ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Drug Abuse (NIDA only);Mental Health;Networking and Information Technology R&D (NITRD);Neurosciences;Opioid Misuse and Addiction;Opioids;Prevention;Sleep Research;Substance Misuse;Telehealth

ORG_CITY: CHARLESTON

ORG_DEPT: PSYCHIATRY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Medication for opioid use disorder (MOUD) is the first-line treatment for opioid use disorder (OUD), and although difficulties sleeping are highly prevalent, persistent, and connected to negative treatment outcomes in persons receiving MOUD, treatment options for sleep problems are limited. The present study will develop and test a mobile application to meet this treatment need for an easily disseminated, evidence-based, behavioral sleep intervention for those receiving MOUD. This approach to treatment has the potential to be expanded and significantly impact sleep problems, which are common across all types of substance use disorders.

PI_NAMEs: WILKERSON, ALLISON  (contact)

PROGRAM_OFFICER_NAME: SEYMOUR, KAREN ELIZABETH

PROJECT_TERMS: abuse liability;acceptability and feasibility;Address;Adherence;Anxiety Disorders;Behavior Therapy;Behavioral;behavioral sleep intervention;Books;Breathing;Circadian Rhythm Disorder;Circadian Rhythms;Clinical;clinical care;Clinical Research;Cognitive;Cognitive Therapy;Control Groups;Data;Data Analyses;Data Collection;Development;Diagnostic;digital health;Dropout;Education;effective intervention;evidence base;Evidence based intervention;experience;Feedback;Goals;improved;Individual;instrument;Integrative Therapy;Intervention;intervention delivery;Interview;Literature;Manuals;Measures;medication for opioid use disorder;medication-assisted treatment;Medicine;member;Mental Depression;mHealth;mobile application;Mobile Health Application;Mood Disorders;National Institute of Drug Abuse;Nature;Nightmare;opioid use disorder;Pain;Patients;Persons;pharmacologic;Pharmacotherapy;pilot test;Polysomnography;poor sleep;Population;premature;Preparation;Program Development;programs;Protocols documentation;Provider;Public Health;Quality of Care;Randomized;randomized, clinical trials;Randomized, Controlled Trials;Recovery;recruit;Relapse;Reporting;Research;Risk;Risk Factors;Running;Schedule;skills;Sleep;sleep difficulty;Sleep Disorders;sleep health;Sleeplessness;smartphone application;Structure;Substance Use Disorder;substance use treatment;Suicide;Symptoms;Testing;Time;tool;Training;Treatment outcome;usability;Vulnerable Populations;Weight maintenance regimen;Work

PROJECT_TITLE: Development of an mHealth Behavioral Sleep Medicine Intervention for use during Medication Assisted Treatment for Opioid Use Disorder

STUDY_SECTION: IPTA

STUDY_SECTION_NAME: Interventions to Prevent and Treat Addictions Study Section[IPTA]


ADMINISTERING_IC: NS

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Genetics;Neurosciences;Stem Cell Research;Stem Cell Research - Embryonic - Human

ORG_CITY: GAINESVILLE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: NEUROSURGERY

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: PROJECT NARRATIVE  We will develop generalizable and potentially transformative methods to selectively target the RNA repeat expansions that cause >30 incurable neuromuscular diseases and genetically-defined dementia. Indeed, we will expand the repertoire of drug action to: (i) exploit RNA repeat structures to synthesize their own drugs in only disease-affected tissues; (ii) recruit endogenous nucleases directly to RNA repeat expansions selectively; and (iii) harness the activity of natural RNA decay pathways to eliminate the disease-causing RNA. These studies could establish a completely new paradigm for studying human disease pathology caused by toxic structured RNAs and will deliver molecules to study RNA biology and tools to inform target engagement in situ and in vivo.

PI_NAMEs: DISNEY, MATTHEW D (contact)

PROGRAM_OFFICER_NAME: RANGANATHAN, SRIKANTH

PROJECT_TERMS: Affect;Alleles;Award;Base Pairing;Biology;Chemicals;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Defect;Dementia;design;Disease;drug action;drug synthesis;Engineering;Ensure;flexibility;Foundations;Fragile X Syndrome;Funding;Gene Silencing;Genes;Genetic Polymorphism;Health;Human;human disease;In Situ;in vivo;innovation;Introns;Investments;Mediating;Methods;Microsatellite Repeats;Modality;molecular recognition;Neuromuscular Diseases;novel;nuclease;Oligonucleotides;Open Reading Frames;Pathology;Pathway interactions;Patients;Pharmaceutical Preparations;preclinical development;programs;recruit;Research;RNA;RNA Decay;Site;small molecule;Structure;Therapeutic;Tissues;tool;Toxin;Transcript;Untranslated Regions;Work

PROJECT_TITLE: Design of precision small molecules targeting RNA repeating transcripts to manipulate and study disease biology


ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

ORG_CITY: BERKELEY

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

ORG_STATE: CA

PHR: PROJECT NARRATIVE Neurodegenerative diseases resulting from nucleotide triplet expansions, such as HD and ALS, lack any disease-modifiying therapy. We will establish a first-in-class paradigm for the use of in vivo gene editing for these diseases - allele-specific excision of the disease-causing expansion - and reduce it to preclinical and regulatory practice. To this end we will (i) develop a mutually synergistic suite of CRISPR-Cas9 preclinical leads for both mutant HTT and mutant C9ORF92; (ii) using multiple innovative viral and nonviral delivery formulations, perform IND-enabling preclinical pharmacology, toxicology, CMC, and biodistribution studies; (iii) advance an AAV-formulated CRISPR-Cas approach for HD to IND, and for ALS - to pre-IND.

PI_NAMEs: DOUDNA, JENNIFER A (contact)

PROGRAM_OFFICER_NAME: LAVAUTE, TIMOTHY M

PROJECT_TERMS: Alleles;Amyotrophic Lateral Sclerosis;Animal Model;animal tissue;Animals;Behavior;Biodistribution;Biological Assay;Biotechnology;brain parenchyma;brain tissue;brain volume;C9ALS;C9ORF72;cell transformation;Cells;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Collaborations;Convection;CRISPR therapeutics;CRISPR/Cas technology;Dedications;Dependovirus;design;Development;Disease;disease model;Dose;efficacy evaluation;efficacy study;Engineering;Excision;experience;Feedback;Fibroblasts;Formulation;Genes;Genetic;genome editing;genome editor;Guide RNA;Haplotypes;Heterozygote;Histologic;Human;Huntington Disease;improved;In Vitro;in vivo;Induced pluripotent stem cell derived neurons;Injections;innovation;Investigational Therapies;knock-down;Lead;lead candidate;manufacture;Mendelian disorder;Modeling;Molecular;mortality;mouse model;Mus;mutant;Mutation;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;Neurons;nonhuman primate;novel;Nucleotides;Outcome;Pathogenicity;Patients;peptide amphiphiles;Pharmacology;Pharmacology and Toxicology;Phenotype;postmitotic;pre-clinical;Preparation;prevent;Process;Production;programs;Property;Rattus;Reagent;Research;Research Personnel;Research Project Grants;Resources;response;Ribonucleoproteins;Rodent Model;Route;screening;Serotyping;Side;Sum;synergism;System;Technology;Testing;Therapeutic;therapeutic genome editing;Therapeutic Index;tool;Toxic effect;Toxicology;Transfection;Triplet Multiple Birth;Viral;Virus;Work

PROJECT_TITLE: Correction of Neurological Disease via Allele Specific Excision of Pathogenic Repeats

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MGG-G(70)R]


NIH_SPENDING_CATS: Neurodegenerative;Neurosciences

PI_NAMEs: URNOV, FYODOR D (contact)

PROJECT_TERMS: Adopted;Agreement;Alleles;Biological Assay;Budgets;Charge;Clinical;Clinical Protocols;Clinical Trials;Collaborations;Communication;Consult;Consultations;Data;Dedications;Dependence;Disease;Disease remission;Documentation;Education;Ensure;Evaluation;Event;Excision;Expenditure;experience;first-in-human;Funding;genome editing;Genomics;Goals;Human Resources;Individual;Industry;Infrastructure;Institution;Investigational Therapies;Laboratories;Lead;Leadership;Learning;Liquid substance;Management Information Systems;meetings;Molecular;Monitor;Nerve Degeneration;Nervous System Disorder;Occupational activity of managing finances;operation;Outcome;Pamphlets;Pathogenicity;payment;Persons;Physician Executives;Play;Preparation;Process;program dissemination;programs;Reagent;Reporting;Research;Research Personnel;Research Project Grants;Resolution;Resource Allocation;Resource Sharing;Resources;Role;Safety;Schedule;Services;Specific qualifier value;Specimen;System;Therapeutic;timeline;Training;Travel;virtual;Vision;Work

PROJECT_TITLE: Administrative Core

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-MGG-G]


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: BOSTON

ORG_NAME: MASSACHUSETTS GENERAL HOSPITAL

ORG_STATE: MA

PHR: OVERALL PROJECT NARRATIVE Blood cell production is the result of distinctive, heterogeneous individual primitive cells collectively generating mature cell offspring and when one of those primitive cells acquires a mutation, we propose that how it will behave depends on features present in the cell of origin and how the mutation affects cell signaling. Specific molecular features of the mutant clone may then provide predictive information about the pathogenic potential of a clone. Further, the metabolic alterations accompanying modified cell behavior can reveal exploitable vulnerabilities to guide testable, low intensity approaches to reducing clonal burden.

PI_NAMEs: SCADDEN, DAVID T (contact)

PROGRAM_OFFICER_NAME: BAI, C BRIAN

PROJECT_TERMS: Address;Affect;Alleles;Area;Automobile Driving;Behavior;Biological Models;Biological Process;Biology;biomarker development;Blood Cells;cell behavior;Cells;Chemicals;Clinical;Clone Cells;comparative;Computer Analysis;Dependence;disease phenotype;DNA Sequence Alteration;DNMT3a;Epigenetic Process;epigenome;Event;Exhibits;fitness;functional outcomes;Funding;Gene Expression Regulation;Gene Frequency;gene regulatory network;Generations;Genetic;genetic variant;Goals;Grant;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Heterogeneity;Impairment;improved;in vivo;Individual;Inflammatory;inflammatory milieu;innovative technologies;insight;Intervention;Investigation;Maintenance;Metabolic;Metabolism;Modeling;Molecular;Molecular Profiling;mutant;Mutation;new technology;offspring;Outcome;Pathogenicity;Penetrance;Pharmaceutical Preparations;preclinical evaluation;primitive cell;Production;progenitor;programs;Research Personnel;Resources;response;Risk;risk prediction;Signal Transduction;single cell genomics;Somatic Mutation;stem;stem cells;Stimulus;Stress;Testing;therapy development;Translations;Transplantation;Work

PROJECT_TITLE: Functional consequences of stem and progenitor cell heterogeneity

STUDY_SECTION: HLBP

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP(JA)]


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

ORG_CITY: ITHACA

ORG_DEPT: PHYSICS

ORG_NAME: CORNELL UNIVERSITY

ORG_STATE: NY

PHR: Navigating an environment requires constantly sensing and integrating information from surroundings in addition to generating coordinated motor commands. Understanding the neural mechanisms of the entire transformation process from multisensory integration to motor execution is critical to understand and treat diseases with impaired sensory-motor coordination, such as cerebellar ataxia, a deficit that manifests as a poorly tuned control system. This proposal will leverage advantages of a highly tractable model system, the fruit fly, to determine how sensory systems collect and integrate diverse information and how it guides navigational decisions and generate fast motor outputs in the nervous system, ultimately discovering the neural circuit motifs shared by many species including humans.

PI_NAMEs: COHEN, ITAI  (contact);COWAN, NOAH JOHN;FOX, JESSICA ;KIM, SUNG SOO

PROGRAM_OFFICER_NAME: DAVID, KAREN KATE

PROJECT_TERMS: Affect;Air Movements;Anatomy;Animals;Behavior;Behavioral;behavioral response;Biological;Biological Models;Biosensor;body sense;Brain;Calcium;cell type;Cells;Cerebellar Ataxia;Collaborations;Complex;Computer Models;Computer software;Conflict (Psychology);connectome;control theory;Darkness;Data;Decision Making;Development;Disease;Drosophila genus;Drosophila melanogaster;dynamic system;Electron Microscopy;Environment;Environmental Wind;Esthesia;experimental study;Eye;fly;Flying body movement;Generations;Genetic;Goals;Hand;Human;Human Engineering;Image;imaging study;Impairment;innovation;Magnetism;Mammals;Mechanics;Methods;Microscope;miniaturize;Modality;Modeling;Monitor;Motion;Motor;Motor output;multimodality;multisensory;Muscle;Nerve;Nervous System;neural;neural circuit;neural network;Neural Pathways;neuromechanism;neuromuscular;Neurons;optogenetics;Organ;patch clamp;Pathway interactions;Photons;Physiological;Positioning Attribute;predictive modeling;Process;reconstruction;Reflex action;resilience;Resolution;response;Rotation;Seminal;sensor;Sensory;sensory feedback;sensory integration;sensory stimulus;sensory system;Skeletal muscle structure of neck;Speed;Stimulus;System;Systems Theory;Technology;Testing;theories;Time;tool;two-photon;vestibular system;Visual;visual information

PROJECT_TITLE: Cross-Modal Sensory Interactions, Processing, and Representation in the Drosophila Brain


NIH_SPENDING_CATS: Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

PROJECT_TERMS: Accountability;Agreement;Communication;Data Analyses;data sharing;Fostering;Hematopoiesis;Heterogeneity;Individual;Leadership;Publications;Reporting;stem;stem cells;United States National Institutes of Health

STUDY_SECTION_NAME: Heart, Lung, and Blood Program Project Study Section[HLBP]


PROJECT_TERMS: adenovirus mediated delivery;Alleles;Animal Model;Biological;Biological Assay;Biological Models;Cell Culture Techniques;Cell Line;Cell model;Cells;Collaborations;Complement;Data;design;Development;DNA;DNA Resequencing;Ensure;Excision;Experimental Animal Model;experimental study;Feedback;Genome;genome editing;genome-wide;Genome-wide Unbiased Identification of DSBs Enabled by sequencing;Genomic DNA;Genomics;Guide RNA;Human;in vivo;Induced Neurons;insertion/deletion mutation;Laboratories;Laboratory Personnel;Lead;life span;Logistics;Management Information Systems;Measures;Mission;Modeling;Monitor;Nervous System Disorder;Neurons;nonhuman primate;Nuclear Pore Complex;nuclease;off-target site;Outcome;Outcome Assessment;Participant;Pathogenicity;Performance;pre-clinical;Pre-Clinical Model;preclinical efficacy;preclinical safety;programs;Reagent;Reporting;Research;Research Project Grants;Resources;Rodent;Rodent Model;Role;Safety;Sampling;screening;Site;Specificity;Specimen;Standardization;Therapeutic;Tissues;Validation;Variant;Work

PROJECT_TITLE: Resource Core I: Genomic Outcomes Core


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

PI_NAMEs: BUENROSTRO, JASON DANIEL (contact)

PROJECT_TERMS: Algorithms;Alleles;ATAC-seq;Bar Codes;Binding;Biological Assay;causal variant;cell behavior;Cell Differentiation process;Cell Nucleus;Cell Physiology;cell type;Cells;Chromatin;Chromatin Structure;Collaborations;Communities;community-centered;computational pipelines;computerized data processing;Consultations;cost;cost effective;cost effectiveness;Data;Data Analyses;data integration;data management;Data Set;data sharing;design;Development;Disease;Dissection;Distal;DNA Sequence Alteration;Educational workshop;epigenomics;experience;Experimental Designs;Experimental Models;experimental study;Functional disorder;Gene Activation;Gene Expression;Gene Expression Regulation;gene regulatory network;Genes;Genetic Transcription;Genomics;Hematopoiesis;Hematopoietic;hematopoietic differentiation;hematopoietic tissue;Heterogeneity;Human;innovation;interactive visualization;Joints;Maps;Measurement;Measures;Mediating;member;Methods;Modeling;multiple omics;Mus;Mutation;Nucleic Acid Regulatory Sequences;online resource;Output;Process;Production;programs;Protocols documentation;Quality Control;regenerative biology;Regulation;Regulatory Element;Resolution;Resources;RNA;Role;Rotation;sample collection;Sampling;Schedule;Series;single cell genomics;single-cell RNA sequencing;Source;stem;stem cell biology;stem cells;Technology;Tissues;tool;transcription factor;transcriptome sequencing;transcriptomics;Universities;web interface;Work;XCL1 gene;Zebrafish

PROJECT_TITLE: Core A - Establishing the regulatory mechanisms defining cellular function


NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Behavioral and Social Science;Biotechnology;Brain Disorders;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

PI_NAMEs: VAN LAAR, VICTOR STEVEN (contact)

PROJECT_TERMS: Acceleration;Address;adeno-associated viral vector;Alleles;Amyotrophic Lateral Sclerosis;Animal Disease Models;Animal Experiments;Animals;aromatic L-amino acid decarboxylase deficiency;Behavior;Behavior assessment;Behavioral;Biochemical;Biological;Biological Assay;Blood - brain barrier anatomy;Brain;Bypass;C9ORF72;Cells;Central Nervous System;Central Nervous System Diseases;Cerebrospinal Fluid;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Cognitive;Collection;Communication;Convection;Data;Development;Disease;disease model;dosage;Dose;Drug Delivery Systems;drug efficacy;Drug or chemical Tissue Distribution;Drug Targeting;efficacy evaluation;Ensure;Equilibrium;Excision;Freezing;gene therapy;Genes;Genetic;Genomic DNA;Genomics;Glioblastoma;Huntington Disease;in vivo;Infusion procedures;interest;Investigation;Investigational Drugs;Laboratories;Location;Measurement;Mediating;Methods;Mission;Molecular;mortality;Motor;mouse model;Multiple System Atrophy;Mus;Nervous System Disorder;Neurodegenerative Disorders;Neurons;neurosurgery;Outcome;Output;Parkinson Disease;Pathogenicity;Pathologic;Perfusion;Pharmaceutical Preparations;Phenotype;pre-clinical;Program Research Project Grants;programs;Rattus;Reporter;Research;Research Personnel;Research Project Grants;research study;Resources;Ribonucleoproteins;Rodent;Rodent Model;Route;safety assessment;Sampling;Services;Shipping;Standardization;System;targeted treatment;Techniques;Testing;therapeutic genome editing;Therapeutic Intervention;timeline;Tissues;trait;vector;Virus;Weight;Work

PROJECT_TITLE: Resource Core II: In Vivo Core


ADMINISTERING_IC: AI

FUNDING_MECHANISM: SBIR-STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biotechnology;Eye Disease and Disorders of Vision;Genetics;Infectious Diseases;Orphan Drug;Rare Diseases;Sexually Transmitted Infections;Wound Healing and Care

ORG_CITY: DOYLESTOWN

ORG_NAME: FOX CHASE CHEMICAL DIVERSITY CENTER, INC

ORG_STATE: PA

PHR: NARRATIVE Herpes Keratitis is the leading cause of corneal blindness in the USA and the world. The significant emergence of acyclovir-resistant herpes virus in eye infections necessitates the development of a new, safe and effective drug. The goal of this research is to prevent loss of vision by continuing the development of a novel, n0n-toxic drug that specifically targets herpes virus that infects the eye.

PI_NAMEs: REITZ, ALLEN BERNARD (contact);RICCIARDI, ROBERT PAUL

PROGRAM_OFFICER_NAME: DAVIS, MINDY I

PROJECT_TERMS: 3-Dimensional;Acyclovir;Address;alpha helix;analog;Anatomy;Anti-viral Agents;anti-viral efficacy;Area;Binding;Biological Assay;Blindness;Cells;Chemicals;Clinical;Cornea;corneal epithelium;corneal scar;Corneal Ulcer;crosslink;Crystallization;Cyclic Peptides;Development;Disease;Dissociation;DNA;DNA biosynthesis;Dose;Drug Kinetics;drug resistant virus;efficacy study;efficacy testing;emerging virus;Engineering;Ensure;Epithelial Cells;Evaluation;Exhibits;experience;Exposure to;Eye;Eye Infections;Face;Failure;Formulation;Gene Mutation;genital herpes;genotoxicity;Goals;Herpes Labialis;Herpesviridae;Herpesviridae Infections;Herpesvirus 1;Herpetic Keratitis;Histopathology;Human;In Vitro;in vivo;Individual;Infection;Keratitis;Lead;Liposomes;Measures;Medical;Modeling;Mutagenicity Tests;mutant;novel;ocular surface;Oryctolagus cuniculus;Patients;Penetration;peptide A;Peptide Hydrolases;Peptides;Permeability;Persons;Pharmaceutical Preparations;Physiological;Polymerase;Population;pre-IND studies;preclinical development;Preclinical Drug Development;prevent;Property;protein protein interaction;Proteins;Publishing;Recurrence;Research;residence;Resistance;Risk;risk mitigation;Running;Safety;safety testing;scale up;Series;small molecule;Solubility;Solvents;standard care;stapled peptide;Surface;Testing;Therapeutic;three dimensional cell culture;thymidine kinase 1;Time;Tissues;Toxic effect;uptake;Vascularization;Viral;viral DNA;Viral Load result;Virus;Virus Replication;Vision

PROJECT_TITLE: Optimizing a Stapled-Peptide That Specifically Targets HSV-1 to Treat Herpes Ocular Keratitis


ADMINISTERING_IC: CA

IC_NAME: NATIONAL CANCER INSTITUTE

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

ORG_CITY: CHICAGO

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: RUSH UNIVERSITY MEDICAL CENTER

ORG_STATE: IL

PHR: Project Narrative Triple negative breast cancer (TNBC) is an aggressive breast cancer type with few treatment options and poor prognosis. A defining characteristic of TNBC is loss or inactivation of a protein called p53. We identified a drug combination that targets TNBC cells when where p53 is lost or inactivated, and we want to test this drug combination against TNBC tumors in mice and determine the mechanisms involved.

PI_NAMEs: MAKI, CARL G (contact)

PROGRAM_OFFICER_NAME: VENKATACHALAM, SUNDARESAN

PROJECT_TERMS: Acceleration;Affect;aggressive breast cancer;Aneuploidy;aurora B kinase;Breast Cancer Cell;cancer subtypes;cancer type;carcinogenesis;Cell Death;Cells;Centromere;Characteristics;Chromosomal Instability;Chromosomal Stability;chromosome missegregation;Chromosome Segregation;Clinical Trials;Data;Defect;DNA;Drug Combinations;drug testing;ETS1 gene;ETS2 gene;Fatty acid glycerol esters;Grant;Heterochromatin;histone methylation;histone methyltransferase;histone modification;Hypersensitivity;Implant;inhibitor;Kinetochores;knock-down;Malignant Breast Neoplasm;Malignant Neoplasms;mammary;Methylation;Microtubules;Mitosis;Mitotic;Modeling;Monitor;Mus;mutant;Mutate;Mutation;overexpression;Patient-derived xenograft models of breast cancer;Phosphorylation;Predisposition;Prognosis;Proteins;recruit;repository;response;Role;targeted treatment;Testing;Therapeutic;TP53 gene;transcription factor;triple-negative invasive breast carcinoma;tumor;tumor growth;Tumor Suppression

PROJECT_TITLE: A synthetic lethal approach for targeting p53 deficient triple negative breast cancer


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Autism;Basic Behavioral and Social Science;Behavioral and Social Science;Biomedical Imaging;Brain Disorders;Clinical Research;Intellectual and Developmental Disabilities (IDD);Mental Health;Mental Illness;Neurosciences;Pediatric

ORG_CITY: DAVIS

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: We have previously monitored brain and behavioral development in nearly 300 autistic and typically developing children in the MIND Institute’s Autism Phenome Project. Up to 4 MRI scans have been carried out when the child is between 3 and 12 years of age and we propose to do an additional scan between 14-17. We have discovered that subgroups of children with autism have different, altered patterns of brain development. We have also found that 69% have serious anxiety symptoms and nearly 30% of children improve in symptom severity whereas 18% increase and about 50% stay the same. We propose to evaluate brain and behavioral changes as these children enter adolescence. The goal is to enable more effective targeted treatments for defined subgroups of individuals with autism.

PI_NAMEs: AMARAL, DAVID G (contact);NORDAHL, CHRISTINE WU

PROGRAM_OFFICER_NAME: GILOTTY, LISA

PROJECT_TERMS: 11 year old;12 year old;5 year old;Address;Adolescence;Adolescent;adolescent with autism spectrum disorder;Age;age effect;Amygdaloid structure;Anterior;Anxiety;Anxiety Disorders;anxiety spectrum disorders;anxiety symptoms;Atrophic;autism spectrum disorder;autism symptoms;autistic;autistic children;Autopsy;Behavior;Behavioral;Biological;Brain;Brain region;Characteristics;Child;Clinical;cognitive performance;cohort;comparison group;Complex;Conscious;Coupling;Cross-Sectional Studies;Data;Development;Diagnosis;Diagnostic;Dorsal;Education;executive function;Exhibits;Face Processing;Family;Goals;gray matter;Growth;imaging study;improved;Individual;individuals with autism spectrum disorder;Insula of Reil;Intellectual functioning disability;Knowledge;Language;Link;Longitudinal Studies;Magnetic Resonance Imaging;model of autism spectrum disorder;Monitor;Motor Cortex;MRI Scans;network models;neural;neural network;Neurobiology;novel;Pattern;pediatrician;peer;phenome;Phenotype;programs;Puberty;Reporting;Research;Risk Taking;Scanning;Severities;sex;Staging;Structure;Subgroup;Symptoms;Teenagers;Testing;Thick;Time;verbal;Visual Cortex

PROJECT_TITLE: Brain and Behavioral Development in Autism Spectrum Disorder

STUDY_SECTION: CPDD

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


PROJECT_TERMS: Acceleration;Alleles;Animal Model;animal tissue;Animals;Antibodies;Back;Biochemical;Biological;Biological Assay;Biological Markers;Brain;Capsid;Cardiovascular system;cell fixing;cell type;Cells;chemokine;Clustered Regularly Interspaced Short Palindromic Repeats;Confocal Microscopy;Consultations;cytokine;Data;data dissemination;data management;delivery vehicle;Development;digital;Enzyme-Linked Immunosorbent Assay;Evaluation;Excision;Gene Expression;Gene Targeting;genome editing;genome editor;Genomic DNA;Genomics;Glass;Hematoxylin and Eosin Staining Method;Histologic;Huntington gene;Image Analysis;Immune;immunogenicity;Immunoglobulins;Immunohistochemistry;Immunology procedure;in vivo;innovation;knock-down;Laboratories;Libraries;Liquid substance;Mass Spectrum Analysis;Measures;Mediating;Microscopic;Microscopy;Mission;molecular pathology;molecular phenotype;Monitor;mutant;Nervous System Disorder;Neuroglia;Neurons;neuropathology;next generation sequencing;Nuclear;Nucleic Acids;Outcome;Output;Pathogenicity;Pathology;Phenotype;Play;Polymerase Chain Reaction;pre-clinical;pre-clinical research;preclinical study;Preparation;Process;Production;programs;protein expression;protein TDP-43;Proteins;Proteome;Proteomics;Research;Research Project Grants;Research Support;Resources;Role;Safety;Sampling;Scanning;Scientist;Serology;Serum;Services;Slide;Stains;System;timeline;Tissues;tool;Toxic effect;Training;transcriptome;transcriptome sequencing;transcriptomics;Western Blotting;Work

PROJECT_TITLE: Resource Core III: Biological Impacts Core


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

PI_NAMEs: CAMARGO, FERNANDO  (contact)

PROJECT_TERMS: Age;Bar Codes;Behavior;Biological Assay;Blood Cells;Cell Compartmentation;Cell Lineage;Cells;Clonal Expansion;Data;DNMT3a;DNMT3a mutation;Epigenetic Process;epigenetic regulation;Event;Exhibits;functional outcomes;Genes;Genetic study;genomic tools;Genomics;Genotype;Grant;Hematologic Neoplasms;Hematology;Hematopoiesis;Hematopoietic;Hematopoietic Stem Cell subsets;Hematopoietic stem cells;Hematopoietic System;Heterogeneity;Human;In Vitro;in vivo;Individual;Induced Mutation;insight;Maps;Modeling;Molecular;Monitor;mouse model;Multipotent Stem Cells;mutant;Mutation;novel;Patient Monitoring;Patients;Penetrance;permissiveness;Phenotype;Physiological;Population;Prevalence;Process;Production;programs;Resolution;response;Role;self-renewal;stem;stem cells;Technology;tool;Work

PROJECT_TITLE: Project 1 - Molecular and cellular determinants of hematopoietic clonal expansion


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

ORG_CITY: TALLAHASSEE

ORG_DEPT: CHEMISTRY

ORG_NAME: FLORIDA STATE UNIVERSITY

PHR: The proposed research is relevant to public health because identifying the mechanisms that control the secretory dynamics of insulin and glucagon is ultimately expected to increase understanding of the pathogenesis of perturbed hormone oscillations observed in type II diabetes. The proposed research is relevant to the part of NIH’s mission that pertains to developing fundamental knowledge that enhances human health.

PI_NAMEs: ROPER, MICHAEL GABRIEL (contact)

PROGRAM_OFFICER_NAME: HWA, ALBERT J

PROJECT_TERMS: Agonist;American;antibody test;Back;Biological Assay;Biological Process;Biology;Blood Glucose;blood glucose regulation;Carbachol;Cause of Death;cholinergic;circadian;Communication;Data;Defect;design;Detection;Diabetes Mellitus;Diagnosis;Disease;Disease Progression;Endocrine;extracellular;Feedback;Fluorescence;Fluorescence Anisotropy;Fluorescence Resonance Energy Transfer;Funding;Future;Ganglia;Glucagon;Glucose;glucose uptake;Goals;Health;Hormonal;Hormone secretion;Hormones;Human;Immunoassay;impaired glucose tolerance;improved;in vivo;Individual;innovation;Insulin;Insulin Infusion Systems;insulin secretion;islet;Islets of Langerhans;Knowledge;Laboratories;Link;Measurement;Measures;Metabolic Diseases;Methods;Microfluidic Microchips;Microfluidics;Mission;Modeling;Muscarinic M3 Receptor;Myocardial Infarction;neural;Neuropathy;Non-Insulin-Dependent Diabetes Mellitus;Organ;Pancreas;Pancreatic Hormones;parallelization;Pathogenesis;Patients;Pattern;Perfusion;Periodicals;Persons;Phase;Physiologic pulse;Population;Prediabetes syndrome;Progress Reports;Public Health;Receptor Activation;Regulation;Research;Risk;Speed;Stroke;System;Technology;Testing;Therapeutic;therapeutic development;Time;United States National Institutes of Health;Work

PROJECT_TITLE: Microfluidic Devices For Determining Dynamics Of Islets of Langerhans

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


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

ORG_DEPT: GENETICS

PHR: Narrative Noroviruses are a major cause of diarrheal disease throughout the world. Using a novel mouse model of norovirus disease, we will elucidate mechanisms underlying norovirus gastroenteritis and identify key host-virus interactions in this disease process.

PI_NAMEs: KARST, STEPHANIE M (contact)

PROGRAM_OFFICER_NAME: ALARCON, RODOLFO M

PROJECT_TERMS: Acceleration;Acute;acute infection;Adult;Animal Model;Attenuated;B-Lymphocytes;Biological Assay;Biological Models;Biology;cell type;Cells;cellular targeting;Childhood;Data;Dendritic Cells;Diarrhea;diarrheal disease;Disease;Ensure;Enteral;enteric infection;Epithelial Cells;Epithelium;Event;Feces;Gastroenteritis;Gastrointestinal Diseases;gastrointestinal epithelium;Genetic;Genetic Determinism;Genetic Transcription;Human;Immune;Immune Targeting;Immunocompetent;Immunologics;Infection;innovation;insight;interdisciplinary approach;Intestinal Diseases;intestinal epithelium;Intestines;Laboratory mice;Lymphocyte;Macrophage;Maps;Modeling;mouse model;Mus;Neonatal;neonatal infection;neonatal mice;neonate;neutrophil;Norovirus;novel;Oral;Outcome;Pathogenesis;Pathogenicity;Pathologic;Peyer's Patches;Predisposition;Primary Infection;Process;pup;Research;Resistance;RNA;Rotavirus Infections;secondary lymphoid organ;Severity of illness;Small Intestines;Symptoms;System;T-Lymphocyte;Testing;Tissues;Tropism;Viral;Viral Proteins;Virulence;Virulence Factors;Virulent;Virus;virus genetics;virus host interaction;Virus Replication;Work

PROJECT_TITLE: Elucidation of Pathogenic Mechanisms underlying Norovirus Diarrhea

STUDY_SECTION: VIRB

STUDY_SECTION_NAME: Virology - B Study Section[VIRB]


NIH_SPENDING_CATS: Bioengineering;Biotechnology;Brain Disorders;Gene Therapy;Genetics;Huntington's Disease;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases

PI_NAMEs: LONSER, RUSSELL  (contact)

PROJECT_TERMS: Acute;adeno-associated viral vector;Alleles;Animal Model;Animals;Autopsy;Basal Ganglia;behavior test;Binding;Biodistribution;Brain;Brain region;brain tissue;Capsid;cell transformation;Clinic;Clinical;Clinical Trials;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Contracts;Convection;Corpus striatum structure;CRISPR/Cas technology;Data;delivery vehicle;Dependovirus;design;Disease;disease phenotype;DNA;DNA Double Strand Break;Dose;effective therapy;efficacy evaluation;efficacy testing;Engineering;Ensure;Enzymes;Evaluation;Excision;Exons;experimental study;feasibility testing;Fibroblasts;first-in-human;gain of function mutation;gene therapy;Genes;genome editing;Genomics;Guide RNA;Guidelines;Haplotypes;Hereditary Disease;Human;Huntington Disease;Huntington gene;In Vitro;Induced pluripotent stem cell derived neurons;Injections;Investigational Drugs;Investigational New Drug Application;knock-down;Lead;Length;Macaca fascicularis;Magnetic Resonance Imaging;Mediating;meetings;Molecular;mouse model;Movement Disorders;Mus;mutant;Mutation;Nervous System Disorder;Neurodegenerative Disorders;neurogenetics;neuron loss;nonhuman primate;novel;Onset of illness;Organ;Pathogenicity;Patients;Peripheral;Persons;polyglutamine;pre-clinical;pre-Investigational New Drug meeting;Process;programs;progressive neurodegeneration;Proteins;putamen;Rattus;Recombinants;repaired;Reporting;research clinical testing;Research Project Grants;RNA;Rodent;Safety;Satellite Viruses;screening;Serotyping;Severities;Site;Specific qualifier value;System;Testing;Thalamic structure;Therapeutic;tissue/cell culture;Tissues;Toxic effect;Toxicology;transduction efficiency;Translating;United States Food and Drug Administration;vector

PROJECT_TITLE: Research Project I: AAV-CRISPR to Treat Huntington's Disease


ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: PROJECT NARRATIVE Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for more than a third of all deaths each year. CVD risk factors develop in young adulthood and impact a person's risk for CVD events later in life. This study will use advanced statistical methods to combine data from 20 longitudinal studies in order to better understand CVD risk factor trajectories across the life course and their association with CVD on a diverse sample of the United States population.

PI_NAMEs: DANIELS, MICHAEL J;SIDDIQUE, JUNED  (contact)

PROGRAM_OFFICER_NAME: ANAYA, GABRIEL

PROJECT_TERMS: adjudication;Adult;Age;age related;Agreement;Behavior;Blood Pressure;Cardiovascular Diseases;cardiovascular disorder prevention;cardiovascular disorder risk;cardiovascular health;cardiovascular risk factor;Cause of Death;Cessation of life;Characteristics;Cholesterol;Clinical;clinical development;clinically relevant;cohort;Cohort Studies;Communities;critical period;Data;Data Pooling;Data Set;Development;Diagnostic tests;Disease;Disease Outcome;Education;emerging adult;Evaluation;Event;flexibility;follow-up;Geographic Locations;Goals;Health;health difference;human old age (65+);Individual;innovation;Intervention;Life;Life Cycle Stages;life span;Life Style;lifetime risk;Literature;Longitudinal cohort study;Longitudinal Studies;Measurement;Measures;men;middle age;Modeling;older adult;Outcome;Participant;Persons;Pharmaceutical Preparations;phenotypic data;Physiological;Population;preservation;Prevention strategy;Process;Prospective, cohort study;Race;Research;Research Personnel;Resources;response;Risk;Risk Factors;Role;Sampling;sex;Statistical Methods;Time;Training;treatment strategy;United States;Validation;Vital Status;Work;young adult

PROJECT_TITLE: Combining longitudinal cohort studies to examine cardiovascular risk factor trajectories across the adult lifespan and their association with disease

STUDY_SECTION: CHSB

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


ADMINISTERING_IC: DE

ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

IC_NAME: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

NIH_SPENDING_CATS: Cancer;Cervical Cancer;Dental, Oral, and Craniofacial Disease;Genetics;Infectious Diseases;Sexually Transmitted Infections;Women's Health Research

ORG_CITY: RICHMOND

ORG_DEPT: DENTISTRY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Human papillomaviruses are causative agents in a number of ano-genital and oral cancers; HPV causes 5% of all cancers. There are no therapeutics that target the virus to assist with the alleviation of this disease burden and the focus of this application is to enhance our understanding of the HPV16 life cycle in order to identify novel therapeutic targets. We have discovered a novel cellular complex, WRN-SAMHD1-MRN, that regulates the HPV16 life cycle and will dissect the role of this complex in regulation of HPV replication levels and fidelity; we will also investigate how HPV influences host DNA replication and the innate immune response.

PI_NAMEs: MORGAN, IAIN  (contact)

PROGRAM_OFFICER_NAME: CHEN, ZHONG

PROJECT_TERMS: adaptive immune response;Anogenital cancer;Biological Assay;burden of illness;Cell Death;Cell Line;Cell Proliferation;Cells;Cervical;Collaborations;Complex;CRISPR/Cas technology;Cytoplasm;Data;Disease;DNA;DNA biosynthesis;DNA Damage;DNA Double Strand Break;DNA Repair;DNA replication fork;endonuclease;enzyme activity;Enzymes;Gene Activation;Gene Expression;Genetic Recombination;Genome;Goals;Head and Neck Cancer;helicase;homologous recombination;HPV positive;human disease;Human papilloma virus 31;Human Papillomavirus;Human papillomavirus 16;Immune Response Genes;Immunotherapy;innate immune mechanisms;Innate Immune Response;Integration Host Factors;keratinocyte;Knowledge;LacZ Genes;Lesion;Life Cycle Stages;malignant mouth neoplasm;Malignant Neoplasms;Measures;member;Modeling;Mutagenesis;new therapeutic target;novel;novel strategies;novel therapeutic intervention;Outcome;Pathogenicity;Pathway interactions;Phenotype;Publishing;recruit;Regulation;replication stress;Reporting;response;Retinoblastoma Protein;Role;SIRT1 gene;Stimulator of Interferon Genes;System;targeted treatment;Testing;therapeutic target;Time;TP53 gene;transcriptome sequencing;Tumor Suppressor Proteins;Viral;Viral Genome;Virus;Virus Diseases;Virus Replication

PROJECT_TITLE: Determining how a Werner helicase (WRN) tumor suppressor complex regulates the human papillomavirus 16 life cycle

STUDY_SECTION: VIRA

STUDY_SECTION_NAME: Virology - A Study Section[VIRA]


NIH_SPENDING_CATS: Kidney Disease;Regenerative Medicine

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

PHR: Modified Public Health Relevance Section  The proposed research is relevant to the public health because AKI, increasing in incidence, represents a major public health concern with high human and financial costs. Other than supportive treatment through dialysis, there are no established therapeutic interventions to improve survival, limit injury, or promote recovery in patients with AKI. Upon conclusion, we will provide new insights into how systemic HIF-2 activation affects postischemic kidney injury and repair through tryptophan metabolism, and this discovery will create novel therapeutic opportunities in the field of AKI.

PI_NAMEs: KAPITSINOU, PINELOPI P. (contact)

PROGRAM_OFFICER_NAME: SADUSKY, ANNA BURKART

PROJECT_TERMS: Acute Renal Failure with Renal Papillary Necrosis;Address;Affect;anaerobic glycolysis;angiogenesis;Anti-Inflammatory Agents;Area;Attenuated;bHLH-PAS factor HLF;Cell Proliferation;Cell Respiration;Cells;Cellular Metabolic Process;Cytoprotection;Data;Dialysis procedure;effective therapy;Environment;Erythropoiesis;Financial cost;Genes;Genetic;Genetic Models;Glycolysis;Goals;Hospitalization;Human;Hypoxia;Hypoxia Inducible Factor;hypoxia inducible factor 1;improved;Incidence;Inflammation;Injury;injury and repair;injury prevention;Injury to Kidney;innovation;insight;Intensive Care Units;Investigation;Investigational Therapies;Ischemia;Kidney;kidney repair;Knowledge;Kynurenic Acid;Kynurenine;Mediating;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Morbidity - disease rate;mortality;N'-formylkynurenine;new therapeutic target;novel;novel therapeutics;Oxidative Phosphorylation;Oxygen;Pathway interactions;Patients;pharmacologic;prevent;Process;Procollagen-Proline Dioxygenase;promote resilience;protective effect;Protein Isoforms;Public Health;public health relevance;Publishing;Recovery;renal ischemia;repaired;Reperfusion Injury;Research;response;Role;sensor;Serum;Signal Transduction;Tertiary Protein Structure;Testing;Therapeutic Intervention;tissue injury;tissue repair;Tissues;transcription factor;transcriptomics;translational applications;Tryptophan;Tryptophan 2,3 Dioxygenase;Tryptophan Metabolism Pathway;uptake

PROJECT_TITLE: Harnessing hypoxia responses to treat postischemic kidney injury and inflammation

STUDY_SECTION: PBKD

STUDY_SECTION_NAME: Pathobiology of Kidney Disease Study Section[PBKD]


NIH_SPENDING_CATS: Genetics;Hematology;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

PROJECT_TERMS: Affect;Alleles;Assessment tool;Bar Codes;Bone Marrow;Cell Compartmentation;Cells;Cellular Metabolic Process;Clonal Deletion;Clonal Hematopoietic Stem Cell;Data;Dependence;Diagnosis;DNA Sequence Alteration;Epigenetic Process;Frequencies;Gene Frequency;Genetic Transcription;genetic variant;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Heterogeneity;in vivo;insight;Intervention;loss of function;Mediating;Metabolic;metabolomics;Methods;Molecular;mutant;Mutate;Mutation;neoplastic;overexpression;Pathologic;Pathway interactions;Patient risk;pharmacologic;Phenotype;programs;progression risk;Risk;risk mitigation;risk stratification;Somatic Mutation;SOX4 gene;stem;stem cells;Stress;synergism;Testing;Therapeutic Intervention;transcription factor;Validation

PROJECT_TITLE: Project 2 - Cell of origin contributions and vulnerabilities in clonal hematopoiesis


ORG_CITY: PHILADELPHIA

ORG_NAME: UNIVERSITY OF PENNSYLVANIA

PHR: Recent studies have shown that endothelial-to-mesenchymal transition (EndMT) is potentially the key driving force behind the development and progression of atherosclerosis. We have now identified a metabolic step that seems critical to the control of EndMT, and for which we are developing new therapeutic approaches. The proof of this discovery will open new therapeutic possibilities for treating diseases such as heart attacks, stroke, pulmonary hypertension and peripheral vascular disease.

PI_NAMEs: ARANY, ZOLTAN P (contact);SIMONS, MICHAEL

PROGRAM_OFFICER_NAME: CATANIA, SELEN MURATOGLU

PROJECT_TERMS: Acetates;Acetyl Coenzyme A;Acetylation;anaerobic glycolysis;Animal Model;Arterial Disorder;Arterial Fatty Streak;Atherosclerosis;Blood Vessels;Bypass;Cellular Metabolic Process;Chronic;Citrates;clinical practice;Cytoplasm;Data;defined contribution;Development;Disease;driving force;efficacy testing;Endothelial Cells;Endothelium;Enzymes;Event;Feedback;Generations;Genetically Engineered Mouse;Glucose;Goals;Hypoxia;In Vitro;in vitro testing;in vivo;in vivo evaluation;Inflammation;inhibitor;Link;Mass Spectrum Analysis;Mesenchymal;Metabolic;Metabolic Activation;Metabolic Control;Metabolic Pathway;Metabolism;Mitochondria;mouse model;Mus;Myocardial Infarction;nanoparticle;nanoparticle delivery;novel;novel therapeutic intervention;novel therapeutics;Oral;Paint;Pathology;Pathway interactions;Peripheral Vascular Diseases;Phosphorylation;Physiological;Play;prevent;Prevention;Process;Production;Protein Acetylation;pulmonary arterial hypertension;Pulmonary Hypertension;Pyruvate;pyruvate dehydrogenase;Pyruvate Dehydrogenase Complex;Regulation;RNA Interference;Role;side effect;Signal Transduction;Site;Smooth Muscle Myocytes;Source;Stroke;success;targeted treatment;Techniques;Testing;Therapeutic;Therapeutic Agents;therapeutic evaluation;therapeutic target;therapeutically effective;Transforming Growth Factor beta;Translating;translational approach;Transplantation;vascular inflammation

PROJECT_TITLE: Acetate and Endothelial Pathobiology

STUDY_SECTION: BBHV

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Alzheimer's Disease Related Dementias (ADRD);Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Biotechnology;Brain Disorders;Dementia;Frontotemporal Dementia (FTD);Gene Therapy;Genetics;Neurodegenerative;Neurosciences;Orphan Drug;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

PI_NAMEs: CLELLAND, CLAIRE  (contact)

PROJECT_TERMS: Acceleration;Address;Adult;Alleles;Alzheimer's disease related dementia;Amyotrophic Lateral Sclerosis;Base Pairing;Biodistribution;Biological Markers;Brain;C9ALS;C9ORF72;cell type;Cells;Cessation of life;Clinic;Clinical;clinical phenotype;Clinical Trials;Clinical Trials Design;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Convection;Cortical Cord;CRISPR therapeutics;CRISPR/Cas technology;curative treatments;design;disability;Dose;effective therapy;Excision;experimental study;Frontotemporal Dementia;frontotemporal lobar dementia amyotrophic lateral sclerosis;Gene Combinations;gene replacement;gene therapy;Genes;Genetic;genome editing;Goals;Guide RNA;Health Expenditures;Heterozygote;Human;Immune response;In Vitro;in vivo;in vivo Model;Induced pluripotent stem cell derived neurons;Injections;Lead;lead optimization;Mitotic;Motor Neurons;mouse model;Mus;mutant;Mutation;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;Neurons;nonhuman primate;novel;novel therapeutic intervention;Outcome;Pathogenicity;Pathologic;patient derived induced pluripotent stem cells;Patients;postmitotic;pre-clinical;preservation;Proteins;rational design;Rattus;Reagent;Reporter;Research;Research Project Grants;response;risk minimization;Site;Specificity;Spinal Cord;System;Technology;Testing;Therapeutic;therapeutic candidate;Therapeutic Index;Therapeutic Intervention;therapeutic target;tool;Toxicology;Validation;Ventricular;Virus

PROJECT_TITLE: Research Project II: AAV-CRISPR to Treat Amyotrophic Lateral Sclerosis


PI_NAMEs: TENEN, DANIEL G (contact)

PROJECT_TERMS: Address;Affect;Assessment tool;Behavior;Biological Markers;cancer cell;cell behavior;Cell Differentiation process;cell growth regulation;Cell Line;Cell Maintenance;Cell Physiology;Cell Survival;Cells;Characteristics;Chromatin;Clonal Expansion;Clonal Hematopoietic Stem Cell;Complex;cytokine;Cytokine Signaling;Data;Data Analyses;data integration;Data Set;data sharing networks;Diagnosis;DNA Methylation;DNMT3a mutation;Dysmyelopoietic Syndromes;Ecosystem;Environment;Epigenetic Process;experimental study;extracellular;Functional disorder;Gene Expression;Genetic Transcription;Glycolysis;Hematological Disease;Hematopoiesis;hematopoietic differentiation;hematopoietic stem cell expansion;Hematopoietic stem cells;Heterogeneity;IL6 gene;Immune;improved;in vivo;Inflammation;Inflammatory;inflammatory milieu;Kinetics;Lead;leukemic transformation;Link;loss of function;Maintenance;Malignant - descriptor;MAP Kinase Gene;Maps;Marrow;Mediating;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Methods;Mitochondria;mitochondrial metabolism;Molecular;mouse model;mutant;Mutation;Myelogenous;NF-kappa B;Outcome;p38 Mitogen Activated Protein Kinase;Pattern;Population;Population Dynamics;pre-clinical;Pre-Clinical Model;Preleukemia;premalignant;Process;programs;Proliferating;Proteomics;Publications;Recurrence;Research;Resolution;response;Risk;Role;Signal Pathway;Signal Transduction;Stat3 protein;stem;stem cells;stemness;Stimulus;Testing;Therapeutic;Therapeutic Intervention;transcription factor;transcriptomics;Work

PROJECT_TITLE: Project 3 - Transcriptional and epigenetic heterogeneity of stem/progenitor cells


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

PI_NAMEs: MURTHY, NIREN  (contact)

PROJECT_TERMS: Alleles;Alzheimer's Disease;amphiphilicity;Anatomy;Animals;Antibodies;Behavioral;Biochemical;Biological Assay;Brain;Brain Diseases;brain tissue;brain volume;Charge;Chemicals;Clinical;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Convection;Corpus striatum structure;CRISPR therapeutics;design;Development;Diffuse;Disease;disease model;DNA Sequence Alteration;Endotoxins;Enzymes;Excision;experimental study;Formulation;genome editing;Goals;Guide RNA;Human;Huntington Disease;Huntington gene;immune activation;immunogenicity;Inflammation;Infusion procedures;Injections;Life;macromolecule;manufacture;Methodology;Methods;Modeling;mouse model;Mus;mutant;nanoparticle;Nervous System Disorder;Neurons;overexpression;Parkinson Disease;Pathogenicity;Patients;Peptides;pre-clinical;Process;Property;Proteins;Protocols documentation;rational design;Rattus;Reagent;Research Project Grants;Risk;Safety;safety study;Site;Toxicology;Transfection;Vendor;Viral;Virus

PROJECT_TITLE: Research Project III: RNP-CRISPR to Treat Huntington's Disease


NIH_SPENDING_CATS: Biotechnology;Cardiovascular;Congenital Heart Disease;Congenital Structural Anomalies;Heart Disease;Pediatric;Rare Diseases

ORG_CITY: BALTIMORE

ORG_NAME: UNIVERSITY OF MARYLAND BALTIMORE

ORG_STATE: MD

PHR: NARRATIVE  During the last ten years, it has become apparent that deregulation or disruption of proteins residing at the Intercalated Disk (ICD), the unique membrane microdomain that mediates the mechanical and electrical coupling of cardiomyocytes, leads to cardiac defects and development of severe or lethal cardiomyopathies. The proposed studies will provide important and novel information about the modulation of a major component of the ICD, N-cadherin, via the enzymatic activity of the obscurin Ser/Thr kinase domain 1. Elucidating the molecular mechanisms that underlie cell-cell adhesion and communication in cardiac muscle during normalcy will allow us to understand how these are altered or compromised during congenital heart disease, and thus enable us to develop new, effective, and targeted therapies.

PI_NAMEs: KONTROGIANNI-KONSTANTOPOULOS, AIKATERINI  (contact)

PROGRAM_OFFICER_NAME: ADHIKARI, BISHOW B

PROJECT_TERMS: Address;Adherens Junction;Adhesions;Affect;Affinity;Aging;Aortic Valve Stenosis;Arrhythmogenic Right Ventricular Dysplasia;Binding;Biochemical;Biological;Biological Assay;Calmodulin;Cardiac;Cardiac Myocytes;cardiogenesis;Cardiomyopathies;Catalytic Domain;Cell Communication;Cell-Cell Adhesion;Classification;Communication;congenital heart abnormality;Coupling;Cytoplasmic Tail;Cytoskeletal Proteins;Development;Dilated Cardiomyopathy;Disease;Dominant-Negative Mutation;effective therapy;Electrophysiology (science);Family;Fibronectins;Gene Delivery;Genes;Health;Heart;heart defect;Heart Diseases;Heart failure;Human;Immunoglobulins;In Vitro;in vivo;Injections;Intercalated disc;Kinetics;Knock-in Mouse;Left ventricular non-compaction;Link;Mass Spectrum Analysis;Mechanics;Mediating;member;Membrane;Membrane Microdomains;Missense Mutation;Modeling;Molecular;Morphology;mouse model;Mus;Mutagenesis;Mutate;Mutation;Myocardium;Myosin Light Chain Kinase;N-Cadherin;next generation sequencing;Normalcy;novel;novel therapeutics;obscurin;overexpression;Pathogenesis;Pathogenicity;Patients;phosphoproteomics;Phosphorylation;Phosphotransferases;Physiological;Play;Pre-Clinical Model;Property;Protein Isoforms;Protein Truncation;Proteins;Role;Sarcolemma;Sequence Homology;Signal Transduction;Site;Striated Muscles;Structure;Surface Plasmon Resonance;Tachycardia;targeted treatment;therapy development;Time;Variant;Viral;Work;young adult

PROJECT_TITLE: Obscurin-kinase 1/N-cadherin: a new signaling axis in cardiac structure/function

STUDY_SECTION: MPPB

STUDY_SECTION_NAME: Integrative Myocardial Physiology/Pathophysiology B Study Section[MPPB]


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

ORG_CITY: NEW YORK

ORG_DEPT: PEDIATRICS

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: NARRATIVE Household food insecurity during infancy is a risk factor for later childhood obesity. In this pilot and feasibility study, we will randomly assign infant-parent dyads with household food insecurity to either 1) the Food FARMacia mobile food pantry intervention with self-directed meal preparation support or 2) self-directed meal preparation support. In addition to examining feasibility, acceptability, and satisfaction, we will estimate intervention effects on infant weight characteristics and explore potential mediators to inform a subsequent full- scale trial.

PI_NAMEs: WOO BAIDAL, JENNIFER AIMEE (contact)

PROGRAM_OFFICER_NAME: OSGANIAN, VOULA

PROJECT_TERMS: Academy;Acceleration;acceptability and feasibility;Address;adverse event monitoring;Age;American;arm;attentional control;Biometry;Body mass index;Characteristics;Child;Childhood;Clinical;clinical care;Clinical Nutrition;Clinical Trials;Communities;community clinical linkage;Consumption;Control Groups;COVID-19 pandemic;Data;Diabetes Mellitus;Diet;dietary;Dietary Practices;Disparity;efficacious intervention;efficacy testing;Electronic Health Record;Eligibility Determination;Enrollment;Ethnic Origin;Etiology;experience;Family;fatty liver disease;Feasibility Studies;feeding;Food;food insecurity;Foundations;Future;Goals;Growth;Growth and Development function;Health;health disparity populations;health information technology;Healthcare Systems;healthy weight;High Prevalence;Hispanic;Household;improved;Income;Inequity;infancy;Infant;Intervention;intervention effect;Latino Population;Life;Life Expectancy;Measures;Mediator;Medicine;Metabolic;multidisciplinary;National Institute of Diabetes and Digestive and Kidney Diseases;New York City;nutrition;Obesity;obesity in children;Observational Study;Outcome;Parents;pediatric patients;Pediatrics;Phase;Pilot Projects;Play;Population;population health;Population Heterogeneity;Preparation;Prevalence;prevent;Primary Care;primary care visit;Procedures;Professional Organizations;Qualitative Research;Race;Randomized;randomized trial;randomized, clinical trials;Recommendation;recruit;Reduce health disparities;Research;Research Methodology;response;Risk;Risk Factors;Role;routine screening;satisfaction;screening;Self Direction;Site;socioeconomic disparity;Stress;Structure;sugar;sweetened beverage;therapy development;Time;United States;Weight

PROJECT_TITLE: Food FARMacia: Reducing Childhood Obesity in Households with Food Insecurity

STUDY_SECTION: LCBH

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


PI_NAMEs: ZON, LEONARD IRA (contact)

PROJECT_TERMS: Adult;adult stem cell;Aftercare;aged;Aging;antagonist;Anti-Inflammatory Agents;Automobile Driving;Bar Codes;Biochemistry;Biological Assay;Blood Cells;calreticulin;Cell Communication;cell type;Cells;chemical genetics;Chemicals;Choline;Clonal Hematopoietic Stem Cell;Clonality;Clone Cells;Clustered Regularly Interspaced Short Palindromic Repeats;Color;Coupled;Dependence;Development;Disease;DNA Sequence Alteration;DNMT3a;DNMT3a mutation;Dysmyelopoietic Syndromes;Early Diagnosis;Eating;Embryo;Epigenetic Process;Equilibrium;Experimental Genetics;experimental study;Fishes;Flow Cytometry;Gene therapy trial;Genes;Genetic;Genetic Screening;genetic variant;Goals;Growth;Hematological Disease;Hematopoiesis;Hematopoietic;Hematopoietic stem cells;Heterogeneity;Human;in vivo;Individual;inhibitor;Lead;Macrophage;mature animal;Metabolic;Metabolic Pathway;Metabolism;metabolomics;Methods;Modeling;Monitor;mosaic;Mutagenesis;mutant;Mutate;Mutation;NR4A1 gene;Orthologous Gene;Outcome;Pathway interactions;Persons;pharmacologic;Role;Signal Transduction;small molecule;Sorting;stem;stem cell niche;stem cells;Surface;Syndrome;System;targeted treatment;Techniques;Technology;Testing;Therapeutic;Transplantation;transplantation therapy;Work;Zebrafish

PROJECT_TITLE: Project 4 - Mechanisms of establishing clonal dominance


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

ORG_CITY: LA JOLLA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE Healthy cognitive processing is associated with well-defined oscillatory neuronal activity, and some aspects of brain oscillations have been reported to be disrupted in any of the major psychiatric and neurological diseases. Selectively targeting brain oscillations for treatment could thus profoundly improve cognitive function in disease. To provide a foundation for such therapies, our objective is to show to what extent brain stimulation affects local neural computations as well as long-distance communication between brain regions, and our studies will therefore provide a neurobiological foundation for further developing invasive and non-invasive brain stimulation therapies.

PI_NAMEs: LEUTGEB, STEFAN  (contact)

PROGRAM_OFFICER_NAME: BABCOCK, DEBRA J

PROJECT_TERMS: Address;Affect;Air Movements;Alzheimer's Disease;Anterior;Area;Award;Brain;Brain Diseases;Brain region;Breathing;Cells;Code;Cognitive;cognitive function;Communication;Coupling;Cues;Data;Dependence;Devices;Disease;Dorsal;entorhinal cortex;Epilepsy;experimental study;Feedback;Foundations;Frequencies;Hippocampus;Impairment;improved;interest;Lateral;Medial;Memory;Mental Depression;Mental disorders;Motor;Mus;Nervous System Disorder;neural;Neurobiology;Neurons;noninvasive brain stimulation;Nose;Odors;olfactory bulb;Olfactory Pathways;olfactory sensory neurons;optogenetics;Pacemakers;Parkinson Disease;Pattern;Performance;Periodicity;Phase;piriform cortex;Population;Population Dynamics;Prefrontal Cortex;programs;Reporting;Respiration;Sampling;Schizophrenia;Sensory;Short-Term Memory;targeted treatment;Task Performances;Testing

PROJECT_TITLE: Dependence of memory on precisely coordinated oscillations

STUDY_SECTION: LMDN

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


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Emerging Infectious Diseases;Infectious Diseases;Microbiome;Nutrition

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: Project Narrative RORgt+ group 3 innate lymphoid cells play an important role in infection/inflammation. The proposed experiments will provide novel insights into the role of iron metabolism in ILC3s, and the Ahr-CD71 axis in regulation of RORgt+ cell maintenance and function under the steady state and during infections. Infectious diseases have been increasingly exacting a substantial toll on health in US, and the knowledge gained in this study will help the development of new therapeutic strategies by exploiting the Ahr-CD71-iron axis in ILC3s to combat infection and control inflammation.

PI_NAMEs: ZHOU, LIANG  (contact)

PROGRAM_OFFICER_NAME: HUDSPETH, KELLY

PROJECT_TERMS: Ablation;Affect;Aryl Hydrocarbon Receptor;Binding;Cell Compartmentation;Cell Line;Cell Maintenance;Cell Physiology;Cells;Citrobacter rodentium;combat;Communicable Diseases;Complex;cytokine;Data;Development;Disease;Elements;Environmental Impact;experimental study;Funding;Genetic Transcription;global health;Glycolysis;Health;HIF1A gene;Homeostasis;host microbiome;IL17 gene;Immune;Immune response;Immune system;Immunity;Immunology;in vivo;Infection;Inflammation;insight;interleukin-22;Intestinal Mucosa;Intestines;Iron;iron deficiency;iron metabolism;Knowledge;Lymphocyte;Lymphoid Cell;Maintenance;Mediating;Metabolic;Metabolism;microbiome;microbiota;Mitochondria;Modeling;mouse genetics;Mus;novel;novel therapeutic intervention;nutrition;Oxidative Phosphorylation;pathogen;Pathway interactions;Play;Predisposition;Production;Proliferating;promoter;receptor;receptor expression;Regulation;Research;Role;Salmonella typhimurium;T-Cell Activation;Testing;TFRC gene;Tissues;tool;transcription factor;Transcriptional Regulation;transcriptomics;uptake

PROJECT_TITLE: Regulation of Gut Innate Lymphoid Cells by Ahr

STUDY_SECTION: III

STUDY_SECTION_NAME: Innate Immunity and Inflammation Study Section[III]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

FUNDING_MECHANISM: TRAINING, INSTITUTIONAL

IC_NAME: NATIONAL INSTITUTE ON AGING

NIH_SPENDING_CATS: Aging

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

ORG_NAME: JOHNS HOPKINS UNIVERSITY

PHR: Project Narrative This program addresses a critical need of the field of gerontology for scholars who combine quantitative expertise with immersion in science on aging. Such scholars are crucial because cutting-edge research on aging involves complex data on persons' biological and clinical characteristics, physical and social environments, and health care utilization. Only with such scholars' leadership can data be collected and analyzed so as to yield valid scientific discoveries on improved outcomes for our older population.

PI_NAMEs: BANDEEN-ROCHE, KAREN J. (contact)

PROGRAM_OFFICER_NAME: TORRES, DELANY

PROJECT_TERMS: Aging;Biometry;Epidemiology

PROJECT_TITLE: Epidemiology and Biostatistics of Aging


ADMINISTERING_IC: HG

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

NIH_SPENDING_CATS: Genetics;Human Genome;Neurosciences

ORG_CITY: Los Angeles

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: Alternative splicing is a major mechanism that generates the diverse proteome during development and is frequently disrupted in many human diseases. We develop a new technology, SHARCLIP, to build a transcriptome-wide structure-interaction map for pre-mRNP complexes on which alternative splicing occurs. This technology and resource will help understand mechanisms of splicing-related diseases and empower future RNA-targeting therapeutics.

PI_NAMEs: LU, ZHIPENG  (contact)

PROGRAM_OFFICER_NAME: CHADWICK, LISA

PROJECT_TERMS: 3-Dimensional;Acylation;Alternative Splicing;Amino Acids;Antisense Oligonucleotides;Base Pairing;Benchmarking;Binding;Binding Proteins;Biochemical;brain cell;Cell Differentiation process;Cell Line;Cell Lineage;cell type;Cells;Chemicals;Chemistry;Chromatin;Chromatin Interaction Analysis by Paired-End Tag Sequencing;Classification;Clustered Regularly Interspaced Short Palindromic Repeats;Code;Complex;computational pipelines;computerized tools;crosslink;Data;Development;Disease;Elements;empowerment;Event;Exons;experimental study;Formaldehyde;Free Energy;Future;Genes;Genetic;Genetic Diseases;Genome;genome editing;HepG2;high dimensionality;high throughput technology;Human;human disease;human induced pluripotent stem cells;Hydroxyl Radical;in vivo;invention;K-562;Laws;Ligation;Malignant Neoplasms;Maps;Mass Spectrum Analysis;Measures;Mediating;messenger ribonucleoprotein;Methods;Modeling;Molecular;Molecular Biology;Molecular Conformation;mRNA Precursor;multiple omics;Muscular Dystrophies;Mutation;Nerve Degeneration;Nervous System Disorder;Neurodegenerative Disorders;neurodevelopment;Neuronal Differentiation;new technology;Phylogenetic Analysis;Play;precision medicine;predictive modeling;Process;programs;protein complex;protein function;Protein Isoforms;protein protein interaction;Proteins;Proteome;Publishing;Regulation;Resources;RNA;RNA Binding;RNA Folding;RNA Processing;RNA Splicing;RNA-Binding Proteins;RNA-Protein Interaction;RNA-targeting therapy;Role;Site;Spinal Muscular Atrophy;stem;Structure;System;targeted treatment;Technology;Testing;therapeutic target;Thermodynamics;three dimensional structure;three-dimensional modeling;tool;transcriptome;Variant

PROJECT_TITLE: Decoding global RNP topologies in splicing regulation

STUDY_SECTION: GCAT

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


NIH_SPENDING_CATS: Cancer;Immunotherapy;Skin Cancer

ORG_NAME: THOMAS JEFFERSON UNIVERSITY

PHR: PROJECT NARRATIVE Pharmacological targeted inhibitors and immune checkpoint antibodies are FDA-approved for the treatment of advanced-stage skin melanoma; however, there are limitations to both types of therapies. This multi-disciplinary application aims to establish rationally-designed therapeutic approaches to trigger an anti-tumor immune response which will have significant clinical implications that address a prominent need in cancer treatment.

PI_NAMEs: ALNEMRI, EMAD S;APLIN, ANDREW ERIC (contact)

PROGRAM_OFFICER_NAME: KUO, LILLIAN S

PROJECT_TERMS: adaptive immune response;Address;Adjuvant;Affect;anti-CTLA4;anti-PD-1;anti-tumor immune response;Antibodies;Apoptosis;Apoptotic;Bioinformatics;Biological Assay;Biology;BRAF gene;cancer cell;cancer therapy;CASP3 gene;Caspase;CD8-Positive T-Lymphocytes;Cell Death;Cell Therapy;Cells;checkpoint inhibition;checkpoint therapy;chemotherapy;Clinical;Clinical Trials;Collaborations;Communication;Complement;Cutaneous Melanoma;cytokine;Data;Dendritic Cells;design;Disease Resistance;DNA;Drug Tolerance;Eating;Excision;Exclusion;Exhibits;FDA approved;Goals;Growth;High Mobility Group Proteins;Immune;immune cell infiltrate;immune checkpoint;Immune checkpoint inhibitor;Immune response;Immune system;immunogenic;immunogenic cell death;immunogenicity;Immunotherapy;improved;in vivo;in vivo Model;Incidence;inducible gene expression;inhibitor;insight;ipilimumab;Knock-out;Knockout Mice;Leucocytic infiltrate;Link;Malignant Neoplasms;Mediating;MEKs;Melanoma;Melanoma Cell;Melanoma patient;Modeling;Molecular;multidisciplinary;mutant;Nature;neoantigens;neoplastic cell;Nivolumab;novel;novel therapeutic intervention;Pathway interactions;Patients;Pattern;pembrolizumab;Pharmaceutical Preparations;pharmacologic;Phosphorylation;Population;pre-clinical;prevent;Process;Publishing;Quality of life;rational design;Regimen;Regulation;Residual Neoplasm;Resistance;resistance mechanism;response;Role;Signal Pathway;Signal Transduction;single cell analysis;small molecule;standard of care;Stress;synergism;T-Lymphocyte;targeted treatment;Testing;Therapeutic;Toxic effect;TP53 gene;treatment response;treatment strategy;tumor;tumor growth;tumor-immune system interactions;Tumor-infiltrating immune cells;Work

PROJECT_TITLE: Mechanisms of cell death in cutaneous melanoma

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


ORG_CITY: SAN FRANCISCO

ORG_DEPT: RADIATION-DIAGNOSTIC/ONCOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

PHR: Narrative Ultra-high dose rate radiotherapy a.k.a. FLASH radiotherapy has shown the potential to drastically reduce the normal tissue toxicity without compromising tumor cell killing. However, the delivery of FLASH is hampered by the limitations inherent to existing radiotherapy platforms. We propose to develop a groundbreaking new X-ray system ROAD to achieve the needed FLASH dose rate for significantly improved cancer radiotherapy efficacy.

PI_NAMEs: AGUSTSSON, RONALD ;SHENG, KE  (contact)

PROGRAM_OFFICER_NAME: OBCEMEA, CEFERINO H

PROJECT_TERMS: Acceleration;Algorithms;arm;Biological;Cancer Patient;cancer radiation therapy;cell killing;Clinical;Collaborations;Complex;Computer software;Development;Disease;Dose;Dose Rate;dosimetry;effective therapy;Electron Beam;electron energy;Electrons;Face;Foundations;Human;image guided radiation therapy;improved;industry partner;Intensity modulated proton therapy;Intensity-Modulated Radiotherapy;Linear Accelerator Radiotherapy Systems;Mechanics;Medical;Methods;Modeling;Movement;neoplastic cell;Normal tissue morphology;Output;Oxygen;Patients;Penetration;Photons;Plant Leaves;prevent;Process;Production;proton therapy;Protons;Radiation;Radiation therapy;Radiobiology;research clinical testing;Roentgen Rays;Safety;scale up;Scanning;Shapes;Speed;Spottings;success;System;Technology;technology development;Testing;Therapeutic;Time;tissue injury;Toxic effect;Treatment Efficacy;tumor;Uncertainty

PROJECT_TITLE: Development of an ultra-high dose rate rotational linac for FLASH Radiotherapy


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

PHR: The apicoplast organelle is required for the survival of malaria parasites in humans and for parasite transmission to mosquitoes. Our goal is to identify and characterize parasite genes responsible for maintaining the apicoplast using forward and reverse genetics approaches. These studies will identify novel proteins essential for the survival of malaria parasites and have significant implications for the development of therapeutics targeting blood stage malaria parasites and parasite transmission.

PI_NAMEs: PRIGGE, SEAN TAYLOR (contact)

PROGRAM_OFFICER_NAME: MCGUGAN, GLEN C

PROJECT_TERMS: Abbreviations;Acyl Carrier Protein;Address;Aspartate;Biochemical Pathway;Biology;Blood;Bypass;Carbamoyl Transferases;CCI-779;Coenzyme A;combat;Complement;Culicidae;cysteine desulfurase;Cytosol;Deaminase;Dependence;Dephospho-CoA kinase;design;Development;Dihydrofolate Reductase;Dihydroorotate dehydrogenase;Diphosphates;drug development;Drug resistance;Drug Targeting;Engineering;Enterobacteria phage P1 Cre recombinase;Enzymes;Event;experimental study;fatty acid biosynthesis;Ferredoxin;Ferredoxin-NADP Reductase;Flavin Mononucleotide;forward genetics;Functional disorder;Future;Genes;Genetic;genetic approach;Genetic Screening;Genome;Glutamine;Goals;Human;Individual;inhibitor;inorganic phosphate;Insertional Mutagenesis;insight;Investments;Iron;Isomerase;isopentenyl pyrophosphate;isoprenoid;knock-down;Knowledge;Ligands;LoxP-flanked allele;Maintenance;Malaria;Maps;Membrane;Metabolic;Metabolic Pathway;Metabolism;Methods;mevalonate;Molecular;NAD(P)+ transhydrogenase;nanopore;Neomycin;new therapeutic target;novel;Nuclear;Organelles;Oxidoreductase;parasite resource;Parasites;Pathway interactions;Phenotype;Plastids;Play;Process;protein function;protein transport;Proteins;pyruvate dehydrogenase;Research;response;reverse genetics;Role;S-Adenosylhomocysteine;S-Adenosylmethionine;segregation;Site;Source;Sulfur;System;Tacrolimus Binding Proteins;targeted sequencing;Tetracyclines;therapeutic development;therapeutic target;tool;transmission process;Transposase;Vesicle;zygote

PROJECT_TITLE: Determinants of apicoplast maintenance in malaria parasites

STUDY_SECTION: PTHE

STUDY_SECTION_NAME: Pathogenic Eukaryotes Study Section[PTHE]


ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

PHR: Project Narrative  The proposed research is relevant to a variety of diseases that affect the public health, including hypertension, pulmonary hypertension, and atherosclerosis. Specifically, we plan to focus on unique metabolites (small-molecule products of human metabolism) that can modulate the function of an important cell type in the blood vessel that contributes to these diseases, the vascular smooth muscle cell. Our plan is to study the effects of these unique metabolites on vascular smooth muscle cell metabolism and function, with the hope that we can identify potential novel metabolic therapies that can prevent or treat these common global cardiovascular diseases.

PI_NAMEs: LOSCALZO, JOSEPH  (contact)

PROJECT_TERMS: Address;Aerobic;aerobic glycolysis;Affect;alpha ketoglutarate;Animal Model;Atherosclerosis;Binding;Biological Markers;Blood Vessels;Branched-Chain Amino Acids;branched-chain-amino-acid transaminase;c-myc Genes;caldesmon;calponin;Cardiovascular Diseases;Cell Physiology;cell type;Cells;Cellular Metabolic Process;Complex;Data;Disease;Dose;Energy-Generating Resources;Essential Amino Acids;experimental study;Family;Gene Expression;Generations;Genes;Genetic Transcription;Glutamates;Glycolysis;HK2 gene;Human;Hydroxylation;Hypertension;Hypoxia;Hypoxia Inducible Factor;Impairment;insight;Isoleucine;Keto Acids;Leucine;Mediating;Metabolic;Metabolism;Molecular;Molecular Weight;Monitor;mRNA Expression;normoxia;novel;overexpression;Oxidative Phosphorylation;Oxygen;Parents;Patients;PDPK1 gene;Phenotype;Platelet-Derived Growth Factor;platelet-derived growth factor BB;prevent;Process;Procollagen-Proline Dioxygenase;programs;protein expression;Proteins;Public Health;pulmonary arterial hypertension;Pulmonary Hypertension;Reaction;Regulation;Research;Rodent Model;Role;SLC2A1 gene;small molecule;Smooth Muscle Myocytes;Source;Stimulus;Tertiary Protein Structure;Transaminases;transcription factor;transcriptome;Ubiquitination;Valine;Vascular Smooth Muscle;VHL protein

PROJECT_TITLE: Branched-chain Keto-acids and Aerobic Glycolysis in Vascular Smooth Muscle Cells

STUDY_SECTION: IVPP

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


NIH_SPENDING_CATS: HIV/AIDS;Infectious Diseases

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: PROJECT NARRATIVE HIV persists in a latent state in CD4+ T cells in patients on antiretroviral therapy (ART). We have recently shown that latent virus can be reactivated by targeting the non-canonical (nc) NF-κB pathway in SIV-infected, ART-treated rhesus macaques. In this proposal, we aim to pursue a deeper and broader understanding of the latency reversal induced by ncNF-κB signaling and its potential to reduce persistent reservoirs using an innovative “kick and kill” approach. The knowledge we gain may bring us closer to an HIV cure.

PI_NAMEs: CHAHROUDI, ANN M (contact)

PROGRAM_OFFICER_NAME: SANDERS, BRIGITTE E

PROJECT_TERMS: Adherence;Anatomy;Animal Model;Antibodies;antiretroviral therapy;Apoptosis;arm;Bar Codes;BCL1 Oncogene;Binding;Biological;Blood;Caspase;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;Cells;Clinical;Collaborations;Combined Modality Therapy;curative treatments;Data;design;Ensure;Event;exhaust;experimental study;Family;FDA approved;Future;HIV;HIV Infections;humanized mouse;Immune;Immune system;Immunologics;Impairment;In Vitro;in vivo;Induction of Apoptosis;Infusion procedures;inhibitor;innovation;Interruption;Intervention;Knowledge;Macaca;Macaca mulatta;mathematical model;Measurement;memory CD4 T lymphocyte;Methodology;mimetics;Mitochondria;Modeling;Morbidity - disease rate;mortality;nonhuman primate;novel;novel strategies;Pathway interactions;Patients;Pharmaceutical Preparations;Plasma;Predictive Factor;Proteins;Proviruses;Recording of previous events;Recrudescences;Regimen;Reporting;Research;Research Personnel;response;Rest;RNA;Safety;Shock;Signal Pathway;Signal Transduction;SIV;small molecule;Sorting;Source;success;synergism;T cell response;T-Cell Activation;T-Lymphocyte Subsets;Testing;Therapeutic;therapeutic target;Tissues;transcriptomics;Viral;viral rebound;Viral reservoir;viral RNA;Viremia;Virus;Virus Latency;Work

PROJECT_TITLE: Enhanced latency reversal and reservoir clearance in macaques

STUDY_SECTION: HIVD

STUDY_SECTION_NAME: HIV Immunopathogenesis and Vaccine Development Study Section[HIVD]


NIH_SPENDING_CATS: Cancer;Immunotherapy

ORG_CITY: HACKENSACK

ORG_NAME: HACKENSACK UNIVERSITY MEDICAL CENTER

ORG_STATE: NJ

PHR: Understanding the immune cellular organization driven by IL33 in the TME open doors to rationale design of novel combinational therapy to meet the pressing clinical need for improvement of responses to current cancer immunotherapy.

PI_NAMEs: LU, BINFENG  (contact)

PROGRAM_OFFICER_NAME: LIU, YIN

PROJECT_TERMS: Address;anti-tumor immune response;antitumor effect;Bioinformatics;cancer immunotherapy;cancer infiltrating T cells;cancer therapy;Carcinoma;CD4 Positive T Lymphocytes;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Line;Cell Nucleus;Cells;Clinical;Clinical Data;Combined Modality Therapy;CTLA4 gene;cytokine;Data;design;Down-Regulation;effector T cell;Epithelial Cells;Equilibrium;exhaustion;Family;Human;IL6 gene;Immune;immune checkpoint blockade;Immune checkpoint inhibitor;immunogenic;immunoregulation;Immunosuppression;improved;In Vitro;in vivo;Infection;Interleukin-1;Interleukin-13;interleukin-21;interleukin-21 receptor;Interleukins;Link;Lung;Machine Learning;Mediating;member;Messenger RNA;Modeling;Molecular;mouse model;Mus;neoplasm immunotherapy;neoplastic cell;novel;Pattern;PD-1 blockade;Play;prevent;programmed cell death protein 1;receptor;Regulatory T-Lymphocyte;response;Role;Signal Transduction;single cell genomics;Skin;Solid Neoplasm;synergism;Testing;Therapeutic Effect;Tissues;tool;Treatment Efficacy;tumor;Tumor Cell Line;Tumor Escape;tumor growth;tumor microenvironment;Tumor Tissue;Tumor-Derived;Tumor-infiltrating immune cells

PROJECT_TITLE: Study of the IL-33-driven immune cell organization underpinning responses to immune checkpoint blockade cancer therapy

STUDY_SECTION: CII

STUDY_SECTION_NAME: Cancer Immunopathology and Immunotherapy Study Section[CII]


ADMINISTERING_IC: AR

IC_NAME: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

ORG_DEPT: PATHOLOGY

PHR: Desmosomes are classically considered to provide mechanical support to the epidermis by connecting stress-resisting intermediate filaments to sites of cell-cell adhesion through the essential anchoring protein desmoplakin. But desmosomes are much more dynamic than this classic definition implies. Here we will determine what controls desmoplakin dynamics to create desmosomes with different properties during early and late stages of epidermal regeneration, and how interfering with these dynamics contributes to skin disease.

PI_NAMEs: GREEN, KATHLEEN JANEE (contact)

PROGRAM_OFFICER_NAME: KOCH, PETER

PROJECT_TERMS: 3-Dimensional;Actins;Actomyosin;Address;Adhesions;Animal Model;Apical;Architecture;armadillo proteins;Award;Binding;Cadherins;cell cortex;Cell membrane;Cell-Cell Adhesion;Cells;Complex;Cytoplasm;Cytoskeletal Filaments;Cytoskeleton;desmoglein 1;desmoplakin;Desmosomes;Dimensions;Disease;disease model;disease-causing mutation;Epidermis;Epithelial Cells;Event;Functional disorder;Guanine Nucleotide Exchange Factors;Heart Diseases;human disease;human model;Impairment;In Vitro;Infection;Intercellular Junctions;Intermediate Filament Proteins;Intermediate Filaments;Keratin;keratinocyte;Maintenance;Mass Spectrum Analysis;Mechanics;Mediating;Mediator;Membrane;Molecular;Morphogenesis;Mus;mutant;Mutation;N-terminal;optogenetics;Pathogenesis;Pattern;pharmacologic;Phosphoric Monoester Hydrolases;physical insult;plakoglobin;plakophilins;polymerization;Polymers;Post-Translational Protein Processing;Proliferating;Property;Proteins;recruit;response;restoration;rho;RNA;RNA-Binding Proteins;Role;scaffold;sensor;Signal Transduction;Site;skin disorder;skin regeneration;Stratification;Stress;Structure;Testing;Tight Junctions;Tissues;Translating;Water;Work

PROJECT_TITLE: Desmoplakin Assembly and Function in Epidermis


ED_INST_TYPE: ORGANIZED RESEARCH UNITS

NIH_SPENDING_CATS: Nutrition;Physical Activity;Prevention

ORG_CITY: BLACKSBURG

ORG_DEPT: MISCELLANEOUS

ORG_NAME: VIRGINIA POLYTECHNIC INST AND ST UNIV

PHR: PROJECT NARRATIVE Regular exercise improves the quality of mitochondria, the power plants, in skeletal muscle with profound health benefits; however, the underlying mechanism(s) remain poorly understood. We have recently discovered physical association of a nutrient/energy sensing enzyme AMPK with mitochondria and obtain preliminary data to show its importance in getting rid of bad mitochondrial. This project will employ the state-of- the-art technologies to elucidate the regulation and function of this mitochondria-associated AMPK, which will help development of effective therapeutics to treat and prevent chronic diseases, such as diabetes.

PI_NAMEs: YAN, ZHEN  (contact)

PROGRAM_OFFICER_NAME: EISENSTEIN, JANA S

PROJECT_TERMS: 5'-AMP-activated protein kinase;Adenine Nucleotides;Adult;Autophagocytosis;Bioenergetics;Biological Models;Biology;Chronic Disease;Color;Complex;CRISPR/Cas technology;Cultured Cells;Data;Deterioration;Development;Diabetes Mellitus;Disease;Dynamin;effective intervention;Electric Stimulation;endurance exercise;Ensure;Enzymes;Exercise;exercise capacity;exercise training;Experimental Designs;Experimental Models;fighting;Fluorescence;Fluorescence Resonance Energy Transfer;Foundations;frailty;functional adaptation;Future;gain of function;Gene Transfer;Health Benefit;Health Promotion;Heart;Holoenzymes;Human;Image;improved;in vivo;inhibitor;innovation;Insulin Resistance;insulin sensitivity;Intervention;Ischemia;Kidney;Knockout Mice;Laboratories;Link;loss of function;Maintenance;Mediating;Membrane Potentials;Metabolic;Metabolism;Mitochondria;Motor;Mus;Muscle;Muscle Cells;Muscle Contraction;Nerve;Non-Insulin-Dependent Diabetes Mellitus;novel;Nutrient;Outer Mitochondrial Membrane;Oxidative Phosphorylation;Oxidative Stress;pharmacologic;Phosphorylation;Phosphotransferases;physical conditioning;Physical Performance;Power Plants;prevent;Prevention;Process;Production;Proteins;Quality Control;Reactive Oxygen Species;Regulation;Reporter;response;Role;Running;sensor;Signal Transduction;Signaling Molecule;skeletal;Skeletal Muscle;Specificity;Stress;Technology;Testing;therapeutic development;therapeutically effective;Tissues;treadmill;two-photon;Visualization

PROJECT_TITLE: mitoAMPK in exercise benefits


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: MEMPHIS

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

ORG_STATE: TN

PHR: Project Narrative/Relevance Statement Emerging pathogens, antibiotic resistance and the danger of pandemics from deadly infectious agents clearly demonstrate that infectious diseases continue to represent a serious worldwide threat to human health. Although it is clear and well documented that new therapeutics are urgently needed to combat this threat, the development of such therapeutics and the necessary basic research to support this development are failing to keep pace with this need. St. Jude Children’s Research Hospital has developed a superb translational research infrastructure well suited for therapeutic development, and this T32 program has been designed to leverage this infrastructure to train top-tier postdoctoral fellows with the necessary skills to lead independent research programs in the discovery of infectious diseases therapeutics.

PI_NAMEs: LEE, RICHARD E. (contact)

PROGRAM_OFFICER_NAME: BROWN, LILIANA L

PROJECT_TITLE: Training in the Design and Development of Infectious Disease Therapeutics

STUDY_SECTION: MID

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


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Aging;Aphasia;Behavioral and Social Science;Brain Disorders;Cerebrovascular;Clinical Research;Clinical Trials and Supportive Activities;Disability Research;Neurosciences;Rehabilitation;Stroke

ORG_CITY: ALBUQUERQUE

ORG_DEPT: OTHER HEALTH PROFESSIONS

ORG_NAME: UNIVERSITY OF NEW MEXICO

ORG_STATE: NM

PHR: PROJECT NARRATIVE The proposed research is relevant to public health because optimizing treatment parameters based on individualized neurophysiology is broadly applicable to clinical populations who may benefit from improvements in function and psychosocial outcomes via adaptive brain reorganization. Thus, the proposed research is relevant to the NIDCD’s mission which seeks fundamental knowledge about the nature and behavior of living systems and to reduce the burden of illness and disability.

PI_NAMEs: RICHARDSON, JESSICA D (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: Address;Adult;Aftercare;Aphasia;aphasia recovery;Area;Behavior;Behavior Therapy;Behavioral;Brain;brain based;brain cell;burden of illness;Chronic;Clinical;clinical translation;Clinical Trials;combinatorial;Combined Modality Therapy;Data;Development;Diffuse;disability;disability burden;dosage;Dose;Down-Regulation;economic impact;Electroencephalography;Elements;Ensure;Failure;Family;follow-up;Foundations;functional gain;functional improvement;functional outcomes;Future;Goals;improved;Individual;individual patient;Inferior;Inferior frontal gyrus;innovation;Intervention;Investigation;Knowledge;knowledge base;Language;language outcome;language processing;Left;Lesion;Magnetic Resonance Imaging;Measures;Methodology;Middle Inferior Frontal Convolution;Mission;Modeling;Names;National Institute on Deafness and Other Communication Disorders;Nature;neurological rehabilitation;neurophysiology;neuroregulation;novel;novel strategies;Organism;Outcome;Participant;Performance;personalized approach;Persons;Population;prevent;psychosocial;psychosocial outcome;Public Health;Recovery;recruit;Reproducibility;Research;Role;Shapes;Source;Stroke;Testing;therapy development;Training;transcranial direct current stimulation;translational potential;treatment optimization;Treatment outcome;treatment research;treatment response;United States;Up-Regulation

PROJECT_TITLE: Optimizing Targeted Interventions for Aphasia

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


ED_INST_TYPE: GRADUATE SCHOOLS

NIH_SPENDING_CATS: Amyotrophic Lateral Sclerosis (ALS);Biotechnology;Brain Disorders;Genetics;Neurodegenerative;Neurosciences;Precision Medicine;Rare Diseases

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: ROCKEFELLER UNIVERSITY

PHR: NARRATIVE While ALS is characterized by the degeneration of “lower” motor neurons in the spinal cord and “upper” motor neurons in the cerebral cortex, the mechanisms that cause this selective vulnerability are unknown given that most disease-related genes are broadly expressed in many cell types throughout the nervous system. The proposed research program will utilize cutting edge molecular, cellular, and anatomical techniques to ask how the endogenous molecular and bioenergetic properties of upper motor neurons may lead to pathology by directly comparing them to a highly related but resilient neuronal population during disease progression in animal models of ALS and in tissue from ALS patients. The results obtained from this work will provide a better understanding of the molecular and cellular pathways that underlie the differential susceptibility of these cell types and identify novel therapeutic targets for clinical intervention.

PI_NAMEs: SCHMIDT, ERIC F (contact)

PROGRAM_OFFICER_NAME: GUBITZ, AMELIE

PROJECT_TERMS: Address;Affinity Chromatography;ALS pathology;ALS patients;Anatomy;Animal Model;Antioxidants;Autopsy;Biochemical;Biochemistry;Bioenergetics;biological adaptation to stress;biomarker identification;Brain Stem;Candidate Disease Gene;candidate identification;cell cortex;Cell Nucleus;Cell Separation;cell type;Cells;cellular resilience;Cerebral cortex;Clinical;comparative;complex IV;Corticospinal Tracts;Data;Diagnosis;Disease;Disease Progression;disease-causing mutation;end stage disease;Engineering;Etiology;Fluorescence;Functional disorder;gain of function;Gene Expression;Gene Expression Profiling;Gene Expression Regulation;Genes;Goals;Grant;human tissue;innovation;Innovative Therapy;Intervention;Label;Link;loss of function;Maps;Measures;Metabolic;metabolomics;Mitochondria;Modeling;Molecular;molecular phenotype;Molecular Profiling;Motor Cortex;Motor Neuron Disease;Motor Neurons;multiple omics;Mus;Mutation;Nerve Degeneration;Nervous System;Neurons;neuropathology;new therapeutic target;novel;novel marker;Nuclear;Onset of illness;Oxidative Phosphorylation;Oxidative Stress;Pathologic Processes;Pathology;Pathway interactions;Patients;Pontine structure;Population;pre-clinical;Pre-Clinical Model;preclinical study;Predisposition;programs;Property;Proteins;Proteomics;Pyramidal Cells;Pyramidal Tracts;Research;resilience;response;Rest;Ribosomes;RNA-Binding Protein FUS;Role;Sorting;Spinal Cord;Symptoms;Techniques;Testing;Thalamic structure;Tissues;Transcript;Transgenic Mice;Translating;translational framework;Up-Regulation;Viral;Viral Vector;Vulnerable Populations;Work

PROJECT_TITLE: Molecular Phenotyping of Cortical Cell Types in ALS-Related Neurodegeneration

STUDY_SECTION: NOMD

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


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Clinical Research;Dementia;Eye Disease and Disorders of Vision;Neurodegenerative;Neurosciences

ORG_DEPT: NEUROSCIENCES

PHR: Project Narrative While a great deal of progress has been made in identifying biomarkers that signal a preclinical phase of Alzheimer’s disease (AD) that occurs after the onset of pathophysiological processes (e.g., amyloid deposition) but prior to the appearance of clinical symptoms, biomarker positivity does not correspond to level of cognitive functioning in preclinical AD, nor does it provide prognostic information about the timeline for future cognitive and clinical decline. There is a critical need for inexpensive and easily administered methods of detecting and staging AD as it runs its course from the preclinical to symptomatic stages. This project will evaluate the ability of two novel cognitive markers – Visual Sensory Binding (VSB) and Visual Short Term Memory Binding (VSTMB) – to detect AD pathophysiological processes and predict impending decline in AD biomarker-positive individuals.

PI_NAMEs: JACOBS, DIANE M. (contact)

PROGRAM_OFFICER_NAME: HSIAO, JOHN

PROJECT_TERMS: Address;Adverse effects;Alzheimer disease detection;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer’s disease biomarker;Amyloid deposition;Appearance;Behavioral;Binding;Biological Markers;biomarker identification;cell type;Clinical;clinical center;Cognition;Cognitive;cognitive function;cognitive performance;Data;Dementia;Detection;detection method;Diagnosis;Diagnostic;diagnostic value;Disease;Early identification;Functional disorder;Future;Genotype;Glycoproteins;Growth Cones;Guidelines;Impaired cognition;Impairment;Individual;innovation;Light;Longitudinal Studies;Measures;Mediating;Mental Depression;mild cognitive impairment;National Institute on Alcohol Abuse and Alcoholism;Nerve Degeneration;Neurocognitive;neurocognitive test;neurofilament;neurogranin;neuronal pentraxin;Neurons;Neuropsychological Tests;non-demented;nonalzheimer dementia;normal aging;novel;older adult;Older Population;Paired-Associate Learning;Participant;Pathologic Processes;Pathology;Performance;Phase;potential biomarker;pre-clinical;predictive modeling;Process;prodromal Alzheimer's disease;prognostic;prognostic value;Proteins;Pyramidal Cells;rate of change;Recommendation;Research;Research Personnel;Resources;Running;Sensory;sensory integration;Severities;Short-Term Memory;Signal Transduction;Source;Staging;Stress Tests;Symptoms;synaptic function;Synaptic Vesicles;Test Result;Testing;timeline;Vision;Visual;Visual impairment;visual information

PROJECT_TITLE: Novel Cognitive Markers of Early Alzheimer's Disease.


ORG_CITY: PROVIDENCE

ORG_NAME: BROWN UNIVERSITY

ORG_STATE: RI

PHR: Project narrative The immune response main function is to control and to eliminate pathogens. We propose to study how a unique population of lymphocytes called Natural Killer cells controls viral infection. The results from these studies will provide insights into strategies to target these cells.

PI_NAMEs: BROSSAY, LAURENT  (contact)

PROGRAM_OFFICER_NAME: GAUTAM, RAJEEV

PROJECT_TERMS: Acute;Affect;Animal Model;Animals;Blood;Calibration;CD8-Positive T-Lymphocytes;CD8B1 gene;Cell Physiology;Cells;Cellular Indexing of Transcriptomes and Epitopes by Sequencing;Chronic;Coenzyme A;Cytomegalovirus;Cytomegalovirus Infections;cytotoxicity;Data;design;Development;Disease Progression;Dose;Effector Cell;Environment;Equilibrium;Evolution;Exhibits;experimental study;Family member;Goals;Herpesviridae;Homologous Gene;Human;Human Herpesvirus 2;Immune;Immune checkpoint inhibitor;Immune response;Immunity;Immunocompromised Host;immunopathology;immunoregulation;Immunosuppression;Impairment;improved;Individual;Infection;Inflammation;insight;interest;Interferons;Lymphocyte;Malignant Neoplasms;migration;Modeling;Murid herpesvirus 1;Mus;Natural Killer Cells;neonate;Organ;pathogen;PD-1 pathway;Phase;Population;Positioning Attribute;Pregnant Women;prevent;Primary Infection;programmed cell death protein 1;Proliferating;receptor;recruit;recurrent infection;Regulation;Reporting;Research;Salivary Glands;Site;Skin;Sorting;Species Specificity;Spleen;Symptoms;T-Lymphocyte;Therapeutic;Tissues;tool;Tropism;tumor;Viral;Virus;Virus Diseases

PROJECT_TITLE: Immune response to MCMV infection in the salivary glands

STUDY_SECTION: IHD

STUDY_SECTION_NAME: Immunity and Host Defense Study Section[IHD]


NIH_SPENDING_CATS: Immunotherapy;Infectious Diseases

ORG_CITY: CAMBRIDGE

ORG_NAME: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

PHR: Project Narrative: A cell's carbohydrate coat serves as an identification card (ID) for the host to detect pathogens, virus-infected, cancerous or other diseased cells. As critical directors of immunity, dendritic cells display many different proteins that can recognize the carbohydrates on normal or disease-causing cells to inhibit or activate immune responses. This project focuses on deciphering these critical dendritic cell “carbohydrate-ID checkers” influence immune responses and on co-opting them to regulate immunity.

PI_NAMEs: KIESSLING, LAURA L (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: adaptive immunity;Affect;Animal Model;anti-cancer;anticancer activity;antigen binding;antigen detection;Antigen Presentation;Antigen Targeting;antigen test;Antigen-Presenting Cells;Antigens;Bacteria;Binding;Biology;Cancerous;candidate identification;Carbohydrates;Cell Shape;Cell surface;Cells;Cellular Immunity;Chemicals;Collaborations;combat;combinatorial;Combinatorics;cytokine;Data;dectin 1;Dendritic Cells;design;Disease;Elasticity;Encapsulated;Exhibits;experimental study;extracellular;feature detection;fungus;Generations;glycosylation;Goals;Grant;Human;human disease;Humoral Immunities;Immune response;Immune signaling;Immune system;Immunity;in vivo;Influentials;Lectin;Ligands;Malignant Neoplasms;mechanical properties;mechanotransduction;Mediator;Membrane;microbial;Molecular;mouse dectin-2;Natural Immunity;Nature;novel;novel strategies;particle;Particulate;pathogen;Pathogen detection;pathogenic fungus;Pattern;Peptides;Polysaccharides;Property;Protein Array;Proteins;receptor;Receptor Signaling;recruit;response;Rest;Role;Shapes;Signal Pathway;Signal Transduction;Specificity;Subunit Vaccines;T cell differentiation;T cell response;T-Lymphocyte;T-Lymphocyte Subsets;Testing;Toll-like receptors;trafficking;transmission process;Tumor Immunity;Vaccines;Viral load measurement;Virus;Virus-like particle

PROJECT_TITLE: Synthetic Ligands for Directing Immune Responses


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Behavioral and Social Science;Brain Disorders;Clinical Research;Data Science;Drug Abuse (NIDA only);Mental Health;Opioid Misuse and Addiction;Opioids;Physical Injury - Accidents and Adverse Effects;Prevention;Substance Misuse;Suicide;Suicide Prevention

ORG_DEPT: PSYCHIATRY

PHR: Project Narrative Many of the individuals who die by suicide are not clearly identified as such by Medical Examiners, and their causes of death are often categorized as undetermined with implications for state and national statistics of suicide and for understanding of the causes of suicide and accidental death. The proposed study aims to improve detection of suicide deaths by using large linked data sets, latent class analysis and psychological autopsy to better distinguish suicide among decedents whose cause of death is currently categorized as “undetermined” and to pinpoint variables that can be used to better identify such cases. In addition to improving the statistics of suicide at state and national level and identifying characteristics that will aid Medical Examiners in identifying suicide and accidental overdose deaths, the study will contribute to a better understanding of real world relationship between drug use and suicide and their impact on individuals, families, peers and society, as highlighted in NIDA’s current Strategic Plan.

PI_NAMEs: NESTADT, PAUL SASHA (contact)

PROGRAM_OFFICER_NAME: KURAMOTO-CRAWFORD, SATOKO JANET

PROJECT_TERMS: Accidents;addiction;Autopsy;career;case-based;Categories;Cause of Death;Cessation of life;Characteristics;Classification;Clinical;Clinical Data;Collaborations;Coroner;Country;Data;Data Collection;Data Linkages;Data Set;data warehouse;demographics;design;Detection;Determination of Death;Development;diverse data;Drug usage;Electronic Health Record;endophenotype;epidemiologic data;Epidemiologist;Epidemiology;epidemiology study;experience;Face;Family;Fellowship;Funding;Future;Generations;Geography;Goals;Grant;improved;Individual;informant;innovation;Intervention;Interview;Investigation;large datasets;Link;Logistic Regressions;Manuscripts;Maryland;Measures;Medical Examiners;mental state;Mentored Patient-Oriented Research Career Development Award;Mentors;Mentorship;Methods;Modeling;mortality;multiple data sources;National Institute of Drug Abuse;novel;Opioid;opioid epidemic;opioid mortality;opioid overdose;opioid use;opioid user;Overdose;overdose death;overdose risk;Pathway interactions;peer;Physicians;Policies;Positioning Attribute;Precipitating Factors;Predisposing Factor;Prevention;preventive intervention;Probability;programs;Protocols documentation;Psychiatric Diagnosis;Psychiatric epidemiology;Psychiatrist;psychologic;Psychological Interview;Public Health;Publications;Recording of previous events;Research;Research Methodology;Research Personnel;Resources;Risk;Risk Factors;Sampling;scaffold;Self-Injurious Behavior;skill acquisition;skills;social;Societies;statistics;Strategic Planning;Subgroup;suicidal;suicidal morbidity;Suicide;Suicide prevention;suicide rate;System;Testing;theories;therapy development;Time;Toxicology;Training;Training Programs;Translating;Validation;Work;Writing

PROJECT_TITLE: Harmonizing Multiple Data Sources And Psychological Autopsy To Characterize Suicides Among Opioid-Related Deaths

STUDY_SECTION: BGES

STUDY_SECTION_NAME: Behavioral Genetics and Epidemiology Study Section[BGES]