;Generations;Glycols;Half-Life;Heart;Histologic;Histology;Homeostasis;Hour;Human;Hydrogels;Hypertrophic Cicatrix;imaging modality;Imaging Techniques;improved;In Situ;In Vitro;in vivo;Inflammation;Inflammatory;Inhibition of Matrix Metalloproteinases Pathway;Injections;innovation;intein;Joints;Kidney;Knowledge;Lasers;Legal patent;Libraries;Link;Liver;Low-Level Laser Therapy;Lung;Matrix Metalloproteinases;Measures;mechanical properties;Mechanics;Methods;Microscopy;Modeling;Molecular;Molecular Weight;Morphology;Myofibroblast;Nitric Oxide Synthase;novel;Operative Surgical Procedures;optical imaging;Optics;optimal treatments;Outcome;Pain;Pathologic;Pathology;Pathway interactions;Patients;peptide hormone;Performance;Persons;Photography;PIK3CG gene;porcine model;Pregnancy;prevent;Property;protein purification;Proteins;psychologic;Radiation;Recombinants;Recurrence;Relaxin;response;Safety;second harmonic;second harmonic generation imaging;Serum;side effect;Signal Transduction;Silicone Gels;single-cell RNA sequencing;Site;Skin;Skin injury;skin wound;Smooth Muscle;Solubility;Spatial Frequency Domain Imaging;standard of care;Structure;System;Testing;Therapeutic;therapeutic protein;Thick;third degree burn;Tissue imaging;Tissue Inhibitor of Metalloproteinases;Tissues;Topical application;Toxic effect;Trauma;Up-Regulation;Uterus;Western Blotting;wound;wound healing

PROJECT_TITLE: A Relaxin-loaded Hydrogel for the Treatment of Hypertrophic Scars

STUDY_SECTION: BMBI

STUDY_SECTION_NAME: Biomaterials and Biointerfaces Study Section[BMBI]


NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Genetics;Macular Degeneration;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: MOSCOW

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF IDAHO

ORG_STATE: ID

PHR: Patterning Genes in Retinal Development  Public Health Impact Statement  This project will discover mechanisms regulating the expression of “tandemly-replicated” cone visual pigment opsin genes, such as those on the human X chromosome encoding the red- and green-sensitive cone opsins. The results of the proposed studies will provide key information regarding endocrine signaling pathways, receptors, and genetic response elements that mediate this regulation. Understanding these regulatory pathways will be important as the Vision Science community develops regenerative medicine-based methods for replacing photoreceptors that are lost to disease or injury.

PI_NAMEs: STENKAMP, DEBORAH L (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TERMS: 3-Dimensional;Age related macular degeneration;Amphibia;ATAC-seq;Award;Birds;cell type;ChIP-seq;Chiroptera;Chromatin;Collaborations;Color blindness;Color Visions;Communities;Cone;CRISPR/Cas technology;Data;Defect;Development;differential expression;differentiation protocol;Disease;Elements;Endocrine;Event;Exons;Eye diseases;Fishes;Fluorescence;Functional disorder;Future;gain of function;Gene Expression;Generations;Genes;Genetic;genetic element;genetic manipulation;genetic resource;Genome;Goals;Grant;Health;Heritability;hormonal signals;hormone response element;Human;human induced pluripotent stem cells;human stem cells;Human X Chromosome;Immersion;In Vitro;in vivo;Injury;insight;Knowledge;Ligands;Link;loss of function;Mammals;Measurement;Mediating;Methods;Modeling;Molecular;Myopia;novel;Nuclear Hormone Receptors;Nucleic Acid Regulatory Sequences;Opsin;Organoids;paralogous gene;Pathway interactions;Pattern;Phenotype;Photoreceptors;Population;Primates;Process;progenitor;promoter;Proteins;Public Health;receptor;regenerative approach;Regenerative Medicine;Regulation;Regulatory Element;Regulatory Pathway;Reporter;response;Response Elements;Retina;Retinal Cone;Retinal Degeneration;Retinal Diseases;Retinal Pigments;Role;sensory system;Sequence Homology;Signal Pathway;Signal Transduction;small molecule;Stargardt's disease;teleost fish;Testing;Therapeutic;Thyroid Function Tests;Thyroid Hormone Receptor;Thyroid Hormones;tool;Transcript;translational applications;Vertebrates;vision science;Visual System;X Chromosome;Zebrafish

PROJECT_TITLE: Patterning Genes in Retinal Development

STUDY_SECTION: BDE

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


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Endocrine Disruptors;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: WEST LAFAYETTE

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: Project Narrative This proposal aims to elucidate sub-cellular compartment homeostasis that is disrupted by developmental PFAS exposure, including PFOA, PFBA, and GenX, that collectively contribute to neurotoxicity later in life by increasing cellular vulnerability to established neuro-risk factors associated with neurodegeneration. We will combine derived human dopaminergic neuronal cells and zebrafish animal model to compare the neurotoxicity of selected PFAS and identify key pathogenic pathways driving the neurodegeneration.

PI_NAMEs: FREEMAN, JENNIFER L. (contact);YUAN, CHONGLI

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: 1-Methyl-4-phenylpyridinium;Accounting;Adult;Aging;Animal Model;Automobile Driving;Behavior;Behavioral;Biological Assay;Blood;Brain;Calcium;Carbon;Cell Differentiation process;Cell Nucleus;Cells;Central Nervous System;Characteristics;Chemical Structure;Chemicals;Chromatin;Communication;comparative;Development;developmental neurotoxicity;Dopamine;dopaminergic neuron;Dose;Drops;Drug Modulation;Embryo;Endoplasmic Reticulum;endoplasmic reticulum stress;Ensure;epidemiology study;Exhibits;Exposure to;Floor;Goals;Homeostasis;Human;human induced pluripotent stem cells;Hydrophobicity;Induced pluripotent stem cell derived human neuron;Interruption;Intervention;Length;Life;lipophobicity;Literature;Measures;Mitochondria;mitochondrial fitness;Modeling;Molecular;Morphology;Nerve Degeneration;Neurodegenerative Disorders;Neurodevelopmental Disorder;neuron development;Neuronal Differentiation;Neuronal Plasticity;Neurons;neurotoxic;neurotoxicity;Neurotoxins;novel;Pathogenicity;Pathway interactions;Pattern;persistent organic pollutants;Phenotype;Poly-fluoroalkyl substances;Population;Property;Regulation;release of sequestered calcium ion into cytoplasm;Research;Residual state;resilience;Risk;Risk Factors;Role;Side;stem cells;Structure;synuclein;Testing;Time;time use;Toxic effect;Toxicokinetics;transcriptomics;Tunicamycin;Work;Zebrafish

PROJECT_TITLE: Comparative neurotoxicity of PFAS

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Clinical Research;Clinical Trials and Supportive Activities;Mental Health

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: Relevance Over the past decade, evidence has emerged of a direct (but only an associative) relationship between pro- inflammatory mediators and impulsive aggression in humans. In this study, we propose to demonstrate a causal relationship between pro-inflammatory proteins and impulsive aggression in human subjects by showing that an acute pro-inflammatory state, via endotoxin challenge, will increase aggressive responding, and increase hostile social cognition to a greater degree in “aggressive”, compared with “non-aggressive”, individuals. If supported, this finding will provide a strong rationale for clinical trials of anti-inflammatory agents in impulsive aggressive individuals.

PI_NAMEs: COCCARO, EMIL FRANK (contact);IRWIN, MICHAEL R

PROGRAM_OFFICER_NAME: SABBAGH, JONATHAN JACOB

PROJECT_TERMS: Acute;Aggressive behavior;Amygdaloid structure;Anger;Animals;Anti-Inflammatory Agents;Anxiety;Behavior Therapy;behavioral response;Clinical Trials;Cognitive Therapy;cortico-limbic circuits;cytokine;Diagnostic;Dimensions;direct application;Disease;Dose;Double-Blind Method;DSM-V;Endotoxins;Face;Feeling;Functional Imaging;Functional Magnetic Resonance Imaging;Grouping;Human;human subject;IL8 gene;improved;Impulsivity;In Vitro;Individual;Inflammation Mediators;Inflammatory;inflammatory marker;Inflammatory Response;Inflammatory Response Pathway;inhibitor;Interleukin-6;Intermittent Explosive Disorders;Intervention;life history;Lipopolysaccharides;mass shooting;Measures;Mental Depression;Mental disorders;Moods;MRI Scans;Outcome Measure;Participant;Patient Self-Report;Personality;Personality Disorders;Persons;physical assault;Physiological;Placebos;Plasma;Population;primary outcome;Program Development;Property;Proteins;Rattus;REM Sleep;Reporting;Research;response;reuptake;Role;Scanning;secondary outcome;Self Assessment;Serotonin;Shock;Signal Transduction;social;social cognition;Societies;Stress;substance use;Temperature;Testing;TNF gene;Whole Blood

PROJECT_TITLE: Inflammatory Challenge in Human Aggression

STUDY_SECTION: APDA

STUDY_SECTION_NAME: Adult Psychopathology and Disorders of Aging Study Section[APDA]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Obesity

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Lay Summary With age, senescent cells accumulate in the body. These cells are toxic and contribute to the development of several age-related diseases. We propose that a high senescent cell burden outside the brain can negatively impact brain tissue and lead to an earlier onset of cognitive decline.

PI_NAMEs: ZHU, YI  (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: 3xTg-AD mouse;Ablation;Adipose tissue;Age;age acceleration;age related;Age-associated memory impairment;age-related disease;Aging;aging population;Alzheimer's Disease;Alzheimer's disease model;Alzheimer's disease pathology;Amyloid beta-42;Amyloid beta-Protein;Attenuated;Automobile Driving;Biology;Body mass index;Brain;brain dysfunction;brain tissue;Caring;CDKN2A gene;Cell Aging;Cell Cycle Arrest;Cell Transplantation;cell type;Cells;Central Nervous System;chemokine;Chronic;Cognitive deficits;cognitive function;Communication;Complement;Complement 3a;cytokine;Cytometry;Data;Dementia;dementia risk;Development;diet-induced obesity;Disease;Disease Progression;Distant;early onset;efficacy evaluation;Endocrine;Endocrine Glands;Enzyme-Linked Immunosorbent Assay;Enzymes;epidemiology study;Family;Fatty acid glycerol esters;Functional disorder;Future;Health Care Costs;Healthcare Systems;Hippocampus;Human;Impaired cognition;Impairment;in silico;in vivo;Individual;Inflammation;Inflammatory;insight;Intervention;intraperitoneal;Investigation;Link;Measures;Mediating;Microglia;middle age;Molecular;mouse model;mRNA Expression;Mus;Nerve Degeneration;Nervous System Disorder;Neurocognitive;Neurodegenerative Disorders;neuroinflammation;neuropathology;new therapeutic target;novel;Obese Mice;Obesity;old mice;Organ;Pathogenesis;Pathogenicity;Pathology;Patients;Peptide Hydrolases;Peptides;Peripheral;Plasma;Play;Prevalence;prevent;Proteome;Proteomics;rapid growth;Research Personnel;response;Risk;Role;senescence;senescence associated secretory phenotype;senescent cell;Serum;Signal Transduction;single cell analysis;single-cell RNA sequencing;Site;social;spatial memory;Stains;Stimulus;Stress;stressor;Surveys;systemic inflammatory response;tau Proteins;therapeutic target;Thinness;Time;Tissues;Transgenic Organisms;Transplantation

PROJECT_TITLE: Investigating the Role of Adipose Senescent Cells in Cognitive Function and Alzheimer's Disease Progression

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 AN-H (55)]


ORG_CITY: PROVIDENCE

ORG_NAME: OCEAN STATE RESEARCH INSTITUTE, INC.

ORG_STATE: RI

PHR: Project Narrative Pulmonary hypertension is a disease where there is narrowing of the blood vessels in the lungs causing the dysfunction and failure in the right side of heart, which are associated with poor prognosis. This proposed study will investigate the reasons that underlie the weakening of the right side of heart with a focus on mechanisms responsible for energy generation in the heart muscle. Should the experiments be successful, we will discover a new way to increase energy generation in the heart muscle in the right side of heart and thereby improve the heart function and outcomes in patients suffering from pulmonary hypertension.

PI_NAMEs: CHOUDHARY, GAURAV ;ZHANG, PENG  (contact)

PROGRAM_OFFICER_NAME: SUTLIFF, ROY L

PROJECT_TERMS: Adult;Apoptosis;Bioenergetics;Blood Vessels;Cardiac Myocytes;Cell Physiology;cell type;Chemicals;Complex;Coupled;Data;Development;Disease;Electron Transport;Energy-Generating Resources;experimental study;Failure;Flavoproteins;Functional disorder;Gene Expression;Generations;Goals;Heart;heart function;Impairment;improved;in vivo;in vivo Model;Knowledge;Link;Lung;Maintenance;Mediating;Mitochondria;Mitochondrial DNA;mitochondrial dysfunction;Mitochondrial Matrix;mitochondrial membrane;Modeling;Molecular;Morbidity - disease rate;Morphology;mortality;Muscle Cells;Muscle Fibers;Myocardial;Myocardium;NADH dehydrogenase (ubiquinone);new therapeutic target;novel;novel strategies;novel therapeutic intervention;Organ;Outcome;Oxidative Phosphorylation;Oxidative Stress;Patients;Pharmaceutical Preparations;Phosphorylation;Play;Ploidies;pre-clinical;preservation;pressure;Production;Prognosis;protein complex;Protein Tyrosine Kinase;protein-tyrosine kinase c-src;Pulmonary Heart Disease;Pulmonary Hypertension;Rattus;Reactive Oxygen Species;Regulation;Respiration;respiratory;Right Ventricular Dysfunction;Right Ventricular Function;Role;Side;SRC gene;targeted treatment;Therapeutic;therapeutic target;Translating;Tyrosine Phosphorylation;Ventricular

PROJECT_TITLE: Role of Mitochondrial c-Src in Right Ventricular Dysfunction in Pulmonary Hypertension

STUDY_SECTION: MPPA

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


NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Brain Disorders;Cerebrovascular;Clinical Research;Disability Research;Neurosciences;Stroke

ORG_CITY: HOUSTON

ORG_DEPT: NEUROSURGERY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE Subarachnoid hemorrhage is a type of stroke which causes significant disabilities in survivors. This study will establish radiographic biomarkers of cerebral edema (CE) and identify new therapeutic targets. This proposal will pave the way for new interventions to target CE and improve outcomes after SAH.

PI_NAMEs: CHOI, HUIMAHN ALEX (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: Address;Affect;antagonist;ATP1A1 gene;Beds;bench to bedside;Biological Markers;Brain;Brain Aneurysms;Brain Edema;Brain hemorrhage;Brain Injuries;brain parenchyma;brain tissue;Cell membrane;Cells;Cellular Membrane;Cerebral Edema;Cerebrospinal Fluid;Clinical;Clinical Markers;Clinical Research;Clinical Trials;Cognitive deficits;cognitive disability;Cultured Cells;Data;Databases;Development;disability;Edema;experimental study;functional disability;Functional disorder;Future;glycoprotein NMB;Hemin;Hospital complications;Hour;Human;Imaging Device;improved outcome;In Vitro;in vitro Model;in vivo;in vivo Model;Injury;Intervention;Investigation;Ion Channel;K ATPase;Long term disability;Magnetic Resonance Imaging;Maintenance;Maryland;Measurement;Measures;Mediating;Medical center;member;Membrane Potentials;Messenger RNA;Methods;MicroRNAs;Modeling;mortality;motor function improvement;Mus;Nervous System Disorder;Neurological disability;Neurons;new therapeutic target;novel;Outcome;Pathway interactions;Patients;Persons;pharmacologic;Photons;Plasma;Play;predict clinical outcome;Process;protein expression;Proteins;Proteomics;radiological imaging;Receptor Protein-Tyrosine Kinases;Roentgen Rays;Role;Rupture;Sampling;Scanning;scavenger receptor;Stroke;Subarachnoid Hemorrhage;Surrogate Markers;Survivors;Swelling;targeted treatment;Techniques;Testing;therapeutic target;therapy development;Transfection;translational approach;Universities;Water;X-Ray Computed Tomography

PROJECT_TITLE: Radiographic markers and therapeutic targets of cerebral edema after SAH

STUDY_SECTION: ANIE

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


NIH_SPENDING_CATS: Acute Respiratory Distress Syndrome;Biotechnology;Genetics;Human Genome;Lung;Rare Diseases

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT SUMMARY The body’s response to injury involves cells of the immune system called macrophages. In this project will explore novel mechanisms focusing on genetic switches contributing to the lung’s ability to respond to injury and inflammation. These new pathways can provide novel approaches to treat hyperinflammatory disease conditions.

PI_NAMEs: NAGY, LASZLO  (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: 3-Dimensional;Acute Lung Injury;airway inflammation;Ambrosia;Anti-Inflammatory Agents;Architecture;Binding;Cells;chemokine;Chimera organism;Chromatin;Chromatin Loop;Chromatin Structure;Disease;Disease Progression;EGR2 gene;Enhancers;Ensure;epigenome;epigenomics;Flow Cytometry;gain of function;Gene Expression;Gene Expression Regulation;Genes;Genetic;Genetic Transcription;genome-wide;Genomic Segment;Grant;Growth;Health;Hi-C;high dimensionality;IL4 gene;IL6 gene;Immune;Immune system;In Vitro;in vivo;Inflammation;Inflammatory;inflammatory modulation;Inflammatory Response;Injury;innovation;insight;Interleukin-4;Ligands;Lipopolysaccharides;loss of function;Lung;Lung Diseases;lung injury;Macrophage;Maps;Mediating;Memory;Modeling;Morbidity - disease rate;mortality;mouse model;Mus;NF-kappa B;novel;novel strategies;Nuclear;Nuclear Hormone Receptors;Nuclear Receptors;p65;Pathologic;Pathway interactions;Peroxisome Proliferators;Pollen;PPAR gamma;Process;programs;promoter;receptor;Receptor Signaling;recruit;regenerative;Regulation;response;response to injury;Risk;Role;rosiglitazone;Shapes;Signal Transduction;single cell technology;Specific qualifier value;STAT6 gene;STAT6 Transcription Factor;synergism;Technology;tissue injury;Toll-like receptors;transcription factor;transcriptomics

PROJECT_TITLE: Nuclear receptor, PPARg in macrophage polarization, hyperinflammatory gene expression and lung injury

STUDY_SECTION: CSME

STUDY_SECTION_NAME: Cell Signaling and Molecular Endocrinology Study Section[CSME]


NIH_SPENDING_CATS: Aging

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF UTAH

PHR: PROJECT NARRATIVE The goal of this proposal is to investigate mechanisms by which amino acids impact cell health when their storage and regulated uptake is altered, as occurs during aging. The results of the experiments will increase our understanding of how metabolite compartmentation within cells is maintained and regulated and how a collapse in amino acid homeostasis contributes to a decline in various cellular systems with age.

PI_NAMEs: HUGHES, ADAM  (contact)

PROGRAM_OFFICER_NAME: OROSZ, ANDRAS

PROJECT_TERMS: Acidity;Address;Age;age related;age related deterioration;age-related disease;Aging;aging process;aging related;Alzheimer's disease model;Amino Acid Permease;Amino Acids;Area;Autophagocytosis;Biological Models;Bypass;Cell Physiology;Cells;combat;Cysteine;Data;detection of nutrient;Deterioration;Development;Disease;Endocytosis;Evaluation;experimental study;Feedback;Functional disorder;Funding;Genes;Genetic Screening;genome-wide;Goals;hallmarks of aging;Health;Homeostasis;Human;Hydrophobicity;Impairment;Individual;insight;interest;Ions;Iron;Knowledge;life span;Link;Lysosomes;Maintenance;Metabolic;Metabolism;Mitochondria;Multivesicular Body;Mutation;Nature;Nutrient;Organelles;Pathway interactions;Property;protein degradation;Regulation;Research;Respiration;Role;Saccharomycetales;Signal Pathway;Signal Transduction;Sirolimus;Surface;System;Testing;Time;Toxic effect;uptake;Vacuole;Work;Yeast Model System;Yeasts

PROJECT_TITLE: Endolysosomal Regulation of Amino Acid Homeostasis in Aging

STUDY_SECTION: CMAD

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cancer;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetics;Microbiome;Pancreatic Cancer;Prevention;Rare Diseases

ORG_CITY: LA JOLLA

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative The overall aim of this project is to engineer whole-cell, living biosensors that can detect tumors within the gastrointestinal system and respond with a diagnostic output. We will integrate our knowledge of synthetic biology, cancer and our clinical expertise to develop, test, and optimize genetic circuits capable of sensing and responding to common gastrointestinal tract cancer mutations in DNA. The motivation is to increase participation in cancer screening, catch gastrointestinal cancers in earlier stages, decrease healthcare costs and improve patient outcomes.

PI_NAMEs: HASTY, JEFF M (contact);KNIGHT, ROB

PROGRAM_OFFICER_NAME: JOHNSON, ERIC MICHAEL

PROJECT_TERMS: Address;Adjuvant Therapy;American;Anaerobic Bacteria;auxotrophy;Bacteria;base;Benign;Biodistribution;Biological Assay;Biosensing Techniques;Biosensor;Blood;cancer cell;cancer type;carcinogenesis;Carcinoma in Situ;Caring;cell free DNA;Cell Line;Cells;Cessation of life;Clinical;Clinical Trials;Coculture Techniques;Colon;Colonoscopy;Colorectal;Colorectal Cancer;colorectal cancer screening;commensal microbes;Competence;Complex;Containment;Control Animal;cost;Data;design;Detection;Development;Diagnosis;Diagnostic;Directed Molecular Evolution;Disease;DNA;DNA analysis;DNA Library;DNA Sequence;driver mutation;Early Diagnosis;Ecosystem;effective therapy;Engineering;Ensure;Environment;Escherichia coli;Event;Excision;experimental study;Feces;fundamental research;Funding;Future;gastrointestinal;gastrointestinal system;Gastrointestinal tract structure;Genetic;Goals;gut microbes;Health;Health Care Costs;Horizontal Gene Transfer;human disease;Immune system;improved;In Situ;In Vitro;in vivo;Inflammation;interest;Intestines;Knowledge;KRASG12D;Left;Location;Malignant neoplasm of gastrointestinal tract;Malignant neoplasm of pancreas;Malignant Neoplasms;mechanical force;metagenomic sequencing;microbial;microbiome;Modeling;Monitor;Motivation;mouse model;multiplex assay;multiplex detection;Mus;Mutation;Mutation Detection;neoplastic;noninvasive diagnosis;Nutritional;Oncogenic;Organoids;Output;Oxygen;Participant;Patient Noncompliance;Patient-Focused Outcomes;Patients;Performance;Population;prevent;Prevention;Production;Prognosis;Progress Reports;Publishing;Reporting;Sampling;Science;screening;Screening for cancer;sensor;sobriety;synthetic biology;System;Techniques;Technology;technology platform;Testing;Therapeutic;Time;Tissues;Transcription Repressor;trial readiness;tumor;tumor DNA;tumor microbiome;Urine;Variant;Work

PROJECT_TITLE: Bacterial biosensors for the prevention of gastrointestinal cancers

STUDY_SECTION: CPSS

STUDY_SECTION_NAME: Cancer Prevention Study Section[CPSS]


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Genetics;Neurosciences;Orphan Drug;Pediatric;Precision Medicine;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: ATHENS

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: Project Narrative HGG-G34 (H3.3G34-mutant high-grade glioma) is a lethal subtype of malignant brain tumor that primarily affects adolescents and young adults. We will employ our newly developed model of HGG-G34 and investigate the molecular mechanisms underlying the formation, progression, and relapse of this tumor subtype.

PI_NAMEs: FUNATO, KOSUKE  (contact)

PROGRAM_OFFICER_NAME: KOTLIAROVA, SVETLANA

PROJECT_TERMS: Accounting;Address;Adolescent and Young Adult;Affect;age group;ATRX gene;Brain;Brain Neoplasms;Cancer Etiology;Cell Line;Cell model;Cells;Cerebral hemisphere;Cessation of life;Characteristics;Child;ChIP-seq;Clinical;clinically relevant;Collaborations;Data;Development;Diagnosis;diagnostic strategy;Dimensions;Disease;Exhibits;experimental study;Foundations;Genetic Transcription;Glioma;Goals;hindbrain;Histones;Human;human embryonic stem cell;inhibitor;innovation;insight;Interneurons;Knock-out;Knowledge;Light;loss of function;Maintenance;Malignant - descriptor;Malignant neoplasm of brain;Malignant Neoplasms;MEKs;Modeling;Molecular;Morphology;mouse model;Mus;mutant;Mutation;Nature;neural;Neuroglia;Neuronal Differentiation;new therapeutic target;Normal Cell;novel;Outcome;Pathogenicity;Patients;personalized approach;personalized diagnostics;personalized medicine;Pilot Projects;Play;Population;Positioning Attribute;prevent;Primary Brain Neoplasms;progenitor;Prognosis;programs;Proliferating;Prosencephalon;Radial;Relapse;Research;Role;safety assessment;Sampling;stem cell model;stem cells;temozolomide;Therapeutic;therapeutic target;therapy resistant;TP53 gene;transcription factor;tumor;Tumor Biology;Tumor Subtype;tumorigenesis;Tumorigenicity;Undifferentiated;Variant;Xenograft Model

PROJECT_TITLE: Developmental programs as vulnerabilities in H3.3G34-mutant high-grade glioma

STUDY_SECTION: CNBT

STUDY_SECTION_NAME: Clinical Neuroimmunology and Brain Tumors Study Section[CNBT]


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

ORG_CITY: IOWA CITY

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: The proposed project addresses the development of a practical and reproducible whole-brain magnetic resonance spectroscopic imaging (MRSI) framework for 3T MRI scanners to improve our understanding of metabolic changes that occur with Alzheimer’s disease. This research has relevance to public health since its successful completion will result in a potential screening tool for Alzheimer’s disease as well as to evaluate response to new treatments.

PI_NAMEs: JACOB, MATHEWS ;LI, YAN ;MAGNOTTA, VINCENT A (contact)

PROGRAM_OFFICER_NAME: HSIAO, JOHN

PROJECT_TERMS: 3-Dimensional;Address;Age;Age-associated memory impairment;Alzheimer's Disease;Alzheimer's disease related dementia;American;Atlases;Biological;Brain;brain metabolism;Brain region;California;Clinical;Clinical Research;cohort;Collaborations;Communities;Compensation;Computer software;Coupled;Data;Databases;deep learning model;Dementia;density;design;Development;Diagnosis;Digital Imaging and Communications in Medicine;Disease;Disease Marker;Documentation;Dropout;Early identification;Feedback;Frequencies;Future;Gender;Goals;Healthcare;healthy volunteer;Human;Image;image reconstruction;image registration;imaging capabilities;Imaging Device;imaging study;Imaging Techniques;improved;Individual;Ionizing radiation;Iowa;Knowledge;Libraries;Licensing;Magnetic Resonance Imaging;magnetic resonance spectroscopic imaging;Maps;Measurement;Memory;Metabolic;metabolic abnormality assessment;metabolic profile;Methods;mild cognitive impairment;Morphologic artifacts;Motion;Neurodegenerative Disorders;new therapeutic target;novel;novel therapeutics;open source;open source tool;Participant;Physiologic pulse;Process;Protocols documentation;Public Health;Quality Control;recruit;Reporting;Reproducibility;Research;Research Personnel;Resolution;response;response biomarker;Running;Sampling;San Francisco;Scanning;Screening procedure;sex;Signal Transduction;Software Validation;spectroscopic survey;Structure;Testing;Therapeutic Agents;tool;treatment response;Universities;Variant;Vendor;Visual;Visualization;Work

PROJECT_TITLE: High Resolution MRSI for Alzheimer's Disease and Related Dementias

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MCST-Q (81)]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF NURSING

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

NIH_SPENDING_CATS: Behavioral and Social Science;Breastfeeding, Lactation and Breast Milk;Clinical Research;Clinical Trials and Supportive Activities;Dissemination and Implementation Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Nutrition;Pediatric;Prevention;Social Determinants of Health;Women's Health Research

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: PROJECT NARRATIVE The proposed project seeks to evaluate the effectiveness and implementation of the Breastfeeding Education Support Tool for Baby (BEST4Baby) intervention, an mHealth-supported community-based peer counselor breastfeeding intervention for mothers in India. Given that rates of optimal infant feeding practices have remained stagnant over the past two decades in India, and that India is the most populous country and icontributes one-fifth of all global live births, this project could have major global health implications if the intervention is found to improve maternal breastfeeding practices and infant clinical outcomes. The project will also provide evidence needed to adopt BEST4Baby nationally and in other low resource communities.

PI_NAMEs: DERMAN, RICHARD J;SHORT, VANESSA L (contact)

PROGRAM_OFFICER_NAME: ROSS, SHARON A

PROJECT_TERMS: Adopted;Adoption;Age Months;arm;Behavior;Breast Feeding;Child;Child Development;Child Health;Childhood;Clinical;Communities;community based evaluation;comparison control;Consolidated Framework for Implementation Research;Control Groups;cost comparison;Counseling;Country;critical period;Data;Development;Disease;disorder prevention;Disparity;early childhood;Education;effectiveness evaluation;effectiveness/implementation hybrid;Enrollment;Exclusive Breastfeeding;feeding;Feeding behaviors;Fogarty International Center;Funding;Future;global health;group intervention;Growth;Growth and Development function;Health;health disparity;Health education;Health Priorities;Health Promotion;Health system;Healthcare Systems;Human Development;Human Milk;hybrid type 1 trial;implementation barriers;implementation facilitators;implementation framework;improved;Income;India;infancy;Infant;Infant Health;Intake;Intervention;Live Birth;Low income;Maternal Behavior;Measurement;Methods;mHealth;Mission;Mobile Health Application;Morbidity - disease rate;mortality;Mothers;National Institute of Child Health and Human Development;neurodevelopment;nutrition;Nutritional status;Outcome;Participant;peer;peer support;Persons;Pilot Projects;Play;postnatal period;Pregnancy;Pregnant Women;prenatal;Professional counselor;programs;Public Health;Randomized;Randomized, Controlled Trials;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Recommendation;Research;Research Personnel;Resource-limited setting;Role;Site;Standardization;support tools;Testing;Time;Training;Translating;Translations;treatment as usual;two-arm study;UNICEF;Visit;Woman;World Health Organization

STUDY_SECTION: HPC

STUDY_SECTION_NAME: Health Promotion in Communities Study Section[HPC]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Hematology

ORG_DEPT: PHARMACOLOGY

ORG_NAME: NORTHEASTERN UNIVERSITY

PHR: PROJECT NARRATIVE Using unique computational tools, we design GIRK-isoform specific small molecule partial inhibitors to maintain heart rate variability, while correcting Atrial fibrillation. These drugs will help decipher the role of these channels in platelet-mediated thrombosis to control Afib and Stroke.

PI_NAMEs: LOGOTHETIS, DIOMEDES E. (contact)

PROGRAM_OFFICER_NAME: TJURMINA, OLGA A

PROJECT_TERMS: Address;Affect;Age;Aging;Agonist;Alcohols;Animal Model;Anti-Arrhythmia Agents;Area;Arrhythmia;Atrial Fibrillation;Award;Binding;Binding Sites;Biological Assay;Biology;Blood Platelets;Blood Vessels;Body part;Cardiac;Cardiac health;cardiovascular health;Cell membrane;Cells;Chemicals;Chronic;Coagulation Process;computerized tools;Coupled;Cytoplasm;Data;Dependence;design;Disease;Drug Binding Site;Drug Design;drug development;drug discovery;Drug Kinetics;Drug or chemical Tissue Distribution;Drug Targeting;Endowment;Ensure;Epinephrine;Equilibrium;Exposure to;Extracellular Matrix;Feedback;Fibrinolytic Agents;Functional disorder;Funding;Future;Generations;Genetic Complementation Test;GIRK1 subunit, G protein-coupled inwardly-rectifying potassium channel;GIRK4 subunit, G protein-coupled inwardly-rectifying potassium channel;Grant;GTP-Binding Proteins;Health;Heart;Heart Atrium;Heart Rate;heart rate variability;Hemorrhage;Hemostatic Agents;In Vitro;in vivo;indexing;inhibitor;Injury;Investments;inward rectifier potassium channel;Ion Channel;Lipids;Manuals;Manuscripts;Mediating;Medical;Membrane;Minor;molecular dynamics;mortality risk;Mus;Mutation;Myocardial Infarction;patch clamp;Pharmaceutical Preparations;pharmacologic;Phenotype;Phosphatidylinositols;Phosphorylation;Physiology;Platelet Activation;Platelet aggregation;Preparation;Prevalence;prevent;Process;Protein Isoforms;Publications;receptor;recruit;Regulation;Risk;Role;Seminal;Serotonin;side effect;Signal Transduction;Site;small molecule;Specificity;Stroke;structural determinants;Structure;synergism;System;Testing;Thrombin;Thrombosis;thrombotic;Thromboxane A2;Thrombus;tool;Toxic effect;Translating;Vagus nerve structure;vascular injury;Ventricular;virtual library;Work;Xenopus oocyte

PROJECT_TITLE: Structural Determinants of PIP2 Regulation

STUDY_SECTION: MPPB

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


NIH_SPENDING_CATS: Aging;Biotechnology;Eye Disease and Disorders of Vision;Macular Degeneration;Neurodegenerative;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Transplantation

ORG_CITY: Aurora

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: NARRATIVE These studies would lead to preclinical evidence on the feasibility of retinal regeneration with stem cell-derived retinal transplants. This in turn, would be paradigm-shifting in terms of standard of care, as this transplant could become the first available treatment for restoring vision in patients affected by end-stage dry-AMD.

PI_NAMEs: CANTO-SOLER, MARIA VALERIA  (contact)

PROGRAM_OFFICER_NAME: FORTRESS, ASHLEY

PROJECT_TERMS: 3-Dimensional;Accounting;Address;Affect;Age related macular degeneration;Amacrine Cells;Atrophic;Automobile Driving;Blindness;cell replacement therapy;Cell Therapy;Cell Transplantation;cell type;Cells;Communication;Cone;Degenerative Disorder;design;Detection;Developed Countries;Dryness;Evaluation;Event;ganglion cell;Goals;human induced pluripotent stem cells;implantation;in vivo;innovation;Lead;Light;light transmission;macula;Miniature Swine;Modeling;multimodality;Natural regeneration;Neurons;Nonexudative age-related macular degeneration;novel;Operative Surgical Procedures;Outcome;Patients;Photoreceptors;Physiological;post-transplant;pre-clinical;regenerative therapy;Resolution;response;Retina;retina transplantation;Retinal Degeneration;retinal regeneration;Rod;sight restoration;standard of care;Stem cell transplant;stem cells;Structure of retinal pigment epithelium;Synapses;Technology;Testing;Tissue Transplantation;Transplantation;Vision

PROJECT_TITLE: Cell-based therapies for retinal degeneration

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


NIH_SPENDING_CATS: Aging;Arthritis;Bioengineering;Biomedical Imaging;Chronic Pain;Clinical Research;Osteoarthritis;Pain Research

ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: NARRATIVE Synovial inflammation (synovitis) plays a role in the onset, pathogenesis and is a key target for disease modifying drugs in Osteoarthritis (OA), a leading cause of pain, reduced joint function, and disability. While associations between synovitis and OA are known, our understanding of the role of synovitis in OA has been hampered by a lack of a non-invasive and non-contrast methods to evaluate synovitis. This work aims to develop new, non- contrast MRI methods to assess synovial inflammation in knee OA and to demonstrate their predictive power for OA whole joint disease progression and both prediction and monitoring of treatment response.

PI_NAMEs: KOGAN, FELIKS  (contact)

PROGRAM_OFFICER_NAME: ZHENG, XINCHENG

PROJECT_TERMS: Adrenal Cortex Hormones;Affect;Agreement;Anti-Inflammatory Agents;arthropathies;Benchmarking;Bilateral;Biopsy;bone;Capillary Permeability;Cartilage;Clinical Research;Contralateral;contrast enhanced;contrast imaging;Contrast Media;cost;Data;Degenerative polyarthritis;Detection;Development;Diffusion;Diffusion Magnetic Resonance Imaging;disability;Disease;Disease Progression;Early Diagnosis;economic cost;effusion;Evaluation;Excision;fluorodeoxyglucose positron emission tomography;Gadolinium;Histologic;Histology;Hypertrophy;Image;imaging biomarker;Imaging Device;imaging modality;immune activation;Inflammation;Inflammatory;inflammatory marker;Injections;innovation;intravenous injection;joint function;Joints;kidney dysfunction;Knee;Knee Osteoarthritis;knee pain;knee replacement arthroplasty;Link;Liquid substance;Magnetic Resonance Imaging;magnetic resonance imaging biomarker;Measurement;Measures;Meniscus structure of joint;Methods;Modeling;Monitor;Morphology;Motion;Musculoskeletal;neglect;novel;novel imaging technique;Operative Surgical Procedures;Pain;Pathogenesis;Pathway interactions;patient population;Patients;Pharmaceutical Preparations;Phase;Play;predicting response;Prevalence;prevent;Productivity;Property;Quality of life;Reference Standards;Relaxation;research study;Resolution;response;Role;Scanning;Sensitivity and Specificity;Severities;Severity of illness;Signal Transduction;spatial relationship;Steroids;Structure;Symptoms;Synovial Membrane;Synovitis;Technology;Testing;Time;Tissues;tool;treatment response;Validation;validation studies;Vascularization;Work

PROJECT_TITLE: Novel Non-Contrast MRI to Assess Synovitis in Osteoarthritis

STUDY_SECTION: EITA

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


ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: Narrative The proposed motion correction technology developments and translations will have a significant impact on both currently used clinical protocols and emerging new applications as in the evaluation of patients with Ischemia and No Obstructive Coronary Artery Disease (INOCA), heart failure with preserved ejection fraction (HFpEF) or aortic stenosis.

PI_NAMEs: LIU, CHI  (contact)

PROGRAM_OFFICER_NAME: HALLER, JOHN WAYNE

PROJECT_TERMS: animal data;Animal Model;Aortic Valve Stenosis;attenuation;bulk motion;cancer imaging;Cancer Patient;Cardiac;Caring;Clinical;Clinical Protocols;Collaborations;Computer software;Coronary;Coronary Angiography;Coronary Arteriosclerosis;Data;deep learning;denoising;Development;Devices;EFRAC;Evaluation;Event;Grant;Half-Life;Heart failure;heart motion;Hospitals;Human;Image;improved;industry partner;Injections;Ischemia;Joints;Kinetics;Malignant neoplasm of lung;Maps;Methodist Church;Methods;Modality;Motion;Noise;novel;Patient Selection;Patients;PET/CT scan;Physics;Positron-Emission Tomography;preservation;prototype;Radiation exposure;Research;Resistance;respiratory;Rest;Series;Stress;success;Technology;technology development;temporal measurement;Time;Tracer;Translating;Translations;Uncertainty;University Hospitals;Validation

PROJECT_TITLE: Development and Translation of Advanced Motion Correction Technologies for Cardiac PET/CT

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


ADMINISTERING_IC: AI

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Infectious Diseases

ORG_CITY: PISCATAWAY

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: RUTGERS, THE STATE UNIV OF N.J.

ORG_STATE: NJ

PHR: Ricin is one of the most potent toxins known and a type B biothreat agent and the related Shiga toxins (Stxs) produced by E. coli (STEC) and Shigella dysenteriae remain enormous global health problems because at present, there is no known therapy against ricin or STEC. The proposed studies will develop novel small molecules that inhibit ricin and Shiga toxin 2 a by targeting their interactions with the ribosome. The findings are expected to be of great impact as they address the unmet need to develop novel ricin and STEC therapeutics by targeting toxin/ribosome interactions.

PI_NAMEs: TUMER, NILGUN E (contact)

PROGRAM_OFFICER_NAME: BAQAR, SHAHIDA

PROJECT_TERMS: Active Sites;Acute;Adopted;Affinity;Allosteric Regulation;analog;Animal Model;Antidotes;Binding;Binding Proteins;Binding Sites;Biological Assay;Bioterrorism;biothreat;C-terminal;Catalytic Domain;Categories;Cause of Death;Cell model;Cells;Chemicals;Child;Classification;Complex;Conserved Sequence;cost estimate;Cryoelectron Microscopy;cytotoxicity;Depurination;design;Development;diarrheal disease;Disease;Distant;Docking;Dysentery;efficacy evaluation;Elements;Escherichia coli EHEC;Evaluation;Face;Fluorescence Polarization;foodborne pathogen;Gastrointestinal Diseases;Generations;global health;Glycine decarboxylase;Hemolytic-Uremic Syndrome;Hemorrhagic colitis;holotoxins;Hydrophobicity;Immunologics;improved;inhibitor;innovation;insight;Lead;Location;Mammalian Cell;Molecular Conformation;Molecular Weight;Morbidity - disease rate;mortality;nanomolar;novel;novel strategies;Outcome;Pathogenesis;Peptides;peptidomimetics;physical property;Poison;Process;Proteins;Quantitative Reverse Transcriptase PCR;Regulation;Reporting;Research;Ribosomal Interaction;Ribosomes;Ricin;Roentgen Rays;scaffold;Series;Shiga Toxin;Shiga-Like Toxin II;Shigella;Shigella dysenteriae;Site;small molecule;small molecule inhibitor;Solubility;Structure;Structure-Activity Relationship;success;Supportive care;Surface Plasmon Resonance;Targeted Toxins;Testing;Therapeutic;therapeutic target;tool;Toxic effect;Toxin;Trefoil Motif;trend;virtual;Work;X-Ray Crystallography

PROJECT_TITLE: Small molecule inhibitors targeting the ribosome binding site of ricin and Shiga toxin

STUDY_SECTION: MSFA

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


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Eye Disease and Disorders of Vision;Liver Disease;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: DREXEL UNIVERSITY

PHR: PROJECT NARRATIVE: Metastatic uveal melanoma is one of the deadliest cancers – often associated with metastatic dissemination to the liver. Given that there is only one FDA-approved agent that improves survival by just six months, we are compelled to investigate novel treatment avenues to combat metastatic uveal melanoma. In this proposal we seek to gain mechanistic insights and highlight therapeutic vulnerabilities associated with the unique interplay between the liver microenvironment and uveal melanoma metastases.

PI_NAMEs: HARTSOUGH, EDWARD  (contact)

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: Adult;Amino Acids;Antioxidants;biological adaptation to stress;Biological Assay;Carrier Proteins;Cell Death;Cell Line;Cell Survival;Cells;chemotherapy;Clinical;Coculture Techniques;combat;Data;Data Set;Diagnosis;Disease;Dose;efficacy evaluation;erastin;experience;experimental study;Family;FDA approved;Genes;Genetic;Goals;Hepatic;Hepatocyte;Immune checkpoint inhibitor;Immune response;Immunity;immunogenic cell death;improved;In Vitro;in vivo;in vivo Model;inhibitor;innovation;insight;knock-down;knockout animal;Kupffer Cells;Lesion;Link;Lipid Peroxides;Lipids;Liver;Liver neoplasms;Macrophage;Malignant Neoplasms;Melanoma Cell;Melanoma patient;Metabolic;Metastatic Melanoma;Metastatic Neoplasm to the Liver;Methodology;migration;Modality;Modeling;Monitor;multiple omics;mutant;Neoplasm Metastasis;novel;novel therapeutics;Oxidative Stress;Pathway interactions;Patients;Pattern;Peripheral;Phagocytes;pharmacologic;Phenocopy;Predisposition;Prognosis;Protein Secretion;Proteins;Radiation therapy;Reactive Oxygen Species;Refractory;repository;Resistance;response;Selenium;Selenium Compounds;Selenocysteine;selenoprotein;Shapes;Signal Transduction;Slice;small hairpin RNA;standard care;Stress;Stress and Coping;Supplementation;System;Testing;Therapeutic;trait;transcriptomics;Tropism;tumor-immune system interactions;Up-Regulation;Uveal Melanoma

PROJECT_TITLE: Exploiting oxidative stress response in uveal melanoma liver metastases

STUDY_SECTION: CCB

STUDY_SECTION_NAME: Cancer Cell Biology Study Section[CCB]


ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: PROJECT NARRATIVE Chronic viral infections such as HBV, HCV, and HIV cause significant morbidity and mortality globally. Although T lymphocytes confer critical protection against viral infections, T cells often become dysfunctional or ‘exhausted’ in response to persistent pathogens. This proposal will investigate how key epigenetic regulators control T cell exhaustion in the setting of chronic infection, which may provide insights into novel therapeutic strategies to restore function to exhausted cells.

PI_NAMEs: MILNER, JOHN JUSTIN (contact)

PROGRAM_OFFICER_NAME: JIANG, CHAO

PROJECT_TERMS: acute infection;Binding;Biological Assay;BRD2 gene;Bromodomain;Bromodomains and extra-terminal domain inhibitor;CD8-Positive T-Lymphocytes;Cell Physiology;Cells;Cellular biology;Chromatin;Chronic;chronic infection;Clinical;Clinical Trials;Data;Disease;Enhancers;Epigenetic Process;epigenetic regulation;exhaust;exhaustion;Family;functional restoration;Gene Expression;Generations;Genes;Genetic;genetic approach;Genetic Enhancer Element;Genetic Screening;genome-wide;Germ Cells;Hepatitis B Virus;Hepatitis C virus;HIV;Human;immune checkpoint blockade;Immune system;Immunologics;improved;In Vitro;in vivo;Individual;Infection;Inflammatory;inhibitor therapy;insight;interest;Lymphocytic choriomeningitis virus;Malignant Neoplasms;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;novel;novel therapeutic intervention;pathogen;pharmacologic;programs;Reader;Reporting;response;Role;Specific qualifier value;stemness;T cell differentiation;T cell response;T-Lymphocyte;Tertiary Protein Structure;Testing;Therapeutic;transcription factor;transcriptomics;treatment strategy;Virus Diseases

PROJECT_TITLE: Epigenetic regulation of T cell differentiation during infection

STUDY_SECTION: CMIA

STUDY_SECTION_NAME: Cellular and Molecular Immunology - A Study Section[CMIA]


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Mental Health;Pediatric;Prevention;Social Determinants of Health

ORG_DEPT: MISCELLANEOUS

PHR: NARRATIVE The burden of mental health disorders among children in low- and middle-income countries (LMICs) such as Tanzania is an urgent global public health issue that must be addressed by interventions that target the upstream drivers of mental illness. The objective of this study is to identify malleable features of the primary school environment that longitudinally impact mental health outcomes and foster resilience among adversity-exposed youth in Tanzania. The study will inform the development of effective whole school interventions to promote mental health among children in Tanzania and other LMICs.

PI_NAMEs: MAMAN, SUZANNE ;REYES, H. LUZ MCNAUGHTON (contact)

PROGRAM_OFFICER_NAME: CAMPBELL-ROSEN, HOLLY RENEE

PROJECT_TERMS: Address;Adolescent;adolescent mental health;Adult;Age;Anxiety;Attenuated;Buffers;Caregivers;Child;child depression;Child Mental Health;Childhood;childhood adversity;Cognitive;cognitive function;cognitive process;Country;Data;Data Collection;Delaware;deprivation;Development;Dimensions;disability;early adolescence;early life adversity;effective intervention;Elements;Emotional;emotional functioning;Environment;experience;Exposure to;fifth grade;Fostering;Goals;Health Services Accessibility;improved;Income;Individual;informant;Interruption;Intervention;Interview;Life Cycle Stages;Link;low and middle-income countries;Measurement;Measures;Mediation;Mental disorders;Mental Health;Mental health promotion;Methods;Modeling;multi-component intervention;neglect;Outcome;Parents;Pathway interactions;peer;Perception;Physical environment;Play;Policies;Population;Poverty;Prevention approach;Primary Schools;Process;professional atmosphere;promote resilience;Psychometrics;Public Health;Qualitative Research;Random Allocation;Research;resilience;Role;Safety;Sampling;school environment;Schools;Shapes;social;Social Environment;Social Functioning;Social Processes;Structure;Students;Suicide;Surveys;System;systematic review;Tanzania;teacher;Testing;therapy development;Time;tool;Translating;treatment services;Validity and Reliability;violence exposure;Well in self;Work;Youth

PROJECT_TITLE: School Environment as a Social Driver of Youth Mental Health Trajectories in Mwanza, Tanzania

STUDY_SECTION: SPIP

STUDY_SECTION_NAME: Social Psychology, Personality and Interpersonal Processes Study Section[SPIP]


NIH_SPENDING_CATS: Breast Cancer;Cancer;Genetics;Lung;Prevention;Women's Health Research

ORG_CITY: TAMPA

ORG_NAME: H. LEE MOFFITT CANCER CTR & RES INST

ORG_STATE: FL

PHR: While we have significantly advanced the therapeutic options for breast cancer over the past decades, recurrent disease, often in a highly aggressive metastatic form, occurs years or even decades after remission and represents a significant hurdle in our ability to effectively cure breast cancer patients. Recurrent disease is thought to be powered by a process known as dormancy, which is when disseminated cancer cells from primary tumors temporarily inactivate and later re-awaken in a metastatic form; despite known to occur for over 60 years, our understanding of the molecular circuits that regulate this process is very limited, which has hindered the development of efficacious therapeutics that target disease relapse and prevent patient mortality. Here, we aim to gain a deep understanding of the cell-intrinsic pathways that drive dormancy and allow breast cancer cells to retain vitality in this state as well as how these cell-intrinsic pathways are fine-tuned by the environment at secondary organs with the overarching goal of unveiling new therapeutic targets for inactive breast cancer cells and thereby lead to the development of targeted therapies that can effectively prevent recurrent metastatic disease in breast cancer patients.

PI_NAMEs: DA SILVA GOMES, ANA  (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: Adjuvant Therapy;Affect;Biology;Breast;Breast Cancer Cell;breast cancer metastasis;Breast Cancer Patient;breast cancer progression;cancer cell;Cell Cycle;Cell Cycle Progression;Cell Reprogramming;Cells;Characteristics;Chromatin;chromatin remodeling;Clinical;Complex;CXCL5 gene;Data;Deposition;Development;Disease;Disease remission;Down-Regulation;Environment;Environmental Risk Factor;Epigenetic Process;Event;Fibroblasts;Foundations;Future;Genes;Genetic;Genetic Transcription;Goals;Histone H3;Histone H3.3;Histones;Homeostasis;Hypoxia;intravital imaging;Knowledge;Lead;Lung;Malignant - descriptor;Malignant Breast Neoplasm;Mediating;Metabolic;Metabolic Pathway;Metabolic stress;Metastatic breast cancer;Metastatic/Recurrent;Molecular;Molecular Chaperones;mortality;Nature;Neoplasm Metastasis;new therapeutic target;Operative Surgical Procedures;Organ;Oxidation-Reduction;Pathologic;Pathway interactions;Patient Care;Patients;Physiological;Positioning Attribute;prevent;Primary Neoplasm;Process;programs;Proliferating;Promoter Regions;Publishing;Pulmonary Fibrosis;Recurrence;Recurrent disease;Regulation;Resistance;response;Role;Site;standard of care;System;targeted treatment;Testing;Therapeutic;therapeutic target;therapy resistant;Time;tumorigenesis;tumorigenic;Variant;Woman;Work

PROJECT_TITLE: Epigenetic and metabolic bottlenecks of tumorigenesis

STUDY_SECTION: TEHM

STUDY_SECTION_NAME: Tumor Evolution, Heterogeneity and Metastasis Study Section[TEHM]


NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Mental Health;Mental Illness;Microbiome;Neurosciences;Physical Injury - Accidents and Adverse Effects;Post-Traumatic Stress Disorder (PTSD);Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: EAST LANSING

ORG_NAME: HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES

ORG_STATE: MI

PHR: Project Narrative  Veterans and the general public who suffer from traumatic brain injury (TBI) are at a significantly higher risk of developing psychiatric disorders such as posttraumatic stress disorder (PTSD), anxiety, and depression. A growing body of evidence demonstrates that TBI can disrupt the balance of gut microbiota, leading to a condition known as gut microbiota dysbiosis, which is strongly associated with psychiatric disorders. The objective of this project is to investigate the role of extracellular vesicles (EVs) derived from gut microbiota dysbiosis induced by TBI in the pathophysiology of comorbid psychiatric-like behaviors as well as explore the therapeutic potential of beneficial bacterial EVs by targeting the serotonergic system and neuroinflammation in a preclinical model of TBI, which will not only provide novel insights into the molecular mechanisms underlying psychiatric complications following TBI but also have the potential to facilitate the development of microbial- based approaches for the prevention and treatment of TBI in patients.

PI_NAMEs: LIU, XIANSHUANG  (contact);XIONG, YE

PROGRAM_OFFICER_NAME: AWWAD, HIBAH OMAR

PROJECT_TERMS: Ablation;Affect;Anabolism;Animals;Anxiety;anxiety-like behavior;Bacteria;bacterial genetics;Behavior;behavioral impairment;Biocompatible Materials;Cells;Communication;comorbidity;Data;Development;Diagnosis;Disease;dysbiosis;effective therapy;efficacious treatment;Engineering;Equilibrium;evidence base;Exposure to;extracellular vesicles;Feces;Functional disorder;Gene Expression;Gene Expression Profile;General Population;Gnotobiotic;gut microbiota;high risk;Immune response;Impairment;Incidence;Individual;Inflammation;Inflammatory Response;insight;intercellular communication;JAK2 gene;Lactobacillus brevis;Macrophage;Mediating;Memory impairment;Mental Depression;Mental disorders;microbial;microbial based therapy;microbiota composition;Microglia;Molecular;Mus;nanovesicle;Nerve Degeneration;neuroinflammation;Neurons;novel;novel therapeutics;Occupational;Pathogenesis;Pathway interactions;Patients;Play;Post-Traumatic Stress Disorders;Pre-Clinical Model;prevent;Prevention approach;Probiotics;psychiatric comorbidity;psychologic;psychosocial;Research;response;RNA;Role;serotonergic regulation;Serotonergic System;Serotonin;Signal Pathway;STAT3 gene;Stat3 protein;Stress;suicidal risk;TBI treatment;Testing;Therapeutic;Therapeutic Effect;Transfer RNA;Transgenic Mice;Traumatic Brain Injury;Tryptophan;Tryptophan Metabolism Pathway;vesicular release;Veterans;Virulence

PROJECT_TITLE: Investigating the role of gut-derived extracellular vesicles in PTSD following TBI

STUDY_SECTION: BINP

STUDY_SECTION_NAME: Brain Injury and Neurovascular Pathologies Study Section[BINP]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics;Human Genome

PHR: PROJECT NARRATIVE R-loops are RNA-DNA hybrids that normally help regulate gene expression, yet they can also lead to genome instability and have been implicated in diverse diseases ranging from cancer to neurological disorders. The proposed studies will elucidate the mechanisms that lead to the formation of deleterious R loops and the processes by which they are removed from the chromatin. Ultimately, a deeper understanding of these mechanisms may reveal strategies to harness R-loop metabolism for therapeutic purposes.

PI_NAMEs: CIMPRICH, KARLENE A (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Binding;Biological;Biological Assay;BRCA1 gene;BRCA2 gene;Cancer-Predisposing Gene;Cell Death;Cell Physiology;Cells;Characteristics;Chromatin;Chromosomes;Complication;coping;Cytoplasm;Data;Digestion;Disease;DNA;DNA biosynthesis;DNA Damage;DNA Repair;DNA replication fork;endonuclease;Equilibrium;Event;Excision;experimental study;Foundations;Gene Expression;Genetic Transcription;Genome;genome integrity;Genome Stability;Genomic approach;Genomic Instability;genomic locus;Genomics;Goals;helicase;human disease;Hybrids;Inflammatory;Innate Immune Response;Interphase Cell;Lesion;Malignant Neoplasms;Mammalian Cell;mammalian genome;Maps;Mediating;Metabolism;Methods;Modeling;Nature;Nervous System Disorder;Neurodegenerative Disorders;novel;Nuclear;nuclease;Nucleotide Excision Repair;Pathology;Pathway interactions;Polymerase;Predisposition;Process;programs;Purines;recruit;Recurrence;repaired;Reporting;Research;Resolution;RNA;RNA chemical synthesis;RNA Degradation;Role;S phase;SETX gene;Single-Stranded DNA;Site;Source;Spatial Distribution;Structure;System;Technology;Testing;Therapeutic;Transgenes

PROJECT_TITLE: Mechanisms of R-loop-Associated Genome Instability

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Lewy Body Dementia;Neurodegenerative;Neurosciences;Parkinson's Disease;Patient Safety;Rehabilitation

ORG_CITY: LEXINGTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECTIVE NARRATIVE The memory and cognitive deficits observed in Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are largely attributable to a loss of cholinergic function and neurons in the nucleus basalis of Meynert (NBM). Here we propose a Phase I single surgical-center, double-blinded clinical trial involving bilateral autologous peripheral nerve tissue (PNT) into the NBM to address “repair cell” support of cholinergic neurons. The major goal of this trial is to identify the feasibility and safety of bilateral implantation of reparative PNT to the NBM with the eventual goal to improve function of cholinergic neurons in dementia.

PI_NAMEs: GERHARDT, GREG A. (contact);QUINTERO, JORGE E;SLEVIN, JOHN T.;VAN HORNE, CRAIG

PROGRAM_OFFICER_NAME: CLARKE, AKANNI YAO

PROJECT_TERMS: Address;Affect;Agreement;alpha synuclein;Alzheimer's Disease;Amyloid beta-Protein;Area;Autologous;Autopsy;basal forebrain;Basal Nucleus of Meynert;Bilateral;Brain;Cell Therapy;Cell Transplantation;Cells;Cessation of life;cholinergic;cholinergic neuron;Classification;Clinical;Clinical Trials;Cognition;Cognitive;cognitive change;Cognitive deficits;cognitive testing;Colorado;Contralateral;cost;Data;Deep Brain Stimulation;Dementia;Dementia with Lewy Bodies;Deposition;design;Development;Diagnosis;Disease;dopaminergic neuron;Double-Blind Method;Etiology;Evaluation;Family;functional improvement;Future;Globus Pallidus;Goals;Health Care Costs;Histologic;Impaired cognition;Implant;implantation;improved;in vivo;Individual;Literature;Measures;Medical;Memory impairment;Morphology;Motor;Movement Disorder Society Unified Parkinson's Disease Rating Scale;Nerve Tissue;neurocognitive test;Neurodegenerative Disorders;Neurologic;Neurons;neuropathology;Neuropsychological Tests;open label;Operative Surgical Procedures;Outcome;Parkinson's Dementia;Participant;Pathology;Patients;Performance;Peripheral Nerves;pharmacologic;Pharmacological Treatment;Phase;phase 2 study;Phase I Clinical Trials;Phenotype;Population;Procedures;Process;Qualifying;Quality of Life Assessment;regenerative;repaired;restoration;Safety;safety and feasibility;secondary outcome;Secondary to;Serious Adverse Event;Side;Societies;standard of care;Study Subject;Substantia nigra structure;Supporting Cell;sural nerve;symptom treatment;System;tau Proteins;Time;trial design;Universities;Vascular Diseases;Visit

PROJECT_TITLE: Phase I Cell Therapy for Maintaining Cholinergic Circuits in the Spectrum of Alzheimer’s Disease

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


NIH_SPENDING_CATS: Aging;Cancer;Childhood Leukemia;Genetics;Hematology;Human Genome;Pediatric;Pediatric Cancer;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Narrative We propose that the methylation status of osteoblasts is altered by IDH1/2 mutant hematopoietic cells that arise with aging and during age related clonal hematopoiesis (ARCH). We will delineate how epigenetically modified mouse and human stromal cells and osteoblasts provide support for IDH clonal hematopoietic cells to expand and transform to MDS/AML with aging. These studies will identify osteoblast-derived signals that may be targeted therapeutically alone or in combination with current IDH inhibitors to improve treatment or prevent development of IDH mutant MDS/AML.

PI_NAMEs: KOUSTENI, STAVROULA  (contact)

PROGRAM_OFFICER_NAME: WILLIAMS, JOHN

PROJECT_TERMS: Acceleration;Acute Myelocytic Leukemia;Affect;Age;age related;Aging;beta catenin;Bone Marrow;Candidate Disease Gene;catalyst;Cell Lineage;cell stroma;Cells;Chromatin;Clinical;Clonal Evolution;Clonal Expansion;Clonal Hematopoietic Stem Cell;Clonality;Cytogenetics;Data;Development;Diagnosis;Dioxygenases;Disease;Disease Progression;DNA Methylation;driver mutation;Dysmyelopoietic Syndromes;epigenetic aging;Epigenetic Process;Future;gain of function mutation;Genes;Growth;healthy aging;Hematologic Neoplasms;Hematology;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;histone demethylase;histone methylation;Human;Hypermethylation;Impairment;improved;in vivo evaluation;Incidence;inhibitor;Isocitrate Dehydrogenase;Lead;leukemia;leukemia initiating cell;leukemic stem cell;Malignant - descriptor;Marrow;Methylation;methylome;Modeling;Mus;mutant;Mutate;Mutation;Mutation Detection;Myelogenous;Myeloproliferative disease;Osteoblasts;Patients;permissiveness;Plasma;Precancerous Conditions;premalignant;prevent;Process;Property;Proteins;Resistance;response;Risk;Role;Signal Transduction;Somatic Mutation;stem cell function;Stromal Cells;Subgroup;targeted treatment;Time;transcriptome sequencing;Transplantation;tumorigenic;Work

PROJECT_TITLE: Epigenetic deregulation of osteoblasts promotes age related clonality in hematopoietic cells

STUDY_SECTION: SBDD

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


ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

PHR: PROJECT NARRATIVE Old age is the most important unmodifiable risk factor for intracerebral hemorrhage (ICH) and CC-motif chemokine ligand 11 (CCL11) is circulating factor that increases in rodents and humans with aging. CCL11 distorts lung immune response and brain reparative functions that impact ICH-induced damages. We propose that inhibition of CCL11 signaling can be used as new therapeutic approach to treat ICH, especially in old age patients.

PI_NAMEs: JUNG, JOO EUN  (contact)

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: Acute Lung Injury;Affect;Age;age related;aged;Aging;aging brain;aging population;animal old age;Animals;Anti-Inflammatory Agents;Antibodies;antimicrobial;Blood;Blood Vessels;blood-brain barrier disruption;Brain;Brain Injuries;brain repair;cell type;Cells;Cerebral hemisphere hemorrhage;Cessation of life;chemokine;chemokine receptor;Chronic Lung Injury;Circulation;clinical outcome assessment;cytotoxic;Data;Elderly;Exposure to;Free Radicals;Functional disorder;Gene Expression;Gene Expression Profile;Genes;Goals;Hematoma;Homeostasis;Human;human old age (65+);Immune;Immunologics;Impairment;improved;In Vitro;Infiltration;Inflammation;Inflammatory;Injections;Injury;knock-down;Knock-out;Knockout Mice;Ligands;Lung;lung health;Lung immune response;Lung infections;lung injury;Mediating;Microglia;migration;Modeling;Mus;Neurologic Deficit;Neurologic Dysfunctions;Neutralization Tests;neutralizing antibody;Neutralizing antibody assay;neutrophil;novel;novel therapeutic intervention;old mice;older patient;Oropharyngeal;Outcome;Pathologic;Pathology;Pathway interactions;Patients;Persons;Phagocytes;Phagocytosis;Phenotype;Plasma;Play;PPAR gamma;promoter;receptor;repair function;repaired;response;Risk Factors;Rodent;Role;Severities;sex;Signal Transduction;Small Interfering RNA;SOD2 gene;Sorting;Stress;Stroke;stroke outcome;stroke patient;Testing;tissue injury;transcriptome sequencing

PROJECT_TITLE: Pathobiology of ICH in Aging