NIH_SPENDING_CATS: Brain Disorders;Cerebrovascular;Childhood Injury;Infant Mortality;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Preterm, Low Birth Weight and Health of the Newborn;Stroke;Unintentional Childhood Injury

ORG_CITY: ANN ARBOR

ORG_DEPT: EMERGENCY MEDICINE

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Current studies suggest that mitochondrial lipids play a key role in neonatal ischemia/reperfusion (I/R) injury through regulation of programmed cell death. The proposed research aims to investigate the role of cardiolipin, a mitochondrial phospholipid, following I/R injury using advanced cyclic ion mobility mass spectrometry in addition to several transgenic mouse-lines. These experiments aim to build a better understanding of neonatal I/R injury, uncover novel molecular mechanisms, and reveal potential therapeutic targets within mitochondrial lipids.

PI_NAMEs: EMAUS, KATLYNN JOY (contact)

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Anabolism;Animal Model;Antioxidants;Apoptosis;Asphyxia Neonatorum;Automobile Driving;Biological Assay;Blood flow;Brain;Brain Hypoxia-Ischemia;Brain Injuries;Brain region;cardiolipin synthase;Cardiolipins;Cell Death;Cell Survival;Charge;Clinical Research;clinically relevant;conditional knockout;Cre-LoxP;Critical Thinking;cytochrome c;defined contribution;deprivation;Development;disease model;Environment;Enzymes;Evaluation;experimental study;Exposure to;Fostering;Future;gain of function;Gases;Genes;Genetic;Glucose;Homeostasis;Hypoxia;hypoxia neonatorum;Hypoxic Brain Damage;In Vitro;in vivo;Infant;Infant Mortality;Injury;interest;ion mobility;Ischemia;Knock-out;lipidomics;Lipids;Lipolysis;loss of function;LoxP-flanked allele;Machine Learning;machine learning pipeline;Mass Spectrum Analysis;Mentorship;Methodology;Methods;Mitochondria;mitochondrial dysfunction;Modeling;Modification;Molecular;Molecular Analysis;monolysocardiolipin;Morphology;mouse model;Mus;Neonatal;neonatal brain;neonatal hypoxic-ischemic brain injury;neuron loss;Neurons;novel;Outcome;overexpression;oxidative damage;Oxidative Stress;Oxygen;particle;Perinatal;Periodicity;peroxidation;Phospholipase;phospholipase inhibitor;Phospholipids;Play;porcine model;prevent;Production;Protein Isoforms;pup;Quality Control;Reactive Oxygen Species;Regulation;Reperfusion Injury;Reperfusion Therapy;Reporter;Reproducibility;Research;Research Proposals;Role;Sampling;Scientist;Specificity;Spectrometry;Structure;System;Techniques;Technology;Therapeutic;therapeutic target;Tissues;Training;Transgenic Mice;Transgenic Organisms;Translational Research

PROJECT_TITLE: Evaluation of Mitochondrial Cardiolipin Modification in Neonatal Hypoxia/Ischemia Encephalopathy


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: ATLANTA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_FIPS: US

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: NARRATIVE Clostridioides difficile is a spore-forming bacterium that infects 500,000 people annually in the U.S., leading to severe diarrhea and possible death. My goal is to understand the role of the nutrient-sensing protein CodY in preventing sporulation of C. difficile. Since C. difficile spores are the only means of transmission for this pathogen, understanding how spores form is essential for limiting transmission and infection by C. difficile.

PI_NAMEs: MONTEIRO, MARCOS PAULO (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: Alleles;Amino Acids;Atmosphere;Bacteria;bile salts;Binding;Binding Sites;Biochemical;Biological Assay;Branched-Chain Amino Acids;Candidate Disease Gene;candidate identification;Cells;Cessation of life;Chemicals;Clostridium difficile;Co-Immunoprecipitations;Colitis;Colonic inflammation;Complement;Data;detection of nutrient;Diarrhea;Disinfectants;Electrophoretic Mobility Shift Assay;Experimental Designs;experimental study;Exposure to;Frequencies;Gastrointestinal tract structure;Gene Expression;Gene Expression Profile;gene function;Genes;Genetic;Genetic Transcription;Germination;Goals;Gram-Positive Bacteria;Growth;Guanosine Triphosphate;gut colonization;Health Care Costs;Human;Infection;Ingestion;insight;Intestines;Investigation;knock-down;Knowledge;Lead;Life Cycle Stages;Maps;Microscopy;Molecular;Motility;mutant;Mutate;Nutrient;Nutrient availability;nutrient deprivation;Outcome;Oxygen;pathogen;Persons;Phenotype;Phototherapy;prevent;Production;Proteins;Radiation;Regulation;Repression;Reproduction spores;Role;screening;Signal Pathway;Testing;Toxin;Transcriptional Regulation;transcriptome sequencing;transcriptomics;transmission process;Ultraviolet Rays;United States;Variant;Virulence;Work

PROJECT_TITLE: Identification of CodY-Regulated Factors that Control Sporulation in Clostridioides difficile


ADMINISTERING_IC: HL

ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Heart Disease;Pediatric;Pediatric Cardiomyopathy;Rare Diseases

ORG_CITY: TUCSON

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF ARIZONA

ORG_STATE: AZ

PHR: Project Narrative: Beta-adrenergic stimulation is a key regulator of myofilament diastolic performance in the context of an increase in hemodynamic demand. This proposal focuses on hypertrophic cardiomyopathy mutations that are known to exhibit diastolic dysfunction and impaired responses to the phosphorylation event of Serine 23/24 in cTnI that occurs during beta-adrenergic stimulation. We propose in-silico–in-vitro experimental coupling in order to investigate structural, dynamics, and functional changes induced by phosphorylation and mutations.

PI_NAMEs: CASTILLO, ROMI L (contact)

PROGRAM_OFFICER_NAME: HUANG, LI-SHIN

PROJECT_TERMS: Actins;Adrenergic Agents;Affect;Allosteric Regulation;ATP phosphohydrolase;Behavior;Binding;Binding Sites;Biological Assay;Calcium;Calcium Binding;Cardiac;causal variant;Clinical;Complex;Computer Models;Coupled;Coupling;Cryoelectron Microscopy;Cyclic AMP-Dependent Protein Kinases;Data;Disease;Dissociation;Event;Exercise;Exhibits;Experimental Designs;experimental study;flexibility;Fluorescence Anisotropy;Fluorescence Resonance Energy Transfer;Free Energy;Functional disorder;Genetic;Goals;Health;Heart Diseases;hemodynamics;Hypertrophic Cardiomyopathy;Impairment;in silico;In Vitro;Individual;Induced Mutation;intermolecular interaction;Kinetics;Left;Link;Maps;Measurement;Mediating;Methods;Microfilaments;Modeling;Molecular;molecular dynamics;Monitor;Muscle Contraction;Mutation;novel;Patients;Peptides;Performance;Phenotype;Phosphorylation;Phosphorylation Site;Play;Point Mutation;Process;Proteins;reconstitution;Regulation;Relaxation;Resolution;response;Restrictive Cardiomyopathy;Role;Serine;Severities;Signal Transduction;simulation;Site;stopped-flow fluorescence;Striated Muscles;Structure;Surface;System;Thin Filament;Time;time resolved data;time use;Tropomyosin;Troponin;Troponin C;Troponin I;Troponin T;Variant;Ventricular;Work

PROJECT_TITLE: Blunting of the Myofilament Beta-Adrenergic Response in HCM: Structural-Dynamic Mechanisms


ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative Abdominal aortic aneurysm (AAA) is an expansion of the aorta caused by the breakdown of structural proteins within the vessel wall. There are only surgical options for treating large AAAs that are at the highest risk of rupture, and currently no treatments for small AAA, which will become a high risk if ignored. The proposed research will investigate how a localized delivery system of stem cell secretions can stimulate restoration of structural proteins to pave the way for a new, non-invasive treatment of small AAAs.

PI_NAMEs: MARINI, ANDE XIAOJIE (contact)

PROGRAM_OFFICER_NAME: MEADOWS, TAWANNA

PROJECT_TERMS: 3-Dimensional;Abdominal Aortic Aneurysm;Address;Adipose tissue;Affect;American;Aneurysm;Aorta;aqueous;Blood Vessels;Cell Differentiation process;Cell secretion;Cells;Chronic;Clinical;Collagen;Communication;Computer Models;computerized tools;controlled release;Degenerative Disorder;Deposition;Diameter;Diffuse;Educational process of instructing;Elastic Fiber;Elastin;Encapsulated;Engraftment;Environment;Evaluation;ex vivo perfusion;experimental study;Exposure to;Extracellular Matrix;extracellular vesicles;Family suidae;Fibrin;Flow Cytometry;Foundations;Gel;Gene Expression;Growth;hemodynamics;high risk;In Vitro;innovation;Intervention;Iron;Knowledge;Label;Learning;Life;Magnetism;Mechanics;Medial;men;Mentors;Methods;Modeling;Monitor;mouse model;Movement;nanoparticle;novel;Operative Surgical Procedures;particle;Patients;Penetration;Physiological;preservation;pressure;Property;Proteins;regenerative;regenerative treatment;repaired;Research;restoration;Risk;Rupture;Side;side effect;Silk;Site;skills;Smooth Muscle Myocytes;standard of care;stem cells;Stromal Cells;Structural Protein;surgical risk;System;Technology;Testing;Therapeutic;Thrombus;Time;Tissues;Tunica Adventitia;Universities;uptake;Vascular Smooth Muscle;vesicle transport;vesicular release;Woman

PROJECT_TITLE: Extracellular Vesicle Delivery System for Treatment of Abdominal Aortic Aneurysm


NIH_SPENDING_CATS: Biotechnology;Emerging Infectious Diseases;Genetics;Infectious Diseases

PHR: NARRATIVE Inflammation induced by the bacteria Streptococcus pyogenes is responsible for rapid disease progression, including necrotizing fasciitis and toxic shock syndrome, resulting in morbidity and mortality during invasive infections. My research will investigate host-pathogen interactions to understand how host inflammatory cell death increases S. pyogenes virulence at a genetic level. Understanding mechanisms that drive inflammation will help identify critical targets to correct protective immunity and stall disease progression.

PI_NAMEs: GUERRA, STEPHANIE CORINNE (contact)

PROJECT_TERMS: Acute Rheumatic Heart Disease;alternative treatment;Antibiotics;Antibodies;antimicrobial peptide LL-37;Bacteria;Bacterial Infections;Biological Assay;cathelicidin antimicrobial peptide;Cell Culture Techniques;Cell Death;Cell Density;Cells;Cellular Structures;Cessation of life;chronic infection;Clustered Regularly Interspaced Short Palindromic Repeats;Confocal Microscopy;Cytolysis;Data;Diffusion;Disease;Disease Progression;Distant;Drug Targeting;Engineering;Enzyme-Linked Immunosorbent Assay;erythrogenic toxin;experimental study;Exposure to;fighting;Gene Expression;Gene Expression Regulation;Genetic;Genetic Techniques;Genome;Goals;Health;Healthcare Systems;Heterogeneity;Human;Immune;Immune Evasion;Immune response;Immunity;Impairment;Impetigo;In Vitro;Infection;Infectious Skin Diseases;Inflammation;Inflammatory;inflammatory milieu;insight;Integration Host Factors;keratinocyte;keratinocyte differentiation;Knock-out;lactate dehydrogenase A;Life;Measures;Mediating;Metabolic;Microscopy;Modeling;Morbidity - disease rate;mortality;Mus;mutant;Necrotizing fasciitis;new therapeutic target;Operative Surgical Procedures;pathogen;Pathogenesis;Pathology;Pathway interactions;Patients;Peptide Hydrolases;Peptides;Pharyngitis;Phosphorylation;Play;Population;Production;Regulation;Regulon;Reporter;Research;Resistance;response;Role;Series;Signal Transduction;Signaling Molecule;single cell analysis;Skin;small molecule;Streptococcus pyogenes;System;Testing;three dimensional cell culture;Toxic Shock Syndrome;Toxin;Transforming Growth Factor beta;treatment strategy;United States;Vaccines;Variant;VDAC1 gene;Virulence;Virulence Factors;Virulent;Western Blotting

PROJECT_TITLE: Investigating CovRS activation within skin microenvironments to drive heterogenicity of Streptococcus pyogenes gene expression


ADMINISTERING_IC: DK

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: STANFORD

ORG_DEPT: GENETICS

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: In humans, mutations in a number of core ribosome components lead to ribosomopathies, including Diamond- Blackfan anemia (DBA), which is characterized by fatal bone marrow failure. In all of these cases, the mechanism(s) that would account for cell type specific changes in hematopoietic cells underlying these diseases remain poorly understood. Here, we propose to employ novel technologies to pinpoint how alterations in accurate control of translation causes bone marrow failure in these diseases and identify small molecules that activate translational control as a new targeted therapy for DBA.

PI_NAMEs: BARNA, MARIA  (contact);SAKAMOTO, KATHLEEN M

PROGRAM_OFFICER_NAME: HATTANGADI, SHILPA MANOHAR

PROJECT_TERMS: 5' Untranslated Regions;Address;Adrenal Cortex Hormones;Apoptosis;Biogenesis;Bone marrow failure;Cell Count;Cell Cycle Arrest;cell type;Cells;Characteristics;Chemicals;clinical phenotype;clinically relevant;Congenital Abnormality;craniofacial;Craniofacial Abnormalities;Data;Defect;Development;Diamond-Blackfan anemia;Digit structure;Disease;disease phenotype;EIF4EBP1 gene;Elements;Erythroid;erythroid differentiation;experimental study;Failure;FDA approved;Functional disorder;gain of function;Gene Expression;Genetic;genome-wide analysis;helicase;Hematology;Hematopoietic;high throughput screening;Human;human disease;Impairment;in vivo;Knowledge;Lead;Limb structure;Link;loss of function;Maps;Mediating;Messenger RNA;Methodology;mouse model;Mutation;new technology;new therapeutic target;novel;novel therapeutics;Pathogenesis;Pathologic;Pathway interactions;Pharmacotherapy;Phenotype;Play;Prednisone;Protein Biosynthesis;Ribosomal Proteins;ribosome profiling;Ribosomes;ribosomopathy;RNA;Role;small molecule;Sorting;Specificity;Stress;Structure;Technology;Testing;Therapeutic;Time;Tissues;TP53 gene;Transcript;transcription factor;Translating;translation factor;Translations

PROJECT_TITLE: Investigating and targeting the translational landscape of DBA

STUDY_SECTION: TAG

STUDY_SECTION_NAME: Therapeutic Approaches to Genetic Diseases Study Section[TAG]


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);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Climate-Related Exposures and Conditions;Clinical Research;Dementia;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Neurodegenerative;Neurosciences;Social Determinants of Health;Women's Health Research

ORG_CITY: CAIRO

ORG_COUNTRY: EGYPT

ORG_FIPS: EG

ORG_NAME: AMERICAN UNIVERSITY IN CAIRO

PHR: Project Narrative This project will establish A Longitudinal Study of Egyptian Healthy Aging (“AL-SEHA”) modeled after the US HRS and its sister surveys. Egypt with its large and diverse aging population will add new insights to the international network of harmonized aging studies by representing a population at the intersection of Mediterranean, Arab and African influences, a strongly SES-graded cognitive decline, a large gender divide for elder women, and looming challenges for older citizens due to global warming. AL-SEHA will collect from 20,000 individuals in Egypt aged 50 years and older a baseline and a first follow-up wave including a cognitive assessment, community module, geocoded and environmental data.

PI_NAMEs: BOERSCH-SUPAN, AXEL H;RASHAD, HODA ;SALAMA, MOHAMED  (contact)

PROGRAM_OFFICER_NAME: CHATTERJI, MINKI

PROJECT_TERMS: Affect;Africa;African;age related;aged;Aging;aging mechanism;aging population;Air Pollution;Alzheimer disease screening;Alzheimer's disease related dementia;Alzheimer's disease risk;American;Applied Research;Arab country;Arab World;Arabs;Area;Asia;Budgets;China;Climate;climate change;Cognitive;cognitive testing;Communities;Comparative Study;Complex;Country;Cross-Sectional Studies;Cultural Diversity;Data;Data Analyses;Data Collection;data quality;Databases;Dementia;design;Development;Dimensions;Ecology;Economic Conditions;Economic Development;economic evaluation;Economics;Educational workshop;Egypt;Elderly woman;Elements;Environmental Risk Factor;Equity;Europe;experience;Family;feasibility testing;field survey;follow-up;Foundations;Funding;Gender;gender difference;Genetic;Genetic Variation;Genomics;Geographic Locations;Geography;global health;Global Warming;Government;Health;Health and Retirement Study;Health Sciences;Health Status;Health Surveys;healthy aging;Heat Waves;Human;Impaired cognition;India;Individual;Industrialization;Inequality;Inequity;insight;Institution;instrument;interest;International;Literature;Longitudinal Studies;Measures;member;men;Middle East;Middle Eastern;Mission;Modeling;Morbidity - disease rate;multidisciplinary;Nature;North America;Older Population;outreach;Personal Satisfaction;Pesticides;Policies;Policy Developments;Policy Maker;policy recommendation;Politics;Population;population survey;Positioning Attribute;Prevalence;Probability Samples;Protocols documentation;Psyche structure;Publishing;Questionnaires;Recording of previous events;Research;Retirement;Rural Community;Rural Population;Sampling;Scheme;Secure;Shapes;Sister;social;social determinants;Social Sciences;Societies;socioeconomics;South Africa;South America;success;Surveys;Testing;Time;timeline;tool;Translations;Universities;Urban Community;Urban Population;user-friendly;Variant;Water Pollutants;Woman;Work

PROJECT_TITLE: A Longitudinal Study of Egyptian Healthy Aging (Al-SEHA)

STUDY_SECTION: SSPA

STUDY_SECTION_NAME: Social Sciences and Population Studies A Study Section[SSPA]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

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;Cerebrovascular;Clinical Research;Dementia;Genetics;Lewy Body Dementia;Mental Health;Neurodegenerative;Neurosciences;Prevention;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

PHR: PROJECT NARRATIVE This project aims to ameliorate dementia burden through identifying modifiable environmental risk factors. The project will utilize neurological examination and clinical diagnosis from the National Alzheimer’s Coordinating Center (NACC) Study and repository plasma samples from the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), to determine the metal concentrations, and examine associations of these metals with dementia risk and longitudinal changes in related outcomes. In addition, the concepts learned through this grant and the career development pursued by the investigator, will be readily applicable to his future research focusing on the intersection of environmental epidemiology and dementia.

PI_NAMEs: WANG, XIN  (contact)

PROGRAM_OFFICER_NAME: MARTIN, DAMALI

PROJECT_TERMS: Acceleration;Activities of Daily Living;Affect;Aging;Alleles;alpha synuclein;Alzheimer's Disease;Alzheimer's disease related dementia;Amyloid beta-Protein;Apolipoprotein E;apolipoprotein E-4;Biological;Biometry;blood cerebrospinal fluid barrier;Blood specimen;Blood Vessels;blood-brain barrier crossing;Brain;Cadmium;career;career development;Clinical;clinical diagnosis;Cognition;Cognitive;cognitive testing;Collaborations;data management;Dementia;dementia burden;dementia risk;Development;Disease;Disease Progression;Doctor of Philosophy;education research;Environmental Epidemiology;Environmental Pollutants;Environmental Risk Factor;Equipment and supply inventories;Evaluation;Examinations and Diagnoses;Exposure to;follow-up;Foundations;Frontotemporal Dementia;Funding;gene environment interaction;Genes;Genetic;genetic epidemiology;genetic risk factor;Genotype;Goals;Grant;Human;Incidence;Intervention;Joints;Knowledge;Lead;Learning;Lewy Body Disease;Link;Manganese;Master of Public Health;Measures;Mentored Research Scientist Development Award;Mentors;Mercury;Metal exposure;Metals;Michigan;modifiable risk;Modification;mortality;Nerve Degeneration;Neurobiology;Neurodegenerative Disorders;neurogenetics;Neurologic Examination;Neurology;neuropathology;neuropsychiatric symptom;neuropsychiatry;Neurosciences;neurotoxicity;Neurotoxins;Outcome;Parkinson Disease;Pathologic;Pathology;Pathway interactions;Persons;Plasma;Play;Population;Positioning Attribute;Prevalence;prevent;Prevention;Principal Investigator;programs;protein TDP-43;Proteins;Questionnaires;repository;Research;research clinical testing;Research Personnel;Resources;Risk Factors;Role;Sampling;skills;tau Proteins;Toxic effect;Training;training opportunity;uptake;Vascular Dementia

PROJECT_TITLE: Metals Exposure, Dementia, and Longitudinal Trajectories of Cognition, Functioning, and Neuropsychiatric Symptoms

STUDY_SECTION: AGCD

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


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOL OF MEDICINE & DENTISTRY

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Transplantation

ORG_CITY: ROCHESTER

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF ROCHESTER

ORG_STATE: NY

PHR: Project Narrative This proposal will develop new methods for studying the integration and function of hNPCs transplanted into the mouse brain, thereby providing critical mechanistic insights that will advance the field of stem cell transplantation as a therapy. Mice are one of the major mammalian model organisms for research on stem cell transplant therapy and many organizational principles of cell types and circuits are conserved across evolution, making them critical to understanding neurodegenerative and neurological disorders like Alzheimer’s Disease, Parkinson’s and stroke. This proposal will establish new experimental paradigms to investigate the cell and systems biology of stem-cell transplantation therapies and their functions, thus providing critical clues into why some stem cell strategies are successful and others are not.

PI_NAMEs: PADMANABHAN, KRISHNAN  (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Adolescent;Adult;Affect;Alzheimer's Disease;Animal Model;Animals;Area;awake;biophysical properties;Biophysics;Brain;calcium indicator;Cell Death;Cell Differentiation process;Cell division;Cell Line;cell motility;Cell Proliferation;Cell Therapy;Cell Transplantation;cell type;Cells;Cellular biology;Complex;density;Electrophysiology (science);Engraftment;Evolution;experimental study;functional restoration;Goals;Hippocampus;Human;human induced pluripotent stem cells;Image;imaging modality;Immunohistochemistry;in vivo;in vivo imaging;individual patient;innovation;insight;Link;Methods;migration;model organism;Molecular;Molecular Profiling;multi-photon;Mus;Needs Assessment;Neocortex;nerve stem cell;Nervous System Disorder;neural;neural network;Neurites;Neurodegenerative Disorders;Neuroglia;neuron loss;Neuronal Differentiation;Neurons;neurophysiology;Neurosciences;Nuclear Pore Complex;Parkinson Disease;patch clamp;Pathology;Patients;Physiological;Population;post-transplant;Process;Proliferating;Property;Research;SCID Mice;Shapes;single-cell RNA sequencing;stem cell biology;stem cell therapy;Stem cell transplant;stem cells;Stroke;success;System;Systems Biology;therapy design;Transplantation;transplantation therapy;Treatment Efficacy;two-photon;Visual Cortex;visual stimulus

PROJECT_TITLE: Studying stem cell-based therapies by applying advanced in vivo physiological and imaging methods to transplanted human neural populations in mice

STUDY_SECTION: BNVT

STUDY_SECTION_NAME: Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section[BNVT]


ADMINISTERING_IC: EY

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: NEW HAVEN

ORG_DEPT: PSYCHOLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE A thorough understanding of PPC visual representation characteristics and their interactions with distraction in visual working memory (VWM) can help us better understand the various constraints and limitations of visual processing in VWM and general task performance. It can additionally help us formulate better treatment and rehabilitation plans to facilitate the recovery of PPC functions after lesion. Greater knowledge of PPC function can also provide guidance to the removal of possible PPC tissues due to epilepsy.

PI_NAMEs: XU, YAODA  (contact)

PROGRAM_OFFICER_NAME: FLANDERS, MARTHA C

PROJECT_TITLE: Adaptive visual representation in human posterior parietal cortex

STUDY_SECTION: HCMF

STUDY_SECTION_NAME: Human Complex Mental Function Study Section[HCMF]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: MADISON

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: The Circulating Biomarker Core within the University of Wisconsin – Madison NCI-designated Carbone Cancer Center, led by Facility Manager Dr. Jennifer Schehr, provides centralized liquid biopsy method development, clinical trial sample processing, and assay preparation for regulatory approval for routine clinical use. Dr. Schehr leads the core’s innovative technological problem-solving with her extensive collaborative network leveraging her PhD in immunology, 2 years of FDA-approved assay development, and 9 years of custom liquid biopsy sample processing technology development, supporting 12 active clinical trials, 10 in development and 28 research projects involving 40 investigators, 22 NCI-designated cancer centers, and 10 other institutions. The services of the core aim to accelerate the process from discovery of promising new biomarkers to extensive evaluation for regulatory approval to provide more advanced predictive and pharmacodynamic biomarkers of resistance to clinicians and increase the efficiency of precision medicine approaches for patients with cancer.

PI_NAMEs: SCHEHR, JENNIFER L (contact)

PROGRAM_OFFICER_NAME: OSSANDON, MIGUEL

PROJECT_TERMS: Acceleration;Achievement;assay development;Attention;Biological Assay;Biological Markers;Biology;biomarker discovery;biomarker performance;Biomedical Engineering;Biopsy Specimen;Cancer Biology;Cancer Center;Cancer Center Support Grant;cancer type;circulating biomarkers;Clinical;clinical application;Clinical Research;Clinical Trials;clinically actionable;Collaborations;computerized tools;Country;Custom;data handling;data management;Development;Disease;Doctor of Philosophy;drug development;Education;Evaluation;Faculty;FDA approved;Funding;Future;Grant;Immunology;innovation;innovative technologies;Institution;Investments;Laboratories;Laboratory Finding;Libraries;liquid biopsy;Malignant neoplasm of prostate;Malignant Neoplasms;Messenger RNA;method development;Methods;minimally invasive;Monitor;Mutation;NCI-Designated Cancer Center;Neoplasm Circulating Cells;novel;Nucleic Acids;Patients;Pattern;pharmacodynamic biomarker;Pharmacologic Substance;Plasma;Play;precision medicine;predictive marker;Preparation;Problem Solving;Process;programs;Proteins;recruit;Research;Research Infrastructure;Research Personnel;Research Project Grants;Resistance;Resource Sharing;Role;Sampling;Scientific Advances and Accomplishments;Services;Technology;technology development;tumor;tumor DNA;undergraduate student;Universities;Validation;Wisconsin

PROJECT_TITLE: Development and Deployment of Liquid Biopsies in Bench Research and Clinical Trials in the UW Circulating Biomarker Core

STUDY_SECTION_NAME: Special Emphasis Panel[ZCA1 SRB-1 (M2)]


ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Narrative: Accumulation of pro-inflammatory macrophages in the vessel wall is a hallmark observed in atherosclerosis, an effect that is markedly accelerated in diabetes. Our preliminary studies indicate that a novel macrophage-enriched long non-coding RNA (lncRNA) termed MERRICAL may act to control lesion formation within the vessel wall by regulating macrophage accumulation and pro-inflammatory signaling pathways. The proposed studies will provide a detailed understanding underlying the function of this lncRNA, its interactors, and how to leverage therapeutic manipulation of this lncRNA and its interactors with the goal of developing novel lncRNA-based therapies for the treatment of the accelerated atherosclerotic disease in diabetes.

PI_NAMEs: FEINBERG, MARK W (contact)

PROGRAM_OFFICER_NAME: CHEN, JUE

PROJECT_TERMS: Acceleration;Accounting;Address;Affect;Arterial Fatty Streak;Atherosclerosis;Attention;Biological Process;Biophysics;Cardiovascular system;Carotid Artery Diseases;CCL3 gene;CCL4 gene;Cells;chemokine;Chemotaxis;Cholesterol;Chronic;Code;Complex;Data;Dependence;Detection;Diabetes Mellitus;Diet;Disease;Enzymes;Epigenetic Process;Event;Fatty acid glycerol esters;Foundations;gain of function;Genes;genetic signature;Goals;Histones;Homologous Gene;Human;immune cell infiltrate;Impairment;in vivo;Individual;Inflammasome;Inflammation;Inflammatory;inhibitor;insight;Ischemia;knock-down;Knockout Mice;Lesion;Lipids;Longitudinal Studies;loss of function;Macrophage;Mediating;Medical;Molecular;monocyte;Mus;Myelogenous;Myocardial Infarction;Necrosis;new therapeutic target;novel;novel therapeutic intervention;Nuclear;Play;Process;Proteins;recruit;Regulation;Risk;RNA;Role;Signal Pathway;Signal Transduction;Sucrose;Therapeutic;therapeutic RNA;transcriptome sequencing;Untranslated RNA;Vascular Diseases

PROJECT_TITLE: LncRNA MERRICAL, macrophage chemotaxis, and diabetes-associated atherosclerosis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Biotechnology;Infectious Diseases;Pediatric;Prevention;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: BLACKSBURG

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

ORG_STATE: VA

PHR: NARRATIVE. Syphilis is a sexually transmitted infection that causes significant human disease throughout the world. New diagnostics that accurately detect the syphilis agent, early in disease, would greatly improve patient outcomes by accelerating access to potentially life-saving treatment. We have discovered that the bacterium that causes syphilis sheds unique pieces of its’ cell-wall into its environment as it grows. In this proposal we will develop a diagnostic tool that specifically detects these unusual, released cell wall fragments, and critically assess its performance in human syphilis patient samples.

PI_NAMEs: JUTRAS, BRANDON LYON (contact)

PROGRAM_OFFICER_NAME: GLOCK, JONATHAN A

PROJECT_TERMS: Acceleration;accurate diagnostics;Animal Experimentation;Animal Model;Animals;Antibiotic Therapy;Antigen Targeting;aptamer;Bacteria;Bacterial Infections;Basic Science;Benchmarking;biobank;Biological Assay;Biological Markers;Biology;Birth;Cell Cycle;cell growth;Cell Wall;Cessation of life;Chemicals;Child;Clinic;Communicable Diseases;Communities;Congenital Syphilis;Data;Detection;Development;Diagnosis;Diagnostic;diagnostic platform;Diagnostic tests;diagnostic tool;Disease;DNA;early detection biomarkers;Early Diagnosis;effective therapy;Environment;Excretory function;Experimental Animal Model;extracellular;fetal;General Population;Generations;Genome;Growth;Health;Hour;Human;human disease;Immune response;Immunocompromised Host;improved;Individual;Infection;Knowledge;Label;Lesion;Life;Location;Lyme Disease;Medical;Methods;Monoclonal Antibodies;next generation;novel;novel diagnostics;novel strategies;Order Spirochaetales;Painless;Parents;Patient-Focused Outcomes;Patients;Peptidoglycan;Performance;point-of-care diagnosis;Populations at Risk;Pregnancy;Proteins;Publishing;Radioisotopes;rapid detection;Recombinants;Recycling;Reporting;Research Personnel;Resolution;response;Sampling;Sensitivity and Specificity;Serology;Serology test;Serum;sex;Sexual Transmission;Sexually Transmitted Diseases;Specificity;stillbirth;success;Syphilis;System;targeted treatment;Technology;Testing;transmission process;Treponema;Treponema pallidum;United States;Urine;virtual

PROJECT_TITLE: Released peptidoglycan fragments are a biomarker for early stages of syphilis

STUDY_SECTION_NAME: Special Emphasis Panel[ZAI1 FDS-M (M1)]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Coronaviruses;Coronaviruses Disparities and At-Risk Populations;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Mental Health;Neurosciences;Pediatric;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_DEPT: PSYCHIATRY

PHR: NARRATIVE The project will elucidate the structure of RDoC threat and reward domains across symptom, behavior, and brain units of analysis using data-driven analytics in a sample of 500 participants examined at two points. Moreover, the study will examine the extent to which various types of poverty-related adversities predict threat versus reward processes in a large, representative sample of young adults followed since birth and recruited from families living in poverty. The supplement will enable the aims of the study to be complete despite COVID challenges.

PI_NAMEs: HYDE, LUKE WILLIAMSON;MITCHELL, COLTER M.S.;MONK, CHRISTOPHER STEPHEN (contact)

PROGRAM_OFFICER_NAME: MURPHY, ERIC ROUSSEAU

PROJECT_TERMS: Affect;African American;Age;Anxiety;Behavior;biotypes;Birth;Black American;Black race;Brain;Budgets;Child;Child Welfare;Cities;Clinical;Clinical Psychology;cohort;computerized data processing;Consensus;cost;COVID-19;COVID-19 impact;Creativeness;Cross-Sectional Studies;Data;Data Analyses;Data Collection;data structure;Demography;design;Development;Diffusion Magnetic Resonance Imaging;Disease;emerging adult;Ethnic Origin;exhaust;Exposure to;Family;Functional Magnetic Resonance Imaging;Funding;Future;Goals;improved;Income;Individual;Interview;Investments;Link;Longitudinal cohort;Longitudinal Studies;Low income;lower income families;Magnetic Resonance Imaging;Maintenance;Maps;member;Mental Depression;multimodal data;multimodal modeling;National Institute of Mental Health;Nature;neural;neural circuit;neuroimaging;Neurosciences;pandemic disease;Participant;patient engagement;Patient Self-Report;Persons;Phenotype;Population;Positioning Attribute;post-COVID-19;Poverty;Process;Psychopathology;Race;recruit;Research;Research Domain Criteria;research study;resilience;Resources;response;Rewards;Risk;Sample Size;Sampling;social;Source;Structure;Students;Surveys;Symptoms;Testing;Time;Underrepresented Populations;Visit;young adult

PROJECT_TITLE: Computational examination of RDoC threat and reward constructs in a representative, predominantly low-income, longitudinal sample at increased risk for internalizing disorders (Admin Supplement)


ORG_CITY: STONY BROOK

ORG_DEPT: PHARMACOLOGY

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: PROJECT NARRATIVE By unraveling the molecular mechanism through which DNA replication fork protection determines oncogene- induced senescence and oncogenic transformation, this study will provide new insight into how disruption of replisome activity is linked to oncogene-induced replication stress and fork instability. Fundamental knowledge on the signal transduction pathways essential for this fail-safe tumor suppressive barrier will help develop a strategy that exploits the replication vulnerability of cancer cells as a new therapy and augment the effort to identify potential biomarkers relevant to DNA replication stress in cancer patients.

PI_NAMEs: KIM, HYUNGJIN  (contact)

PROGRAM_OFFICER_NAME: WEINREICH, MICHAEL DALE

PROJECT_TERMS: Acceleration;Affect;Bypass;cancer cell;Cancer Patient;Cancerous;carcinogenesis;cell growth;Cell model;Cells;Complex;Defect;design;Development;disabled;DNA biosynthesis;DNA Damage;DNA replication fork;DNA Replication Induction;Down-Regulation;Epithelial Cells;gain of function;Genome;genome integrity;Genomic Instability;Goals;human model;Impairment;insight;Knowledge;KRASG12D;Lesion;Link;Maintenance;Malignant - descriptor;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;Metastatic Prostate Cancer;Missense Mutation;Mitogens;Modeling;Molecular;mouse model;Mutation;Nature;Neoplasm Metastasis;Non-Malignant;novel;novel therapeutics;Oncogenes;Oncogenic;Organoids;overexpression;Pathway interactions;PIK3CG gene;Play;Polymerase;Post-Translational Protein Processing;potential biomarker;Predisposition;premalignant;Premalignant Cell;pressure;prevent;Process;programs;Prostate;prostate cancer model;prostate cancer progression;prostate carcinogenesis;protective pathway;Proteins;Proto-Oncogene Proteins c-akt;Replication Initiation;replication stress;Resistance;response;restraint;Role;senescence;senescent cell;Signal Transduction;Signal Transduction Pathway;stem;Stimulus;Stress;Testing;Therapeutic;transmission process;tumor;tumor initiation;tumor progression;tumorigenesis;Up-Regulation

PROJECT_TITLE: Roles of TIMELESS in oncogene-induced senescence and oncogenic transformation

STUDY_SECTION: BCO

STUDY_SECTION_NAME: Biochemical and Cellular Oncogenesis Study Section[BCO]


NIH_SPENDING_CATS: Cardiovascular;Congenital Heart Disease;Genetics;Heart Disease;Human Genome;Infant Mortality;Orphan Drug;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human;Sudden Infant Death Syndrome

PHR: Narrative hERG1 is a voltage gated potassium channel that regulates cardiac function. We identified a subdomain of the hERG1 potassium channel, hERG1NP, that is targeted to the nuclei of immature cardiac cells. From the nucleus, the hERG1NP alters gene expression as well as hERG1 channel gating and expression. The approaches that we implement in this grant will define the mechanisms that regulate hERG1NP function and its impact on potassium channel activity and cell function, which will improve the accuracy of predicting the pathogenicity of hERG1NP variants and may inform future drug design targeting this channel.

PI_NAMEs: JONES, DAVID K. (contact)

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: Action Potentials;Adolescence;Arrhythmia;Benign;Biogenesis;Biological Assay;C-terminal;Cardiac;Cardiac Electrophysiologic Techniques;Cardiac Myocytes;cardiogenesis;Cell Line;Cell Nucleus;Cell Physiology;Cells;Childhood;ChIP-seq;Clinical;Clinical Data;Clustered Regularly Interspaced Short Palindromic Repeats;Coiled-Coil Domain;Confocal Microscopy;Data;defined contribution;density;Development;differential expression;Disease;Distal;Drug Design;Electrophysiology (science);Elements;Feedback;fetal;Fetal Death;Functional disorder;Future;Gene Expression;Generations;Genes;Goals;Grant;Heart;Heart Diseases;heart electrical activity;heart function;Human;human disease;human embryonic stem cell;human induced pluripotent stem cells;human pluripotent stem cell;human stem cell-derived;improved;Incidence;indium arsenide;induced pluripotent stem cell derived cardiomyocytes;insight;Ion Channel;Knock-in;Length;Life;Link;Long QT Syndrome;loss of function;Maps;Measures;Mediating;meetings;Membrane;Molecular;Molecular Biology;Morphology;Mus;Mutation;Neonatal;novel;novel therapeutics;Nuclear;Nuclear Protein;Null Lymphocytes;overexpression;Overlapping Genes;patch clamp;Pathogenicity;Physicians;Physiology;polypeptide;Potassium Channel;Predisposition;Proteins;Rattus;Regulation;Role;Site-Directed Mutagenesis;stem cells;sudden cardiac death;Sudden infant death syndrome;Surface;Tail;Testing;Tissues;transcriptome;transcriptome sequencing;Variant;Voltage-Gated Potassium Channel;Work

PROJECT_TITLE: A hERG1 potassium channel subdomain is trafficked to the cardiac nucleus: mechanisms and targets of the hERG1NP

STUDY_SECTION: BBHV

STUDY_SECTION_NAME: Basic Biology of Blood, Heart and Vasculature Study Section [BBHV]


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Data Science;Dissemination and Implementation Research;Genetic Testing;Genetics;Health Services;Heart Disease;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Patient Safety;Pediatric;Pediatric Cardiomyopathy;Precision Medicine;Prevention;Rare Diseases

ORG_CITY: DURHAM

ORG_DEPT: PHYSIOLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: In rare genetic heart disease, early identification of at-risk individuals is important so that disease may be prevented or treated in the patient, but these diseases are often underdiagnosed. In this study, we will use innovative artificial intelligence approaches on heart images and medical record data to identify patients who may have evidence of an undiagnosed rare genetic heart disease, with a focus on hypertrophic cardiomyopathy and transthyretin cardiac amyloidosis. The results of this study could help create algorithms to identify undiagnosed diseases in patients and help guide them towards treatments.

PI_NAMEs: SHAH, SVATI H. (contact);VEMULAPALLI, SREEKANTH ;ZHANG, ANRU

PROGRAM_OFFICER_NAME: ANAYA, GABRIEL

PROJECT_TERMS: Acceleration;Address;Algorithms;Amyloidosis;Artificial Intelligence;biobank;black patient;cardiac amyloidosis;Cardiovascular Diseases;Caring;Clinic;Clinical;cohort;computable phenotypes;cost;Coupled;Data;deep learning;deep learning algorithm;Detection;Development;Diagnosis;Diagnostic;Disease;disease-causing mutation;Early identification;Echocardiography;Electronic Health Record;evidence base;Genes;Genetic;genetic approach;Genetic Models;genetic testing;genetic variant;Genomic approach;Genomic medicine;Goals;Health system;Healthcare Systems;Heart Diseases;heart imaging;Hematological Disease;high risk;Hypertrophic Cardiomyopathy;Image;implementation research;implementation strategy;improved;Individual;innovation;Left ventricular structure;Lung Diseases;Machine Learning;machine learning algorithm;machine learning model;machine learning prediction;Medical Records;Mendelian disorder;model development;Modeling;Morbidity - disease rate;mortality;Outcome;Output;Pathogenicity;Patient Care;patient population;Patients;Penetrance;Performance;Phenotype;Population;population based;Prealbumin;precision genetics;Predictive Analytics;prevent;Prevention;research study;Risk;Sleep Disorders;System;Therapeutic Intervention;Therapeutic Uses;Validation;Variant;variant of unknown significance

PROJECT_TITLE: Machine Learning Guided Precision Genetic Testing for Identification of Monogenic Cardiovascular Disorders

STUDY_SECTION: CDMA

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


ADMINISTERING_IC: DA

ED_INST_TYPE: ORGANIZED RESEARCH UNITS

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Drug Abuse (NIDA only);Pediatric;Prevention;Social Determinants of Health;Substance Misuse

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

PHR: PROJECT NARRATIVE This proposal is to continue the ongoing Monitoring the Future (MTF) Panel study, which has surveyed new nationally representative samples of high school seniors every year since 1976 to track patterns and consequences of substance use and HIV/AIDS risk and protective behaviors. This application covers five new longitudinal data collections in 2023 through 2027 from national samples of adults ages 19 through 65 (approximately 120,000 people total). This application – the MTF Panel – is part of the integrated MTF study; a companion R01 application (the MTF Main) requests funding to continue (a) to collect annual nationally representative cross-sectional data from secondary school students, and (b) to analyze all cross-sectional and longitudinal data.

PI_NAMEs: PATRICK, MEGAN E. (contact)

PROGRAM_OFFICER_NAME: LOPEZ, MARSHA

PROJECT_TERMS: Achievement;addiction;Address;Adolescence;Adolescent;Adult;Affect;Age;age related changes;aged;Alcohol consumption;Alcohols;Annual Reports;Attitude;Basic Science;Behavior;Belief;Cannabis policy;Categories;Cessation of life;cohort;Cohort Effect;college;Communities;Companions;COVID-19;Data;Data Analyses;data archive;Data Collection;Deposition;depressive symptoms;design;Development;Developmental Course;Drug Prescriptions;Drug usage;Drunk driving;Education;Educational workshop;eighth grade;Epidemiology;Ethnic Origin;Etiology;Event;experience;Family;Family member;follow-up;Funding;Future;Gender;Goals;Grant;Health;Heterogeneity;high school;High School Student;HIV;HIV/AIDS;Home;Illicit Drugs;improved;indexing;Individual;Injections;Knowledge;Legal;Life;Life Cycle Stages;Literature;longitudinal dataset;longitudinal design;Longitudinal trends;Longterm Follow-up;marijuana use;Measurement;Medical;Modality;Monitor;Morbidity - disease rate;mortality;National Institute of Drug Abuse;Needle Sharing;Nicotine;novel therapeutics;Occupational;older adult;Online Systems;Pattern;peer;Personal Satisfaction;Persons;Pharmaceutical Preparations;Policies;Population;Prevalence;Prevention;programs;protective behavior;protective factors;Race;Random Allocation;recruit;Reporting;Request for Applications;Research;Research Personnel;research study;Risk;Risk Behaviors;Risk Factors;Role;Sampling;Schools;Sex Behavior;social;Social Environment;socioeconomics;Source;Students;Subcategory;Subgroup;substance misuse;substance use;Substance Use Disorder;Surveys;Symptoms;Teenagers;tenth grade;tobacco products;Tobacco use;Training;transmission process;trend;twelfth grade;United States;United States National Institutes of Health;university student;vaping;Work;young adult

PROJECT_TITLE: Monitoring the Future: A Cohort-Sequential Panel Study of Drug Use, Ages 19-65

STUDY_SECTION: ARM

STUDY_SECTION_NAME: Addiction Risks and Mechanisms Study Section[ARM]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Childhood Injury;Clinical Research;Drug Abuse (NIDA only);Mental Health;Neurosciences;Pediatric;Physical Activity;Physical Injury - Accidents and Adverse Effects;Prevention;Social Determinants of Health;Substance Misuse;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE The ABCD Study consortium uses multimodal brain imaging, cognitive and clinical assessments, bioassays, mobile monitoring, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning in 11,878 9-10 year-olds to be followed over 10 years, to determine the effects of substance use on adolescent brain and cognitive development. This ABCD Research Project Site will follow and assess participants enrolled in the study. These data will be shared with the scientific community to address a comprehensive range of questions concerning youth development.

PI_NAMEs: FAIR, DAMIEN A;FELDSTEIN EWING, SARAH W.;NAGEL, BONNIE J (contact)

PROGRAM_OFFICER_NAME: DEEDS, BETHANY

PROJECT_TERMS: 10 year old;Address;Adolescence;Adolescent;adolescent substance use;Adult;adverse outcome;Affect;Age;Alcohol consumption;Alcohols;Anxiety;assessment application;Athletic Injuries;Behavior;Behavioral;Bioinformatics;Biological;Biological Assay;Biology;Brain;Brain imaging;Caffeine;Calendar;Cannabis;Child;Child Health;Childhood;Clinical assessments;Cognition;Cognitive;cognitive development;cognitive testing;cohort;college;Communities;Country;Data;Data Analyses;Decision Making;design;Development;emerging adult;Emotional;emotional factor;Enrollment;Ensure;Environment;Environmental Exposure;Environmental Risk Factor;Epidemiology;Ethics;Event;experience;Feeling suicidal;Female;follow-up;Funding;gene interaction;Genetic;Health;Impairment;Individual;Informatics;informatics infrastructure;Interview;Life;Link;Longitudinal Studies;marijuana use;Mental Depression;Mental disorders;Mental Health;Methodology;Methods;mobile application;mobile computing;Monitor;multimodality;neural;Neurocognition;Neurocognitive;neurodevelopment;neuroimaging;Neuropsychological Tests;novel;Occupations;Outcome;Parents;Participant;participant enrollment;participant retention;Pathway interactions;Persons;Physical activity;physical conditioning;Privatization;Process;Protocols documentation;Psychopathology;Qualifying;recruit;Recurrence;Registries;Research;research and development;Research Personnel;Research Project Grants;Resource Informatics;Resources;response;retention rate;Risk;Role;Sampling;Schools;Science;Secure;Severities;Siblings;Site;Sleep;sleep pattern;social;Social Functioning;Social isolation;social media;Specific qualifier value;Sports;Standardization;substance use;Symptoms;Technology;Teenagers;Telephone;temporal measurement;Text;Time;Tobacco;Tobacco use;Training;Traumatic Brain Injury;trend;Triplet Multiple Birth;tv watching;Twin Multiple Birth;United States;vaping;Video Games;young adult;Youth

PROJECT_TITLE: 6/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT OHSU


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Depression;Drug Abuse (NIDA only);HIV/AIDS;Infectious Diseases;Mental Health;Mental Illness;Prevention;Substance Misuse;Tobacco;Tobacco Smoke and Health

ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project Narrative The goal of this project is to test whether a novel behavioral activation/problem solving based counseling intervention results in higher rates of smoking cessation than standard behavioral counseling among HIV+ smokers in Botswana. It will also assess whether changes in hypothesized mediators (depressive symptoms, use of substitute reinforcers and avoidance of complementary reinforcers of smoking behavior and problem solving skill) are the mechanisms behind successful quitting.

PI_NAMEs: GROSS, ROBERT  (contact);SCHNOLL, ROBERT ADAM

PROGRAM_OFFICER_NAME: FITZ-RANDOLPH, MARCY ESTHER

PROJECT_TERMS: Abstinence;Address;Adult;Africa;Africa South of the Sahara;African;antiretroviral therapy;Anxiety;Behavior;behavior change;Behavior Therapy;Behavioral;behavioral economics;Botswana;care delivery;Caring;Chronic Obstructive Pulmonary Disease;clinical infrastructure;common symptom;comorbidity;cost;Counseling;Country;Data;Decentralization;depressive symptoms;design;Developing Countries;efficacy evaluation;Epidemic;Evidence based practice;experience;General Population;Goals;Health;health care availability;health care delivery;high risk;HIV;HIV Infections;HIV/AIDS;Income;Individual;Infrastructure;Intervention;intervention effect;low and middle-income countries;Mediating;Mediator;medication compliance;Mental Depression;mobile computing;Modeling;Morbidity - disease rate;mortality;Motivation;Myocardial Infarction;negative affect;Nicotine Dependence;nicotine replacement;novel;Outcome;Pathway interactions;Pattern;Persons;Pharmacotherapy;Pilot Projects;pilot test;Population;primary outcome;Problem Solving;problem solving therapy;Professional counselor;programs;psychological distress;psychological symptom;Public Health;Randomized;randomized trial;reduce tobacco use;reinforcer;relapse risk;Research;Rewards;Risk;Role;Sampling;scale up;Site;skills;Smoker;Smoking;Smoking Behavior;smoking cessation;Smoking Cessation Intervention;Telephone;Testing;Tobacco Dependence;Tobacco smoking behavior;Tobacco use;Tobacco Use Cessation;trial comparing;trial design;Tuberculosis;varenicline;virtual;Withdrawal;working group;years of life lost

PROJECT_TITLE: Testing the Combination of Behavioral Activation and Problem Solving as a Novel Behavioral Smoking Cessation Intervention for Smokers with HIV in Botswana


NIH_SPENDING_CATS: Atherosclerosis;Biotechnology;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Human Genome;Precision Medicine;Prevention

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: PROJECT NARRATIVE Characterizing the genetic basis of plasma lipids has spurred many key paradigms for preventing coronary heart disease – biological insights, risk prediction, and medicines. Whole genome sequencing now offers the prospect of identifying all the potential genetic factors influencing lipids. The goal of this proposal is to surmount several methodological, analytical, and computational challenges to improve risk prediction and tailor preventive care as well as find new genes, which can be therapeutically targeted to efficiently reduce the risk for coronary heart disease.

PI_NAMEs: NATARAJAN, PRADEEP  (contact);PELOSO, GINA MARIE

PROGRAM_OFFICER_NAME: YAN, YE

PROJECT_TERMS: Address;Advocate;All of Us Research Program;Alleles;ANGPTL3 gene;base;biobank;Bioinformatics;Biological;Biological Assay;blood lipid;Cardiovascular system;Cataloging;Catalogs;Cause of Death;Cholesterol;Clinical;clinical development;Code;Complex;Coronary heart disease;Data;Data Set;Databases;Diagnosis;Diagnostic;Diagnostic tests;Dyslipidemias;efficacious treatment;ethnic diversity;Ethnic Origin;exome sequencing;Familial Hypercholesterolemia;Gene Frequency;gene function;gene product;Genes;Genetic;genetic analysis;Genetic Complementation Test;Genetic Models;genetic testing;genetic variant;genome sequencing;genome-wide;genomic variation;Genomics;Genotype;Geography;Goals;Grant;heart disease risk;Heterogeneity;High Density Lipoprotein Cholesterol;High Density Lipoproteins;hypercholesterolemia;improved;Individual;Infrastructure;Inherited;innovation;insertion/deletion mutation;insight;Investments;LDL Cholesterol Lipoproteins;Leadership;lipid disorder;Lipids;Lipoprotein (a);lipoprotein cholesterol;Measures;Medical Genetics;medical specialties;Medicine;Methodology;Methods;Modeling;multiple omics;National Heart, Lung, and Blood Institute;novel;Participant;Pattern;Pharmaceutical Preparations;Phase;Phenotype;Plasma;Population;population based;Population Heterogeneity;Prevalence;prevent;Prevention;Preventive care;Procedures;Productivity;programs;rare variant;Recommendation;Research;Research Personnel;response;Risk;Risk Factors;risk prediction;Risk Reduction;RNA;Role;Sequence Analysis;Sex Chromosomes;Single Nucleotide Polymorphism;Technology;Testing;Therapeutic;therapeutic target;Titrations;trait;Trans-Omics for Precision Medicine;Triglycerides;United States National Institutes of Health;Untranslated RNA;Variant;whole genome;Work

PROJECT_TITLE: Whole genome sequences in ethnically diverse individuals to comprehensively characterize the genetic mechanisms of dyslipidemias

STUDY_SECTION: GHD

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


NIH_SPENDING_CATS: Breast Cancer;Cancer;Women's Health Research

ORG_CITY: Nashville

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: NARRATIVE This proposed research is to investigate the role of exosomes in cancer cell adhesion and migration, and extracellular matrix assembly, which are key events in cancer metastasis and tumor microenvironment maintenance. We will use a novel in vitro assay developed in the laboratory and state-of-the-art imaging techniques to determine the impact of exosome secretion from cancer cells as well as fibroblasts. This project is relevant to public health because it will lead to a greater understanding of the role of exosome secretion in tumor aggressiveness.

PI_NAMEs: SUNG, BONG HWAN  (contact)

PROGRAM_OFFICER_NAME: GEORGE, CHRISTINA DAWN

PROJECT_TERMS: Activated-Leukocyte Cell Adhesion Molecule;Adhesions;angiogenesis;autocrine;Automobile Driving;Biogenesis;breast cancer progression;cancer cell;Cell Adhesion;Cell Adhesion Molecules;Cell Differentiation process;cell motility;Cell Proliferation;Cells;Cellular biology;Development;Endosomes;Event;exosome;Extracellular Matrix;extracellular vesicles;Fibroblasts;Funding;Grant;Image Analysis;Imaging Device;Imaging Techniques;Immunity;in vitro Assay;Invaded;Laboratories;Maintenance;Malignant Breast Neoplasm;Malignant Neoplasms;Mediating;medical schools;Melanoma differentiation associated gene-9;Methods;Motility;Neoplasm Metastasis;novel;paracrine;Pathologic;Physiological;Play;Public Health;Regulation;Research;RNA;Role;Specialist;Testing;tumor;tumor microenvironment;tumor progression;Universities;Work;wound healing

PROJECT_TITLE: Exosome Secretion in Tumor Aggressiveness


NIH_SPENDING_CATS: Clinical Research;Clinical Trials and Supportive Activities;Diabetes;Digestive Diseases;Prevention

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: PROJECT NARRATIVE Patients with Chronic Pancreatitis (CP) and/or Recurrent Acute Pancreatitis (RAP) with Diabetes Mellitus (DM), referred to as CP-DM, have not been studied in prospective intervention trials to test efficacy and safety of anti- hyperglycemic medications. We will conduct a randomized, parallel group, dose escalation Pioglitazone versus Empagliflozin clinical trial in CP-DM (the PEP-DM) Trial lasting 24 weeks. The PEP-DM trial will serve as a precedent for a larger study of anti-hyperglycemic intervention to be conducted in CP-DM by the NIH funded consortium for chronic pancreatitis, diabetes mellitus and pancreatic cancer (CPDPC).

PI_NAMEs: KUDVA, YOGISH C. (contact);YADAV, DHIRAJ

PROGRAM_OFFICER_NAME: UNALP-ARIDA, AYNUR

PROJECT_TERMS: acute pancreatitis;Address;Adverse event;Agonist;Animal Model;Area Under Curve;Beta Cell;blood glucose regulation;Blood Pressure;Body Weight;Body Weight decreased;C-Peptide;C-reactive protein;Cardiovascular Diseases;Cardiovascular system;Cell Physiology;cerebrovascular;chronic pancreatitis;Clinic;Clinical;clinical center;clinical decision-making;Clinical Trials;Cognition;comparison control;Data;data modeling;design;Devices;Diabetes Mellitus;Diabetic Ketoacidosis;Disease;Dose;Education;effective therapy;efficacy evaluation;efficacy testing;Eligibility Determination;Event;Exocrine pancreas;experience;Fibrosis;Funding;Future;GLP-I receptor;Glucagon;Glucose;glycemic control;Glycosylated hemoglobin A;Grant;Heart failure;Human;Hyperglycemia;Hyperlipidemia;Hypoglycemia;Hypoglycemic Agents;impaired glucose tolerance;improved;Individual;Inflammation;inhibitor;insight;Insulin;Insulin Resistance;insulin secretion;Intervention;Intervention Studies;Intervention Trial;Investigation;Ischemia;Ketosis;Kidney;Lead;Malignant neoplasm of pancreas;Measures;Minnesota;Mission;Monitor;Morbidity - disease rate;mortality;Multicenter Studies;National Institute of Diabetes and Digestive and Kidney Diseases;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel;Observational Study;Outcome;Pancreas;Pancreatic Diseases;Pancreatitis;patient population;Patients;Persons;Pharmaceutical Preparations;Phase;Pioglitazone;Population;primary endpoint;prospective;Quality of life;Randomized;randomized, clinical trials;Randomized, Controlled Trials;Recording of previous events;recruit;Recurrence;Reporting;Research Design;response;Retrospective Studies;Risk;Safety;secondary endpoint;Site;Specific qualifier value;systemic inflammatory response;Testing;therapy development;trial design;United States National Institutes of Health;Universities

PROJECT_TITLE: Parallel-group randomized controlled trial of Pioglitazone versus empagliflozin for T3cDM: The PEP-DM Trial

STUDY_SECTION: HSDO

STUDY_SECTION_NAME: Human Studies of Diabetes and Obesity Study Section[HSDO]


ORG_CITY: BALTIMORE

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: Project Narrative  Advancing age is well-known risk factor for infection, sepsis, and multiple organ dysfunction following trauma and major surgical intervention. Impaired gut barrier function is the driving force for infection and systemic inflammatory response in many critical conditions. However, our current understanding of the mechanisms underlying the increased vulnerability to gut barrier dysfunction during aging remains poor and, as a result, effective therapies to preserve intestinal barrier integrity in older patients are limited. Studies proposed here will uncover novel mechanisms underlying the pathogenesis of gut barrier dysfunction in elderly patients and will also establish a fundamental basis for developing new effective therapeutics to improve gut barrier integrity by targeting intestinal epithelial mitochondria via circHIPK3 and HuR.

PI_NAMEs: XIAO, LAN  (contact)

PROGRAM_OFFICER_NAME: FLORES, ROBERTO L

PROJECT_TERMS: Affect;Age;age related;aged;Aging;aging population;Area;Bacteria;Biogenesis;Cell Line;circular RNA;Clinical Research;comorbidity;Complex;Data;driving force;effective therapy;Elderly;Endotoxins;Enhancers;Environment;Epithelial Cells;epithelial repair;Epithelium;Event;Exhibits;Exons;Functional disorder;gain of function;gastrointestinal epithelium;Gene Expression;Gene Expression Profile;Goals;healthy aging;Homeostasis;Host Defense;Human;human old age (65+);HuR protein;immunosenescence;Impairment;improved;in vivo;Infection;infection risk;Injury;intestinal barrier;intestinal epithelium;Intestines;Knockout Mice;Knowledge;Leaky Gut;Link;Literature;loss of function;Mammalian Cell;Messenger RNA;MicroRNAs;Mitochondria;mitochondrial metabolism;mouse model;mRNA Precursor;mRNA Stability;mRNA Translation;Mucous Membrane;Mus;Natural regeneration;novel;novel therapeutics;old mice;older patient;Operative Surgical Procedures;Organ;Organoids;overexpression;Paneth Cells;Pathogenesis;Pathologic;Pathology;Patients;Play;Populations at Risk;Porifera;Post-Transcriptional Regulation;post-trauma;posttranscriptional;preservation;prevent;Process;Regulation;response;Risk;Risk Factors;RNA;RNA-Binding Proteins;Role;Sepsis;Site;Small intestine mucous membrane;Stress;Stroke;Surface;systemic inflammatory response;Testing;therapeutically effective;Tissues;Trans-Activators;Transcript;Transcription Process;Transgenic Organisms;Translations;Trauma;Untranslated RNA;wound

PROJECT_TITLE: Roles of circHIPK3 and HuR in aging gut barrier function

STUDY_SECTION: DHMI

STUDY_SECTION_NAME: Digestive System Host Defense, Microbial Interactions and Immune and Inflammatory Disease Study Section[DHMI]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Drug Abuse (NIDA only);Mental Health;Neurosciences;Opioid Misuse and Addiction;Opioids;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prescription Drug Misuse;Preterm, Low Birth Weight and Health of the Newborn;Substance Misuse;Women's Health Research

ORG_DEPT: VETERINARY SCIENCES

ORG_NAME: TUFTS UNIVERSITY BOSTON

PHR: The use and abuse of prescription opioids in females of reproductive age has dramatically increased over the past two decades. One consequence of this escalated use has been an upsurge in the number of babies born with opioids in their bloodstream, many of whom develop neonatal opioid withdrawal syndrome. The goals of the current set of studies are to address this public health issue using a preclinical model of oxycodone self-administration in female rats which will allow us to investigate neurodevelopmental modifications and adult outcomes associated with maternal opioid intake.

PI_NAMEs: BYRNES, ELIZABETH M (contact)

PROGRAM_OFFICER_NAME: WU, DA-YU

PROJECT_TERMS: Abstinence;abuse liability;addiction liability;Address;Adolescence;Adult;Adult Children;Age;Animal Model;Animals;Behavioral;Biological;Biological Availability;Blood Circulation;Body Weight;Body Weights and Measures;Brain region;Buprenorphine;Child;Circulation;Clinical;clinically relevant;Conceptions;Data;Development;Dose;Drug Prescriptions;early pregnancy;Epigenetic Process;Event;experience;experimental study;Female;fetal;fetal opioid exposure;Genetic Transcription;Glucocorticoids;Goals;improved;Impulsive Behavior;Infant;Intake;intergenerational;Intravenous;intravenous administration;Literature;maternal opioid use;Measures;Mediating;Metabolism;Methadone;Methyl-CpG-Binding Protein 2;Modeling;Modification;Neonatal;Neonatal Abstinence Syndrome;neonatal outcome;neurodevelopment;neurodevelopmental effect;offspring;Opiate Addiction;Opioid;opioid abuse;opioid exposure;opioid misuse;Opioid replacement therapy;opioid use;opioid use disorder;opioid use in pregnancy;Oral;Outcome;Oxycodone;oxycodone self-administration;Pattern;Pharmaceutical Preparations;postnatal;postnatal development;postnatal period;pre-clinical;Pre-Clinical Model;Pregnancy;pregnant;prenatal;prescription opioid;prescription opioid abuse;Public Health;Qualifying;Rattus;reproductive;Reproductive Biology;response;Risk;Self Administration;Severities;sex;species difference;Standardization;Stress;Substance abuse problem;Substance Use Disorder;symptom treatment;Symptoms;Testing;Treatment Protocols;Ultrasonics;vocalization;Weight Gain;Withdrawal;Woman;Work

PROJECT_TITLE: Oxycodone, Neonatal Opioid Withdrawal Syndrome, and Adult Abuse Liability

STUDY_SECTION: NMB

STUDY_SECTION_NAME: Neurobiology of Motivated Behavior Study Section[NMB]


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

ORG_CITY: KHON KAEN

ORG_COUNTRY: THAILAND

ORG_FIPS: TH

ORG_NAME: KHON KAEN UNIVERSITY

PHR: Project Narrative The administration of epidermal growth factor receptor (EGFR) targeted therapies to cancer patients invariably leads to the development of drug resistance, mainly caused by a mesenchymal-epithelial transition (MET) amplification. This innovative research project addresses this issue by rigorously developing smart transformable EGFR/MET-targeting peptide nanoparticles for treatment of cancers with acquired resistance to EGFR-targeted therapies due to MET amplification. The successful completion of this project will not only lead to the creation of new classes of safe and effective targeted nanotherapeutics against cancers but also open avenues for the advancement of functional nanomaterials in biomedical applications.

PI_NAMEs: MAHALAPBUTR, PANUPONG  (contact)

PROGRAM_OFFICER_NAME: POVLICH, LAURA

PROJECT_TERMS: acquired drug resistance;Address;Affinity;alpha helix;anti-cancer;Applications Grants;aqueous;aspirate;Award;beta pleated sheet;Binding;biomaterial compatibility;Bypass;California;cancer cell;Cancer cell line;Cancer Patient;cancer therapy;cancer type;career development;career networking;Cell surface;Characteristics;chemical stability;Chemicals;chemotherapy;Clinical;Clinical Research;Colorectal Cancer;combinatorial;Computer Assisted;Cytotoxic agent;design;Development;Development Plans;Drug resistance;drug resistance development;effector T cell;Engineering;Enzymes;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;epithelial to mesenchymal transition;Epithelium;Exhibits;Fogarty International Center;gain of function;Gel;Grant;high throughput screening;Human;immunogenicity;In Situ;In Vitro;in vivo;Incidence;Individual;innovation;Laboratories;Lead;Leadership;Libraries;Malignant Breast Neoplasm;Malignant neoplasm of cervix uteri;Malignant neoplasm of liver;Malignant neoplasm of lung;Malignant Neoplasms;Manuscripts;Mechanics;Mesenchymal;Molecular;Monoclonal Antibodies;mortality;nanofibrillar;nanomaterials;nanoparticle;nanoscale;Nanostructures;nanotherapeutic;overexpression;Pathway interactions;Patients;Peptide Library;peptide structure;Peptide Synthesis;Peptides;Pharmaceutical Preparations;Pharmacologic Substance;Phase;Phase Transition;Phosphorylation;PIK3CG gene;Plasma;Preparation;Process;Property;Proteins;Public Health;Publications;receptor;refractory cancer;Reporting;Research;Research Personnel;Research Project Grants;Resistance;resistance mechanism;response;risk minimization;scaffold;screening;self assembly;side effect;Site;skills;small molecule;Solid;Study Section;targeted agent;targeted treatment;Techniques;Technology;Thailand;Therapeutic;Toxin;Treatment Efficacy;tumor;tumor microenvironment;Tyrosine Kinase Inhibitor;United States National Institutes of Health;Universities;World Health Organization;Writing

PROJECT_TITLE: Development of a smart transformable nanotherapeutic against cancers with acquired resistance to EGFR-targeted therapies caused by MET amplification

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 ICP-P (55)]


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

ORG_NAME: DANA-FARBER CANCER INST

PHR: PROJECT NARRATIVE Salmonella is an important human pathogen and estimated by the CDC to cause more foodborne diseases than any other pathogen. Over one million estimated cases of Salmonella foodborne illnesses occur in the United States every year, with an economic burden of approximately $3.7 billion dollars per year. We will develop a method for measuring the molecular states of individual Salmonella cells during infection to devise new treatment strategies against Salmonella infection.

PI_NAMEs: HORMOZ, SAHAND  (contact);ROSENTHAL, ADAM

PROGRAM_OFFICER_NAME: ALEXANDER, WILLIAM A

PROJECT_TERMS: Antibiotic Resistance;antibiotic tolerance;Antibodies;Atlases;Bacillus;Bacteria;Bacterial RNA;Bar Codes;Biological;Cell Count;Cell Fraction;cell type;Cells;Clostridium perfringens;Communities;computational pipelines;computer framework;cost effective;Data Analyses;DNA;DNA Probes;Economic Burden;effective therapy;Environment;Escherichia coli;experimental study;foodborne illness;Gene Expression Profile;Genes;Genetic Materials;Genetic Transcription;Gnotobiotic;gut microbes;gut microbiome;Heterogeneity;high throughput technology;human pathogen;Immune;Immune system;In Vitro;in vitro Model;in vivo;in vivo Model;Individual;Infection;Intestines;Mammalian Cell;Measures;Metabolic;Methods;Microbial Biofilms;microbiota;Microfluidics;Modeling;Molecular;Motility;mouse model;Mus;Nature;novel therapeutic intervention;Organoids;pathogen;Pathogenesis;Pathogenicity;Persons;Physiological;Poly(A) Tail;Population;Process;Proteins;Protocols documentation;Reagent;response;Running;Salmonella;Salmonella enterica;Salmonella infections;sequencing platform;single-cell RNA sequencing;System;Technology;technology platform;Testing;Therapeutic Intervention;tool;Transcript;transcriptome;transcriptome sequencing;United States;Virulence;Virulent

PROJECT_TITLE: High-throughput single-cell RNA sequencing of bacteria to uncover cell states involved in pathogenesis

STUDY_SECTION: BV

STUDY_SECTION_NAME: Bacterial Virulence Study Section [BV]


ADMINISTERING_IC: AA

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Biotechnology;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Human Genome;Patient Safety;Precision Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Substance Misuse

PHR: PROJECT NARRATIVE Acamprosate and naltrexone are important medications used in the treatment of alcohol use disorder (AUD) but many AUD patients fail to respond to therapy with these drugs. We have used “Multiple Omics” (i.e., genomics, transcriptomics, proteomics, and metabolomics) to identify biomarkers for acamprosate treatment response which we will now pursue to define underlying biological mechanisms. We will also study stem-cell (iPSC)- generated brain organoids derived from AUD patients treated with these drugs that will be exposed to acamprosate and naltrexone to identify additional biomarkers and pathways to help us understand mechanisms responsible for variation in response to these important AUD drugs.

PI_NAMEs: HO, MING-FEN ;WEINSHILBOUM, RICHARD M. (contact)

PROGRAM_OFFICER_NAME: SENEVIRATNE, CHAMINDI

PROJECT_TERMS: acamprosate;Address;alcohol abuse therapy;alcohol response;alcohol use disorder;alcoholism therapy;bioinformatics tool;Biological;Biological Markers;Biology;biomarker identification;Blood specimen;Brain;Candidate Disease Gene;cell type;Cells;Characteristics;Chromatin;Chromium;Clinic;Clinical;Clinical Trials;cohort;Cohort Studies;CRISPR/Cas technology;Data;Data Set;Development;Disease;Exposure to;Foundations;Functional disorder;Funding;Gene Expression;Gene Expression Profile;Gene Expression Regulation;Generations;Genes;Genetic Transcription;genome wide association study;Genomics;Grant;Human;human induced pluripotent stem cells;individual patient;individual variation;individualized medicine;induced pluripotent stem cell;induced pluripotent stem cell technology;Inflammatory;inflammatory marker;innovation;insight;Knowledge;Libraries;metabolomics;Molecular;Multiomic Data;multiple omics;Naltrexone;National Institute on Alcohol Abuse and Alcoholism;new therapeutic target;novel;novel marker;optimal treatments;Organoids;Outcome;participant enrollment;Pathway interactions;patient derived induced pluripotent stem cells;Patient Recruitments;Patients;Peripheral;Pharmaceutical Preparations;Pharmacogenomics;Pharmacometabolomics;Pharmacotherapy;phase II trial;Phenotype;Plasma;potential biomarker;protein biomarkers;Proteomics;Publishing;recruit;Regimen;Research;Research Design;response;Sampling;Sampling Studies;Series;single cell sequencing;stem cells;Structure;Systems Biology;Testing;Therapeutic Agents;transcriptomics;Treatment outcome;treatment response;Variant;XCL1 gene

PROJECT_TITLE: Alcohol Use Disorder: Acamprosate Pharmacometabolomics-informed Pharmacogenomics

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


NIH_SPENDING_CATS: Cancer;Prostate Cancer;Radiation Oncology;Urologic Diseases

ORG_CITY: LEXINGTON

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE Radiation-resistant prostate cancer (RR-PCa) is highly unpredictable which frequently results in cancer recurrence in many patients. This project aims to 1) establish the underlying mechanism(s) of mitochondrial biogenesis that contribute to RR-PCa cell survival and metabolism and 2) determine if targeting inherent mitochondria and radiation-acquired mitochondria, can overcome RR-PCa. The successful completion of this project will establish a new and significant therapeutic platform for making radiation therapy more effective.

PI_NAMEs: CHAISWING, LUKSANA  (contact)

PROGRAM_OFFICER_NAME: PRASANNA, PAT G

PROJECT_TERMS: Animal Model;Antibiotics;Azithromycin;Biochemical;Biogenesis;bioluminescence imaging;cancer cell;cancer heterogeneity;cancer recurrence;cancer subtypes;cancer survival;catalase;Cell Death;Cell Survival;Cells;Cellular Metabolic Process;Cessation of life;Clinical Treatment;Computer software;Coupled;Cytoplasm;Data;Dose;Electron Transport;Enzymes;Event;Exhibits;External Beam Radiation Therapy;Failure;FDA approved;fractionated radiation;Growth;high risk;Homeostasis;Hydrogen Peroxide;Image;Impairment;improved;In Vitro;in vivo;inhibitor;insight;knock-down;Macrolides;Magnetic Resonance Imaging;Malignant neoplasm of prostate;Malignant Neoplasms;Mediating;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Mitochondria;mitochondrial dysfunction;mitochondrial metabolism;Mitochondrial Proteins;Molecular;mortality;mtTF1 transcription factor;Mus;Normal Cell;novel;novel therapeutics;overexpression;Oxidation-Reduction;Oxidative Phosphorylation;Pathway interactions;patient derived xenograft model;Patients;Pharmaceutical Preparations;Phase;prevent;Property;Prostate;prostate cancer cell;prostate cancer model;Protein Array;Proteins;prototype;Radiation;radiation delivery;radiation resistance;Radiation therapy;Radiation Tolerance;radioresistant;Reactive Oxygen Species;Recurrence;Regulation;Research Design;Resistance;Resistance development;Resolution;response;Site;stable isotope;success;superresolution microscopy;tempol;Testing;Therapeutic;Time;Translating;Translational Repression;Translations;Treatment Efficacy;tumor;tumor growth;tumor heterogeneity;Visualization;Xenograft Model

PROJECT_TITLE: Targeting Mitochondrial Redox Capacity to Overcome Cancer Subtype that Regrowth After Radiation

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Genetics;Human Genome;Orphan Drug;Ovarian Cancer;Precision Medicine;Rare Diseases;Uterine Cancer;Women's Health Research

ORG_DEPT: OBSTETRICS & GYNECOLOGY

PHR: Project Narrative Gynecological cancers with genetic alterations (e g. BRCA1/2 mutation, CCNE1 amplification, ARID1A mutation), provide opportunities for synthetic lethality approaches to cancer therapy. We have established a large library of gynecological cancer patient-derived xenograft and organoid models and now plan to expand to include rare tumor types. We plan to test new therapies that exploit genetic alterations with the ultimate goal of moving new therapies into the clinic.

PI_NAMEs: XU, HAINENG  (contact)

PROGRAM_OFFICER_NAME: SONG, MIN-KYUNG H

PROJECT_TERMS: Advanced Malignant Neoplasm;ARID1A gene;Biological Markers;biomarker identification;BRCA mutations;cancer therapy;CCNE1 gene;Cell Line;Cells;Clinic;Combined Modality Therapy;CRISPR screen;Critical Pathways;Defect;DNA Damage;Drug Combinations;drug discovery;Endometrial Carcinoma;Exhibits;Genetic;Genetic Predisposition to Disease;Genomics;Goals;homologous recombination;homologous recombination deficiency;Imaging Device;Immune system;inhibitor;inhibitor therapy;Libraries;Malignant Female Reproductive System Neoplasm;Malignant neoplasm of ovary;Modeling;molecular imaging;Mutation;Nature;novel therapeutics;Oncogenes;Organoids;Outcome;Ovarian Clear Cell Tumor;patient derived xenograft model;Patients;Phase Ib Clinical Trial;Phase II Clinical Trials;Platinum;Poly(ADP-ribose) Polymerase Inhibitor;Pre-Clinical Model;predicting response;predictive signature;rare cancer;Research;Resistance;response;Sampling;Serous;targeted treatment;Tertiary Protein Structure;Testing;transcriptomics;tumor;Woman

PROJECT_TITLE: Overcoming treatment-resistant gynecological cancers by combination of DNA damage response inhibitors


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_CITY: MINNEAPOLIS

ORG_DEPT: ORTHOPEDICS

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: PROJECT NARRATIVE Ostechondritis dissecans (OCD) is a developmental orthopaedic disease affecting children and young adults. It is characterized by formation of osteochondral flaps or fragments within joints which cause pain and disability and predispose to early onset osteoarthritis. In the current proposal, our objective is to establish how alterations in the vascular supply to the epiphyseal growth cartilage, along with biomechanical trauma, contribute to the development, progression, and healing of OCD lesions.

PI_NAMEs: TOTH, FERENC  (contact)

PROGRAM_OFFICER_NAME: PINTUCCI, GIUSEPPE

PROJECT_TERMS: Adolescent;Affect;Animal Model;Architecture;Area;arthropathies;Athletic;Autopsy;Biomechanics;Blood Vessels;Brain Concussion;burden of illness;Cartilage;Characteristics;Child;Clinical;clinical decision-making;Clinical Management;clinically relevant;Degenerative polyarthritis;design;Development;disability;Disease;disorder prevention;Distal;Early Intervention;early onset;Ensure;Evaluation;Evidence based treatment;Exercise;Experimental Designs;Exposure to;Failure;Femur;Gene Expression Profile;Genetic;Goals;Growth;healing;Histologic;Human;in vivo;Interruption;Ischemia;ischemic lesion;Island;Joints;Knee;Knowledge;Legg-Perthes Disease;Lesion;Magnetic Resonance Imaging;Molecular;Monitor;Nature;Necrosis;Operative Surgical Procedures;Orthopedics;osteochondral tissue;Osteochondritis Dissecans;Osteochondrosis;Pain;Pathogenesis;Pathway interactions;Patients;pharmacologic;Physiologic Ossification;Play;porcine model;Postoperative Period;pre-clinical;Preventive measure;Process;Resolution;Risk;Risk Factors;Role;Severities;Stress;substantia spongiosa;Testing;transcriptomics;Translations;Trauma;Treatment Protocols;Vascular blood supply;Vascular Diseases;vascular injury;Work;young adult

PROJECT_TITLE: The role of vascular failure and biomechanical stress in the development, progression and healing of osteochondritis dissecans lesions

STUDY_SECTION: SBSR

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


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cardiovascular;Clinical Research;Heart Disease;Lung;Prevention;Pulmonary Hypertension;Rare Diseases

ORG_CITY: CHICAGO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE: We are tackling a deadly heart condition called pulmonary hypertension (PH), where the risk of death is seven times higher than normal. Our focus is on its most severe form, Pulmonary Arterial Hypertension (PAH), which usually gives patients only three years to live. Diagnosing PAH quickly and accurately is crucial because treatments are most effective only at earlier stages of the disease, and using its treatments on similar conditions can be harmful. However, current tests are expensive, complicated, invasive, and can take up to 4 years to provide the first diagnosis. By integrating mathematical modeling, advanced MRI imaging, and physics (fluid dynamics), this application goal is to develop a new, quick, noninvasive one-scan solution, the '4D Right-Heart virtual catheter’, to transform how we diagnose and monitor this life-threatening condition, offering faster diagnosis, better outcomes and making care more timely accessible to these suffering patients.

PI_NAMEs: ELBAZ, MOHAMMED  (contact)

PROGRAM_OFFICER_NAME: XIAO, LEI

PROJECT_TERMS: 3-Dimensional;4D MRI;Acceleration;accurate diagnosis;Address;Agreement;Anatomy;Aortic Valve Stenosis;Apical;Caring;Catheterization;Catheters;Cessation of life;Chronic Disease;Classification;Clinic;Clinical;clinically significant;Complex;cost;Cross-Sectional Studies;Death Rate;Detection;Development;Diagnosis;Diagnostic;diagnostic tool;digital;Disease;Early Diagnosis;Echocardiography;effective therapy;Eligibility Determination;Enrollment;Evaluation;follow-up;Goals;healthy volunteer;Heart;heart function;hemodynamics;high risk;Hospitalization;hypertension control;hypertension treatment;Image;improved;improved outcome;Individual;innovation;Kinetics;Life;Liquid substance;Magnetic Resonance Imaging;mathematical model;Measures;Methods;Modeling;Monitor;mortality risk;MRI Scans;Noise;non-invasive imaging;noninvasive diagnosis;novel;novel marker;Outcome;Outcome Study;Patients;Physics;pressure;Probability;Process;Prognosis;prognostic;prognostic significance;Protocols documentation;pulmonary arterial hypertension;Pulmonary artery structure;Pulmonary Hypertension;pulmonary venous hypertension;Quality of life;Radial;Reproducibility;Resolution;Right atrial structure;Right Ventricular Dysfunction;right ventricular failure;Right ventricular structure;Risk;Scanning;screening;Series;Severities;Site;Speed;Symptoms;Technology;Testing;Thoracic aorta;tool;Uncertainty;Vascular remodeling;Vendor;virtual;Viscosity;volunteer;Walking

PROJECT_TITLE: 4D virtual Catheter (4D vCath) for multi-factorial hemodynamics in pulmonary hypertension

STUDY_SECTION: BTSS

STUDY_SECTION_NAME: Bioengineering, Technology and Surgical Sciences Study Section[BTSS]


NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Opioid Misuse and Addiction;Opioids;Social Determinants of Health;Substance Misuse

ORG_CITY: COLUMBIA

ORG_DEPT: ADMINISTRATION

ORG_NAME: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Substance Use Disorder (SUD) affects 46.3 million Americans and their communities and Sexual and Gender Minorities (SGMs) face higher rates of SUD than other groups due to complex factors like stigma and discrimination. Our innovative project aims to engage SGM patients to work with researchers to improve SUD treatment services and research. This work will provide valuable insights for healthcare practitioners, policymakers, and SGM community advocates, leading to tailored, patient-centered care for this underserved population.

PI_NAMEs: FIVECOAT, JAIME ERIN;KENNEDY, ANN BLAIR ;NATAFGI, NABIL M. (contact)

PROJECT_TERMS: Address;Adherence;Adult;adverse outcome;Advocate;Affect;American;Applications Grants;Automobile Driving;barrier to care;Bisexual;Caring;Characteristics;Clinical;Collaborations;Communities;Community Actions;community partners;Competence;Complex;Consultations;culturally appropriate intervention;Data;design;Development;Discrimination;Disparity;Ensure;evidence base;experience;experimental study;Face;Family;Family member;Focus Groups;Fostering;Funding;Gays;gender minority community;gender minority group;Goals;Health;health empowerment;Healthcare;Helping to End Addiction Long-term;Heterogeneity;High Prevalence;illicit drug use;Improve Access;improved;Individual;innovation;insight;Institution;Intervention;Interview;Knowledge;Lesbian;Lesbian Gay Bisexual Transgender Queer;Lived experience;member;men;Mental disorders;Mental Health;Methods;Minority;minority patient;Modality;Opiate Addiction;Opioid;opioid misuse;opioid use disorder;Outcome;patient engagement;patient oriented;patient response;Patient-Centered Care;Patients;Persons;physical conditioning;Play;Policies;Policy Maker;preference;Prevalence;Process;programs;prospective;Provider;Psychological Factors;Public Health;Recovery;Research;research and development;Research Personnel;Research Priority;Research Project Grants;Research Training;Role;Sex Orientation;Sexual and Gender Minorities;sexual minority;sexual minority disparity;sexual minority group;sexual minority men;Shapes;shared decision making;social factors;social stigma;Speed;Stigmatization;Stress;structural determinants;substance use;Substance Use Disorder;substance use treatment;success;telehealth;therapy development;Training;Treatment outcome;treatment research;treatment services;Underserved Population;United States National Institutes of Health;virtual patient;Woman;Work

PROJECT_TITLE: PRIDE-CARES Center: Patient-Responsive Initiatives for Diverse Engagement - LGBTQ+ Community Action in Research to Eliminate Substance Use Disorder

STUDY_SECTION_NAME: Special Emphasis Panel[ZDA1 SAI-E (M1)]


NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

ORG_DEPT: BIOMEDICAL ENGINEERING

PHR: Project Narrative Glaucoma is the second leading cause of blindness worldwide and the leading cause among African Americans. Effective lowering of intraocular pressure is neuroprotective and preserves vision. The goals of the present proposal are to develop novel technologies to objectively assess and monitor the tissue that regulates intraocular pressure, with age, in different disease subtypes, and in response to different therapies; this work is the first step in a continuum of research leading to early and accurate diagnosis of, and effective personalized therapy for, glaucoma.

PI_NAMEs: ETHIER, C ROSS;FARSIU, SINA  (contact);STAMER, W DANIEL

PROGRAM_OFFICER_NAME: GOVER, TONY DOUGLAS

PROJECT_TERMS: 3-Dimensional;accurate diagnosis;African American population;Age;Anatomy;aqueous;Architecture;automated segmentation;Behavior;Blindness;C57BL/6 Mouse;Clinical;clinically relevant;Computer software;Coupled;Data Set;Disease;disease model;disorder subtype;Early Diagnosis;Elements;Engineering;Eye;Eye diseases;Fibrosis;Funding;Glaucoma;Goals;Heterogeneity;histological specimens;Histology;Homeostasis;Human;Image;Imaging technology;in vivo;kinase inhibitor;Knowledge;Learning;Magnetism;Measurement;Medical;Methods;middle age;Modeling;Monitor;Morphologic artifacts;Mus;neuroprotection;new technology;novel;Ocular Hypertension;optic nerve disorder;Optical Coherence Tomography;Optics;Outcome;Pathology;Pathway interactions;Patients;Pattern;personalized medicine;Pharmaceutical Preparations;pharmacologic;Pharmacotherapy;Physiologic Intraocular Pressure;Physiological;Physiology;Pigments;Pilocarpine;Positioning Attribute;preservation;prevent;Primary Open Angle Glaucoma;Process;Productivity;Property;Regulation;Research;Resolution;response;Rho-associated kinase;Robotics;Sampling;segmentation algorithm;standard of care;Steroids;Structure;Structure of sinus venosus of sclera;System;Techniques;Technology;Testing;Time;time use;Tissues;tomography;Trabecular meshwork structure;Tracer;Training;ultra high resolution;Vacuole;Variant;Visible Radiation;Vision;Visualization;Work

PROJECT_TITLE: Quantitative assessment of glaucomatous conventional outflow dynamics

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 NV-P (81)]


ADMINISTERING_IC: HS

IC_NAME: AGENCY FOR HEALTHCARE RESEARCH AND QUALITY

ORG_CITY: ATLANTA

ORG_DEPT: PEDIATRICS

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Project Narrative Pharmacotherapy for childhood nephrotic syndrome is effective albeit highly complex. In this proposed study, we will carry out a systematic evaluation of factors that influence the ability of socially disadvantaged patients and families to choose the right treatment for them, and then create tools to support them in decision making centered around their needs. We anticipate that the findings will contribute to the understanding of influences on medication selection in this complex childhood kidney disease and produce the first tools to support shared decision making to improve care quality and reduce health disparities in childhood nephrotic syndrome.

PI_NAMEs: WANG, CHIA-SHI  (contact)

PROGRAM_OFFICER_NAME: ZHANG, XINZHI

PROJECT_TITLE: Supporting shared decision making in childhood nephrotic syndrome to improve care for children of racial and ethnic minority and low income background

STUDY_SECTION: HEOR

STUDY_SECTION_NAME: Healthcare Effectiveness and Outcomes Research[HEOR]


NIH_SPENDING_CATS: Cancer;Immunotherapy

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE Nucleotide metabolism is effectively targeted by anti-cancer agents, but their use is limited by toxicity to non- transformed cells, especially anti-cancer immune cells. Here, we strive to gain a more complete understanding of nucleotide metabolism—from sensing mechanisms to the response to nucleotide depletion—to enable sophisticated anti-cancer strategies that target cancer cells while sparing normal and immune cells.

PI_NAMEs: POSSEMATO, RICHARD LEWIS (contact)

PROGRAM_OFFICER_NAME: WILLIS, KRISTINE AMALEE

PROJECT_TERMS: Acute;Affect;Allografting;Allosteric Regulation;Anabolism;analog;anti-cancer;Antineoplastic Agents;Apoptosis;Biogenesis;Bypass;cancer cell;Cancer Model;cancer therapy;cancer type;caspase-activated deoxyribonuclease;Cell Compartmentation;Cell Cycle Arrest;Cell Cycle Checkpoint;Cell Cycle Regulation;Cell Death;Cell Physiology;cell type;Cells;Cellular Metabolic Process;Chronic;Clinical;clinically relevant;Compensation;Cytarabine;cytosine analog;Data;Engineering;experience;Feedback;Future;gemcitabine;Genetic Screening;Goals;Hyperactivity;Immune;Immunotherapy;improved;In Vitro;in vivo;inhibitor;innovation;insight;Knowledge;Malignant Neoplasms;MDM2 gene;Metabolic;Metabolism;Methods;Modeling;Molecular;Molecular Analysis;Mus;mutant;Normal Cell;novel;nucleotide metabolism;Nucleotides;Pathway interactions;Pre-Clinical Model;Pyrimidine;pyrimidine metabolism;Pyrimidine Nucleotides;Pyrimidine Synthesis Inhibition;Regulation;replication stress;Research;response;restraint;reverse genetics;Ribonucleotides;Ribosomes;Stress;T-Cell Activation;targeted agent;Testing;Therapeutic;therapeutic target;Toxic effect;TP53 gene;treatment response;tumor;Tumor Immunity;tumor metabolism;tumor microenvironment;Tumor-infiltrating immune cells;tumorigenesis;Uridine;Work

PROJECT_TITLE: Functional Relevance of Pyrimidine Sensing and Response Pathways in Tumor Metabolism and Cancer Therapy

STUDY_SECTION: CCB

STUDY_SECTION_NAME: Cancer Cell Biology Study Section[CCB]


ADMINISTERING_IC: HD

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

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

NIH_SPENDING_CATS: Congenital Structural Anomalies;Dental, Oral, and Craniofacial Disease;Dietary Supplements;Genetics;Human Genome;Nutrition;Pediatric;Prevention

ORG_CITY: KANSAS CITY

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF MISSOURI KANSAS CITY

ORG_STATE: MO

PHR: Project Narrative This project will address a critical gap in our knowledge regarding factors that influence the risk that a child will be born with cleft lip/palate and, equally importantly, how severe that presentation will be. The latter is the major determinant of the number of craniofacial surgeries that the child will endure. Specifically, the project will investigate the impact of maternal dietary vitamin A levels and its interaction with specific cleft genes as well as how early developmental events in the embryo influence severity of the presentation of cleft lip/palate.

PI_NAMEs: COX, TIMOTHY CHILTON (contact)

PROGRAM_OFFICER_NAME: TOYAMA, REIKO

PROJECT_TERMS: 3-Dimensional;Age;Alleles;Animal Model;Area;Biological Availability;Birth;Cells;Child;cilium biogenesis;Cleft Lip;cleft lip and palate;Cleft lip with or without cleft palate;Cleft Palate;Clinical;clinical care;clinical translation;clinically relevant;Complex;Congenital Abnormality;Counseling;craniofacial;craniofacial development;Data;Defect;Development;Diet;dietary;Dietary Intervention;Dietary Supplementation;effective intervention;Embryo;Environment;Epigenetic Process;Event;Exhibits;Face;Family;Family history of;folic acid supplementation;Frequencies;Frontonasal Prominence;Future;gastrulation;Gene Expression;gene interaction;Genes;Genetic;genetic approach;Genetic Predisposition to Disease;Genetic Risk;genetic risk factor;genetic variant;Glean;Health;Hepatic;Hormones;Human;imaging modality;improved;in utero;Incidence;indexing;Individual;Inherited;insight;Intervention;Knock-out;Knowledge;Lead;Left;Malnutrition;Maxillary Prominence;microCT;Modeling;molecular asymmetry;mother nutrition;Mothers;mouse model;multidisciplinary;multiple omics;Mus;mutant;Mutant Strains Mice;Nature;Neural Tube Defects;novel;Nutritional status;Operative Surgical Procedures;Organ;Outcome;Parents;Patients;Penetrance;Phenotype;Physiological;Population;Predisposition;Pregnancy;preventive intervention;Randomized;RBP4 gene;Recovery;Recurrence;Regimen;response;Retinol Binding Proteins;Risk;Risk Factors;Risk Reduction;risk variant;Role;Route;Secondary Palate;Severities;SHH gene;Side;Signal Transduction;single cell ATAC-seq;single cell sequencing;Single Nucleotide Polymorphism;single-cell RNA sequencing;Situs Inversus;Study models;success;Technology;Teratogens;Testing;Three-Dimensional Imaging;Time;Tissues;Variant;Vitamin A

PROJECT_TITLE: Impact of maternal dietary vitamin A on risk and severity of cleft lip/palate in genetically sensitized embryos

STUDY_SECTION: SBDD

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


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Epilepsy;Genetics;Human Fetal Tissue;Human Genome;Neurodegenerative;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_DEPT: NEUROLOGY

PHR: Proposal narrative Poison exons are used throughout neurodevelopment and their aberrant splicing can cause disease. We aim to use cutting-edge technologies to identify cell-type specific maps of poison exons in neurodevelopment, understand their genomic characteristics, and how they are alternatively spliced, towards identifying genetic variants that can lead to aberrant splicing.

PI_NAMEs: CARVILL, GEMMA LOUISE (contact)

PROGRAM_OFFICER_NAME: WHITTEMORE, VICKY R

PROJECT_TERMS: acquired epilepsy;Address;Alternative Splicing;Anti-sense RNA;Antibodies;Antisense Oligonucleotide Therapy;Antisense Oligonucleotides;Atlases;Brain;brain tissue;candidate identification;cell type;Cells;Cerebrum;Characteristics;Childhood;Clinical Trials;Codon Nucleotides;combinatorial;Communities;Conceptions;Cortical Malformation;Cycloheximide;Data;data integration;Data Set;Development;Disease;Dorsal;Elements;Epilepsy;Exons;fetal;Future;Genes;Genetic;Genetic Predisposition to Disease;genetic variant;Genome;genome sequencing;Genomics;Human;human fetal brain;Immunoprecipitation;Individual;induced pluripotent stem cell;Induced pluripotent stem cell derived neurons;insight;interest;knock-down;Knowledge;Lead;machine learning method;Maps;Mass Spectrum Analysis;multidisciplinary;Mus;Nervous System Disorder;Neurodegenerative Disorders;neurodevelopment;Neurodevelopmental Disorder;Neurologic;Nonsense-Mediated Decay;novel;Organoids;Outcome Study;overexpression;Pathogenicity;Patients;Poison;poison control;premature;prevent;Process;Property;Protein Isoforms;Proteins;Proteomics;rare variant;Regulation;Reporter;Research;RNA;RNA Splicing;RNA-Binding Proteins;RNA-targeting therapy;Role;SCN1A protein;single cell sequencing;Specificity;Spliceosomes;stem cell model;stem cell organoids;Technology;Time;Tissues;Transcript;transcriptome;transcriptome sequencing;Validation;Variant;web-based tool;Western Blotting

PROJECT_TITLE: Poison exons in epilepsy and neurodevelopment

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]