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;Bioengineering;Machine Learning and Artificial Intelligence;Neurosciences

ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative Normal hearing depends on the brain’s ability to anticipate and suppress responses to self-generated vocal sounds, while impaired suppression generates auditory hallucinations. We aim to show how vocal motor signals suppress auditory activity in the brain, thus informing how hearing works in health and disease.

PI_NAMEs: MOONEY, RICHARD D (contact)

PROGRAM_OFFICER_NAME: POREMBA, AMY

PROJECT_TERMS: Acoustics;Address;Animal Vocalization;Arousal;Auditory;Auditory area;auditory feedback;Auditory Hallucination;auditory processing;auditory stimulus;Auditory system;autoencoder;Behavior;Behavioral;Bone Conduction;Brain;Cells;Communication;Complex;Computing Methodologies;Courtship;deaf;Disease;Electrodes;Electrophysiology (science);excitatory neuron;experience;experimental study;Feedback;Female;flexibility;Functional disorder;Funding;Genetic;Goals;Grant;Head;Head Movements;Health;Hearing;Human;Image;Impairment;in vivo;inhibitory neuron;insight;Interneurons;Knowledge;Learning;Locomotion;machine learning method;male;Maps;Measures;Methods;Monitor;Monkeys;Motor;Motor Cortex;Movement;multi-electrode arrays;multiphoton imaging;Mus;Neurons;normal hearing;novel;Optical Methods;Optics;optogenetics;Pathway interactions;Physiological;prevent;Process;Production;Property;Pyramidal Cells;Resolution;response;Signal Transduction;social;Social Environment;Social isolation;sound;Speech;Stimulus;Synapses;Techniques;Testing;Thalamic structure;Time;tool;two-photon;Ultrasonics;unsupervised learning;vocalization;Work

PROJECT_TITLE: Motor Modulation of Auditory Processing

STUDY_SECTION: SMI

STUDY_SECTION_NAME: Sensorimotor Integration Study Section[SMI]


ADMINISTERING_IC: MH

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF EDUCATION

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Mental Health;Pediatric

ORG_CITY: COLLEGE PARK

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_FIPS: US

ORG_NAME: UNIV OF MARYLAND, COLLEGE PARK

ORG_STATE: MD

PHR: PROJECT NARRATIVE Mother-child social interactions play an important role in the mother-to-child transmission of social anxiety; however, the dynamic social processes through which children acquire social anxiety from their mothers are not fully understood. In the proposed project, we will examine the following hypotheses: 1) higher levels of negative maternal verbal communication regarding social situations will mediate the influence of maternal social anxiety on children’s laboratory-based social fear, 2) greater mother-child dyadic rigidity characterized by perseveration in the state of child attending to negative maternal input will mediate the influence of maternal social anxiety on children’s laboratory-based social fear, and 3) more negative maternal verbal communication and dyadic rigidity will mediate the positive association between maternal social anxiety and child social anxiety 6 months later. Findings from this project will provide insight into the dynamic social processes by which mothers transfer social anxiety to their children and identify potential targets for intervention efforts aimed at preventing childhood social anxiety.

PI_NAMEs: ZEYTINOGLU, SELIN  (contact)

PROGRAM_OFFICER_NAME: BECHTHOLT, ANITA JEAN

PROJECT_TERMS: 12 year old;adverse outcome;Age;Anxiety;anxiety symptoms;Attention;Child;Childhood;childhood anxiety;Code;Communication;Data;Development;Drops;dyadic interaction;dynamic system;Emotional;Face;Family;Fright;Genetic;Glass;information gathering;insight;Intervention;Knowledge;Laboratories;Learning;Life;Mediating;Mental Health;Methods;Mother-Child Relations;Mothers;novel;Outcome;Participant;Pathway interactions;Pattern;peer;peer victimization;Play;prevent;Prevention;Questionnaires;Research;Role;Same-sex;Schools;Shapes;social;social anxiety;Social Interaction;social learning;Social Processes;social situation;Stimulus;Testing;theories;Time;Training;transmission process;verbal;Vertical Disease Transmission;Visit;Visual attention;visual tracking

PROJECT_TITLE: Mother-Child Dynamics in the Transmission of Social Anxiety: The Roles of Maternal Verbal Communication and Child Attention

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-F16-L(21)L]


ADMINISTERING_IC: NS

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: STANFORD

ORG_DEPT: NEUROSURGERY

ORG_NAME: STANFORD UNIVERSITY

ORG_STATE: CA

PHR: PROJECT NARRATIVE Stroke, the leading cause of disability in the US, has very limited treatment options; recovery after stroke can occur, and our group has demonstrated the use of optogenetics to selectively stimulate key brain regions to promote recovery. Our goal in this proposal is to investigate the role of key brain circuit dynamics during post-stroke recovery using multimodal approaches. Results from our studies will advance the understanding of how stroke affects brain circuit dynamics and how brain stimulations alter circuits to promote recovery, which is a crucial step in developing effective treatments that improve functional recovery after stroke.

PI_NAMEs: STEINBERG, GARY K (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Address;Affect;Animals;Area;Automobile Driving;behavior test;Biological;Brain;Brain Diseases;Brain Mapping;Brain region;brain remodeling;Calcium;calmodulin-dependent protein kinase II;Cause of Death;Cell Count;cell type;Characteristics;Cholesterol;cholesterol biosynthesis;Clinical Research;Corpus striatum structure;Data;design;disability;effective therapy;Event;excitatory neuron;Female;Frequencies;functional improvement;Functional Magnetic Resonance Imaging;Future;G Protein-Coupled Receptor Signaling;Genes;Goals;Grant;High-Throughput RNA Sequencing;Image;imaging system;Imaging Techniques;improved;Individual;Infarction;inhibitory neuron;insight;Intervention;Location;male;Maps;Medical;Metabolism;Microscope;Molecular;Molecular Profiling;Molecular Target;Motor Cortex;multimodality;Mus;Nervous System Disorder;neural;neural circuit;neuroimaging;Neurons;neuroregulation;new therapeutic target;optogenetics;partial recovery;Parvalbumins;Pathway interactions;Population;portability;post stroke;promoter;Recovery;Recovery of Function;Reporting;Resolution;Role;sex;Sex Differences;Site;Somatosensory Cortex;Stains;Stroke;stroke outcome;stroke recovery;Techniques;Testing;Thalamic structure;Therapeutic;Therapeutic Intervention;Time;tool;transcriptome;transcriptome sequencing;transcriptomic profiling;Translating;Validation

PROJECT_TITLE: Optogenetic Approaches to Study Post-Stroke Recovery Mechanisms

STUDY_SECTION: ANIE

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


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: La Jolla

ORG_NAME: SALK INSTITUTE FOR BIOLOGICAL STUDIES

PHR: PROJECT NARRATIVE Mitochondria are essential cell components with many functions in metabolism, signaling and immunity. Mitochondria have DNA that is inherited from your mother that we have shown activates a unique set of genes in another cell compartment called the nucleus. This project will examine how signaling between mitochondria and the nucleus impacts colorectal cancer and its treatment.

PI_NAMEs: HARGREAVES, DIANA CLARE;SHADEL, GERALD  (contact)

PROGRAM_OFFICER_NAME: WILLIS, KRISTINE AMALEE

PROJECT_TERMS: antiviral immunity;ApcMin/+ mice;ARID1A gene;cancer cell;Cancer Etiology;Cancer Model;Cell Compartmentation;Cell Nucleus;Cell Separation;Cells;Cellular Structures;Cessation of life;Chemoresistance;chemotherapy;Chromatin;chromatin remodeling;Chromatin Remodeling Factor;Chromatin Structure;Colonic Neoplasms;Colorectal Cancer;Communication;Complex;Cytoplasm;Data;Disease;DNA;DNA Damage;DNA Double Strand Break;DNA Repair;effective therapy;enzyme model;Event;Exhibits;Gene Expression Profile;Genes;Genomics;Goals;Heterozygote;Homeostasis;Human;human model;Immune signaling;Immunity;In Vitro;in vivo;Inherited;Interferons;intestinal tumorigenesis;Intestines;Investigation;Knock-out;Knockout Mice;Lead;Malignant Neoplasms;MC38;MCC gene;Mediating;member;men;Metabolism;Mitochondria;Mitochondrial DNA;Modeling;Morphology;Mothers;mouse model;Mus;Mutate;Mutation;Nature;neoplastic cell;novel;Nuclear;null mutation;Organelles;oxidation;PARP9 gene;Pathway interactions;programs;repaired;Resistance;restriction enzyme;Role;Sampling;Signal Pathway;Signal Transduction;Stress;Structure;Testing;therapeutic target;tumor;Tumor Suppressor Proteins;tumorigenesis;Up-Regulation;virtual;Woman

PROJECT_TITLE: Mitochondria-to-Nucleus Signaling in Colorectal Cancer

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


ADMINISTERING_IC: ES

ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Genetics;Human Genome;Prevention

ORG_CITY: GAINESVILLE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Genetic differences between people and populations can impact the risk of adverse effects from environmental exposures. Improved understanding of the relationship between genetic susceptibility and the environment is critical to protecting public health. Current approaches have had limited success in identifying human health relevant interactions. We propose a fundamentally different approach to functional assess commonly variant human genes for their role in specific environmental exposures which could enable more effective human risk assessment.

PI_NAMEs: VULPE, CHRISTOPHER D (contact)

PROGRAM_OFFICER_NAME: DUNCAN, CHRISTOPHER GENTRY

PROJECT_TERMS: 3-Dimensional;Adverse effects;adverse outcome;Affect;Biological;biological adaptation to stress;Candidate Disease Gene;candidate identification;Cell Differentiation process;Cell Line;Cell model;Cell Proliferation;Cells;Chemicals;Clustered Regularly Interspaced Short Palindromic Repeats;comparative;Complex;Coupled;CRISPR library;CRISPR screen;Databases;Dose;drug candidate;Environment;Environmental Exposure;environmental stressor;Evaluation;Exposure to;Frequencies;gene environment interaction;Gene Expression;Genes;Genetic;genetic association;Genetic Predisposition to Disease;Genetic Transcription;genetic variant;Genetic Variation;Health;Human;Human Genetics;improved;Individual;Libraries;loss of function;loss of function mutation;Measures;Metabolic;Mutation;Organoids;Outcome;Pathway interactions;Persons;Phenotype;Physiological;Population;Predisposition;Preventive;Public Health;Reporter;resilience;Resources;response;Risk;Risk Assessment;risk mitigation;Role;single-cell RNA sequencing;Stress;stressor;success;Therapeutic;tool;toxicant;Toxicant exposure;Toxicogenomics;Toxicology;Toxin;Validation;Variant;vector

PROJECT_TITLE: CRISPR screens of population relevant genes governing toxicant resilience


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Antimicrobial Resistance;Genetics;Infectious Diseases;Malaria;Orphan Drug;Rare Diseases;Vector-Borne Diseases

ORG_CITY: NEW YORK

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: Piperaquine is a vital drug in the fight against malaria, yet resistance has emerged in Southeast Asia. Our project will predict the risk that resistance emerges and spreads in Africa and will identify the causal genetic factors in Plasmodium falciparum parasites. We will also define the molecular basis of resistance and identify new chemical compounds that can suppress the resistance pathway in parasites.

PI_NAMEs: FIDOCK, DAVID A (contact)

PROGRAM_OFFICER_NAME: MO, ANNIE X  Y

PROJECT_TERMS: Africa;African;Amodiaquine;Anti-malarials;Artemisinins;asexual;Binding;Biological Assay;Blood;burden of illness;Cessation of life;Chemicals;Chemoprevention;Child;Chloroquine;Chloroquine resistance;clinical efficacy;Clinical Research;Clinical Trials;Combined Modality Therapy;Computer Models;cost;design;Drug Combinations;Drug Efflux;Drug Kinetics;Drug Metabolic Detoxication;Drug Targeting;Essential Drugs;Falciparum Malaria;fighting;fitness;Funding;gene-editing approach;Genes;Genetic;Genetic Crosses;Genetic Determinism;Globin;Growth;Half-Life;Haplotypes;Heme;Hemoglobin;hemozoin;high throughput screening;Human;In Vitro;Individual;Infection;inhibitor;innovation;insight;Investigation;Lead;Luciferases;Malaria;Maps;Measures;Mediating;Mediator;Mefloquine;Metabolism;Microbial Drug Resistance;Molecular;Morbidity - disease rate;mortality;mutant;Mutation;National Institute of Allergy and Infectious Disease;novel;overexpression;Parasite resistance;Parasites;Pathway interactions;Peptides;Pharmaceutical Preparations;Plasma;plasmepsin;Plasmodium falciparum;Population;Pregnant Women;pressure;prevent;Prevention strategy;Protein Isoforms;proteoliposomes;quinoline;Recrudescences;Research Support;Resistance;resistance allele;resistant Plasmodium falciparum;Risk Assessment;risk prediction;Role;Rwanda;Safety;Source;Southeastern Asia;success;symptom treatment;Testing;Transgenes;transmission process;Treatment Failure;Uganda;Vacuole;Variant;Vulnerable Populations

PROJECT_TITLE: Elucidating the molecular basis of piperaquine resistance in Plasmodium falciparum

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AIDC-B(83)]


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

ORG_CITY: BALTIMORE

ORG_DEPT: NEUROSCIENCES

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project narrative Mechano-sensory hair cells within our ear are essential for our ability to detect sound. Hair cells are not regenerated and their loss is a leading cause for deafness in humans. In our proposal, we will investigate whether re-activation of the progenitor-specific genes Lin28b and follistatin will enable supporting cells to re-activate a progenitor-like state and allow them to regenerate lost hair cells. We anticipate that insights gained from our study will provide exiting new avenues for cell-based hearing restoration efforts.

PI_NAMEs: DOETZLHOFER, ANGELIKA  (contact)

PROGRAM_OFFICER_NAME: FREEMAN, NANCY

PROJECT_TERMS: Ablation;Activins;Address;Adolescent;Adult;Alleles;antagonist;Attenuated;Auditory;Biological Assay;candidate selection;cell dedifferentiation;cell determination;cell injury;Cell Proliferation;Cell Reprogramming;Cells;Cochlea;cochlear development;Cre lox recombination system;CRISPR/Cas technology;Cues;Data;deafness;Diphtheria Toxin;Disease;Doxycycline;Ear;experimental study;Fluorescent in Situ Hybridization;Follistatin;Gene Expression Profile;gene function;gene network;Generations;Genes;hair cell regeneration;Hair Cells;Hearing;hearing impairment;hearing restoration;Human;In Vitro;in vitro Model;in vivo;in vivo regeneration;inducible Cre;insight;Knock-out;Labyrinth;LoxP-flanked allele;mature animal;Mediating;Mitotic;mouse genetics;mouse model;Mus;Natural regeneration;Neonatal;neonatal mice;notch protein;novel;Organoids;overexpression;paralogous gene;Persons;pluripotency;progenitor;programs;Publishing;regenerative;Regenerative capacity;Regenerative response;repair strategy;response;RNA-Binding Proteins;Role;Signal Transduction;single molecule;single-cell RNA sequencing;sound;stem-like cell;Supporting Cell;Testing;Therapeutic;tool;transcriptome;Transforming Growth Factor Beta 2;Transgenes;Transgenic Mice;Transgenic Organisms;Trauma;Up-Regulation

PROJECT_TITLE: The function of LIN28B and follistatin in supporting cell reprogramming and hair cell regeneration in the murine cochlea

STUDY_SECTION: AUD

STUDY_SECTION_NAME: Auditory System Study Section[AUD]


ORG_CITY: BAR HARBOR

ORG_NAME: JACKSON LABORATORY

ORG_STATE: ME

PHR: Public Health Relevance/Narrative Understanding the molecular basis of immune responses is important to the development of vaccines, fighting infectious diseases and designing cancer immunotherapy. Using samples from herpes zoster vaccination studies, we will perform cutting-edge high-coverage metabolomics to learn how individuals respond to vaccination differently, and how metabolic phenotypes influence the immune responses. The scientific findings in this project shall guide vaccine development, trials, and therapeutic designs.

PI_NAMEs: LI, SHUZHAO  (contact)

PROGRAM_OFFICER_NAME: DUPUY, LESLEY CONRAD

PROJECT_TERMS: adaptive immune response;Antibodies;Attenuated;Biological Assay;cancer immunotherapy;Cells;chemical group;cohort;Communicable Diseases;Data;Data Analyses;design;Early identification;fighting;Gene Combinations;Gene Expression;Genes;Herpes zoster disease;Human;Immune;Immune response;Immunology;improved;Individual;individual response;individual variation;Infection;Inositol Phosphate Metabolism Pathway;insight;Learning;lipidomics;Lipids;Measurement;Measures;Metabolic;Metabolic Pathway;metabolic phenotype;metabolomics;Molecular;multiple omics;Participant;Pathway interactions;Pattern;Peripheral Blood Mononuclear Cell;Plasma;predictive modeling;Public Health;public health relevance;Regulation;Reporting;Research;response;sample archive;Sampling;Signal Transduction;single-cell RNA sequencing;small molecule;small molecule libraries;steroid metabolism;T cell response;Testing;Therapeutic;Time;tool;transcriptomics;Vaccination;vaccine development;vaccine immunogenicity;vaccine trial;vaccine-induced immunity;Vaccines;Work;Zoster Vaccine

PROJECT_TITLE: ImmunoMetabolomics of Zoster Vaccines

STUDY_SECTION: VMD

STUDY_SECTION_NAME: Vaccines Against Microbial Diseases Study Section[VMD]


ED_INST_TYPE: SCHOOLS OF PHARMACY

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: MISSOULA

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF MONTANA

ORG_STATE: MT

PHR: PROJECT NARRATIVE NMDA receptors mediate excitatory neurotransmission in the central nervous system and play important roles in neuronal development and synaptic plasticity. They are also implicated in many neurological and psychiatric disorders, and subunit-selective modulation of NMDA receptors by targeting a single GluN2 subunit in specific brain regions or neuronal cell types could be therapeutically beneficial in a number of diseases. We will investigate novel subunit-selective allosteric modulators and glycine site agonists. These experiments will uncover novel structural and mechanistic features of NMDA receptor modulation and provide new avenues for basic and translational research, as well as facilitate the development of novel therapeutic agents.

PI_NAMEs: HANSEN, KASPER BOE (contact)

PROGRAM_OFFICER_NAME: UMANAH, GEORGE KWABENA ESSIEN

PROJECT_TERMS: Acute;Adult;Affect;Agonist;Basic Science;Binding;Binding Sites;blood-brain barrier penetration;Brain;Brain region;Cartoons;cell type;Central Nervous System;Central Nervous System Diseases;Chemicals;clinical efficacy;Collaborations;Crystallography;design;Development;dimer;Disease;Electrophysiology (science);Endowment;experimental study;extracellular;Funding;Glutamate Receptor;Glutamates;Glycine;Glycine Receptors;granule cell;Hippocampus;Hydrophobicity;improved;interest;Interneurons;Investigation;Ligand Binding;Ligands;Mediating;Mental disorders;Molecular Conformation;Mus;Mutagenesis;N-Methyl-D-Aspartate Receptors;N-Methylaspartate;N-terminal;Nervous System Disorder;neuron development;Neurons;Neurosciences Research;neurotransmission;NMDA receptor 2A;NMDA receptor A1;novel;novel therapeutics;Penetration;Pharmaceutical Chemistry;pharmacologic;Phase;Play;Population;pre-clinical;Property;Pyramidal Cells;receptor;Receptor Signaling;Recombinants;research and development;response;Rodent;Role;scaffold;Serine;Site;Site-Directed Mutagenesis;Slice;Structure;Synapses;Synaptic plasticity;Therapeutic;Therapeutic Agents;therapeutic target;Translating;Translational Research;Variant

PROJECT_TITLE: Structural and functional investigation of allosteric NMDA receptor modulation

STUDY_SECTION: BPNS

STUDY_SECTION_NAME: Biophysics of Neural Systems Study Section[BPNS]


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

ORG_CITY: BOSTON

ORG_NAME: DANA-FARBER CANCER INST

ORG_STATE: MA

PHR: Project Narrative CDC7 protein is a cell cycle kinase that is found at abnormally high levels in several types of human tumors. This study will test whether inhibition of CDC7 kinase might represent a powerful therapeutic strategy for treatment of a subset of human cancers. This work may lead to a novel therapeutic approach for cancer patients, centered on CDC7 inhibition. !

PI_NAMEs: SICINSKI, PETER  (contact)

PROGRAM_OFFICER_NAME: CERO, CHERYL

PROJECT_TERMS: Acute;Adult;anti-cancer;Apoptosis;Breast Cancer Model;cancer cell;Cancer cell line;Cancer Model;Cancer Patient;cancer therapy;cancer type;casein kinase II;CDC2 gene;CDK2 gene;CDK4 gene;Cell Cycle;Cell Cycle Proteins;Cell division;cell motility;Cell Nucleus;Cell Physiology;Cell Proliferation;cell type;Cells;Cellular Structures;chemical genetics;Chemicals;Clinical Trials;Cyclin D1;Cyclin-Dependent Kinase Inhibitor 2A;DNA biosynthesis;Down-Regulation;Embryonic Development;Epithelium;follow-up;G1 Phase;genetic approach;Goals;Homologous Protein;Human;Hyperactivity;In Vitro;in vivo;in vivo evaluation;Individual;Inhibition of Cell Proliferation;Invaded;Knock-in Mouse;Knockout Mice;KRP protein;Laboratories;Libraries;Malignant Breast Neoplasm;Malignant Neoplasms;Mammalian Cell;Maps;Mesenchymal;mimetics;Modeling;Molecular;Molecular Analysis;mouse model;Mouse Strains;Mus;mutant;Mutate;neoplastic cell;Normal Cell;Normal tissue morphology;novel;novel therapeutic intervention;Oncogenic;Organism;overexpression;Patients;Phosphorylation;Phosphorylation Site;Phosphotransferases;Play;Pre-Replication Complex;Pregnancy;Proliferating;Protein Deficiency;protein function;Protein Inhibition;Proteins;Report (document);Reporting;Resistance;response;Role;S phase;Saccharomycetales;Signal Transduction;small molecule;Somatic Cell;Testing;Textbooks;Therapeutic;therapeutic target;tool;TP53 gene;treatment strategy;triple-negative invasive breast carcinoma;tumor;tumorigenesis;Work;yeast protein;Yeasts

PROJECT_TITLE: CDC7 kinase in normal and cancer cells: potential implications for cancer treatment

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


ORG_CITY: CHARLOTTESVILLE

ORG_NAME: UNIVERSITY OF VIRGINIA

ORG_STATE: VA

PHR: PROJECT NARRATIVE Epilepsy resulting from brain infection, tumors or injury presents with tissue remodeling that employs protein- degrading enzymes. These enzymes may damage “perineuronal nets,” an important protective coat around inhibitory neurons. The loss of this coat slows neuronal firing, making these neurons less inhibitory and giving rise to seizures. This proposal investigates how perineuronal nets may be causally involved in epilepsy and may suggest a completely different therapeutic approach to ameliorate this disease.

PI_NAMEs: SONTHEIMER, HARALD W (contact)

PROGRAM_OFFICER_NAME: CHURN, SEVERN BORDEN

PROJECT_TITLE: Role of Perineuronal Nets in Epilepsy

STUDY_SECTION: CNNT

STUDY_SECTION_NAME: Clinical Neuroplasticity and Neurotransmitters Study Section[CNNT]


ED_INST_TYPE: OVERALL MEDICAL

NIH_SPENDING_CATS: Brain Disorders;Genetics;Intellectual and Developmental Disabilities (IDD);Neurosciences;Pediatric;Rare Diseases;Rett Syndrome;Women's Health Research

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: Project Narrative This proposal extends successful work funded by a NIH Director's Transformative Research Award to apply a site-directed RNA editing approach to repair mutations in neurological disorders. We focus on guanosine to adenosine mutations that underlie several neurological disorders, including Rett syndrome, our model for testing basic and translational hypotheses related to the technology because of symptom reversibility in Rett mice. Our recent results show, for the first time with any editing method, widespread in vivo repair of an endogenous protein (MeCP2) in CNS neurons.

PI_NAMEs: MANDEL, GAIL  (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Address;Adenosine;Adolescent;Adult;Amino Acids;Astrocytes;Award;Back;Bacteriophages;base;Base Pairing;Behavior;Binding;Biological Assay;Brain;Brain region;Catalytic Domain;Cell Line;Cells;cellular imaging;Chromatin;chromatin protein;Code;Codon Nucleotides;Complementary DNA;CRISPR/Cas technology;Data;Deamination;design;Disease;Dose;dsRNA adenosine deaminase;Elements;Enzymes;Exhibits;experimental study;Female;Funding;Future;Genes;Genetic Enhancer Element;genome editing;Guanosine;Guide RNA;Hand Strength;Hippocampus;Human;human model;Hybrids;Immune response;improved;In Vitro;in vivo;Injections;Inosine;Length;male;Measures;Methods;Methyl-CpG-Binding Protein 2;Mismatch Repair;Mobility decline;Modeling;Molecular;Morphology;mouse model;Mus;mutant;Mutation;Neonatal;Nervous System Disorder;neural;Neurologic;Neurons;next generation;Nonsense Codon;Nonsense Mutation;novel;nuclease;Pathogenicity;Patients;Peptides;Peripheral;Phenotype;Population;Positioning Attribute;posttranscriptional;prevent;Process;promoter;Proteins;Publishing;Reagent;recruit;repaired;Research;Respiration;Rett Syndrome;RNA;RNA Binding;RNA Editing;RNA Phages;Serotyping;Site;Specificity;Stereotyping;Symptoms;Technology;Testing;Therapeutic;Time;tool;transcription factor;transcriptome sequencing;transcriptomics;Transfection;Translations;United States National Institutes of Health;Viral;Virus;Work

PROJECT_TITLE: Repair of neurological disorders through RNA editing

STUDY_SECTION: MNG

STUDY_SECTION_NAME: Molecular Neurogenetics Study Section[MNG]


NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: AMHERST

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: STATE UNIVERSITY OF NEW YORK AT BUFFALO

PHR: Project Narrative Membrane Associated RING CH (MARCH) family of proteins were recently found to restrict HIV-1 replication by blocking envelope incorporation in the budding virions in the producer cells. Nevertheless, many questions remain regarding the role of this family of proteins during HIV-1 infection. A better understanding of the antiretroviral mechanism of MARCH proteins and its effect on HIV-1 infection has the potential to be utilized for the development of new therapeutic strategies.

PI_NAMEs: STAVROU, SPYRIDON  (contact)

PROGRAM_OFFICER_NAME: NOVAK, LEIA KAYE

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Affect;Anti-Retroviral Agents;Antigen Presentation;antiviral drug development;Bypass;Cell fusion;Cell membrane;Cell Membrane Proteins;Cell Physiology;Cell Surface Proteins;Cell Surface Receptors;Cells;Cellular Membrane;Clinical;Development;Drug Targeting;env Genes;Excision;Exclusion;Family;Fingers;Genetic;Genetic Polymorphism;Genome;genome sequencing;Genomics;Glycoproteins;Goals;Histocompatibility Antigens Class II;HIV;HIV Infections;HIV-1;Homologous Gene;Human Herpesvirus 8;Immune response;Infection;Integration Host Factors;Macrophage;Mediating;member;Membrane;MHC Class II Genes;monocyte;Mutate;Mutation;novel therapeutic intervention;Play;Predisposition;pressure;prevent;Production;programs;Protein Family;Proteins;Reagent;receptor;receptor binding;Regulation;Reporting;Research;Resistance;Retroviridae;Retroviridae Infections;Role;System;Therapeutic;Time;Ubiquitin family;ubiquitin ligase;ubiquitin-protein ligase;Ubiquitination;United States National Institutes of Health;Viral;Viral Proteins;Virion;Virus;vpr Genes

PROJECT_TITLE: MARCH Proteins, Members of a Host Protein Family that Targets HIV

STUDY_SECTION: HVCD

STUDY_SECTION_NAME: HIV Molecular Virology, Cell Biology, and Drug Development Study Section[HVCD]


ADMINISTERING_IC: GM

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Hematology;Human Genome;Rare Diseases

ORG_DEPT: BIOCHEMISTRY

PHR: Project Narrative: DNA fragility generated by alternative DNA secondary structures is a known cause of many human diseases, occurs in normal DNA processes, and can be affected by cellular activities, environmental and chemical exposures, and nucleotide sequences. We propose to investigate the role of alternative DNA structure in the generation of topoisomerase II-mediated DNA breaks, to evaluate DNA structure-rich and break-prone regions as a biomarker for cancer susceptibility, and to use naturally occurring sequence variants to identify structure characteristics contributing to DNA fragility. This work will reveal a new aspect of the molecular mechanism for DNA structure-driven fragility, and eventually lead to development of novel diagnostic measures for cancer caused by the DNA fragility-directed mutations.

PI_NAMEs: WANG, YUH-HWA  (contact)

PROGRAM_OFFICER_NAME: MASKERI, BAISHALI

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Affect;Antineoplastic Agents;Base Sequence;Benign;Binding;Binding Proteins;Binding Sites;Biological Assay;Biological Markers;cancer biomarkers;Cancer Etiology;Cell Physiology;Cells;Characteristics;Chemical Agents;Chemical Exposure;chemotherapeutic agent;Chemotherapy-Oncologic Procedure;Chromosome Fragile Sites;Chromosomes;Clinical;clinical application;Complex;Data;Development;disease diagnostic;Disease susceptibility;DNA;DNA Maintenance;DNA Structure;DNA-Directed RNA Polymerase;Dose;Environmental Exposure;enzyme activity;Evaluation;Excision;experimental study;Exposure to;Foundations;Frequencies;Future;Gene Rearrangement;Generations;Genes;Genetic Transcription;Genome;genome-wide;Genomic Instability;Genotype;Hematopoietic stem cells;high risk population;Human;human disease;Human Genome;In Vitro;Individual;insertion/deletion mutation;Ligation;Malignant Neoplasms;Maps;Measures;Mediating;Metabolism;Mind;Modeling;Molecular;Monitor;Mutation;Normal Cell;novel diagnostics;Outcome;Pathologic;Patients;personalized medicine;Pharmaceutical Preparations;Physiological;Population;Predisposition;Process;promoter;Residual state;response;Risk Assessment;Role;screening;Signal Transduction;Single Nucleotide Polymorphism;Single-Stranded DNA;Site;stem;Stress;Structure;Superhelical DNA;Testing;Therapeutic;Therapy-Related Acute Myeloid Leukemia;Time;Topoisomerase II;Topoisomerase-II Inhibitor;Transcription Initiation Site;Untranslated RNA;Variant;Work;Yeasts

PROJECT_TITLE: Genome-wide DNA Secondary Structure Analysis to Investigate DNA Fragility

STUDY_SECTION: GCAT

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


NIH_SPENDING_CATS: Autoimmune Disease;Brain Disorders;Multiple Sclerosis;Neurodegenerative;Neurosciences

PHR: PROJECT NARRATIVE Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are known to be T cell-mediated autoimmune diseases. However, less understood is the relationship between initial innate immune activities and CNS autoimmunity. In this proposal, we will elucidate crosstalk between the innate immune system and the central nervous system through the dectin-1 receptor to identify novel therapeutic targets for neuroprotection.

PI_NAMEs: SHINOHARA, MARI L. (contact)

PROGRAM_OFFICER_NAME: UTZ, URSULA

PROJECT_TERMS: Address;Adjuvant;Animal Model;Astrocytes;Autoimmune Diseases;Brain;C Type Lectin Receptors;cell type;Cell Wall;Cells;Central Nervous System;CNS autoimmunity;Cues;Cuprizone;Cytoprotection;Data;dectin 1;Demyelinations;Disease;Equilibrium;Experimental Autoimmune Encephalomyelitis;experimental study;fungus;Goals;Immune;Immune checkpoint inhibitor;Immune system;Immunologic Receptors;Infection;Infiltration;Inflammation;Inflammatory;Innate Immune System;innovation;Lead;Ligands;Mediating;Modeling;Molecular;Multiple Sclerosis;Mus;Mycoses;Myeloid Cells;Nerve Degeneration;neuroinflammation;neuropathology;neuroprotection;new technology;new therapeutic target;novel;oncostatin M;Pathology;Play;programmed cell death ligand 1;protective effect;receptor;Role;Signal Induction;Signal Pathway;Signal Transduction;Sterility;superresolution microscopy;Symptoms;T-Lymphocyte;Testing;Therapeutic Intervention

PROJECT_TITLE: Protective role of Clec7a/dectin-1 in CNS autoimmunity

STUDY_SECTION: CNBT

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


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Biotechnology;Building Research Capacity at Institutions with Limited NIH Funding;Genetics;Human Genome;Neurosciences

ORG_CITY: LOS ANGELES

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Genomic technologies are revolutionizing biomedical research and increasingly permeating all aspects of biosciences research and medicine. This development has triggered a huge need for genomic data analysis expertise among researchers and professionals. There is a particular need for this expertise among researchers in the neuroscience community and this proposal aims to provide training in genomic analysis to undergraduate students who are interested in careers in neuroscience.

PI_NAMEs: ESKIN, ELEAZAR  (contact);OPHOFF, ROEL A

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Address;Bioinformatics;Biological Sciences;Biomedical Research;Brain Diseases;career;cohort;collaboratory;Communities;Computational Biology;Data Analyses;Development;Doctor of Philosophy;Education Projects;Educational workshop;experience;Faculty;faculty community;frontier;Funding;Future;Genetic;genomic data;Genomics;Goals;graduate school;hands on research;Health;Infrastructure;interest;Learning;Medicine;Mentors;Minority-Serving Institution;National Institute of Neurological Disorders and Stroke;Nervous System Disorder;neurobehavioral;neurogenetics;neurogenomics;Neurosciences;next generation sequencing;Participant;programs;recruit;Research;Research Personnel;Research Project Grants;Schools;Science;skills;Structure;Student recruitment;student training;Students;summer program;summer research;Technology;Training;undergraduate research experience;undergraduate student

PROJECT_TITLE: Undergraduate Research Experiences in Neurogenetics and Neurogenomics


NIH_SPENDING_CATS: Bioengineering;Biomedical Imaging;Cancer;Clinical Research;Health Services;Lung;Lung Cancer;Precision Medicine;Prevention

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

ORG_STATE: WA

PHR: Project Narrative This work aims to develop innovative statistical methods for analyzing phase III and IV biomarker studies to accelerate biomarker development for cancer early detection. The proposed research is essential for analyzing two high-impact collaborative studies for pancreatic cancer and lung cancer early detection; it will also yield guidelines for addressing several critical issues in current practice, including: 1) primary endpoint selection and proper strategies to assess screening efﬁcacy in phase IV trials, 2) utilization of phase IV studies in phase III biomarker panel development, and 3) combination of studies with differential screening modalities and eligibility criteria when estimating design parameters for biomarker clinical utility trials.

PI_NAMEs: HUANG, YING  (contact)

PROGRAM_OFFICER_NAME: HODGES, NICHOLAS AARON

PROJECT_TERMS: Acceleration;Address;Algorithms;anti-cancer research;Biological Markers;biomarker development;biomarker panel;biomarker performance;biomarker validation;cancer biomarkers;Cancer Detection;cancer site;cancer therapy;Characteristics;Clinical;clinical application;clinical diagnosis;clinical practice;cohort;Cohort Analysis;Cohort Studies;computed tomography screening;Consumption;Cost efficiency;Data;Data Analyses;design;Development;Diabetes Mellitus;Diagnosis;dissemination trial;Early Detection Research Network;Early Diagnosis;efficacy evaluation;Eligibility Determination;Failure;Future;Guidelines;Hybrids;improved;innovation;Laboratories;Lead;low dose computed tomography;lung cancer screening;Malignant neoplasm of pancreas;Malignant Neoplasms;Medical Research;Methodology;Methods;Modality;novel;Participant;Phase;phase 3 study;phase 4 study;phase IV trial;precision medicine;primary endpoint;Procedures;Process;programs;prospective;Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial;Research;Research Design;Research Personnel;Resources;Sampling;Scientific Advances and Accomplishments;screening;Screening for cancer;screening guidelines;software development;Specimen;Statistical Methods;Target Populations;Testing;Time;tool;Translating;user-friendly;Validation;validation studies;Work

PROJECT_TITLE: Accelerating biomarker development through novel statistical methods for analyzing phase III/IV studies

STUDY_SECTION: CBSS

STUDY_SECTION_NAME: Cancer Biomarkers Study Section[CBSS]


NIH_SPENDING_CATS: Biotechnology;Cancer;Chronic Pain;Neurofibromatosis;Neurosciences;Orphan Drug;Pain Research;Rare Diseases

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

PHR: NARRATIVE Patients with Schwannomatosis (SWN) overwhelmingly present with intractable, debilitating chronic pain. There is currently no curative treatment for this disease, treatment for SWN is limited to invasive surgery, which carries significant risk of further nerve damage. Our project will i) provide pivotal cellular and molecular mechanistic insights into the role of tumor (HMGB1)–neuron (CCL2)–macrophage (IL-6) crosstalk in causing pain in SWN, and ii) employ FDA-approved IL-6 and EGFR inhibitors to simultaneously alleviate pain and control tumor growth in SWN. If successful, our results will inform the design and catalyze the initiation of clinical trials in SWN to improve treatment.

PI_NAMEs: MAO, JIANREN ;XU, LEI  (contact)

PROGRAM_OFFICER_NAME: MORRIS, JILL A

PROJECT_TERMS: Adoptive Transfer;Afferent Neurons;Amplifiers;Bone Marrow;Cell Line;chemokine;chronic pain;clinical translation;Clinical Trials;clinically relevant;combinatorial;Compensation;curative treatments;cytokine;design;Development;Disease;efficacy evaluation;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;Etiology;experimental study;FDA approved;Genetic;Genetic Diseases;Goals;Growth;HMGB1 gene;improved;Induced Neurons;Infiltration;Inflammation;Inflammatory;insight;Interleukin-6;Lesion;Lifelong disability;Ligands;loss of function;Macrophage;Modeling;Molecular;mouse model;Mus;nerve damage;Neurilemmoma;neuronal tumor;Neurons;neutralizing antibody;new therapeutic target;Non-Malignant;novel;novel therapeutics;Operative Surgical Procedures;Pain;pain reduction;patient derived xenograft model;Patients;Peripheral Nerves;Pharmaceutical Preparations;pharmacologic;Production;recruit;Research;response;Risk;Role;Schwannomatosis;sciatic nerve;Sensory;Signal Transduction;Spinal Ganglia;Spinal nerve structure;Testing;Treatment Efficacy;tumor;tumor growth;Tumor-Derived;Vertebral column

PROJECT_TITLE: Co-Targeting IL-6 and EGFRsignaling for the Treatment of Schwannomatosis and Associated Pain

STUDY_SECTION: CMBG

STUDY_SECTION_NAME: Cellular and Molecular Biology of Glia Study Section[CMBG]


ED_INST_TYPE: UNIVERSITY-WIDE

NIH_SPENDING_CATS: Cancer;Immunotherapy;Urologic Diseases

ORG_CITY: BRONX

ORG_NAME: ALBERT EINSTEIN COLLEGE OF MEDICINE

PHR: The proposed research is directly relevant to public health and NIH’s mission, because our program will result in new functional and mechanistic understanding of a new immune checkpoint pathway in human bladder cancer. This new insight will directly translate into novel immunotherapies for the treatment of human bladder cancer.

PI_NAMEs: ZANG, XINGXING  (contact)

PROGRAM_OFFICER_NAME: HU, ZHANG-ZHI

PROJECT_TERMS: Acceleration;anti-PD-L1 antibodies;Basic Science;Biology;Bladder;cancer type;CD276 gene;CD28 gene;CD8-Positive T-Lymphocytes;CD80 gene;Cells;checkpoint inhibition;Clinical;Clinical Management;Clinical Research;combinatorial;Computational Biology;Coupled;CTLA4 gene;Cytoplasmic Tail;Data;Development;Disease;effective therapy;Endogenous Retroviruses;experience;Family;Family member;FDA approved;Future;Human;Human Biology;humanized mouse;Immune;immune checkpoint;Immune checkpoint inhibitor;Immunoglobulin Domain;Immunoglobulins;Immunologist;Immunosuppression;Immunotherapy;inhibitor;innovation;insight;ITIM;Killer Cells;Knowledge;Malignant neoplasm of urinary bladder;Malignant Neoplasms;Mediating;Medical Oncology;member;Membrane;Mission;Modeling;Molecular;Monkeys;Monoclonal Antibodies;mouse model;multidisciplinary;Mus;Natural Killer Cells;new therapeutic target;novel;Oncologist;Outcome;overexpression;Pathway interactions;Patients;PD-1/PD-L1;PDL1 inhibitors;Phylogenetic Analysis;programmed cell death ligand 1;programmed cell death protein 1;programs;Public Health;Publishing;Qualifying;Rattus;Reagent;receptor;Recurrence;Research;Research Personnel;Resources;response;Signal Transduction;Survival Rate;System;Testing;therapeutic target;Translating;Translational Research;Treatment Efficacy;Trees;United States;United States National Institutes of Health;Urologist;Urology;VTCN1 gene;Work

PROJECT_TITLE: A New Immune Checkpoint Pathway in Human Bladder Cancer

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-OTC-D(08)F]


ORG_CITY: CLEVELAND

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: CLEVELAND CLINIC LERNER COM-CWRU

ORG_STATE: OH

PHR: PROJECT NARRATIVE Basic science exploration of cancer promoting molecules led to patient impacting drug discoveries which now promote the search for new molecular targets. The proposed project is designed to understand a recently discovered function of one of the most important cancer promoting proteins, Mcl-1. Data garnered from this set of studies will bring both timely and clinically important information for current cancer targeting drug design.

PI_NAMEs: MELENHORST, JAN J (contact)

PROGRAM_OFFICER_NAME: FORRY, SUZANNE L

PROJECT_TERMS: Ablation;Adult;Apoptosis;Apoptotic;Automobile Driving;Basic Science;Bcl-2 Homology Domain;BCL-2 Protein;BCL2 gene;Binding;biological adaptation to stress;Biological Assay;Calmodulin;cancer cell;Cancer Model;Cell Nucleus;Cells;Cessation of life;Chemoresistance;chemotherapy;Clinical;Clinical Trials;Colon Carcinoma;Colorectal;Colorectal Cancer;combinatorial;Complex;coping;Data;design;Doxorubicin;Drug Design;drug discovery;Drug Targeting;Enzymes;Event;Failure;Family;Family member;Gene Expression;Genes;Goals;Human;Hydrophobicity;improved outcome;In Vitro;in vivo;inhibitor;insight;interest;knock-down;Knock-out;Malignant Neoplasms;MCL1 gene;Mediating;member;Messenger RNA;Metabolic;Mitochondria;Modeling;Molecular;molecular domain;Molecular Target;mRNA Stability;NADPH Oxidase;neoplastic cell;novel;novel therapeutic intervention;novel therapeutics;Nuclear;Nuclear Protein;Nuclear Translocation;overexpression;Oxidation-Reduction;Oxidative Stress Induction;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacologic Substance;Play;Post-Transcriptional Regulation;posttranscriptional;prevent;Production;programs;Protein Binding Domain;protein complex;Protein Family;Proteins;Proteomics;Reaction;Reactive Oxygen Species;Recombinant Proteins;Regulation;Reporting;Resistance;response;RNA Stability;Role;small molecule;small molecule inhibitor;Solid Neoplasm;synergism;Testing;Therapeutic;Therapeutic Intervention;Transcript;tumor;Tumor Bank;United States;Up-Regulation

PROJECT_TITLE: Mechanisms of nuclear Mcl-1 mediated chemoresistance

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 2 Study Section[MCT2]


NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Colorectal Cancer;Digestive Diseases;Genetics;Immunotherapy;Women's Health Research

ORG_NAME: BOSTON CHILDREN'S HOSPITAL

PHR: Most colorectal cancers are microsatellite stable (MSS) and do not respond to checkpoint inhibitor therapy; they have poor prognosis when they have spread locally or have metastasized. By contrast the minority of colorectal tumors with high microsatellite instability (MSI-high), which have defects in DNA mismatch repair, respond to checkpoint inhibitor therapy and have good prognosis. Here we will investigate a tumor-targeted gene knockdown strategy to convert immunologically cold MSS tumors to immunologically responsive MSI-high tumors, which we hypothesize will dramatically improve clinical outcome when used on its own or when combined with chemotherapy or checkpoint inhibitors.

PI_NAMEs: LIEBERMAN, JUDY  (contact)

PROGRAM_OFFICER_NAME: CHEN, WEIWEI

PROJECT_TERMS: Affinity;aggressive breast cancer;antitumor effect;aptamer;cancer cell;cancer diagnosis;cancer infiltrating T cells;cancer stem cell;Carcinoma;CD8-Positive T-Lymphocytes;Cells;checkpoint therapy;chemokine;chemotherapy;Chimera organism;Clinical;colon cancer cell line;colon cancer patients;Colorectal Cancer;Colorectal Neoplasms;CXCL13 gene;Death Rate;Defect;Dependence;design;Disease;DNA;DNA Adducts;DNA Damage;Epithelium;Fibroblasts;Gene Expression;Gene Expression Profile;Genes;Genetic Transcription;Genetically Engineered Mouse;Graft Enhancements;Human;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;Immune response;Immunocompetent;immunodeficiency;Immunologic Surveillance;Immunologics;Immunotherapy;Implant;improved;Infiltration;Inflammation;Inflammatory;Interferons;Intervention;Intestines;Killer Cells;knock-down;LGR5 gene;Link;Macrophage;Malignant Neoplasms;Mammary Neoplasms;Metalloproteases;metastatic colorectal;Methods;Microsatellite Instability;Microsatellite Repeats;Minority;Mismatch Repair;Mismatch Repair Deficiency;Modeling;monocyte;Mus;Mutate;Mutation;Myeloid Cells;neoantigens;Neoplasm Metastasis;neutrophil;Neutrophil Infiltration;Operative Surgical Procedures;Organoids;Outcome;Pharmaceutical Preparations;Phenotype;Prognosis;programs;promoter;recruit;repair enzyme;repaired;Resistance;resistance mechanism;response;Small Interfering RNA;small molecule inhibitor;Somatic Mutation;stem cells;subcutaneous;Subcutaneous Injections;T-Lymphocyte;TACSTD1 gene;Testing;Therapeutic;Tissues;triple-negative invasive breast carcinoma;tumor;Tumor Antigens;tumor growth;Tumor Immunity;Tumor Tissue;Tumor-infiltrating immune cells;virtual

PROJECT_TITLE: Tumor-targeted disruption of mismatch repair in microsatellite stable colorectal cancer


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Immunization;Immunotherapy;Infectious Diseases;Orphan Drug;Prevention;Rare Diseases

ORG_DEPT: SURGERY

PHR: RELEVANCE TO PUBLIC HEALTH Several New World mammarenaviruses (NWMs) cause a severe life-threatening hemorrhagic fever syndrome and pose a significant public health risk and threat to national security. In the absence of FDA-approved vaccines or therapeutics, there is an urgent need to develop antiviral therapies that are broadly applicable to the treatment of NWM hemorrhagic fever. The goal of this project is to advance the development of a novel antibody-based therapeutic approach for the treatment of severe NWM infections.

PI_NAMEs: GOWEN, BRIAN B.;PENICHET, MANUEL L (contact)

PROGRAM_OFFICER_NAME: DYALL, JULIE

PROJECT_TERMS: Advanced Development;aerosolized;Affinity;Americas;Anti-viral Therapy;Antibodies;Antibody Therapy;antigen binding;Antigens;antiviral drug development;Apical;Argentinian Hemorrhagic Fever;Attenuated;Autoimmune Diseases;Avidity;Binding;Binding Sites;Biodistribution;Blood;Bolivian Hemorrhagic Fever Virus;Case Fatality Rates;Cell Culture Techniques;Cells;chimeric antibody;Clinic;Clinical;Combined Modality Therapy;Complement 1q;convalescent plasma;Cross Reactions;Development;Dimensions;Disease;Disease Outbreaks;DNA;Dose;Drug Kinetics;Exhibits;Fc Receptor;FDA approved;Functional disorder;Glycoproteins;Goals;GTPBP1 gene;Hemochromatosis;Human;human data;IgG1;Immunoglobulin M;Impairment;In Vitro;Infection;Inhalation;interest;Interferon alpha;interferon alpha receptor;International;Iron;Junin virus;Life;Ligands;Light;Macaca fascicularis;Mammalian Cell;Membrane Glycoproteins;Modeling;Molecular Weight;Monitor;monomer;Morbidity - disease rate;mortality;Mus;mutant;National Security;Nature;nonhuman primate;novel;novel therapeutic intervention;novel therapeutics;Organ;particle;Pathogenesis;Pathogenicity;polymeric IgM;Population;prevent;priority pathogen;Property;Proteins;Public Health;receptor;Risk;Rodent;Surface Plasmon Resonance;Survivors;Syndrome;Testing;TFRC gene;Therapeutic;Therapeutic antibodies;therapeutic candidate;therapeutic target;Toxic effect;Transferrin;Transgenic Mice;transmission process;uptake;Vaccines;vector;Viral;Viral Hemorrhagic Fevers;Viral Load result;Viral Physiology;Virus;virus envelope;Zoonoses

PROJECT_TITLE: Antibody-based therapeutic strategy for New World mammarenavirus hemorrhagic fever

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AIDC-B(82)]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Genetics;Heart Disease;Heart Disease - Coronary Heart Disease;Regenerative Medicine

ORG_CITY: CHAPEL HILL

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: Public Health Relevance: Heart disease is the leading cause of morbidity and mortality in the developed world. Because cardiomyocytes in the heart have limited regenerative potential in response to injury, loss of cardiomyocytes results in impaired pump function and heart failure. Our strategy to reprogram endogenous cardiac fibroblasts into contractile cardiomyocyte-like cells holds promise as a novel therapy for the treatment of this prevalent and morbid disease.

PI_NAMEs: QIAN, LI  (contact)

PROGRAM_OFFICER_NAME: WONG, RENEE P

PROJECT_TERMS: Acute myocardial infarction;Cardiac;Cardiac Myocytes;cardiac repair;Cardiovascular Physiologic Processes;Cells;Cicatrix;clinical application;Developmental Cell Biology;Disease;Doctor of Philosophy;epigenetic regulation;Fibroblasts;functional improvement;Funding;GATA4 gene;Genetic Transcription;Grant;Heart;Heart Diseases;Heart failure;Heart Injuries;Human;Impairment;improved;in vivo;in vivo evaluation;Induced Cardiomyocytes;insight;Knowledge;Laboratories;mathematical model;Mechanics;Modeling;Molecular;Morbidity - disease rate;mortality;multiple omics;Mus;Myocardium;National Heart, Lung, and Blood Institute;Natural regeneration;novel;novel therapeutics;Pathologic Processes;Patients;Post-Transcriptional Regulation;Postdoctoral Fellow;programs;public health relevance;Pump;regeneration potential;response to injury;stem cell biology;System;Time;Tissues;Training;transcription factor

PROJECT_TITLE: Altering Cardiac Cell Fate for Heart Repair


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

NIH_SPENDING_CATS: Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

ORG_STATE: CT

PHR: This application will test the hypotheses that: 1) during homeostasis marrow-resident cells are the principal source of osteoclast precursors (OCP), while during states of inflammation or fracture repair, circulating cells are a significant OCP source and 2) there are different mechanisms regulating OCP homing, engraftment and differentiation between healthy and disease states. Experiments are proposed that will define the phenotype and identify mechanisms that regulate OCP maturation into osteoclasts in homeostasis and examine OCP homing engraftment and differentiation from the circulation during bone inflammation and fracture repair.

PI_NAMEs: LORENZO, JOSEPH A (contact)

PROGRAM_OFFICER_NAME: CHEN, FAYE H

PROJECT_TERMS: Adoptive Transfer;Age;Blood;bone;Bone callus;Bone Diseases;bone fracture repair;Bone Marrow;Bone Resorption;bone turnover;Calvaria;Cells;chemokine receptor;Circulation;CX3CR1 gene;Data;defined contribution;Development;Disease;disease model;Drug Targeting;Engraftment;experimental study;Femoral Fractures;Fracture;Gene Deletion;Goals;Health;Home;Homeostasis;Homing;in vivo;Inflammation;Inflammatory;Kinetics;Label;Marrow;Modeling;Molecular;Monitor;Mus;Myelogenous;Osteitis;osteoclast progenitor;Osteoclasts;Osteolysis;Osteolytic;Parabiosis;Phenotype;Population;Process;progenitor;recruit;repaired;Role;Signal Transduction;Site;Source;Spleen;stem cell migration;stem cell population;Testing;therapy design;therapy development;Time;TNF gene;trafficking;Vascular blood supply

PROJECT_TITLE: Studies of Osteoclast Lineage in Health and Diseases

STUDY_SECTION: SBDD

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


ORG_CITY: BIRMINGHAM

ORG_DEPT: NEUROLOGY

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: SULT4a1 protein levels significantly decrease in stroke and potentially lead to mitochondrial dysfunction via alteration in peroxiredoxin-dependent redox homeostasis. SULT4a1 is essentially required for neural survival. SULT4a1 protects against peroxide-induced cell injury and oxygen glucose deprivation-mediated cell death in neurons, making SULT4a1 a strong candidate for evaluation of neuroprotection in stroke.

PI_NAMEs: ANDRABI, SHAIDA A. (contact)

PROGRAM_OFFICER_NAME: BOSETTI, FRANCESCA

PROJECT_TERMS: Age;Back;Biological Assay;Biotin;Brain;brain tissue;Cause of Death;Cell Death;Cell Death Signaling Process;cell injury;Cell Survival;Cells;Cessation of life;Co-Immunoprecipitations;Coagulation Process;Complex;Cytosol;Data;deprivation;disability;Disease;Drug Metabolic Detoxication;Electron Microscope;Enzymes;Evaluation;Experimental Models;Exposure to;Family;Functional disorder;Gene Targeting;Genus Hippocampus;Glucose;Homeostasis;Hydrogen Peroxide;Image;In Vitro;in vivo;Inflammatory Response;knock-down;Knockout Mice;Knowledge;Ligation;Literature;live cell imaging;Magnetic Resonance Imaging;Mechanics;Mediating;Mediator;member;MG132;microscopic imaging;Middle Cerebral Artery Occlusion;Mitochondria;mitochondrial dysfunction;Modeling;Morbidity - disease rate;Mus;neural;Neurons;neuroprotection;new therapeutic target;novel;novel strategies;Oxidation-Reduction;Oxygen;Pathway interactions;Pattern;Peroxides;peroxiredoxin;peroxiredoxin I;pharmacologic;Phenotype;post stroke;Process;Proteins;Proteomics;Recycling;Regulation;Role;Secondary to;small hairpin RNA;Stains;Stroke;stroke model;sulfotransferase;System;targeted treatment;Therapeutic Intervention;therapeutic target;therapeutically effective;Thrombectomy;TXN gene;Ubiquitin;ubiquitin-protein ligase;Vertebrates;Viral

PROJECT_TITLE: SULT4a1, a novel neuroprotective protein in stroke

STUDY_SECTION: NOMD

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


NIH_SPENDING_CATS: Bioengineering;Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: The software developed in this project will allow researchers to more accurately quantify and interpret brainwave data recorded from healthy individuals in basic science studies and from patients in translational and clinical science studies. It will allow research on normal and abnormal brain function to progress more rapidly, leading to a better understanding, diagnosis, and treatment of diseases of mind and brain.

PI_NAMEs: LUCK, STEVEN J (contact)

PROGRAM_OFFICER_NAME: BENNETT, YVONNE MARIE

PROJECT_TERMS: Address;Adoption;Affective;Algorithms;Automatic Data Processing;Automation;base;Basic Science;Biological;Black Box;Brain;Brain Diseases;brain dysfunction;Clinical;Clinical Research;Clinical Sciences;Clinical Trials;Cognition;Cognitive;Complement;Complex;Computer software;computerized data processing;cost effectiveness;Data;Data Analyses;data quality;data visualization;design;Development;Diagnosis;Disease;Documentation;Electroencephalography;Emotions;Event-Related Potentials;Experimental Designs;flexibility;Functional disorder;Functional Magnetic Resonance Imaging;Funding;Genetic study;Goals;Grant;graphical user interface;Human;Human Resources;improved;Individual;innovation;Laboratories;Learning;Licensing;Link;Measures;Methods;millisecond;Mind;Motor;Neurology;Neurosciences;open source;open source tool;Paper;Patients;Pattern;Perception;Procedures;programs;Psychiatry;Psychology;Publications;Publishing;Reproducibility;Research;Research Personnel;Resolution;Resources;Science;Sensory;Signal Transduction;simulation;skills;software development;Sorting;Source;System;Systems Analysis;Techniques;temporal measurement;Textbooks;Time;tool;Training;Translational Research;trend;usability;Writing

PROJECT_TITLE: ERPLAB: Extensible, open source software for analysis of event-related potentials


NIH_SPENDING_CATS: Aging;Biotechnology;Genetics;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Non-Human

ORG_CITY: CHICAGO

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

ORG_STATE: IL

PHR: Project Narrative: In this project, we will directly visualize cell migration and proliferation promoted by a miRNA in intact skin using live imaging. We will also probe underlying mechanism mediated by the miRNA and its targets in balancing epidermal proliferation and differentiation in the epidermis and stimulating hair follicle growth. Knowledge gained from the proposed studies will provide new insights into our basic understanding of skin stem cells at molecular, cellular and tissue levels, with important therapeutic implications.

PI_NAMEs: YI, RUI  (contact)

PROGRAM_OFFICER_NAME: BELKIN, ALEXEY

PROJECT_TERMS: Actins;Address;Adherens Junction;Adult;Affect;animal old age;Animals;appendage;Basal Cell;Biological Process;Biology;Cell Adhesion;Cell division;Cell membrane;Cell Migration Induction;cell motility;Cell Proliferation;cell type;Cells;cellular imaging;computational pipelines;Computer Analysis;Cytoskeleton;Data;Embryo;Environmental Hazards;Epidermis;Epithelial Cells;epithelial stem cell;Equilibrium;experimental analysis;experimental study;Gene Expression;Gene Expression Regulation;Genes;Genetic;genetic analysis;genomic tools;Genomics;Germ;Growth;Hair;Hair follicle structure;Homeostasis;Image;imaging capabilities;imaging system;in vivo;Individual;insight;Ion Channel;juvenile animal;Knowledge;Liquid substance;live cell imaging;Longitudinal Studies;Maintenance;Maps;Mechanics;mechanotransduction;Mediating;Messenger RNA;MicroRNAs;migration;Molecular;Molecular Probes;mouse genetics;mouse model;multi-photon;novel;old mice;Organ;Pathogenesis;Pathway interactions;Piezo 1 ion channel;Play;Population;posttranscriptional;premature;Proliferating;Property;Regenerative Medicine;Regulation;RNA;Role;Site;Skin;Skin Aging;skin organogenesis;stem;stem cell migration;stem cell population;stem cells;Stratum Basale;Stress;Techniques;Therapeutic;Tissues;tool;transcriptome;Untranslated RNA;Visualization

PROJECT_TITLE: Genetic Analysis of MicroRNA Functions in Skin Stem Cells In Vivo


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

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

ORG_CITY: BERKELEY

ORG_DEPT: PSYCHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project narrative This project focuses on understanding how the hippocampus encodes a cognitive map and how it communicates this information to orbitofrontal cortex in order to improve learning. Dysfunction of both these brain areas has been implicated in a wide variety of neuropsychiatric disorders, including schizophrenia, depression, anxiety, and post-traumatic stress disorder. Understanding the contribution of this pathway could lead to an important target for future therapeutic interventions.

PI_NAMEs: WALLIS, JONI D (contact)

PROGRAM_OFFICER_NAME: ROSSI, ANDREW F

PROJECT_TITLE: Hippocampal-orbitofrontal interactions and reward learning


ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE The current project will identify the role of toxins generated by intestinal bacteria in the pathogenesis of brain microbleeds. This research proposal is relevant to public health because there are over 20 million Americans who have chronic kidney disease and these persons are at increased risk for microbleeds (tiny spots of bleeding in the brain) which lead to stroke and dementia. We hope that our work will provoke investigations into gut-directed therapies that will decrease brain microbleeds and preserve quality of life for people living with chronic kidney disease.

PI_NAMEs: LAU, WEI LING  (contact)

PROGRAM_OFFICER_NAME: DALEY, WILLIAM PATRICK

PROJECT_TERMS: 16S ribosomal RNA sequencing;Adenine;Affect;Age;Aging;American;Amines;Amino Acids;Animals;Antibiotics;Bacteria;Bacterial Translocation;behavioral study;Bioinformatics;Blood;Blood - brain barrier anatomy;Blood Circulation;Blood Preservation;Blood Vessels;Brain;brain endothelial cell;Brain hemorrhage;brain magnetic resonance imaging;cardiovascular risk factor;Cardiovascular system;Cells;Cerebrovascular Disorders;Chronic;Chronic Kidney Failure;Continuous Infusion;Dementia;Development;Dialysis patients;Dialysis procedure;Diet;Diffuse;disease model;Disease Progression;effective intervention;Endothelium;Enterocytes;Female;Fermentation;Functional disorder;Future;Gastrointestinal tract structure;glial activation;Goals;gut dysbiosis;gut microbes;gut microbiome;gut-brain axis;Hemorrhage;High Prevalence;Histology;Human Resources;Hypertension;Impaired cognition;Implant;improved;In Vitro;in vivo;Indican;indoxyl;Infiltration;Intervention;Intestines;Investigation;Kidney;Knowledge;Magnetic Resonance Imaging;male;Mass Spectrum Analysis;metabolomics;Microbe;microbial;microbiome alteration;Microglia;Modeling;monolayer;Morbidity - disease rate;Mus;Nephrectomy;novel therapeutics;Operative Surgical Procedures;Organ;Outcome;Oxidative Stress;Oxidative Stress Induction;Oxides;Pathogenesis;Pathogenicity;Pathway interactions;Patients;Persons;Pilot Projects;platelet function;Population;Population Study;preservation;Prevalence;Production;Proteins;Public Health;Publications;Quality of life;Renal function;Research;Research Proposals;Risk;Risk Factors;Role;Route;Sex Differences;Spottings;Stroke;Stroke prevention;subcutaneous;Sulfate;systemic inflammatory response;Technology;Tight Junctions;tool;Toxin;United States;Urea;Uremia;Work

PROJECT_TITLE: Gut-Derived Toxins and Brain Microbleeds in Chronic Kidney Disease

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Bioengineering;Brain Disorders;Cerebrovascular;Dementia;Neurodegenerative;Neurosciences;Vascular Contributions to Cognitive Impairment and Dementia (VCID)

ORG_CITY: RENO

ORG_NAME: UNIVERSITY OF NEVADA RENO

ORG_STATE: NV

PHR: Project Narrative: Our long-term goal is to better understand a broad array of physiological and pathological brain processes and ultimately uncover treatments for neurological disorders such as stroke and vascular dementia. Findings from the proposed project will reveal insights into the integration of different signaling pathways required to regulate blood flow distribution matching with metabolic demands. This will map out the landscape and build an important foundation for understanding brain blood flow in health and disease and ultimately provide the basis for correctly interpreting fMRI data, a technique that has been used extensively in medical diagnostics as well as unearth potential treatments.

PI_NAMEs: TRAN, CAM HA THAI (contact)

PROGRAM_OFFICER_NAME: HEWETT, SANDRA JEANNE

PROJECT_TERMS: Address;Affect;alertness;Anesthetics;Animals;Architecture;Area;Astrocytes;Attention;awake;Biosensor;Blood;Blood capillaries;Blood flow;Blood Vessels;Brain;brain health;Brain region;cell type;Cells;Cerebrovascular Circulation;cholinergic;clinical diagnostics;Communication;Complement;connexin 40;Data;designer receptors exclusively activated by designer drugs;Development;Disease;Elements;Endothelium;Ensure;Equilibrium;Event;fluorescence imaging;Foundations;Functional Magnetic Resonance Imaging;Gap Junctions;glutamatergic signaling;Glutamates;Goals;Health;hemodynamics;Hyperemia;in vivo;insight;Investigation;Knock-out;Knockout Mice;Laboratories;Laser Scanning Microscopy;Lesion;Maps;Mediating;Metabolic;Microcirculation;Modeling;Molecular;Mus;neocortical;Nervous System Disorder;neural;Neurons;neuroregulation;Neurotransmitters;neurovascular coupling;neurovascular unit;noradrenergic;novel;novel diagnostics;novel strategies;novel therapeutics;Nutrient;optogenetics;Outcome;Oxygen;Pathologic;Pathway interactions;Perfusion;Pharmacogenetics;Physiological;Physiological Processes;postsynaptic;Preparation;Process;Regulation;Research;response;Role;Sensory;Serotonergic System;Serotonin;side effect;Signal Pathway;Signal Transduction;Slice;spatiotemporal;Stroke;Surface;Synapses;Systems Integration;Techniques;Testing;Time;tool;two-photon;Vascular blood supply;Vascular Dementia;vasoactive agent;vasoconstriction;Vasodilation;Vasomotor;Vibrissae;Wakefulness;Work

PROJECT_TITLE: Integrated Cerebral Blood Flow Regulation

STUDY_SECTION: BINP

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Genetics;Hematology;Lymphatic Research;Lymphoma;Orphan Drug;Rare Diseases

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: Project Narrative T-cell lymphomas (TCL), comprising ≈15% of non-Hodgkin lymphomas (NHL) in North America, are molecularly heterogeneous, poorly understood, and are associated with poor clinical outcomes, as most patients will develop recurrent or refractory disease that is resistant to currently available therapies, particularly if their TCL expresses the transcription factor GATA-3. We will investigate the role of Notch and GATA-3, a Notch target gene, in T-cell lymphoma pathogenesis and will develop novel therapeutic strategies targeting these transcriptional regulators.

PI_NAMEs: WILCOX, RYAN A (contact)

PROGRAM_OFFICER_NAME: JHAPPAN, CHAMELLI

PROJECT_TERMS: Acetylation;Address;Antibodies;Binding;Biotin;Bromodomain;CDKN2A gene;Cells;Characteristics;Chemoresistance;chemotherapy;Chimeric Proteins;chromatin remodeling;Chromosome Deletion;Clinical;cytokine;Data;Diagnosis;Disease Progression;Disease remission;Disease Resistance;DNA Binding;Dominant-Negative Mutation;EP300 gene;gain of function;GATA3 gene;Genes;Genetic;Genetic Heterogeneity;Genetic Transcription;Genetically Engineered Mouse;Goals;high risk;Human;Impairment;improved outcome;innovation;Knowledge;Ligands;Ligase;loss of function;Lymphoma;Lymphoma cell;Lymphomagenesis;Macrophage;Mediating;Minority;Molecular;Mus;Mutate;new therapeutic target;Non-Hodgkin's Lymphoma;North America;notch protein;novel;novel therapeutic intervention;novel therapeutics;Outcome;p300/CBP-Associated Factor;Pathogenesis;patient derived xenograft model;Patient-Focused Outcomes;Patients;pharmacologic;Progressive Disease;Proliferating;Proteins;PTEN gene;Published Comment;rational design;Recurrence;Recurrent disease;Refractory Disease;Repression;Resistance;Role;Signal Transduction;small molecule;SMARCB1 gene;Specimen;SWI/SNF Family Complex;T-Cell Development;T-Cell Lymphoma;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Therapeutic;therapeutic development;therapeutic target;TP53 gene;transcription factor;Transcriptional Regulation;Transgenes;tumor microenvironment;Tumor Suppressor Genes

PROJECT_TITLE: Notch and GATA-3 as novel therapeutic targets in T-cell lymphomas

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics - 1 Study Section[MCT1]


NIH_SPENDING_CATS: Neurosciences

ORG_CITY: WALTHAM

ORG_DEPT: BIOLOGY

ORG_NAME: BRANDEIS UNIVERSITY

PHR: PROJECT NARRATIVE Neurons can communicate with each other via electrical and chemical signals, as well as membrane-bound packets called extracellular vesicles. These vesicles carry cargo that can contribute to normal brain function, but in neurological disorders including Parkinson’s and Alzheimer’s Diseases, they can also spread toxic proteins throughout the brain. Our research will help us understand how extracellular vesicles are packaged, released and spread in the nervous system, and may identify new strategies to treat a wide variety of neurological diseases.

PI_NAMEs: RODAL, AVITAL ADAH (contact)

PROGRAM_OFFICER_NAME: MILLER, DANIEL L

PROJECT_TERMS: Acute;Alzheimer's Disease;Behavior;Binding;Biochemistry;Biogenesis;Brain;Carrier Proteins;Cell membrane;cell type;Cells;Cellular Membrane;Chemicals;Clathrin;Communication;Complex;Data;Defect;Disease;Drosophila genus;Endocytosis;Endosomes;Event;experimental study;extracellular vesicles;Foundations;Genetic;genetic approach;Goals;Human;imaging approach;in vivo;insight;intercellular communication;Knowledge;Link;Lipids;live cell imaging;Mediating;Membrane;Membrane Protein Traffic;Microscopy;Monitor;Morphogenesis;Morphology;mutant;Nature;Nerve;Nervous System;Nervous System Disorder;Nervous System Physiology;Neurodegenerative Disorders;Neuroglia;Neurons;novel;Nucleic Acids;optogenetics;Parkinson Disease;Pathologic;Pathology;Pathway interactions;Phosphotransferases;Physiological;Plasma;Play;Population;presynaptic;Presynaptic Terminals;Process;Proteins;rab11 protein;Receptor Signaling;Recycling;Regulation;Research;Resolution;response;retrograde transport;Role;Route;scaffold;Signal Transduction;Sorting;Synapses;Synaptic Membranes;Synaptic Transmission;SYNJ1 gene;Testing;Therapeutic;tool;trafficking;Vesicle;vesicular release;Work

PROJECT_TITLE: Roles of Recycling Endosomes in Neuronal Extracellular Vesicle Cargo Traffic

STUDY_SECTION: NC

STUDY_SECTION_NAME: Neuronal Communications Study Section[NC]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Lung;Lung Cancer

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Relevance: NSCLC is the most common and deadly form of cancer in the US and worldwide, and new therapies are urgently needed. Our work will clarify how to optimally deploy SHP2-Is, which recently entered the clinic, in NSCLC, define potential resistance mechanisms, and potentially suggest new combination therapies for this deadly disease.

PI_NAMEs: NEEL, BENJAMIN G. (contact);WONG, KWOK KIN

PROJECT_TERMS: adduct;Affect;Allografting;anti-tumor immune response;Apoptosis;Binding;Biology;Cancer Biology;cancer cell;cancer therapy;cell type;Cells;checkpoint receptors;Chimeric Proteins;Clinic;clinical efficacy;Color;Complex;CRISPR screen;CRISPR/Cas technology;Cytokine Receptors;Data;Disease;driver mutation;drug efficacy;Drug resistance;efficacy evaluation;Ensure;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor;exome;Expanded CRISPR-compatible cellular indexing of transcriptomes and epitopes by sequencing;experimental study;Extracellular Signal Regulated Kinases;Family;Flow Cytometry;gain of function;Genetically Engineered Mouse;genome-wide;Genomics;Genotype;Goals;Growth;Guanine Nucleotide Exchange Factors;Guanosine Triphosphate Phosphohydrolases;Immune;immune checkpoint;Immune checkpoint inhibitor;immunogenicity;Immunologic Receptors;Immunology procedure;Immunotherapy;improved;In Vitro;Infiltration;inhibitor;Kinetics;KRAS2 gene;Life;Locales;loss of function;Lymphoid Cell;Malignant neoplasm of lung;Malignant Neoplasms;MEKs;Modality;Molecular;Mus;mutant;Mutation;Myeloid Cells;neoplastic cell;new combination therapies;Non-Small-Cell Lung Carcinoma;novel therapeutic intervention;novel therapeutics;Oncogenic;Oral;Pathway interactions;Patient-Focused Outcomes;Patients;Peptides;Phase I Clinical Trials;phase I trial;Phosphoric Monoester Hydrolases;Population;Positioning Attribute;prevent;programmed cell death protein 1;Proliferating;protein phosphatase inhibitor-2;Protein Tyrosine Kinase;Proteins;Proteome;PTPN11 gene;Publishing;Receptor Activation;Receptor Protein-Tyrosine Kinases;Receptor Signaling;Recurrence;Recurrent tumor;Relapse;Resistance;Resistance development;resistance mechanism;resistance mutation;response;Role;scaffold;senescence;Signal Pathway;Signal Transduction;src Homology Region 2 Domain;targeted treatment;Testing;Therapeutic;transcriptome;Treatment Efficacy;tumor;tumor growth;tumor microenvironment;Tyrosine Kinase Receptor Inhibition;Work;Xenograft procedure

PROJECT_TITLE: Response and resistance to SHP2 inhibitors alone and in combination in Non-Small Cell Lung Cancer

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Brain Cancer;Brain Disorders;Cancer;Clinical Research;Genetics;Neurosciences;Rare Diseases

ORG_CITY: CINCINNATI

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: UNIVERSITY OF CINCINNATI

PHR: Co-targeting S6 and TAM kinases in PTEN-deficient glioblastoma Narrative The application is to investigate the mechanistic functions of the S6 and TAM kinase families as critical mediators of tumor growth and metabolism in PTEN-deficient glioblastoma. The outcome of the proposed research program will be a biological understanding that will inform strategic development of future approaches in glioblastoma therapy.

PI_NAMEs: PLAS, DAVID R (contact)

PROGRAM_OFFICER_NAME: KONDAPAKA, SUDHIR B

PROJECT_TERMS: Address;Adolescence;Adult;Affect;Age;Agreement;Apoptotic;Autoimmunity;Biological;Biological Models;Birth;Body Size;cBioPortal;cell type;Cells;Clinical Trials;Cohort Studies;Combined Modality Therapy;CRISPR/Cas technology;crizotinib;cytotoxic;cytotoxicity;Data;Development;drug development;efficacy evaluation;Embryonic Development;Event;experimental study;Family;Family member;FDA approved;Future;Genetic;genetic analysis;genetic approach;Genetic Transcription;genome editing;Glioblastoma;Glioma;Growth;hematopoietic tissue;inhibitor;Knock-out;leukemia;life span;Ligands;Link;Macrophage;Malignant - descriptor;Malignant neoplasm of brain;Malignant Neoplasms;Mammals;Mediating;Mediator;member;MERTK gene;Metabolic;Metabolic Pathway;Metabolism;Methylation;Microglia;Molecular Target;Mus;Mutation;Names;Neuroglia;Obesity;Oncology;Outcome;paralogous gene;Pathway interactions;patient derived xenograft model;Patients;Perinatal mortality demographics;Phagocytosis;pharmacologic;Pharmacologic Substance;Phase;Phenotype;Pheochromocytoma;Phosphorylation;Phosphotransferases;Physiological;Prognosis;programs;promoter;Protein Kinase;protein kinase inhibitor;Protein Tyrosine Kinase;PTEN gene;Receptor Protein-Tyrosine Kinases;Reporting;Research;Resistance;response;Ribosomal Protein S6 Kinase;Sampling;Signal Transduction;Solid;System;targeted treatment;Technology;Testing;The Cancer Genome Atlas;Therapeutic;tumor;tumor growth;tumor metabolism;Tumor Suppressor Proteins;TYRO3 gene;Tyrosine;Tyrosine Kinase Inhibitor;Up-Regulation;Validation;Work

STUDY_SECTION: TCB

STUDY_SECTION_NAME: Tumor Cell Biology Study Section[TCB]


PHR: NARRATIVE An elevated level of lipoprotein(a) [Lp(a)] is an independent causal risk factor for cardiovascular disease. This proposal evaluates the effects of dietary changes consistent with evidence-based guidelines on Lp(a) properties using three randomized controlled feeding trials—the largest and most diverse platform. The findings will improve our understanding of Lp(a) atherogenic properties and their modulators during a common, everyday condition affecting a large segment of the population.

PI_NAMEs: BYAMBAA, ENKHMAA  (contact)

PROGRAM_OFFICER_NAME: WOLZ, MICHAEL

PROJECT_TERMS: Address;Adopted;Adult;Affect;African American population;apolipoprotein Lp(a+);Biological;Black Populations;Carbohydrates;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular disorder therapy;cardiovascular risk factor;Characteristics;Cholesterol;Clinical;Complex;Data;Diet;dietary;dietary guidelines;Dietary Intervention;Environment;Ethnic Origin;evidence based guidelines;feeding;Funding;Genes;Genetic;Genetic Polymorphism;Goals;healthy lifestyle;Heart;Heterogeneity;improved;Individual;Inflammatory;Insulin Resistance;Intake;Knowledge;Laboratories;LDL Cholesterol Lipoproteins;Life Style Modification;lipidomics;Lipoprotein (a);Lipoproteins;Maps;Measures;Mediating;Meta-Analysis;Metabolic;Metabolic syndrome;Modeling;non-genetic;Nonpharmacologic Therapy;particle;Pattern;Phospholipids;Plasma;Population;precision nutrition;Prevention;Property;Race;Randomized;Recommendation;Regimen;Research;response;Risk;Saturated Fatty Acids;Subgroup;Testing;thrombogenesis;United States National Institutes of Health;Unsaturated Fats

PROJECT_TITLE: Lp(a) and Oxidized Phospholipids - Impact of Diets

STUDY_SECTION: CHSB

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


NIH_SPENDING_CATS: Biotechnology;Infectious Diseases

ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: Project Narrative Many human diseases exhibit circadian rhythmicity in their symptoms and pathology, including asthma, rheumatoid arthritis and other disorders of the immune system. Our study will bridge the gaps in understanding of the circadian proteins CRY1/2 in host innate immune response. The results of this study offer the potential to develop new therapeutics for infectious and autoimmune diseases.

PI_NAMEs: LI, SHITAO  (contact)

PROGRAM_OFFICER_NAME: KELLY, HALONNA R

PROJECT_TERMS: Adaptor Signaling Protein;Alanine;Asthma;Attenuated;Autoimmune Diseases;autoinflammatory diseases;Binding;C-terminal;circadian;Circadian Rhythms;Communicable Diseases;Consensus;cryptochrome;cryptochrome 2;Data;Dimerization;Docking;Exhibits;Genes;Germ Lines;Glutamic Acid;Goals;Host Defense;Human;human disease;hydrophilicity;Immune;Immune System Diseases;in vivo;Influenza A virus;Innate Immune Response;Innate Immune System;Interferon Type I;IRF3 gene;Knock-out;Knowledge;Literature;Mediating;mimetics;Molecular;Mutation;Natural Immunity;novel;novel therapeutics;Nucleic Acids;pathogen;Pathology;Pattern;Pattern recognition receptor;Periodicity;Phosphorylation;Phosphorylation Site;Pilot Projects;Polyubiquitin;Production;Proteins;Proteomics;recruit;Rheumatoid Arthritis;Role;Signal Pathway;Signal Transduction;Site;Stimulator of Interferon Genes;Symptoms;TBK1 gene;Testing;TLR3 gene;TRAF2 gene;Tretinoin;Ubiquitination;Virus Diseases

PROJECT_TITLE: Phosphorylation mimetic motif of cryptochrome proteins blocks IRF3 activation

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Genetics;Networking and Information Technology R&D (NITRD)

ORG_CITY: NEW HAVEN

ORG_DEPT: CHEMISTRY

ORG_NAME: YALE UNIVERSITY

PHR: Project Narrative State-of-the-art NMR techniques, site-directed mutagenesis and computational studies based on microsecond molecular dynamics/network analysis, and simulations of NMR spectra will explore allosteric pathways in CRISPR- Cas9, an innovative therapeutic tool with widely demonstrated capabilities for genome editing.

PI_NAMEs: BATISTA, VICTOR S (contact)

PROGRAM_OFFICER_NAME: CHO, THOMAS Y

PROJECT_TERMS: Acceleration;Active Sites;Allosteric Regulation;Allosteric Site;Amino Acids;Binding;Biological;Biological Assay;biomacromolecule;Biomedical Engineering;biophysical analysis;biophysical techniques;Clustered Regularly Interspaced Short Palindromic Repeats;Communication;Complex;Computer Simulation;computer studies;Computing Methodologies;Coupling;CRISPR/Cas technology;Deoxyribonucleases;Distant;DNA;drug discovery;Drug Targeting;endonuclease;Engineering;Ensure;Enzymes;experimental study;flexibility;genome editing;Guidelines;improved;innovation;insight;interest;Joints;Liquid substance;Macromolecular Complexes;Mediating;Methodology;Methods;millisecond;Modernization;Molecular;molecular dynamics;Motion;Mutagenesis;mutant;Mutation;network models;novel;nuclease;Nucleic Acids;Pathway Analysis;Pathway interactions;precision medicine;Process;programs;Property;protein complex;Protein Engineering;Proteins;rational design;Relaxation;Research;Research Personnel;response;RNA;Role;Signal Transduction;simulation;Site;Site-Directed Mutagenesis;small molecule inhibitor;Specificity;Spliceosomes;Structure;System;Techniques;Tertiary Protein Structure;Therapeutic;tool;transmission process;Universities

PROJECT_TITLE: Studies of Allostery between Multi-domain Proteins and Nucleic Acid Complexes

STUDY_SECTION: MSFD

STUDY_SECTION_NAME: Macromolecular Structure and Function D Study Section[MSFD]


NIH_SPENDING_CATS: Cardiovascular;Heart Disease;Neurodegenerative;Neurosciences;Orphan Drug;Pediatric;Rare Diseases

ORG_DEPT: VETERINARY SCIENCES

PHR: The present proposal will test the efficacy of two fumarate-based drugs, dimethyl fumarate (DMF) and its derivative IMF, to prevent or delay the development of lethal cardiomyopathy in Friedreich's ataxia (FA). Currently, there are no drug therapies that ameliorate FA cardiomyopathy and most with FA die of the cardiomyopathy in their 30s. We will identify the optimal dosing and determine underlying cardioprotective mechanisms of these drugs in validated mouse models of FA which can generate important pre-clinical data because it would address the primary cause of mortality in Friedreich's patients.

PI_NAMEs: DEDKOVA, ELENA N. (contact)

PROJECT_TERMS: Aconitate Hydratase;Address;Affect;Age;Animals;Ataxia;Biochemical;Biogenesis;Biological Assay;Body Weight decreased;Cardiac;Cardiac Output;Cardiomyopathies;cardioprotection;Cell Death;Cessation of life;Clinical Trials;Complex;Data;Defect;design;Development;Dose;Drug Kinetics;drug testing;Drug usage;efficacy testing;enzyme activity;Enzymes;Equilibrium;extend lifespan;FDA approved;Fibroblasts;Fibrosis;frataxin;Freezing;Friedreich Ataxia;Fumarates;Gender;Hand Strength;Heart;heart defect;Heart failure;heart function;Heart Hypertrophy;Histone Deacetylase;Histopathology;Human;Impairment;improved;in vivo;Inherited;Iron;knock-down;Knockout Mice;Left Ventricular Ejection Fraction;Left Ventricular Hypertrophy;Libraries;Mediating;Mitochondria;Mitochondrial Proteins;mortality;mouse model;Multiple Sclerosis;multiple sclerosis treatment;Mus;Muscle;Muscle function;Muscle Mitochondria;mutant;Myocardial dysfunction;Myocardium;Myopathy;Necrosis;Neurologic Deficit;novel therapeutic intervention;Oxidation-Reduction;Patients;Pharmaceutical Preparations;Pharmacotherapy;phase 1 study;Physiological;pre-clinical;prevent;Prodrugs;Proteomics;Psoriasis;Recovery of Function;response;Role;Rotarod Performance Test;Safety;Sampling;Sensory;sex;Signal Pathway;Skeletal Muscle;Stroke Volume;Succinate Dehydrogenase;Sulfur;Survival Analysis;Symptoms;Testing;Thick;Time;Tissues;Toxicology;Two-Dimensional Echocardiography;Weight;Wheelchairs;Work

PROJECT_TITLE: Fumarate drugs rescue cardiac dysfunction in mouse models of Friedreich's ataxia

STUDY_SECTION: MIM

STUDY_SECTION_NAME: Myocardial Ischemia and Metabolism Study Section[MIM]


ORG_CITY: HOUSTON

ORG_NAME: BAYLOR COLLEGE OF MEDICINE

ORG_STATE: TX

PHR: PROJECT NARRATIVE We will examine how the brain adapts to newly synthesized motion signals, through regeneration, to control the critical function of gaze stabilization. With vestibular loss, gaze stability is severely compromised throughout life, but newly developing technologies offer to replace lost receptor signals through regenerative or gene therapies. We believe these studies are significant, timely, and necessary in order to provide key insights into a paradigm shift in vestibular pathology treatment.

PI_NAMEs: DICKMAN, J DAVID (contact)

PROGRAM_OFFICER_NAME: POREMBA, AMY

PROJECT_TERMS: Amphibia;Animals;awake;Behavior;behavioral response;Bilateral;Birds;Brain;cell motility;Columbidae;Compensation;Complex;Corwin;Development;Dyes;dynamic system;Exhibits;Eye;Eye Movements;Fiber;Fishes;Frequencies;gaze;gene therapy;Goals;Hair Cells;Head;Head Movements;Human;improved;insight;Lesion;Life;Mammals;Mediating;Morphology;Motion;motion sensitivity;Motor;Natural regeneration;nerve supply;neural;neural circuit;neural correlate;Neurons;new technology;oculomotor;Pathology;Patients;Pattern;Phenotype;Property;Proprioception;Prosthesis;receptor;Receptor Signaling;Recovery;Recovery of Function;regenerative;regenerative therapy;rehabilitation paradigm;Reptiles;response;sensorimotor control mechanism;Signal Transduction;Space Perception;Spinal Cord;System;Technology;Testing;Time;Travel;Type I Hair Cell;Type II Hair Cell;Vertebrates;Vestibular function;Vestibular Hair Cells;Vestibular loss;vestibular system;Vision;Visual Accommodation

PROJECT_TITLE: Gaze recovery during vestibular regeneration


ORG_CITY: HERSHEY

ORG_NAME: PENNSYLVANIA STATE UNIV HERSHEY MED CTR

ORG_STATE: PA

PHR: PROJECT NARRATIVE Exercise is well known to stimulate thin fiber sensory nerves in contracting muscles. Stimulation of these nerves reflexively activates the sympathetic nervous system, an effect which causes vasoconstriction in the heart, kidneys and the skeletal muscles. In hearts whose coronary arteries are narrowed by disease, this vasoconstriction can cause chest pain and fatal arrhythmias. Likewise, in muscles, whose arteries are narrowed by disease, this vasoconstriction can cause muscle ischemia and result in pain that is only relieved by the cessation of exercise (i.e., intermittent claudication). Over time, the exaggerated pressor responses to exercise in patients whose arteries perfusing the vascular of the legs can result in thickening of the walls of the heart, which is maladaptive, and irregular heart rhythms, some of which are not compatible with life.

PI_NAMEs: KAUFMAN, MARC PETER (contact);RUIZ-VELASCO, VICTOR

PROGRAM_OFFICER_NAME: REID, DIANE M

PROJECT_TERMS: Acids;afferent nerve;Animal Disease Models;Animal Model;arm;Arrhythmia;Arteries;ASIC channel;Attention;Attenuated;Blood flow;Blood Vessels;Brain Stem;Cardiac;Cardiovascular system;Chest Pain;Contracts;Coronary artery;CRISPR/Cas technology;Decerebration procedure;Disease;Epidemiology;Exercise;experimental study;femoral artery;Fiber;Generations;Goals;Health;Heart;Heart Contractilities;Heart Rate;heart rhythm;high risk;Hindlimb;Hour;Hydrogen-Ion Concentration;Individual;Intermittent Claudication;Ischemia;Kidney;knock-down;Knock-out;Lactic acid;Leg;Legal patent;Life;Ligation;Limb structure;mechanical stimulus;Metabolic;Muscle;Muscle Contraction;Muscle Form Glycogen Phosphorylase;mutant;Myocardial;Myocardial Infarction;Names;Nerve;neuromechanism;normotensive;Oxygen;Pain;Patients;Pattern;Perfusion;Peripheral;Peripheral arterial disease;pharmacologic;Play;Preparation;pressure;prevent;Production;Protein Isoforms;Rattus;receptor;Reflex action;response;Role;sensor;Signal Transduction;Skeletal Muscle;Small Interfering RNA;Spinal Cord;Stimulus;Stroke;Sympathetic Nervous System;Technology;Testing;Thinness;Time;Trees;Triceps Brachii Muscle;Vascular blood supply;Vascular resistance;vasoconstriction

PROJECT_TITLE: Role played by Acid Ion Sensing Channels in Peripheral Artery Disease

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


NIH_SPENDING_CATS: Cancer;Digestive Diseases;Liver Cancer;Liver Disease;Rare Diseases

ORG_CITY: MADISON

ORG_DEPT: PEDIATRICS

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: PUBLIC HEALTH STATEMENT The proposed research contributes to human health by increasing our understanding of the interplay between the immune system and cancer. Here we focus on the role of neutrophils, white blood cells that fight infection but also contribute to chronic inflammation, in the initiation and progression of cancer. We are interested in tumor genes and neutrophil genes that regulate cancer progression and how these pathways can be targeted to facilitate the development of new treatments for cancer.

PI_NAMEs: HUTTENLOCHER, ANNA  (contact)

PROGRAM_OFFICER_NAME: WOODHOUSE, ELIZABETH

PROJECT_TERMS: Adaptive Immune System;Address;Adhesives;Affect;Behavior;cancer cell;cancer immunotherapy;cancer therapy;cell motility;cell transformation;Cells;Chronic;design;Development;Disease Progression;early onset;Effector Cell;Epithelial Cells;Exhibits;Fibrolamellar Hepatocellular Carcinoma;fighting;Gene Expression;Genes;Goals;Growth;Growth Factor;Health;Human;human disease;IL6 gene;Immune system;improved;in situ imaging;Infection;Inflammation;Inflammatory;Innate Immune Response;Innate Immune System;interest;Knowledge;Leukocytes;Link;liver cancer model;Macrophage;Malignant neoplasm of liver;Malignant Neoplasms;Mediating;Melanoma;Modeling;Motility;Myelogenous;neutrophil;Neutrophil Infiltration;Oncogenes;paracrine;Pathway interactions;Phosphoric Monoester Hydrolases;Play;Population;Positioning Attribute;Public Health;Reactive Oxygen Species;real-time images;recruit;Regulation;Research;response;Role;Signal Pathway;Signal Transduction;STAT3 gene;Testing;Therapeutic;Time;translating ribosome affinity purification and RNA-sequencing;tumor;tumor microenvironment;tumor progression;tumorigenesis;TXN gene;Work;wound healing;Zebrafish

PROJECT_TITLE: Adhesive regulation during cell migration

STUDY_SECTION: ICI

STUDY_SECTION_NAME: Intercellular Interactions Study Section[ICI]


NIH_SPENDING_CATS: Building Research Capacity at Institutions with Limited NIH Funding;Clinical Research;Neurosciences;Pediatric

ORG_CITY: SAN FRANCISCO

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

ORG_STATE: CA

PHR: Through UCSF Summer Research Experiences in Neuroscience, high school students from backgrounds underrepresented in the sciences will further their educational and scientific careers, while deepening their knowledge and understanding of cutting-edge neuroscience research. This project will also help research scientists learn how to mentor students from backgrounds different from their own; thereby equipping these researchers to be more effective mentors throughout their careers. Ultimately, these efforts will help diversify the health science field, which has been repeatedly cited as a mechanism for addressing disparities in health and healthcare.

PI_NAMEs: NIELSEN, KATHERINE M (contact);WITZEL, LAKISHA

PROGRAM_OFFICER_NAME: MATTHEWS, MARGUERITE

PROJECT_TERMS: Address;Awareness;Biomedical Research;Brain;California;career;cohort;college;College Preparation;Counseling;Coupling;Degree Completion;Development;Education;Educational workshop;essays;experience;Experimental Designs;Faculty;Family;Fostering;graduate school;graduate student;health disparity;Health education;Health Sciences;Healthcare;high school;High School Student;Internships;Knowledge;Learning;matriculation;Measures;Mentors;Nervous System;Nervous System Disorder;Neurodegenerative Disorders;Neurology;Neurosciences;Neurosciences Research;Neurosurgical Procedures;Outcome;Partner in relationship;Pathway interactions;Patient Self-Report;Peer Review;Postdoctoral Fellow;posters;prevent;Publications;Readiness;Research;Research Personnel;Research Project Grants;role model;San Francisco;Science;science education;Scientist;skills;Structure;student mentoring;Students;summer program;summer research;Surveys;symposium;United States National Institutes of Health;Universities;Visit;web site;Writing


NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Cost Effectiveness Research;Dissemination and Implementation Research;HIV/AIDS;Infectious Diseases;Maternal Health;Mental Health;Pediatric;Pediatric - AIDS;Perinatal Period - Conditions Originating in Perinatal Period;Prevention;Women's Health Research

ORG_CITY: KANSAS CITY

ORG_DEPT: FAMILY MEDICINE

ORG_NAME: UNIVERSITY OF KANSAS MEDICAL CENTER

ORG_STATE: KS

PHR: Project Narrative/Public Health Relevance This trial will evaluate a web-based, system-level intervention that addresses persistent gaps in PMTCT care by facilitating guideline-adherent services to optimize HIV prevention and maternal health. The HIV Infant Tracking System (HITSystem) 2.1 will prospectively follow HIV-positive pregnant women through 6 months postpartum, employing accessible technologies to ensure complete and timely engagement in clinical care, and robust management of maternal viral loads during critical windows for preventing new HIV infections. Such improvements are essential before low resource countries can close the remaining gaps and eliminate mother- to-child transmission of HIV.

PI_NAMEs: KESSLER, SARAH FINOCCHARIO (contact)

PROGRAM_OFFICER_NAME: SENN, THERESA ELAINE

PROJECT_TERMS: 2 arm randomized control trial;Acquired Immunodeficiency Syndrome;Address;Adoption;AIDS prevention;antenatal;antiretroviral therapy;Appointment;arm;Breast Feeding;Caring;Cessation of life;Childhood;Clinical;clinical care;cost;cost effective;cost effectiveness;cost-effectiveness evaluation;Country;Data;design;Documentation;early pregnancy;effective intervention;Effectiveness;efficacy evaluation;eHealth;Enrollment;Ensure;evidence base;follow-up;Fostering;Goals;Government;Grant;Guideline Adherence;Guidelines;Health care facility;High Prevalence;high risk;HIV;HIV diagnosis;HIV Infections;HIV Seropositivity;Hospitals;Human immunodeficiency virus test;implementation fidelity;improved;Infant;Interruption;Intervention;Kenya;Life;Maintenance;Maternal Health;Measures;medication compliance;Modeling;Monitor;Mother-to-child HIV transmission;Mothers;Online Systems;Participant;patient engagement;patient retention;pediatric human immunodeficiency virus infection;perinatal HIV;Perinatal transmission;pilot test;Postpartum Period;Postpartum Women;Pregnancy;Pregnant Women;prevent;Prevention;prospective;Provider;Proxy;public health relevance;Randomized;Randomized, Controlled Trials;Reach, Effectiveness, Adoption, Implementation, and Maintenance;Regimen;Resources;Sampling;scale up;Schedule;service delivery;Services;Site;standard of care;success;System;Technology;Test Result;Testing;Text Messaging;therapy development;Time;transmission process;Update;uptake;Vertical Disease Transmission;Viral;Viral Load result;Visit;web-based intervention;Woman;World Health Organization

PROJECT_TITLE: Evaluating the HITSystem to Improve PMTCT Retention and Maternal Viral Suppression in Kenya

STUDY_SECTION: HIBI

STUDY_SECTION_NAME: HIV/AIDS Intra- and Inter-personal Determinants and Behavioral Interventions Study Section[HIBI]


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

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: NARRATIVE Nearly half of the human genome is comprised of mobile DNA elements that are commonly recognized as sources of genetic mutations to drive cancer development. We recently discovered that the epigenetic silencing of L1 retrotransposons, the autonomously mobile DNA, is required for the propagation of AML- initiating cells, thus establishing an unexpected ‘tumor-suppressive’ function for retrotransposon activity in myeloid leukemia. Elucidating the functional and mechanistic roles of L1 retrotransposons in leukemia pathogenesis and in response to anti-leukemia agents will establish a previously unrecognized regulatory pathway in cancer pathobiology, whose intervention may lead to improved anti-leukemia therapies.

PI_NAMEs: XU, JIAN  (contact)

PROGRAM_OFFICER_NAME: KLAUZINSKA, MALGORZATA

PROJECT_TERMS: Acute Myelocytic Leukemia;acute myeloid leukemia cell;Affect;antileukemic agent;Biology;cancer initiation;Cell Cycle;Cells;Chemoresistance;Chromatin;Chromosome abnormality;Clonal Evolution;Complex;CRISPR interference;CRISPR screen;CRISPR-mediated transcriptional activation;Dependence;Development;differentiation in vitro;Disease;DNA;DNA Damage;DNA Sequence Alteration;DNA Transposable Elements;Elements;Epigenetic Process;epigenetic regulation;epigenetic silencing;Functional disorder;Generations;Genetic;genome integrity;Genomic Instability;Genomics;Goals;Hematopoiesis;Hematopoietic stem cells;high risk;Human;human DNA;Human Genome;Impairment;improved;in vivo;Inflammatory;innovation;Insertional Mutagenesis;Interferon Type I;Intervention;Junk DNA;L1 Elements;Length;leukemia;leukemia initiating cell;leukemia treatment;leukemogenesis;Link;Long Interspersed Elements;Maintenance;Malignant - descriptor;Malignant Neoplasms;Mediating;Messenger RNA;Modeling;Molecular;mouse model;Mus;Myelogenous;Myeloid Leukemia;Oncogenes;overexpression;Pathogenesis;Pathway interactions;Patients;pharmacologic;Phenocopy;Phenotype;Physiological;Prognosis;Prognostic Marker;Proteins;Regulatory Pathway;Repression;Resistance;response;Retrotransposition;Retrotransposon;Role;self-renewal;Signal Pathway;Signal Transduction;Somatic Mutation;Source;targeted treatment;Testing;Therapeutic;Transgenic Organisms;transposon/insertion element;treatment response;tumor;Untranslated RNA;Variant;Work;Xenograft procedure

PROJECT_TITLE: Elucidating the Functional and Mechanistic Roles of LINE-1 Retrotransposons in Myeloid Leukemia

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


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

ORG_CITY: WHITE PLAINS

ORG_NAME: WINIFRED MASTERSON BURKE MED RES INST

ORG_STATE: NY

PHR: Public Health Relevance: In patients with amyotrophic lateral sclerosis (ALS) and the related motor neuron disease (MND) primary lateral sclerosis (PLS), deficits in motor control occur as a consequence of the degeneration of corticospinal neurons (CSNs). Therefore, understanding the cellular and molecular mechanisms underlying corticospinal circuits in ALS mouse models will provide important information for developing new therapeutic avenues for addressing ALS patients.

PI_NAMEs: SHNEIDER, NEIL ALAN;YOSHIDA, YUTAKA  (contact)

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Address;Adult;advanced disease;Affect;ALS patients;Amyotrophic Lateral Sclerosis;Anatomy;Animal Experiments;Animal Model;Axon;Behavioral Assay;Biological Models;causal variant;Clinical;Complex;Data;Defect;dexterity;Disease;disease phenotype;Disease Progression;Dorsal;Electromyography;Electrophysiology (science);Functional disorder;Genes;grasp;Human;Impairment;improved;in vivo;Interneurons;Label;Lateral;Link;mad itch virus;Maintenance;Manuals;microstimulation;Modeling;Molecular;Motor;motor behavior;motor control;Motor Neuron Disease;Motor Neurons;Motor Skills;mouse model;Movement;Mus;Muscle denervation procedure;Mutant Strains Mice;Mutation;Nerve Degeneration;Neuroanatomy;Neuronal Dysfunction;Neurons;neuropathology;new therapeutic target;novel;novel therapeutics;Pathogenesis;Pathology;Patients;Pattern;Phenotype;postnatal;Predisposition;Primary Lateral Sclerosis;public health relevance;Regional Anatomy;Research;Role;Signal Transduction;Signs and Symptoms;skills;Spinal;superoxide dismutase 1;Synapses;Testing;Viral

PROJECT_TITLE: Corticospinal Neuron Dysfunction and Degeneration in ALS: Testing the Role of Corticomotor Connectivity in Motor Neuron Disease

STUDY_SECTION: CDIN

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