ORG_CITY: Princeton

ORG_NAME: PRINCETON UNIVERSITY

ORG_STATE: NJ

PHR: NARRATIVE The proposed work takes a structural approach to investigate the machinery responsible for sorting and transporting proteins and lipids among the compartments of eukaryotic cells. Mutations in many components of this machinery have been shown to perturb cellular architecture and function, resulting in human disease.

PI_NAMEs: HUGHSON, FREDERICK M (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Architecture;Attention;Awareness;base;Binding;biochemical tools;Biological Process;Carrier Proteins;Cell membrane;Cells;Chimeric Proteins;Closure by clamp;Coated vesicle;Collaborations;Complex;Coupled;Cryoelectron Microscopy;design;Disease;Eukaryotic Cell;Exocytosis;experimental study;falls;flexibility;Foundations;Future;Goals;human disease;improved;In Vitro;in vivo;Infection;laser tweezer;Lasso;late endosome;Lipids;Lysosomes;Mediating;Membrane;membrane assembly;Membrane Fusion;Modification;Molecular Chaperones;Mutation;nanomachine;Neurons;neurotransmitter release;optic tweezer;Organelles;Pathway interactions;Pattern;Process;Productivity;programs;protein function;Protein Sortings;Proteins;Proteomics;Reaction;reconstitution;Reporting;Research;Role;single molecule;SNAP receptor;Sorting;Structure;Surface;Synapses;syntaxin binding protein 1;System;Therapeutic Intervention;Thermodynamics;trafficking;Vacuole;Vesicle;vesicle transport;virtual;Work;X-Ray Crystallography;Yeasts

PROJECT_TITLE: Structural Analysis of Membrane Tethering and Fusion Proteins

STUDY_SECTION: MBPP

STUDY_SECTION_NAME: Membrane Biology and Protein Processing Study Section[MBPP]


ADMINISTERING_IC: CA

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Biotechnology;Breast Cancer;Cancer;Cancer Genomics;Genetics;Human Genome;Immunotherapy;Precision Medicine;Prevention;Women's Health Research

ORG_CITY: MEMPHIS

ORG_COUNTRY: UNITED STATES

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF TENNESSEE HEALTH SCI CTR

ORG_STATE: TN

PHR: NARRATIVE: This proposal utilizes a novel model of triple negative breast cancer (TNBC) which has been created by systematically crossing a spontaneous model of TNBC into the BXD family, the largest and best characterized murine genetic reference population, to discover and validate genetic modifiers of tumor aggression and response to therapy. The BXD-TNBC hybrids demonstrate significant, heritable variation in tumor phenotypes which have yielded candidate genes using systems genetics and cross-species comparisons of existing human databases. The generation of this reliable, reproducible, and robust resource will enable the discovery of genetic and environmental modifiers which will be leveraged to further understand TNBC to maximally improve patient outcomes.

PI_NAMEs: MAKOWSKI-HAYES, LIZA  (contact)

PROGRAM_OFFICER_NAME: FINGERMAN, IAN M

PROJECT_TERMS: Address;Affect;Aggressive behavior;anti-PD-L1;Antigens;Bioinformatics;Body Weight decreased;Breast Cancer cell line;breast cancer genomics;Breast Cancer Model;Breast Cancer Patient;breast cancer progression;Cancer Burden;cancer therapy;Candidate Disease Gene;candidate validation;causal variant;chemotherapy;Clinical;Combined Modality Therapy;Computing Methodologies;Data;Data Set;Databases;Diet;Disease;Environment;Family;FDA approved;gene conservation;gene environment interaction;Gene Modified;gene network;Generations;Genes;Genetic;genetic analysis;genetic approach;Genetic Heterogeneity;Genetic Models;Genetic Predisposition to Disease;genetic resource;genetic variant;Genetic Variation;Genetically Engineered Mouse;Genome;genome sequencing;genome wide association study;genomic locus;genomic variation;Genomics;Goals;Heritability;Heterogeneity;High Fat Diet;Human;Human Genetics;Hybrids;immune checkpoint blockade;Immunology;Immunotherapy;Impairment;improved;In Vitro;in vivo;Inbreeding;Individual;Individual Differences;innovation;Investigation;lead candidate;Link;Malignant Breast Neoplasm;Mediating;Methods;Modeling;Molecular;mouse model;Mus;Neoplasm Metastasis;neoplasm resource;novel;Obesity;Outcome;Paclitaxel;Pathology;Patient Care;Patient-Focused Outcomes;Patients;personalized medicine;Phenotype;Pilot Projects;Pliability;Population;pre-clinical;Pre-Clinical Model;Predisposition;Quantitative Trait Loci;Recombinants;Reproducibility;Research Personnel;Resources;Risk;Risk Factors;Sampling;segregation;Severities;Susceptibility Gene;System;targeted treatment;trait;Translating;transplant model;Treatment Efficacy;treatment response;triple-negative invasive breast carcinoma;tumor;tumor initiation;Validation;Variant;Weight;Weight Gain;whole genome;Work

PROJECT_TITLE: Determining susceptibility loci in triple negative breast cancer using a novel pre-clinical model

STUDY_SECTION: CG

STUDY_SECTION_NAME: Cancer Genetics Study Section[CG]


ADMINISTERING_IC: DC

IC_NAME: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

NIH_SPENDING_CATS: Neurosciences

ORG_CITY: DURHAM

ORG_DEPT: GENETICS

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Narrative: Understanding the molecular mechanism of how olfactory receptors recognize multitude of odorants lays the foundation to our understanding of the olfactory system. The proposed interdisciplinary research will develop computational methods using machine learning techniques, concurrent with in vitro cell based assays and cryo-EM studies to push this understanding forward by enhancing the in vitro expression of olfactory receptors and enabling the structure-function studies. The combination of computational methods and experiments will provide unprecedented insights into mechanisms of odorant-olfactory receptor recognition and map the residues involved in such recognition events.

PI_NAMEs: MANGLIK, AASHISH ;MATSUNAMI, HIROAKI  (contact);VAIDEHI, NAGARAJAN

PROGRAM_OFFICER_NAME: SULLIVAN, SUSAN L

PROJECT_TERMS: Acceleration;Address;Affinity;Agonist;Amino Acid Sequence;antagonist;Back;Binding;Binding Sites;Biochemical;Biochemistry;Biological Assay;Carrier Proteins;Cell Line;Cell surface;Cells;Charge;chemical binding;Chemicals;Collaborations;Communities;Computing Methodologies;Cryoelectron Microscopy;Data;design;detection platform;Detergents;Development;Docking;Engineering;Event;Evolution;experience;experimental study;Family;Family member;feeding;Foundations;G-Protein-Coupled Receptors;Goals;Grant;GTP-Binding Proteins;Human;improved;In Vitro;innovation;insight;Interdisciplinary Study;Kidney;Knowledge;large scale production;Ligand Binding;Ligands;Machine Learning;Malignant Neoplasms;Maps;Mediating;Modeling;Molecular;molecular modeling;mutant;Nose;novel;novel strategies;Odorant Receptors;Odors;Olfactory Pathways;olfactory receptor;Outcome;overexpression;Physiology;predictive test;Production;Property;Prostate;Protein Family;protein purification;Protein Sequence Analysis;Publishing;receptor;receptor binding;receptor expression;receptor function;Recombinants;Role;Signal Transduction;Skin;small molecule;Smell Perception;structural biology;Structural Models;Structure;success;System;Techniques;Technology;Testing;thermostability;Tissues;tool;Volatilization;Work

PROJECT_TITLE: Enhancing olfactory receptor expression for biochemical studies of odorant-receptor interactions


ADMINISTERING_IC: GM

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Genetics

ORG_CITY: MIAMI

ORG_DEPT: CHEMISTRY

ORG_NAME: FLORIDA INTERNATIONAL UNIVERSITY

ORG_STATE: FL

PHR: Project Narrative The goal of this project is to advance our knowledge on the structure, mechanism, interactions and regulation of type IA topoisomerases found in all life forms. The results will facilitate the discovery of much needed new antibiotics leads against bacterial topoisomerase I, a validated drug target for treatment of drug resistant infections. The investigation will also develop tools that can be used in vivo to differentiate the dual DNA and RNA topoisomerase activity of human topoisomerase 3B implicated in neurodevelopment and genome stability.

PI_NAMEs: TSE-DINH, YUK-CHING  (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Active Sites;Address;Affect;Antibiotic Resistance;Antibiotics;Bacterial DNA Topoisomerase I;Biochemical;Biological Assay;Cell Physiology;Complementary DNA;Complex;DNA;DNA-Directed RNA Polymerase;Drug resistance;Enzymes;Face;Future;Genetic Recombination;Genetic Transcription;Genome;Genome Stability;Genus Mycobacterium;global health;Goals;Human Activities;In Vitro;in vivo;Infection;insight;Investigation;Knowledge;Life;Ligands;Ligation;Measures;Modeling;Molecular;Molecular Conformation;molecular dynamics;Movement;mutant;Mutation;neurodevelopment;new therapeutic target;pathogenic bacteria;Play;prevent;Regulation;Relaxation;repaired;Replication-Associated Process;Research;Research Activity;RNA;Role;Seminal;single molecule;Single-Stranded DNA;small molecule;Structure;Superhelical DNA;targeted treatment;tool;TOP1 gene;Topoisomerase;Topoisomerase III;Toxin;X-Ray Crystallography

PROJECT_TITLE: Structure, Mechanism and Interactions of Type IA Topoisomerases

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


ADMINISTERING_IC: VA

IC_NAME: Veterans Affairs

ORG_CITY: BIRMINGHAM

ORG_NAME: BIRMINGHAM VA MEDICAL CENTER

ORG_STATE: AL

PHR: Systemic lupus erythematosus (SLE) is a devastating autoimmune disease that is characterized by high autoantibody titers and elevated type I interferon (IFN) responses. Our use of powerful new techniques, including single cell gene expression analysis, has generated data indicating a universal natural safe- guardian pathway that locks the B-cell at a type I IFN quiescent non-responsive status. The loss of this pathway promotes the maturation of self-antigen reactive B cells stimulated by type I IFN. This paradigm shifting hypothesis will be tested using advanced in vivo and in vitro techniques to distinguish the roles of intrinsic B cell defects and environmental signals; test the proposed imprinting of the maturing B cells and its effects on quiescent induction and maintenance; and test if the intrinsic or imprinted B cell defects correspond to B-cell dysregulation in SLE patients at the Birmingham VA Medical Center.

PI_NAMEs: MOUNTZ, JOHN D (contact)

PROJECT_TERMS: anergy;Autoantibodies;Autoantigens;Autoimmune Diseases;autoreactive B cell;B-Cell Activation;B-Cell Antigen Receptor;B-Cell Development;B-Lymphocytes;BACH2 gene;Beta Cell;bioinformatics pipeline;Cell Cycle;Cell surface;Cell Surface Proteins;Cells;Characteristics;Clinical;Competence;Coupled;cytokine;Data;Dedications;Defect;Development;diagnostic strategy;Differentiation Antigens;Disease;disease phenotype;Disease remission;Down-Regulation;Endosomes;Environmental Risk Factor;Equilibrium;Equipment;Evaluation;Event;Exhibits;experimental study;Failure;Flow Cytometry;Gene Expression Profiling;Genes;Genetic Transcription;Goals;high dimensionality;Human;IFNAR1 gene;Immune;Immune System Diseases;Immunoglobulin D;immunoglobulin D receptor;Immunoglobulin M;Immunologic Factors;Immunologics;imprint;improved;In Vitro;in vivo;innovation;Interferon Receptor;Interferon Type I;Interferon Type II;Interferons;Interleukin 4 Receptor;Interleukin-4;ITGAX gene;Knock-in Mouse;Knock-out;Laboratories;Lupus;lupus prone mice;Maintenance;Mature B-Lymphocyte;Measures;Mediating;Medical center;Modeling;mouse model;Mus;novel;novel diagnostics;novel therapeutic intervention;Pathogenesis;Pathogenicity;Pathway interactions;Patients;peripheral tolerance;Phenotype;Plasma Cells;Plasmablast;prevent;Prognosis;programs;Proteins;Receptor Signaling;recruit;response;Rest;Role;Series;Signal Transduction;single cell analysis;Sorting;Structure of germinal center of lymph node;Systemic Lupus Erythematosus;Techniques;Testing;Therapeutic;therapeutic target;TLR7 gene;transcription factor;transcriptome;transcriptomics;type I interferon receptor;uptake

PROJECT_TITLE: Cytokine-mediated B-cell development in lupus


ORG_CITY: Chicago

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: NORTHWESTERN UNIVERSITY

ORG_STATE: IL

PHR: Project Narrative The cellular position of mitochondria is intimately connected to both mitochondrial and cellular function. Central to mitochondrial positioning are molecular tethers, which exert spatial, temporal, and contextual control over the position of the organelle and anchor mitochondria to other organelles forming sites of contact that facilitate interorganelle communication. The goal of the proposed project is to understand the mechanism and regulation of mitochondrial tethers and the multifunctional interorganelle contact sites they create, providing insight into ways regulated mitochondrial tethering can be harnessed to influence mitochondrial function and overall cellular homeostasis and fitness.

PI_NAMEs: LACKNER, LAURA L (contact)

PROJECT_TITLE: Investigating the molecular mechanism and function of mitochondrial tethering


FUNDING_MECHANISM: OTHER RESEARCH-RELATED

NIH_SPENDING_CATS: Biotechnology;Cancer;Clinical Research;Congenital Structural Anomalies;Genetics;Immunotherapy;Orphan Drug;Pediatric;Rare Diseases

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: PROJECT NARRATIVE:  Therapies aimed at unleashing the immune system to attack cancer have demonstrated remarkable effectiveness in recent years for some patients but fail to benefit many others. This project builds on the recent discovery that targeting an RNA editing protein called ADAR1 can trigger anti-viral immunity and markedly improve responses to these immunotherapies. Specifically, it aims to better define the mechanisms by which targeting ADAR1 can make immunotherapy work better and to discover new ways of triggering these mechanisms.

PI_NAMEs: ISHIZUKA, JEFFREY J. (contact)

PROGRAM_OFFICER_NAME: LIM, SUSAN E

PROJECT_TERMS: ADAR1;Advisory Committees;Anti-viral Response;Antibodies;Antigen Presentation;antiviral immunity;autoinflammatory;Award;cancer care;cancer immunotherapy;cancer type;CCL25 gene;Cell Line;checkpoint inhibition;Chemicals;chemokine;Chest;Clinical;clinical practice;clinical training;Combination immunotherapy;Complex;CRISPR screen;CRISPR/Cas technology;CXCL10 gene;CXCL11 gene;cytokine;Dana-Farber Cancer Institute;Disease;Double-Stranded RNA;Drug Targeting;Effectiveness;Enzymes;Event;Fellowship Program;Funding;Future;Genes;Genetic;genetic approach;genome editing;Goals;Grant;Gynecologic;Hematology;Human;I-antigen;immune cell infiltrate;immune checkpoint;immune checkpoint blockade;Immune response;Immune system;Immunologic Techniques;Immunotherapy;improved;in vivo;in vivo Model;Infiltration;Inflammation;Inflammatory;innate immune checkpoint;instructor;Interferons;Interleukin-6;K-Series Research Career Programs;Knock-out;Lead;Major Histocompatibility Complex;Malignant Neoplasms;Manuscripts;Mediating;Mediator;Medical Oncology;medical schools;Mentors;Mentorship;Minority;Modeling;Mus;Mutation;Natural Immunity;Natural Killer Cells;Nature;Neoplasm Transplantation;neoplastic cell;new therapeutic target;novel;novel drug class;novel strategies;novel therapeutic intervention;nucleic acid inhibitor;Nucleic Acids;Oncology;overexpression;Patients;PD-1/PD-L1;PDL1 pathway;Phenocopy;Phenotype;Positioning Attribute;programmed cell death protein 1;programs;Proteins;pseudotoxoplasmosis syndrome;Publishing;RANTES;recruit;Research;Research Personnel;Resistance;resistance mechanism;Resources;response;response biomarker;RNA Editing;Scientist;standard of care;success;System;targeted treatment;tenure track;Testing;Therapeutic;therapeutic development;Time;tool;Training;Transplantation;Treatment Protocols;TREX1 protein;tumor;tumor microenvironment;tumor-immune system interactions;Tumor-infiltrating immune cells;Work

PROJECT_TITLE: Triggering Innate Immunity in Tumor Cells to Overcome Resistance to Immunotherapy

STUDY_SECTION: NCI

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


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

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

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

ORG_STATE: NY

PHR: PROJECT NARRATIVE The treatment of malaria is vitally dependent on artemisinin-based combination therapies (ACTs), yet their continued efficacy is threatened by the emergence and spread of drug-resistant strains of the causative agent, the parasite Plasmodium falciparum. Here we test the hypothesis that the emergence of K13 mutations in Africa will cause artemisinin resistance, but with a fitness cost that is likely to hinder its dissemination in high- transmission settings. We will also define determinants of resistance ACT partner drugs, providing molecular markers to inform regional malaria treatment and control strategies designed to mitigate the impact of multidrug resistance in Africa.

PI_NAMEs: FIDOCK, DAVID A (contact)

PROGRAM_OFFICER_NAME: JOY, DEIRDRE A

PROJECT_TERMS: Address;Adoption;Africa;African;Alleles;Amodiaquine;Anti-malarials;Artemisinins;asexual;Asian;Automobile Driving;Bar Codes;benflumetol;Biological;Biological Assay;Biomass;Blood;Cambodia;Cambodian;Candidate Disease Gene;Cessation of life;Chromosome 12;Combined Modality Therapy;Containment;cost;Country;CRISPR/Cas technology;Data;deep sequencing;design;Development;Drug resistance;Drug usage;drug-sensitive;Effectiveness;Endocytosis;Eritrea;Face;Failure;Falciparum Malaria;fitness;Genes;Genetic;Genetic Crosses;genome sequencing;Genomics;Geography;Growth;Haplotypes;Heme;Hemoglobin;humanized mouse;Immunity;improved;In Vitro;innovation;insight;loss of function mutation;Malaria;Maps;Mediating;Microbial Drug Resistance;molecular marker;Morbidity - disease rate;mortality;Multi-Drug Resistance;mutant;Mutation;National Institute of Allergy and Infectious Disease;novel;Parasite resistance;Parasites;Pharmaceutical Preparations;Plasmodium falciparum;Point Mutation;Population;pressure;Prevalence;programs;Proteins;pyronaridine;Quantitative Trait Loci;Research Support;Resistance;resistance mutation;resistant Plasmodium falciparum;resistant strain;Risk;Rwanda;Southeastern Asia;Structure;Testing;Time;tool;transmission process;Treatment Failure;treatment strategy;Uganda;whole genome

PROJECT_TITLE: Defining P. falciparum resistance to artemisinin-based combination therapies

STUDY_SECTION: DDR

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


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Biotechnology;Emerging Infectious Diseases;Genetics;Infectious Diseases

ORG_CITY: HOUSTON

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: RICE UNIVERSITY

ORG_STATE: TX

PHR: Project Narrative  In order to cause infections, bacteria must sense antimicrobial peptides produced by the human immune system and respond by activating resistance and other virulence genes. Here, we will use a cutting-edge genetic engineering technology to reveal how bacteria use a specialized two-component system pathway to detect these antimicrobial peptides and what role those processes play in causing infections. We will also develop new peptides that “jam” this two-component system, and could lead to sorely-needed antibacterial therapeutics. 1

PI_NAMEs: TABOR, JEFFREY JAY (contact)

PROGRAM_OFFICER_NAME: ERNST, NANCY L

PROJECT_TERMS: Acceleration;Address;Amino Acids;Anti-Bacterial Agents;anti-microbial drug;anti-microbial peptide;antimicrobial;Bacteria;Binding;Biochemical;Biological;Biology;biophysical analysis;biophysical properties;cathelicidin;cathelicidin antimicrobial peptide;Cells;Cessation of life;Computer Analysis;cost;Cytoplasm;Dangerousness;design;DNA sequencing;enteric infection;Enterobacteriaceae;Epithelial Cells;Epithelium;Escherichia coli;experimental study;Family;Fluorescence-Activated Cell Sorting;Food Contamination;Future;gastrointestinal;Gene Expression;Genes;Genetic Engineering;Genetic Transcription;Goals;Homologous Gene;Human;Immune;Immune system;in vivo;Infection;Ingestion;inhibitor;Innate Immune System;insight;intestinal epithelium;Invaded;Knowledge;Laboratories;Link;Location;Macrophage;Measures;Mediating;Membrane;Methods;Modeling;Mus;mutant;Mutation Analysis;Names;new technology;next generation;novel;Organism;pathogen;pathogenic bacteria;Pathogenicity;Pathway interactions;peptide chemical synthesis;Peptide Library;Peptides;Phosphorylation;Physiological;Play;pressure;prevent;Process;promoter;Property;protein-histidine kinase;reconstitution;Reporter Genes;Resistance;resistance gene;response;Role;Salmonella typhimurium;sensor;sensor histidine kinase;Signal Transduction;Signal Transduction Pathway;Site;Specificity;Structure;Surface;synthetic peptide;Synthetic Peptide Libraries;System;Systemic infection;Technology;Therapeutic;Time;United States;Virulence;virulence gene;Water;Work

PROJECT_TITLE: High-throughput characterization of antimicrobial peptide-PhoPQ interactions

STUDY_SECTION: BACP

STUDY_SECTION_NAME: Bacterial Pathogenesis Study Section[BACP]


ORG_CITY: PITTSBURGH

ORG_DEPT: BIOLOGY

ORG_NAME: CARNEGIE-MELLON UNIVERSITY

ORG_STATE: PA

PHR: PROJECT NARRATIVE This proposal describes research to study how ribosomes are assembled in yeast and Hela cells, and how ribosome biogenesis is interconnected with the structure and function of the nucleolus, the cellular compartment where ribosomes are made. As the ribonucleoprotein machines that catalyze protein synthesis in all cells, ribosomes are essential for and closely linked to the growth, proliferation, and adaptation of cells. Consequently, dysregulation of ribosome synthesis or nucleolar structure results in cancers, anemias, neurodegenerative diseases, and a variety of developmental disorders.

PI_NAMEs: WOOLFORD, JOHN L. (contact)

PROJECT_TERMS: Address;Affect;Anemia;ATP phosphohydrolase;Automobile Driving;Binding;Biogenesis;Biological Assay;cell growth;Cell Nucleolus;Cell Proliferation;Cells;Complex;Cytoplasm;developmental disease;Disease;Drops;Energy consumption;Enzymes;Eukaryota;Event;experimental study;fluidity;genetic approach;Genetic Transcription;Goals;Growth;Hela Cells;Human;In Vitro;in vivo;Individual;Investigation;Learning;Link;Malignant Neoplasms;Mediating;Modeling;Modification;Molecular Conformation;Molecular Genetics;Morphology;mutant;Nature;Neurodegenerative Disorders;Nucleoplasm;particle;Physical condensation;premature;prevent;Production;Progress Reports;Proliferating;Property;Protein Biosynthesis;protein protein interaction;Proteins;Radial;Regulation;Research;Ribonucleoproteins;Ribosomal Biogenesis Pathway;Ribosomal Proteins;Ribosomal RNA;Ribosomes;RNA;RNA Helicase;Saccharomyces cerevisiae;Series;Solvents;Structure;Surface;Tertiary Protein Structure;Testing;Transcript;Visualization;Yeasts

PROJECT_TITLE: Yeast Ribosome Biogenesis

STUDY_SECTION: MGA

STUDY_SECTION_NAME: Molecular Genetics A Study Section[MGA]


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

ORG_CITY: DALLAS

ORG_NAME: UT SOUTHWESTERN MEDICAL CENTER

PHR: Project Narrative The mechanisms underlying M. tuberculosis (Mtb) transmission are poorly understood. We recently identified a nociceptive-neuron activating, cough-inducing molecule from Mtb called sulfolipid-1 (SL-1). We will discover the signaling mechanism triggered by SL-1 in neurons and in experimental animals. We also identified a second nociceptive molecule and propose to characterize its activity in parallel to studies on SL-1. Finally, we will develop a safe and effective system for measuring Mtb transmission from naïve to infected animals that will simultaneously determine other factors associated with transmission including Mtb-induced cough and aerosolized Mtb particle production. We will then use this system to analyze the transmission dynamics of Mtb strains lacking cough inducing molecules to determine relationships between Mtb genes and transmissibility. This approach represents the first systematic analysis of cough-inducing molecules in mycobacterial transmission.

PI_NAMEs: SHILOH, MICHAEL  (contact)

PROGRAM_OFFICER_NAME: ROBINSON, RICHARD THOMAS

PROJECT_TERMS: aerosolized;Animal Experiments;Animal Model;Animals;Bacteria;Binding;Biochemical;Biochemistry;Biological;Biological Assay;Biological Models;Cavia;Cells;Cholera Toxin;Complex;Coughing;CRISPR/Cas technology;Data;Diarrhea;Disease;disease transmission;Electrophysiology (science);epidemiology study;experimental study;Foundations;Future;G-Protein-Coupled Receptors;Genes;Genetic;genetic approach;Genus Mycobacterium;glycolipid receptor;Glycolipids;Goals;Human;human disease;Immunohistochemistry;in vivo;in vivo evaluation;Individual;Infection;inhibitor;insight;Knock-out;Laboratories;Lipids;Measures;Mediating;Mediation;Modeling;Molecular;Molecular Biology;mutant;mycobacterial;Mycobacterium tuberculosis;Nebulizer;Neurons;Nociception;Nociceptors;novel;Orphan;Pain;particle;pathogen;pathogenic bacteria;Persons;polyketide synthase;Population;Prevalence;Production;protein complex;Proteins;receptor;Recording of previous events;Research;response;Route;screening;Signal Transduction;success;sulfolipids;sulfotransferase;Symptoms;System;Techniques;Testing;Tissues;transmission process;Tuberculosis;Vibrio cholerae;Virulence;Virulent;Work;World Health

PROJECT_TITLE: Mechanisms of cough in Mycobacterium tuberculosis transmission

STUDY_SECTION: HIBP

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


NIH_SPENDING_CATS: Biotechnology;Cancer;Childhood Leukemia;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Gene Therapy;Gene Therapy Clinical Trials;Genetics;Hematology;Immunotherapy;Orphan Drug;Pediatric;Pediatric Cancer;Precision Medicine;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: PROJECT NARRATIVE Chimeric antigen receptor T-cell therapy targeting CD19 (CAR19) has revolutionized the treatment landscape for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia. Unfortunately, however, approximately 50% of children relapse after initial response to CAR19 and their subsequent survival is dismal. This proposal aims to optimize outcomes after post-CAR19 relapse through two mutually informative approaches: 1) A phase 1/2 clinical trial testing the delivery of a novel, dual-antigen targeted CAR designed to overcome the primary mechanisms of CAR19 failure; and 2) An advanced comparative effectiveness study to determine optimal existing salvage treatment approaches for post-CAR19 relapse.

PI_NAMEs: MYERS, REGINA M (contact)

PROGRAM_OFFICER_NAME: RADAEV, SERGEY

PROJECT_TERMS: Adult;Antigen Targeting;arm;Award;B-Cell Acute Lymphoblastic Leukemia;Biological Markers;cancer clinical trial;cancer immunotherapy;CAR T cell therapy;career;CD19 Antigens;CD19 gene;Cell Therapy;chemotherapy;Child;Childhood;chimeric antigen receptor T cells;clinical epidemiology;Clinical Investigator;Clinical Research;Clinical Trials;Clinical Trials Design;cohort;comparative effectiveness;comparative effectiveness study;compare effectiveness;conventional therapy;Cytotoxic agent;Data;data pipeline;data resource;design;Disease remission;Disease-Free Survival;early phase clinical trial;effective therapy;efficacy outcomes;Enrollment;Environment;Epidemiologic Methods;Epidemiology;epidemiology study;evidence base;experience;Failure;Foundations;Frequencies;Goals;Hematologic Neoplasms;Hematopoietic Stem Cell Transplantation;high risk;Immune;Immunotherapy;immunotherapy clinical trials;improved;improved outcome;Infrastructure;innovation;Instruction;instructor;International;Investigational Therapies;K-Series Research Career Programs;Lead;leukemia;Malignant Childhood Neoplasm;Mediating;Mentorship;Methodology;Methods;multidisciplinary;Mus;next generation;next generation sequencing;novel;novel strategies;novel therapeutics;Outcome;Outcomes Research;patient prognosis;Patients;Pediatric Hospitals;Pediatric Oncology;Pediatrics;Pennsylvania;Phase;phase 1 study;phase I trial;Phase I/II Clinical Trial;Philadelphia;Physicians;Predictive Value;Process Assessment;Prognosis;programs;Proxy;randomized, clinical trials;Recommendation;Refractory;Relapse;Research;Research Infrastructure;Residual Neoplasm;Resources;response;Safety;safety outcomes;Scientist;secondary analysis;specific biomarkers;targeted treatment;Testing;Therapeutic;Time;Toxic effect;Training;Transplant Recipients;treatment strategy;Universities;Variant;young adult

PROJECT_TITLE: Optimizing outcomes for children and young adults with relapse of B-cell acute lymphoblastic leukemia after CD19-targeted chimeric antigen receptor T-cell therapy


FUNDING_MECHANISM: TRAINING, INDIVIDUAL

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative This proposal outlines nickel-catalyzed carbon-carbon bond-forming strategies to synthesize hindered stereocenters with α-heteroatom functionality. These motifs are abundant in drug scaffolds and biologically active molecules but can be challenging to efficiently prepare through current methods. Expediating their syntheses will broaden the accessible chemical space in the development of novel pharmaceutical candidates.

PI_NAMEs: BELEH, OMAR  (contact)

PROGRAM_OFFICER_NAME: JONES, LATAISIA CHERIE

PROJECT_TERMS: Academia;Acids;Acylation;Adopted;Alcohols;Amines;Amino Acids;Amino Alcohols;Area;bioactive natural products;Bypass;Carbon;Chemicals;Complex;Coupling;Development;Dissociation;driving force;drug candidate;drug development;drug discovery;drug synthesis;forging;Free Radicals;functional group;Future;Generations;Goals;Hydrogen;improved;In Situ;Industry;Intercept;interest;ketal;Ketones;Ligands;Mediator;Methodology;Methods;Molecular Conformation;Natural Products;Nickel;novel;Outcome Study;Pathway interactions;Pharmaceutical Preparations;Pharmacologic Substance;Process;Production;Reaction;Reagent;scaffold;unnatural amino acids

PROJECT_TITLE: Nickel Cross-Coupling Cascades with α-Heteroatom Radicals to Prepare Sterically Hindered Alcohols and Amines


NIH_SPENDING_CATS: Cancer;Genetics

ORG_NAME: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

PHR: NARRATIVE This study is challenging the functional interaction between XAF1 and p53 and its relevance to cancer risk. Our recent genomic findings identified mutations in both genes that co -segregate in individuals at high risk for cancer, sarcomas and multiple tumors. The goal of the project is to address the disparities in outcome among individuals carrying the same TP53 mutation.

PI_NAMEs: ZAMBETTI, GERARD PAUL (contact)

PROGRAM_OFFICER_NAME: LIU, ZHIHUI

PROJECT_TERMS: Address;Adrenocortical Carcinoma;Age;Alleles;Apoptosis;Apoptotic;Azoxymethane;Biochemical;Brazil;cancer risk;Carcinogens;cell type;Cellular Stress;Child;Clinical;colon carcinogenesis;Colon Carcinoma;Databases;Diagnosis;Disparity;epigenetic silencing;established cell line;Family;Feedback;founder mutation;gain of function;gene function;General Population;Genes;Genetic;Genetic Engineering;Genomics;Goals;Haplotypes;Heterogeneity;High-Risk Cancer;Human;In Vitro;in vivo;Incidence;Individual;Inherited;interest;International Agency for Research on Cancer;Knock-in;Knock-in Mouse;Knock-out;Knockout Mice;loss of function;Malignant Neoplasms;Mediating;Modeling;mouse model;Mus;mutant;mutant mouse model;Mutation;mutation carrier;Newborn Infant;Nonsense Mutation;novel;Oncogenes;Outcome;p53 Signaling Pathway;Phenotype;Physiological;Population;Predisposition;Reporting;Role;Sarcoma;segregation;Signal Transduction;Sodium Dextran Sulfate;Structure;Tissues;TP53 gene;Transactivation;tumor;Tumor Cell Line;Tumor Suppression;Tumor Suppressor Genes;Tumor Suppressor Proteins;tumorigenesis;variant of unknown significance;XAF1 gene

PROJECT_TITLE: XAF1 IN P53 SIGNALING, APOPTOSIS AND TUMOR SUPPRESSION

STUDY_SECTION: CAMP

STUDY_SECTION_NAME: Cancer Molecular Pathobiology Study Section[CAMP]


NIH_SPENDING_CATS: Chronic Pain;Natural Products;Neurosciences;Pain Research

ORG_CITY: SALT LAKE CITY

ORG_NAME: UNIVERSITY OF UTAH

ORG_STATE: UT

PHR: Project Narrative  A group of marine snails (Conus) have evolved complex venoms that allow them to catch fish; this project aims at understanding how the diverse venom components act to change the physiology of fish and other vertebrates, including humans. Because each individual component of the venom acts like a drug,these individual venom compounds have great biomedical potential; one has become an approved drug for pain, and two others reached human clinical trials (for epilepsy and spinal cord injury pain). By greatly increasing the number of defined venom components, and having insight into how each acts, many more therapeutic and diagnostic uses should emerge.

PI_NAMEs: OLIVERA, BALDOMERO M (contact);RAGHURAMAN, SHRINIVASAN ;SAFAVI-HEMAMI, HELENA

PROGRAM_OFFICER_NAME: JUSTINOVA, ZUZANA

PROJECT_TERMS: Achievement;Affect;alpha-bungarotoxin receptor;Alzheimer's Disease;Animals;basal forebrain;Basic Science;Behavior;bioactive natural products;Biochemical;Biological;Biological Assay;Biological Models;biophysical properties;Calcium;cell type;Chemicals;chronic pain;Clinical Trials;Collection;Complex;Cone;Conotoxin;Consumption;Conus genus;Conus Venom;Development;Diagnostic;Electrophysiology (science);Epilepsy;FDA approved;Fishes;Functional disorder;ganglion cell;Gland;Goals;Grant;Hour;Human;imaging platform;improved;Individual;inhibitor;insight;Investigation;Ion Channel;Ion Channel Gating;Laboratories;Libraries;Ligands;Link;macromolecule;Macrophage;marine;marine natural product;Methods;Molecular;Molecular Target;Mus;National Institute of General Medical Sciences;Natural Products;Nervous System;neuroethology;Nicotinic Receptors;novel;novel strategies;Pain;pathogen;Pathology;Peptides;Pharmaceutical Chemistry;Pharmaceutical Preparations;pharmacologic;Pharmacology;Physiological;Physiology;Potassium Channel;programs;Proteomics;Purinoceptor;Rationalization;receptor;Resources;Respiratory distress;Role;Route;Science;screening;Snail Venoms;Snails;spinal cord injury pain;Spinal Ganglia;Structure;System;Therapeutic;Time;tool;transcriptomics;Venoms;Vertebrates;voltage;Voltage-Gated Potassium Channel

PROJECT_TITLE: “Conus venom peptides and their molecular targets: Using pharmaconomics and neuroethology as a framework for discovery”

STUDY_SECTION: SBCB

STUDY_SECTION_NAME: Synthetic and Biological Chemistry B Study Section[SBCB]


ADMINISTERING_IC: MH

IC_NAME: NATIONAL INSTITUTE OF MENTAL HEALTH

NIH_SPENDING_CATS: Anxiety Disorders;Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Mental Health;Mental Illness;Neurosciences;Pediatric;Physical Injury - Accidents and Adverse Effects;Post-Traumatic Stress Disorder (PTSD);Social Determinants of Health;Violence Research;Youth Violence

ORG_CITY: SAN ANTONIO

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: NARRATIVE Posttraumatic stress disorder in adolescence impairs neurobiological networks underlying cognitive, social and emotional skills. Neuroimaging research that seeks to identify the neural mechanisms of treatments for PTSD could lead to novel treatments, but progress has been slow using current methods. The proposed study uses an innovative approach to identify neural mechanisms of specific phases of trauma-focused therapy for youth with PTSD, allowing a new understanding of brain changes associated with the process of therapy.

PI_NAMEs: GARRETT, AMY S (contact)

PROGRAM_OFFICER_NAME: BORJA, SUSAN EILEEN

PROJECT_TERMS: abuse victim;Adolescence;Adolescent;Aftercare;Age;age difference;Amygdaloid structure;Anterior;Behavioral;biomarker development;boys;Brain;brain dysfunction;Brain region;Child;Clinical Trials;Cognitive;cognitive function;Cognitive Therapy;Communities;Consultations;coping;Cues;Data;Development;Dorsal;Early Intervention;effective therapy;efficacious treatment;Emotional;emotional functioning;evidence base;executive function;experience;flexibility;Functional Magnetic Resonance Imaging;girls;Goals;gray matter;habituation;Impairment;improved;Individual Differences;innovation;interpersonal trauma;Investigation;Learning;Left;Link;Long-Term Effects;Methods;Modeling;neural;Neuroanatomy;neurobiological mechanism;Neurobiology;neuroimaging;neuromechanism;novel;novel strategies;Participant;Patients;Pattern;personalized medicine;Phase;physical abuse;Population;post-traumatic stress;Post-Traumatic Stress Disorders;Process;Provider;Psychotherapy;Randomized;Randomized, Controlled Trials;recruit;reduce symptoms;Regulation;Research;response;Scanning;Series;Severities;sex;Sexual abuse;skill acquisition;skills;social;Social Functioning;social skills;Structure;symptom treatment;symptomatic improvement;Symptoms;Testing;Therapeutic;time interval;Trauma;trauma exposure;treatment as usual;Treatment Protocols;trial design;Violence;white matter;Youth

PROJECT_TITLE: Neural connectivity before and after each of the three treatment phases of trauma-focused therapy for adolescent posttraumatic stress

STUDY_SECTION: NPAS

STUDY_SECTION_NAME: Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section[NPAS]


ADMINISTERING_IC: EB

IC_NAME: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

NIH_SPENDING_CATS: Bioengineering;Data Science;Microbiome

ORG_CITY: BOSTON

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: NORTHEASTERN UNIVERSITY

ORG_STATE: MA

PHR: Project Narrative We develop efﬁcient, interpretable, and scalable mathematical models and related tools for modeling and integrat- ing various omics data, reconstructing the topology of microbial communities, and acquiring the most informative data. These tools will enable a deep understanding of the fundamentals of biology in microbial communities and impact multiple aspects of our lives, including protecting humans or plants against diseases or developing next-generation biofuels and biological remediation systems needed for sustainable growth.

PI_NAMEs: IMANI, MAHDI  (contact)

PROGRAM_OFFICER_NAME: FEHR, TUBA HALISE

PROJECT_TERMS: 16S ribosomal RNA sequencing;Bacteria;Bayesian Analysis;Bayesian learning;Behavior;Biological;Biological Process;Biology;community building;Complex;Computing Methodologies;cost;Data;data integration;Data Set;Databases;design;Differential Equation;Disease;dynamic system;Genes;genome sequencing;Goals;Growth;high dimensionality;Human;improved;invention;Learning;learning strategy;mathematical model;Metabolic;Metagenomics;metatranscriptomics;Methods;Microbe;microbial;microbial community;Microbial Genome Sequencing;Modeling;Molecular Profiling;multidimensional data;Multiomic Data;multiple omics;network models;next generation;nonbinary;novel;Plants;Play;Policies;Process;Proteins;Proteomics;Psychological reinforcement;reconstruction;remediation;Research;Research Infrastructure;Research Personnel;Series;Shotguns;Signal Transduction;small molecule;System;Systems Biology;Techniques;Technology;temporal measurement;Time;tool;transcriptomics;user friendly software

PROJECT_TITLE: Bayesian Dynamical Modeling of Microbial Communities

STUDY_SECTION: MABS

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


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Biomedical Imaging;Clinical Research;Digestive Diseases;Health Services

PHR: Project Narrative Endoscopic retrograde cholangiopancreatography (ERCP) has transformed the treatment of pancreaticobiliary diseases in the United States (US) but outcomes of the procedure, and it’s most dreaded complication, post- ERCP pancreatitis, can vary by the physician performing the procedure. Despite this known variability, there have been no national population-based studies aimed at understanding the patient, provider, and system level factors that influence these variations and whether potential interventions, such as selective referral to high volume physicians, may mitigate these risks. Understanding factors that contribute to variations in care, as proposed in this project, has the potential to improve patient outcomes, reduce the cost of care after an ERCP, and shape future policy initiatives around the practice and delegation of ERCP resources in the US.

PI_NAMEs: TAVAKKOLI, ANNA  (contact)

PROGRAM_OFFICER_NAME: SERRANO, KATRINA JANE

PROJECT_TERMS: Acceleration;Address;Adverse event;Award;beneficiary;care costs;career;career development;Caregivers;Caring;Case Mixes;Clinical;cohort;comorbidity;complex data;Complication;cost;cost effectiveness;Data;Data Set;Decision Analysis;demographics;Development;Digestive System Disorders;Disease;economic evaluation;Educational Intervention;Endoscopic Retrograde Cholangiopancreatography;Endoscopy;Ensure;Environment;Equipment;Evaluation;Evidence based intervention;Expenditure;experience;Facilities and Administrative Costs;Financial Hardship;Foundations;Future;Gastroenterologist;Goals;Health Care Costs;health care service utilization;health economics;Health Services Research;Health system;high risk;Hospitals;improved;Incidence;Inpatients;Intervention;Interview;Liver diseases;Logistic Regressions;Measurable;Measures;medical specialties;Medicare;Mentors;Modeling;Morbidity - disease rate;multilevel analysis;Outcome;Outpatients;Pancreatitis;Patient Care;Patient-Focused Outcomes;Patients;Phase;Physicians;Policies;Policy Maker;Population Study;Procedures;Productivity;productivity loss;prospective;Prospective cohort;Provider;Reporting;Research;Research Personnel;Resources;risk mitigation;Sample Size;sex;Shapes;Societies;Statistical Data Interpretation;Statistical Methods;success;Surveys;System;Texas;Training;United States;Universities;Variant;Work

PROJECT_TITLE: Evaluation of Multi-level factors Associated with post-ERCP Outcomes

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Digestive Diseases and Nutrition C Study Section[DDK-C]


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: BALTIMORE

ORG_DEPT: SURGERY

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: PROJECT NARRATIVE Cognitive decline and incident dementia are major clinical and public health problems that significantly impact the growing population of older ESRD adults. Secondary hyperparathyroidism (SHPT), characterized by elevated PTH, represents an ESRD-specific modifiable risk factor for cognitive decline and incident dementia in older ESRD adults. We hypothesize that PTH likely causes cognitive decline and incident dementia both directly and indirectly via release of other SHPT biomarkers and can be modified with treatment.

PI_NAMEs: MATHUR, AARTI  (contact)

PROGRAM_OFFICER_NAME: FRANKOWSKI, DAVID WITT

PROJECT_TERMS: abstracting;Accounting;Adult;Affect;Aftercare;Age;Alkaline Phosphatase;Ancillary Study;Binding;Biological Markers;Brain;Cardiovascular system;Clinical;clinical decision-making;clinical practice;Cognition;Cognitive;cognitive function;cohort;Computerized Medical Record;Data;Data Collection;Data Set;Decision Making;Decision Trees;Dementia;dementia risk;design;Diagnosis;disability risk;Elderly;Eligibility Determination;End stage renal failure;Enrollment;Etiology;executive function;Fracture;frailty;Funding;hazard;high risk;Hospitalization;Impaired cognition;improved;individualized medicine;Infrastructure;Kidney Transplantation;Literature;Longitudinal cohort study;Measures;Mediating;Methods;Minerals;Modeling;modifiable risk;Modification;Morbidity - disease rate;mortality;Nephrology;Neurocognitive;Neuropsychology;novel;novel marker;Odds Ratio;older patient;Older Population;Operative Surgical Procedures;Outcome;Parathyroidectomy;patient oriented;Patients;Persons;Pharmacotherapy;Physicians;pilot test;Population;Process;prognostication;prospective;Provider;PTH gene;Public Health;receptor;Risk;Risk Factors;risk stratification;Sampling;Secondary Hyperparathyroidism;Secondary to;Serum;Surgeon;systematic review;Testing;tool;Transplant Recipients;treatment guidelines;usability;web-based tool

PROJECT_TITLE: Cognitive Decline and Incident Dementia in Older Patients with Secondary Hyperparathyroidism

STUDY_SECTION: ASG

STUDY_SECTION_NAME: Aging Systems and Geriatrics Study Section[ASG]


ED_INST_TYPE: OVERALL MEDICAL

ORG_CITY: PORTLAND

ORG_NAME: OREGON HEALTH & SCIENCE UNIVERSITY

ORG_STATE: OR

PHR: PROJECT NARRATIVE Although combination antiretroviral therapy (cART) has significantly improved the life expectancy of people living with HIV infection, cART alone cannot cure the infection and must be taken for life to prevent disease progression. In this project, we will determine whether a therapeutic vaccination strategy that utilizes a messenger ribonucleic acid (mRNA)-based vaccine platform, can enhance cellular immunity in SIV-infected rhesus macaques on cART and establish high-level, long-term control of SIV replication after cART cessation.

PI_NAMEs: OKOYE, AFAMEFUNA  (contact)

PROGRAM_OFFICER_NAME: SANDERS, BRIGITTE E

PROJECT_TERMS: Acute;Address;anti-CD20;Antigens;antiretroviral therapy;antiviral immunity;B-Lymphocytes;Binding;biopharmaceutical industry;Blood;booster vaccine;CD8-Positive T-Lymphocytes;Cellular Immunity;Clinical;Clinical assessments;Clinical Research;clinical translation;cohort;Collaborations;cytokine;Data;design;Development;Disease Progression;Disease remission;DNA;Dose;Economic Burden;Ensure;Epitope Mapping;Epitopes;experimental study;Frequencies;GAG Gene;Generations;Genes;Germany;Goals;Health;HIV;HIV Infections;HIV vaccine;Human;Immune;Immune response;Immunity;immunogenic;Immunologics;improved;Individual;Infection;Injections;Life;Life Expectancy;lymph nodes;Lymphoid Tissue;Macaca mulatta;Measurable;Mediating;Messenger RNA;novel therapeutic intervention;Patients;Peptides;Persons;Plasma;Positioning Attribute;prevent;Primary Infection;Prognosis;Recrudescences;Regimen;relapse prevention;response;Risk;RNA;RNA vaccine;Route;safety and feasibility;Site;SIV;SIV Vaccines;Societies;Specificity;Stains;T cell response;T-Lymphocyte Epitopes;Technology;Therapeutic;therapeutic vaccine;therapy design;Time;tool;tositumomab;Vaccinated;Vaccination;vaccination protocol;vaccination schedule;vaccination strategy;Vaccine Design;vaccine efficacy;vaccine platform;Vaccine Therapy;Vaccines;vector;vector control;vector vaccine;Viral;Viral Load result;viral rebound;Viral reservoir;Virus;Virus Diseases;Virus Replication;Withdrawal

PROJECT_TITLE: Development of an mRNA-Based Therapeutic HIV/AIDS Vaccine

STUDY_SECTION: HIVD

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


NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_DEPT: PHARMACOLOGY

PHR: When suffering starvation, bacteria produce a universally conserved second messenger, ppGpp, which reprograms cellular physiology, arrests growth, and thereby enhances bacterial persistence against antibiotic treatment. By developing two innovative techniques to identify RNA-metabolite and protein-metabolite interactions, respectively, this proposal will examine the roles of small-molecule metabolites in coordinating various cellular activities in response to ppGpp induction. The proposed research will provide new insights on the mechanisms of ppGpp-mediated growth arrest, and elucidate key regulatory interactions required for bacterial persistence: these interactions may serve as targets for the design of anti-persistence drugs.

PI_NAMEs: WANG, BOYUAN  (contact)

PROGRAM_OFFICER_NAME: BLATCH, SYDELLA ANNE

PROJECT_TERMS: alpha ketoglutarate;Amino Acids;Antibiotic Therapy;Antibiotics;aptamer;Attenuated;Bacteria;Binding;Binding Proteins;Binding Sites;Biochemical;Biochemical Pathway;Biological Assay;Biology;Biophysics;candidate identification;Cell Physiology;Cell Wall;Cells;Chemistry;computational pipelines;Data;design;Drug Design;environmental stressor;Enzymes;Escherichia coli;Fatty Acids;Filtration;Gene Expression;genetic approach;genetic resistance;Genetic Transcription;Glutamate Dehydrogenase;Growth;Guanosine;Guanosine Triphosphate Phosphohydrolases;in vitro activity;in vivo;in vivo evaluation;innovation;insight;interest;Isocitrate Dehydrogenase;Libraries;Ligands;Mass Spectrum Analysis;Mediating;Metabolic;Metabolic Pathway;Metabolism;Metabolite Interaction;metabolomics;Methods;Molecular;novel;nuclease;Nucleotides;Organism;Pathway interactions;Pharmaceutical Preparations;Physiological;Point Mutation;Predisposition;Process;Production;programs;protein metabolite;Proteins;Proxy;Repression;Research;response;Ribosomes;RNA;RNA Binding;RNA Stability;Role;Second Messenger Systems;Signal Transduction;small molecule;Starvation;Structure;Techniques;Testing;time use;Transcript;transcriptome;transcriptome sequencing;translation factor;Translations;Ultrafiltration;Validation;Work

PROJECT_TITLE: In-depth characterization of the metabolic effect of the bacterial alamorne ppGpp

STUDY_SECTION: NSS

STUDY_SECTION_NAME: NSS


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Behavioral and Social Science;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Dementia;Mental Health;Neurodegenerative;Neurosciences;Prevention;Rehabilitation;Sleep Research

ORG_NAME: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC

PHR: PROJECT NARRATIVE There is accumulating evidence indicating that sleep disturbance could lead to Alzheimer's disease (AD) pathology and related cognitive decline; therefore, understanding the effects of sleep interventions on cognition could enhance our understanding of sleep disturbance as a modifiable risk factor for AD. The current K23 proposal aims to examine this important research question by investigating neurocognitive effects of two sleep interventions (cognitive-behavioral therapy for insomnia [CBTI] and acoustic slow-wave activity enhancement [SWAE]) and their underlying mechanisms in individuals with amnestic mild cognitive impairment (aMCI). The overarching goal of this project is to support a research career to study sleep interventions as novel therapeutic approaches to prevent or delay AD progression.

PI_NAMEs: KIM, HYUN  (contact)

PROGRAM_OFFICER_NAME: HAAKENSON, CHELSEA MARIE

PROJECT_TERMS: abeta accumulation;Acceleration;Acoustics;Activities of Daily Living;Adult;Aftercare;aged;Aging;Alzheimer's Disease;Alzheimer's disease pathology;Alzheimer's disease related dementia;Alzheimer's disease risk;Alzheimer’s disease biomarker;amnestic mild cognitive impairment;Amyloid beta-Protein;Attention;Benzodiazepines;Brain;career;career development;Clinical;clinical trial implementation;Clinical Trials;Clinical Trials Design;Cognition;Cognitive;cognitive change;cognitive function;Cognitive Therapy;Communities;Complex;Data;Dementia;design;Detection;Development;Development Plans;Disease Progression;Doctor of Philosophy;Doctor's Degree;Early Diagnosis;Education;Electroencephalography;Episodic memory;executive function;Fostering;Functional disorder;Future;glial activation;Goals;Health;Impaired cognition;improved;indexing;Individual;Intervention;Knowledge;Learning;Maps;Measures;Mediating;Memory;Mentored Patient-Oriented Research Career Development Award;Methodology;modifiable risk;Modification;Monitor;Nerve Degeneration;neurobiological mechanism;Neurobiology;Neurocognitive;Neuropsychological Tests;Neuropsychology;Neurotoxins;non rapid eye movement;novel;novel therapeutic intervention;older adult;Outcome;Performance;Plasma;poor sleep;Postdoctoral Fellow;preservation;prevent;Property;Psychology;Psychometrics;Randomized;recruit;Research;Research Personnel;Research Project Grants;Research Training;resilience;restoration;Risk;Risk Factors;Role;Science;Scientist;Severities;skills;Sleep;Sleep Disorders;Sleep disturbances;Sleep Fragmentations;Sleeplessness;Structure;sustained attention;Symptoms;tau Proteins;tau-1;Testing;Time;Tissues;tool;Training;training opportunity;Universities;Visuospatial

PROJECT_TITLE: Sleep Interventions and Neurocognitive Outcomes in Amnestic Mild Cognitive Impairment

STUDY_SECTION: AGCD

STUDY_SECTION_NAME: Career Development for Clinicians/Health Professionals Study Section [AGCD-3]


ORG_CITY: SEATTLE

ORG_NAME: VA PUGET SOUND HEALTHCARE SYSTEM

ORG_STATE: WA

PHR: Nearly one in four VA patients is affected by type 2 diabetes, a rate 2.5 times higher than the general US population. T2D is the leading cause of blindness, end-stage renal disease and amputations in the VA population, exerting a significant burden on Veterans as well as the VA health care system. Insufficient release of insulin from the pancreatic islet β cell is a critical defect in the pathogenesis of type 2 diabetes. Recent work has highlighted a key role for the islet vasculature in supporting normal health and function of the islet β cell, while also showing islet vascular pathology in type 2 diabetes. This proposal will investigate novel mechanisms underlying the development of this islet vascular pathology and its effect to impair β-cell function and survival. The findings from this work will also be relevant for the microvascular disease that affects many tissues in T2D. These studies may therefore pave the way for development of new vascular-targeted therapies which could treat multiple aspects of T2D pathology.

PI_NAMEs: HULL-MEICHLE, REBECCA LUCY;TONG, JENNY  (contact)

PROJECT_TERMS: 3-Dimensional;Address;Affect;Amputation;Amyloid;Animal Model;Beta Cell;Blindness;Blood capillaries;Blood flow;Blood Vessels;Brain;C-Type Lectins;Cell Death;Cell model;Cell Physiology;Cell Survival;cell type;Cells;Crossbreeding;cytotoxicity;Data;Defect;Deposition;Development;Diabetes Mellitus;Diabetic Nephropathy;Diabetic Retinopathy;End stage renal failure;endocrine pancreas development;Endothelial Cells;Endothelium;Extracellular Matrix;Extravasation;Failure;Family;Functional disorder;Health;Healthcare Systems;Homeostasis;Human;human data;Hyperglycemia;Impairment;In Vitro;in vivo;Inflammation;Insulin;islet;islet amyloid polypeptide;Islet Cell;Islets of Langerhans;kidney fibrosis;Knowledge;Mediating;Mediator;member;Microvascular Dysfunction;Modeling;Molecular;Mus;neuroinflammation;Non-Insulin-Dependent Diabetes Mellitus;novel;Nutrient;Pancreas;Paracrine Communication;Pathogenesis;Pathology;Pathway interactions;Patients;Pericytes;Peripheral;Play;Population;Predisposition;prevent;response;Role;Signal Transduction;Slice;Source;targeted treatment;Tissues;Toxic effect;transcriptome sequencing;Transgenic Mice;vascular abnormality;Vascular Diseases;vascular inflammation;Vascularization;Veterans;Work

PROJECT_TITLE: Mechanisms and Impact of Islet Vascular Inflammation in Diabetes


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Aging;Assistive Technology;Bioengineering;Brain Disorders;Clinical Research;Clinical Trials and Supportive Activities;Neurodegenerative;Neurosciences;Parkinson's Disease;Rehabilitation

ORG_CITY: DURHAM

ORG_DEPT: NEUROSURGERY

ORG_NAME: DUKE UNIVERSITY

PHR: This project seeks to help people with severe Parkinson disease improve their treatment options and therapy through novel approaches including both dual deep brain stimulation electrode treatment and advanced closed loop medical device technology. The adaptive control of Parkinson symptoms will be based on local field potentials, internal and external accelerometers, and wearable measurement devices. These studies will make important contributions to public health, building upon rapid advances in technology to give subjects improved surgical and symptomatic therapy for a common illness, Parkinson disease. Additionally, this clinical research will also help improve our understanding of how a combination of intrinsic brain signals and wearable device information can be used as part of a novel surgical treatment to provide better clinical solutions to the affected subjects through automatic, dynamic device adjustments.

PI_NAMEs: TURNER, DENNIS ALAN (contact)

PROGRAM_OFFICER_NAME: FRANKOWSKI, MEGAN MICHELLE

PROJECT_TERMS: Accelerometer;Accounting;Affect;Algorithms;Architecture;Bilateral;Biological Markers;biomarker selection;Bradykinesia;Brain;Clinic;Clinical;clinical outcome measures;Clinical Research;Clinical Trials;cohort;comparative;comparative efficacy;Complex;Coupling;Data;Deep Brain Stimulation;Devices;Disease Outcome;Dose;Dyskinetic syndrome;Electrodes;energy efficiency;experimental study;FDA approved;Feedback;flexibility;Frequencies;Funding;Globus Pallidus;Goals;Guidelines;Home;Human;Implant;implantation;improved;innovation;Institutional Review Boards;internal control;machine learning model;Measurement;Measures;Medical Device;motor symptom;neural;Noise;novel;novel strategies;Operative Surgical Procedures;Outcome;Parkinson Disease;Patient-Focused Outcomes;Patients;Pattern;Persons;Pharmaceutical Preparations;Phase;Physicians;Physiologic pulse;Physiological;Policies;Postoperative Period;Procedures;programs;Prospective cohort;Public Health;reduce symptoms;Research;response;sensor;Signal Transduction;Site;Sleep;smart watch;Structure of subthalamic nucleus;success;Surrogate Markers;symposium;symptom management;symptom treatment;Symptoms;synergism;System;Technology;Testing;Time;Tremor;Update;Walking;wearable device;wearable sensor technology

PROJECT_TITLE: An Integrated Biomarker Approach to Personalized, Adaptive Deep Brain Stimulation in Parkinson Disease

STUDY_SECTION: NSD

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


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Clinical Research;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Vector-Borne Diseases

ORG_CITY: BAMAKO

ORG_COUNTRY: MALI

ORG_FIPS: ML

ORG_NAME: UNIV OF SCIENCES, TECH & TECH OF BAMAKO

PHR: Project Narrative The recent epidemics of Ebola in West Africa and the current COVID-19 pandemic highlight the need for a critical mass of well-trained scientists and health research professionals capable of studying and responding appropriately, and in timely manner, to emerging infectious diseases outbreaks. This training program offers high-level training in field and laboratory epidemiology, translational clinical research, public health emergency management and genomic characterization and surveillance of emerging infectious pathogens. This proposed project is a south-south collaborative research training program between the University of Bamako (USTTB) and the University of Conakry in Guinea, supported by Johns Hopkins University and NIAID. It will contribute to a more coordinated cross-border approach of public health preparedness and response to emerging infectious diseases epidemics.

PI_NAMEs: DOUMBIA, SEYDOU  (contact)

PROGRAM_OFFICER_NAME: SINA, BARBARA J

PROJECT_TERMS: Africa;African;Border Crossings;Certification;Clinical Research;clinical translation;Collaborations;Country;COVID-19;COVID-19 pandemic;Disease;doctoral student;Ebola;Ebola Hemorrhagic Fever;Educational Curriculum;Emerging Communicable Diseases;Epidemic;Epidemiology;Faculty;future epidemic;Genomics;Guinea;Health Professional;Infectious disease threat;Infectious Diseases Research;Laboratories;Laboratory Diagnosis;laboratory experience;Lassa Fever;Malaria;Mali;member;Mentors;National Institute of Allergy and Infectious Disease;neglected tropical diseases;new outbreak;online course;pathogen;pathogenic virus;programs;Public Health;public health emergency;public health research;Public Health Schools;Qualifying;Research;Research Personnel;response;Science;Scientist;Side;skills;Student Selections;Students;technology/technique;Training;Training Programs;United States National Institutes of Health;Universities

PROJECT_TITLE: Mali-Guinea Emerging Infectious Disease Research Training Program (Mali-Guinea EID-RTP)

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AIDC-Z(55)]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Digestive Diseases;Esophageal Cancer;Genetics;Human Genome;Machine Learning and Artificial Intelligence;Prevention;Rare Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Human

ORG_CITY: TEMPE

ORG_DEPT: OTHER BASIC SCIENCES

ORG_NAME: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS

ORG_STATE: AZ

PHR: Narrative Precancerous conditions like Barrett’s esophagus transform into cancer through a process of evolution at the cell level. We propose to measure the rate of evolution in Barrett’s esophagus tissues and test if those rates predict which patients are likely to develop esophageal cancer.

PI_NAMEs: MALEY, CARLO  (contact)

PROGRAM_OFFICER_NAME: DIVI, RAO L

PROJECT_TERMS: Barrett Esophagus;Bayesian Analysis;Benign;Biological Markers;Biopsy;Cancer Patient;cancer risk;Cell model;Cells;Cessation of life;Classification;Clinic;Clinical;Clonal Expansion;cohort;Collection;Consensus;cost;Data;Decision Trees;Detection;Development;Diagnosis;Disease;Early Intervention;Epigenetic Process;Equilibrium;Esophageal Adenocarcinoma;Esophageal Tissue;Esophagectomy;Evolution;Future;Generations;Genes;Genetic;Genetic Models;genome sequencing;genome wide methylation;Genomics;Heritability;high risk;indexing;Individual;Intervention;Length;Life;Malignant neoplasm of esophagus;Malignant Neoplasms;Measures;Methylation;Modeling;Morbidity - disease rate;mortality risk;Mutation;Neoplasms;Outcome;overtreatment;Parameter Estimation;Pathway interactions;patient subsets;Patients;Persons;Phenotype;Phylogenetic Analysis;Phylogeny;Physicians;Population Genetics;Population Sizes;Precancerous Conditions;predictive modeling;premalignant;prevent;Process;Prospective cohort;random forest;Resources;Risk;Risk Assessment;risk stratification;Selection for Treatments;Signal Transduction;Single Nucleotide Polymorphism;standard of care;stem cell population;stem cells;Stress;Surface;System;Testing;Time;Tissues;tool;treatment response;Trees;tumor;tumor progression;whole genome

PROJECT_TITLE: Modeling Neoplastic Progression in Barrett's Esophagus - Renewal -2


NIH_SPENDING_CATS: Hematology;Kidney Disease;Osteoporosis;Rare Diseases;Sickle Cell Disease;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human

ORG_CITY: FARMINGTON

ORG_NAME: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

PHR: Project Narrative Sickle cell disease (SCD) is a hemoglobinopathy associated with severe bone abnormalities including osteoporosis, yet tragically, there are no effective therapies or confirmed mechanisms for SCD-associated bone disease. Since fibroblast growth factor 23 (FGF23) is increased in human anemia, and serum FGF23 and hypophosphatemia are increased in humanized Townes SCD mice (that are anemic but not in renal failure), we posit that FGF23 cross-talk involving bone, kidney, and blood contributes to osteoporosis in SCD mice. We will investigate the mechanism(s) and therapeutic potential of an FDA-approved FGF23 blocking antibody for treating SCD-associated bone disease.

PI_NAMEs: HURLEY, MARJA MARIE (contact)

PROGRAM_OFFICER_NAME: CHAN, KEVIN E

PROJECT_TERMS: absorption;Adult;Affect;Age;Anemia;Apoptosis;BFU-E;Biochemical;Blocking Antibodies;Blood;bone;Bone Density;Bone Diseases;Bone Infarction;bone loss;Bone Marrow;bone marrow hyperplasia;Bone Marrow Involvement;bone strength;bone turnover;Cell Cycle;Chronic;Data;Diphosphates;Dual-Energy X-Ray Absorptiometry;effective therapy;Erythrocytes;Erythroid;Erythroid Cells;Erythroid Progenitor Cells;Erythropoiesis;Erythropoietin;Etiology;Familial hypophosphatemic bone disease;FDA approved;fibroblast growth factor 23;Fibroblast Growth Factor Receptors;Future;Gender;General Population;Hematopoietic stem cells;Hemoglobinopathies;Hip region structure;Histologic;Homeostasis;Hormonal;Hormones;Human;Hypophosphatemia;Immunoglobulin G;Impairment;improved;In Vitro;in vivo;Inflammation;inorganic phosphate;Inorganic Phosphate Transporter;iron deficiency;Ischemia;Kidney;Kidney Failure;Mechanics;Menopausal Status;Messenger RNA;microCT;mineralization;Mitogen-Activated Protein Kinases;Molecular;Molecular Analysis;mouse model;Mus;Necrosis;neutralizing antibody;novel;osteoblast differentiation;Osteoblasts;Osteomalacia;Osteoporosis;Pathogenesis;Pathology;Patients;Phenotype;Physiologic calcification;prevent;Process;Production;progenitor;Proteins;Reporting;response;Risk Factors;RNA analysis;Role;Secondary to;Serum;Serum Markers;Sickle Cell;Sickle Cell Anemia;Signal Pathway;Signal Transduction;Sodium;sodium-phosphate cotransporter proteins;Stromal Cells;targeted treatment;Testing;Therapeutic;Urine;Vitamin D Deficiency;wasting

PROJECT_TITLE: Role of FGF23 in Bone, Kidney, Blood, Crosstalk in Sickle Cell Disease Mice

STUDY_SECTION: SBDD

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


NIH_SPENDING_CATS: Clinical Research;Infectious Diseases;Orphan Drug;Rare Diseases;Sexually Transmitted Infections;Urologic Diseases;Vector-Borne Diseases;Women's Health Research

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: Project Narrative The proposed research is relevant to public health because it addresses the unmet need for adequate treatment strategies for female genital schistosomiasis (FGS), which causes persistent genital mucosal disease in approximately 70% of women despite treatment with anti-schistosome praziquantel therapy. By identifying genital mucosal immune, epithelial, and viral alterations that persist after praziquantel therapy, we may identify novel therapeutic strategies that could include modifying the host mucosal immune response, promoting epithelial healing, and suppressing mucosal viral shedding. Therefore, this proposed research is relevant to the NIH's mission of fostering “innovative research strategies… for protecting and improving health,” as well as specifically responsive to the NIAID's goal to better understand and treat one of “the world's most intractable and wide-spread diseases,” with potential to improve the lives of millions of girls and women suffering from chronic FGS in Africa.

PI_NAMEs: DOWNS, JENNIFER ALZOS (contact)

PROGRAM_OFFICER_NAME: RAO, MALLA R

PROJECT_TERMS: Address;Affect;Africa;Aftercare;Age;Animals;Autopsy;Bladder;Brush Cell;Case Series;CD14 gene;CD3 Antigens;CD8B1 gene;cell type;Cells;Cervical;Chronic;chronic pain;cohort;Collecting Cell;cytokine;Cytometry;cytotoxic;Cytotoxic T-Lymphocytes;Data;Depressed mood;Disease;drug standard;egg;Enrollment;eosinophil;Epithelial Cells;Epithelium;Excretory function;experience;Female genitalia;female reproductive tract;Fibroblasts;Fibrosis;Flare;follow-up;Fostering;Frequencies;Functional disorder;Gene Expression;Genes;genital herpes;Genitalia;Genitourinary system;girls;Goals;Granuloma;healing;Health;Health Priorities;Helminths;Hemorrhage;Herpesviridae Infections;Hour;Human;Human Herpesvirus 2;Immune;immune function;Immune response;Immunity;immunoreaction;immunoregulation;Impaired healing;Impairment;improved;Infection;Infertility;innovation;Intervention;Knowledge;latent virus activation;Link;Macrophage;Magnetism;Matrix Metalloproteinases;metagenomic sequencing;migration;Mission;Molecular;Morbidity - disease rate;Mucosal Immune Responses;Mucosal Immunity;Mucous Membrane;Mus;National Institute of Allergy and Infectious Disease;neglected tropical diseases;neovascularization;new therapeutic target;novel;novel therapeutic intervention;Pain;Parasites;Pathology;Pathway interactions;Peptide Hydrolases;persistent symptom;Pharmacotherapy;Pilot Projects;Praziquantel;Predisposition;prevent;Proteins;Public Health;reactivation from latency;Recurrence;Reproductive Health;reproductive tract;Research;RNA purification;Schistosoma;Schistosoma haematobium;Schistosomiasis;seropositive;Signal Pathway;superinfection;Swab;Symptoms;Tanzania;Testing;Tight Junctions;Tissues;transcriptome;transcriptome sequencing;treatment strategy;trend;United States National Institutes of Health;Urine;Vagina;venule;Viral;virome;Virus;Virus Diseases;Virus Shedding;Virus-like particle;Widespread Disease;Woman;Women's cohort;Work;World Health Organization

PROJECT_TITLE: Genital Immune, Mucosal, and Viral Effects of Female Genital Schistosomiasis in Tanzania

STUDY_SECTION: CRFS

STUDY_SECTION_NAME: Clinical Research and Field Studies of Infectious Diseases Study Section[CRFS]


NIH_SPENDING_CATS: Biomedical Imaging;Cancer;Clinical Research;Immunotherapy;Orphan Drug;Rare Diseases;Skin Cancer

ORG_CITY: NEW HAVEN

ORG_NAME: YALE UNIVERSITY

PHR: Project Narrative This project is relevant to patients with melanoma and renal cell carcinoma who are being treated with immunotherapy. We will develop a non-invasive imaging strategy that can potentially determine who will respond to these treatments early in the course of therapy to spare non-responders from physical and financial toxicity.

PI_NAMEs: KLUGER, HARRIET M. (contact);MARQUEZ-NOSTRA, BERNADETTE

PROGRAM_OFFICER_NAME: WANG, YISONG

PROJECT_TERMS: Affect;Affinity;anatomic imaging;Antibodies;Antigens;Binding;Biodistribution;Biological Markers;biophysical chemistry;Biopsy;cancer cell;cancer imaging;Cd68;CD8-Positive T-Lymphocytes;CD8B1 gene;Cells;Chelating Agents;Clinical Trials;clinically relevant;clinically significant;Combination immunotherapy;Combined Modality Therapy;Complement;Cytotoxic agent;cytotoxic CD8 T cells;Cytotoxic T-Lymphocytes;Data;digital;Early treatment;financial toxicity;Foundations;Future;Goals;Image;imaging probe;Imaging Techniques;Immune;Immune system;Immunoglobulin G;immunological status;Immunophenotyping;Immunotherapy;In Situ;In Vitro;in vitro Assay;in vivo;Infiltration;Inflammatory;Isotopes;Macrophage;Macrophage Activation;Measures;Melanoma Cell;Metastatic Melanoma;Methods;Modeling;mouse model;Mus;Neoplasm Metastasis;non-invasive imaging;novel;Pathology;pathology imaging;Patients;predicting response;Prediction of Response to Therapy;preservation;Property;Radioimmunoconjugate;Radioisotopes;radioligand;Regimen;Renal Cell Carcinoma;Resistance;Resistance development;response;single photon emission computed tomography;Spatial Distribution;Specificity;subcutaneous;T-Lymphocyte;Techniques;Testing;Time;Tissues;tool;Toxic effect;treatment response;tumor;tumor microenvironment;Tumor-associated macrophages;uptake;Work

PROJECT_TITLE: Dual-isotope SPECT imaging and immunophenotyping of immune cells to determine response to immunotherapy

STUDY_SECTION: CONC

STUDY_SECTION_NAME: Clinical Oncology Study Section[CONC]


NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Clinical Research;Pediatric;Prevention

ORG_CITY: WEST LAFAYETTE

ORG_NAME: PURDUE UNIVERSITY

ORG_STATE: IN

PHR: Project Narrative This project will describe how developmental profiles of lexico-semantic skills in a diverse population of 18-42 month-old children relate language disorder and delay outcomes at 48 months. Therefore, this project has relevance for clinicians who are interested in early diagnosis of children at risk for later language impairments, and will contribute to our understanding of the roots and emergence of language disorders.

PI_NAMEs: BOROVSKY, ARIELLE  (contact)

PROGRAM_OFFICER_NAME: STORKEL, HOLLY LYNN

PROJECT_TERMS: Address;Affect;Age;Child;Clinical;Data;Development;Diagnostic;Early Diagnosis;early experience;Early identification;Environment;experience;Future;Goals;Graph;Growth;Health;improved;Individual;Individual Differences;Infant;insight;interest;Intervention;Knowledge;Language;Language Delays;Language Development;Language Development Disorders;Language Disorders;language impairment;language outcome;language processing;Lead;Learning;Learning Skill;lexical;Manuals;Maps;Measurement;Measures;Methodology;Modeling;novel;Nursery Schools;Outcome;Population Heterogeneity;prevent;Production;Productivity;Public Health;rapid growth;recruit;Reporting;Research;Research Personnel;response;Risk;Sampling;School-Age Population;Schools;Semantics;skills;social;specific language impairment;Structure;timeline;Toddler;Traction;verbal;visual tracking;Vocabulary;word learning

PROJECT_TITLE: Lexico-semantic abilities in early language growth and delay

STUDY_SECTION: LCOM

STUDY_SECTION_NAME: Language and Communication Study Section[LCOM]


ORG_CITY: OKLAHOMA CITY

ORG_NAME: OKLAHOMA CITY VA MEDICAL CENTER

ORG_STATE: OK

PHR: Project Narrative The national prevalence and mortality due to chronic liver diseases (CLDs) and hepatocellular carcinoma (HCC) in VA health care users have increased by approximately 3-fold during the last decade. Effective treatment for HCC represents unmet medical needs. Understanding the key mechanisms of liver disease progression to HCC will help develop effective treatments for these devastating diseases. This project will test the hypothesis that doublecortin-like kinase 1 (DCLK1)/β- catenin signaling axis is a key mediator of tumorigenesis and immune dysregulation in the tissue microenvironment of CLDs, which collectively stimulates the transformation of liver cells and modify innate immunity for supporting tumor growth. The proposed work will help define an attractive new anti-DCLK1 approach to prevent and treat HCC in US Veterans including the general public.

PI_NAMEs: HOUCHEN, COURTNEY WAYNE (contact)

PROJECT_TERMS: acute liver injury;Alcoholic Liver Diseases;Apoptosis;Automobile Driving;beta catenin;Binding;Biological Assay;cancer cell;Carbon Tetrachloride;Cells;chemotherapy;chronic liver disease;Chronic viral hepatitis;Cirrhosis;Clinical;Complex;cytokine;Cytoskeleton;Data;Deletion Mutation;Development;Diabetes Mellitus;Diethylnitrosamine;Disease;Disease Progression;effective therapy;Etiology;Fibrosis;Flow Cytometry;General Population;Goals;Healthcare;Healthcare Systems;Hepatic;Hepatitis B Vaccination;Hepatitis C Therapy;Hepatocyte;hepatoma cell;Heterogeneity;Histology;Immune;Immune response;immunoregulation;Immunosuppression;Immunotherapy;improved;in vivo;Incidence;Inflammation;Inflammatory;Inflammatory Response Pathway;inhibitor;Injury;Innate Immune Response;Interleukin-1 beta;Interleukin-10;Interruption;Intracellular Transport;Kupffer Cells;Liver;liver cancer model;Liver Cirrhosis;Liver diseases;Liver Fibrosis;liver injury;Liver neoplasms;Macrophage;Malignant neoplasm of liver;Malignant Neoplasms;Mediating;Mediator;Medical;Metabolic Diseases;Methods;Microtubules;Molecular Target;monocyte;mortality;mouse model;Mus;Mutation;Natural Immunity;neoplastic cell;nonalcoholic steatohepatitis;Nude Mice;Obesity;Oncogenic;Organ;overexpression;Parents;Pathway interactions;Patient-Focused Outcomes;Patients;phosphoproteomics;Phosphorylation;Phosphotransferases;Point Mutation;polarized cell;Prevalence;prevent;Prevention approach;Primary carcinoma of the liver cells;Process;Property;Proteins;Publishing;Radiation;Regulation;Reporting;Risk Factors;Role;screening;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Site;Solid Neoplasm;stemness;TCF7L2 gene;Testing;Tissues;TNF gene;Transplantation;treatment effect;tumor;tumor growth;tumor heterogeneity;Tumor Markers;tumor microenvironment;tumor xenograft;tumorigenesis;tumorigenic;Tumorigenicity;Unresectable;Veterans;Viral;Work;Xenograft Model

PROJECT_TITLE: Molecular targeting of DCLK1 signaling in hepatocellular carcinoma


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

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

PHR: PROJECT NARRATIVE This proposal investigates how related bacterial species, including the facultative intracellular pathogen Salmonella enterica serovar Typhimurium, deploy proteolysis as a significant virulence strategy. It aims to define how conserved proteins stimulate and inhibit proteolysis of substrates to achieve infection, as well as to identify the signals controlling expression of critical virulence determinants within and across species.

PI_NAMEs: GROISMAN, EDUARDO  (contact)

PROGRAM_OFFICER_NAME: ALEXANDER, WILLIAM A

PROJECT_TERMS: Achievement;Adaptor Signaling Protein;Amino Acid Sequence;antagonist;Antibiotic Resistance;antibiotic tolerance;ATP-Dependent Proteases;Bacteria;Bacteria sigma factor KatF protein;Bacterial Physiology;Behavior;Biological;Cells;Chimera organism;design;Disease;Disparate;endopeptidase La;Enteral;Enterobacteriaceae;Equilibrium;Escherichia coli;experience;experimental study;Gastroenteritis;Genes;Grant;Growth;Human;Infection;innovation;Kinetics;Knowledge;Macrophage;Mediating;Messenger RNA;Microbe;Molecular Chaperones;Mus;Natural History;natural resistance-associated macrophage protein 1;new therapeutic target;novel;novel therapeutic intervention;pathogen;Pathogenesis;Peptide Hydrolases;Physiological;Play;Polymyxin B;prevent;programs;protein degradation;Proteins;Proteolysis;Research;Resistance;RNA;Role;Salmonella typhimurium;Sigma Factor;Signal Transduction;Specificity;Starvation;Stress;Testing;Tissues;Typhoid Fever;Virulence;Virulence Factors;virulence gene;Yersinia pestis

PROJECT_TITLE: How Regulated Proteolysis Controls Bacterial Virulence

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-AIDC-A(06)]


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

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: PROJECT NARRATIVE  Olfactory dysfunction is often a first symptom of several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. A better understanding of the basic neural circuitry and functional properties of the olfactory system may provide clues to the etiology of these diseases, as well as potential diagnostic mechanisms.

PI_NAMEs: ZAK, JOSEPH DONALD (contact)

PROGRAM_OFFICER_NAME: SABRI, MERAV

PROJECT_TERMS: Acute;Advisory Committees;Alzheimer's Disease;Animals;Area;awake;Award;Axon;Back;Behavioral;Brain;calcium indicator;Cells;Central Nervous System;Classification;Complex;Complex Mixtures;Detection;Development;Diagnostic;Disease;Environment;Etiology;experience;experimental study;Feedback;Future;Genetic;Goals;granule cell;in vivo;Individual;innovation;insight;Interneurons;Ion Channel Gating;Laboratories;Learning;light gated;Measurement;Measures;Mediating;Mentors;Modality;Modification;multiphoton microscopy;Mus;nerve supply;neural circuit;Neurodegenerative Disorders;Neurons;Neurosciences;novel;novel strategies;Odors;olfactory bulb;Olfactory dysfunction;Olfactory Pathways;Optics;optogenetics;Outcome;Outcome Study;Output;Parkinson Disease;Pattern;Phase;Physiological;piriform cortex;Play;Population;Positioning Attribute;postsynaptic;Process;Property;Research Personnel;response;Rewards;Role;Scheme;Sensory;sensory input;sensory stimulus;sensory system;Shapes;Site;Stimulus;Symptoms;Synapses;Technical Expertise;Testing;Training;Universities;Update;Vision;Weight;Work

PROJECT_TITLE: Learning-mediated plasticity in cortical feedback projections to the olfactory bulb

STUDY_SECTION: CDRC

STUDY_SECTION_NAME: Communication Disorders Review Committee[CDRC]


ED_INST_TYPE: SCHOOLS OF VETERINARY MEDICINE

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Emerging Infectious Diseases;Infectious Diseases;Rare Diseases;Vector-Borne Diseases

ORG_CITY: FORT COLLINS

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: NARRATIVE Aedes aegypti is the primary mosquito vector that transmits the arboviruses, dengue, Zika, chikungunya and yellow fever in the Western Hemisphere. These studies will identify biochemical pathways that change in the mosquito following infection with these viruses. They will also identify how the endosymbiont Wolbachia used to control virus transmission in Aedes aegypti may be metabolically competing with the virus. Identifying the biochemical pathways that are integral to mosquito biology and to transmission of these viruses provide a novel avenue to interfere with vector transmission of the virus.

PI_NAMEs: PERERA, RUSHIKA  (contact)

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Acute;Aedes;antagonist;Arboviruses;Bacteria;Biochemical Pathway;Biological;Biology;Blood Vessels;Cell Culture Techniques;Chikungunya fever;Choking;Country;Culicidae;Dengue Fever;Dengue Hemorrhagic Fever;Dengue Shock Syndrome;Dengue Virus;density;disease transmission;endosymbiont;Energy Metabolism;Ensure;Environment;Event;Extravasation;Family;Fever;fitness;Flaviviridae;Foundations;Genome;Geographic Distribution;Heritability;Human;In Vitro;Infection;Insecta;Insecticide Resistance;Life;Life Cycle Stages;Link;lipid biosynthesis;Lipids;Lipolysis;Maintenance;Marketing;Measures;Mediating;Membrane;Metabolic;Metabolic Pathway;metabolic phenotype;Metabolism;metabolome;Midgut;mitochondrial metabolism;Modeling;Nature;novel;novel strategies;Nutrient;Parasites;pathogen;Pathway interactions;permissiveness;Persons;Phenotype;Population;pressure;Refractory;Resistance development;Resources;Risk;RNA Viruses;Serotyping;Site;Sphingolipids;Structure;success;symbiont;Syndrome;Therapeutic;Tissues;Translations;transmission process;Vaccinee;Vaccines;vector;vector competence;vector mosquito;vector transmission;Vectorial capacity;Viral;Viral Load result;Viral Physiology;Viral Proteins;viral resistance;viral transmission;Virion;Virus;Virus Replication;Wolbachia;Work;World Health Organization;Yellow Fever;zika fever

PROJECT_TITLE: Metabolic basis of mosquito-endosymbiont-virus interactions

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


ADMINISTERING_IC: HL

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Cardiovascular;Heart Disease

ORG_CITY: CHICAGO

ORG_DEPT: PATHOLOGY

ORG_NAME: NORTHWESTERN UNIVERSITY AT CHICAGO

PHR: Project Narrative Despite the prevalence of heart failure with preserved ejection fraction (HFpEF), existing therapies are ineffective and demonstrate the desperate need for a novel therapeutic target. This project aims to understand how the macrophage anti-inflammatory receptor MerTK may be driving HFpEF, as patients present with elevated serum levels of soluble Mer. Specifically, how MerTK signaling may promote upregulation of fibrotic pathways within cardiac macrophages and how this can be targeted to ameliorate disease will be explored.

PI_NAMEs: FILIPP, MALLORY  (contact)

PROGRAM_OFFICER_NAME: HUANG, LI-SHIN

PROJECT_TERMS: Affect;Anti-Inflammatory Agents;Apoptotic;arm;Automobile Driving;Biopsy;Blood;Cardiac;Cardiac Myocytes;cardiac repair;cardioprotection;Cell Survival;Cells;Cellular Stress;Characteristics;Chronic;chronic inflammatory disease;Classification;Clinic;Clinical;Collaborations;comorbidity;coronary fibrosis;cytokine;Data;Defect;Development;Diabetes Mellitus;Disease;driving force;E-Selectin;Echocardiography;effective therapy;EFRAC;Endothelial Cells;Engineering;Epidemic;exercise intolerance;Failure;Family;Fatigue;Fatty acid glycerol esters;Fibrosis;Functional disorder;Gene Expression;Generations;Genetic Transcription;Heart;Heart failure;heart failure with reduced ejection fraction;Homeostasis;Hypertension;Impairment;In Vitro;in vivo;Incidence;Individual;ineffective therapies;Inflammation;Inflammatory;Innate Immune System;insight;ischemic injury;Knock-out;Left;Left ventricular structure;Leukocytes;Lipids;Liquid substance;Macrophage;Macrophage Activation;Metabolic syndrome;migration;Molecular;monocyte;mortality;mouse model;Mus;Myelogenous;Myocardial dysfunction;Myocardium;new therapeutic target;Nitric Oxide;nitrosative stress;Obesity;Pathway interactions;Patients;Peptide Hydrolases;Phagocytosis;Phase;Plasma;Play;preservation;Prevalence;prevent;Prevention;Production;profibrotic cytokine;Proteins;Reactive Oxygen Species;receptor;Relaxation;Resistance;Resolution;response;Risk Factors;Role;Secondary to;Serum;Signal Pathway;Signal Transduction;single-cell RNA sequencing;small molecule inhibitor;Stress;Subcategory;Symptoms;Syndrome;systemic inflammatory response;targeted treatment;Testing;therapeutic evaluation;therapeutic target;Tissues;transcriptional reprogramming;Transforming Growth Factor beta;Treatment Failure;Up-Regulation;uptake;Validation;Vascular Cell Adhesion Molecule-1;Ventricular;Ventricular Remodeling

PROJECT_TITLE: MerTK as a new target to understand and ameliorate HFpEF


NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Bioengineering;Biotechnology;Emerging Infectious Diseases;Genetics;Immunization;Infectious Diseases;Influenza;Networking and Information Technology R&D (NITRD);Pneumonia and Influenza;Prevention;Vaccine Related

ORG_CITY: CAMBRIDGE

ORG_COUNTRY: UNITED KINGDOM

ORG_FIPS: UK

ORG_NAME: UNIVERSITY OF CAMBRIDGE

ORG_ZIPCODE: CB2 1TN

PHR: PROJECT NARRATIVE Since 1968, there has, on average every three years, been a vaccine mismatch for A/H3N2 due to antigenic evolution between the time of vaccine strain selection and the following influenza season when the vaccine is used. In the proposed work we test the “fitness exchange” hypothesis as the underlying mechanism of seasonal influenza virus evolution. Further we build a prediction framework that integrates empirical and computation data in a way that can directly inform the vaccine strain selection process, offering the possibility to see into the evolutionary future of the virus and make vaccine strain selection decisions informed by this information. This work is not solely judging the relative fitness of existing viruses, but is generating and testing viruses that have yet to evolve.

PI_NAMEs: SMITH, DEREK JAMES (contact)

PROGRAM_OFFICER_NAME: BOZICK, BROOKE ALLISON

PROJECT_TERMS: Affect;Amino Acid Substitution;Amino Acids;Antibodies;Area;Binding Sites;Biological Assay;Codon Nucleotides;Computer Models;computerized tools;cost;Data;data integration;data streams;Development;Disease;Evolution;fitness;fitness test;Future;Genetic;Genetic Variation;Goals;Growth;Hemagglutinin;Human;Immune;Immunity;improved;In Vitro;Influenza;Influenza A virus;Influenza A Virus, H3N2 Subtype;influenza virus vaccine;influenzavirus;Investigation;Laboratories;Maps;Measurement;Measures;Methods;Modeling;Modernization;Molecular;Molecular Evolution;mutant;Mutation;Nature;neutralizing antibody;novel;Pattern;Phenotype;Population;Positioning Attribute;Process;Proteins;receptor binding;Recommendation;Resolution;Resources;response;Risk Reduction;RNA Viruses;sample fixation;seasonal influenza;Seasons;Serology;Site;Statistical Models;Surface;Testing;Time;transmission process;Use Effectiveness;Vaccination;vaccine candidate;vaccine effectiveness;Vaccines;Variant;Viral;Virus;virus testing;Work

PROJECT_TITLE: Integrating measurements of immune escape and in vitro replication with computational models to understand and predict the antigenic evolution of seasonal A/H3N2 influenza viruses


NIH_SPENDING_CATS: Biotechnology;Cancer;Cancer Genomics;Childhood Leukemia;Clinical Research;Clinical Trials and Supportive Activities;Genetics;Hematology;Human Genome;Orphan Drug;Pediatric;Pediatric Cancer;Rare Diseases

ORG_CITY: PHILADELPHIA

ORG_NAME: CHILDREN'S HOSP OF PHILADELPHIA

PHR: Project Narrative Children and young adults with T-cell lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T- LL) are usually treated the same. We have new data from clinical trials showing that T-ALL and T-LL patients respond differently to glucocorticoids and proteasome inhibitors. We need to understand why they responded differently so we can develop better treatments and cure more patients.

PI_NAMEs: HERMISTON, MICHELLE L.;HORTON, TERZAH M;TEACHEY, DAVID T. (contact);WOOD, BRENT L

PROGRAM_OFFICER_NAME: AGRAWAL, LOKESH

PROJECT_TERMS: Acute T Cell Leukemia;Adrenal Cortex Hormones;Architecture;arm;Automobile Driving;Award;Biological;Biological Factors;Biology;Bone Marrow;Bortezomib;cancer cell;Cells;chemotherapy;Child;Clinical;Clinical Data;Clinical Trials;cohort;comparison group;Cranial Irradiation;CRISPR/Cas technology;Cytotoxic Chemotherapy;Data;data integration;Data Set;differential expression;Disease;Disease-Free Survival;Drug resistance;exome sequencing;Flow Cytometry;Genes;Genome;genome sequencing;genomic data;genomic profiles;genomic profiling;Genomics;Germ Lines;Glucocorticoids;Goals;heat-shock factor 1;high risk;improved;improved outcome;inhibitor;innovation;International;lead candidate;leukemia treatment;leukemia/lymphoma;leukemogenesis;Lymphoblastic Leukemia;Lymphoblastic Lymphoma;Marrow;next generation;novel;novel therapeutics;Outcome;Pathway interactions;patient derived xenograft model;Patients;Pediatric Oncology Group;Phase III Clinical Trials;phase III trial;Positioning Attribute;prophylactic;Proteasome Inhibitor;Proteins;Proteome;proteomic signature;Proteomics;Randomized;Relapse;relapse patients;relapse risk;Resistance;resistance factors;response;Risk;Sampling;single cell genomics;single-cell RNA sequencing;Slide;small molecule inhibitor;Steroid Resistance;Steroids;T-Lymphocyte;Testing;Time;Tissues;transcriptome;transcriptome sequencing;transcriptomic profiling;transcriptomics;treatment response;tumor;Vertebral column;whole genome;young adult

PROJECT_TITLE: Improving risk allocation and developing novel therapies for children with T-ALL and T-LL

STUDY_SECTION: DT

STUDY_SECTION_NAME: Developmental Therapeutics Study Section[DT]


NIH_SPENDING_CATS: Atherosclerosis;Cardiovascular;Clinical Research;Heart Disease;Heart Disease - Coronary Heart Disease;Prevention

ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

ORG_STATE: CA

PHR: There are an estimated 310,000 sudden deaths from heart disease in the United States each year. These deaths are the result of a fatal heart rhythm disturbance most often occurring in patients with underlying coronary artery disease who do not have evidence for severe heart damage. The present study aims to more accurately identify people who are at risk for developing life-threatening heart rhythm disturbances using blood tests and electrocardiograms (ECGs) so that we can intervene and prevent these sudden deaths.

PI_NAMEs: ALBERT, CHRISTINE M (contact);CHENG, SUSAN ;COOK, NANCY R

PROGRAM_OFFICER_NAME: TINSLEY, EMILY

PROJECT_TERMS: Accounting;Address;adjudication;advanced analytics;Area;Arrhythmia;base;Biological Assay;Biological Markers;Blood Platelets;Blood Tests;Cardiac;Cardiac Death;Cause of Death;Cessation of life;Clinical;clinically relevant;cohort;Cohort Studies;Collaborations;Coronary Arteriosclerosis;Coronary heart disease;cost effective;cost efficient;Data;design;Development;Dimensions;Disease Outcome;Eicosanoids;Electrocardiogram;Event;Fatty Acids;follow-up;Functional disorder;Funding;General Population;Genetic;genome-wide;Genotype;Goals;heart damage;Heart Diseases;heart rhythm;high risk;Image;Implantable Defibrillators;improved;Individual;Inflammatory;Infrastructure;innovation;insight;Intervention;Investments;Knowledge;Left Ventricular Ejection Fraction;Life;Life Expectancy;Machine Learning;machine learning method;Methods;Modeling;Molecular Profiling;mortality;mortality risk;multimodal data;multimodality;National Heart, Lung, and Blood Institute;neglect;novel;novel strategies;Pathway interactions;Patients;Persons;Phenotype;Population;Populations at Risk;Positioning Attribute;predictive modeling;prevent;Prevention;Prevention Research;Primary Prevention;Procedures;Prospective Studies;Prospective, cohort study;Proteins;Proteomics;Public Health;randomized trial;Research Personnel;Resources;Resuscitation;retention rate;Risk;Risk Marker;risk prediction;risk prediction model;risk stratification;Sudden Death;Therapeutic;Time;tool;United States;Validation;Ventricular Arrhythmia;Ventricular Fibrillation;Ventricular Tachycardia;Work

PROJECT_TITLE: PRE-DETERMINE: Advancing Sudden Arrhythmic Death Prediction in Coronary Artery Disease in the Absence of Severe Systolic Dysfunction

STUDY_SECTION: CCHS

STUDY_SECTION_NAME: Clinical Integrative Cardiovascular and Hematological Sciences Study Section[CCHS]


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

NIH_SPENDING_CATS: Genetics;Human Genome;Stem Cell Research;Stem Cell Research - Embryonic - Non-Human

ORG_CITY: BOSTON

ORG_DEPT: DENTISTRY

ORG_NAME: HARVARD MEDICAL SCHOOL

PHR: PROJECT NARRATIVE Imprinting disorders are rare epigenetic disorders that encompass multiple tissues and many of them lead to growth, endocrine and neurological defects with lasting affects during the lifespan of the affected individual. Knowledge obtained from the studies described herein may help inform the design of novel therapeutic and diagnostic approaches for these disorders.

PI_NAMEs: KOTA, SATYA K. (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: 14q32;Affect;Alleles;autosome;Bioinformatics;Biotin;Biotinylation;Cells;Chimeric Proteins;Chromosomes;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;CRISPR/Cas technology;Data;Defect;design;Development;diagnostic strategy;Disease;DNA Methylation;DNA Sequence;dosage;Elements;Embryo;embryo tissue;Embryonic Development;embryonic stem cell;Endocrine;Enhancers;Epigenetic Process;epigenome editing;Evaluation;experience;Gametogenesis;Gene Expression;Gene Expression Profile;Generations;Genes;Genome;genome editing;Genomic Imprinting;Genotype;Growth;Health;Homeostasis;Human;Human Chromosomes;human model;Hybrids;imprint;Individual;Knowledge;Label;Lead;life span;Ligase;Maintenance;mammalian genome;Mammals;Mass Spectrum Analysis;maternal imprint;Maternal uniparental disomy;Methodology;Methylation;Modeling;Molecular;Mus;mutant;Names;Nature;Neurologic;novel diagnostics;novel therapeutics;Parents;paternal imprint;Paternal uniparental disomy;Pathologic;Pattern;Play;Postembryonic;Process;protein complex;Protein Dynamics;Protein Region;Proteins;Proteome;Proteomics;Rare Diseases;recruit;Regulation;Research;Research Personnel;Research Proposals;RNA;Role;stem cell model;Structure;Syndrome;Technology;Testing;Tissues;Training;Transgenic Organisms;Uniparental Disomy;Untranslated RNA;X Inactivation

PROJECT_TITLE: Systematic elucidation of allele specific proteome at Imprint Control Regions

STUDY_SECTION: GHD

STUDY_SECTION_NAME: Genetics of Health and Disease Study Section[GHD]


NIH_SPENDING_CATS: Aging;Kidney Disease

ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: PROJECT NARRATIVE The objective of this application is to examine the novel working hypothesis that CX3CL1 signaling pathway is specifically required for RMs (CX3CR1 positive) longevity, fate, dynamics, and immune metabolic responses under normal conditions during the aging process and pathologic conditions. Successful completion of these Aims will advance our understanding of tissue macrophage biology, and specifically of renal macrophages. This will allow for improved design and development of therapeutics for kidney diseases that block or induce specific signaling pathways.

PI_NAMEs: QIN, XUEBIN  (contact)

PROJECT_TERMS: Ablation;Acute;Address;Adult;Age;aged;aging process;Antibodies;Binding;Biological;Biology;Birth;Bone Marrow;Brain;Cell surface;Cells;Coculture Techniques;Complement;Cre driver;CX3CL1 gene;design;Development;Disease;Embryo;Epithelial Cells;Fetal Liver;Flow Cytometry;Fluorescence;Fractalkine;Genetic Recombination;Glomerulonephritis;Homeostasis;Human;Immune;Immunologic Surveillance;improved;In Vitro;inducible Cre;Injections;Kidney;Kidney Diseases;Knock-out;Label;Leukocytes;Liver;Longevity;Lung;Macrophage;Maintenance;Mediating;Membrane;Metabolic;metabolic profile;Modeling;Molecular;monocyte;Mus;Myeloid Cells;Natural regeneration;novel;old mice;Pathologic;Peripheral;Population;Property;Protein Isoforms;PTPRC gene;Renal function;renal ischemia;Renal Tissue;repaired;Reperfusion Injury;Reporter;Reporting;response;Role;Serum;Signal Pathway;Signal Transduction;single-cell RNA sequencing;Stains;Streptococcus intermedius;System;Testing;therapeutic development;Tissues;Toxin;Transgenic Organisms;Tubular formation;Yolk Sac

PROJECT_TITLE: Renal Macrophage Biology

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1-IDIA-D(90)]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Clinical Research;Genetics;Hematology;Human Genome;Immunotherapy;Lymphatic Research;Lymphoma;Microbiome;Nutrition;Orphan Drug;Precision Medicine;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: Project Narrative Diffuse large B-cell lymphoma (DLBCL), the most common aggressive B cell lymphoma, is a significant clinical problem, with only 60% of patients cured; how lymphoma cells evade host defenses is poorly understood. Growing evidence suggests that gut microbiota play important roles in regulating immunity and that diversity and species of gut bacteria may impact the response to treatment. The proposed study is the first large scale prospective and longitudinal evaluation of the relationship between the gut microbiota in DLBCL, systemic immunity, and treatment response; if successful this research will uncover a new minimally toxic therapeutic paradigm, which will profoundly impact clinical care for lymphoma patients.

PI_NAMEs: DIEFENBACH, CATHERINE SIBYL (contact)

PROGRAM_OFFICER_NAME: FILIPSKI, KELLY

PROJECT_TERMS: adaptive immunity;Adriamycin PFS;anti-tumor immune response;Antibiotics;antigen-specific T cells;B-Cell Lymphomas;Behavior;Biological;Blood;Blood specimen;CD14 gene;Cells;Chronic;Chronology;Clinical;clinical care;Communities;Cyclophosphamide;cytokine;Data;Detection;Development;Diagnosis;Diet;dietary;Disease-Free Survival;Etiology;Evaluation;experimental study;Failure;Family;fecal transplantation;Feces;follow-up;Functional Imaging;Future;Goals;Growth;gut bacteria;gut microbiome;gut microbiota;Hodgkin Disease;Homeostasis;Host Defense;Human;Immune;immune activation;Immune checkpoint inhibitor;Immune system;Immunity;Immuno-Chemotherapy;immunoregulation;Immunotherapy;improved;Inferior;innovation;insight;Intervention;Investigation;large cell Diffuse non-Hodgkin's lymphoma;Lead;Link;lipopolysaccharide-binding protein;Lipopolysaccharides;Lymphoma;Lymphoma cell;Malignant Neoplasms;Mathematics;Measurement;Mediator;Medical;Metagenomics;Methodology;Methods;Microbe;microbial;microbial based therapy;microbial composition;microbial products;microbiome signature;microbiota;microbiota composition;microbiota profiles;Mus;Myeloid Cells;Natural Immunity;neoplastic cell;novel;Organism;Outcome;Pathway interactions;Patients;Peptides;personalized therapeutic;PET/CT scan;Pharmaceutical Preparations;Phenotype;Play;Population;Prednisone;probiotic therapy;prospective;protein biomarkers;Research;response;rituximab;Role;Sampling;Shotgun Sequencing;Solid Neoplasm;stool sample;Structure;Supportive care;T memory cell;T-Lymphocyte;targeted treatment;Taxon;temporal measurement;Testing;Therapeutic;therapy outcome;Time Series Analysis;Transcript;treatment duration;Treatment Failure;Treatment outcome;treatment response;Vincristine;Work

PROJECT_TITLE: A prospective evaluation of the gut microbiome as a mediator of lymphoma treatment outcome and systemic immunity

STUDY_SECTION: CHSB

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