NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Liver Disease;Organ Transplantation;Transplantation

ORG_CITY: Columbus

ORG_NAME: OHIO STATE UNIVERSITY

PHR: PROJECT NARRATIVE Liver transplantation is limited by the donor organ quality; however, preservation of donor allograft integrity will significantly improve the outcome following transplantation. Our studies will test the therapeutic benefit of a tissue repair protein, MG53, delivered via normothermic ex-vivo liver perfusion to preserve and rescue liver function prior to and after liver transplant surgery.

PI_NAMEs: BLACK, SYLVESTER M (contact)

PROGRAM_OFFICER_NAME: SHERKER, AVERELL H

PROJECT_TERMS: Acetaminophen;Acute;Allografting;Animal Model;Biochemical;Biological;Black race;Blood;Blood Circulation;Cardiac Death;Cell membrane;Cell Survival;Cellular Structures;Circulation;Collaborations;Communities;Data;defined contribution;Development;Dose;Eligibility Determination;end stage liver disease;extracellular;falls;Formulation;Functional disorder;Goals;Heart;hepatocellular injury;Hepatocyte;hepatocyte injury;hepatoprotective;Human;Hypoxia;Imaging Device;imaging study;implantation;improved;improved outcome;Injury;injury and repair;Injury to Kidney;Ischemia;Kidney;Knowledge;live cell imaging;Liver;Liver Dysfunction;liver function;liver injury;liver preservation;liver transplantation;Lung;Measurable;Mediating;member;Membrane;Modality;Modeling;Molecular;Morbidity - disease rate;mortality;Mus;Muscle;novel;Organ Donor;organ injury;Organ Preservation;Organ Procurements;Organ Transplantation;Outcome;Overdose;Pathway interactions;Patients;Perfusion;Pharmaceutical Preparations;Phase;Phosphorylation;Physiological;Play;Predisposition;preservation;prevent;Principal Investigator;prophylactic;Protein Family;Proteins;Rattus;Reagent;Recombinants;repaired;Reperfusion Therapy;Research Design;Research Personnel;Risk;Rodent;Role;Safety;Scientist;Signal Transduction;Skeletal Muscle;Stress;Surgeon;Testing;Therapeutic;Therapeutic Agents;Therapeutic Effect;therapeutic evaluation;tissue repair;Tissues;Transgenic Mice;Translational Research;Transplantation;Transplantation Surgery;TRIM Family;Waiting Lists;Warm Ischemia

PROJECT_TITLE: Preservation of DCD Allograft Integrity for Liver Transplantation

STUDY_SECTION: HBPP

STUDY_SECTION_NAME: Hepatobiliary Pathophysiology Study Section[HBPP]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Neurosciences;Physical Activity;Physical Injury - Accidents and Adverse Effects;Physical Rehabilitation;Rehabilitation;Spinal Cord Injury;Traumatic Head and Spine Injury

ORG_CITY: PHILADELPHIA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_FIPS: US

ORG_NAME: DREXEL UNIVERSITY

ORG_STATE: PA

PHR: Narrative We will pursue studies in an incomplete model of chronic spinal cord injury (SCI), examining how a repeated treatment of transcutaneous stimulation contributes to decrease spasticity, hyperreflexia and improve motor function. We will determine if 6 weeks of repeated transcutaneous stimulation initiated acutely after injury before spasticity develops, or chronically once spasticity is established, leads to 1) a return in spinal inhibition, 2) an increase in motor output 3) improves locomotor recovery when delivered prior to a step-training program. Understanding the mechanisms underlying the beneficial effect of non-invasive interventions is critical to optimize clinical intervention and fast-track its use in the SCI community.

PI_NAMEs: COTE, MARIE-PASCALE  (contact)

PROGRAM_OFFICER_NAME: BAMBRICK, LINDA LOUISE

PROJECT_TERMS: Acute;Address;Aftercare;Animals;awake;Baclofen;Behavioral;behavioral outcome;Botulinum Toxins;Cell Nucleus;Cells;Chronic;Clinic;Clinical;clinical application;clinical practice;clinically relevant;Communities;Contusions;cost;Cytomegalovirus;design;Development;Dizziness;Electrodes;Equilibrium;evidence base;experience;experimental study;Feedback;Goals;H-Reflex;Hindlimb;Homosynaptic Depression;Hyperreflexia;improved;Individual;Injections;Injury;Intervention;Knowledge;Lead;Lesion;Locomotor Recovery;Locomotor training;Lumbar spinal cord structure;Manuals;Measures;Mental Depression;Modeling;Monitor;Motor;Motor Activity;Motor Evoked Potentials;motor function improvement;motor function recovery;Motor Neurons;Motor output;motor recovery;Movement;Muscle;National Institute of Neurological Disorders and Stroke;Neuronal Plasticity;Neurostimulation procedures of spinal cord tissue;Pathway interactions;Persons;pharmacologic;presynaptic;prevent;programs;Rattus;Recovery of Function;Reflex action;Rehabilitation therapy;Reporting;Research Project Grants;response;restoration;Sedation procedure;Severities;side effect;Site;skills;Spasm;spasticity;Spinal;Spinal Cord;Spinal cord injury;spinal reflex;Stains;Step training;Stretching;Swimming;Symptoms;Synapses;synaptic inhibition;Synaptic Transmission;Testing;Therapeutic;Time;time use;tizanidine;Toes;Touch sensation;Training Programs;transcutaneous stimulation;transmission process;Treatment Protocols;treatment strategy;United States National Institutes of Health

PROJECT_TITLE: Mechanisms of Action Contributing to Decrease Spasticity and Improve Motor Recovery with Repeated Transcutaneous Stimulation After Spinal Cord Injury

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Immunization;Immunotherapy;Infectious Diseases;Neurosciences;Prevention;Sexually Transmitted Infections;Vaccine Related;Women's Health Research

ORG_CITY: IRVINE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

ORG_STATE: CA

PHR: PROJECT NARRATIVE Traditional protein-based subunit vaccine strategies are effective at generating antibody responses but incapable of boosting robust memory T cell responses. The goal of this translational project is to develop a prime/pull therapeutic genital herpes vaccine, using new antigen delivery systems, to boost the number and function of antiviral tissue-resident memory CD4+ and CD8+ T cells. The insights gained from this translational vaccine research will inform the design of a prime/pull therapeutic genital herpes vaccine to be tested in the clinic.

PI_NAMEs: BENMOHAMED, LBACHIR  (contact)

PROGRAM_OFFICER_NAME: CONNOLLY, KRISTIE LEE

PROJECT_TERMS: Abbreviations;adeno-associated viral vector;Adult;Affect;Afferent Neurons;Age Years;Animal Model;Anti-viral Agents;Antibodies;Antibody Response;Antigens;Axon;B-Lymphocytes;Back;booster vaccine;candidate identification;Cavia;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;chemokine;Clinic;Clinical Trials;CXCL10 gene;CXCL11 gene;CXCL9 gene;CXCR3 gene;Data;design;Disease;Disease Outbreaks;Epithelium;FDA approved;Foundations;genital herpes;Goals;guinea pig model;healing;Herpesviridae Infections;HIV;Human;human disease;Human Herpesvirus 2;Immunity;improved;Infection;innovation;insight;Knowledge;latent infection;latent virus activation;Lesion;Licensing;Life Cycle Stages;Ligands;Medical;Memory;men;Mission;Modeling;multidisciplinary;nanoparticle;National Institute of Allergy and Infectious Disease;Neonatal Mortality;neonate;Nervous System Disorder;Neurons;neurotropic;novel;Peripheral;Persons;Pharmacotherapy;Phenotype;pre-clinical;preclinical study;Prevalence;prevent;Primary Infection;prophylactic;protective efficacy;Protein Subunits;Proteins;psychologic;Publishing;reactivation from latency;Recurrence;reproductive tract;Ribonucleotide Reductase Subunit;Risk;Safety;Satellite Viruses;Scientist;self assembly;seropositive;Simplexvirus;Site;Spinal Ganglia;Subunit Vaccines;Surface;Symptoms;System;T cell response;T memory cell;T-Lymphocyte;Testing;Therapeutic;therapeutic vaccine;Tissues;transcriptome sequencing;transcriptomics;translational goal;Travel;United States;Vaccine Research;vaccine strategy;Vaccine Therapy;Vaccines;Vagina;vaginal infection;vector;Viral;viral transmission;Virion;Virus;Virus Replication;VP 16;Woman

PROJECT_TITLE: A Novel Prime/Pull Therapeutic Vaccine Strategy to Prevent Recurrent Genital Herpes

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: NEW YORK

ORG_DEPT: PATHOLOGY

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Project Narrative  Our studies indicate that USP7 inhibition activates p53-mediated tumor suppression by downregulating both Mdm2 and Mdmx and induces p53-independent tumor growth suppression by destabilizing N-Myc and PD-L1. The major hypothesis to be tested here is whether USP7 inhibitors are more effective and better therapeutic agents for the treatment of human cancers.

PI_NAMEs: GU, WEI  (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Address;antitumor effect;Biological Assay;cancer cell;Cancer Patient;cancer therapy;Clinical Data;Clinical Trials;dosage;Dose Limiting;Down-Regulation;Event;Exhibits;Genotoxic Stress;Goals;high throughput screening;Human;Immunity;Immunotherapy;In Vitro;in vivo;inhibitor;Malignant Neoplasms;MDM2 gene;Mediating;mouse model;Mutate;Mutation;Neuroblastoma;new therapeutic target;Normal tissue morphology;novel;overexpression;Pathway interactions;Patients;PD-1 pathway;PD-1/PD-L1;Peptides;programmed cell death ligand 1;Proteins;Publishing;Resistance;restoration;Role;Signal Transduction;small molecule;small molecule inhibitor;Solubility;T-Lymphocyte;Testing;Therapeutic;Therapeutic Agents;therapeutically effective;Toxic effect;TP53 gene;tumor;tumor growth;Tumor Suppression;tumorigenesis;ubiquitin isopeptidase;Validation

PROJECT_TITLE: Novel small molecule USP7 Inhibitors for p53 activation and cancer therapy

STUDY_SECTION: DMP

STUDY_SECTION_NAME: Drug Discovery and Molecular Pharmacology Study Section[DMP]


NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Clinical Research;Neurodegenerative;Neurosciences;Rare Diseases

ORG_CITY: CHICAGO

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF CHICAGO

ORG_STATE: IL

PHR: Project Narrative  Amyotrophic lateral sclerosis is a uniformly fatal neurodegenerative disease that is difficult to diagnose in large part because there is no way to objectively measure the loss of the brain's signals to muscles. In this proposal, we will test the validity of a quick, inexpensive and painless biomarker of ALS known as intermuscular coherence in the real-world environment of the neurology clinic. If validated, intermuscular coherence could speed the diagnosis of ALS and the initiation of treatment, allow for objective measures of disease progression, and provide a way of quantifying the effects of future therapies in clinical trials.

PI_NAMEs: ISSA, NAOUM P;REZANIA, KOUROSH  (contact)

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Age;age effect;ALS patients;Amyotrophic Lateral Sclerosis;amyotrophic lateral sclerosis therapy;Animal Model;Biological Markers;Brain;Brain Injuries;Cessation of life;Clinic;Clinical;clinical development;Clinical Trials;cohort;Data;Diagnosis;diagnostic criteria;Disease;Disease Progression;drug development;Electromyography;Eligibility Determination;Enrollment;Environment;Equipment;Ethnic Origin;Evaluation;Frequencies;Future;Health Services Accessibility;Human;improved;in vivo;Measurement;Measures;Methods;Monitor;Motor;Motor Cortex;Motor Neurons;Multicenter Studies;Multicenter Trials;Muscle;Neurodegenerative Disorders;Neurology;neuron loss;Neuronal Dysfunction;neurophysiology;nonhuman primate;novel marker;Painless;Patients;potential biomarker;Progressive Disease;Race;Reporting;Respiratory Failure;Sensitivity and Specificity;sex;Signal Transduction;Specificity;Speed;Spinal;Spinal Cord;Subgroup;Surface;Symptoms;System;Testing;Therapeutic Intervention;Time;validation studies

PROJECT_TITLE: Intermuscular coherence: A novel biomarker for upper motor neuron dysfunction in ALS

STUDY_SECTION: CNN

STUDY_SECTION_NAME: Clinical Neuroscience and Neurodegeneration Study Section[CNN]


ADMINISTERING_IC: ES

ED_INST_TYPE: SCH ALLIED HEALTH PROFESSIONS

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Contraception/Reproduction;Endocrine Disruptors;Endometriosis;Estrogen;Pain Research;Prevention;Women's Health Research

ORG_CITY: FAIRFAX

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: GEORGE MASON UNIVERSITY

ORG_STATE: VA

PHR: PUBLIC HEALTH RELEVANCE: Endometriosis affects 6-11% of premenopausal women, causing pain, infertility, and billions of dollars in U.S. health care related costs annually. The proposed study aims to elucidate the influence of mixtures of endocrine disrupting chemicals measured in uterine tissue on endometriosis. This work will provide critical data on the role that per- and polyfluoroalkyl substances and persistent organic pollutants play in endometriosis at the target tissue level.

PI_NAMEs: POLLACK, ANNA ZULEMA (contact)

PROGRAM_OFFICER_NAME: BOYLES, ABEE

PROJECT_TERMS: Address;Adipose tissue;Affect;aged;analytical tool;biobank;Biological;California;Chemicals;clinical center;cohort;cost;Data;Development;Diabetes Mellitus;Diagnosis;Diet;Disease;Dose;Endocrine Disruptors;Endometrial;endometriosis;Endometrium;Enrollment;Environmental Exposure;epidemiology study;Estrogens;Etiology;experimental study;Female Genital Diseases;Future;Goals;Growth;Healthcare;Hormonal;Hormones;Human;Implant;Incidence;Infertility;Laparoscopic Surgical Procedures;Literature;Measures;Modeling;modifiable risk;National Institute of Child Health and Human Development;Natural History;novel;Operative Surgical Procedures;organochlorine pesticide;Outcome;Outcome Study;Pain;persistent organic pollutants;Play;Policies;Policy Maker;pollutant;Poly-fluoroalkyl substances;polybrominated diphenyl ether;Polychlorinated Biphenyls;Population;predictive modeling;Premenopause;prevent;Proxy;Public Health;public health relevance;Research Personnel;Resources;Risk Factors;Role;Scientific Advances and Accomplishments;Serum;Severities;Source;Stress;Testing;Tissues;Utah;Uterus;Visualization;Woman;Women's Health;Work

PROJECT_TITLE: Investigating Mixtures of Pollutants and Endometriosis in Tissue (IMPLANT) Study

STUDY_SECTION: IRAP

STUDY_SECTION_NAME: Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section[IRAP]


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Biotechnology;Brain Disorders;Gene Therapy;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: CHAMPAIGN

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

PHR: PROJECT NARRATIVE Amyotrophic lateral sclerosis (ALS) is a debilitating and invariably fatal disorder that can be caused by mutations in superoxide dismutase 1 (SOD1). We have developed an approach to inactivate the production of this mutant protein in vivo using CRISPR base editing, a gene-editing modality capable of introducing precise single-base substitutions in DNA, but without the requirement for a mutagenic DNA break. Now, we aim to refine this strategy by optimizing its targeting specificity, its editing capabilities, its pharmacokinetics and its safety for the ultimate goal of developing a permanently effective gene therapy for ALS.

PI_NAMEs: GAJ, THOMAS  (contact);PEREZ-PINERA, PABLO

PROGRAM_OFFICER_NAME: BOSHOFF, CHRIS

PROJECT_TERMS: Address;adenovirus mediated delivery;Adverse effects;Amyotrophic Lateral Sclerosis;amyotrophic lateral sclerosis therapy;Antisense Oligonucleotides;base;base editing;base editor;Brain;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;CRISPR/Cas technology;Dependovirus;Disease;Disease Progression;DNA;Dose;Drug Kinetics;effective therapy;efficacy evaluation;Ensure;Financial Hardship;Foundations;Future;gain of function mutation;gene editing technology;Gene Expression;Gene Silencing;gene therapy;Genes;Goals;Half-Life;Histologic;illness length;Immune response;Immunologics;Immunology;in vivo;Infusion procedures;innovation;Interdisciplinary Study;Lead;Life Cycle Stages;Link;Macaca fascicularis;meetings;Messenger RNA;Methods;Modality;Modeling;Molecular;Motor Neurons;mouse model;mutant;Mutation;Nervous System;Nervous System Disorder;neurotoxic;Nonhomologous DNA End Joining;nonhuman primate;novel;novel strategies;nuclease;Outcome;Paralysed;Pathway interactions;Patients;preclinical development;Probability;Production;Program Development;programs;Property;Proteins;recruit;Regimen;Reporting;Research;Risk;RNA Processing;Running;Safety;safety assessment;scaffold;Severities;Single base substitution;Specific qualifier value;Specificity;Spinal Cord;superoxide dismutase 1;Technology;therapeutic candidate;Therapeutic Effect;therapy development;Time;Toxicology;Variant;virtual

PROJECT_TITLE: Optimization of an in vivo base editing strategy to treat SOD1-linked ALS

STUDY_SECTION: NSD

STUDY_SECTION_NAME: Neurological Sciences and Disorders B Study Section[NSD-B]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: DALLAS

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

ORG_STATE: TX

PHR: The assembly and remodeling of RNA:protein complexes by DEAD-box proteins is a critical process in cells, and its dysregulation contributes to a range of human diseases, from inherited ribosomopathies to the progression of cancer and viral infection. Despite the central importance of these conserved RNA remodeling enzymes, we have only a basic understanding of their substrates, activity and regulation in cells. Using the large ribosomal biogenesis pathway, we are pursuing a combinatorial approach to determine the molecular functions of DEAD-box proteins in vitro and in vivo. !

PI_NAMEs: ERZBERGER, JAN PETER (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Affinity;ATP Hydrolysis;ATP phosphohydrolase;Binding;Biochemical;Biogenesis;Biological;biological adaptation to stress;Biological Models;Biophysics;cancer type;Cell Physiology;Cells;cofactor;Color;combinatorial;Complex;Coupling;crosslink;Cryoelectron Microscopy;Cytolysis;Defect;density;design;developmental disease;Disease;Dominant-Negative Mutation;Elements;Ensure;Enzymes;experimental study;Family;Freezing;Genetic;genetic manipulation;Genetic Recombination;Health;Heart;helicase;Heterogeneity;HIV;Hour;Human;human disease;Hybrids;improved;In Vitro;in vivo;Inherited;innovation;Kinetics;Life;Light;Malignant Neoplasms;Maps;Mass Spectrum Analysis;Messenger RNA;Methodology;milligram;Molecular;Monitor;Movement;mutant;Nature;novel;particle;Pathway interactions;Play;Point Mutation;Process;protein complex;protein function;Proteins;Proteome;Protocols documentation;Publishing;Quality Control;Reagent;reconstitution;reconstruction;Regulation;Research;Resolution;Ribonucleoproteins;Ribosomal Biogenesis Pathway;Ribosomes;ribosomopathy;RNA;RNA Processing;RNA Splicing;RNA Viruses;Role;Sampling;Signal Transduction;spatiotemporal;Structure;Telomere Maintenance;Testing;Time;tool;Translations;tumor progression;viral RNA;Virus Diseases;Visualization;West Nile;Yeasts

PROJECT_TITLE: Integrated studies of DEAD-box ATPase function during large ribosomal subunit maturation

STUDY_SECTION: MGA

STUDY_SECTION_NAME: Molecular Genetics A Study Section[MGA]


NIH_SPENDING_CATS: Cancer;Colorectal Cancer;Digestive Diseases;Immunotherapy;Liver Disease

ORG_CITY: SAN FRANCISCO

ORG_DEPT: SURGERY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Project Narrative Over the last decade, colon cancer and CRLM have increased in young U.S. men and women resulting in a 1% annual increase in mortality. The proposed research is relevant to public health because the discovery of strategies to optimize anti-tumor immune responses in this dis- ease is ultimately expected to improve patient outcomes compared to the best current thera- pies. Despite the exciting results of immunotherapy and checkpoint blockade in many previously therapy-resistant malignancies, the field is currently stymied in how to utilize this technology to battle microsatellite stable (>95%) colon cancer, and, as a result, the proposed research is rele- vant to the NIH's mission to develop improved immunotherapy approaches of novel combina- tions to define how immunosuppressive tumor promoting environments can be overcome.

PI_NAMEs: MAKER, AJAY V. (contact)

PROGRAM_OFFICER_NAME: ZAMISCH, MONICA

PROJECT_TERMS: Adult;anti-CTLA-4 therapy;anti-CTLA4;anti-tumor immune response;Antitumor Response;Autologous;Biology;cancer cell;Cancer Etiology;Cause of Death;Cells;Clinical;clinically relevant;colon cancer metastasis;colon cancer patients;Colon Carcinoma;Colonic Neoplasms;Colorectal;Combination immunotherapy;Combined Modality Therapy;CTLA4 blockade;cytotoxic;Data;Disease;Engineering;Environment;Goals;Human;humanized mouse;Immune;immune checkpoint blockade;Immune response;Immune system;Immunologic Stimulation;Immunotherapy;improved;in vivo Model;Incidence;Infiltration;innovation;Knowledge;Ligands;Liver;Lymphocyte;Lymphocyte Activation;Lymphocyte Function;lymphocyte proliferation;Lymphocytic Infiltrate;Malignant neoplasm of gastrointestinal tract;Malignant Neoplasms;Mediating;men;metastatic colorectal;Metastatic Neoplasm to the Liver;Methods;Microsatellite Repeats;Mission;mortality;mouse model;Mus;Neoplasm Metastasis;neoplastic cell;novel;novel strategies;oncolysis;Oncolytic;Operative Surgical Procedures;Outcome;overexpression;Paper;patient derived xenograft model;Patient-Focused Outcomes;Patients;pre-clinical;Pre-Clinical Model;Proliferating;Public Health;Publishing;Quality of life;reconstitution;Reproducibility;Research;Resected;response;Signal Transduction;Site;stem;System;T cell infiltration;T-Lymphocyte;Technology;Testing;Therapeutic;therapeutically effective;therapy resistant;trafficking;Translating;translational impact;Treatment Protocols;tumor;Tumor Expansion;tumor microenvironment;Tumor Promotion;United States National Institutes of Health;Viral;Woman

PROJECT_TITLE: Stimulating Lymphocyte Activation Combined with Inhibition of Immunosuppressive Signals in Colon Cancer Metastases

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Physical Injury - Accidents and Adverse Effects;Prevention;Regenerative Medicine;Wound Healing and Care

ORG_STATE: OH

PHR: Project Narrative Corneal wounds are complicated and common consequences of surgery, trauma, burns, and oxidative injury; inflammation and corneal neovascularization from corneal injuries are a leading cause of vision loss worldwide. There are currently no effective treatment options available to corneal neovascularization associated with injuries and development of new therapeutic options would benefit a large number of people. This project will clarify the role of a repair molecule in the cornea and conduct proof-of-principle studies for mitigating inflammation as well as neovascularization to treat complicated corneal wounds.

PI_NAMEs: CHANDLER, HEATHER ;ZHU, HUA  (contact)

PROGRAM_OFFICER_NAME: MCKIE, GEORGE ANN

PROJECT_TERMS: Ablation;Acute;Animals;Antibodies;Aqueous Humor;Attenuated;Binding;Biochemical;Blindness;Blood Vessels;Bone Marrow;Bone Marrow Transplantation;Burn injury;CASP1 gene;Cell Death;Cell membrane;Cell model;Cells;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Cornea;Corneal Diseases;corneal epithelial wound healing;corneal epithelium;Corneal Injury;Corneal Neovascularization;corneal regeneration;corneal scar;cytokine;Cytoplasmic Granules;Data;Development;Disease;Disulfiram;Doxycycline;effective therapy;Epithelial Cells;Epithelium;Etiology;experimental study;Fibrosis;Film;gene repair;Genetic;Growth;healing;Health;Homeostasis;Human;immune cell infiltrate;immune function;improved;In Vitro;in vivo;in vivo Model;Infiltration;Inflammation;Inflammatory;inhibitor;injured;Injury;injury and repair;Innate Immune Response;Interleukin-1 beta;Knock-out;Liposomes;live cell imaging;Macrophage;Mediating;Membrane;Modeling;Molecular;Mus;Mutagenesis;mutant;neovascularization;neutrophil;Neutrophil Infiltration;novel;novel therapeutics;Operative Surgical Procedures;Optics;Outcome;Outcomes Research;overexpression;oxidative damage;Pathologic;Pathway interactions;Pattern;Peptide Hydrolases;Peroxidases;Persons;pharmacologic;Phase;Play;prevent;Prevention;Process;protective effect;Protein Family;Proteins;Publishing;Reactive Oxygen Species;Recombinants;Regulation;repair function;repaired;reparative process;Resistance;response;Rodent Model;Role;Safety;Signal Transduction;Structure;Testing;tissue repair;Tissues;tool;Topical application;Transforming Growth Factor beta;Trauma;TRIM Family;Vascularization;Vision;Visual impairment;Wild Type Mouse;wound healing

PROJECT_TITLE: Inhibiting neovascularization for corneal wound healing

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


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: NARRATIVE The proposed project will generate a new technology making it possible to execute multiple genetic manipulations in a pre-programmed, sequential manner in cells. This advance will provide a means of recording information about a cell’s history (i.e. where it came from, whether it was exposed to a toxin or hormone) in its genome for reading by DNA sequencing.

PI_NAMEs: MERRILL, BRADLEY J (contact)

PROGRAM_OFFICER_NAME: YEH, ALVIN TIEN-WEI

PROJECT_TERMS: Bar Codes;beta catenin;Biological Process;biological systems;Biology;cell age;Cell Cycle;Cell division;Cell Lineage;Cell Physiology;cell type;Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Code;comparative;CRISPR/Cas technology;Dependence;design;Developmental Biology;DNA;DNA biosynthesis;DNA Sequence;DNA sequencing;Elements;Engineering;Event;Excision;experimental study;Exposure to;flexibility;G1 Phase;gene editing technology;genetic manipulation;Genetic Transcription;Genome;genome editing;Goals;Hormones;Individual;innovation;Instruction;interest;Link;Malignant Neoplasms;Mammalian Cell;Measurement;Mediating;Methods;Names;new technology;next generation;novel;nuclease;Positioning Attribute;prevent;Process;promoter;prototype;Reading;reconstitution;Recording of previous events;Records;repaired;Research;RNA;RNA Sequences;Sampling;Series;Signal Pathway;Signal Transduction;Special Equipment;stem cell biology;stem cells;System;Technology;Time;Toxin;WNT Signaling Pathway

PROJECT_TITLE: Harnessing multiplexed Cas9 genome editing for sequential genetic manipulations and recording activities in cell lineages

STUDY_SECTION: CMT

STUDY_SECTION_NAME: Cellular and Molecular Technologies Study Section[CMT]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Antimicrobial Resistance;Biotechnology;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Lung;Microbiome;Pediatric

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: NARRATIVE  Efforts to improve outcomes of lower respiratory tract infections (LRTI), the leading cause of infectious disease-related death in children worldwide, have been hampered by a lack of diagnostic tests capable of reliably informing decisions for targeted antimicrobial therapy. We will develop and test a novel metagenomic sequencing-based approach for LRTI diagnosis and rule-out by studying an existing prospective, multicenter cohort of critically ill children with acute respiratory failure. Our methods aim to change the paradigm of pulmonary diagnostics by enabling simultaneous detection of pathogens, antimicrobial resistance, the airway microbiome and the host’s response from a single sample of respiratory fluid.

PI_NAMEs: LANGELIER, CHARLES  (contact)

PROGRAM_OFFICER_NAME: NATARAJAN, ARUNA R

PROJECT_TERMS: accurate diagnosis;Acute;Acute respiratory failure;Address;adjudication;Admission activity;Adult;adverse drug reaction;adverse outcome;Algorithms;Antibiotics;antimicrobial;Antimicrobial Resistance;aspirate;Biological;Biological Testing;case control;Categories;Centers for Disease Control and Prevention (U.S.);Cessation of life;Child;Child Mortality;Childhood;Clinical;clinical predictors;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;co-infection;cohort;commensal microbes;Communicable Diseases;cost;Coupled;CRISPR/Cas technology;Critical Illness;Critically ill children;Culture-independent methods;Data;design;Detection;Diagnosis;Diagnostic;diagnostic criteria;Diagnostic tests;Elasticity;Elements;emerging antimicrobial resistance;Exclusion;Future;Gene Expression;genomic data;global health;Hour;Immune response;improved;improved outcome;Infection;infection management;Inflammatory;Inflammatory Response;Invaded;Lead;Liquid substance;Lower Respiratory Tract Infection;Lung;Mechanical ventilation;Medicine;metagenomic sequencing;Metagenomics;Methods;Microbe;microbial;microbial genomics;microbiome;Modeling;nanopore;next generation sequencing;novel;novel strategies;pathogen;Pathogen detection;pathogenic microbe;Patient-Focused Outcomes;Patients;performance tests;Population;Predictive Value;prospective;rapid detection;Rapid diagnostics;research clinical testing;Research Personnel;Resistance;resistance gene;resistome;respiratory;respiratory disorder diagnosis;respiratory microbiome;respiratory microbiota;Respiratory System;Sampling;Specimen;Syndrome;Technology;Testing;Time;Tissues;tool;Trachea;Transcript;transcriptome;transcriptomics;Viral;Work

PROJECT_TITLE: Integrated Host/Microbe Metagenomics to Improve Lower Respiratory Tract Infection Diagnosis in Critically Ill Children

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-PSE-N(90)]


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Clinical Research;Genetics;Human Genome;Precision Medicine;Skin Cancer

ORG_DEPT: GENETICS

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Project narrative Targeted therapies for melanoma promise to eradicate melanoma, but drug resistance remains an impediment to cures. We have developed approaches to analyzing the specific subpopulations of cancer that are resistant to drug, and are identifying the molecular pathways we can exploit to block resistant cells from forming.

PI_NAMEs: HERLYN, MEENHARD F;RAJ, ARJUN  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Affect;Bar Codes;Biological;Biology;BRAF gene;cancer cell;cancer drug resistance;Categories;Cell Line;Cell Survival;Cells;cellular transduction;Combined Modality Therapy;Complement;CRISPR/Cas technology;Development;Distant;DNA;Drug resistance;Epigenetic Process;Evolution;Gene Expression;Genes;genome-wide;Growth;Human;human model;Image;Immunotherapy;In Vitro;in vivo;in vivo Model;Individual;inhibitor;inhibitor therapy;kinase inhibitor;Libraries;MAP2K1 gene;MAP3K1 gene;MEKs;Melanoma;Melanoma Cell;Minor;Modeling;Molecular;Molecular Target;mouse model;mutant;Mutation;Nature;neoplastic cell;novel;novel strategies;novel therapeutic intervention;novel therapeutics;Organ;Pathway interactions;patient derived xenograft model;Patients;Pattern;Pharmaceutical Preparations;Pharmacotherapy;Phenotype;Population;preclinical study;programs;Proliferating;rational design;Relapse;relapse patients;repository;Resistance;Resistance development;resistance mechanism;Resistance Process;response;RNA;RNA analysis;Signal Pathway;single-cell RNA sequencing;Specimen;System;targeted treatment;Testing;Therapeutic;three dimensional cell culture;Time;transcriptomics;Treatment outcome;treatment response;treatment strategy;tumor;Tumor Cell Line;tumor heterogeneity;Validation

PROJECT_TITLE: Understanding and Overcoming Resistance to BRAF/MEK Kinase Inhibitors in Melanoma


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

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

ORG_DEPT: DENTISTRY

PHR: Project Narrative The intestinal parasite Cryptosporidium is a leading cause of diarrhea and death in immunocompromised individuals and malnourished children, and sterile immunity requires CD4+ T cells. Using a novel model antigen system, I have found that parasite-speciﬁc CD4+ T cell responses require type 1 conventional dendritic cells and evidence for a Th17 response associated with resistance to this infection. This project will investigate regulation of the CD4+ T cell response to Cryptosporidium through cross-disciplinary approaches in parasitology and mucosal immunology, furthering eﬀorts in treatment and prevention of an important source of childhood morbidity and mortality.

PI_NAMEs: COHN, IAN  (contact)

PROGRAM_OFFICER_NAME: PESCE, JOHN T

PROJECT_TERMS: adaptive immune response;Address;Antigen Presentation;Antigens;Architecture;Blocking Antibodies;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Physiology;Cells;Cessation of life;Child;Childhood;Cryptosporidiosis;Cryptosporidium;cytokine;Data;Defect;Dendritic Cells;Development;Diarrhea;diarrheal disease;Disease;Engineering;enteric infection;Epithelial Cells;Flow Cytometry;Generations;Genes;Genetic;genetic approach;high dimensionality;Human;IL17 gene;Immune system;Immunity;Immunocompetent;Immunocompromised Host;Immunology;in vivo;Individual;Infection;Inflammation;Interferon Type II;Interleukin-12;interleukin-22;Intestinal Diseases;intestinal epithelium;Intestinal parasite;Intestines;Investigation;Knock-out;Knowledge;large scale data;Learning;Maintenance;Malnutrition;Measures;Modeling;Morbidity - disease rate;mortality;mouse genetics;mouse model;Mucous Membrane;Mus;novel;Parasite Control;Parasites;Parasitology;pathogen;Phenotype;Physicians;Population;Prevention;Production;Regulation;Resistance to infection;response;Rest;Role;Scientist;single-cell RNA sequencing;skills;Small Intestines;Source;Sterility;System;T cell regulation;T cell response;T-Lymphocyte;Testing;Th1 Cells;Training;transcription factor;Transgenic Organisms;vaccine development;Work

PROJECT_TITLE: Regulation of CD4+ T cells in Cryptosporidium infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F07C-M(20)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Neurosciences;Physical Injury - Accidents and Adverse Effects;Traumatic Brain Injury (TBI);Traumatic Head and Spine Injury

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: PROJECT NARRATIVE Traumatic brain injury (TBI) is a major public health issue, which has a significant impact upon our healthcare system. Economic analyses of the annual cost of TBI-related disabilities range from $4.5 billion in direct expenditure (medical care and services) to $70.6 billion in injury-related work loss and disability. Our long- range goal is to determine the underlying mechanism(s) that cause injury-induced memory impairment and to continue to determine potential mechanisms and sites that can be leveraged into therapeutic regimes that can be translated from the bench to the clinic to ameliorate memory dysfunction in TBI patients.

PI_NAMEs: COHEN, AKIVA S (contact)

PROGRAM_OFFICER_NAME: AWWAD, HIBAH OMAR

PROJECT_TERMS: Action Potentials;Affect;Animal Model;Area;behavioral study;bench to bedside;Brain Concussion;Brain Injuries;Caring;Cause of Death;cell type;Child;Cholecystokinin;cost;Data;dentate gyrus;Direct Expenditure;disability;Discrimination;economic evaluation;Episodic memory;Equilibrium;fluid percussion injury;Frequencies;Functional disorder;genetic manipulation;Goals;Health;Healthcare Systems;Hippocampus;Human;Impaired cognition;Impairment;improved;In Vitro;in vivo;inhibitory neuron;Injury;innovation;Interneurons;Lateral;Learning;Life;Link;Measures;Mediating;Medical;Memory;Memory impairment;mild traumatic brain injury;Neurologic;neuronal circuitry;Neurons;Parvalbumins;Pathology;Performance;Persons;Population;Predisposition;Public Health;Research;Rodent;Services;Site;spatial memory;Stimulus;Study models;Survivors;Symptoms;synaptic inhibition;Synaptic Transmission;TBI Patients;Testing;Therapeutic;Time;Translating;Traumatic Brain Injury;United States;Work;young adult

PROJECT_TITLE: INJURY-INDUCED SPATIAL MEMORY IMPAIRMENTS ARE LINKED TO UNCOORDINATED HIPPOCAMPAL NEURONAL FIRING

STUDY_SECTION: ANIE

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


NIH_SPENDING_CATS: Asthma;Genetics;Lung

ORG_CITY: INDIANAPOLIS

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Project Narrative Asthma is a type of allergic airway disease that currently requires life-long medical management. We are investigating the role of a type of T cell that may exacerbate this disease. This investigation will inform pathology of allergic airway diseases and identify targets for disease intervention.

PI_NAMEs: NIESE, MICHELLE  (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Address;Affect;Airway Disease;Allergens;Allergic;allergic airway disease;Allergic Disease;Allergic inflammation;allergic response;Asthma;asthmatic;Binding;CD4 Positive T Lymphocytes;Cell Culture Techniques;Cell secretion;Cells;Child;Chromatin;Chromatin Structure;chromosome conformation capture;Chronic;Chronic Disease;chronic respiratory disease;Culture Media;cytokine;Data;defined contribution;Development;Disease;Enhancers;Euchromatin;Heterochromatin;histone modification;In Vitro;in vivo;insight;Integral Membrane Protein;Interleukin-13;Interleukin-9;Intervention;Investigation;knock-down;Lung;Mediating;Medical;member;Membrane Proteins;Modeling;mouse model;mRNA Expression;Mus;Necrosis;new therapeutic target;Pathogenesis;Pathogenicity;Pathology;Phenotype;polarized cell;Population;Production;promoter;Promoter Regions;protein expression;Reporting;response;Role;Severities;Severity of illness;Signal Transduction;single-cell RNA sequencing;Small Interfering RNA;Symptoms;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Th2 Cells;TNF gene;transcription factor;tumor

PROJECT_TITLE: Effect of TL1A on Th9 cell Polarization and Pathogenicity


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Social Determinants of Health

ORG_CITY: ANN ARBOR

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative This Summer Research Education Experience (Undergirding Potential – UP Program) collaborative training program is a partnership among University of Michigan and two historically black universities, Fisk University and Hampton University. We will train Fisk and Hampton undergraduates to be future leaders in environmental health sciences to accelerate discoveries into how environmental exposures affect human health and promote improvements in public health. Our program intends to contribute to a more effective and diverse workforce in environmental health sciences by engaging underrepresented students in research intensive experiences and inspiring them to continue their professional careers in environmental health sciences.

PI_NAMEs: CHARLES, SIMONE M (contact)

PROGRAM_OFFICER_NAME: HUMBLE, MICHAEL C

PROJECT_TERMS: Acceleration;Address;Affect;Air Pollutants;Area;Bachelor's Degree;Biological Markers;Biology;career;Career Choice;Chemistry;climate-related exposures;Collaborations;Communication;community college;Complement;data to knowledge;Degree program;Development;Discipline;Diverse Workforce;doctoral student;Ecology;Education;Education Projects;education research;Educational Activities;Educational workshop;Engineering;environmental enrichment for laboratory animals;Environmental Epidemiology;Environmental Exposure;Environmental Health;environmental health disparity;environmental justice;Environmental Science;environmental toxicology;Epigenetic Process;Evaluation;evidence base;experience;Faculty;faculty mentor;Feedback;Future;Genetic;Genomics;global health;Goals;Graduate Education;graduate school;graduate student;Grant;hands on research;Health;health science research;Health Sciences;Heavy Metals;Historically Black Colleges and Universities;Hour;Human;improved;Institution;interest;Internships;Intervention;Knowledge;Laboratories;lectures;Malignant Neoplasms;Mathematics;Measures;meetings;Mentors;Mentorship;Methods;Michigan;Mission;Modeling;Molecular;multidisciplinary;National Institute of Environmental Health Sciences;Outcome;outreach;Participant;peer;peer coaching;Pesticides;Physics;Plastics;Population;Postdoctoral Fellow;pre-doctoral;Prevention;Process;programs;Proteomics;Public Health;Public Health Schools;Records;recruit;Research;Research Project Grants;Research Training;response;responsible research conduct;Risk;Scholarship;Science;Site;skills;Strategic Planning;Structure;student mentoring;Student Selections;Students;success;summer program;summer research;symposium;tool;Toxicant exposure;Toxicology;Training;Training and Education;Training Programs;transcriptomics;Travel;undergraduate research;undergraduate student;Underrepresented Students;Universities;university student;Work

PROJECT_TITLE: Undergraduate research training for diversity in environmental health sciences


ED_INST_TYPE: HOSPITALS

NIH_SPENDING_CATS: Cancer;Clinical Research;Dental, Oral, and Craniofacial Disease;Digestive Diseases;Infectious Diseases;Precision Medicine;Prevention;Radiation Oncology;Rare Diseases;Sexually Transmitted Infections

ORG_CITY: HOUSTON

ORG_NAME: UNIVERSITY OF TX MD ANDERSON CAN CTR

PHR: PROJECT NARRATIVE Despite declining smoking rates in the U.S, the incidence of squamous cell carcinoma of the oropharynx (SCCOP) continues to increase dramatically, largely attributed to an increase in HPV prevalence; and as such, our public health SCCOP prevention paradigm must expand beyond tobacco and alcohol control. Identification of serum noncoding RNA-related biomarkers for patients with tumor HPV(+) SCCOP would have a major public health impact; and such novel noncoding RNA-related biomarkers could refine the prognostication of HPV(+) SCCOP, allowing for better selection of SCCOP patients for treatment deintensification and potentially other HPV-associated diseases. This has implications for our understanding of the molecular mechanism of HPV(+) SCCOP as well as an opportunity to significantly impact the screening and more personalized treatment of HPV(+) SCCOP for better survival and quality of life.

PI_NAMEs: LI, GUOJUN  (contact)

PROGRAM_OFFICER_NAME: FILIPSKI, KELLY

PROJECT_TERMS: Affect;Alcohols;Behavior;Bioinformatics;Biological Markers;Cancer Patient;Cell Line;Clinical;cohort;Diagnosis;Disease;Disease-Free Survival;Epidemiology;Etiology;Exhibits;functional outcomes;Genes;Genetic Transcription;Heterogeneity;HPV negative;HPV positive;Human;Human papilloma virus infection;human papilloma virus oropharyngeal squamous cell carcinoma;Human Papillomavirus;Immunologic Surveillance;improved;In Vitro;Incidence;Individual;individualized medicine;Infection;Inflammatory Response;interest;knock-down;Life;Malignant Neoplasms;malignant oropharynx neoplasm;Methods;MicroRNAs;Molecular;Morbidity - disease rate;Mutation;novel;novel marker;Oncogenes;Oncogenic;Oropharyngeal Squamous Cell Carcinoma;Outcome;Pathway interactions;patient biomarkers;patient prognosis;patient screening;patient stratification;Patients;personalized medicine;Physicians;Pilot Projects;Population;Population Study;predictive modeling;Predisposition;Prevalence;Prevention;Preventive vaccine;Prognosis;prognostic;Prognostic Marker;prognostication;Public Health;Quality of life;Radiation therapy;Radiation Tolerance;recruit;reduce tobacco use;response;Risk;screening;Serum;Smoking;smoking prevalence;surveillance strategy;survival prediction;Tissues;Tobacco;treatment response;treatment strategy;trend;tumor;Tumor Markers;Tumor Suppressor Proteins;University of Texas M D Anderson Cancer Center;Untranslated RNA;Vaccination;young adult

PROJECT_TITLE: Immuno-inflammatory Response Non-coding RNAs as Predictors of HPV Status & Outcome of Oropharyngeal Cancer Patients

STUDY_SECTION: CHSB

STUDY_SECTION_NAME: Cancer, Heart, and Sleep Epidemiology B Study Section[CHSB]


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

ORG_CITY: GALVESTON

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF TEXAS MED BR GALVESTON

PHR: PUBLIC HEALTH RELEVANCE This project will develop a new imaging tool to promote early detection of oral cancer, which accounts for nearly 640,000 new cases of cancer worldwide each year. We will develop a handheld wand that fits in the mouth and will illuminate the surface with light to highlight areas suspicious for early cancer and then image below the surface to see if cellular changes associated with high-risk precancer and cancer are found in those sites. This capability is aimed to improve biopsy guidance over the current practice of direct observation by the eye and palpation, ultimately improving patient survival.

PI_NAMEs: LI, XINGDE ;LIANG, RONGGUANG ;VARGAS, GRACIE  (contact)

PROGRAM_OFFICER_NAME: DARDZINSKI, BERNARD JOSEPH

PROJECT_TERMS: Address;Affect;Agreement;Animal Model;Animals;Area;Biochemical;biomarker identification;Biopsy;Carcinoma;cellular imaging;Cervix Uteri;Clinic;Clinical;clinical translation;Coupled;Detection;detection sensitivity;Development;Devices;Diagnostic;Early Diagnosis;Early identification;Early treatment;Engineering;Epithelium;Evaluation;Excision;Eye;Feedback;Fluorescence;Generations;Goals;high risk;Histology;Histopathology;Human;human imaging;Human Papillomavirus;human tissue;Image;imaging biomarker;imaging capabilities;Imaging Device;improved;in vivo;in vivo imaging;Incidence;instrument;Intraepithelial Neoplasia;Knowledge;Label;Lesion;Light;malignant mouth neoplasm;Malignant neoplasm of cervix uteri;Malignant Neoplasms;malignant oropharynx neoplasm;Measures;Metabolic;Methodology;Methods;Microscopic;microscopic imaging;Microscopy;Modality;Molecular;molecular imaging;Morbidity - disease rate;Morphology;mortality;Mucous Membrane;multi-photon;Neoplasms;neoplastic;non-invasive imaging;novel;Operative Surgical Procedures;Optical Biopsy;Optics;Oral;Oral cavity;oral cavity epithelium;Oral mucous membrane structure;Oropharyngeal;Oropharyngeal Squamous Cell Carcinoma;Outcome;Outcomes Research;Palpation;Pathology;Patient-Focused Outcomes;Patients;Performance;performance tests;Pilot Projects;pre-clinical;preclinical study;premalignant;public health relevance;Recurrence;Recurrent disease;Resolution;Robotics;Sampling;Sampling Studies;screening;Screening for Oral Cancer;second harmonic;Sensitivity and Specificity;Site;Specificity;Spectrum Analysis;Surface;Survival Rate;Testing;Tissues;Translating;Treatment outcome;Visual

PROJECT_TITLE: Bimodal Intraoral imaging device for detection of oral epithelial neoplasia


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Genetics;Infectious Diseases;Lung;Rare Diseases;Tuberculosis

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE Mycobacterium tuberculosis (Mtb) is an exceptionally successful human pathogen largely due to its unique mechanism of replication and the bacteria’s ability to slow or halt growth to promote its survival in vivo. The goal of this proposal is to define two novel regulatory networks that control Mtb cell division, and to demonstrate this regulation is important during tuberculosis infection, even when Mtb enters a slow or non-replicative state. Ultimately, this proposal will utilize cutting-edge genetic technology to interrogate the function of two previously uncharacterized, essential genes and determine how they function in vivo, which can aid with improving and developing therapeutics for treating tuberculosis.

PI_NAMEs: MARKS, FRANCES  (contact)

PROGRAM_OFFICER_NAME: MENDEZ, SUSANA

PROJECT_TERMS: Actinobacteria class;Acute;adaptive immune response;Affect;Alanine;analog;Antibiotics;Bacteria;Bacterial Infections;Binding Sites;Cell division;Cell Division Process;Cell Wall;Cells;cellular imaging;Cellular Structures;Chromosome Segregation;Chronic;Complex;CRISPR interference;Data;daughter cell;Defect;Development;disease model;DNA Binding;Drug Targeting;Essential Genes;Gene Expression;gene function;gene repression;Genes;Genetic;genetic technology;Genomics;Goals;Granuloma;Growth;Guide RNA;Homologous Gene;Host Defense;human pathogen;Immune;Immune response;Impairment;improved;In Vitro;in vivo;Infection;insight;knock-down;Lead;Macrophage;meter;Methods;Microscopy;Modeling;Morphology;mouse model;Mus;mutant;mycobacterial;Mycobacterium tuberculosis;novel;nutrient deprivation;Organism;pathogen;Pathogenesis;Persons;Phagosomes;Phenotype;Play;Population;Population Heterogeneity;Process;Proliferating;Proteins;Regulation;Regulatory Pathway;Regulon;Replication-Associated Process;Repression;Role;Sagittaria;Stains;Stress;Structure;success;Technology;Testing;Tetracyclines;Therapeutic;transcription factor;Translating;Tuberculosis;tuberculosis drugs;tuberculosis treatment;Visualization;Work

PROJECT_TITLE: Investigating genetic regulators of Mycobacterium tuberculosis cell division and their role in persistent tuberculosis infection


NIH_SPENDING_CATS: Biotechnology;Cancer;Climate-Related Exposures and Conditions;Contraception/Reproduction;Endocrine Disruptors;Genetics;Pediatric;Pregnancy;Prevention

ORG_CITY: WASHINGTON

ORG_NAME: GEORGETOWN UNIVERSITY

ORG_STATE: DC

PHR: Narrative Environmental exposures are known to leave molecular marks in paternal sperm and this molecular memory of past exposures can be transmitted, independent of DNA, to the next generation and affect their risk of disease. Our preliminary studies in mice show that paternal exposure to the pesticide DDT leads to placental alterations and fetal growth restriction, predisposing offspring to metabolic disease and cancer and we now propose to investigate whether sperm miRNAs (and possibly other small RNAs) are mechanistically linked to changes in placenta development. Defining the mechanisms by which paternal exposure to DDT and other environmental chemicals can promote changes in fetal and placenta development is critical to reducing diseases such as diabetes and cancer and could lead to potential placental biomarkers of parental exposure.

PI_NAMEs: DE ASSIS, SONIA  (contact)

PROGRAM_OFFICER_NAME: SCHUG, THADDEUS

PROJECT_TERMS: Acceleration;Adult;Affect;Age;Agriculture;American;Androgen Receptor;Animals;Attention;Biological Markers;blastocyst;Breast Cancer Risk Factor;C57BL/6 Mouse;Cell Culture Techniques;cell type;Cells;Chemicals;Child;chromatin remodeling;combat;Conceptions;Country;Data;Defect;Developing Countries;Development;Diabetes Mellitus;dichlorodiphenyltrichloroethane;Disease;disorder risk;DNA;Dose;early life exposure;Embryo;Endocrine Disruptors;Environment;environmental chemical;Environmental Exposure;Environmental Pollutants;Enzymes;epidemiology study;Epididymis;Epigenetic Process;Epithelial Cells;Epithelium;Europe;Euthanasia;experimental study;Exposure to;extracellular vesicles;EZH2 gene;Fathers;fetal;Fetal Development;Fetal Growth;Fetal Growth Retardation;Fetal Reduction;Fetal Tissues;Food;Gene Expression;Generations;Genetic Transcription;Genomic Segment;Goals;Growth;Half-Life;Health;Histology;Immigrant;Impairment;In Vitro;in vivo;Injections;Insecta;Link;Literature;Low Birth Weight Infant;Malaria;male;Malignant Neoplasms;Memory;men;Metabolic Diseases;Metabolic dysfunction;Microinjections;MicroRNAs;Minority;Molecular;Morphology;Mouse Cell Line;mouse model;Mus;National Institute of Environmental Health Sciences;next generation;non-genetic;Nutrient;offspring;Paternal Exposure;Pesticides;Phenotype;Placenta;Placentation;Population;pregnant;Preventive;programs;Proteins;Public Health;Publishing;Recommendation;reproductive;RNA;Role;sensor;Signal Transduction;Small RNA;Source;sperm cell;stem cell fate specification;Strategic Planning;Testing;Testis;tool;Toxic Environmental Substances;toxicant;Transcriptional Regulation;transcriptome sequencing;transmission process;trophoblast;United States;Untranslated RNA;Vascularization;zygote

PROJECT_TITLE: Paternal DDT exposure and programming of metabolic dysfunction and cancer in offspring: Understanding the role of sperm mirnas and placenta development

STUDY_SECTION: SIEE

STUDY_SECTION_NAME: Systemic Injury by Environmental Exposure[SIEE]


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

NIH_SPENDING_CATS: Brain Disorders;Neurosciences;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_DEPT: PSYCHOLOGY

ORG_NAME: OHIO STATE UNIVERSITY

PHR: The persistence of neural stem cells in isolated niches of the adult brain offers a potentially unique source of plasticity and regeneration. Understanding how neural stem cells contribute to adult brain plasticity is critical to determining the health-relevance of these cell populations. The proposed experiments will dissect the functional role of neural stem cell secreted proteins in modulating the physiology and behavioral function of the adult hippocampus, a brain region which mediates essential memory and affect functions which are impaired in numerous brain diseases and injuries.

PI_NAMEs: KIRBY, ELIZABETH DIANA (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Acute;Adult;adult neurogenesis;Affect;Amino Acids;Astrocytes;autocrine;Behavioral;behavioral response;Brain;Brain Diseases;brain health;Brain Injuries;Brain region;cell type;Cells;Cognitive;Collection;Coupled;cytokine;Cytoplasmic Granules;Data;dentate gyrus;Dimensions;Disease;emotion regulation;emotional functioning;Emotions;excitotoxicity;experimental study;Exposure to;Functional disorder;functional improvement;Gatekeeping;Genetic Code;Goals;Growth Factor;Health;Hippocampus;Homeostasis;Impairment;indexing;Individual;Influentials;Injury;insight;knock-down;life span;Literature;Mammals;Mediating;Memory;Modeling;Natural regeneration;nerve stem cell;neural;neurogenesis;Neurons;Neurophysiology - biologic function;paracrine;Parahippocampal Gyrus;Pattern;Physiology;pleiotropism;Population;Process;Production;progenitor;Protein Isoforms;Protein Secretion;Proteins;Recovery;Regulation;Reporting;Research;response to injury;Role;Shapes;Signal Transduction;Source;source localization;stem;stem cell proliferation;stem cells;Testing;Therapeutic;Time;tissue regeneration;Tissues;Transgenic Organisms;Undifferentiated;Vascular Endothelial Growth Factors;viral rescue;Work

PROJECT_TITLE: Regulation of adult hippocampal function by the neural stem and progenitor cell secretome

STUDY_SECTION: NCF

STUDY_SECTION_NAME: Neurogenesis and Cell Fate Study Section[NCF]


NIH_SPENDING_CATS: Genetics;Neurosciences

ORG_CITY: WORCESTER

ORG_NAME: UNIV OF MASSACHUSETTS MED SCH WORCESTER

ORG_STATE: MA

PHR: Project narrative Brain development requires precise mechanisms for ensuring that connections between neurons are properly formed. When these processes go awry, neural connections fail to form appropriately and brain function is compromised. We are studying the functions of newly identified molecules that perform key roles in shaping neural connections. Our work will have a foundational impact for human health by providing important knowledge and potential targets relevant to treatments for patients suffering from neurodevelopmental and neuropsychiatric disorders.

PI_NAMEs: FRANCIS, MICHAEL M (contact)

PROGRAM_OFFICER_NAME: CHURN, SEVERN BORDEN

PROJECT_TERMS: Address;Adolescent;Adult;Area;autism spectrum disorder;Biological Models;Brain;Caenorhabditis elegans;Cell Physiology;Cerebellum;cholinergic;Cholinergic Receptors;Chromatin;connectome;Defect;Dendrites;Dendritic Spines;Development;Developmental Process;Electron Microscopy;Ensure;Event;experimental study;F-Actin;Funding;Gene Targeting;Genes;Genetic;genetic approach;Genetic Models;Genetic Screening;Genetic study;Genetic Transcription;Goals;Health;homeodomain;Homologous Gene;Human;in vivo;innovation;Investigation;Knowledge;light microscopy;Modeling;Molecular;Molecular Analysis;Molecular Genetics;Motor;Nematoda;Nervous System;Nervous System Disorder;neural;neural circuit;Neurodevelopmental Disorder;Neurons;neuropsychiatric disorder;neuropsychiatry;new growth;novel;novel strategies;Pathway interactions;Patients;Pattern;Physiology;Positioning Attribute;postsynaptic;presynaptic;Process;programs;receptor;Regulation;Role;Schizophrenia;Shapes;Signal Transduction;Somatosensory Cortex;Specific qualifier value;Stimulus;Structure;Synapses;synaptogenesis;System;Testing;therapeutic candidate;Therapeutic Intervention;tool;transcription factor;transcriptome sequencing;Vertebral column;Visual System;Work

PROJECT_TITLE: Molecular Analysis of Neural Circuit Excitation and Inhibition

STUDY_SECTION: SYN

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


NIH_SPENDING_CATS: Biomedical Imaging;Biotechnology;Cancer;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Prostate Cancer;Racial and Ethnic Minority Health Research;Urologic Diseases

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: There is an urgent unmet need to develop innovative, effective therapies against aggressive prostate cancer subtypes. The goal of this project is to develop novel cyclic peptide therapeutics targeting the enzymatic activity of a metalloprotease that we found to be overexpressed in non-androgen receptor driven disease and the prostate cancer of African American men. This approach has significant clinical potential to result in new treatment modalities for subtypes of prostate cancer that are currently incurable.

PI_NAMEs: LEBEAU, AARON MATTHEW (contact)

PROGRAM_OFFICER_NAME: AGYIN, JOSEPH KOFI

PROJECT_TERMS: Address;Affect;African American;alanine aminopeptidase;androgen deprivation therapy;Androgen Receptor;Anti-androgen Therapy;Antibodies;Binding;bioaccumulation;Biochemical;Biodistribution;Biological Assay;Biopsy;cancer cell;cancer subtypes;Caucasians;Cell Line;Cell surface;chelation;Chemistry;Clinic;Clinical;clinical translation;clinically relevant;combat;Complex;Copper;Cryoelectron Microscopy;curative treatments;Cyclic Peptides;Data;Development;dimer;Disease;Dose;Drug Design;effective therapy;Elements;Exhibits;Formalin;Frequencies;Generations;Goals;Human;imaging study;Immunohistochemistry;In Vitro;in vitro Model;in vivo;inhibitor;innovation;insight;Investigation;Label;Life;Ligand Binding;Malignant neoplasm of prostate;Membrane;men;Metalloproteases;Metastatic Prostate Cancer;Modality;Molecular Conformation;molecular imaging;Monitor;monomer;Mus;nanomolar;novel;novel therapeutics;nuclear imaging;Organ;overexpression;Paraffin Embedding;patient population;Patients;peptide drug;Peptide Hydrolases;Peptides;Phage Display;Pharmaceutical Preparations;Positron-Emission Tomography;Prostate Adenocarcinoma;prostate cancer cell;prostate cancer model;Prostate Cancer therapy;Protease Inhibitor;racial disparity;Radiolabeled;rational design;Receptor Signaling;Research;Resistance;Screening for Prostate Cancer;seryl-proline;Specificity;subcutaneous;Substrate Specificity;targeted treatment;Therapeutic;therapeutic candidate;therapeutic development;therapeutic target;therapy development;Tissue Embedding;Tissue Microarray;Tissues;tool;Toxic effect;Treatment Efficacy;Treatment Protocols;treatment response;tumor;Tumor Burden;Variant;X-Ray Crystallography;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Cyclic Peptide Protease Inhibitors for the Treatment of Prostate Cancer

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


ORG_CITY: NORMAN

ORG_DEPT: CHEMISTRY

ORG_NAME: UNIVERSITY OF OKLAHOMA

ORG_STATE: OK

PHR: Project Narrative: This proposal seeks to develop a facile method of synthesizing polyprenyl-diphosphates, precursors in the synthesis of thousands of valuable isoprenoids. The utility of the platform will be demonstrated for the synthesis of cannabinoid and squalene analogs for their potential therapeutic applications.

PI_NAMEs: SINGH, SHANTERI  (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TITLE: A Chemoenzymatic Approach to Accessing Novel Isoprenoid Scaffolds

STUDY_SECTION: MSFA

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


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Eye Disease and Disorders of Vision;Gene Therapy;Genetics;Nanotechnology

ORG_CITY: CINCINNATI

ORG_NAME: UNIVERSITY OF CINCINNATI

PHR: Posterior eye diseases affect more than a million people in the United States each year. The present project will develop an ocular drug delivery system based on RNA technology to deliver nucleotide-based drugs into the eye to treat posterior eye diseases. It will be a great benefit to the public if an effective drug delivery system can replace repeated intravitreal injections and allow effective nucleotide-based drug delivery for the treatments of these diseases.

PI_NAMEs: LI, KEVIN S. (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TERMS: 3D Print;Adverse effects;Affect;Age related macular degeneration;Angiogenesis Inhibitors;Animal Model;Animals;Antibody Therapy;aptamer;Bacteriophages;bevacizumab;Biological;Catalytic RNA;Cell Culture Techniques;Cells;Characteristics;chemical stability;Chronic Disease;Clinical Trials;Confocal Microscopy;Cornea;Cytomegalovirus Retinitis;Data;design;Development;Disease;Dissociation;DNA;DNA Packaging;Drug Delivery Systems;drug discovery;Drug Kinetics;Drug or Chemical;Drug Stability;experimental study;Eye;Eye diseases;fluorescence imaging;Fluorescence Microscopy;fomivirsen;Goals;Implant;In Vitro;in vivo;Injections;intravitreal injection;Ligands;macromolecule;Membrane;Methods;MicroRNAs;Modeling;Monitor;Monoclonal Antibodies;Motor;Mus;nanoparticle;nanoparticle delivery;nanosystems;Nanotechnology;neovascular;new technology;novel;Nucleotides;oculomotor;Oligonucleotides;Oryctolagus cuniculus;particle;Particle Size;pegaptanib;Persons;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetics and pharmacodynamics;Platelet-Derived Growth Factor;Polymers;Posterior eyeball segment structure;Proteins;Reporter;Research;Resistance;Retina;RNA;RNA Phages;Route;scaffold;Sclera;Silicone Elastomers;Small Interfering RNA;small molecule;Structure;Structure of retinal pigment epithelium;System;systemic toxicity;Technology;Therapeutic;Therapeutic Agents;Therapeutic Effect;therapeutic RNA;therapeutic siRNA;Thermodynamics;Tissues;Toxic effect;Transfection;United States;uptake

PROJECT_TITLE: RNA Nanosystem for Posterior Eye Drug Delivery


ORG_CITY: PHOENIX

ORG_NAME: ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER

ORG_STATE: AZ

PHR: Project Narrative Subarachnoid hemorrhage resulting from an intracranial aneurysm rupture results in severe morbidity and high mortality. This project will study the potential contributions of Neutrophil Extracellular Traps (NETs) to the development of intracranial aneurysmal rupture. The results may explain will be a basis for future studies to develop new therapies that target NETs and platelet-neutrophil interactions for the prevention of aneurysmal rupture.

PI_NAMEs: HASHIMOTO, TOMOKI  (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: adverse outcome;Amidines;Aneurysm;Antibodies;Aspirin;Atherosclerosis;Blood Platelets;Blood Vessels;Cessation of life;Clinical;Clinical Research;Clip;comparison control;Deoxyribonucleases;Deposition;Development;Disease;DNA;Endothelium;Enzymes;extracellular;Fibrin;Functional disorder;Future;Human;Inflammation;inhibitor;insight;Intracranial Aneurysm;ITGAM gene;ITGB2 gene;Knockout Mice;Laboratories;Leukocyte Elastase;Link;Macrophage;Mediating;migration;Morbidity - disease rate;mortality;mouse model;Mus;neutrophil;Neutrophil Activation;Neutrophil Infiltration;new therapeutic target;P-Selectin;pathogen;Patients;Peroxidases;pharmacologic;Plasma;Platelet Activation;Platelet aggregation;prevent;Prevention;Protein Inhibition;Protein-arginine deiminase;Resolution;Risk;Role;Rupture;Ruptured Aneurysm;Site;Sterility;Structure;Subarachnoid Hemorrhage;Testing;Therapeutic;Thrombosis;Thrombus;Tissues;vascular inflammation;Vasculitis;Venous Thrombosis;Work

PROJECT_TITLE: Mechanisms for intracranial aneurysm rupture


ORG_NAME: BAYLOR COLLEGE OF MEDICINE

PHR: PROJECT NARRATIVE Dysregulation of the mammalian target of rapamycin (mTOR) signaling pathway has been associated with epilepsy, a neurological disorder characterized by spontaneous recurrent seizures. By using a multidisciplinary approach that combines mouse genetics, molecular biology, pharmacology, EEG recordings, phosphoproteomics and behavioral studies, we aim to define the molecular mechanism by which activation of the mTOR signaling pathway leads to seizures, with a specific focus on mTOR complex 2. Our studies will not only provide new fundamental insights into the biological basis of epilepsy, but they could lead to the development of new therapies for seizure disorders.

PI_NAMEs: CHIN, JEANNIE  (contact);NOEBELS, JEFFREY

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TERMS: Acute;Adverse effects;Animal Model;anti-epileptic agents;Anticonvulsants;Antisense Oligonucleotides;Behavior assessment;Behavioral;behavioral study;Binding;Biological;Brain;Cell Physiology;cell type;Chronic;Complex;Cre lox recombination system;Data;defined contribution;Development;Economics;Electroencephalography;Electroporation;Epilepsy;Etiology;experimental study;FRAP1 gene;Functional disorder;Genetic;Genetic Models;Goals;Human;humanized mouse;improved;in utero;Individual;inhibitor;Injections;insight;interdisciplinary approach;Kainic Acid;Kinetics;Measures;Mediating;Modeling;Molecular;Molecular Biology;Molecular Genetics;mouse genetics;mouse model;mTORopathies;Mus;Mutation;Nervous System Disorder;Neurons;neurophysiology;novel;novel therapeutics;Pathway interactions;Pentylenetetrazole;Periodicity;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phenotype;phosphoproteomics;Phosphorylation;Pilocarpine;prevent;Prosencephalon;Proteomics;PTEN gene;Public Health;Publishing;Recurrence;Regulator Genes;Role;Seizures;Signal Pathway;Signal Transduction;Sirolimus;social;Technology;Temporal Lobe Epilepsy;Testing;Therapeutic;treatment strategy

PROJECT_TITLE: Mechanism and role of mTORC2 in seizure reduction

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Genetics;Neurosciences

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE Insects transmit a wide variety of diseases to hundreds of millions of people each year, and the geographic ranges of some of these diseases have been increasing. Many of these insects rely on their chemosensory systems to identify their human hosts, their food, and their mates. This project is designed to elucidate how these systems operate and could lead to new means of manipulating them so as to control these insect vectors of disease.

PI_NAMEs: CARLSON, JOHN R (contact)

PROGRAM_OFFICER_NAME: SULLIVAN, SUSAN L

PROJECT_TERMS: Affect;Afferent Neurons;Alleles;Anatomy;Animals;Attention;Back;Behavior;Behavioral;Biological;Biological Models;Biology;Chemicals;Code;Communication;Complex;connectome;Courtship;Data;design;Detection;Disease;Drosophila genus;Drosophila melanogaster;Electrophysiology (science);Environment;Experimental Designs;experimental study;Exposure to;Female;fly;Food;Fruit;gain of function;Gene Cluster;gene function;Genes;genetic analysis;Geography;Goals;Human;human disease;Hybrids;Hydrocarbons;Individual;Insect Control;insect disease vector;Insect Vectors;Insecta;insight;Label;Leg;Life;Logic;loss of function;male;Maps;mating behavior;Measures;Mediating;Molecular;Molecular Genetics;mutant;Mutation;neural circuit;Neurons;new technology;Odors;olfactory stimulus;optogenetics;Organ;Organism;Orthologous Gene;Output;Partner in relationship;Perception;Persons;Pheromone;Pheromone Receptors;postsynaptic neurons;receptor;Receptor Gene;Reporter;response;Role;Sensory;sensory input;Sensory Receptors;sensory system;Series;sex;Sex Behavior;Signal Transduction;Specificity;System;Taste Perception;Technology;Testing;Tissues;Translating;transmission process

PROJECT_TITLE: Analysis of Chemosensory Receptor Genes

STUDY_SECTION: CSS

STUDY_SECTION_NAME: Chemosensory Systems Study Section[CSS]


NIH_SPENDING_CATS: Biotechnology;Genetics;Infant Mortality;Lung;Maternal Health;Neonatal Respiratory Distress;Pediatric;Perinatal Period - Conditions Originating in Perinatal Period;Pregnancy;Preterm, Low Birth Weight and Health of the Newborn;Prevention;Pulmonary Hypertension;Rare Diseases;Women's Health Research

ORG_CITY: Loma Linda

ORG_DEPT: PEDIATRICS

ORG_NAME: LOMA LINDA UNIVERSITY

PHR: PROJECT NARRATIVE Chronic intrauterine hypoxia, which can result from pregnancy at high altitude or from many common pregnancy complications, is associated with adverse neonatal outcomes, including pulmonary hypertension of the newborn. The mechanism by which the fetus adapts to hypoxia, resulting in this disease, is unknown. We will utilize a well-established large animal model of neonatal pulmonary hypertension, combined with methods of manipulating gene expression, to test for the involvement of a specific hypoxia-sensitive microRNA pathway in this disease.

PI_NAMEs: BLOOD, ARLIN B (contact);WILSON, SEAN M;ZHANG, LUBO

PROGRAM_OFFICER_NAME: NATARAJAN, ARUNA R

PROJECT_TERMS: Acclimatization;Address;Adult;Altitude;Animal Model;Animals;antioxidant therapy;Antioxidants;Ascorbic Acid;Attenuated;Birth;Blood flow;Blood gas;Blood Vessels;Calcium;Cell Hypoxia;Chronic;cigarette smoking;Communication;Death Rate;design;Development;Disease;Electron Microscopy;Epigenetic Process;Exposure to;fetal;Fetal Development;Fetal Sheep;Fetus;fetus hypoxia;Flow Cytometry;Functional disorder;Gene Expression;genetic manipulation;gestational hypoxia;HIF1A gene;Hypoxia;hypoxia inducible factor 1;Image;In Situ;in utero;In Vitro;in vivo;Incidence;Iron;knock-down;lamb model;large-conductance calcium-activated potassium channels;Link;Lung;Measures;Mediating;Methodology;Methods;MicroRNAs;Mitochondria;mitochondrial dysfunction;Modality;Molecular;Myography;Neonatal;neonatal outcome;neonatal pulmonary hypertension;Newborn Infant;novel;Outcome;Oxidative Stress;patch clamp;Pathogenicity;Pathway interactions;Persons;pharmacologic;Placental Insufficiency;Play;postnatal;Potassium Channel;Pre-Eclampsia;Predisposing Factor;Pregnancy;Pregnancy Complications;Pregnant sheep;prevent;Production;Proteins;Pulmonary artery structure;pulmonary function;Pulmonary Hypertension;Reactive Oxygen Species;Relaxation;response;Rodent;Role;Ryanodine Receptor Calcium Release Channel;Sheep;Stress;Sulfur;Sulofenur;Term Birth;Testing;Therapeutic;Tissues;Translations;Vasodilation;Work

PROJECT_TITLE: Mechanisms of newborn pulmonary hypertension caused by chronic intrauterine hypoxia

STUDY_SECTION: PN

STUDY_SECTION_NAME: Pregnancy and Neonatology Study Section[PN]


ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: PROJECT NARRATIVE Ischemic stroke causes damage to the blood brain barrier (BBB) and contributes to the long term neurological deficits. To date, most stroke therapies have not considered the repair of this BBB damage after stroke. The long-term goal of the research is to understand the biochemical processes involved in the repair and restoration of BBB function, which can provide novel insights for the design of more effective neuroprotective strategies.

PI_NAMEs: BEGUM, GULNAZ  (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Acceleration;angiogenesis;Area;Astrocytes;astrogliosis;beta catenin;Biochemical;Biochemical Process;Blood - brain barrier anatomy;Blood Preservation;Blood Vessels;blood-brain barrier function;Brain;brain endothelial cell;Brain Hypoxia-Ischemia;Brain Ischemia;C57BL/6 Mouse;Cell Proliferation;central nervous system vasculature;cerebral microvasculature;Cerebrovascular Circulation;Cerebrum;design;Endothelial Cells;Endothelium;Gene Expression;Genes;Genetic Transcription;Genotype;Glial Fibrillary Acidic Protein;Glutamates;Goals;Impairment;improved;Infarction;insight;Ischemia;Ischemic Brain Injury;Ischemic Stroke;Knockout Mice;Knowledge;Laser Speckle Imaging;Ligands;Maintenance;Mediating;Messenger RNA;Middle Cerebral Artery Occlusion;Molecular;mouse model;mRNA Expression;Mus;Neurologic Deficit;neurological recovery;neuroprotection;neurovascular coupling;neurovascular injury;novel;novel therapeutics;Pathologic;Pathway interactions;Permeability;pharmacologic;Play;post stroke;preservation;Process;Protein Isoforms;protein structure;Proteins;Protons;receptor;Recovery;Regulation;repaired;Reporter;Research;response;restoration;Role;Signal Pathway;Signal Transduction;Signaling Protein;Sodium;stroke therapy;Structure;Swelling;Testing;Therapeutic Agents;Tight Junctions;tissue repair;transcriptome;transcriptome sequencing;transcytosis;Up-Regulation;uptake;Vascular Endothelial Cell;Wild Type Mouse;WNT Signaling Pathway

PROJECT_TITLE: Astrocytes-Mediated Regulation of Wnt/b-Catenin Pathway in Ischemic Brain

STUDY_SECTION: BINP

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


ADMINISTERING_IC: FD

IC_NAME: FOOD AND DRUG ADMINISTRATION

ORG_NAME: NATIONAL ACADEMY OF SCIENCES

PHR: Project Narrative Understanding how the nervous system develops, functions, ages, and interacts with the environment—in both health and disease—and developing safe and efficacious interventions for nervous system disorders are deeply challenging. Many federal agencies are involved in this endeavor, including the National Institutes of Health, the Food and Drug Administration, the National Science Foundation, the Department of Veterans Affairs, and the Department of Defense, as well as academic institutions, private sector companies, disease-focused organizations, and philanthropic foundations, both in the United States and worldwide. The National Academies of Sciences, Engineering, and Medicine’s Forum on Neuroscience and Nervous System Disorders provides a neutral venue for leaders from across these groups to exchange information, ideas, and differing perspectives, with ultimate goal of contributing to accelerating the pace of discovery in neuroscience research and the development of therapies for nervous system disorders.

PI_NAMEs: STROUD, CLARE  (contact)

PROGRAM_OFFICER_NAME: CARLSEN, CHRISTOPHER


ORG_CITY: MINNEAPOLIS

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: PUBLIC HEALTH RELEVANCE Temporal lobe epilepsy is the most common form of epilepsy in adults, and up to 40% of patients are not adequately treated with current treatment options. This proposal examines the potential for the cerebellum to be an effective target for intervention.

PI_NAMEs: KROOK-MAGNUSON, ESTHER  (contact)

PROJECT_TERMS: Adult;Affect;Animals;Anterior;Area;behavioral outcome;Brain region;Cell Nucleus;cell type;Central Lateral Nucleus;Cerebellar Cortex;Cerebellar Nuclei;Cerebellar vermis structure;Cerebellum;Chronic;cingulate cortex;Clinical;Data;design;Electric Stimulation;Electrophysiology (science);Epilepsy;experimental study;Fiber;Funding;Future;Hippocampus;Immunohistochemistry;improved;improved outcome;in vivo;in vivo calcium imaging;insight;Interneurons;Intervention;Investigation;Lead;Literature;Mediating;Methods;mouse model;Neurons;new therapeutic target;novel;novel therapeutics;Nucleus fastigii;Optics;optogenetics;Outcome;Output;Pathway interactions;Patients;public health relevance;Seizures;success;successful intervention;Temporal Lobe;Temporal Lobe Epilepsy;Testing;Thalamic structure;Time;tool;translational potential;Work

PROJECT_TITLE: Hippobellum: Cerebellar influence on the hippocampus and temporal lobe seizures

STUDY_SECTION: CNNT


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Neurodegenerative diseases, such as Alzheimer's, amyotrophic lateral sclerosis and frontotemporal dementia, are devastating disorders for which there are few treatments. Insight gained from simple organism studies that model these diseases, like Drosophila, to provide biological and mechanistic insight can provide the foundation for novel therapeutic advances. We propose to apply the power of this system to these diseases, to reveal molecular underpinnings and the foundation for treatments.

PI_NAMEs: BONINI, NANCY M (contact)

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Alzheimer's Disease;Amyotrophic Lateral Sclerosis;Biological;Brain;Cells;Cessation of life;Clinical;Complex;Degenerative Disorder;Dementia;Disease;disease model;Drosophila genus;Drosophila melanogaster;Economic Burden;extend lifespan;Familial disease;Family;fly;Foundations;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;Genes;Genetic;Genetic Screening;Genetic study;gut microbiota;Healthcare;healthspan;Human;in vivo;innovation;insight;interdisciplinary approach;interest;Mammalian Cell;Medical;model organism;Modeling;Molecular;Molecular Genetics;Motor Neuron Disease;Nervous System;Neurodegenerative Disorders;Neurons;novel;novel strategies;novel therapeutics;Organism;Paralysed;Parkinson Disease;Pathologic;Pathway interactions;Patients;programs;Research;Risk Factors;Societies;Study models;System;Therapeutic;Tissues;Toxic effect;Traumatic Brain Injury

PROJECT_TITLE: Molecular Genetic Insight into Neurodegenerative Disease from Drosophila


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Childhood Leukemia;Genetics;Hematology;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: GRAND RAPIDS

ORG_NAME: VAN ANDEL RESEARCH INSTITUTE

PHR: PROJECT NARRATIVE Pediatric leukemia patients bearing Mixed-lineage leukemia (MLL) gene translocations are associated with dismal prognosis and poor response to standard treatments. This proposal aims to identify small-molecule inhibitors that target the histone acetylation reading function of ENL, which is essential for the functions of MLL-fusions in leukemia. The proposed study will provide tool compounds to interrogate the functions of ENL and for further drug development for targeted therapy of MLL-translocated leukemias.

PI_NAMEs: WEN, HONG  (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Acetylation;Acute Lymphocytic Leukemia;Acute Myelocytic Leukemia;Adult;Automation;Binding;Biochemical;Biological Assay;Biophysics;Bromodomains and extra-terminal domain inhibitor;Calorimetry;Cell Line;Cells;Characteristics;Child;Childhood Leukemia;Chimeric Proteins;ChIP-seq;Chromatin;Chromosomal translocation;Complex;cytotoxicity test;Development;Disease;disorder subtype;driver mutation;Drug Design;drug development;effective therapy;Evolution;Exhibits;Fluorescence Polarization;Future;Gene Expression;Gene Expression Regulation;Gene Rearrangement;gene translocation;genome-wide;Goals;Growth;high throughput screening;Histone Acetylation;Histone H3;histone methyltransferase;Histones;Human;In Vitro;in vivo;Infant;inhibitor;innovation;Lead;leukemia;Leukemic Cell;Lysine;Maintenance;Measurement;Methylation;Methyltransferase;Mixed-Lineage Leukemia;MLL gene;MLLT3 gene;Molecular;Nature;Neonatal Leukemia;Oncogenic;Pathogenesis;Pathway interactions;Patients;Peptides;Pharmaceutical Preparations;pharmacologic;preclinical study;Prognosis;Proliferating;Reader;Reading;response;scaffold;Series;small molecule;small molecule inhibitor;small molecule libraries;standard care;Structure;synergism;targeted treatment;Testing;Therapeutic;Titrations;tool;transcriptome;treatment strategy;Triage;Validation

PROJECT_TITLE: Discovery of small molecules targeting the histone acetylation reader ENL

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-BST-F(55)R]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Gene Therapy;Genetics;Hematology;Human Genome;Nanotechnology;Orphan Drug;Rare Diseases;Sickle Cell Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: STORRS-MANSFIELD

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF CONNECTICUT STORRS

PHR: Project Narrative PNAs are synthetic pieces of DNA that can bind to the chromosomes of cells in a targeted manner and stimulate recombination of the target site with single-stranded donor DNAs to produce gene editing, with extremely low off target effects compared to other approaches. We will test the novel PNAs for correction of a sickle cell-associated mutation in the β-globin gene in blood stem cells, using nanoparticle-mediated delivery via IV administration in mice. We expect this work to yield potent PNAs and nanoparticle based approach to achieve curative gene editing for sickle cell disease.

PI_NAMEs: BAHAL, RAMAN  (contact)

PROGRAM_OFFICER_NAME: QASBA, PANKAJ

PROJECT_TERMS: Acids;Adult;Affinity;Anemia;Automobile Driving;base;beta Globin;beta Thalassemia;Binding;Binding Sites;Biology;biomaterial compatibility;Biomedical Engineering;Blood;Bone Marrow;Bone Marrow Stem Cell;carcinogenesis;CD34 gene;Cells;Charge;chemical synthesis;Chemicals;Chemistry;Chromatin;Chromosomes;clinical application;clinical practice;clinically relevant;Closure by clamp;Codon Nucleotides;CRISPR/Cas technology;curative treatments;deep sequencing;design;Development;digital;Disease;disease phenotype;DNA;DNA Binding;DNA Damage;DNA Repair;DNA Repair Gene;Drug Delivery Systems;Embryo;Encapsulated;Event;Extramedullary Hematopoiesis;Fibroblasts;Formulation;Foundations;Frequencies;gene correction;Gene Expression;gene replacement therapy;gene therapy;Gene Transfer;Generations;Genes;Genetic Diseases;genetic manipulation;Genetic Materials;Genetic Recombination;Genome;genome sequencing;Genomic DNA;Genomics;Glycolates;Goals;Hematological Disease;Hematopoietic;Hematopoietic stem cells;Hemoglobin concentration result;homologous recombination;Human;Human Genetics;human model;improved;in vivo;Individual;Inflammatory Response;Injections;innovation;interest;Intravenous;intravenous administration;Intravenous infusion procedures;Invaded;Measures;Mediating;Mendelian disorder;Methods;minimally invasive;Modification;Morphology;mouse model;Mus;Mutation;nanoparticle;Nanotechnology;nanotherapeutic;Nature;next generation;Normal Range;novel;nuclease;nucleic acid analog;Nucleic Acids;nucleobase;Pathway interactions;Patients;Penetrance;Peptide Nucleic Acids;Peptides;Phenotype;Positioning Attribute;Proto-Oncogene Protein c-kit;Reagent;recruit;repaired;Resistance;Reticulocyte count;Risk;RNA;self-renewal;Sickle Cell;Sickle Cell Anemia;Site;Small Interfering RNA;Specificity;Spleen;Splenomegaly;Stem Cell Factor;synthetic nucleic acid;System;Tail;targeted nucleases;Technology;Testing;Therapeutic;therapeutic genome editing;Toxic effect;Translating;Vertebral column;Viral;whole genome;Work;zinc finger nuclease

PROJECT_TITLE: Developing next generation synthetic nucleic acid analogous for sickle cell disease gene editing

STUDY_SECTION: MCH

STUDY_SECTION_NAME: Molecular and Cellular Hematology Study Section[MCH]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Digestive Diseases

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

PHR: PROJECT NARRATIVE Recovery from acute pancreatitis, an inflammatory disease of the pancreas, relies on crosstalk between immune and epithelial cells. Signaling from the immune cytokine IL22, protects pancreatic cells from injury and is regulated by IL22 binding protein. This research proposal will define the adaptive response of IL22 binding protein and IL22 signaling in acute pancreatitis with the goal of identifying strategies to enhance protection and regeneration of pancreatic cells.

PI_NAMEs: FRANKEL, TIMOTHY LOUIS (contact)

PROGRAM_OFFICER_NAME: SERRANO, JOSE

PROJECT_TERMS: 3-Dimensional;Acinar Cell;Acinus organ component;acute pancreatitis;Admission activity;Affinity;Anabolism;analog;Anti-Inflammatory Agents;Area;Arginine;autocrine;Autocrine Communication;Autophagocytosis;Binding;Binding Proteins;biobank;Biochemical;Biology;Body System;cell injury;Cell Line;Cells;Cessation of life;Cholecystokinin;Clinical;clinically relevant;cohort;Communication;cost;cytokine;Data;Dendritic Cells;Development;Disease;Disease Progression;Dose;Drops;Enzymes;Epithelial Cells;Epithelium;Equilibrium;experience;Flow Cytometry;Gastroenterologist;gastrointestinal;Gastrointestinal tract structure;Genes;Goals;Histologic;Homeostasis;Hospitalization;Host Defense;Human;Immune;Immune signaling;Immunity;improved;In Vitro;in vivo;Inflammation;Inflammatory;Injury;insight;Interleukin Suppression;interleukin-22;Knock-out;Knockout Mice;Knowledge;Malignant - descriptor;Measures;Mediator;Metabolism;Methods;mouse model;Mus;Natural regeneration;necrotic tissue;novel;Organ;Organ failure;organ repair;overexpression;oxidation;Pancreas;Pancreatic Diseases;Pancreatic Injury;Pancreatitis;paracrine;Paracrine Communication;pharmacologic;Physicians;Physiology;Prevalence;prevent;Production;protein expression;Protein Secretion;receptor;Recovery;Research Personnel;Research Proposals;response;response to injury;Retinoic Acid Receptor;Retinoic Acid-Binding Proteins;Role;Sampling;Scientist;Serum;Severities;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Sorting;Source;Testing;Therapeutic;tissue injury;tissue repair;Tissues;Transgenic Mice;Transgenic Organisms;Tretinoin;United States

PROJECT_TITLE: Epithelial-immune cell crosstalk during injury and recovery in acute pancreatitis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-DNPD-A(01)]


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

PHR: High-Grade gliomas, including diffuse intrinsic pontine glioma (DIPG), are a highly lethal childhood brain tumor for which there are no efficacious therapies. Our studies have identified a possible mechanism that promotes the maintenance of blood-brain barrier function in gliomas, which likely plays a role in tumor pathogenesis and treatment resistance. By examining the cellular and molecular mechanisms responsible for blood-brain barrier specification and maintenance, this proposal will provide a broader understanding of blood- vascular differences across brain tumor subtypes and provide insight will be crucial for improving treatments and outcomes for all brain tumor patients.

PI_NAMEs: PHOENIX, TIMOTHY N (contact)

PROGRAM_OFFICER_NAME: FOUNTAIN, JANE W

PROJECT_TERMS: Adult;Affinity;Agonist;angiogenesis;Angiopoietins;ANGPT1 gene;antagonist;Astrocytes;Blood;Blood - brain barrier anatomy;Blood brain barrier dysfunction;Blood Vessels;blood-brain barrier function;blood-brain barrier penetration;Brain;Brain Neoplasms;Cell Lineage;cell type;Cells;Childhood;Childhood Brain Neoplasm;Clinical Trials;CRISPR/Cas technology;Data;Development;differential expression;Diffuse intrinsic pontine glioma;Disease;efficacious treatment;Electroporation;Endothelium;experimental study;Future;gain of function;Gene Expression Profile;Genetic Transcription;Genome;genomic profiling;Glioma;glioma cell line;H3 K27M mutation;high throughput screening;Histologic;Human;improved;in utero;in vivo;inhibitor;insight;Knock-out;Link;Location;loss of function;Maintenance;Malignant Glioma;Malignant neoplasm of brain;Methods;Modeling;Molecular;molecular subtypes;mouse model;Mus;Mutation;neoplastic cell;Nervous System Disorder;oligodendrocyte progenitor;Oligodendroglia;overexpression;Pathogenesis;Pathway interactions;patient stratification;Patient-Focused Outcomes;Patients;Pattern;Pharmaceutical Preparations;Phenotype;Play;preclinical trial;predicting response;progenitor;programs;Recurrence;Regulation;Reporter;response to injury;Role;Signal Pathway;Signal Transduction;small molecule;Specific qualifier value;stem cells;Techniques;Testing;Therapeutic;therapy resistant;TIE-2 Receptor;tool;transgene expression;treatment and outcome;Treatment outcome;treatment strategy;tumor;Tumor Subtype;whole genome;Work

PROJECT_TITLE: Regulation of Angpt1 and DIPG blood-brain barrier integrity by H3K27M mutations

STUDY_SECTION: CNBT

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


ADMINISTERING_IC: HD

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

ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Narrative The most common structural neural defect is meningomyelocele, with risk of disease modified by environmental folic acid. The goal of this Program is to decipher the molecular causes of meningomyelocele using human populations, to uncover developmental mechanisms in mouse and frog, and to clarify the mechanisms by which folic acid dietary supplementation reduces disease risk.

PI_NAMEs: GLEESON, JOSEPH G (contact)

PROGRAM_OFFICER_NAME: KOSTER, MARANKE IRENE

PROJECT_TERMS: Affect;Alleles;American;Animal Model;Attention;Bioinformatics;Brain Stem;Candidate Disease Gene;candidate validation;Central Nervous System;Child;Chromatin;Clustered Regularly Interspaced Short Palindromic Repeats;cohort;Collaborations;Communication;Communities;computerized data processing;computerized tools;Congenital Abnormality;cost estimate;Country;Custom;Data;data harmonization;data quality;de novo mutation;Defect;design;Development;Diagnosis;dietary;Dietary Supplementation;disability;Disease;disease mechanisms study;disorder prevention;disorder risk;DNA;DNA Methylation;DNA Sequence Alteration;DNA Sequencing Facility;Embryo;Ensure;epigenome;epigenomics;exome;Family;Folic Acid;Folic acid fortification;folic acid supplementation;gene environment interaction;gene interaction;Genes;Genetic;Genetic Engineering;Genetic Transcription;genome sequencing;Genotype;Geography;Goals;Heritability;Human;human model;Hydrocephalus;improved;Incidence;inclusion criteria;Inherited;interest;International;Knock-in;Knock-out;Knowledge;Learning Disabilities;Live Birth;Measures;Meningomyelocele;Modeling;Molecular;Molecular Genetics;Monitor;Morbidity - disease rate;mortality;Mus;mutant;Mutate;Mutation;Network-based;neural;Neural Tube Closure;Neural Tube Defects;neuromechanism;next generation sequencing;Outcome;Patients;Penetrance;Phenotype;Population;programs;Proteins;Protocols documentation;Rana;recruit;Recurrence;Research;Research Personnel;Risk;Risk Factors;Risk Reduction;risk variant;Role;Running;Secure;Seizures;social media;Source;Spinal Dysraphism;Structural Congenital Anomalies;Technology;tool;transcriptome;United States National Institutes of Health;Variant;whole genome;Work;Xenopus;Xenopus laevis

PROJECT_TITLE: Developmental Mechanisms of Human Meningomyelocele


NIH_SPENDING_CATS: Biotechnology;Congenital Structural Anomalies;Genetics;Human Genome;Pediatric;Rare Diseases;Spina Bifida

PROJECT_TERMS: Administrator;Animal Model;Animals;Applications Grants;Bioinformatics;Budgets;Businesses;Child;Clinical;Collaborations;Colorado;Core Grant;Data;design;Development;Diagnosis;Disparate;educational atmosphere;Epigenetic Process;epigenomics;Faculty;functional genomics;gene environment interaction;Genetic;genetic approach;Genetic Screening;genome sequencing;Genomics;Goals;Grant;Group Meetings;Hour;Human;Human Genome Project;improved;Individual;innovation;insight;Institution;Knowledge;meetings;member;Meningomyelocele;Modeling;Molecular Diagnosis;multidisciplinary;Mus;Nature;Neural Tube Defects;Prevention;programs;Rana;Research;Research Personnel;Resources;response;reverse genetics;Sampling;Scientist;single cell sequencing;Structural Congenital Anomalies;Structural defect;symposium;Techniques;technological innovation;Technology;Training and Education;Translations;Travel;Universities;whole genome;Work

PROJECT_TITLE: Core A - Administrative  Core


NIH_SPENDING_CATS: Clinical Research;Genetics;HIV/AIDS;Human Genome;Infectious Diseases

ORG_CITY: ANN ARBOR

PHR: Project Narrative Combination antiretroviral therapy results in the elimination of nearly all actively infected cells. However, the small reservoir of remaining cells represents a crucial barrier to eradicating the infection. Discovery of markers that identify these cells or biochemical factors that facilitate their eradication could enable new strategies that will advance treatment approaches towards a cure.

PI_NAMEs: COLLINS, KATHLEEN L. (contact);WELCH, JOSHUA

PROGRAM_OFFICER_NAME: REFSLAND, ERIC WILLIAM

PROJECT_TERMS: Acute;Address;Affect;antiretroviral therapy;ATAC-seq;Atlases;Basic Science;Biochemical;Bioinformatics;Biological Markers;biomarker identification;Cell Lineage;Cell model;Cell Separation;cell type;Cells;Chromatin;Chromium;Clinical Treatment;Clonal Expansion;Complement;computer framework;Computer Models;Computing Methodologies;Data;Development;differentiation in vitro;Disease;DNA;env Gene Products;epigenome;epigenomics;Foundations;Gene Expression;Genetic Markers;Genetic Transcription;Genome;Goals;Granulocyte-Macrophage Colony-Stimulating Factor;hematopoietic differentiation;Histone Deacetylase Inhibitor;HIV;Human;In Vitro;Infection;insight;integration site;latent infection;Link;Macrophage;Maps;Marker Discovery;Methods;Modeling;multiple omics;novel;Patients;Pattern;Population;Proviruses;Reporter;Residual state;RNA;Sampling;Shock;single cell analysis;single cell ATAC-seq;single-cell RNA sequencing;Site;Surveys;System;Time;TNF gene;transcriptome;transcriptomics;Viral;Viral Genome;Viral reservoir;Virion;Virus Activation;Virus Integration;Virus Latency;Work;XCL1 gene

PROJECT_TITLE: Integrative Single-Cell Analysis of Transcriptome, Epigenome, and Lineage in HIV Latency and Activation


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

ORG_CITY: PORTLAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative According to the World Health Organization estimates, one-third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. The profound success of this bacteria in causing disease is due to its inherent ability to effectively modulate the host's cellular lipid biosynthetic pathways including sphingolipids to subvert the immune system. We will therefore aim to identify and characterize the sphingolipid types that are used by Mycobacterium to invade, persist, and propagate inside the immune cells.

PI_NAMEs: TAFESSE, FIKADU G. (contact)

PROGRAM_OFFICER_NAME: ROBINSON, RICHARD THOMAS

PROJECT_TERMS: Anabolism;analog;antimicrobial;Bacteria;base;Binding;Biological;Biosensor;CASP1 gene;Caspase;Cell Line;Cell Physiology;Cells;Cellular Membrane;Ceramides;Cessation of life;Cholesterol;Collaborations;combat;Complex;CRISPR/Cas technology;Data;Defect;Disease;Eicosanoids;Energy-Generating Resources;Engineering;Enzymes;Fatty Acids;Foamy Macrophage;Genes;genome editing;Genus Mycobacterium;Goals;Granuloma;Growth;Histologic;Homeostasis;host-microbe interactions;human pathogen;Immune;Immune system;Immunity;Incidence;Individual;Infection;Inflammasome;Inflammation;Invaded;Investigation;Knock-out;Laboratories;latent infection;lipid mediator;lipid metabolism;lipidome;Lipids;M. tuberculosis genome;Macrophage;Mammalian Cell;Metabolic;Metabolism;Microbe;microbicide;Mycobacterium tuberculosis;new therapeutic target;novel;pathogen;Pathogenesis;Pathologic;Pathway interactions;Phagocytes;Phagocytosis;physical property;Population;prevent;Process;Reporting;Role;Salmonella enterica;small molecule inhibitor;Sphingolipids;Sphingomyelins;Sphingosine;success;Technology;Testing;Time;tool;trafficking;Tuberculosis;uptake;Vertebral column;Virulent;Visualization;Work;World Health Organization

PROJECT_TITLE: Determining the role of sphingolipids in Mycobacterium tuberculosis infection

STUDY_SECTION: HIBP

STUDY_SECTION_NAME: Host Interactions with Bacterial Pathogens Study Section[HIBP]


ORG_CITY: CLEVELAND

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

PHR: Project Narrative Human cells contain a large multi-tRNA synthetase complex (MSC), consisting of 8 aminoacyl-tRNA synthetases and 3 non-synthetase proteins. The structure and function of the MSC are poorly understood, but mutations in seven human genes encoding MSC-resident proteins cause central nervous system disorders, child-onset hypomyelinating leukodystrophy and progressive microcephaly. Our long-term goal is to elucidate the structure, assembly, and function of the MSC, which in turn will illuminate the potential role of a dysfunctional MSC in health and disease.

PI_NAMEs: FOX, PAUL L (contact);GOGONEA, VALENTIN

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: 3-Dimensional;Alleles;Amino Acids;Amino Acyl-tRNA Synthetases;Architecture;Atrophic;Binding;Biochemical;Cell Physiology;Cells;Central Nervous System Diseases;Cerebrum;Child;Complex;Computer software;Coupled;Critical Thinking;crosslink;Crosslinker;Cytoplasm;Cytoplasmic Protein;Data;Data Analyses;Defect;density;design;Disease;DNA Sequence Alteration;Etiology;Event;Exhibits;experimental study;Fluorescence;fluorescence imaging;Functional disorder;Genes;Genetic;Glutamine-tRNA ligase;Goals;Grant;Health;Human;Impaired cognition;improved;insight;instrumentation;interest;knock-down;Length;leukodystrophy;Mammalian Cell;Mass Spectrum Analysis;Messenger RNA;Methods;Microcephaly;Modeling;Molecular;molecular modeling;motor impairment;mRNA Translation;Multiprotein Complexes;Mutate;Mutation;Myelin;Neurodegenerative Disorders;neuropathology;Nomenclature;Pathologic;Pathology;Peptides;Photobleaching;Positioning Attribute;programs;Protein Biosynthesis;protein complex;protein crosslink;Proteins;Reporting;Ribosomes;Role;Scaffolding Protein;Seizures;single molecule;Sodium Chloride;spatial relationship;Specificity;Stimulus;stoichiometry;Structural Models;Structure;Sulfoxide;Testing;tool;Translations

PROJECT_TITLE: The mammalian multi-tRNA synthetase complex

STUDY_SECTION: MGA

STUDY_SECTION_NAME: Molecular Genetics A Study Section[MGA]