NIH_SPENDING_CATS: Biotechnology;Genetics;Lung;Pulmonary Fibrosis;Rare Diseases;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: BOSTON

ORG_NAME: BOSTON UNIVERSITY MEDICAL CAMPUS

PHR: Project Narrative Idiopathic pulmonary fibrosis (IPF) causes significant morbidity and mortality in the US today. Treatments are often ineffective and the development of novel therapeutics is hampered due to lack of available human in vitro models that are needed to understand pathogenesis or develop novel drug therapies. This proposal develops a new human organoid culture system, using patient-specific cells to model IPF in vitro.

PI_NAMEs: KOTTON, DARRELL N. (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: ABCA3 gene;age acceleration;alveolar epithelium;Basal Cell;biobank;Biological Assay;Biological Models;cell repository;Cells;Collaborations;Data;Development;differentiation in vitro;Disease;disorder risk;Engineering;Epithelial Cells;Epithelium;Event;Fibroblasts;fibrogenesis;Fibrosis;Functional disorder;Genes;Genetic Polymorphism;Genetic Recombination;genetic variant;genome wide association study;Goals;high-throughput drug screening;Human;human induced pluripotent stem cells;Hybrid Cells;idiopathic pulmonary fibrosis;In Vitro;in vitro Model;in vivo;Individual;induced pluripotent stem cell;Interstitial Lung Diseases;Interstitial Pneumonia;knock-down;Literature;Lung;lung basal segment;Mesenchymal;Mesenchyme;mitochondrial dysfunction;Modeling;Morbidity - disease rate;mortality;MUC5B gene;mutant;Mutation;Myofibroblast;novel;novel therapeutics;open source;Organoids;overexpression;Pathogenesis;Pathway interactions;Patients;Pharmacotherapy;Phenotype;Publishing;Pulmonary Fibrosis;Recombinants;Reporter;repository;response;Sampling;scale up;Secretory Cell;single-cell RNA sequencing;Source;System;Telomerase;telomere;Telomere Shortening;Testing;three dimensional cell culture;Tissues;TP53 gene

PROJECT_TITLE: Developing a patient-specific organoid model of pulmonary fibrosis using iPSCs


ADMINISTERING_IC: MH

ARRA_FUNDED: N

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Infectious Diseases;Mental Health;Networking and Information Technology R&D (NITRD);Prevention;Telehealth

ORG_CITY: PROVIDENCE

ORG_COUNTRY: UNITED STATES

ORG_FIPS: US

ORG_NAME: RHODE ISLAND HOSPITAL

ORG_STATE: RI

PHR: HIV medications can be very effective at helping patients have longer, healthier lives. However, many patients do not take their HIV medications as prescribed. The proposed study aims to test a promising HIV medication adherence health coaching intervention delivered primarily via a smartphone application.

PI_NAMEs: RAMSEY, SUSAN E (contact)

PROGRAM_OFFICER_NAME: STIRRATT, MICHAEL JAMES

PROJECT_TERMS: acceptability and feasibility;Address;Adherence;Age;antiretroviral therapy;Behavioral;Clinical;clinical care;comparison intervention;cost;dashboard;Data;Development;Disease Progression;disorder risk;Dose;Effectiveness;Electronics;fitbit;follow-up;Goals;Health;HIV;improved;Individual;interest;Intervention;intervention effect;intervention refinement;Interview;life span;Link;Literature;Measures;Mediation;medication compliance;medication nonadherence;mHealth;mhealth interventions;Minor;Monitor;Morbidity - disease rate;mortality;Motivation;multi-component intervention;Notification;novel;Participant;patient engagement;Patients;Persons;Pharmaceutical Preparations;Pilot Projects;pilot test;Play;Protocols documentation;Public Health;Randomized;Randomized, Controlled Trials;recruit;Research;resistant strain;Resources;response;Risk;Role;Sampling;Secure;Self Efficacy;sex;Site;skills;smartphone application;success;Testing;therapy adherence;therapy development;Time;transmission process;treatment effect;Treatment Efficacy;United States;Viral;Viral Load result;viral transmission;Virus;Work

PROJECT_TITLE: mHealth Facilitated Intervention to Improve Medication Adherence among Persons Living with HIV


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Brain Disorders;Breastfeeding, Lactation and Breast Milk;Cerebral Palsy;Cerebrovascular;Childhood Injury;Genetics;Neurosciences;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Physical Injury - Accidents and Adverse Effects;Preterm, Low Birth Weight and Health of the Newborn;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Stroke;Traumatic Head and Spine Injury;Unintentional Childhood Injury

ORG_CITY: DURHAM

ORG_DEPT: PEDIATRICS

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: PROJECT NARRATIVE: Brain injuries in premature infants remain the leading cause of cerebral palsy and other neurodevelopmental deficits including cognitive delays and blindness. This project supports the preclinical development and translation of small molecules we discovered in human maternal breast milk that repair damaged brain tissue and reverse motor deficits in animal models of perinatal brain injury.

PI_NAMEs: BENNER, ERIC J (contact)

PROGRAM_OFFICER_NAME: KOENIG, JAMES I

PROJECT_TERMS: Acetylation;Adult;Affect;Alleles;Animal Model;Arginine;Biological Assay;Blindness;Brain;Brain Injuries;brain tissue;care costs;cell behavior;Cell Maturation;Cells;Cerebral Palsy;Child;Childhood;ChIP-seq;Cholesterol;Chronic;Cognitive;Complex;Data;Development;Diffuse;Disease;Dose;effective therapy;efficacy evaluation;efficacy testing;Environment;Epilepsy;Exposure to;Future;Generations;Genetic;genetic approach;Genome;Goals;Human;Human Milk;Hypoxia;hypoxia neonatorum;Immunoprecipitation;improved;In Vitro;in vivo;Infant;Inflammation;Inflammatory;Injury;injury and repair;innovation;Intellectual functioning disability;Lead;life time cost;Live Birth;Lysine;Mass Spectrum Analysis;Mediating;Modeling;Molecular;Morphology;Motor;motor deficit;Motor disability;mouse model;Multiple Sclerosis;Mutate;Myelin;myelination;Neonatal;Neonatal Brain Injury;neonatal mice;neonatal period;neonate;nerve stem cell;nestin protein;Neurodevelopmental Deficit;Neurologic Deficit;Neurological outcome;novel;novel therapeutics;oligodendrocyte lineage;oligodendrocyte progenitor;Oligodendroglia;Outcome;Peptides;Perinatal Brain Injury;Post-Translational Protein Processing;postnatal;preclinical development;precursor cell;Premature Infant;repaired;response;Risk;Risk Factors;Role;Safety;SHH gene;Signaling Molecule;Site;small molecule;smoothened signaling pathway;Specific qualifier value;stem cell fate;stem cell population;stem cells;Stroke;subventricular zone;Testing;Therapeutic;therapeutic development;tool;transcription factor;Translating;Translations;Transmission Electron Microscopy;Traumatic Brain Injury;treatment response;treatment strategy;Ventricular;Vulnerable Populations;white matter injury;Work

PROJECT_TITLE: Mechanisms of oxysterol-induced oligodendrogenesis

STUDY_SECTION: DBD

STUDY_SECTION_NAME: Developmental Brain Disorders Study Section[DBD]


ADMINISTERING_IC: DE

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Dental, Oral, and Craniofacial Disease;Emerging Infectious Diseases;Genetics;HIV/AIDS;Human Genome;Infectious Diseases;Rare Diseases

ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: Project Narrative The goal of this study is to characterize the high-order genomic organization of KSHV and to investigate the transcriptomic and epigenomic regulations of KSHV at the single cell level using three-dimensional (3D) organotypic oral tissue infection model that closely resembles in vivo oral transmission. This will provide insights into KSHV oral transmission and complication.

PI_NAMEs: JUNG, JAE U (contact)

PROGRAM_OFFICER_NAME: BACCAGLINI, LORENA

PROJECT_TERMS: 3-Dimensional;Adopted;Affect;ATAC-seq;Auxins;Bioinformatics;Blood;Cell Culture Techniques;cell type;Cells;ChIP-seq;Chromatin;Chromatin Conformation Capture and Sequencing;Chromatin Loop;Chromatin Structure;chromosome conformation capture;Complication;Development;Endothelial Cells;Epigenetic Process;epigenetic regulation;epigenome;epigenomics;Epithelial Cells;Epithelium;Etiology;Euchromatin;Gene Expression;Gene Expression Profile;Genes;Genetic;Genetic Transcription;Genomics;global run on sequencing;Goals;Grant;Heterochromatin;histone modification;Histones;HIV Infections;Human Herpesvirus 8;in vivo;Infection;insight;Integration Host Factors;Kaposi Sarcoma;latent infection;Lead;Lesion;Life Cycle Stages;Lytic;lytic gene expression;lytic replication;Malignant lymphoid neoplasm;Mediating;Modeling;mutant;Mutation;Oral;oral cavity epithelium;oral infection;oral lesion;oral status;oral tissue;Palate Kaposi's Sarcoma;particle;Pattern;Play;programs;Promoter Regions;Regulation;Role;Route;Saliva;Seminal fluid;single cell ATAC-seq;single cell sequencing;single-cell RNA sequencing;Site;Structure;Technology;Testing;three dimensional cell culture;three-dimensional modeling;Tissue Model;transcription factor;transcriptomics;transmission process;Viral;Viral Genes;viral genomics;Virus Replication

PROJECT_TITLE: KSHV Epigenetic Regulation


NIH_SPENDING_CATS: Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Fragile X Syndrome;Genetics;Intellectual and Developmental Disabilities (IDD);Mental Health;Neurosciences;Pediatric;Rare Diseases

ORG_CITY: BALTIMORE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: This proposed studies are designed to understand the contribution of subtypes of oxytocin neurons to social reward behaviors in the progression and development of Autism spectrum disorder (ASD) using modern cell type specification tools that can be used in combination optogenetic technologies. The successful completion of this work will fulfill an unmet need for neuroscientists attempting to dissect the synaptic and circuit basis of social behavior and provide new insight into the pathophysiology of ASD social behavior impairments. Given the high prevalence of disrupted social cognition as a core clinical feature of a number of neuropsychiatric diseases, including autism, any advancement in our understanding of neural circuitry and ASD associated brain development promises to improve pharmaco- and neural circuit approaches for the treatment of individuals with relevant social behavior deficits.

PI_NAMEs: DOLEN, GUL  (contact)

PROGRAM_OFFICER_NAME: BREEDEN, ANDREW LEE

PROJECT_TERMS: Ablation;Acute;Address;Adult;autism spectrum disorder;Behavior;Behavioral;behavioral impairment;behavioral phenotyping;Brain;Cell Count;Cell model;cell type;Cells;Characteristics;Child;Chronic;Clinical;conditioned place preference;critical period;design;Development;Disease;effective therapy;Electrophysiology (science);Exhibits;experimental study;FMR1 gene;Fragile X Syndrome;Functional disorder;functional genomics;gene function;Genetic;genetic manipulation;High Prevalence;Human;Hypothalamic structure;Impairment;improved;Individual;information processing;insight;Laboratories;learned behavior;Learning;Link;Literature;Long-Term Depression;Measurement;Modeling;Modernization;Molecular;Mus;Mutation;neural circuit;Neurons;neuropsychiatric disorder;novel;Nucleus Accumbens;optogenetics;Oxytocin;parvocellular;patch clamp;Pathogenesis;Pathogenicity;Patients;peer;pharmacologic;Phenotype;Predisposition;Property;Protein Biosynthesis;Proteins;Publishing;Research;reward dysfunction;Rewards;risk variant;Role;Slice;social;Social Behavior;Social Behavior Disorders;social cognition;Social Conditions;social deficits;Specific qualifier value;Synapses;Synaptic plasticity;Technology;Testing;Therapeutic;Therapeutic Intervention;therapeutic target;tool;Transcript;Translating;treatment duration;Treatment Efficacy;Work

PROJECT_TITLE: Characterization of the role of Fmr1 in oxytocin neuronal subtypes


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: IOWA CITY

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF IOWA

ORG_STATE: IA

PHR: The goal of this project is to reveal new molecular mechanisms that regulate Cav2.1 channel function at the synapse and their role in regulating synaptic transmission in neuronal circuits in the mammalian central nervous system. Given the importance of CaV2 channels in regulating synaptic transmission, as well as the pathological consequences of aberrant SV release, we envision that our findings will provide fundamental insights into how information is encoded by the nervous system, facilitating the development of treatments for a wide range of neurological and neuropsychiatric disorders.

PI_NAMEs: YOUNG, SAMUEL MATTHEW (contact)

PROGRAM_OFFICER_NAME: LEENDERS, MIRIAM

PROJECT_TERMS: Action Potentials;Alternative Splicing;Ataxia;Auditory;Brain Stem;Cells;Central Nervous System;conditional knockout;Data;Development;Electron Microscopy;Electrophysiology (science);Epilepsy;experimental study;Genetic Transcription;Glutamates;Goals;gutless adenoviral vector;Human;Hybrids;Impairment;insight;Kinetics;Knockout Mice;Knowledge;Location;Maps;Measures;Mediating;Migraine;Modeling;models and simulation;Molecular;mouse model;mutant;Nervous System;Nervous System Disorder;Nervous System Physiology;neuronal circuitry;neuropsychiatric disorder;neurotransmission;neurotransmitter release;novel;Output;P-Q type voltage-dependent calcium channel;patch clamp;Pathologic;postsynaptic;preference;presynaptic;Presynaptic Terminals;Protein Isoforms;protein protein interaction;Proteins;Publishing;Regulation;Role;Signal Transduction;Spike Potential;Synapses;Synaptic Transmission;Synaptic Vesicles;therapy development;tool;trafficking;Transgenic Mice;Variant;vesicular release;Viral Vector;voltage

PROJECT_TITLE: Presynaptic regulation of neurotransmitter release in mammalian neuronal circuits

STUDY_SECTION: SYN

STUDY_SECTION_NAME: Synapses, Cytoskeleton and Trafficking Study Section[SYN]


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

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

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: Project Narrative Many serious mental illnesses, including depression and addiction, are characterized by disruption of the ability to experience and seek out pleasure and rewards. A clear connection has been established between these mental health issues and adversity early in life, and an understanding of the mechanisms behind this connection is crucial to identifying those at risk and implementing preventative or mitigative strategies. The proposed research will examine the neurobiological mechanisms by which the paraventricular nucleus of the thalamus, an important component of the brain’s reward circuit, contributes of early life adversity-provoked disturbances in reward seeking and mental health.

PI_NAMEs: KOOIKER, CASSANDRA LEIGH (contact)

PROGRAM_OFFICER_NAME: PINARD, COURTNEY ROSE

PROJECT_TERMS: addiction;Adult;Animals;Anterior;Behavior;behavior influence;behavioral impairment;Brain;cell type;Cells;Child;Cognitive;Data;Decision Making;density;Development;early life adversity;Emotional;emotional experience;Environment;experience;experimental study;food consumption;Future;Genetic;Genetic Recombination;Health;Human;Impairment;Intervention;Knowledge;Label;Life;Link;Location;Long-Term Effects;Mediating;Mental Depression;Mental Health;Modeling;Molecular;Mood Disorders;motivated behavior;Mus;neurobiological mechanism;Neurons;Neuropeptides;pharmacologic;Phenotype;pleasure;Population;Positioning Attribute;Post-Traumatic Stress Disorders;Poverty;Prevention;Process;Psychopathology;Published Comment;receptor;Repression;Research;Rewards;Risk;Role;severe mental illness;sex;Stimulus;Structure;Structure of paraventricular nucleus of thalamus;Testing;Transgenic Mice;Trauma;United States;Urine;Wild Type Mouse

PROJECT_TITLE: The thalamic paraventricular nucleus mediates the influence of early-life adversity on reward-seeking behaviors


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Genetics;Human Genome;Rare Diseases

ORG_DEPT: DENTISTRY

ORG_STATE: MA

PHR: PROJECT NARRATIVE The goal of this revised application is to investigate how the aberrantly increased nuclear β-catenin/CBP branch of the Wnt/β-catenin signaling pathway promotes progression of early head and neck cancer tumors to metastatic disease. Based on our collective published and preliminary studies focused on oral cancer, a major subsite of head and neck cancer, we hypothesize that β-catenin/CBP activity induces distinct aggressive cell subpopulations which can be abolished by pharmacological inhibition of β-catenin/CBP signaling leading to reduced metastasis and improved patient outcomes. We now propose to integrate genomic, epigenetic, molecular and structural approaches to characterize the mechanisms responsible for the generation of aggressive cells with associated gene signatures, pathway networks and protein assemblies, and to identify new strategies for improving treatments for head and neck cancer patients.

PI_NAMEs: KUKURUZINSKA, MARIA A. (contact);MONTI, STEFANO ;VARELAS, XARALABOS

PROGRAM_OFFICER_NAME: OKI, NOFFISAT

PROJECT_TERMS: Acetylation;Adhesions;advanced disease;Alcohols;antagonist;anti-PD-1;Automobile Driving;Benign;beta catenin;Binding;Binding Proteins;Biochemical;Biological Markers;Biology;cancer stem cell;Cancerous;carcinogenesis;Carcinoma;Cell Differentiation process;Cell Line;Cells;Cetuximab;chemotherapy;chromatin immunoprecipitation;Chromatin Structure;Collaborations;combat;Complex;Computing Methodologies;Coupled;Cyclic AMP;Cyclic AMP Response Element;Data;Development;Diagnosis;Disease;DNA Sequence Alteration;draining lymph node;E-Cadherin;Elements;Embryo;Epidermal Growth Factor Receptor;Epigenetic Process;epigenomics;Event;FDA approved;Gene Expression;Gene Expression Profile;Generations;genetic signature;Genomics;Goals;Head and Neck Cancer;head and neck cancer patient;Head and Neck Squamous Cell Carcinoma;histone acetyltransferase;histone methyltransferase;HPV negative;HPV-negative head and neck cancer;Human;Immunotherapy;improved;Inhibition of Cell Proliferation;insight;Knowledge;Lesion;malignant mouth neoplasm;Malignant Neoplasms;Maps;Mediating;Mesenchymal;Metastatic Neoplasm to Lymph Nodes;Methylation;MLL gene;Molecular;Monoclonal Antibodies;Morbidity - disease rate;mortality;mouse model;mouth squamous cell carcinoma;Neoplasm Metastasis;novel therapeutic intervention;Nuclear;Nude Mice;Oncogenic;Oral cavity;Oral Characters;oral lesion;Outcome;Pathway interactions;Patient-Focused Outcomes;Patients;pharmacologic;Phenotype;Prognostic Marker;prognostic value;Progressive Disease;Proteins;Publishing;recruit;Resistance;response;restoration;Role;Signal Pathway;Signal Transduction;single-cell RNA sequencing;small molecule;small molecule inhibitor;stem cell genes;stemness;Survival Rate;targeted treatment;Testing;The Cancer Genome Atlas;therapy resistant;Tobacco;trait;Transcription Initiation Site;transcriptome sequencing;treatment response;tumor;tumor growth;tumor progression;Tumor stage;tumor xenograft;Work;Zebrafish

PROJECT_TITLE: Defining the β-catenin/CBP-catenin/CBP axis in head and neck cancer

STUDY_SECTION: TPM

STUDY_SECTION_NAME: Tumor Progression and Metastasis Study Section[TPM]


ADMINISTERING_IC: DC

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Assistive Technology;Bioengineering;Clinical Research;Hearing Loss;Neurosciences;Rehabilitation

ORG_CITY: CHARLESTON

ORG_DEPT: OTOLARYNGOLOGY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Due to expanding cochlear implant (CI) candidacy and awareness, the number of adult CIs performed annually continues to increase. This project is relevant to public health as it examines modifiable factors that can be used to improve speech understanding in CI recipients, which could in turn improve quality of life in hundreds of thousands of individuals with hearing loss. This is relevant to the NIH’s mission as it seeks and applies knowledge to enhance human life.

PI_NAMEs: SCHVARTZ-LEYZAC, KARA CHANTAL (contact)

PROGRAM_OFFICER_NAME: RIVERA-RENTAS, ALBERTO L

PROJECT_TERMS: 12 year old;Accounting;Acoustic Nerve;Acoustic Stimulation;Action Potentials;Adult;Affect;Animals;Auditory;Auditory area;Auditory Evoked Potentials;Awareness;Bilateral Hearing Loss;Clinical;Cochlear Implants;Code;Cueing for speech;Cues;Data;deaf;Dementia;density;Detection;Devices;early onset;Electrodes;FDA approved;hard of hearing;hearing impairment;high risk;Hospitalization;Human;improved;Individual;Individual Differences;Knowledge;Laboratory Animals;Life;Measures;Mental Depression;Mission;Modeling;Modification;Nerve Fibers;neural;neuromechanism;Neurons;neuroprosthesis;normal hearing;novel strategies;Outcome;Patients;Perception;Performance;Persons;Physiologic pulse;Population;programs;Psychophysics;Public Health;Pulse Rates;Quality of life;Rehabilitation therapy;Role;Signal Transduction;Site;sound;Speech;speech recognition;spiral ganglion;Stimulus;Structure;success;Techniques;Time;Time Perception;tool;Training;United States;United States National Institutes of Health;Voice;Work

PROJECT_TITLE: CI Neural Mechanisms

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


NIH_SPENDING_CATS: Genetics;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Embryonic - Human;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: Albany

ORG_NAME: REGENERATIVE RESEARCH FOUNDATION

ORG_STATE: NY

PHR: The cerebral cortex develops from embryonic cells that divide and differentiate to produce the diverse sets of neurons and glia that constitute the adult cortical architecture. This process is tightly regulated over time so that the cortex is built in an orderly manner, which is essential to achieve normal function. Here we propose to identify and study genes that regulate the production of different cortical cells over time. We will carry out this work in mouse and in human using stem cell technology, which has the potential to reveal new knowledge about how the human cortex forms, and how neural stem cells can be activated to counteract developmental and neurodegenerative disorders.

PI_NAMEs: TEMPLE, SALLY  (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Address;Adult;Architecture;Candidate Disease Gene;cell cortex;Cell Cycle;Cell division;Cells;Cerebral cortex;Characteristics;Code;Complex;Data;daughter cell;Development;developmental disease;Disease;Embryo;embryo cell;Environmental Risk Factor;gene network;Generations;Genes;Heterogeneity;Human;Image Analysis;In Vitro;in vivo;Knowledge;Life;Methods;Mus;nerve stem cell;Neurodegenerative Disorders;Neuroglia;Neurons;novel;Pregnancy;Process;Production;progenitor;Proliferating;Radial;receptor;regenerative therapy;release factor;RNA-Binding Proteins;Role;screening;segregation;Specific qualifier value;stem cell fate;stem cell technology;stem cells;stemness;Structure;Structure of choroid plexus;Testing;therapy development;Time;transcriptome sequencing;Translations;Untranslated RNA;Vascular Endothelial Cell;Work

PROJECT_TITLE: Defining Characteristics of Cortical Progenitor Cells over Time in Mouse and Human


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences;Pediatric;Rare Diseases;Spinal Muscular Atrophy

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Neuronal control of movement is extensively studied not only because it underlies fundamental human behaviors  but  also  because  diseases  that  affect  the  motor  system  represent  a  significant  burden  for  human  health.  Stasimon is an ER--resident transmembrane protein with an important yet molecularly undefined role in health  and  disease  of  the  motor  system.  This  proposal  describes  a  multidisciplinary  effort  aimed  to  establish  the  essential requirement of Stasimon for motor function and its contribution to the neurodegenerative disease SMA  at the molecular, cellular and circuit levels.

PI_NAMEs: PELLIZZONI, LIVIO  (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Affect;Afferent Neurons;Animal Model;Behavior;Behavioral;Biological Assay;brain pathway;Breathing;cell growth regulation;Cell model;cell type;Cells;cellular targeting;Central Nervous System;Cessation of life;conditional knockout;Data;Deafferentation procedure;Deglutition;design;Development;Disease;Event;Functional disorder;Gene Delivery;Gene Mutation;Goals;Health;Homeostasis;Human;human disease;in vivo;Induced Mutation;Inherited;Integral Membrane Protein;Interneurons;Knockout Mice;Knowledge;Link;Lipids;Locomotion;Mammalian Cell;Mediating;Mediator;member;Membrane Biology;Mitochondria;mitochondrial membrane;Molecular;Morphology;Motor;motor control;motor deficit;motor disorder;Motor Neurons;mouse model;Movement;multidisciplinary;Mus;Muscle;Mutant Strains Mice;neural circuit;Neurobiology;Neurodegenerative Disorders;Neuromuscular Diseases;neuron loss;neuronal circuitry;neuronal survival;Neurons;novel;Pathogenesis;Pathogenicity;Pathology;Pathway interactions;Pattern;Peripheral;Physiological;Process;Property;Proprioceptor;Publishing;Regulation;Respiration;restoration;Role;Sensory;Shapes;Site;skeletal muscle wasting;SMN deficiency;SMN protein (spinal muscular atrophy);Spinal;Spinal Muscular Atrophy;spinal reflex;Synapses;synaptic function;Synaptic Transmission;System;Systems Development;Testing;Translating;Viral;Work

PROJECT_TITLE: Essential role of Stasimon in motor circuit development and disease

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_DEPT: DERMATOLOGY

PHR: While immunotherapies and kinase inhibitors can successfully treat metastatic melanoma, they are not routinely used to treat melanomas that have not yet disseminated systemically secondary to their side effects. Our recent work suggests that RhoJ plays a dual role in tumor biology- it promotes tumor formation while also controlling the ability of endothelial cells to form vessels in and around tumors. Here we propose that RhoJ plays a selective role in tumor formation, tumor angiogenesis, and lymphangiogenesis. We test this hypothesis using genetically engineered mice, advanced imaging and genomics, and newly developed RhoJ inhibitors. Completion of these studies will identify a new therapeutic strategy that can be used to treat early stage melanoma and other cancers.

PI_NAMEs: GANESAN, ANAND K (contact)

PROGRAM_OFFICER_NAME: WOODHOUSE, ELIZABETH

PROJECT_TERMS: 3-Dimensional;Acceleration;Actins;angiogenesis;Animals;Apoptotic;Autoimmune;Biology;Blood Vessels;BRAF gene;Bromodeoxyuridine;cell growth;Cells;Characteristics;Critical Pathways;Dermal Neoplasm;Dermis;Distant;Endothelial Cells;Epidermis;Focal Adhesions;Genes;Genetically Engineered Mouse;Genomics;Growth;Hair follicle structure;Health;Histologic;Human;human model;Image;Immunotherapy;In Vitro;in vivo;in vivo imaging;inhibitor;Invaded;kinase inhibitor;Label;lymph nodes;Lymphangiogenesis;Lymphatic;lymphatic development;Lymphatic Endothelial Cells;lymphatic vessel;Malignant Neoplasms;Measures;melanocyte;Melanoma;Melanoma Cell;Melanoma Tumor;Metastatic Melanoma;Metastatic Neoplasm to Lymph Nodes;Metastatic Neoplasm to the Lung;migration;Modeling;Molecular;Monomeric GTP-Binding Proteins;mouse model;mutant;Neoplasm Metastasis;neoplastic cell;Nevi and Melanomas;Nevus;novel;novel therapeutic intervention;Nutrient;Oncogenes;Organ;Patients;pharmacologic;Play;prevent;Prognosis;Publishing;recruit;Role;Secondary to;side effect;Signal Transduction;single cell genomics;Skin;small molecule;stem cells;Stress;Stress Fibers;Testing;Therapeutic;Therapeutic Agents;therapeutic target;three-dimensional modeling;Tissues;Transgenic Mice;tumor;Tumor Angiogenesis;Tumor Biology;tumor growth;tumor initiation;tumor progression;Tumor Promotion;Tumor stage;Tumor-Associated Process;unpublished works;Vascular Endothelial Cell;Vascularization;Work;Xenograft Model

PROJECT_TITLE: Identifying Therapeutic Targets for Stage III Melanoma


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;HIV/AIDS;Immunization;Infectious Diseases;Lung;Orphan Drug;Patient Safety;Pediatric;Prevention;Rare Diseases;Tuberculosis;Vaccine Related;Vaccine Related - AIDS;Women's Health Research

ORG_CITY: PARKTOWN

ORG_COUNTRY: SOUTH AFRICA

ORG_FIPS: SF

ORG_NAME: WITS HEALTH CONSORTIUM (PTY), LTD

PHR: PROJECT NARRATIVE HIV and TB constitute major threats to human health. Progress in understanding and managing HIV has been revolutionary and rapidly translated into practice. For epidemic control, we still require an effective HIV vaccine, biomedical interventions to solve adherence issues in treatment and prevention, and a cure. Similarly, an effective TB vaccine must still be found.

PI_NAMEs: GRAY, GLENDA E (contact);MOHAPI, LERATO ;PANCHIA, RAVINDRE

PROGRAM_OFFICER_NAME: ROBY, GREGG A,

PROJECT_TERMS: Address;Adherence;Adolescent;Adult;Age;AIDS prevention;Anti-Retroviral Agents;Child;Childhood;clinical development;Clinical Management;Clinical Research;clinical research site;Clinical Trials;Clinical Trials Network;Clinical Trials Unit;Clinics and Hospitals;Collaborations;Communities;comorbidity;Development;Diagnosis;Disease remission;Drug Kinetics;drug-sensitive;Ensure;Epidemic;epidemic response;Ethics;Ethnic Origin;Evaluation;Formulation;Funding;Gender;Generations;Geography;Goals;Health;Hepatitis B;high risk population;HIV;HIV Infections;HIV prevention trials network;HIV vaccine;HIV/AIDS;HIV/TB;Human;Human Milk;Immune;improved;Incidence;Infant;Infection;innovation;International;International Maternal Pediatric Adolescent AIDS Clinical Trials;Intervention;Investments;Joints;Lead;Leadership;Medicine;Methods;Monoclonal Antibodies;neonate;Neurocognitive;novel;Oral;Pathway interactions;pediatric human immunodeficiency virus;pediatric human immunodeficiency virus infection;Persons;Phase;Positioning Attribute;pre-exposure prophylaxis;pregnancy prevention;Pregnant Women;preservation;Prevalence;prevent;Prevention;programs;racial diversity;Regimen;Research;Research Personnel;Research Support;Resistance;Role;Safety;Scientist;side effect;Social Behavior;South Africa;South African;STI prevention;success;Technology;Testing;Therapeutic;Therapeutic Clinical Trial;Time;Translating;transmission process;treatment as prevention;trial design;Tuberculosis;tuberculosis treatment;Tuberculosis Vaccines;United Nations;United States National Institutes of Health;vaccination strategy;vaccine immunogenicity;vaccine trial;Vaccines;Vertical Disease Transmission;Woman

PROJECT_TITLE: PHRU-Setshaba Clinical Trials Unit


NIH_SPENDING_CATS: Brain Disorders;Neurosciences

ORG_DEPT: NEUROLOGY

PHR: PROJECT NARRATIVE Essential tremor (ET) is among the most common neurological disorders, but how tremor is generated in ET patients remains poorly understood. Currently, treatment options for ET are very limited and many people with ET are significantly impaired in their personal and professional lives. The proposed research will take recent genetic and neuropathological discoveries in ET into functional understanding of how structural and molecular changes due to aberrant calcium handling in the brain can lead to tremor, and the knowledge gained will serve as foundation for therapy development to treat ET and prevent disability.

PI_NAMEs: FAUST, PHYLLIS L;KUO, SHENG-HAN  (contact)

PROGRAM_OFFICER_NAME: DOPERALSKI, ADELE ELIZABETH

PROJECT_TERMS: Address;Affect;American;Anatomy;Autopsy;Biochemical;Biochemistry;Brain;Calcium;Calcium Channel;cell injury;Cell Physiology;Cellular Stress;Cerebellar Cortex;Cerebellar Diseases;Cerebellum;Chronic;Clinical;Data;Disability prevention;disabled;Disease;DNA Sequence Alteration;Endoplasmic Reticulum;Essential Tremor;Event;Foundations;Funding;Generations;Genetic;High Prevalence;Human;Human Pathology;Impairment;improved;in vitro Assay;in vivo;Infusion procedures;insight;Intention Tremor;Kinetics;Knowledge;Lead;Light;Macromolecular Complexes;Measurement;Measures;Modeling;Molecular;Morphology;mouse genetics;mouse model;Mus;National Institute of Neurological Disorders and Stroke;Nervous System Disorder;neuroimaging;neuropathology;neurotensin mimic 1;Observational Study;Parkinson Disease;Pathologic;Pathway interactions;Patients;Pattern;Persons;Pharmacology;Phenotype;Phosphoric Monoester Hydrolases;Phosphorylation;Phosphotransferases;Physiological;Physiology;Point Mutation;Population;Property;Purkinje Cells;Research;Research Personnel;Role;Ryanodine Receptor Calcium Release Channel;Severities;Site;Slice;Sorting;Specificity;Spinocerebellar Ataxias;Synapses;targeted treatment;Testing;Therapeutic;therapeutic target;therapy development;Time;Transcript;transcriptome sequencing;Treatment Failure;Tremor;United States National Institutes of Health

PROJECT_TITLE: Targeting Cerebellar Endoplasmic Reticulum Calcium Handling in Essential Tremor

STUDY_SECTION: CDIN

STUDY_SECTION_NAME: Chronic Dysfunction and Integrative Neurodegeneration Study Section[CDIN]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: ANN ARBOR

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative Pulmonary fibrosis is characterized by an accumulation of activated collagen-producing fibroblasts causes progressive lung scarring leading rapid death. Current therapy is only modestly effective and this could be due to off target effects on multiple different cell types. DDR2 is an attractive target because it is highly expressed on the surface of fibroblasts and may therefore be amenable to specific inhibitors or as a target for immunotherapy using a novel chimeric antigen receptor system.

PI_NAMEs: KESHAMOUNI, VENKATESHWAR G;KIM, KEVIN KEEWOUN (contact)

PROJECT_TERMS: Acute Lung Injury;Acute Respiratory Distress Syndrome;Antibodies;antifibrotic treatment;Ants;Apoptosis;Attenuated;Automobile Driving;Binding;cancer cell;CD94 Antigen;cell type;Cells;Cessation of life;chimeric antigen receptor;chimeric antigen receptor T cells;clinical effect;Clonal Expansion;Collagen;Collagen Type I;coronary fibrosis;Data;DDR1 gene;discoidin domain receptor 2;Disease;Effector Cell;efficacy evaluation;engineered NK cell;Epithelial Cells;Family;Feedback;Fibrillar Collagen;Fibroblasts;Fibrosis;fibrotic lung;Future;idiopathic pulmonary fibrosis;Immunotherapy;improved outcome;inhibitor;Lung Diseases;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;member;Mesenchymal;Modeling;Mus;Natural Killer Cell Immunotherapy;Natural Killer Cells;nintedanib;novel;partial response;Pathway interactions;PDPK1 gene;Peptides;pharmacologic;Phosphatidylinositide 3-Kinase Inhibitor;phosphoproteomics;Phosphorylation;PIK3CG gene;Profibrotic signal;programs;Protein Tyrosine Kinase;Pulmonary Fibrosis;receptor internalization;Receptor Protein-Tyrosine Kinases;Receptor Signaling;Regulation;Reporting;Resistance;Safety;selective expression;Signal Pathway;Signal Transduction;small molecule inhibitor;success;Surface;Syndrome;System;Systemic Scleroderma;T-Lymphocyte;Technology;Testing;Therapeutic;therapeutic target;Toxic effect;Transforming Growth Factor beta;Tyrosine Kinase Inhibitor

PROJECT_TITLE: Targeting Fibroblast Discoidin Domain Receptor 2 for Immunotherapy to Pulmonary Fibrosis

STUDY_SECTION: LIRR

STUDY_SECTION_NAME: Lung Injury, Repair, and Remodeling Study Section[LIRR]


NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;HIV/AIDS;Immunization;Infectious Diseases;Maternal Health;Mental Health;Neurosciences;Orphan Drug;Pediatric;Pediatric - AIDS;Prevention;Rare Diseases;Tuberculosis;Vaccine Related;Vaccine Related - AIDS;Women's Health Research

PHR: The overarching research agenda for the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network includes four priority areas 1) novel and durable treatment of human immunodeficiency virus (HIV); 2) strategies for antiretroviral treatment-free remission; 3) tuberculosis prevention, diagnosis and treatment; and 4) prevention and management of HIV-associated co-infections and complications. The Network’s research in these areas will focus specifically on pregnant and postpartum women and infants, children and adolescents with and/or affected by HIV, with the ultimate goal of ending the worldwide epidemic in these populations. We will actively engage communities and other research partners to address these scientific and public health priorities.

PI_NAMEs: NACHMAN, SHARON A (contact)

PROGRAM_OFFICER_NAME: LOMBO RODRIGUEZ, TANIA

PROJECT_TERMS: Acceleration;Address;Adolescent;Adolescent and Young Adult;adolescent woman;Adult;Affect;Africa;Aftercare;Americas;Anatomy;Anti-Retroviral Agents;anti-viral efficacy;Antibodies;Antigen-Antibody Complex;Antigens;antiretroviral therapy;Area;Asia;Binding;CD4 Positive T Lymphocytes;Central Nervous System;Child;Childhood;Clinical Research;clinical research site;Clinical Trials;Clinical Trials Network;co-infection;Collaborations;Communities;community engagement;comorbidity;Development;Diagnosis;Disease;Disease Marker;Disease Progression;Disease remission;disorder prevention;Dose;drug development;Drug Industry;Drug Interactions;Drug Kinetics;Drug resistance in tuberculosis;effective intervention;efficacy evaluation;Ensure;Epidemic;Evaluation;Executive Dysfunction;experience;Goals;HIV;HIV Infections;HIV vaccine;HIV-infected adolescents;HIV/TB;Hour;Immunologic Markers;Immunotherapy;improved;Infant;Infection;innovation;interest;International Maternal Pediatric Adolescent AIDS Clinical Trials;Intervention;Lactation;Leadership;Licensing;Licensure;Life;Location;Maternal and Child Health;Mediating;Mental Depression;Mental disorders;Mental Health;Methods;model development;National Institute of Allergy and Infectious Disease;Neurocognitive;neuroprotection;neurotoxic;neutralizing antibody;novel;novel strategies;novel therapeutics;novel vaccines;operation;Outcome;perinatal HIV;Pharmaceutical Preparations;pharmacometrics;Phase;Population;Post-Traumatic Stress Disorders;Postpartum Women;Predisposition;Pregnancy;pregnant;Pregnant Women;preservation;prevent;Prevention;Preventive;Property;Prophylactic treatment;Public Health;public health priorities;Regimen;Research;Research Design;Research Personnel;research study;Role;Safety;Site;Social Behavior;Therapeutic;Therapeutic Intervention;Time;tool;Treatment outcome;treatment response;Tuberculosis;tuberculosis treatment;Tuberculosis Vaccines;United States National Institutes of Health;Vaccines;Virus;Woman

PROJECT_TITLE: IMPAACT Leadership Group


NIH_SPENDING_CATS: Antimicrobial Resistance;Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Prevention;Social Determinants of Health;Urologic Diseases;Women's Health Research

ORG_CITY: SAN FRANCISCO

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: PROJECT NARRATIVE Community-onset antimicrobial resistant (AMR) urinary tract infections (UTI) are a growing public health threat, particularly for women. The objective of this proposal is to identify individual- and neighborhood-level risk factors, predominant genotypes, and complications for UTI caused by extended-spectrum beta-lactamase- producing Escherichia coli (E. coli) (ESBL-E. coli), as well as temporal and spatial clusters of ESBL-E. coli. This approach requires the application of a combination of social, spatial, and molecular epidemiology methods which can be applied to other AMR infections.

PI_NAMEs: RAPHAEL, EVA  (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Address;Affect;Age;Anti-microbial susceptibility;Antibiotics;Antimicrobial Resistance;antimicrobial resistant infection;antimicrobial resistant pathogen;Award;Behavior;Benign;California;career;Case/Control Studies;Characteristics;Clinical;Clinical Management;Clinical Research;cohort;Communicable Diseases;Communities;community setting;community transmission;community-level factor;Data;Data Collection;design;Diagnosis;Diet;Disease Outbreaks;Electronic Health Record;Epidemiologic Methods;Epidemiologist;Escherichia coli;Escherichia coli Infections;Ethnic Origin;Evaluation;experience;Extended spectrum Beta lactamase producing Escherichia coli;Extended-spectrum β-lactamase;Family Practice;Food;food consumption;Food Contamination;Future;Genitourinary system;Genotype;Geographic Distribution;Geography;Goals;Grant;Health;health care availability;health care settings;health inequalities;Healthcare;Healthcare Systems;improved;Incidence;Income;Individual;Infection;Information Systems;International;Intestines;K-Series Research Career Programs;Longitudinal Studies;Mentors;Methods;Molecular Epidemiology;Neighborhoods;novel;older patient;older women;Organism;Outcome;pathogen;pathogenic Escherichia coli;Patient Outcomes Assessments;Patients;Phenotype;Population Heterogeneity;Positioning Attribute;Predisposition;Prevalence;prevent;Prevention;Prevention strategy;Probability;Process;professor;programs;Public Health;Questionnaires;Race;racial difference;recurrent infection;Reporting;Research;Research Methodology;Research Personnel;Resistance;Risk;Risk Factors;safety net;Sampling;San Francisco;Scientific Advances and Accomplishments;skills;social;social epidemiology;social factors;Source;spatial epidemiology;Training;Translating;transmission process;Transportation;Travel;trend;Universities;Urinary tract infection;Woman;women's diagnosis;Work

PROJECT_TITLE: Community-onset urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in women of diverse backgrounds

STUDY_SECTION: MID

STUDY_SECTION_NAME: Microbiology and Infectious Diseases B Research Study Section[MID-B]


ED_INST_TYPE: EARTH SCIENCES/RESOURCES

NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: RIVERSIDE

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

PHR: PROJECT NARRATIVE  The major objective of this application is to understand the repair and human health consequences of a unique group of DNA alkylation products, alkyl-phosphotriester lesions. The outcome of the proposed research will improve our understanding about the implications of alkylated DNA lesions in the etiology of human cancer development and may provide important knowledge basis for developing better cancer chemotherapy.

PI_NAMEs: WANG, YINSHENG  (contact)

PROGRAM_OFFICER_NAME: OKANO, PAUL

PROJECT_TERMS: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol;4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone;adduct;Affect;alkyl group;Alkylating Agents;Alkylation;animal tissue;Binding;Biological;Biological Assay;Biology;Bypass;carcinogenesis;Carcinogens;Cells;chemical synthesis;Chemicals;Chemistry;chemotherapeutic agent;Chemotherapy-Oncologic Procedure;Chromatin;CRISPR/Cas technology;Data;design;Development;Dinucleoside Phosphates;DNA;DNA Adducts;DNA Alkylation;DNA biosynthesis;DNA Damage;DNA lesion;DNA Replication Inhibition;DNA-Directed DNA Polymerase;drinking water;Epigenetic Process;Etiology;experimental study;exposed human population;Exposure to;Frequencies;genetic information;Genetic Transcription;genome editing;genome integrity;Health;Histones;Human;human disease;Human Genome;improved;Induced Mutation;inorganic phosphate;insight;Investigation;Knowledge;Lesion;Liver;Lung;Malignant Neoplasms;Mammalian Cell;Measures;Metabolic Activation;Methods;Methylation;Modification;Molecular;Mutagenesis;Mutagens;N'-nitrosonornicotine;Nitrosamines;nucleobase;Oligodeoxyribonucleotides;Outcome;Oxygen;pyridine;Rattus;repaired;Research;Risk Assessment;Rodent;Role;Shuttle Vectors;Site;Testing;Tissues;Tobacco;Tobacco smoke;Veins;Vertebral column

PROJECT_TITLE: Chemistry and Biology of Alkyl Phosphotriester Lesions

STUDY_SECTION: CE

STUDY_SECTION_NAME: Cancer Etiology Study Section[CE]


NIH_SPENDING_CATS: Biotechnology;Clinical Research;Digestive Diseases;Food Allergies;Genetics;Human Genome;Prevention

ORG_CITY: CINCINNATI

ORG_NAME: CINCINNATI CHILDRENS HOSP MED CTR

PHR: Project Narrative The proposed research is relevant to public health because understanding the genetic and immunologic features of eosinophilic esophagitis (EoE) is expected to contribute to better diagnostics and treatments for this emerging disease. Thus, this proposal is relevant to the part of NIH's mission that pertains to fostering fundamental creative discoveries and innovative research strategies as a basis for ultimately protecting health.

PI_NAMEs: ROTHENBERG, MARC E. (contact)

PROGRAM_OFFICER_NAME: MINNICOZZI, MICHAEL

PROJECT_TERMS: 2p23;adaptive immunity;Adult;advanced disease;Allergic;base;Binding;Biological;Biological Models;Biological Products;causal variant;CD4 Positive T Lymphocytes;Cell Physiology;Childhood;Chromatin;Chromosomes;Chronic;Chronic Disease;Clinical;cohort;Creativeness;Custom;Data;Databases;Defect;Deglutition Disorders;design;desmoglein 1;Diagnostic;Disease;Disease susceptibility;Dissection;eosinophil;Eosinophilia;Eosinophilic Esophagitis;Epithelial Cells;Epithelium;Esophageal Diseases;Esophageal Tissue;Esophagus;Evaluation;Expression Profiling;Extracellular Space;FDA approved;follow-up;Food;food antigen;Fostering;Functional disorder;gene product;Genes;Genetic;genetic approach;genetic association;Genetic Polymorphism;Genetic Predisposition to Disease;genetic variant;genome wide association study;genome-wide;genomic locus;Genomics;Goals;Grant;Health protection;Heritability;Histologic;Human;Hyperplasia;Immune response;Immunity;Immunologics;Impairment;improved;In Vitro;in vivo Model;Inflammatory;Inflammatory Response;innovation;Interleukin-13;Interleukin-4;Interleukin-5;Lead;Longitudinal Studies;Lung;Maps;Mediating;Meta-Analysis;Mission;Morbidity - disease rate;Mus;Natural Immunity;novel;overexpression;Pain;Pathogenesis;Pathway interactions;Pharmaceutical Preparations;Predisposition;Process;Production;programs;Proteomics;Public Health;Research;response;risk variant;Role;Series;Single Nucleotide Polymorphism;Skin;Susceptibility Gene;System;T-Lymphocyte;targeted agent;Testing;Th2 Cells;Therapeutic;tool;transcriptomics;Transgenic Organisms;TSLP gene;United States National Institutes of Health;Validation;Variant;Vomiting

PROJECT_TITLE: Genetic and Immunological Dissection of Eosinophilic Esophagitis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-GGG-F(03)M]


NIH_SPENDING_CATS: Biomedical Imaging;Breast Cancer;Cancer;Clinical Research;Clinical Trials and Supportive Activities;Prevention;Women's Health Research

ORG_CITY: PITTSBURGH

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

ORG_STATE: PA

PHR: Project Narrative  One of the primary criticisms of mammography is that it leads to unneeded stress and anxiety from identification and biopsy of non-cancerous findings. Contrast-enhanced mammography (CEM) has the potential to significantly reduce biopsy rates for commonly seen benign breast lesions while preserving very high cancer detection. This study is focused on that value proposition and, if successful, could impact the lives of hundreds of thousands of women annually.

PI_NAMEs: ZULEY, MARGARITA L (contact)

PROGRAM_OFFICER_NAME: KIM, BOKLYE

PROJECT_TERMS: Adopted;American College of Radiology;anatomic imaging;Anatomy;Anxiety;Appearance;Architecture;Area;Benign;Biopsy;Breast;Breast biopsy;Breast Cancer Detection;breast lesion;calcification;Cancer Detection;cancer diagnosis;Case Study;case-based;Categories;Characteristics;Classification;Classification Scheme;Clinical;Clinical Trials;Consent;contrast enhanced;cost effective;Coupled;Databases;Detection;Diagnosis;Diagnostic;Evaluation;expectation;Frequencies;Heterogeneity;Image;improved;indexing;Institutional Review Boards;Iodine;Kinetics;Lesion;Magnetic Resonance Imaging;Malignant Neoplasms;Mammography;Maps;novel;Outcome;Pathology;Patients;Performance;Perfusion;personalized approach;Pilot Projects;Predictive Value;preservation;Probability;Procedures;prospective;Prospective Studies;Protocols documentation;Publications;radiologist;Reader;Recommendation;Research Design;response;Risk;ROC Curve;Sampling;Schedule;screening;Sensitivity and Specificity;Site;soft tissue;standard of care;Stress;Testing;Time;tomosynthesis;trend;Tumor Biology;ultrasound;Uncertainty;United States;Update;Woman

PROJECT_TITLE: Contrast Enhanced Mammography (CEM) to Reduce Biopsy Rates for Less Than Highly Suspicious Breast Abnormalities: a Prospective Study

STUDY_SECTION: CTIS

STUDY_SECTION_NAME: Clinical Translational Imaging Science Study Section[CTIS]


ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Cardiovascular disease remains the leading cause of morbidity and mortality. Genetic perturbations are casually associated with cardiovascular risk factors and the development of heart disease. The goal of this proposal is to better understand how a new class of genes known as long noncoding RNAs (lncRNAs) contribute to cardiovascular disease and directly test whether targeting a lncRNA can be beneficial therapeutically.

PI_NAMEs: SALLAM, TAMER  (contact)

PROGRAM_OFFICER_NAME: LIU, LIJUAN

PROJECT_TERMS: Address;Affect;Affinity;Animals;Atherosclerosis;ATP binding cassette transporter 1;Binding;Binding Sites;Biological;Biological Assay;Biology;Bone Marrow;burden of illness;Cardiometabolic Disease;cardiometabolism;Cardiovascular Diseases;cardiovascular risk factor;Cardiovascular system;Cells;Cessation of life;Cholesterol;Chromatin;Coronary Arteriosclerosis;Cues;Data;defined contribution;Development;Diagnostic;Diet;dietary;disease phenotype;efficacy testing;Ensure;epigenomic profiling;Evolution;fatty liver disease;Foam Cells;gain of function;Gene Expression;Gene Expression Regulation;gene therapy;Genes;Genetic;genome wide association study;genome-wide;Goals;heart disease risk;Heart Diseases;Hepatic;Homeostasis;Human;human disease;Immune signaling;improved;in vivo;in vivo evaluation;Inflammation;innovation;insight;Junk DNA;Knock-out;Knowledge;Lesion;Licensing;Link;lipid metabolism;Lipids;Liver;loss of function;Macrophage;Manuscripts;Metabolic;Metabolic Diseases;Metabolism;Methodology;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;nonalcoholic steatohepatitis;novel;Pathologic Processes;Pathway interactions;Phenotype;Physiological;Plasma;Play;pleiotropism;preference;Recurrence;Regulation;Reporting;reverse cholesterol transport;Role;screening;Series;Specificity;Sterols;Testing;Therapeutic;therapeutic RNA;therapeutic target;tool;trait;Treatment Efficacy;treatment strategy;Untranslated RNA;Work

PROJECT_TITLE: Licensing LncRNAs in Atherosclerosis

STUDY_SECTION: AICS

STUDY_SECTION_NAME: Atherosclerosis and Inflammation of the Cardiovascular System Study Section[AICS]


NIH_SPENDING_CATS: Clinical Research;Cystic Fibrosis;Infectious Diseases;Lung;Pediatric;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Researchers still do not understand the mechanisms behind the progressive and irreversible lung damage that ultimately causes respiratory failure in patients with cystic fibrosis (CF). Our proposed research aims to identify the mechanisms that drive this progressive lung deterioration in CF. Ultimately, our goal is to identify potential therapeutic targets that, in conjunction with the current CFTR modulator therapies, will help prevent progressive lung tissue damage in CF patients.

PI_NAMEs: BRUSCIA, EMANUELA MARINA (contact)

PROGRAM_OFFICER_NAME: LACHOWICZ-SCROGGINS, MARRAH ELIZABETH

PROJECT_TERMS: Affect;Bacteria;Bacterial Infections;Blood Cells;Bone Marrow;CD34 gene;Cell Separation;Cells;Chronic;chronic inflammatory disease;Cicatrix;Cystic Fibrosis;cystic fibrosis mouse;cystic fibrosis patients;Cystic Fibrosis Transmembrane Conductance Regulator;Data;Delta F508 mutation;Deterioration;Development;Disease;drug efficacy;Epigenetic Process;Exposure to;Feedback;fighting;Functional disorder;Gene Expression Profile;Genes;Goals;hematopoietic stem cell differentiation;Hematopoietic stem cells;Host Defense;Human;Immune;Immunity;immunodeficient mouse model;Immunologic Memory;Immunology;Impairment;improved;Individual;Infection;Inflammation;Inflammatory;Inflammatory Response;innovation;Investigation;Knockout Mice;Life Expectancy;Lipopolysaccharides;Lung;Lung immune response;Lung infections;lung injury;Macrophage;Mediating;memory acquisition;Methodology;migration;Modeling;monocyte;mouse model;Mus;Myeloid Progenitor Cells;novel;Pathogenesis;Pathogenicity;Pathologic;Pathway interactions;pharmacologic;prevent;Pseudomonas aeruginosa;Publishing;Pulmonary Cystic Fibrosis;pulmonary function;Pulmonary Inflammation;Pulmonary Pathology;Recovery;recruit;Research;Research Personnel;Respiratory Failure;response;Signal Transduction;stem cells;Structure of parenchyma of lung;Technology;Testing;Therapeutic Intervention;therapeutic target;therapeutically effective;Time;Tissues;Training;Transforming Growth Factor beta;Translating;Umbilical Cord Blood Transplantation;Work;Xenograft Model

PROJECT_TITLE: Pathogenic monocyte response to chronic lung inflammation in cystic fibrosis

STUDY_SECTION: LCMI

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


NIH_SPENDING_CATS: Clinical Research;Dental, Oral, and Craniofacial Disease;Pediatric;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_CITY: COLLEGE STATION

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

ORG_STATE: TX

PHR: Project Narrative Our research proposal seeks to elucidate fundamental aspects of how endochondrogenesis contributes to the mandible formation and trauma repair. Finishing this study will fill the knowledge gap in this largely unknown but vital area, and create a foundation for developing novel approaches to accelerate future mandible trauma repair process.

PI_NAMEs: JING, YAN  (contact)

PROGRAM_OFFICER_NAME: THIRUMANGALATHU, SHOBA

PROJECT_TERMS: Acceleration;Address;Adolescent;Allografting;angiogenesis;Animal Model;Anterior;Apoptosis;Area;Biology;bone;bone cell;Bone necrosis;Bone Regeneration;carcinogenesis;career;Cartilage;cartilage transplantation;Cells;Cellular biology;Child;Chondrocytes;Chondrogenesis;Classification;Clinical Skills;Complex;craniofacial;Data;Developmental Biology;Embryo;Epiphysial cartilage;Failure;Fetus;Foundations;Future;Goals;Growth;healing;Human;Infant;Isogenic transplantation;Knowledge;Laboratories;Learning;Mandible;Meckel's cartilage;medical specialties;Mentors;Mesenchymal Stem Cells;Molecular;Molecular Biology;mouse model;Mus;Newborn Infant;novel;novel strategies;novel therapeutic intervention;Orthodontic;Osteogenesis;Play;postnatal;Process;Productivity;progenitor;Program Development;programs;Publications;Reagent;Recording of previous events;repaired;Reporting;Research;Research Proposals;Role;scaffold;Scientist;Series;skeletal;Solid;Source;stem cell biology;stem cell fate;Structure;Technical Expertise;Testing;tissue regeneration;Tissues;Training;transdifferentiation;Trauma;Vascularization;Work

PROJECT_TITLE: To define the novel roles of endochondrogenesis in mandible formation and trauma repair

STUDY_SECTION: DSR

STUDY_SECTION_NAME: National Institute of Dental and Craniofacial Research Special Grants Review Committee[DSR]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Contraception/Reproduction;Endocrine Disruptors;Genetics;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Prevention;Social Determinants of Health

PHR: Narrative We are all exposed to a plethora of environmental chemicals, which if they enter our bodies can have detrimental effects on function and health, but importantly can also potentially affect the health of our children and grandchildren. This project will capitalise on a unique animal model that has been established within the UK, brings together expertise from the Universities of Michigan, Glasgow (UK) and Nottingham (UK) to investigate the mechanisms by which a mother’s exposure to a real life cocktail of chemicals during pregnancy can affect the long-term metabolic and reproductive health of her offspring and that of subsequent generations.

PI_NAMEs: EVANS, NEIL PRICE;LEA, RICHARD ;PADMANABHAN, VASANTHA  (contact)

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: Acute;Adult;Adverse effects;Affect;Animal Model;Animals;Behavior;Biological;bone;Cells;Chemical Exposure;Chemicals;Child;Chronic;Complex;Complex Mixtures;Conceptions;Data;Development;DNA Methylation;Early Intervention;Endocrine;Endocrine disruption;Environment;environmental chemical;environmental chemical exposure;Environmental Risk Factor;Epigenetic Process;Etiology;Evaluation;Exhibits;exosome;exposed human population;Exposure to;Face;Female;Fertility;Fertilizers;Functional disorder;functional outcomes;Future Generations;Generations;Genetic Transcription;Germ Cells;grandchild;Health;Healthcare;Hepatocyte;Human;improved;Incidence;Industrialization;insight;intergenerational;Life;life span;Link;male;Manure;Maternal Exposure;Measures;Mediating;Mediator;Metabolic;Metabolic Diseases;Metabolic syndrome;Metabolism;Michigan;Mission;Modeling;Modification;Mothers;National Institute of Environmental Health Sciences;Neonatal;No-Observed-Adverse-Effect Level;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;novel strategies;Obesity;offspring;pharmacologic;Phenotype;Policies;Policy Developments;Pregnancy;Pregnant sheep;prenatal exposure;Prevalence;prevent;Prevention strategy;Publishing;Reproduction;reproductive;reproductive development;reproductive function;Reproductive Health;Resources;Seminal Plasma;Sentinel;Sewage;sex;Sheep;Solid;System;Testing;transgenerational epigenetic inheritance;translational model;transmission process;Universities;Untranslated RNA;Waste Products

PROJECT_TITLE: Transgenerational consequences of pre-conceptional and in utero exposure to real-life chemical mixtures on fertility and metabolic health

STUDY_SECTION: ICER

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


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: DURHAM

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: DUKE UNIVERSITY

PHR: Project Narrative  Our project focuses on COPII, a system of proteins that transports cargoes from one part of the cell (the endoplasmic reticulum) towards another (the Golgi). COPII is required for healthy cell and tissue physiology, and mutations in COPII genes cause a variety of inherited human diseases of the nervous system and skeleton, yet the mechanisms that cells use to regulate COPII activity are largely unknown. We will take an interdisciplinary approach to study an emerging form of COPII regulation in which sugars are attached to COPII proteins to adjust their functions.

PI_NAMEs: BOYCE, MICHAEL S (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Address;Award;Biochemical;Biological;Biological Process;Brefeldin A;Capsid Proteins;Cell Cycle Progression;Cell membrane;Cell Physiology;Cell Proliferation;Cells;Cellular biology;Chemicals;Chondrocytes;Collagen;Complex;Cues;Data;Defect;Development;Disease;Dysplasia;Endoplasmic Reticulum;experimental study;extracellular;First Independent Research Support and Transition Awards;Functional disorder;Genes;genetic approach;Glucose;glycoproteomics;glycosylation;Goals;Golgi Apparatus;Hematological Disease;Hematology;Homeostasis;Human;human disease;Human Pathology;Individual;Inherited;insight;interdisciplinary approach;Kinetics;Knowledge;Link;Location;Mammalian Cell;Mass Spectrum Analysis;Mediating;Membrane;Metabolic;Metabolism;Methods;Modification;Molecular;Mutation;Nervous System Disorder;Neurologic;Normal Cell;Normal tissue morphology;novel;Nutrient;O-GlcNAc transferase;Osteogenesis Imperfecta;paralogous gene;Pathologic;Pathway interactions;peptide O-linked N-acetylglucosamine-beta-N-acetylglucosaminidase;Phosphorylation;Physiological;Physiology;pointed protein;Prevalence Study;protein complex;Protein Glycosylation;protein protein interaction;Protein Secretion;Protein Sortings;protein transport;Proteins;Proteome;Proteomics;Regulation;response;Role;Signal Transduction;Sirolimus;Site;Skeleton;Sorting;Starvation;Stimulus;Stress;sugar;Surgical sutures;System;Tissues;trafficking;Vertebrates;Vesicle;Work;Zebrafish

PROJECT_TITLE: Control of COPII vesicle trafficking by intracellular protein glycosylation

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


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Clinical Research;Clinical Trials and Supportive Activities;Emerging Infectious Diseases;Immunization;Infectious Diseases;Influenza;Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: NASHVILLE

ORG_NAME: VANDERBILT UNIVERSITY MEDICAL CENTER

ORG_STATE: TN

PHR: PROJECT NARRATIVE The goal of the Vanderbilt VTEU is to leverage the robust clinical research environments at four major US institutions to conduct high quality clinical research across the age spectrum and covering multiple infectious diseases. We will focus on our areas of strength, which includes early phase clinical trials of new vaccines and therapeutics; innovative laboratory assays; rapid enrollment, including enrollment of special populations; subject matter expertise across infectious diseases, including bacterial, viral, respiratory, parasitic, and sexually transmitted infections; and training of young vaccinologists and clinical trialists.

PI_NAMEs: CREECH, CLARENCE BUDDY (contact)

PROGRAM_OFFICER_NAME: LARKIN, BRENDA D

PROJECT_TERMS: Academic Medical Centers;Adult;Age;antibiotic resistant infections;Area;Articulation;Award;Bacterial Infections;Biological Assay;Biological Products;career;career development;Child;Childhood;Clinical;Clinical Investigator;Clinical Research;clinical research site;Clinical Trials;Collaborations;Communicable Diseases;comorbidity;Conduct Clinical Trials;Data;design;Development;Disease;early phase clinical trial;Education;Elderly;Emerging Communicable Diseases;emerging pathogen;Enrollment;Environment;ethnic diversity;Evaluation;experience;Faculty;Feasibility Studies;Fellowship;Fostering;Funding;Geography;Goals;Home;Human;Immune response;Immunity;Immunization;immunogenicity;Immunologist;Individual;Infant;Infection;Influenza;influenza virus vaccine;innovation;Institution;International;Intervention;Laboratories;Laboratory Scientists;Lead;Leadership;Licensure;life span;Malaria;Malaria Vaccines;Medical;Medical center;Mentors;Mentorship;Methods;Modeling;Mycoses;next generation;novel;novel strategies;novel therapeutics;novel vaccines;Nurses;pandemic influenza;pandemic response;Parasitic infection;pathogen;Pathogenesis;Pennsylvania;Pertussis Vaccine;Peru;Pharmaceutical Preparations;Phase;Physicians;Pneumococcal vaccine;Population;Population Heterogeneity;Positioning Attribute;Pregnant Women;Prevention;Principal Investigator;Procedures;Process;Protocols documentation;Qualifying;recruit;Research;Research Infrastructure;Research Personnel;research study;respiratory;response;Safety;Scientist;Sexually Transmitted Diseases;Site;Smallpox Vaccine;Special Population;Standardization;Systems Biology;Tissues;tool;Training;United States National Institutes of Health;Universities;Vaccination;vaccine immunogenicity;Vaccine Research;vaccine trial;Vaccines;vaccinology;Viral;Virus Diseases;Visit;volunteer;Washington;Work

PROJECT_TITLE: Vanderbilt Vaccine and Treatment Evaluation Unit


NIH_SPENDING_CATS: Clinical Research;Genetics;Human Genome;Kidney Disease;Organ Transplantation;Transplantation

ORG_DEPT: SURGERY

PHR: NARRATIVE We have discovered that the expression of cytokines by B cells prior to kidney transplantation can identify patients who are at increased risk for rejection and loss of their transplants. B cell cytokines remain stable and the immunological risk associated with this stability appears pre-determined in some patients, while in others the cytokine expression changes after transplantation along with the patient’s risk status. The proposed study will identify the genetic regulatory mechanisms that maintain stability vs. plasticity in the B cells, allowing us to accurately determine a patient’s risk for rejection prior to transplantation, and individualize immunosuppression, while providing novel insights into the mechanisms that regulate immunological reactivity.

PI_NAMEs: CHERUKURI, ARAVIND  (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Acute;Adult;Advisory Committees;Affect;allograft rejection;Allografting;antimicrobial;ATAC-seq;Autoimmune;Autoimmune Diseases;B-Cell Acute Lymphoblastic Leukemia;B-Lymphocyte Subsets;B-Lymphocytes;Basic Science;Bioinformatics;Biological Markers;Biology;Biopsy;bisulfite sequencing;career;Cells;Characteristics;Chronic;Clinical;Clinical Sciences;Clinical Trials Design;cytokine;Cytokine Gene;demographics;Diagnosis;Dialysis procedure;differential expression;DNA;End stage renal failure;Epigenetic Process;epigenetic regulation;Exhibits;Fibrosis;Gene Expression;Genes;Genetic;Genetic Crossing Over;Genetic Polymorphism;Genetic Transcription;Genetic Variation;Genomics;Goals;Graft Survival;high risk;Human;Human Genetics;Immune response;Immunologics;Immunology;Immunosuppression;Individual;individual patient;Inflammation;Injury;insight;Interleukin-10;International;kidney allograft;Kidney Transplantation;Lead;Maps;Mentors;Methylation;Monitor;Multicenter Studies;novel;Outcome;Patient risk;patient stratification;Patients;peripheral blood;Physicians;post-transplant;predictive marker;Predictive Value;prevent;prospective;Records;recruit;Research;Research Personnel;response;Risk;Risk Assessment;risk stratification;Scientist;Single Nucleotide Polymorphism Map;skills;Statistical Models;System;Techniques;tenure track;Testing;therapeutic target;Time;TNF gene;Training;Transcriptional Regulation;transcriptome;transcriptome sequencing;translational applications;Translational Research;Transplant Recipients;Transplantation;Transplantation Immunology;treatment choice;tumor;unsupervised learning

PROJECT_TITLE: Epigenetic Regulation of Regulatory B Cell Cytokine Expression and Allograft Rejection

STUDY_SECTION: AITC

STUDY_SECTION_NAME: Allergy, Immunology, and Transplantation Research Committee[AITC]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Bioengineering;Nanotechnology

ORG_CITY: SALT LAKE CITY

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: PROJECT NARRATIVE Exposure to inorganic nanoparticles can have adverse human health effects. In this application we aim to understand how properties of silica nanoparticles such as size, porosity, surface modification, and geometry influence the fate and function of macrophages, bone marrow toxicity, and immune adverse effects.

PI_NAMEs: GHANDEHARI, HAMID  (contact)

PROGRAM_OFFICER_NAME: RAVICHANDRAN, LINGAMANAIDU V

PROJECT_TERMS: Acute;Address;Adsorption;Adverse effects;Affect;Animal Model;Animals;Antibodies;Applications Grants;Bacteria;Biodistribution;Biological;biomaterial compatibility;Blood;Bone Marrow;Cell Cycle;Cell division;Cessation of life;Characteristics;Chronic;Cues;cytotoxicity;density;Dependence;Dose;Drug Carriers;Drug Delivery Systems;Exposure to;Female;Frequencies;Gene Expression;Generations;Genes;Genetic Transcription;genotoxicity;Geometry;granulocyte;Health;Hormones;Human;Immune;immune function;Immune response;Immune signaling;Immune system;Immunoglobulin G;Immunoglobulin M;Immunologics;immunotoxicity;In Vitro;in vivo;Inbred BALB C Mice;Inflammasome;Inflammatory;Inflammatory Response;innovation;Intravenous;intravenous administration;intravenous injection;Investigation;Knowledge;Leukocytes;Liver;Liver Extract;Lung;Lymphocyte;Macrophage;male;Maximum Tolerated Dose;Mediating;Metabolic Clearance Rate;Metabolism;Modification;Molecular;monocyte;Mononuclear;Mus;nano;nanoparticle;neutrophil;Organ;overexpression;particle;patient population;peripheral blood;Phagocytes;Phenotype;Pluripotent Stem Cells;Porosity;Proliferating;Property;Proteins;Rattus;Recovery;response;Safety;sex;side effect;Signal Pathway;Signal Transduction;Silicon Dioxide;Spleen;Surface;System;Testing;Time;Tissues;Toxic effect;uptake;Variant;Whole Blood;women versus men

PROJECT_TITLE: BIOLOGICAL FATE AND BIOCOMPATIBILITY OF SILICA-BASED NANOCONSTRUCTS

STUDY_SECTION: NANO

STUDY_SECTION_NAME: Nanotechnology Study Section[NANO]


PHR: Of the 150,000 patients annually undergoing coronary artery bypass grafting (CABG) surgery in the U.S., 35% develop complications whose impact may outweigh the operation’s benefit. Despite being vastly understudied, surgical technical skills and non-technical practices likely contribute to variability in the rate of these complications. As a necessary prerequisite for targeted quality improvement, we currently seek to: (i) identify potentially modifiable technical skills and non-technical practices associated with complications following CABG surgery, and (ii) evaluate the feasibility of using an objective computer-based platform for automated identification and tracking of significant intraoperative determinants of risk-adjusted patient complications.

PI_NAMEs: LIKOSKY, DONALD S (contact);PAGANI, FRANCIS D;YULE, STEVEN

PROGRAM_OFFICER_NAME: HALLER, JOHN WAYNE

PROJECT_TERMS: Adoption;Awareness;Cardiac Surgery procedures;Cardiopulmonary Bypass;Caring;Characteristics;clinical practice;Clinical Research;Communication;Complication;Computers;Coronary Artery Bypass;Data;Ensure;Environment;Evaluation;evidence base;Expenditure;Goals;hemodynamics;high dimensionality;Hospital complications;Hospitals;Human;Human Activities;implementation research;improved;Individual;instrument;Intraoperative Care;Leadership;Length of Stay;Link;Maps;Measures;Medical;member;mortality;Multicenter Studies;multidisciplinary;National Heart, Lung, and Blood Institute;novel;operation;Operative Surgical Procedures;Outcome;Patient risk;Patients;peer;Performance;Phase;Phase Transition;Physicians;Process;Provider;psychologic;Research;Risk Adjustment;Risk Factors;skills;Societies;Source;Structure;Surgeon;surgery outcome;Surgical complication;System;Taxonomy;Technical Expertise;Thoracic Surgeon;Variant;Video Recording;Videotape

PROJECT_TITLE: Novel Assessments of Technical and Non-Technical Cardiac Surgery Quality

STUDY_SECTION: HSOD

STUDY_SECTION_NAME: Health Services Organization and Delivery Study Section[HSOD]


ORG_CITY: IOWA CITY

ORG_NAME: UNIVERSITY OF IOWA

PHR: Project Narrative Epilepsy is a very common neurological disease with high morbidity and mortality. The proposed studies will help to better understand how the mitochondrial Ca2+ uniporter (MCU) contributes to the regulation of neural network activity and susceptibility to seizures and epilepsy, as well as to establish the role of MCU in neuronal damage associated with epilepsy. This work is expected to provide mechanistic insight into strong anticonvulsant effects of MCU deletion, thereby laying a foundation for future translational research focused on MCU.

PI_NAMEs: USACHEV, YURIY M (contact)

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TERMS: Affect;Anticonvulsants;behavior test;Behavioral;Bioenergetics;calmodulin-dependent protein kinase II;Cause of Death;Cell Death;Chronic;Cognitive deficits;Complex;Data;Development;Electroconvulsive Shock;Electrophysiology (science);Epilepsy;excitatory neuron;excitotoxicity;Fluorescent Probes;Foundations;Future;Generations;Genetic Engineering;Glutamates;high risk;Hippocampus;Impaired cognition;In Vitro;in vivo;Induced Neurons;Inner mitochondrial membrane;insight;Intervention;Intractable Epilepsy;Knock-out;Knockout Mice;Mitochondria;Modeling;Morbidity - disease rate;mortality;motor deficit;mouse model;Mus;Nervous System Disorder;neural;neural network;neuron loss;neuronal excitability;Neurons;neuroprotection;neuroregulation;neurotoxicity;novel;optogenetics;patch clamp;patient population;Patients;Persons;Pharmacologic Substance;Pilocarpine;Pilot Projects;Play;Predisposition;presynaptic;prevent;Process;Property;psychiatric comorbidity;Regulation;Role;Seizures;Sensory;Signal Transduction;Slice;sudden unexpected death in epilepsy;Synapses;synaptic function;Synaptic Transmission;Temporal Lobe Epilepsy;Testing;therapeutic target;Toxic effect;Translational Research;transmission process;uptake;Work

PROJECT_TITLE: The mitochondrial Ca2+ uniporter in the regulation of neural activity and susceptibility to seizures


NIH_SPENDING_CATS: Behavioral and Social Science;Biodefense and Related Countermeasures;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Emerging Infectious Diseases;HIV/AIDS;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Infectious Diseases;Orphan Drug;Pediatric;Prevention;Rare Diseases;Tuberculosis;Women's Health Research

PHR: 8. Project Narrative The Wits HIV Research Group Clinical Trials Unit (WHRG CTU) consists of four pleuripotent Clinical Research Sites-The Wits Helen Joseph Hospital CRS, The Wits RHI Shandukani Maternal and Child CRS, Wits RHI Hillbrow Health Precinct Ward 21 CRS and the Wits RHI Research Centre. The WHRG CTU research agenda includes HIV treatment, HIV-associated infections and HIV-related cancers; HIV prevention; TB treatment and prevention (including MDR-TB) and Hepatitis. The CTU conducts research across key populations, including adolescent girls and young women, men who have sex with men, transgender populations and female sex workers; as well as vulnerable populations such as neonates, infants, older children, pregnant and breastfeeding women to a high standard of quality, which has been recognized locally and internationally.

PI_NAMEs: REES, HELEN ;SANNE, IAN MATTHIAS (contact)

PROGRAM_OFFICER_NAME: COATES, CINDY KAREN

PROJECT_TERMS: Adolescent;Adult;AIDS clinical trial group;AIDS prevention;antiretroviral therapy;Blinded;Breast Feeding;Child;Childhood;clinical center;clinical development;Clinical Research;clinical research site;Clinical Trials;Clinical Trials Cooperative Group;Clinical Trials Network;Clinical Trials Unit;Collaborations;Communities;community engagement;comorbidity;Conduct Clinical Trials;Contracts;Data;data management;Development;Elements;Ensure;Epidemic;Equipment;Ethics;experience;Female Adolescents;female sex worker;Funding;Good Clinical Practice;Health;Hepatitis;high risk;high standard;HIV;HIV prevention trials network;HIV/AIDS;Hospitals;Individual;Infant;Infection;Infrastructure;Infusion procedures;Injectable;Institution;International;International Maternal Pediatric Adolescent AIDS Clinical Trials;Investigational Drugs;Joints;Laboratories;Leadership;Legal;Malignant Neoplasms;Medicine;men who have sex with men;Mentors;microbicide;Monoclonal Antibodies;Morbidity - disease rate;mortality;Multidrug-Resistant Tuberculosis;National Institute of Allergy and Infectious Disease;neonate;Occupational activity of managing finances;Office of Administrative Management;Oral;patient population;Persons;Pharmacy facility;Phase;Policies;Population;population based;pregnant;Pregnant Women;Prevention;Prevention Research;Procedures;Process;randomized trial;Reapplication;recruit;Research;Research Activity;Research Infrastructure;Research Personnel;Sampling;Site;South Africa;Structure;study population;Testing;Therapeutic;Training;transgender;transmission process;treatment research;Tuberculosis;tuberculosis treatment;U-Series Cooperative Agreements;United States National Institutes of Health;vaccine trial;Vaccines;VTN gene;Vulnerable Populations;ward;Wit;Woman;young woman

PROJECT_TITLE: Wits HIV Research Group CLINICAL TRIAL UNIT (CTU) reapplication


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

ORG_CITY: DALLAS

ORG_DEPT: PSYCHIATRY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: PROJECT NARRATIVE Although malfunctions of temporal association learning represent well-described findings in human patients suffering from schizophrenia and Alzheimer's disease, it remains unknown about the neural mechanisms that drive and regulate temporal association learning. Our proposed studies aim to mechanistically understand neural circuits and their neural processes in entorhinal cortical-hippocampal networks for driving and regulating temporal association learning. Our proposed studies will uncover neural substrates for temporal association memory and novel learning-dependent gatekeeper circuit for the regulation of trace fear conditioning, and potentially, the circuit mechanism can be a pharmaceutical new target for preventing inadequate memory formation.

PI_NAMEs: KITAMURA, TAKASHI  (contact)

PROGRAM_OFFICER_NAME: VICENTIC, ALEKSANDRA

PROJECT_TERMS: Alzheimer's Disease;Association Learning;Automobile Driving;Behavioral Paradigm;Calcium;Cells;CHRM1 gene;Cognitive;conditioned fear;Data;Disinhibition;Dopamine D1 Receptor;entorhinal cortex;Episodic memory;Event;field study;FOS gene;Gatekeeping;genetic manipulation;Goals;Hippocampus;Human;Image;in vivo;in vivo calcium imaging;Knockout Mice;Knowledge;Learning;locus ceruleus structure;Maps;Medial;Mediating;Memory;metabotropic glutamate receptor type 1;Modeling;Molecular;Motor;Muscarinic Acetylcholine Receptor;neural;neural circuit;Neural Inhibition;Neurobiology;neuromechanism;Neurons;novel;optogenetics;Patients;Performance;Pharmacologic Substance;prevent;Process;Pyramidal Cells;Receptor Activation;Regulation;Research;Role;Schizophrenia;segregation;Sensory;System;Testing;Theoretical model;Transgenic Mice;Ventral Tegmental Area;Viral

PROJECT_TITLE: Neural circuit mechanisms for temporal association learning

STUDY_SECTION: LAM

STUDY_SECTION_NAME: Neurobiology of Learning and Memory Study Section[LAM]


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

ORG_CITY: HANOVER

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: DARTMOUTH COLLEGE

ORG_STATE: NH

PHR: Currently, there is no drug or strategy that targets or eliminates dormant Toxoplasma gondii infection. This project will identify and validate a metabolic basis to eliminate the dormant stage of Toxoplasma gondii infection. The results obtained in this work will advance mechanistic understanding of dormancy, and will illuminate and test new strategies that can eliminate the dormant stage of infection.

PI_NAMEs: BZIK, DAVID J (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TITLE: Metabolic basis for the persistence of dormant Toxoplasma gondii infection


NIH_SPENDING_CATS: Brain Disorders;Cancer;Lung;Lymphatic Research;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Tuberous Sclerosis;Women's Health Research

ORG_CITY: LUBBOCK

ORG_NAME: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER

PHR: PROJECT NARRATIVE The treatment options for patients with lymphangioleiomyomatosis (LAM) are very limited. Therefore, the goal of this research is to provide the pre-clinical proof-of-concept that targeting the extracellular vesicle pathway could be considered as new therapy for LAM.

PI_NAMEs: KARBOWNICZEK, MAGDALENA  (contact);YU, JANE

PROGRAM_OFFICER_NAME: VUGA, LOUIS J

PROJECT_TERMS: Address;Adverse effects;Affect;Biogenesis;Biological Markers;cancer stem cell;CCI-779;Cell Separation;Cells;Circulation;Clinical Trials;Data;drug repurposing;Drug Targeting;experimental study;Extracellular Matrix;extracellular vesicles;Fibroblasts;Foundations;FRAP1 gene;Genotype;Goals;Growth;Image;improved outcome;In Vitro;in vivo;Individual;inhibitor;Integrins;Knockout Mice;Knowledge;Lead;loss of function mutation;Lung;Lung Lymphangioleiomyomatosis;Lymphangioleiomyomatosis;Malignant Neoplasms;Mediating;Metastatic Neoplasm to the Lung;migration;Modeling;mouse model;mTOR Inhibitor;Mus;Myometrial;myometrium;Neoplasm Metastasis;new therapeutic target;novel;novel therapeutics;Null Lymphocytes;Pathogenesis;Pathway interactions;Patients;Pharmaceutical Preparations;Plasma;pre-clinical;Production;programs;Proliferating;Property;Proteome;Publishing;pulmonary function;Research;Respiratory Insufficiency;Role;Sampling;Sarcoma;Signal Pathway;Sirolimus;Smooth Muscle Tumor;Source;SRC gene;stem;stemness;System;Testing;tissue culture;TSC1/2 gene;tumor;tumor progression;uptake;Uterus;vesicular release;Woman

PROJECT_TITLE: Investigate the role of extracellular vesicles in promoting the progression of pulmonary lymphangioleiomyomatosis

STUDY_SECTION: TME

STUDY_SECTION_NAME: Tumor Microenvironment Study Section[TME]


ORG_CITY: MILWAUKEE

ORG_NAME: VERSITI WISCONSIN, INC.

ORG_STATE: WI

PHR: Project Narrative Public Health Relevance: The proposed project aims to investigate the signaling mechanisms underlying platelet activation and thrombosis in the context of inflammation. This research is quite relevant to public health in that current anticoagulant strategies are imperfect and the studies proposed herein to determine the role of platelet activation signaling in thromboinflammation may lead to subsequent development of rational therapies to treat and/or prevent thrombosis.

PI_NAMEs: BRANCHFORD, BRIAN R (contact)

PROGRAM_OFFICER_NAME: AGRAWAL, NITIN

PROJECT_TERMS: antagonist;Anticoagulants;Antiplatelet Drugs;base;Binding;Biological Assay;Blood Platelets;Blood Vessels;Cardiovascular system;career;career development;Cell Communication;Cells;Child;Childhood;Circulation;Clinical;cytokine;Data;design;Development;Development Plans;Disease;Distal;DNA;Endothelial Cells;Enzyme-Linked Immunosorbent Assay;Event;experience;experimental group;extracellular;Future;Genes;Genetic;Goals;Growth;Health;Hemorrhage;Histone H3;Homeostasis;In Vitro;in vivo;Inflammation;Inflammatory;inhibitor;Injury;ITGB3 gene;Kinetics;knowledge base;Leukocytes;Ligands;Mediating;meetings;Membrane;Mentors;Mentorship;Microfluidics;Modeling;mouse model;Mus;Names;neutrophil;novel;novel strategies;Pathway interactions;pharmacologic;Phosphatidylserines;Physicians;PIK3CG gene;Plasma;Platelet Activation;platelet function;Positioning Attribute;prevent;Protein Tyrosine Kinase;Public Health;public health relevance;rational design;Receptor Protein-Tyrosine Kinases;Reperfusion Injury;Reporting;Research;Research Personnel;response;RNA Splicing;Role;Sampling;Scholarship;Scientist;Signal Pathway;Signal Transduction;Signaling Molecule;skills;small molecule inhibitor;Structure of parenchyma of lung;Surface;Surface Plasmon Resonance;System;Testing;thromboinflammation;Thrombosis;Thrombus;Tissues;TNF gene;Training;Transgenic Mice;Translational Research;Up-Regulation;Variant;Western Blotting;Wild Type Mouse

PROJECT_TITLE: The role in inflammation in platelet activation and thrombosis

STUDY_SECTION: MCBS

STUDY_SECTION_NAME: NHLBI Mentored Clinical and Basic Science Study Section[MCBS(OA)]


NIH_SPENDING_CATS: Biotechnology;Lung;Pulmonary Fibrosis;Rare Diseases;Regenerative Medicine

ORG_CITY: ROCHESTER

ORG_NAME: MAYO CLINIC ROCHESTER

ORG_STATE: MN

PHR: Project Narrative Idiopathic Pulmonary Fibrosis is characterized by progressive scarring of the lung, but how the lung normally reverses scarring to functionally repair tissue is not well understood. The proposed studies will establish robust models in which to study extracellular matrix deposition, the defining characteristic of scarring, and its degradation and resorption. The proposed models will use both primary human fibroblasts and ex vivo tissues cultured from the lungs of individuals with IPF, providing new insight into the failure of scar resorption in IPF, and new targets through which to promote this critical process.

PI_NAMEs: TSCHUMPERLIN, DANIEL J. (contact)

PROGRAM_OFFICER_NAME: GOMEZ, CHRISTIAN RENE

PROJECT_TERMS: Address;Age;Alveolar;Animal Model;Appearance;Architecture;Biological;Biological Assay;Biological Models;Cell Communication;cell type;Cells;Cellular Assay;Characteristics;Chemicals;Cicatrix;Collagen;crosslink;Cyclic AMP;Data;Deposition;Disease;Environment;Epigenetic Process;Extracellular Matrix;Failure;Fibrillar Collagen;Fibroblasts;Fibrosis;fibrotic lung;Gases;Goals;high throughput screening;Human;idiopathic pulmonary fibrosis;Impairment;In Vitro;Individual;insight;Lung;lung repair;Macrophage;Mediating;Mediator;Metabolic;method development;miniaturize;Modeling;Molecular;Natural regeneration;novel;Organoids;Participant;Pathogenesis;Pathway interactions;Patients;pharmacologic;Physiological;Process;Pulmonary Fibrosis;repaired;Research;Signal Transduction;Slice;Sorting;Stimulus;Structure of parenchyma of lung;System;Testing;Therapeutic;therapeutic evaluation;Therapeutic Intervention;tissue culture;tissue repair;Tissues;tool;Variant;ventilation

PROJECT_TITLE: Therapeutic ECM Resorption in Cellular Systems and Precision Cut Lung Slices.


ORG_DEPT: PEDIATRICS

PHR: PROJECT NARRATIVE We and others have reported a role for pro-inflammatory “inflammasomes” in neurodegenerative disorders. Proposed studies will determine how exposure to pesticides that increase the risk of developing Parkinson’s disease (PD) can activate the inflammasomes in important brain cell types. Completion of the proposed work will improve our understanding of inflammation while informing rapidly advancing efforts to develop therapeutic agents designed to target the inflammasomes so that they can be used for the treatment of PD.

PI_NAMEs: HAVRDA, MATTHEW CHARLES (contact)

PROGRAM_OFFICER_NAME: HOLLANDER, JONATHAN

PROJECT_TERMS: age related chronic disease;age related neurodegeneration;Aging;Agricultural Workers;Alleles;Animals;Autopsy;Behavior;Biological;Biological Markers;Biology;Blood;Brain;brain cell;candidate identification;Cell Death;Cell Line;cell type;Cells;Cellular Stress;Central Nervous System;Clinic;Clinical Trials;cohort;combat;Complex;cytokine;Data;design;Detection;Development;diagnostic development;diagnostic tool;Disease;Disinhibition;Distress;dopaminergic neuron;Drug Targeting;Etiology;Exocytosis;Exposure to;Foundations;gain of function;gene environment interaction;Gene Modified;Genetic;healthy volunteer;Heavy Metals;Hyperactivity;improved;Incidence;Inflammasome;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;innovation;liquid chromatography mass spectrometry;loss of function;Mediating;Mediator;Microglia;Mitochondria;Modeling;Monitor;monocyte;mouse model;Multiprotein Complexes;Mus;Nerve Degeneration;Neurodegenerative Disorders;neuroinflammation;Neurons;neuroprotection;novel;Organism;Oxidative Stress;paracrine;Parkinson Disease;Parkinsonian Disorders;Pathway interactions;Patients;Pattern recognition receptor;pesticide exposure;Pesticides;Pharmaceutical Preparations;Phosphotransferases;Plasma;Predisposition;Process;promoter;Proteins;Publishing;Reporting;Risk;Role;Rotenone;Signal Transduction;small molecule therapeutics;Sterility;symptomatology;Symptoms;synuclein;Testing;Therapeutic Agents;Time;Tissues;Toxic Environmental Substances;toxicant;Toxicant exposure;Translating;translational study;Validation;Vesicle;Whole Organism;Work

PROJECT_TITLE: Mechanisms of pesticide-induced neuroinflammation and parkinsonism in aging mice.

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging;Brain Disorders;Genetics;Neurodegenerative;Neurosciences;Parkinson's Disease;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human

ORG_CITY: GAINESVILLE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative One of the common and unexplained features of Parkinson’s disease (PD) pathology is accumulation of iron in brain regions that are affected by the disease. Our published and preliminary data support a role of the PD gene LRRK2 in iron dyshomeostasis in neurons. We set out to interrogate the role of LRRK2 in affecting the way neurons handle iron, and thus leading to iron accumulation and neurodegeneration.

PI_NAMEs: MAMAIS, ADAMANTIOS  (contact)

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: Address;adenovirus mediated delivery;Affect;AGFG1 gene;autosome;Binding;Biochemical;Biological Assay;brain iron;Brain region;Cells;CRISPR/Cas technology;Cytoplasm;Data;Deposition;Disease;dopaminergic neuron;Dyes;Etiology;Event;experimental study;Future;Genes;Guanosine Triphosphate;Guanosine Triphosphate Phosphohydrolases;Heterozygote;Homeostasis;Human;human induced pluripotent stem cells;Image;imaging probe;In Vitro;in vivo;induced pluripotent stem cell;Induced pluripotent stem cell derived human neuron;Inductively Coupled Plasma Mass Spectrometry;Injections;Iron;iron metabolism;Knock-in Mouse;Link;live cell imaging;LRRK2 gene;Messenger RNA;Methods;Microscopy;Missense Mutation;Mitochondria;motor symptom;mutant;Mutation;Nerve Degeneration;Neuroglia;Neurons;novel;overexpression;Oxidative Stress;Parkinson Disease;pars compacta;Pathogenicity;Pathologic;Pathology;Patients;pharmacologic;Phenotype;Phosphorylation;Phosphotransferases;Physiological;Process;Production;Protein Family;protein protein interaction;Proteins;Publishing;rab GTP-Binding Proteins;Reporting;Role;Severities;Signal Transduction;sporadic Parkinson's Disease;Substantia nigra structure;System;Threonine;Up-Regulation;Western Blotting

PROJECT_TITLE: Dysregulation of iron homeostasis by mutant LRRK2 in human neurons

STUDY_SECTION: NOMD

STUDY_SECTION_NAME: Neural Oxidative Metabolism and Death Study Section[NOMD]


NIH_SPENDING_CATS: Aging;Breast Cancer;Cancer;Cancer Genomics;Estrogen;Genetics;Human Genome;Nutrition;Obesity;Prevention;Stem Cell Research;Stem Cell Research - Nonembryonic - Human;Women's Health Research

ORG_CITY: WASHINGTON

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: Project Narrative Obesity increases the hormone estrone, and both obesity and high estrone levels correlate with increased postmenopausal ER+ breast cancer risk. We investigate how actions of the dominant postmenopausal estrogen, estrone differ from premenopausal estradiol and how estrone stimulates unique gene expression patterns to drive the increased risk and mortality from hormone sensitive breast cancer after menopause. This work may reveal how obesity-related inflammation is linked to postmenopausal estrone and increased breast cancer risk and mortality, and ultimately help identify new therapeutic targets for ER+ breast cancer.

PI_NAMEs: SLINGERLAND, JOYCE MARIE (contact)

PROGRAM_OFFICER_NAME: BERA, TAPAN K

PROJECT_TERMS: 3-Dimensional;Adipocytes;American;Binding;Breast;Breast Cancer Cell;Breast Cancer cell line;breast cancer metastasis;Breast Cancer Risk Factor;Breast Cancer therapy;cancer cell;cancer prevention;cancer stem cell;CCL2 gene;cell type;Cells;ChIP-seq;Chromatin;Chronic;cytokine;Cytokine Gene;Data;Development;Drug resistance;epithelial to mesenchymal transition;ESR1 gene;Estradiol;Estrogen receptor positive;Estrogens;Estrone;Euchromatin;Expression Profiling;falls;Fatty acid glycerol esters;Gene Activation;Gene Expression;Gene Expression Profile;Gene Expression Regulation;gene induction;gene repression;Genes;genetic corepressor;Genetic Transcription;Grant;Growth;Heterochromatin;hormone therapy;Hormones;Human;IL6 gene;In Vitro;in vivo;Inflammation;Inflammatory;Ligands;Link;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Mammary Neoplasms;matrigel;MCF7 cell;Mediating;Molecular Conformation;mortality;mutant;Mutation;Neoplasm Metastasis;new therapeutic target;novel;Nuclear;Obesity;Obesity Epidemic;Oncogenes;Oncogenic;Organoids;Ovarian;p65;Postmenopause;Premenopause;Prevalence;Prevention strategy;Prognosis;programs;receptor binding;recruit;Regulation;Repression;Repressor Proteins;response;Response Elements;Risk;Sampling;Site;stem cell expansion;Testing;Thinness;Tissues;Trans-Activators;transcription factor;transcriptome;transcriptome sequencing;tumor;tumor growth;tumor initiation;tumor progression;Tumor Promotion;tumorigenesis;Woman;Work;Xenograft procedure

PROJECT_TITLE: Mechanistic Links Between Changing Estrogen Profiles, Inflammation and the Increased Risk and Metastasis of Breast Cancer in Obese Women

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Child Abuse and Neglect Research;Childhood Injury;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Pediatric;Physical Injury - Accidents and Adverse Effects;Unintentional Childhood Injury;Violence Research

ORG_CITY: BOSTON

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Project Narrative The key contribution of this proposal is the development, evaluation, and validation of a machine learning (ML) technique to improve the radiologist’s ability to date infant clavicle fractures—a common, telltale sign of inflicted injury in infants. If successful in the fulfillment of aims, this work will constitute the first rigorously tested and verified application of ML to date fractures with unprecedented precision and accuracy—as well as help buttress the diagnosis of abuse by determining if fractures of different ages are present. We expect this scientific innovation will enable the radiologist to more accurately detect, diagnose and treat this prevalent, life-threatening form of infant maltreatment.

PI_NAMEs: TSAI, ANDY  (contact)

PROGRAM_OFFICER_NAME: MAHOLMES, VALERIE

PROJECT_TERMS: 1 year old;Age;Algorithms;Artificial Intelligence;Birth;Blinded;bone;bone fracture repair;Cessation of life;Chest;Child;Child Abuse;clavicle;Clavicle Fracture;Clinical;Computational algorithm;Computers;Data;Databases;Development;Diagnosis;Educational process of instructing;Environment;Evaluation;experience;Fracture;Goals;healing;Image;improved;Individual;Infant;infant maltreatment;Injury;innovation;Investigation;Learning;Legal;Life;Literature;Logistic Models;long bone;Machine Learning;machine learning algorithm;Modeling;Morphology;Multiple Trauma;Outcome;Pattern;Performance;perpetrators;Play;Positioning Attribute;Public Health;radiologist;Radiology Specialty;Regression Analysis;Research Personnel;rib bone structure;Role;Site;skeletal injury;Skeletal Survey;social;support tools;Techniques;Testing;Time;timeline;tool;Training;Translating;traumatic event;Tubular formation;Validation;Work

PROJECT_TITLE: Machine learning Approaches to Radiological Dating of Infant Clavicle Fractures"


ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

PHR: PROJECT NARRATIVE This application focuses on the roles of the activation of the immune cells within visceral adipose tissue during sepsis in the elderly. We investigate how inflammasome activated-macrophages and adipose B cells contribute to impaired lipolysis during sepsis. The cellular signaling mechanisms that are identified will provide new therapeutic targets to reduce morbidity to septic infection in the elderly.

PI_NAMEs: CAMELL, CHRISTINA  (contact)

PROGRAM_OFFICER_NAME: TILAHUN, MULUALEM ENYEW

PROJECT_TERMS: Address;Adenosine;Adipocytes;Adipose tissue;Age;age related changes;aged;B-Lymphocytes;Bacterial Infections;Binding;Catecholamines;Cells;Chronic;Cyclic AMP-Dependent Protein Kinases;cytokine;Data;ecto-nucleotidase;Elderly;Endotoxemia;Environment;Event;Gram-Negative Bacteria;growth differentiation factor 3;Homeostasis;Hospitalization;Hydrolysis;Immune;immune activation;Immune system;Impaired cognition;Impairment;improved;Individual;Infection;Inflammaging;Inflammasome;Inflammation;Inflammatory;inhibitor;innovation;insulin sensitivity;Interleukin-1 beta;K-Series Research Career Programs;Life;Lipase;Lipids;Lipolysis;Lipopolysaccharides;Macrophage;Mediating;Mediator;Metabolic;Metabolic dysfunction;Metabolic Pathway;Metabolic syndrome;Modeling;Molecular;Morbidity - disease rate;mortality;mouse model;Mus;Myeloid Cells;new therapeutic target;Nonesterified Fatty Acids;old mice;older patient;Older Population;Operative Surgical Procedures;Organ;Organism;pathogenic bacteria;Pathway interactions;Pattern;pharmacologic;Population;Predisposition;prevent;Production;Purinergic P1 Receptors;receptor;response;Risk;Role;Sepsis;septic;Serum;Signal Pathway;Signal Transduction;single-cell RNA sequencing;sterol esterase;Survivors;Testing;therapeutic target;Tissue Expansion;Tissues;TLR4 gene;TNF gene;Triglycerides;Visceral

PROJECT_TITLE: Role of adipose tissue inflammaging and metabolic dysfunction during sepsis

STUDY_SECTION: CMAD

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