NIH_SPENDING_CATS: Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Studies in mammals have identified the FoxA family of regulatory proteins as among the most important in forming and maintaining internal organs during normal development and in preventing cancer and metabolic disease. Nonetheless, the complexity of mammalian (human) development and the redundant activities of the three mammalian FoxA proteins make it challenging to fully understand how these key proteins do their jobs. By focusing on the single family member in Drosophila and on a single relatively simple organ, we can begin to understand important details about how FoxA proteins control organ size, shape, position and function.

PI_NAMEs: ANDREW, DEBORAH J (contact)

PROJECT_TERMS: 3-Dimensional;Acute;Address;Affect;Apical;Architecture;Binding;Binding Sites;Biological Models;Cell Death;Cell Shape;Cells;Cessation of life;Chromatin;Consensus;Development;DNA Binding;Drosophila genus;Embryo;Enhancers;Epithelium;Event;Family;Family member;fitness;Gene Expression;Genes;Genetic;genetic regulatory protein;gland development;Head;hepatic necrosis;Hindgut;Histones;Homeostasis;Human;Human Development;Integral Membrane Protein;Kidney;Learning;Lipids;Liver;liver-specific protein;Lung;Maintenance;Malignant Neoplasms;Mammals;Maps;Mechanics;Mediating;Metabolic Diseases;migration;Modeling;Molecular;Morphogenesis;Morphology;Motor;mutant;Mutation;Myosin Type II;non-muscle myosin;Nucleic Acids;Occupations;Organ;organ growth;Organ Size;outer surface lipoprotein;Pancreas;Participant;Physiological;Physiology;Play;Positioning Attribute;prevent;Primitive foregut structure;protein function;Proteins;recruit;Regulation;Regulatory Pathway;Repression;Role;Salivary Glands;Shapes;Site;Specific qualifier value;sugar;Testing;Time;Tissues;tool;transcription factor;Tube;two-dimensional;vertebrate embryos;Winged Helix;Work;zygote

PROJECT_TITLE: Formation of the Drosophila salivary gland

STUDY_SECTION_NAME: Development - 1 Study Section[DEV1]


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Bioengineering

ORG_CITY: BETHLEHEM

ORG_COUNTRY: UNITED STATES

ORG_DEPT: PHYSICS

ORG_FIPS: US

ORG_NAME: LEHIGH UNIVERSITY

ORG_STATE: PA

PHR: Project Narrative We will study the dynamics of the actin cytoskeleton within cells, which regulates their shape and motion, such as during organism development, differentiation, neuron function, or cancer cell metastasis. To address the complexity of cellular dynamics, the project combines mathematical modeling with experimental studies by collaborators. If successful, this basic science would underpin future medical research based on an understanding of cellular function.

PI_NAMEs: VAVYLONIS, DIMITRIOS  (contact)

PROGRAM_OFFICER_NAME: MILLER, RITA K

PROJECT_TERMS: Accounting;Actins;Address;Basic Science;Bayesian Analysis;Behavior;Binding;Biological Models;Biological Process;biophysical model;cancer cell;Cell membrane;cell motility;Cell Physiology;Cells;Collaborations;Computer Models;constriction;Cytokinesis;Cytoskeleton;Development;experimental study;Filament;Fission Yeast;Focal Adhesions;Future;Grain;Lead;Link;Macromolecular Complexes;mathematical model;Measures;Mechanics;Medical Research;Membrane;Methods;Microfilaments;Modeling;Molecular;molecular imaging;Motility;Motion;Myosin ATPase;Myosin Type V;Neoplasm Metastasis;Neurons;novel;Organism;Pattern;Physical condensation;polarized cell;polymerization;Polymers;programs;Regulation;Research;Role;Shapes;Signal Transduction;single molecule;Spatial Distribution;Structure;System;Testing;transmission process;Tubular formation;ultra high resolution;Universities

PROJECT_TITLE: Modeling mechanisms in cytokinesis, cell polarization and motility

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CB-Y(55)R]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Skin Cancer

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: Project Narrative The studies in this grant proposal address the molecular mechanisms driving melanoma metastasis and resistance to drug-targeted therapies focusing on collateral metabolic and epigenetic-dependent vulnerabilities. These mechanisms are central to our understanding of melanoma progression and treatment.

PI_NAMEs: PUIGSERVER, PERE  (contact)

PROGRAM_OFFICER_NAME: AULT, GRACE S

PROJECT_TERMS: Acute;Address;Applications Grants;Attenuated;Automobile Driving;Bioenergetics;Biogenesis;Blocking Antibodies;BRAF gene;cancer cell;Cell Line;Cells;Chromatin;Chronic;Clinical;Clinical Management;clinical risk;clinically relevant;combinatorial;Data;Dependence;Disease;Disease remission;Drug resistance;Drug Targeting;Ensure;Enzymes;Epigenetic Process;established cell line;expectation;Experimental Designs;EZH2 gene;Failure;Gene Expression;Gene Expression Profile;Genetic;Growth;Heterogeneity;Histones;Human;immune checkpoint;Immune system;In Vitro;in vivo;Invaded;Link;Malignant Neoplasms;Melanoma;Melanoma Cell;Melanoma patient;Metabolic;Metabolism;Metastatic Melanoma;Mitochondria;Modeling;Molecular;Molecular Target;Neoplasm Metastasis;Oncogenes;Oncogenic;Outcome Study;patient prognosis;Patients;Pattern;Pharmaceutical Preparations;Primary Lesion;Process;promoter;Promoter Regions;recruit;Refractory;Relapse;Reporting;Repression;Resistance;response;Role;Site;Skin Cancer;small molecule;Specimen;targeted treatment;Therapeutic;therapy resistant;trait;Transcription Coactivator;transcriptome;Treatment outcome;treatment response;tumor;tumor behavior;Variant;Vertical Growth Phase;whole genome

PROJECT_TITLE: Metabolic and epigenetic dependencies in melanomas during metastasis and targeted-drug resistance

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


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Congenital Structural Anomalies;Genetics;Pediatric;Prevention;Rare Diseases

ORG_CITY: LA JOLLA

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

ORG_STATE: CA

PHR: Public Health Relevance Marfan Syndrome is a genetic disease that affects about 1 in 5000 people. The most life-threatening manifestation of Marfan Syndrome is widening of the aorta, which can lead to acute aortic rupture and death; current treatments of the aortic disease are suboptimal. In this project, we propose to define mechanisms causing the aortic disease, and develop a new treatment.

PI_NAMEs: PILZ, RENATE B (contact)

PROGRAM_OFFICER_NAME: STABLEY, JOHN N

PROJECT_TERMS: Acute;Adhesions;Adrenergic Agents;Adrenergic Antagonists;Adrenergic beta-Antagonists;Affect;Age;age related;Alleles;analog;Aneurysm;Antioxidants;Aorta;Aortic Aneurysm;Aortic Diseases;Aortic Rupture;Apoptosis;ascending aorta;Attenuated;autosome;Cardiovascular Abnormalities;catalase;Cell Physiology;Cells;Cessation of life;Chest;cobinamide;Collagen;Complement;Cyclic GMP;Cyclic GMP-Dependent Protein Kinases;Data;Deposition;Development;Diameter;Disease;Dissection;DNA;Dose;drinking water;Drug Metabolic Detoxication;Elastic Fiber;Elastin;Enzymes;extracellular;Extracellular Matrix;Extracellular Matrix Degradation;Extracellular Matrix Proteins;Eye Abnormalities;FBN1;fibrillin;Fibrosis;Functional disorder;gain of function mutation;Gene Expression;Gene Expression Profile;Generations;Genetic Diseases;Goals;Grant;Histology;Human;Human Milk;Impairment;improved;In Vitro;in vivo;induced pluripotent stem cell;Inherited;inhibitor;knock-down;Knock-out;Legal patent;Life;Lipids;loss of function mutation;LoxP-flanked allele;Maintenance;Marfan Syndrome;Matrix Metalloproteinases;Mechanical Stress;Medial;Microfibrils;mimetics;Mitochondria;mouse model;Mus;mutant;Mutation;Nitric Oxide;Nitric Oxide Synthase;nitrosative stress;novel;Oral;overexpression;oxidation;Oxidative Stress;Pathology;Pathway interactions;Patients;Peroxonitrite;Persons;pharmacologic;Phenotype;Play;postnatal;premature;Prevalence;prevent;Production;Proliferating;Propranolol;Protein Isoforms;Proteins;public health relevance;Reactive Inhibition;Reactive Nitrogen Species;Reactive Oxygen Species;repaired;Reporting;Role;Schedule;Signal Transduction;skeletal abnormality;small hairpin RNA;Smooth Muscle Myocytes;Source;stress activated protein kinase;stress kinase;Superoxide Dismutase;Superoxides;Tamoxifen;Testing;Thoracic Aortic Aneurysm;Time;Transgenes;treatment strategy;Up-Regulation;Vitamin B 12

PROJECT_TITLE: A novel treatment of aortic disease in Marfan Syndrome targeting oxidative stress and PKG dysregulation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-CVRS-Q(02)]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Breast Cancer;Cancer;Prevention;Women's Health Research

ORG_CITY: AMHERST

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

ORG_STATE: NY

PHR: Breast cancer is the most commonly diagnosed cancer among American women. To minimize the morbidity and mortality of this disease, we propose to develop a single photon emission breast tomography scanner with great imaging performance to carry out radionuclide tracer based molecular breast imaging. This scanner will use much less radioactivity and be able to detect smaller tumors than its state-of-art counterparts. In this proposed work, we will design, evaluate, and optimize the configurations of the scanner.

PI_NAMEs: YAO, RUTAO  (contact)

PROGRAM_OFFICER_NAME: TORNAI, MARTIN PAUL

PROJECT_TERMS: 3-Dimensional;Abbreviations;American;Anatomy;Architecture;Back;Breast;breast cancer diagnosis;breast imaging;cancer diagnosis;Clinical;Clinical Trials;Collimator;Computer Simulation;contrast imaging;cost;Dedications;design;Detection;detection platform;detector;Development;Diagnostic tests;Disease;effective therapy;Electroplating;Evaluation;Event;Gamma Rays;Image;image reconstruction;imaging detector;Imaging Phantoms;imaging system;Imaging technology;improved;Individual;Lesion;Lifting;Location;Malignant Breast Neoplasm;Malignant Neoplasms;Mammography;Measures;Mechanics;Methods;Molecular;Morbidity - disease rate;Morphology;mortality;novel;Pathologic;Pathway interactions;Patients;Performance;Photons;Play;Positioning Attribute;prevent;Property;prototype;Radiation Dose Unit;Radioactivity;Radioisotopes;Radiopharmaceuticals;Reporting;Resolution;response;Rod;Role;Scheme;screening;Screening for cancer;Screening procedure;Side;Signal Transduction;stem;Structure;System;Technology;Testing;tomography;Tracer;tumor;Woman;Work

PROJECT_TITLE: Self-collimating Single Photon Emission Breast Tomography System with Three-Dimensional Sparse Position-Sensitive Detectors

STUDY_SECTION: ITD

STUDY_SECTION_NAME: Imaging Technology Development Study Section[ITD]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Obesity;Clinical Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Obesity;Pediatric;Prevention;Rural Health;Sleep Research;Social Determinants of Health

ORG_CITY: Aurora

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE Obesity and subsequently type 2 diabetes are increasingly common in pubertal youth, and with a greater degree of insulin resistance, earlier onset of beta-cell failure, and earlier need for insulin therapy than in adults. Medication responses in existing studies in youth-onset type 2 diabetes are poorer than similar studies in adults, with evidence that this aggressive phenotype is leading to earlier onset of diabetes complications. As a result, we now propose to recruit youth with obesity early in puberty and follow them longitudinally over time with serial assessments of insulin sensitivity and secretion, free-living glycemia, physical activity and sleep, mental health and stress, body composition, pubertal stage, and store samples for additional future analyses, with a new focus on understanding the unique, early contributors to development of type 2 diabetes in youth.

PI_NAMEs: KELSEY, MEGAN MORIARTY;NADEAU, KRISTEN JANE (contact)

PROGRAM_OFFICER_NAME: BROADNEY, MIRANDA MARGUERITE

PROJECT_TERMS: Acute;Address;Adolescent;Adult;adverse childhood events;Affect;Age;Amputation;Anxiety;Attention;Behavior;Behavior monitoring;Beta Cell;Biolectric Impedance;Biological;biomarker identification;Blood Banks;Body Composition;Body mass index;bullying;cardiometabolism;Cardiovascular system;Cell Physiology;Child;Chronic;Circadian Rhythms;Code;Collaborations;Communities;comorbidity;comparison control;Complications of Diabetes Mellitus;COVID-19;Creativeness;Data;Data Analyses;design;Deterioration;Development;Diabetes Mellitus;Diabetes prevention;Diabetic Angiopathies;Diagnostic;Discrimination;Disease;Dual-Energy X-Ray Absorptiometry;early onset;Ecological momentary assessment;Education;Enrollment;Ethnic Origin;Event;Exposure to;Failure;Family;Feces;follow-up;Future;Genetic;Gestational Diabetes;glycemic control;Glycosylated hemoglobin A;Goals;Hair;Health Care Costs;health disparity;health equity promotion;Health Services Accessibility;high risk;Hormones;Hydrocortisone;impaired glucose tolerance;In Situ;Incidence;Income;Individual;innovation;Insulin;Insulin Resistance;insulin secretion;insulin sensitivity;Intervention;Intervention Studies;Interview;Lead;Lipids;Machine Learning;Magnetic Resonance Imaging;Measures;medication compliance;member;Mental Depression;Mental Health;Metabolic;Metformin;Methodology;microaggression;Monitor;Morbidity - disease rate;Myocardial Infarction;National Institute of Diabetes and Digestive and Kidney Diseases;Newly Diagnosed;Non-Insulin-Dependent Diabetes Mellitus;novel;Obesity;OGTT;optimal treatments;Oral;Outcome;pandemic disease;Participant;Pattern;Perception;Pharmaceutical Preparations;Phenotype;Physical activity;Physiological;Pilot Projects;Polysomnography;Population;Poverty;predictive modeling;prevent;Prevention approach;Prevention strategy;Productivity;progression risk;Psychological Factors;psychosocial;Psychosocial Assessment and Care;Psychosocial Factor;Puberty;Questionnaires;Race;racial minority;racism;Recording of previous events;recruit;response;Risk;Risk Factors;Role;rural area;Rural Community;Sampling;Schedule;screening;sedentary lifestyle;Site;Sleep;Sleep disturbances;social;Social status;Standardization;Stress;Stroke;Time;treatment response;type 2 diabetes in children;urban area;Urban Community;Urine;Visit;Weight Gain;Youth

PROJECT_TITLE: What Activates Type 2 diabetes in Children (WATCH)


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Neurosciences;Rare Diseases

ORG_CITY: STANFORD

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: STANFORD UNIVERSITY

PHR: PROJECT NARRATIVE Enteroviruses are ubiquitous pathogens causing a number of important human diseases including poliomyelitis, myocarditis, acute flaccid myelitis and the common cold. Rhinovirus infections are a major cause of severe asthma exacerbations and non-poliovirus enteroviruses such as EV-A71 cause severe neuropathogenesis in children. Our contributions will have wide-reaching impacts as the identified cellular genes and molecular mechanisms are likely to provide new targets for therapeutic interventions, in addition to fundamentally advancing the fields of viral infection, immunity and protein methylation.

PI_NAMEs: CARETTE, JAN E (contact)

PROGRAM_OFFICER_NAME: PARK, EUN-CHUNG

PROJECT_TERMS: Actins;Acute;acute flaccid myelitis;Address;asthma exacerbation;Biology;Cell Physiology;cell type;Cells;Child;Common Cold;Communicable Diseases;Complex;Coxsackie Viruses;Cryoelectron Microscopy;Crystallography;Data;Enteral;Enterovirus;Enterovirus 68;Enterovirus 71;Enterovirus Infections;Family Picornaviridae;Genes;Genome;Goals;Growth;Health;Human;human disease;Human poliovirus;Immunity;Immunocompetent;In Vitro;in vivo;Infection;Injections;innate immune mechanisms;insight;Integration Host Factors;Invaded;Knock-out;Knowledge;Medical;member;Methods;Methylation;Methyltransferase;microbial;Modeling;Molecular;mouse model;Mus;Mutation;Myocarditis;neonate;neural;Neurologic Symptoms;Neuropathogenesis;new therapeutic target;novel;novel strategies;Oral;oral infection;Paralysed;pathogen;Pathogenesis;Play;Poliomyelitis;Polyproteins;Protein Methylation;Protein Methyltransferases;Proteins;Proteomics;Regulation;Rhinovirus;Rhinovirus infection;RNA replication;RNA Viruses;Role;screening;Site;Structure;Testing;Therapeutic Intervention;Tissues;Translations;transmission process;Veterinary Medicine;Viral;Viral Nonstructural Proteins;Viral Pathogenesis;viral RNA;Viremia;Virus;Virus Diseases;virus host interaction;Virus Replication

PROJECT_TITLE: Host determinants of enterovirus RNA replication and in vivo neuropathogenesis

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


NIH_SPENDING_CATS: Aging;Biomedical Imaging;Cardiovascular;Contraception/Reproduction;Heart Disease;Hypertension;Maternal Health;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Prevention;Women's Health Research

ORG_CITY: WINSTON-SALEM

ORG_NAME: WAKE FOREST UNIVERSITY HEALTH SCIENCES

ORG_STATE: NC

PHR: Project Narrative Advanced maternal age represents a steadily increasing public health concern and is a poorly studied risk factor for cardiovascular disease in offspring later in life due to an unfavorable intrauterine environment during fetal development. We propose to use a combination of minimally-invasive imaging and sampling techniques to follow pregnant female monkeys over time to compare maternal cardiac function and placental blood flow in aged vs. young pregnancies, while also evaluating current adult offspring from aged vs. young pregnancies for evidence of early cardiovascular disease. Through a better understanding of abnormal changes that occur in both mothers and their offspring from pregnancies at advanced age, we may be able to identify new targets for therapies and critical timing for intervention that can prevent or delay the onset of cardiovascular disease.

PI_NAMEs: CILVIK, SARAH N (contact)

PROGRAM_OFFICER_NAME: SHANBHAG, SUJATA MADHUKAR

PROJECT_TERMS: 14 year old;8 year old;9 year old;Address;Adult;Adult Children;advanced maternal age;adverse outcome;adverse pregnancy outcome;Affect;age related;aged;Anatomy;Animal Model;Biological Markers;biomarker evaluation;Biopsy;Birth;Blood;Blood flow;Blood Pressure;Blood specimen;Blood Vessels;Breeding;Cardiac;cardiac magnetic resonance imaging;Cardiovascular Diseases;Cardiovascular Physiology;cardiovascular risk factor;Cardiovascular system;Child;Chronic;circulating biomarkers;clinically relevant;contrast enhanced;coronary fibrosis;Data;Developed Countries;Development;Diet;disease model;early childhood;Echocardiography;EFRAC;Elderly;Environment;Evaluation;experience;extracellular;Female;fetal;Fetal Development;Fetal Growth;Fetal Growth Retardation;Functional disorder;Gestational Diabetes;Health;heart function;Histologic;Histology;Human;Hypertension;Image;Imaging Techniques;Impairment;Intervention;intrauterine environment;Ischemia;Knowledge;Life;Longitudinal Studies;male;Maternal Age;Measurement;Measures;Mediator;medical schools;minimally invasive;Modeling;Monkeys;Mothers;multidisciplinary;neonate;new therapeutic target;nonhuman primate;offspring;older adult;Outcome;Pathway interactions;Perfusion;perinatal outcomes;Physiological;Physiology;Placenta;Placental Insufficiency;Placentation;Pre-Clinical Model;Pre-Eclampsia;Pregnancy;pregnant;prevent;Public Health;Recovery;Renin-Angiotensin-Aldosterone System;reproductive;reproductive senescence;reproductive success;Research;Research Personnel;Research Project Grants;response;Risk;Risk Factors;Rodent;Sampling;serial imaging;Spontaneous abortion;stillbirth;Techniques;Testing;therapeutic target;Time;Tissues;Ultrasonography;ultrasound;Umbilical Blood;Umbilicus;United States National Institutes of Health;Universities;Uterus;vervet;Woman;young adult

PROJECT_TITLE: Developmental Origins of Cardiovascular Disease in Offspring from Non-Human Primate Pregnancies at Advanced Maternal Age

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


ORG_CITY: SEATTLE

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PHR: Project Narrative The proposed project is aimed at elucidating the mechanisms of the biosynthesis of β-lactam antibiotics by isopenicillin N-synthase (IPNS), and the oxidation of cysteine by the tumor suppressor enzyme cysteine dioxygenase (CDO). Small-molecule intermediate-analogues, low-temperature electronic absorption and Mössbauer spectroscopy, spectro-electrochemistry, and T-dependent kinetics will be used to probe key steps in the enzyme mechanism.

PI_NAMEs: KOVACS, JULIA A (contact)

PROGRAM_OFFICER_NAME: ASLAN, KADIR

PROJECT_TITLE: Understanding How Thiolates Promote Dioxygen Chemistry


NIH_SPENDING_CATS: Genetics;Human Genome

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Narrative My research program is devoted to understanding fundamental DNA repair mechanisms and their influence on cancer etiology and response to therapy. We will continue to approach these central questions by utilizing unique systems that we have developed to investigate the molecular events underlying (1) the influence of chromatin on DNA repair mechanism, and (2) interactions between repair mechanisms that affect genome maintenance. These pursuits will provide insights into adaptive responses of cancers that use noncanonical homology directed repair mechanisms to maintain telomere length.

PI_NAMEs: GREENBERG, ROGER A (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: 3'-nuclease;Affect;Agreement;cancer cell;Cancer Etiology;Cell Cycle;Cells;Chromatin;Chromosomes;Coupled;Couples;Deoxyribonucleases;design;DNA;DNA biosynthesis;DNA Damage;DNA Double Strand Break;DNA Repair;DNA Structure;DNA-Directed DNA Polymerase;Double Strand Break Repair;ds-DNA;Elements;Event;examination questions;Funding;gain of function;Genetic Epistasis;Genetic Recombination;Genome;genome integrity;helicase;homologous recombination;Human;Hybrids;In Vitro;insight;Knowledge;Length;Lesion;Link;Maintenance;Malignant Neoplasms;Maps;Mass Spectrum Analysis;Mediating;Mesenchymal;Methods;Modeling;Molecular;Molecular and Cellular Biology;Names;nuclease;Pathway interactions;Polymerase;Principal Investigator;Process;Productivity;programs;Proliferating;Proteins;Proteomics;Publishing;recombinational repair;reconstitution;recruit;repaired;replication stress;Research;response;S phase;Series;Stretching;Structure;System;telomere;telomere damage;Telomere Maintenance;Telomere Recombination;Testing;Time;treatment response;Ubiquitin;Ubiquitination;Visualization

PROJECT_TITLE: DNA double-strand break chromatin alterations and genome integrity

STUDY_SECTION: RTB

STUDY_SECTION_NAME: Radiation Therapeutics and Biology Study Section[RTB]


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Precision Medicine;Women's Health Research

PHR: PROJECT NARRATIVE Some patients with HER2-positive metastatic breast cancer do exceptionally well, remaining on first-line therapy indefinitely without evidence of disease progression. Tracking minimal residual disease in the blood may help guide treatment in patients with HER2+ MBC and allow us to explore whether some patients might be cured.

PI_NAMEs: PARSONS, HEATHER ANNE (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: advanced breast cancer;Aftercare;Bioinformatics;Biological Assay;Blood;Blood Tests;blood-based biomarker;Breast Cancer Patient;career;Caring;cell free DNA;Clinical;Clinical Investigator;clinical predictors;Clinical Trials;Clonal Evolution;Cross-Sectional Studies;Dana-Farber Cancer Institute;Detection of Minimal Residual Disease;Development;Diagnosis;Diagnostic;Disease;Disease Progression;Disease-Free Survival;Distant;ERBB2 gene;exceptional responders;experience;Fingerprint;Future;Goals;improved;improved outcome;Intention;Knowledge acquisition;liquid biopsy;Malignant Breast Neoplasm;Medical Oncologist;Mentors;Metastatic breast cancer;Mutation;Newly Diagnosed;No Evidence of Disease;novel;Outcome;palliative;patient subsets;Patient-Focused Outcomes;Patients;Population;predictive marker;Progression-Free Survivals;prospective;prospective test;Recurrence;Recurrent disease;Research Personnel;Residual Neoplasm;response;Retrospective Studies;Role;skills;success;Systemic Therapy;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;Time;tool;Training;Translating;treatment optimization;Treatment outcome;treatment response;tumor;Withholding Treatment

PROJECT_TITLE: Can a subset of patients with HER2+ metastatic breast cancer be cured?

STUDY_SECTION: NCI

STUDY_SECTION_NAME: Career Development Study Section (J)[NCI-J]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Huntington's Disease;Neurodegenerative;Neurosciences;Rare Diseases

ORG_DEPT: PHYSIOLOGY

PHR: Neurodegenerative diseases such as Huntington’s Disease and spinocerebellar ataxias are caused by inherited mutations in which the affected gene contains many extra copies of the three bases CAG. This research will develop new tools capable of imaging single RNA molecules to study how these mutations alter the mRNA structure and cause it to aggregate with other RNAs, resulting in cell death. The goal is to understand how these abnormal RNA structures harm neurons and cause deterioration of the brain.

PI_NAMEs: KAISER, CHRISTIAN ;WOODSON, SARAH A. (contact)

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: Address;Affect;Amyotrophic Lateral Sclerosis;base;Base Pairing;Binding Proteins;Biological;Biological Assay;Brain;CAG repeat;Cations;Cell Aggregation;Cell Death;Cell Separation;Cells;Cellular biology;Chemicals;Complex;confocal imaging;Deterioration;Development;Disease;flexibility;fluidity;fluorescence imaging;fluorophore;Future;Gel;Genes;genome wide association study;Goals;Growth;Human;Huntington Disease;Huntington gene;imaging capabilities;In Vitro;Inherited;Kinetics;Knowledge;laser tweezer;Lateral;Link;Liquid substance;Measures;mechanical properties;Messenger RNA;method development;Methods;Microfluidics;Molecular;molecular imaging;molecular pathology;mouse model;mutant;Mutation;Nerve Degeneration;Neurodegenerative Disorders;Neurofibrillary Tangles;Neuroglia;Neurons;neurotoxicity;new therapeutic target;novel strategies;Nucleotides;optic trap;optic tweezer;optical traps;Pathogenesis;Pathogenicity;Pathologic;Physical condensation;physical property;polyglutamine;Process;protein complex;Proteins;Reaction;Research;Risk;RNA;RNA Probes;RNA-Binding Proteins;RNA-Protein Interaction;single molecule;small molecule;small molecule inhibitor;Spectrum Analysis;Spinocerebellar Ataxias;Stress;Stretching;Structure;Testing;Time;tool;Toxic effect;Trinucleotide Repeats;Triplet Multiple Birth;Variant;Work;X-Ray Crystallography

PROJECT_TITLE: Molecular Origins of Neurodegeneration through Force Detangling of Toxic RNA

STUDY_SECTION: MSFB

STUDY_SECTION_NAME: Macromolecular Structure and Function B Study Section[MSFB]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: CHICAGO

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: NARRATIVE Over one hundred de novo loss-of-function mutations in SYNGAP1 have been unambiguously associated with autism and intellectual disability. We uncovered a conserved SYNGAP1 alternative splicing event that is coupled with nonsense-mediated mRNA decay (AS-NMD) during normal mouse and human brain development. This research project aims to determine whether it is feasible to rescue SYNGAP1 haploinsufficiency by suppressing AS-NMD using genetically engineered mice and splice-switching oligonucleotides.

PI_NAMEs: ZHANG, XIAOCHANG  (contact)

PROGRAM_OFFICER_NAME: DRISCOLL, JAMIE DANIELLE

PROJECT_TERMS: 3' Splice Site;Ablation;Alleles;Alternative Splicing;AMPA Receptors;Animals;autism spectrum disorder;Behavior;Behavioral;Brain;Cells;Coupled;Defect;Development;efficacy evaluation;Electrophysiology (science);Elements;Event;Exons;Genetic;genetic approach;Genetically Engineered Mouse;Glutamates;Heterozygote;Hippocampus;Human;Human Development;Impairment;Induced pluripotent stem cell derived human neuron;Induced pluripotent stem cell derived neurons;insight;Intellectual functioning disability;Knock-out;Knockout Mice;Lead;learned behavior;Long-Term Potentiation;loss of function;loss of function mutation;Loss of Heterozygosity;Mediating;Molecular;mouse development;mouse genetics;mouse model;mRNA Decay;Mus;Mutant Strains Mice;Neocortex;neurodevelopment;Neurodevelopmental Disorder;Neurons;Oligonucleotides;patient derived induced pluripotent stem cells;Patients;Phenotype;Physiological;Pilot Projects;postnatal;pre-clinical;protein expression;Protein Isoforms;Proteins;Reagent;Reporting;Research Project Grants;RNA Splicing;success;Synapses;Synaptic plasticity;Synaptic Transmission;SYNGAP1;Testing;therapeutic target;Toxic effect;Vertebral column

PROJECT_TITLE: Rescuing SYNGAP1 haploinsufficiency by redirecting alternative splicing

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Intellectual and Developmental Disabilities (IDD);Machine Learning and Artificial Intelligence;Mental Health;Pediatric

ORG_CITY: PITTSBURGH

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE Emotion regulation (ER) impairments in individuals with autism spectrum disorder (ASD) exacerbate social difficulties and contribute to high rates of co-occurring psychiatric and behavioral problems, psychotropic medication prescription, and inpatient hospitalizations in this population. The proposed study will be a first step toward identifying early mechanisms and markers of ER impairment by examining emotional dynamics in parent-child interactions and their relation to ER development. By examining time-linked biological and behavioral markers of child emotional distress and parent responses, and applying machine learning approaches to examine multimodal relations between variables, the study has the potential to identify specific targets for interventions focused on ER development within the parent-child dyad.

PI_NAMEs: NORTHRUP, JESSIE B (contact)

PROGRAM_OFFICER_NAME: BECHTHOLT, ANITA JEAN

PROJECT_TERMS: 4 year old;Arousal;autism spectrum disorder;autistic children;Behavior;Behavioral;behavioral response;biobehavior;Biological;Caregivers;Child;Child Development;Clinical;Code;Collection;Communication;Complex;Cues;Data;Development;Diagnosis;Distress;Drug Prescriptions;Early identification;emotion regulation;Emotional;emotional distress;Emotions;Environment;experience;Expressed Emotion;Face;Family;Foundations;Fright;Goals;high risk;Home;Hospitalization;Impairment;indexing;Individual Differences;individuals with autism spectrum disorder;Infant;innovation;Inpatients;Intervention;Knowledge;Link;Machine Learning;machine learning method;Measurement;Measures;Mentors;Methodology;Modality;Monitor;multimodality;non-verbal;Nursery Schools;Parent-Child Relations;Parents;peer;Peripheral;Physiological;Physiology;Play;Population;Positioning Attribute;positive emotional state;primary caregiver;Problem behavior;Process;programs;prospective;Psychiatry;Psychologist;Qualifying;Reporting;Research;response;Risk Assessment;Risk Factors;Role;Sampling;scaffold;School-Age Population;Series;showing emotion;Signal Transduction;skills;social;social communication;Social Processes;Stress;Techniques;Testing;Time;Training;Universities;verbal;Videotape

PROJECT_TITLE: Parent-Child Interaction and Emotion Regulation in Preschoolers with Autism Spectrum Disorder

STUDY_SECTION: CPDD

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Cardiovascular;Gene Therapy;Genetics;Heart Disease;Human Genome;Nanotechnology;Orphan Drug;Rare Diseases

PHR: PROJECT NARRATIVE  I aim to develop in vivo genome editing therapeutics to treat dilated cardiomyopathy. I will develop genome editor screens to correct TTN haploinsufficiency and as well as characterize viral and nanoparticle delivery methods for base editors and prime editors in vivo in the mouse. I will combine the best identified tools to treat a mouse model of TTN haploinsufficiency, with the ultimate goal of enabling one-time injectable doses to treat dilated cardiomyopathy and other haploinsufficiency disorders.

PI_NAMEs: NEWBY, GREGORY A. (contact)

PROGRAM_OFFICER_NAME: THAKAR, RAHUL GAUTAM

PROJECT_TERMS: Adult;Affect;Alleles;Animal Model;ATAC-seq;base;base editing;base editor;Binding;Binding Sites;Brain;Cardiac Myocytes;Cell division;cell type;Cells;ChIP-seq;Chromatin;Clinical;Clinical Trials;Databases;Defect;delivery vehicle;Dependovirus;Detection;Dilated Cardiomyopathy;Disease;DNA Sequence Alteration;Dose;Echocardiography;Engineering;Flow Cytometry;Frequencies;Future;Genes;Genetic;Genetic Diseases;Genetic Models;Genetic Transcription;genome editing;genome editor;Goals;Guide RNA;Heart;Heart Diseases;Heart failure;Human;human disease;improved;in vivo;induced pluripotent stem cell;Injectable;Injections;insertion/deletion mutation;interest;Interphase Cell;Intervention;Intravenous;Length;Life;lipid nanoparticle;Liver;Measures;Mentors;Methodology;Methods;Microscopy;Modality;Modeling;mouse genome;mouse model;Mus;Muscle;Mutation;mutation correction;Myocardium;nanoparticle;nanoparticle delivery;nanopolymer;Newborn Infant;Nucleotides;Other Genetics;Outcome;Patients;Persons;Phase;Phenotype;Photography;Point Mutation;Population;Postdoctoral Fellow;precise genome editing;prime editing;prime editor;promoter;Promoter Regions;Rare Diseases;reduce symptoms;repair strategy;repaired;Reporter;screening;Site;Specificity;success;Technology;Therapeutic;therapeutic development;therapeutic genome editing;tissue culture;Tissues;tool;transcription factor;United States;Up-Regulation;Variant;Viral;Work

PROJECT_TITLE: In vivo precision genome editing to correct genetic disease

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome;Immunotherapy

PHR: PROJECT NARRATIVE DNA hypomethylation is a nearly universal feature of cancer but the consequences of this epigenetic change are not well understood. This research proposal will investigate how DNA hypomethylation drives changes in genome organization and transcriptional programs, including activation of endogenous retroviral elements. Defining the functional consequences of DNA hypomethylation is critical for ongoing efforts to apply demethylating therapies for clinical benefit.

PI_NAMEs: JOHNSTONE, SARAH E (contact)

PROGRAM_OFFICER_NAME: LIM, SUSAN E

PROJECT_TERMS: Academia;Advisory Committees;Architecture;Belief;Biology;Burn injury;cancer/testis antigen;career development;Cell Aging;Cell model;Cell Nucleus;Cell Physiology;Cells;cellular engineering;Cessation of life;checkpoint therapy;Chromatin;Clinic;Clinical;Clinical Pathways;Clustered Regularly Interspaced Short Palindromic Repeats;colon cancer patients;Colon Carcinoma;Colonic Neoplasms;Communication;CpG Islands;CRISPR/Cas technology;demethylating therapy;demethylation;Development Plans;DNA;DNA Methylation;DNA Sequence Alteration;Dysmyelopoietic Syndromes;Elements;Endogenous Retroviruses;Engineering;Epigenetic Process;Euchromatin;Faculty;Foundations;Future;gene repression;Gene Silencing;General Hospitals;Genes;Genetic Transcription;Genome;genome-wide;Genomic DNA;Genomic Segment;Genomics;Grant;Heterochromatin;Hypermethylation;Immunity;Immunotherapy;in vitro Model;insight;Invaded;Kinetics;Laboratories;Leadership;leukemia;Link;Malignant - descriptor;Malignant Neoplasms;Massachusetts;Mediating;Mentors;Mentorship;Methods;Methylation;Microscopy;Modeling;neoplastic cell;Normal Cell;novel;Nuclear;Oncogenic;Pathology;Peripheral;Pharmaceutical Preparations;Phenotype;Physicians;Play;Positioning Attribute;Professional Competence;Program Development;programs;Reagent;Recording of previous events;Repetitive Sequence;Repression;Research;Research Proposals;restraint;Role;Scientist;segregation;skills;Solid Neoplasm;stemness;Structure;Technical Expertise;Testing;Therapeutic;tool;Training;tumor;Tumor Immunity;Tumor Suppressor Genes;United States;Up-Regulation;Work;Writing

PROJECT_TITLE: Elucidating the impact of DNA hypomethylation on genome organization and anti-tumor transcriptional programs


NIH_SPENDING_CATS: Biotechnology;Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Neurosciences;Rare Diseases;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Tuberous Sclerosis

ORG_CITY: BERKELEY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: PROJECT NARRATIVE Recent advances in human cell and genome engineering have facilitated the establishment of “disease-in-a- dish” approaches in which the molecular mechanisms of neurological disorders can be investigated directly in human cultured neurons. Using such a system, we will investigate how mutations in genes that cause the neurodevelopmental disorder Tuberous Sclerosis Complex affect human brain cell development and function. In addition to revealing the causes of brain dysfunction, our studies will test manipulations designed to restore normal development and activity.

PI_NAMEs: BATEUP, HELEN S. (contact)

PROGRAM_OFFICER_NAME: LEE, CRYSTAL ANNE

PROJECT_TERMS: 3-Dimensional;Affect;arm;Astrocytes;autism spectrum disorder;Automobile Driving;Autophagocytosis;Behavioral;Binding Proteins;Biological Models;Body System;Brain;brain cell;brain dysfunction;Calcium;Candidate Disease Gene;Caregivers;cell cortex;Cell Differentiation process;Cell Line;Cell Lineage;cell type;Cells;cellular development;cellular engineering;clinically relevant;Complex;Cortical Malformation;cortical tubers;CRISPR interference;design;Development;developmental disease;Disease;disease-in-a-dish;early onset;Embryonic Development;Engineering;Epilepsy;experimental study;FRAP1 gene;Functional disorder;Gene Proteins;Generations;Genes;Genetic;Genetic Engineering;Genetic Transcription;Genome engineering;Goals;Grant;Guide RNA;High Prevalence;Human;human stem cells;Hyperactivity;Image;Impaired cognition;Impairment;improved;Individual;insight;Intellectual functioning disability;Knock-in;Lead;loss of function mutation;Modeling;Molecular;multi-electrode arrays;mutant;Mutation;nerve stem cell;Nervous System Disorder;neural network;Neurodevelopmental Disorder;neurogenesis;Neuroglia;Neurologic;neuronal survival;Neurons;newborn neuron;Operative Surgical Procedures;Organoids;Outcome;Pathology;Pathway interactions;Patient observation;patient variability;pharmacologic;Phenotype;premature;prevent;Production;programs;Role;Sampling;Seizures;Signal Transduction;Slice;small hairpin RNA;stem cell differentiation;System;Testing;TSC1 gene;TSC1/2 gene;TSC2 gene;Tuberous Sclerosis

PROJECT_TITLE: Elucidating the origins of cortical tuber cells using human brain organoid models of TSC

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


NIH_SPENDING_CATS: Autoimmune Disease;Clinical Research;Digestive Diseases;Inflammatory Bowel Disease;Microbiome;Nutrition;Prevention

ORG_CITY: NEW YORK

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: PROJECT NARRATIVE The nature of Inflammatory Bowel Disease (IBD) suggests genetically susceptible individuals are persistently colonized with mildly pathogenic microbial strains or lack colitoprotective strains. The majority of human gut microbiota strains remain stably colonized in our gastrointestinal tract from years to decades. Using microbial strain tracking methods and gnotobiotic mouse models of colitis, we will assess if colitogenic and colitoprotective human gut microbes stably or transiently colonize the human gut microbiota and explore the practical implications for this stability in the context of fecal microbiota transplantation for ulcerative colitis.

PI_NAMEs: FAITH, JEREMIAH JAMES (contact)

PROGRAM_OFFICER_NAME: LUNSFORD, DWAYNE

PROJECT_TERMS: Acute;Affect;Animal Model;Award;Bacteria;Characteristics;Chronic;clinical remission;Clinical Research;Clostridium difficile;Colitis;Collection;Communities;Crohn's disease;Disease;Disease remission;Donor person;Engraftment;Environmental Risk Factor;Escherichia coli;fecal microbiota;fecal transplantation;Future;Gastrointestinal tract structure;Genetic;genome sequencing;Germ-Free;Gnotobiotic;Goals;gut microbes;gut microbiome;gut microbiota;Human;human disease;IL2RA gene;Immune;Immune response;improved;Individual;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Intervention;Intestines;member;metagenomic sequencing;Metagenomics;Methods;Microbe;microbial;microbiome;microbiome composition;microbiota;Minor;Mucosal Immune System;Mucous Membrane;murine colitis;Mus;Nature;novel;novel therapeutic intervention;novel therapeutics;Organism;pathogen;Pathogenicity;Patients;Penetrance;Persons;Pharmaceutical Preparations;Phenotype;Placebos;post-transplant;Predisposition;prevent;Prevention;Randomized, Controlled Trials;Recurrence;Relapse;relapse patients;relapse prediction;Role;Sampling;Severities;Severity of illness;System;T-Lymphocyte;Testing;Therapeutic;Time;Translations;Transplant Recipients;transplantation therapy;Ulcerative Colitis;virtual

PROJECT_TITLE: The Influence Of Gut Microbiota Stability In Inflammatory Bowel Disease

STUDY_SECTION: DHMI

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


FUNDING_MECHANISM: SBIR-STTR RPGS

ORG_CITY: CHARLOTTESVILLE

ORG_NAME: BRIGHTSPEC, INC.

ORG_STATE: VA

PHR: BrightSpec Inc. NIH SBIR Application Project Narrative Novel Sample Introduction Methodologies for Molecular Rotational Resonance (MRR) Spectroscopy NIH SBIR Direct to Phase II BrightSpec, Inc. Project Narrative Small molecule analysis lies at the heart of basic research, and in particular pharmaceutical research, as the understanding and monitoring of biological systems through sensitive measurement of important compounds such as amino acids and sugars, drugs (and related metabolites), and potential toxins and impurities provide critical insight. The proposed project will significantly enhance the ability of researchers to identify and quantify small molecules by combining Laser-Induced Acoustic Desorption (LIAD) sample vaporization with Molecular Rotational Resonance (MRR) detection that is singularly selective to subtle changes in molecular structure. The resulting commercial LIAD-MRR instrument will dramatically expand the range of compounds accessible to this valuable technique with a sensitive, rapid, easy-to-use configuration, allowing researchers to learn more about their samples than currently possible with existing methods and improving the speed of new groundbreaking discoveries.

PI_NAMEs: BLAGOJEVIC, VOISLAV  (contact)

PROGRAM_OFFICER_NAME: BARNES, CHARLES ASHLEY

PROJECT_TERMS: Acceleration;Achievement;Acoustics;Adoption;Affect;Alanine;Amino Acids;Amino Sugars;Applications Grants;Area;Award;Basic Science;Biological;Biological Monitoring;biological systems;Collaborations;Collection;commercial launch;commercialization;Complex Mixtures;cost;Coupling;Cysteine;design;Detection;Development;Dipeptides;drug discovery;Environmental Monitoring;Environmental Pollutants;Evaluation;Feedback;Generations;Grant;Heart;Histidine;Hour;improved;Individual;innovation;insight;instrument;Isomerism;Laboratory Research;Laser vaporization;Lasers;Learning;Legal patent;Letters;manufacture;Marketing;Mass Spectrum Analysis;Measurement;Measures;metabolomics;method development;Methodology;Methods;Molecular;Molecular Structure;Natural Products;Nebulizer;novel;Nuclear Magnetic Resonance;operation;Paper;Peer Review;Peptides;Pharmaceutical Preparations;Pharmacologic Substance;Phase;Preparation;Process;Proline;prospective;prototype;Research;research and development;Research Personnel;Risk;Sampling;screening;Small Business Innovation Research Grant;small molecule;software development;software systems;Solid;Solvents;Specificity;Spectrum Analysis;Speed;Structure;sugar;System;Techniques;Technology;Temperature;Testing;Thick;Time;Toxin;Ultrasonics;United States National Institutes of Health;Universities;Validation;vaporization;Vial device;Volatilization;Work


NIH_SPENDING_CATS: Antimicrobial Resistance;Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Lung;Orphan Drug;Rare Diseases;Tuberculosis

ORG_CITY: SAINT LOUIS

ORG_NAME: FIMBRION THERAPEUTICS, INC.

ORG_STATE: MO

PHR: Project Narrative: Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), is a leading cause of human mortality in the world for a single infectious agent and drug-resistance to standard of care frontline and even second-line antibiotics is increasing, highlighting the need for new therapies. In this application, we propose to develop a series of small molecule compounds for the treatment of TB, resulting in the selection of optimized drug candidates. The proposed studies have the potential to result in the development of a new family of anti- mycobacterials to be used to treat both drug-sensitive and drug-resistant TB.

PI_NAMEs: HANNAN, THOMAS JOSEPH (contact);MCGRANE, LAUREL

PROGRAM_OFFICER_NAME: BOYCE, JIM P

PROJECT_TERMS: Acute;Aerobic;Agar;analog;Animal Model;Anti-Bacterial Agents;Antibiotic Resistance;Antibiotics;Antimicrobial Resistance;Antimycobacterial Agents;Antitubercular Antibiotics;aqueous;Bacteria;bactericide;Biological Availability;Cell Line;Cells;clinically relevant;combat;Combined Modality Therapy;commercial application;cost;cytotoxicity;Development;Disease;dosage;Drops;drug candidate;Drug Design;drug development;drug discovery;Drug Kinetics;Drug resistance;Drug resistance in tuberculosis;Drug resistant Mycobacteria Tuberculosis;drug-sensitive;Energy Metabolism;experimental study;Explosion;Family;functional group;Future;Generations;Goals;Growth;Half-Life;HepG2;human mortality;Hypoxia;improved;In Vitro;in vitro activity;in vitro testing;in vivo;indexing;Infection;Infectious Agent;innovation;Intellectual Property;interest;isoniazid;Isoniazid resistance;Lead;lead candidate;lead optimization;Libraries;Licensing;Liver Microsomes;Lung infections;Marketing;Metabolic;meter;Mission;Modeling;monocyte;mortality;mouse model;Mus;mutant;Mutation;Mycobacterium tuberculosis;Newly Diagnosed;novel;novel drug class;novel therapeutics;Oral;Outcome;Patient Compliance;Patients;Persons;Pharmaceutical Chemistry;Pharmaceutical Preparations;Pharmacologic Substance;Pharmacology;Phase;phase 1 study;Plasma;pre-clinical;Prevalence;Process;Production;Property;Pyridones;Regimen;Renaissance;Resistance;resistant strain;Respiration;Respiratory Chain;Risk;Safety;scaffold;Series;side effect;Small Business Innovation Research Grant;small molecule;Solubility;Spottings;standard of care;Structure-Activity Relationship;success;Testing;Therapeutic;Toxic effect;treatment duration;Tuberculosis;Tuberculosis diagnosis;tuberculosis drugs;tuberculosis treatment

PROJECT_TITLE: Thiazolino-Pyridone Compounds as Novel Drugs for Tuberculosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DCAI-F(12)]


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biomedical Imaging;Emerging Infectious Diseases;Infectious Diseases;Neurosciences;Orphan Drug;Rare Diseases;Tuberculosis

PHR: We will utilize our rabbit model of TB meningitis and in vivo imaging to understand the biodistribution of new TB drugs in infected-brain tissues, develop and optimize new TB treatments regimens for drug-susceptible as well as multi-drug resistant TB meningitis and correlate the effect of intracerebral inflammatory responses and antimicrobial exposures with the treatment outcomes in the same animals in ways that are not feasible with current technologies that require resected tissues or necropsies.

PI_NAMEs: JAIN, SANJAY  (contact)

PROGRAM_OFFICER_NAME: LAUGHON, BARBARA E

PROJECT_TERMS: ABCB1 gene;Affect;Albumins;analog;Animals;antimicrobial;Area;Area Under Curve;Autopsy;Binding Proteins;Biodistribution;blood-brain barrier permeabilization;Brain;brain tissue;Central Nervous System;Cerebrospinal Fluid;Cerebrum;Cessation of life;Chemicals;Child;Clinical;clinical translation;Clinical Trials;cohort;Data;Dexamethasone;disability;Disease;Dose;drug development;Drug Efflux;Drug Exposure;Drug Kinetics;Early Diagnosis;effective therapy;FDA approved;first-in-human;Future;HIV;Human;human disease;Image;Imaging Device;immunopathology;improved outcome;in vivo imaging;Individual;Infection;Inflammation;inflammatory marker;Inflammatory Response;inhibitor;insight;Kinetics;Lesion;Life;Linezolid;liver metabolism;longitudinal positron emission tomography;Lung;Mass Spectrum Analysis;Measurement;Measures;Meningeal Tuberculosis;Modeling;Multi-Drug Resistance;Multimodal Imaging;Mycobacterium tuberculosis;National Institute of Allergy and Infectious Disease;Nervous System Trauma;neurobehavioral test;neuropathology;novel;Oryctolagus cuniculus;Outcome;Parents;pathogen;Patients;Penetration;Pharmaceutical Preparations;pharmacokinetic model;Pharmacotherapy;Plasma;Positron-Emission Tomography;Pre-Clinical Model;Predisposition;prevent;primary outcome;Process;Property;Regimen;Research;Resected;Rifampin;Role;Site;Sterilization;Strategic Planning;Technology;Time;Tissue Sample;Tissues;Tracer;treatment group;treatment optimization;Treatment outcome;Treatment Protocols;Verapamil;Visualization;Vulnerable Populations

PROJECT_TITLE: Preclinical modeling to study Tuberculous Meningitis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDM-T(50)R]


NIH_SPENDING_CATS: Cancer;Emerging Infectious Diseases;Genetics;HIV/AIDS;Hematology;Infectious Diseases;Lymphatic Research;Lymphoma;Rare Diseases

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: Project Narrative Subversion of cellular defense mechanisms is critical for robust Kaposi's sarcoma-associated herpesvirus (KSHV) gene expression, replication and dissemination, and its ability to cause disease. This proposal investigates how cellular RNA quality control mechanisms regulate KSHV gene expression and viral replication as well as the mechanisms KSHV employs to disrupt these restrictive processes. Completion of this proposal will provide fundamental knowledge regarding the interactions between KSHV and cellular gene expression machinery and provide a framework for further therapeutic exploration.

PI_NAMEs: KARIJOLICH, JOHN  (contact)

PROGRAM_OFFICER_NAME: READ-CONNOLE, ELIZABETH LEE

PROJECT_TERMS: 3' Untranslated Regions;Acquired Immunodeficiency Syndrome;Address;antagonist;antiviral immunity;B-Lymphocytes;Biochemical;Biogenesis;Biology;Cell model;Cells;Data;Defense Mechanisms;Development;Disease;Disease Progression;DNA Virus Infections;DNA Viruses;Endoribonucleases;Ensure;Etiology;experimental study;Gammaherpesvirinae;Gene Expression;Genes;Genetic Transcription;genome wide screen;genome-wide;Herpesviridae Infections;Human;Human Herpesvirus 8;Immune response;in vivo;infected B cell;insight;Kaposi Sarcoma;Knowledge;Life Cycle Stages;Link;Literature;Lymphoma cell;Lymphoproliferative Disorders;lytic replication;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;member;Messenger RNA;Methodology;Molecular;mRNA Decay;novel therapeutic intervention;Outcome;pathogen;Pathway interactions;Plants;Positioning Attribute;Predisposition;primary effusion lymphoma;Process;protein complex;Proteins;Quality Control;recombinant virus;recruit;Regulation;Reporting;response;Retroviridae;Ribosomes;RNA;RNA Decay;RNA Degradation;RNA Processing;RNA Viruses;Role;Series;Testing;Therapeutic;Transcript;transcription factor;Transcriptional Activation;transcriptome;transcriptomics;Translations;Viral;Viral Genes;Viral Genome;Viral Proteins;viral RNA;Virus;Virus Replication

PROJECT_TITLE: Restriction of KSHV by cellular RNA decay pathways

STUDY_SECTION: HCAC

STUDY_SECTION_NAME: HIV Coinfections and HIV Associated Cancers Study Section[HCAC]


ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: Project Narrative The proposed research is relevant to public health because IgG antibodies are widely used therapeutically to treat cancer, autoimmune and inflammatory diseases, allergies, infectious disease, as well as transplantation. Although sialylated IgG1 exerts anti- inflammatory properties, little is known regarding the contribution of sialylation to the other IgG subclasses (IgG2-4), or how extracellular sialylation is regulated. The project is relevant to NIH’s mission because they will establish basic immunology knowledge relating to how IgG glycosylation modulates its biological activity, and will enable precise design of tailored effector functions for therapeutic immunoglobulins.

PI_NAMEs: ANTHONY, ROBERT MCCULLOUGH (contact)

PROGRAM_OFFICER_NAME: RICE, JEFFREY S

PROJECT_TERMS: Affinity;Amino Acid Sequence;Anti-Inflammatory Agents;Antibodies;Antibody Therapy;Antigen-Antibody Complex;Attenuated;attenuation;Autoantibodies;Autoimmune;autoimmune arthritis;Autoimmune Diseases;autoimmune inflammation;autoreactivity;B-Lymphocytes;Binding;Biological;Biological Assay;Biology;Biophysics;Blood Platelets;CD209 gene;Cell Lineage;Clinical;Clinical Trials;Communicable Diseases;Data;Deposition;design;Development;Disease;Dissection;Dose;Engineering;Enzymes;Exhibits;experimental study;extracellular;Fc-Gamma Receptor II;Galactose;glycosylated IgG;glycosylation;glycosyltransferase;Goals;Hepatocyte;Hospitals;Hypersensitivity;IgG Receptors;IgG1;IgG2;IgG3;IgG4;Immune response;Immunocompromised Host;Immunoglobulin G;Immunology;improved;In Situ;In Vitro;in vivo;Individual;Inflammation;Inflammatory;innovation;insight;Institution;Intravenous Immunoglobulins;Kidney;Knowledge;Malignant Neoplasms;Mediating;Mission;Modeling;Molecular;mouse model;Mus;Nephritis;nephrotoxicity;novel;Outcome;Pathogenicity;Pathway interactions;Patients;Plasma;Policies;Polysaccharides;Preparation;Property;Public Health;receptor binding;Recombinant Immune Globulin;Regulation;Replacement Therapy;Research;Rheumatoid Arthritis;Role;Sialic Acids;sialylation;Site;success;sugar nucleotide;Systemic Lupus Erythematosus;Testing;Therapeutic;Therapeutic Uses;Thrombocytopenia;Transplantation;United States National Institutes of Health;Wegener's Granulomatosis

PROJECT_TITLE: Harnessing the anti-inflammatory activity of extracellular sialylation of IgG.

STUDY_SECTION: HAI

STUDY_SECTION_NAME: Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]


NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Obesity;Clinical Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Obesity;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

ORG_STATE: OH

PHR: PROJECT NARRATIVE The consortium for the study of the Pathophysiology to Youth- Onset Type 2 diabetes is designed to understand which youth are at greatest to develop type 2 diabetes and how youth-onset type 2 diabetes develops. Cincinnati Children’s Hospital will contribute to the ongoing work of the consortium by providing clinical and research expertise, participating as a high volume center with diverse clinical cohorts, and proposing and supporting future studies using the platform of the consortium. The overarching goal is to develop effective strategies to prevent youth-onset type 2 diabetes.

PI_NAMEs: SHAH, AMY SANGHAVI (contact)

PROGRAM_OFFICER_NAME: BROADNEY, MIRANDA MARGUERITE

PROJECT_TERMS: Address;adipokines;Adolescent;age related;Anxiety;Behavior;Behavioral;Beta Cell;Cell Physiology;Cells;Cessation of life;Characteristics;Child;Childhood;Chronic;Clinical;clinical center;Closure by clamp;cohort;Collaborations;comorbidity;Complex;Coupled;COVID-19 pandemic;Data;design;Development;Diabetes Mellitus;Diagnosis;Diet;Dyslipidemias;early onset;Epidemiology;ethnic difference;Ethnic Origin;experience;Exposure to;Failure;fatty liver disease;Frequencies;Functional disorder;Funding;Funding Opportunities;Future;Genetic;Genetic Risk;Geography;Goals;Health;Hormonal;Hypertension;Incidence;indexing;inflammatory marker;insulin secretion;insulin sensitivity;Intervention;intravenous glucose tolerance test;Investigation;Knowledge;Literature;Longitudinal Studies;Measures;Mental Depression;Metabolic;Monitor;Multicenter Studies;Natural History;Nature;Non-Insulin-Dependent Diabetes Mellitus;Obesity;obesity in children;observational cohort study;OGTT;Pancreas;participant retention;Patients;Pediatric Hospitals;Phenotype;Physical activity;physical inactivity;Polycystic Ovary Syndrome;Positioning Attribute;prenatal exposure;prevent;Prevention;prospective;Prospective Studies;psychosocial;Psychosocial Factor;Puberty;Race;racial difference;Recording of previous events;recruit;Research;response;Risk;Risk Factors;risk selection;Role;Rural;Sampling;SARS-CoV-2 infection;Second Degree Relative;Secondary to;Series;sex;Sex Differences;Site;Sleep;socioeconomics;Stress;Structure of beta Cell of islet;Testing;Time;United States;United States National Institutes of Health;Work;Youth

PROJECT_TITLE: Cincinnati Children's Clinical Center for Targeting the Pathophysiology of Youth-Onset Type 2 Diabetes


ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

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

ORG_CITY: RICHARDSON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF TEXAS DALLAS

ORG_STATE: TX

PHR: PROJECT NARRATIVE Exposure-based therapies are the current gold standard of care for anxiety and fear disorders, including post-traumatic stress disorder (PTSD), and success in exposure therapy depends on the process of extinction of conditioned fear. We have recently demonstrated that exposure paired with vagus nerve stimulation (VNS) enhances extinction of fear-based memories in rats. In the proposed studies, we further test whether VNS-paired exposure also produces longer-lasting and more generalizable extinction of learned fear, and we examine the neural mechanisms by which VNS enhances fear extinction.

PI_NAMEs: MCINTYRE, CHRISTA  (contact);THORN, CATHERINE A

PROGRAM_OFFICER_NAME: VICENTIC, ALEKSANDRA

PROJECT_TERMS: Acceleration;Affect;Amygdaloid structure;Anatomy;Animals;Anxiety;Anxiety Disorders;Area;Arousal;Axon;behavior test;Behavioral;behavioral extinction;Brain;Bypass;Cervical;conditioned fear;conditioning;Coupled;Cues;Data;Development;Disease;Dropout;Emotional;Epinephrine;Exhibits;experience;Experimental Designs;Exposure to;Extinction;fear memory;fighting;Fright;Goals;Hippocampus;Human;Impairment;improved;Individual;Infusion procedures;innovation;insight;Learning;learning extinction;Left;locus ceruleus structure;Maintenance;Medial;Mediating;Memory;memory acquisition;memory consolidation;Microdialysis;neural;neuromechanism;Neuromodulator;Neurons;neuroregulation;noradrenergic;Norepinephrine;optogenetics;Parasympathetic Nervous System;Pathway interactions;patient population;Patients;Pattern;Peripheral;Persons;Play;Post-Traumatic Stress Disorders;pre-clinical;Prefrontal Cortex;prevent;Process;Publishing;Rat Transgene;Rattus;Research;response;Role;Signal Transduction;Site;standard of care;Stimulus;success;Synapses;Synaptic plasticity;Testing;therapeutic development;therapy development;Thinking;Training;Trauma;traumatic event;Tyrosine 3-Monooxygenase;vagus nerve stimulation;Vagus nerve structure;Work

PROJECT_TITLE: Vagus nerve stimulation targets fear pathways to enhance extinction of conditioned fear


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Behavioral and Social Science;Child Abuse and Neglect Research;Childhood Injury;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Mental Health;Pediatric;Physical Injury - Accidents and Adverse Effects;Social Determinants of Health;Violence Research

ORG_DEPT: EMERGENCY MEDICINE

PHR: PROJECT NARRATIVE  Child physical abuse is the source of hundreds of thousands of injuries, hundreds of deaths and billions of dollars in avoidable costs each year. This application will create data infrastructure to support a sustainable, multicenter research network dedicated to the care of physically abused children. By increasing research capacity related to physical abuse, these research resources will allow a new cadre of scientists to improve clinical care, decrease disparities and dramatically advance our understanding of child physical abuse.

PI_NAMEs: CAMPBELL, KRISTINE A;LINDBERG, DANIEL M (contact);WOOD, JOANNE NICOLE

PROGRAM_OFFICER_NAME: GILBERT, LEAH KAYE

PROJECT_TERMS: abuse neglect;Abuse Reporting;Address;Agreement;Award;career;Caring;Cessation of life;Child;Child Abuse;Child Abuse and Neglect;child physical abuse;Child Welfare;Childhood;Clinical;clinical care;Clinical Data;Clinical Practice Variations;Clinical Research;Common Data Element;Communities;community engagement;Consensus;cost;Country;Data;Data Collection;Data Coordinating Center;data infrastructure;Data Linkages;data management;data quality;data resource;Data Set;data sharing;Dedications;Development;Diagnosis;Disparity;disparity reduction;Elements;Ensure;Evaluation;Foundations;Funding;Future;Grant;Health Care Costs;Hospitals;improved;improved outcome;Injury;innovation;Institute of Medicine (U.S.);Institutional Review Boards;Interdisciplinary Study;Intervention;invention;Link;Measures;Medical;Medical Research;medical specialties;meetings;Mentors;Mentorship;Methods;Morbidity - disease rate;mortality;multidisciplinary;Online Systems;Outcome;Pediatric Research;Pediatrics;Performance;Persons;Phase;physical abuse;Physical Sufferings;Process;Productivity;psychologic;Publications;quality assurance;Quality Control;racial disparity;recruit;Reporting;Research;research data dissemination;Research Infrastructure;Research Personnel;Research Priority;Research Project Grants;Research Training;Resources;Scientist;Secure;Sexual abuse;socioeconomic disparity;Source;Structure;success;System;tool;Vertebral column;Work

PROJECT_TITLE: CAPNET - Building Research Capacity in Child Abuse Pediatrics


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

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

ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: Relevance to Public Health Craniofacial malformations are among the most common congenital defects affecting the human population. Understanding how gene regulation is controlled and impacted during normal and pathological craniofacial development is essential for providing better therapeutic interventions and improve human health.

PI_NAMEs: BRUGMANN, SAMANTHA A;PETERSON, KEVIN ANTHONY (contact)

PROGRAM_OFFICER_NAME: SAIFUDEEN, ZUBAIDA

PROJECT_TERMS: Activator Appliances;Address;Affect;Affinity;Alleles;Architecture;Automobile Driving;BHLH Protein;Binding;Binding Sites;Biochemical;Biological Assay;Cell Nucleus;Cells;Central Nervous System;ChIP-seq;Chromatin;Chromatin Remodeling Factor;cofactor;combinatorial;Complement;Complex;Congenital Abnormality;craniofacial;Craniofacial Abnormalities;craniofacial complex;craniofacial development;CRISPR/Cas technology;Data;design;Development;Disease;DNA Binding;Embryonic Development;Engineering;Enhancers;Epigenetic Process;Epitopes;Equation;Erinaceidae;experimental study;Face;Family;Gene Expression Profile;Gene Expression Regulation;gene regulatory network;Genes;Genetic;Genetic Transcription;Health;Human;human disease;improved;in vivo;Individual;innovation;insight;Joints;Knowledge;Length;Limb structure;Malignant Neoplasms;Mandible;Mandibular Prominence;Modality;Modeling;multiple omics;Mus;Mutagenesis;mutant;novel;Output;Pathologic;Pathway interactions;Population;Positioning Attribute;programs;Protein Isoforms;Proteins;Proteolytic Processing;Public Health;Reporter;Research;response;Role;Signal Pathway;single cell analysis;single nucleus RNA-sequencing;Site;skeletogenesis;smoothened signaling pathway;Specificity;stem cell population;Structural Congenital Anomalies;Syndrome;System;tandem mass spectrometry;Technology;Testing;Therapeutic Intervention;Tissues;tool;Transcription Coactivator;transcription factor;Transcription Repressor;Transcriptional Activation;Transcriptional Regulation;Work

PROJECT_TITLE: Predicting Tissue Specific Gli3 Regulatory Activity Using Hand2

STUDY_SECTION: SBDD

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


ED_INST_TYPE: SCHOOLS OF OSTEOPATHIC MEDICINE

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Bioengineering;Brain Disorders;Mental Health;Mental Illness;Networking and Information Technology R&D (NITRD);Neurosciences;Post-Traumatic Stress Disorder (PTSD)

ORG_CITY: STRATFORD

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED

ORG_STATE: NJ

PHR: Project Narrative Anxiety and stress disorders including generalized anxiety disorder, post-traumatic stress disorder, phobias and panic disorder are among the most prevalent mental illnesses, affecting approximately 40 million Americans (18.1%) and costing more than $42 billion a year. Critically, we have evidence suggesting that the development and maintenance of anxiety disorders are attributable to maladaptive fear and avoidance learning, a process partly modulated by the insula. Thus, in this proposal, we aim to investigate the involvement of insular single cell ensembles in aversive learning and develop a novel computational tool to predict future maladaptive aversive learning phenotypes based on the neural signaling in the insula.

PI_NAMEs: KUTLU, MUNIR GUNES (contact)

PROGRAM_OFFICER_NAME: VAZIRI, SIAVASH

PROJECT_TERMS: Adaptive Behaviors;Affect;Algorithms;American;Animal Behavior;Animals;Anterior;Anxiety;Anxiety Disorders;approach/avoidance behavior;Association Learning;Auditory;Aversive Stimulus;avoidance behavior;Avoidance Learning;Behavior;Behavioral;behavioral outcome;behavioral phenotyping;Brain;Brain region;Calcium;Cells;Complex;Computer Models;computerized tools;conditioned fear;coping;cost;Cues;Data;Decision Making;Development;Disease;efficacious treatment;Exhibits;Extinction;fear memory;feeding;Freezing;Fright;functional adaptation;Future;Generalized Anxiety Disorder;Goals;Health Care Costs;Homeostasis;Human;Image;Impairment;in vivo;Individual;Insula of Reil;Intervention;Learning;Maintenance;maladaptive behavior;Mediating;Mediator;Memory;Mental Depression;Mental disorders;Modeling;Mus;neural;neural circuit;Neural Network Simulation;neurobiological mechanism;neuromechanism;Neurons;neurotransmission;Nose;novel;novel strategies;Outcome;Pain;Panic Disorder;Pattern;Phenotype;Phobias;Photons;Population;Positioning Attribute;Post-Traumatic Stress Disorders;Pre-Clinical Model;Process;Psychopathology;Punishment;Regulation;Resistance;response;Rodent;Safety;Sensory;Shock;Signal Transduction;Social Anxiety Disorder;Stress;stress disorder;Structure;Symptoms;Taste Perception;Testing;Thalamic structure;Theoretical model;theories;Training;treatment strategy

PROJECT_TITLE: Predicting maladaptive aversive learning via computational modeling of insular single cell ensemble activity patterns

STUDY_SECTION: LMDN

STUDY_SECTION_NAME: Learning, Memory and Decision Neuroscience Study Section[LMDN]


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Genetics;Hepatitis;Hepatitis - B;Hepatitis - C;Infectious Diseases;Liver Disease

ORG_CITY: Los Alamos

ORG_NAME: TRIAD NATIONAL SECURITY, LLC

ORG_STATE: NM

PHR: Hepatitis B virus (HBV) infects over 260 million people worldwide, causes significant pathology, and is one of the leading causes of liver transplant in the USA. This project joins clinicians and modelers to develop new insights into chronic HBV infection in humans by building multiscale models of disease propagation from the single cell at the intrahepatic (liver) level to the whole organism.

PI_NAMEs: BALAGOPAL, ASHWIN ;RIBEIRO, RUY M (contact)

PROGRAM_OFFICER_NAME: FLORES, AMANDA CHRISTINE

PROJECT_TERMS: Address;anti-PD-1;Anti-viral Agents;Anti-viral Therapy;Antigens;Binding;Biological Markers;Biology;Blood;Cell Nucleus;Cells;Chromosomes;Chronic;Chronic Hepatitis B;Circular DNA;Cirrhosis;Clinical;Clinical Markers;clinically relevant;co-infection;Collaborations;Complex;Data;Data Set;design;Development;Disease;disease model;Distant;end stage liver disease;Equilibrium;extracellular;Genetic Materials;Genetic Transcription;Genome;Hepatitis;Hepatitis B;Hepatitis B Surface Antigens;Hepatitis B Virus;Hepatitis C co-infection;Hepatitis C virus;Hepatitis Viruses;Hepatocyte;HIV;HIV/HCV;Human;Immunotherapy;improved;Infection;Infection prevention;innovation;insight;Interruption;intrahepatic;Island;Knowledge;Life Cycle Stages;Link;Liver;liver biopsy;Liver diseases;liver transplantation;mathematical model;Measurement;Measures;Medicine;Modeling;multi-scale modeling;novel;Nucleic Acids;Organ;Organism;Paper;Pathology;Persons;Phase;Phylogenetic Analysis;Primary carcinoma of the liver cells;Process;Production;Proliferating;Proteins;Publishing;Recurrence;repository;Research;Residual state;RNA;Sampling;single cell analysis;single cell sequencing;Stream;success;Techniques;Testing;Therapeutic;Tissues;tool;Translational Research;Trees;tumorigenesis;United States National Institutes of Health;Vaccines;Variant;Viral;viral DNA;Viral Genome;Viral Pathogenesis;viral RNA;Virion;Virus;Virus Diseases;virus genetics;Virus Replication;Whole Organism

PROJECT_TITLE: NIH: Spatial Models of Intrahepatic Hepatitis Virus Propagation in Humans

STUDY_SECTION: MABS

STUDY_SECTION_NAME: Modeling and Analysis of Biological Systems Study Section[MABS]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Obesity;Clinical Research;Clinical Trials and Supportive Activities;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: PUBLIC HEALTH RELEVANCE US children, especially low-income and Latinx, eat too little fruits and vegetables and whole grains, and too many energy-dense snacks and beverages, dietary behaviors associated with increased morbidity from cardiovascular diseases. The proposed research will build upon prior pilot work to test the efficacy of a novel home-based intervention to improve the diet quality and family food environment of preschool age, low-income, Latinx children. The intervention will target healthy food access, engage parents with video-clips of their own meal time behaviors together with motivational interviewing, in-home cooking demonstrations, and tailored materials based on their child’s appetitive traits.

PI_NAMEs: TOVAR, ALISON  (contact)

PROGRAM_OFFICER_NAME: CLARK, DAVID

PROJECT_TERMS: 5 year old;acceptability and feasibility;Address;Adolescence;Adult;Attention;Behavior;Beverages;Body mass index;Cardiometabolic Disease;Cardiovascular Diseases;Carotenoids;Cessation of life;Child;Child Rearing;Clip;Communities;Community Health Aides;comparison group;contextual factors;cooking;cost;COVID-19;Cues;Dermal;Desire for food;Diet;dietary;Dietary Fiber;Dietary intake;disorder prevention;Dose;Eating;efficacy evaluation;efficacy testing;energy balance;Enrollment;Equipment and supply inventories;ethnic diversity;experience;Exposure to;Family;feasibility testing;feasibility trial;Feedback;feeding;Food;Food Access;food environment;food quality;food resource;food security;fruits and vegetables;group intervention;Health;Health Food;Healthy Eating;High Prevalence;Home;Home visitation;Hour;improved;indexing;Intervention;intervention delivery;intervention effect;Knowledge;Latinx;Latinx population;Life;Low income;Measurement;Measures;Mediator;Morbidity - disease rate;Motivation;motivational enhancement therapy;novel;Nursery Schools;Obesity;Outcome Measure;Parents;Participant;pilot test;Population Heterogeneity;precision nutrition;Preparation;Preschool Child;preventive intervention;primary outcome;Primary Prevention;Printing;Public Health;public health relevance;Randomized, Controlled Trials;Reduce health disparities;Research;Resources;Risk Factors;Satiation;School-Age Population;screening;secondary outcome;Self Efficacy;Shapes;Signal Transduction;social determinants;social health determinants;Strategic Planning;System;Telephone;Testing;Text Messaging;Time;Training;trait;trial design;Unhealthy Diet;United States National Institutes of Health;Work

PROJECT_TITLE: Strong Families Start at Home/Familias Fuertes Comienzan en Casa: A novel Video and Motivational Interviewing Intervention to improve diet quality of low-income, ethnically diverse children

STUDY_SECTION: LCBH

STUDY_SECTION_NAME: Lifestyle Change and Behavioral Health Study Section[LCBH]


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

ORG_CITY: NOTRE DAME

ORG_NAME: UNIVERSITY OF NOTRE DAME

ORG_STATE: IN

PHR: Resistance of Acinetobacter baumannii to carbapenem antibiotics constitutes a major health problem and results in high mortality rates. We propose to design and characterize novel carbapenem antibiotics for treatment of deadly infections caused by this pathogen.

PI_NAMEs: BUYNAK, JOHN D;VAKULENKO, SERGEI  (contact)

PROGRAM_OFFICER_NAME: XU, ZUOYU

PROJECT_TERMS: Acinetobacter baumannii;Affinity;Animals;anti-microbial drug;antibiotic efflux;Antibiotic Resistance;Antibiotic Therapy;Antibiotics;antimicrobial;Antimicrobial Resistance;Applications Grants;aqueous;Bacteria;Bacterial Antibiotic Resistance;beta-Lactamase;Binding;Binding Proteins;carbapenem resistance;carbapenemase;Carbapenems;Cells;Centers for Disease Control and Prevention (U.S.);chemical stability;Clinical;Communicable Diseases;Complex;Contractor;cytotoxicity;Death Rate;design;Development;Drug Kinetics;efflux pump;Enzyme Inhibition;Enzymes;Evaluation;Exhibits;experimental study;Generations;Goals;Health;Healthcare;Human;Hydrolysis;improved;In Vitro;in vivo;in vivo evaluation;Individual;Infection;infection rate;inhibitor;Kidney;Kinetics;Lead;Libraries;Mediating;membrane dipeptidase;Microbiology;microorganism;Microsomes;Modification;Molecular;mouse model;Multi-Drug Resistance;Multidrug-resistant Acinetobacter;mutant;National Institute of Allergy and Infectious Disease;novel;novel therapeutics;pathogen;Penetration;Penicillin-Binding Proteins;periplasm;Pharmaceutical Preparations;Plasma;Plasma Proteins;Positioning Attribute;Predisposition;Production;Property;Resistance;resistance mechanism;Risk;Roentgen Rays;Role;scaffold;Solubility;Structure;Therapeutic;Therapeutic Agents;Toxic effect;Translating;treatment choice;United States;United States National Institutes of Health;uptake;VDAC1 gene

PROJECT_TITLE: Carbapenemase-Stable Carbapenem  Antibiotics  for Treatment of Multidrug-Resistant Acinetobacter baumannii Infections

STUDY_SECTION: DDR

STUDY_SECTION_NAME: Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section[DDR]


NIH_SPENDING_CATS: Childhood Obesity;Clinical Research;Diabetes;Digestive Diseases;Genetics;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Liver Disease;Nutrition;Obesity;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health

ORG_CITY: BIRMINGHAM

ORG_DEPT: NUTRITION

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: PROJECT NARRATIVE Minority youth are at elevated risk for type 2 diabetes (T2D) relative to non-Hispanic whites (NHW), with African-Americans (AA) and Hispanic-Americans (HA) showing the greatest increase in prevalence since 2000. Our overarching hypothesis is that underlying differences in genes and physiology in minority children interact with environmental factors in an adverse manner to increase risk for T2D. This study will follow 100 at-risk youth aged 8-16 yr for 5 years to identify factors that predict conversion to T2D, and determine why conversion to T2D is more likely among minority youth.

PI_NAMEs: ASHRAF, AMBIKA PALLIKUNNATH;GOWER, BARBARA A (contact)

PROJECT_TERMS: Accounting;Adipose tissue;Adult;adverse childhood events;Affect;African American population;Age;aged;Alabama;American;Archives;Beta Cell;Body Composition;Body fat;Body mass index;Carbohydrates;Cell Physiology;Child;Childhood;Chronic stress;Clinic;clinical center;cohort;Collaborations;Data;Deposition;Diabetes Mellitus;diabetes risk;Diet;Dietary Carbohydrates;Dietary Sugars;Dual-Energy X-Ray Absorptiometry;Effectiveness;Effectiveness of Interventions;Endocrinology;Environmental Risk Factor;ethnic disparity;Ethnic Origin;Etiology;Evaluation;Exhibits;Family;Family history of;Fasting;Fatty acid glycerol esters;Fatty Liver;Functional disorder;Future;Genes;Genetic;Genetic Materials;Genetic Polymorphism;Genetic Predisposition to Disease;Genotype;Glucose;glucose monitor;glucose tolerance;Hepatic;Hispanic Americans;hospital care;Impaired fasting glycaemia;impaired glucose tolerance;Impairment;indexing;Individual;Insulin;Insulin Resistance;insulin sensitivity;Intervention;Intervention Studies;intrauterine environment;Leg;Lipids;Liver;Longitudinal cohort study;Measures;Metabolic;metabolomics;minority children;Monitor;Morbid Obesity;Mutation;Non-Insulin-Dependent Diabetes Mellitus;Not Hispanic or Latino;Obesity;obesity risk;OGTT;Outcome Measure;Participant;Pediatric Hospitals;pediatric patients;Peripheral;Phenotype;Physiological;Physiology;Plasma;Prediabetes syndrome;Predictive Factor;predictive modeling;Pregnancy;Prevalence;Probability;Process;progression risk;Proinsulin;Psychosocial Factor;Puberty;Publishing;Race;racial disparity;Recording of previous events;recruit;Research;response;retention rate;Risk;Risk Factors;Scanning;sex;Single Nucleotide Polymorphism;Site;SNP genotyping;Starch;sugar;Technical Expertise;Testing;Tissue Expansion;Universities;Variant;Visit;Weight Gain;Youth

PROJECT_TITLE: Predictors of Youth-Onset Type 2 Diabetes: UAB Clinical Center


ED_INST_TYPE: UNIVERSITY-WIDE

ORG_CITY: MINEOLA

ORG_NAME: NEW YORK UNIVERSITY D/B/A NYU LONG ISLAND SCHOOL OF MEDICINE

PHR: High plasma lipids are a major risk factor for cardiovascular/metabolic diseases. MTP inhibition is a proven target to lower plasma lipids. However, current inhibitors completely block all MTP activities and are associated with serious side effects. Our studies involve understanding the dynamic three dimensional nature of this protein and how it can be used to generate new drugs that target specific regions of the protein to limit drug side effects.

PI_NAMEs: FARBER, STEVEN A;HUSSAIN, M MAHMOOD (contact);RUDDOCK, LLOYD

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: 3-Dimensional;Abetalipoproteinemia;Address;Adverse effects;Amino Acids;apolipoprotein B-48;Apolipoproteins B;Atherosclerosis;Bacteria;Binding;Binding Sites;Biochemical;Biochemistry;Biological;Biological Markers;Blood;cardiovascular disorder risk;cardiovascular risk factor;Cause of Death;Cells;Cellular biology;Complex;Crystallization;design;Developmental Biology;Diabetes Mellitus;Drosophila genus;Drug Side Effects;Family;Family member;Fatty Liver;fatty liver disease;Fishes;flexibility;Future;Genetic;Growth;Human;in vivo;Individual;inhibitor;Insulin Resistance;Intestines;Knowledge;Ligand Binding;Ligands;Lipid Binding;Lipid Mobilization;lipid transfer protein;Lipids;Lipoproteins;Liver;loss of function;Mammalian Cell;Maps;Mediator;member;Metabolic Diseases;Metabolic syndrome;microsomal triglyceride transfer protein;Missense Mutation;Molecular;Molecular Conformation;Morbidity - disease rate;mortality;Mus;mutant;Mutate;Mutation;Mutation Analysis;N-terminal;Nature;new therapeutic target;novel;Obesity;overexpression;paralogous gene;pharmacologic;Phospholipids;Physiological;Plasma;Prevalence;Production;protein complex;Protein Deficiency;Protein Disulfide Isomerase;Protein Inhibition;Protein Region;protein structure;Protein Subunits;Proteins;Risk Factors;Risk Reduction;Role;Scientist;side effect;Site-Directed Mutagenesis;skills;small molecule;Specificity;Steatorrhea;structural biology;Structure;System;Tertiary Protein Structure;Testing;Therapeutic;Triglycerides;Work;Yolk Sac;Zebrafish

PROJECT_TITLE: Mapping MTP lipid transfer activities for better therapeutics

STUDY_SECTION: INMP

STUDY_SECTION_NAME: Integrative Nutrition and Metabolic Processes Study Section[INMP]


NIH_SPENDING_CATS: Cerebrovascular;Congenital Structural Anomalies;Hematology;Lymphatic Research;Pediatric;Rare Diseases

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

ORG_STATE: CA

PHR: RELEVANCE TO PUBLIC HEALTH Our studies are relevant to a vascular disease, so-called hereditary hemorrhagic telangiectasia. The studies focus on a previously unknown mechanism of arteriovenous malformations in hereditary hemorrhagic telangiectasia. Understanding of this new mechanism may lead to the opportunities for the treatment of hereditary hemorrhagic telangiectasia.

PI_NAMEs: YAO, YUCHENG  (contact)

PROGRAM_OFFICER_NAME: GAO, YUNLING

PROJECT_TERMS: Activin A type II receptor;activin receptor-like kinase 1;ACVRL1 gene;Arteries;Arteriovenous malformation;Binding;Blood Vessels;Bypass;capillary bed;Cell Differentiation process;Cell Line;Cell Proliferation;Characteristics;chromatin immunoprecipitation;Data;DNA Binding;DNA sequencing;Double Minutes;Endothelial Cells;Endothelium;Gene Deletion;Genetic Transcription;Hemorrhage;Hereditary hemorrhagic telangiectasia;high risk;Homeobox;Human;In Vitro;in vivo;inhibitor;insight;Lesion;Life;Link;loss of function mutation;Lymphatic Endothelium;Medical;mouse model;Mus;Normal tissue morphology;novel;novel therapeutic intervention;Organ;Patients;Persons;Physiologic arteriovenous anastomosis;prevent;Public Health;repaired;Shunt Device;Specificity;Telangiectasis;Testing;Therapeutic;Therapeutic Intervention;Vascular Diseases;Vascular Endothelial Growth Factor C;Vascular Endothelial Growth Factor Receptor-3;Veins;Wild Type Mouse

PROJECT_TITLE: Erasing ill features of arterial endothelial cells in hereditary hemorrhagic telangiectasia

STUDY_SECTION: IVPP

STUDY_SECTION_NAME: Integrative Vascular Physiology and Pathology Study Section[IVPP]


ED_INST_TYPE: SCHOOLS OF NURSING

NIH_SPENDING_CATS: Behavioral and Social Science;Childhood Obesity;Clinical Research;Diabetes;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Obesity;Pediatric;Prevention;Social Determinants of Health

ORG_CITY: TEMPE

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: NARRATIVE: Type 2 diabetes (T2D) is a complex disease that is the result of multiple factors including biology, behavior, and environment. This study will examine how various factors interact in very high risk youth to cause T2D early in life. Findings from this study will help advance the understanding of T2D in youth in order to design better prevention and treatment programs for children and adolescents.

PI_NAMEs: CHAMBERS, MELISSA ;SHAIBI, GABRIEL QUANTUM (contact)

PROJECT_TERMS: Accelerometer;Adolescence;Adolescent;Age;Area;Arizona;Attention;Behavior;Behavioral;Beta Cell;Biological;Biological Process;Biology;Blood specimen;Cell Physiology;Characteristics;Child;Child health care;Childhood;Clinic;Clinical Research;cohort;Collection;Communities;community advisory board;community engaged approach;Complex;contextual factors;Continuous Glucose Monitor;Cox Proportional Hazards Models;Data;density;design;Diabetes Mellitus;Diabetes prevention;diabetes risk;Disease;Disparity;Dual-Energy X-Ray Absorptiometry;Eating;Ecological momentary assessment;Education;Endocrine;Enrollment;Environment;Environmental Risk Factor;Epigenetic Process;ethnic diversity;ethnic minority population;Ethnic Origin;experience;Exposure to;Family;Family history of;fast food;Fasting;Fatty acid glycerol esters;Functional disorder;Funding;Future;Genetic Predisposition to Disease;Genomics;glucose tolerance;Health;Health behavior;Health behavior and outcomes;health determinants;health equity;Healthcare Systems;Hepatic;high risk;high risk population;Hour;Household;housing instability;Hyperglycemia;improved;Incidence;Individual;Insulin Resistance;insulin secretion;insulin sensitivity;intergenerational;Life;Low income;Magnetic Resonance Imaging;medical specialties;member;metabolomics;minority children;Modeling;Morbid Obesity;National Institute on Minority Health and Health Disparities;Neighborhoods;Non-Insulin-Dependent Diabetes Mellitus;novel marker;Obesity;OGTT;Organ;Outcome;Pancreas;Participant;Phenotype;PhenX Toolkit;Physical activity;Physiological;Physiology;population health;Poverty;Prediabetes syndrome;Predisposition;prenatal exposure;prevent;Prevention program;Process;prospective;Puberty;Race;racial minority population;recruit;Research;Research Personnel;Restaurants;Risk;Risk Factors;Sampling;Science;Services;sex;Single Parent;Site;sleep pattern;social;social determinants;Social Environment;social health determinants;social influence;sociodemographics;structural determinants;Structure of beta Cell of islet;System;Time;treatment program;United States National Institutes of Health;Validation;Visceral fat;Vulnerable Populations;Work;Youth

PROJECT_TITLE: Understanding and Targeting the Pathophysiology of Youth-onset Type 2 Diabetes


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Prevention

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PPROJECT NARRATIVE Atrial fibrillation is the most common heart arrhythmia and the development of new therapeutic approaches requires better understanding of the causes of this arrhythmia. This proposal will focus on the role of molecular pathways that regulate metabolism in the electrical and structural remodeling of the atria. We will test whether drugs targeting metabolic stress pathways can prevent atrial fibrillation.

PI_NAMEs: AKAR, FADI GABRIEL;YOUNG, LAWRENCE H (contact)

PROGRAM_OFFICER_NAME: SHI, YANG

PROJECT_TERMS: Action Potentials;Acute;Aging;Angiotensin II;Arrhythmia;Atrial Fibrillation;autocrine;Autophagocytosis;Biological;Biology;Biopsy;Cardiac;Clinical;Clinical Research;Connexins;Data;Development;Diabetes Mellitus;Disease Progression;Drug Modulation;Drug Targeting;EFRAC;Electrophysiology (science);Evolution;Exercise;Exhibits;experience;Experimental Designs;experimental study;Fibrosis;Foundations;Future;Gene Expression;Genetic;Genetic Models;Genetic Transcription;Goals;Heart Atrium;Heart failure;heart imaging;heart metabolism;Hormones;Human;Hypertrophy;in vivo;innovation;Ion Channel;Ischemia;Left;Link;Maps;Mediating;Metabolic;Metabolic Diseases;Metabolic stress;Metabolism;microCT;Mitochondria;Molecular;mouse model;Mus;novel;novel therapeutic intervention;Obesity;Optics;Oxidative Stress;paracrine;Pathogenesis;Pathologic;Pathway interactions;Patients;pharmacologic;Phosphorylation;Physiological;preclinical study;preservation;prevent;Prevention;Prevention approach;Property;Proteins;Public Health;reconstitution;Reperfusion Injury;Reporting;Research;Resolution;response;Role;Sex Differences;Signal Transduction;small molecule;STK11 gene;Stress;Structure;Testing;Therapeutic;tool;transcription factor;Transcriptional Regulation;Ventricular;Ventricular Remodeling;X-Ray Computed Tomography

PROJECT_TITLE: Metabolic signaling in atrial fibrillation and remodeling

STUDY_SECTION: ESTA

STUDY_SECTION_NAME: Electrical Signaling, Ion Transport, and Arrhythmias Study Section[ESTA]


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

PHR: Public health relevance statement Disorders and disruptions to brain health from disease, traumatic injury, and ageing lead to cognitive functional disabilities affecting a significant population of the United States. The proposed project will use a genetic model system to study the molecular and cellular mechanisms by which brain chemicals function to integrate different senses, as well as how deficits are caused and ameliorated. The proposed research is expected to facilitate broader understanding of normal brain function, and thus better understand dysfunction.

PI_NAMEs: FRYE, MARK ARTHUR (contact)

PROGRAM_OFFICER_NAME: OSBORNE, LESLIE CAROL

PROJECT_TERMS: Affect;Aging;Animals;Ballistics;Basic Science;Behavior;Behavioral;behavioral response;Biogenic Amines;Biological Models;Black Box;Brain;brain health;Cells;chemical function;Chemicals;Cognitive;cognitive function;Collaborations;Complex;Couples;Degenerative Disorder;Detection;detector;disability;Discrimination;Disease;Drosophila genus;falls;fly;Food;functional disability;Functional disorder;Ganglia;Genetic Models;Genetic Techniques;Goals;Home;Human;Image;improved;in vivo;in vivo calcium imaging;Individual;Knowledge;Lead;Link;Locomotion;Logic;Maps;Mission;Modality;Modeling;Molecular;Motion;Motor;Movement;multimodality;multisensory;National Institute of Neurological Disorders and Stroke;Nervous System;neural;neurogenetics;neuronal circuitry;Neurons;neuroregulation;nonhuman primate;Norepinephrine;Octopamine;octopamine receptor;Odors;Olfactory Pathways;Optic Lobe;Optics;optogenetics;Output;Pathology;Pathway interactions;Pattern;Perception;Persons;Population;Process;Property;public health relevance;receptive field;Reflex action;Research;Resolution;response;Saccades;sensor;Sensory;sensory input;sensory integration;Signal Pathway;Signal Transduction;Smell Perception;Smooth Pursuit;Source;Spatial Distribution;Stimulus;Stroke;Synapses;System;Testing;Transcript;Traumatic injury;two-photon;United States;virtual reality;virtual reality system;Vision;Visual;visual control;visual feedback;visual processing;Writing

PROJECT_TITLE: Olfactory neuromodulation of visual circuits and behavior

STUDY_SECTION: SPC

STUDY_SECTION_NAME: Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section[SPC]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Aging;Genetics

ORG_CITY: LITTLE ROCK

ORG_NAME: UNIV OF ARKANSAS FOR MED SCIS

ORG_STATE: AR

PHR: Project Narrative A multitude of environmental agents from food, air and water bombard cells inducing accumulation of reactive oxygen species that lead to oxidative DNA damage, genomic instability and disease. DNA repair pathways, such as base-excision repair and non-homologous end- joining have evolved to counter that damage, yet little is known about the molecular details and structural transactions underlying efficient and mutation-prone or mutation-free repair. Here, using state of the art structural and functional approaches, we determine the impact of the mechanism of DNA polymerase-mediated synthesis that enables repair of oxidative DNA damage in multiprotein DNA repair complexes and the maintenance of genomic stability.

PI_NAMEs: JAMSEN, JOONAS  (contact)

PROGRAM_OFFICER_NAME: HEACOCK, MICHELLE

PROJECT_TERMS: 8-hydroxyguanosine;8-oxo-dGTP;Active Sites;Address;Adenine;Aging;aging related disease;Air;Air Pollution;Architecture;artemis;base;Base Excision Repairs;Base Pairing;Behavior;Biological Assay;Bypass;cancer risk;career;Catalysis;Cells;Chemicals;Complex;Cryoelectron Microscopy;Crystallography;Deoxyguanosine;Development;Disease;Disease Progression;DNA;DNA biosynthesis;DNA lesion;DNA polymerase mu;DNA Repair;DNA Repair Gene;DNA Repair Pathway;DNA-Directed DNA Polymerase;Double Strand Break Repair;effective therapy;Environment;environmental agent;environmental mutagens;Enzymatic Biochemistry;Enzyme Kinetics;enzyme substrate;Enzymes;Etiology;Exposure to;Food;Future;Genome;genome integrity;Genome Stability;Genomic Instability;Goals;Guanosine Triphosphate;human disease;Hydrogen Bonding;insight;Kinetics;Knowledge;Laboratories;Lead;Lesion;Link;Maintenance;Malignant Neoplasms;Mediating;Methods;Mission;Molecular;Molecular Analysis;Multiprotein Complexes;Mutagenesis;mutant;Mutation;National Institute of Environmental Health Sciences;Neurodegenerative Disorders;new technology;Nitrogen;Nonhomologous DNA End Joining;normal aging;Nucleotides;Outcome;oxidative damage;oxidative DNA damage;Oxidative Stress;Oxidative Stress Induction;Oxygen;Phase;Polymerase;Population;Predisposition;prevent;Productivity;protein complex;Proteins;Radiation;Reaction;Reactive Oxygen Species;Repair Complex;repaired;Research;Role;Structure;targeted cancer therapy;therapy development;Training;transversion mutation;Visualization;Water;Work

PROJECT_TITLE: Molecular Architecture of Oxidative Stress Induced Double Strand Break Repair


NIH_SPENDING_CATS: Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Immunotherapy;Prevention;Rare Diseases

ORG_CITY: SAN FRANCISCO

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Early pre-cancerous lesions in the oral cavity can be managed effectively until they become invasive, but currently, we lack an understanding of the biological factors that contribute to or protect against progression. In this study, we will use exciting new advances in tissue imaging that enable the measurement of many proteins expressed within individual cells to investigate the immune response to these tumors. We will test the hypothesis that the types of immune cells present in pre-cancerous lesions and the activation state of these cells are major determinants of progression into invasive cancers.

PI_NAMEs: SPITZER, MATTHEW  (contact)

PROGRAM_OFFICER_NAME: LOPEZ, ORLANDO

PROJECT_TERMS: accurate diagnosis;Adopted;Affect;aggressive therapy;antibody conjugate;Antigen Presentation;Architecture;Benign;Biological Factors;Biological Process;Biopsy;cancer invasiveness;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cell Physiology;Cell Proliferation;Cells;Cessation of life;Chronic;Clinical;Clinical Data;clinical translation;Complex;cytokine;cytotoxic CD8 T cells;Data;Death Rate;Dendritic Cells;Development;Diagnosis;Disease;Distant Metastasis;Early Diagnosis;Early Intervention;Early treatment;Elements;Epithelial Cells;Erythroplasia;exhaust;Exhibits;follow-up;Formalin;Future;Grant;Heavy Metals;Histocompatibility Antigens Class I;Histologic;Human;human data;human tissue;Imaging Techniques;Immune;immune cell infiltrate;Immune response;Immune system;Immunologics;immunosuppressed;immunosuppressive macrophages;Immunotherapy;Individual;Inflammation;Inflammatory;insight;instrumentation;interest;Interferons;Intraepithelial Neoplasia;Ions;Lesion;Localized Disease;Lymphocyte;Macrophage;Malignant - descriptor;malignant mouth neoplasm;Malignant Neoplasms;malignant oropharynx neoplasm;Measurement;Mediating;Microscopic;Modeling;Molecular;Morbidity - disease rate;mouth squamous cell carcinoma;multiplexed imaging;Multiplexed Ion Beam Imaging;Mus;Mutate;Mutation;Myeloid Cells;Neighborhoods;neoantigens;neoplastic cell;neutrophil;novel therapeutics;Oral cavity;oral cavity epithelium;Oral Leukoplakia;oral tissue;overexpression;Paraffin Embedding;Pathologic;Patients;Persons;polarized cell;Predisposing Factor;premalignant;Premalignant Cell;prevent;Process;programmed cell death ligand 1;programs;progression risk;Proteins;Recurrence;Reporter;Resolution;Risk;risk prediction;risk prediction model;risk stratification;Role;Survival Rate;T cell infiltration;T cell response;T-Lymphocyte;Technology;Testing;therapeutic development;Tissue Embedding;Tissue imaging;Tissue Sample;Tissues;training data;treatment strategy;tumor;Tumor Antigens;Tumor Immunity;tumor progression;United States;United States National Institutes of Health;wound healing

PROJECT_TITLE: Immune determinants of progression from Oral Epithelial Dysplasia to Oral Squamous Cell Carcinoma by precision multiplexed imaging

STUDY_SECTION: ODCS

STUDY_SECTION_NAME: Oral, Dental and Craniofacial Sciences Study Section[ODCS]