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

ORG_CITY: BERKELEY

ORG_DEPT: NEUROSCIENCES

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative The proposed project will investigate tertiary sulci — the smallest and latest-developing cortical indentations — in aging and Alzheimer’s disease (AD). While large-scale atrophy patterns in aging and AD are established, fundamental mechanisms underlying individual differences in regional vulnerability and associations between AD pathology and degeneration have not been fully ascertained, and sulcal anatomy has been proposed as an avenue to explore these individual structural differences. This study will probe whether tertiary sulci can serve as structural markers of early degenerative and pathological changes, providing insight into relationships between atrophy, pathology, and cognitive changes in the aging brain from a novel anatomical resolution.

PI_NAMEs: MABOUDIAN, SAMIRA ALESSANDRA (contact)

PROGRAM_OFFICER_NAME: SARE, RACHEL

PROJECT_TERMS: abeta accumulation;abeta deposition;Adult;Affect;Age;age related;Aging;aging brain;aging mechanism;aging related;Alzheimer's Disease;Alzheimer's disease pathology;Amyloid beta-Protein;Anatomy;Architecture;Area;Atrophic;Behavioral;Biometry;Brain;brain metabolism;Brain region;career;career development;Cognition;Cognitive;cognitive change;cognitive development;cognitive neuroscience;Collaborations;Communication;Data Analyses;Dementia;Development;Disease;early onset;Educational process of instructing;emerging adult;Ensure;Environment;Evolution;executive function;Fellowship;Foundations;Frontotemporal Dementia;Functional disorder;Genetic Variation;Global Change;glucose metabolism;Goals;Hippocampus;imaging biomarker;imaging modality;Impaired cognition;Individual;Individual Differences;insight;Investigation;Label;Lateral;Life;Link;Magnetic Resonance Imaging;Manuals;Measures;Medial;Mediating;Memory;Mentorship;Metabolic;metabolic rate;Metabolic stress;Metabolism;Methods;Modeling;Morphology;MRI Scans;multimodal neuroimaging;Nerve Degeneration;neural;Neuroanatomy;Neurobehavioral Manifestations;neuroimaging;neuropathology;Neurosciences;novel;older adult;Onset of illness;Parietal;Parietal Lobe;Participant;Pathologic;Pathology;Pattern;Positron-Emission Tomography;Postdoctoral Fellow;Predisposition;Prefrontal Cortex;prevent;Process;regional atrophy;Research;Resolution;Role;Scanning;Schizophrenia;skills;statistics;Structure;Symptoms;tau Proteins;Techniques;theories;Thick;Thinness;Training;Work;young adult

PROJECT_TITLE: Relationships between sulcal morphology, neuropathology, and cognition in aging and Alzheimer's disease


ADMINISTERING_IC: AI

ARRA_FUNDED: N

ED_INST_TYPE: EARTH SCIENCES/RESOURCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Biodefense and Related Countermeasures;Digestive Diseases;Emerging Infectious Diseases;Foodborne Illness;Genetics;Infectious Diseases;Liver Disease;Microbiome;Rare Diseases

ORG_CITY: RIVERSIDE

ORG_COUNTRY: UNITED STATES

ORG_DEPT: OTHER BASIC SCIENCES

ORG_FIPS: US

ORG_NAME: UNIVERSITY OF CALIFORNIA RIVERSIDE

ORG_STATE: CA

PHR: Project Narrative  Millions of people globally contract the diarrheal pathogen V. cholerae annually. Susceptibility to V. cholerae is mediated in part by resident gut microbes. The function and diversity of these microbial communities are in turn determined by viruses (bacteriophages). These studies will evaluate the contribution of a bacteriophage to alter microbial metabolisms that can alter V. cholerae infection, facilitating the development of new therapeutic approaches.

PI_NAMEs: DEGNAN, PATRICK H (contact);HSIAO, ANSEL

PROGRAM_OFFICER_NAME: ZEITUNI, AMIR E

PROJECT_TERMS: Acids;Address;Affect;Amino Acids;antagonist;Antibiotic Resistance;Automobile Driving;Bacteria;Bacteriophages;Behavior;bile acid metabolism;Bile Acids;Bile fluid;bile salts;Cell Separation;Cholera;colonization resistance;commensal bacteria;Communicable Diseases;Communities;Complex;Contracts;Development;Diarrhea;diarrheal disease;DNA;Engineering;Enzymes;Etiology;Event;experimental study;gastrointestinal;gastrointestinal infection;Gastrointestinal tract structure;Gene Expression;Genes;Genetic Determinism;genome sequencing;Germ-Free;Glycocholic Acid;gut bacteria;gut microbes;gut microbiota;Health;Horizontal Gene Transfer;Human;Hydrolase;in vivo;Infection;insight;Intervention;Invaded;Lead;liquid chromatography mass spectrometry;Lysogeny;Mediating;member;Metabolic;Metabolism;microbial;microbial community;microbiota;microorganism;Modification;Mus;Mutagenesis;novel;novel therapeutic intervention;nutrition;Outcome;pathogen;pathogenic microbe;Pathogenicity;personalized intervention;personalized medicine;Persons;Phenotype;Play;Population;Predisposition;Process;prophylactic;Proteins;Regulon;Reporter;Repression;Research;Resistance;resistance factors;Resistance to infection;Role;Sensory;Structure;Taurocholic Acid;Testing;Time;Tissue-Specific Gene Expression;trait;transcriptome;transcriptome sequencing;Tryptophan;Up-Regulation;Vibrio cholerae;Vibrio cholerae infection;Viral;Virulence;Virulence Factors;virulence gene;Virus;Work

PROJECT_TITLE: Phage mobilization and microbiota dynamics driving colonization resistance to Vibrio cholerae invasion

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 IMII-U (01)]


ADMINISTERING_IC: AG

ED_INST_TYPE: SCHOOLS OF MEDICINE

FUNDING_MECHANISM: TRAINING, INDIVIDUAL

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: LOS ANGELES

ORG_DEPT: PATHOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: PROJECT NARRATIVE Older adults have increased rates of infections and cancers due to declining immune function, which is likely due to alterations in T cell progenitors and inflammatory signaling pathways in the aged microenvironment. We will investigate the causes of T cell decline with age using a newly described mutant mouse model and a novel, in vitro Artificial Thymic Organoid system, which reproducibly produces all stages of T cell development from a single stem cell. Our proposed studies will provide insights into the aging immune system and inform future therapies for regenerative medicine and age-related diseases.

PI_NAMEs: GENSHEIMER, JULIA  (contact)

PROGRAM_OFFICER_NAME: TILAHUN, MULUALEM ENYEW

PROJECT_TERMS: Acceleration;Address;Adipocytes;Affect;Age;age related decline;age-related disease;aged;Aging;anti aging;Appearance;Atrophic;Automobile Driving;Binding;Biological Assay;bone aging;Bone Marrow;Cell Count;Cells;Common Lymphoid Progenitor;Communication;cytokine;Data;Data Analyses;Defect;Degenerative polyarthritis;Development;Dissection;Engraftment;Environment;Excision;Exhibits;Experimental Designs;Female;Frequencies;Future;Gays;Gene Expression;Gene Expression Profile;glycoprotein 130;hematopoietic stem cell aging;Hematopoietic Stem Cell heterogeneity;Hematopoietic stem cells;hematopoietic transplantation;human data;IL6ST gene;immune function;Immune system;Impairment;improved;In Vitro;in vitro Model;in vivo;Infection;infection rate;Inflammatory;insight;Interleukin-6;Interleukin-6 Receptor Alpha Subunit;Investigation;irradiation;Kinetics;Laboratories;Lymphoid;male;Malignant Neoplasms;MAP Kinase Gene;Measures;Mediating;Mentorship;Methods;Modality;Modeling;mouse model;Mus;Musculoskeletal;mutant;mutant mouse model;Mutant Strains Mice;Myelogenous;Myeloid Cells;novel;older adult;Organ;Organoids;Output;Pathway interactions;peripheral blood;Phenotype;Physicians;Population;Predisposition;Process;Production;progenitor;receptor;Receptor Signaling;recruit;regenerative;Regenerative Medicine;regenerative therapy;Rejuvenation;Reproducibility;Role;Scientist;Signal Pathway;Signal Transduction;single-cell RNA sequencing;skills;Skin;stem cell population;stem cells;Stromal Cells;Synovial Membrane;System;T-Cell Development;T-Lymphocyte;Testing;thymocyte;Thymus Gland;tool;Training;transcriptome sequencing;transplant model;Transplantation;Tyrosine;Vaccination;Work;Wound models

PROJECT_TITLE: Role of interleukin-6 signaling on T cell potential of aged hematopoietic stem cells and thymic progenitors

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07B-G (20)]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

NIH_SPENDING_CATS: Bioengineering;Cardiovascular;Coronaviruses;Coronaviruses Therapeutics and Interventions;Emerging Infectious Diseases;Hematology;Infectious Diseases;Prevention;Sepsis

ORG_CITY: ATHENS

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF GEORGIA

ORG_STATE: GA

PHR: PROJECT NARRATIVE The ideal antibacterial and hemocompatible surface would prevent platelet adhesion and activation, thrombosis, and microbial biofilm formation. This research project will develop and evaluate the synergistic effects of S- nitrosothiol functionalized antibiotics to prevent platelet activation/adhesion and provide antimicrobial activity, thereby solving major clinical problems associated with extracorporeal circuit (ECC) applications and enabling successful ECC without heparinization.

PI_NAMEs: BRISBOIS, ELIZABETH JOY;HANDA, HITESH  (contact)

PROGRAM_OFFICER_NAME: GOLDBERG, ILANA GRACE

PROJECT_TERMS: Acetylcysteine;Address;Adhesions;Ampicillin;analytical method;Anti-Bacterial Agents;Antibiotics;Anticoagulation;antimicrobial;Antimicrobial Effect;Attention;Bacteremia;Bacteria;Bacterial Infections;bactericide;Binding;Biocide;Bioreactors;Blood;Blood Coagulation Disorders;Blood Platelets;Blood Vessels;Blood-Borne Pathogens;Candida albicans;Cannulas;Catheters;Cell Line;Cells;Clinical;clinical application;clinical development;Coagulase;Coagulation Process;combat;Combined Antibiotics;Complication;COVID-19;COVID-19 pandemic;COVID-19 patient;Critical Illness;Data;Devices;early phase clinical trial;Embolism;Ensure;Exhibits;Extracorporeal Circulation;Extracorporeal Membrane Oxygenation;Generations;Goals;Heart failure;Hematological Disease;hemocompatibility;Hemodialysis;Hemorrhage;Heparin;high risk;Immobilization;improved;In Vitro;in vitro Bioassay;Individual;Infection;infection rate;Lead;Legal patent;Life;Measures;Mechanical ventilation;Mechanics;Medical;Microbial Biofilms;Modeling;Modification;N-acetylpenicillamine;Nitric Oxide;Nitric Oxide Donors;Nosocomial Infections;Obstruction;Oryctolagus cuniculus;Oxygenators;Patient Admission;Patient Care;Patients;Platelet Activation;Polymers;prevent;Prevention;Property;Pseudomonas aeruginosa;Pulmonary Thromboembolism;Reporting;Research Project Grants;Respiratory Failure;Risk;S-Nitrosothiols;Safety;Sepsis;Staphylococcus aureus;Staphylococcus epidermidis;Sterilization;success;Surface;System;Technology;Testing;thrombogenesis;Thrombophilia;Thrombosis;Thrombus;Translations;Tube;Vascular Endothelial Cell;Work

PROJECT_TITLE: Nitric Oxide Functionalized Antibiotics to Combat Infections and Thrombosis for Extracorporeal Life Support

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BBBT-X (83)]


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

ORG_CITY: Newark

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: RUTGERS BIOMEDICAL AND HEALTH SCIENCES

ORG_STATE: NJ

PHR: PROJECT NARRATIVE Drug tolerance, a non-heritable, reversible state of slow growth which enhances survival to antibiotic treatment, is a major barrier to successfully treating Tuberculosis (TB), which remains the public health challenge of our time. This study will identify unique drug targets in a clinically significant, drug tolerant Mycobacterium tuberculosis (Mtb) strain lacking a key glycerol kinase (glpK), by assessing the role of lipid metabolism and host macrophage phenotypes on drug tolerance under biologically relevant conditions. This innovative project has the potential to greatly shorten the length of antibiotic regimens, reducing relapse as well as TB mortality by producing highly translatable data that will unlock impactful new treatments against a clinically significant strain of Mtb.

PI_NAMEs: JOHNSON, KYLA ELISE (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: Address;Adherence;Affect;Antibiotic Therapy;Antibiotics;Bar Codes;Carbon;Cause of Death;Cell Separation;Characteristics;Cholesterol;Cholesterol Homeostasis;Clinical;clinically relevant;clinically significant;Communicable Diseases;Complex;CRISPR interference;Data;differential expression;DNA Sequence Alteration;Dose;drug development;drug efficacy;Drug Modulation;Drug resistance;Drug Targeting;Drug Tolerance;Environment;Essential Genes;Exhibits;experimental study;Frameshift Mutation;Genes;Genetic;Genetic Polymorphism;Genetic study;Genetic Transcription;Glycerol;Glycerol Kinase;Goals;Growth;Heritability;improved;improved outcome;In Vitro;in vivo;Infection;innovation;Integration Host Factors;Intracellular Accumulation of Lipids;knock-down;knockout gene;Label;Length;Libraries;lipid metabolism;Macrophage;Measurement;Metabolic;Metabolism;Modeling;mortality;multidrug tolerance;Multidrug-Resistant Tuberculosis;Mus;mutant;Mutation;Mycobacterium tuberculosis;Nature;new therapeutic target;novel therapeutics;Outcome;overexpression;pathogen;Pathway interactions;Patients;Pharmaceutical Preparations;Pharmacotherapy;Phase;Phenotype;Physiological;Population;Public Health;Regimen;Relapse;Research;response;Role;Sampling;Source;Sputum;stressor;Testing;Time;tool;Transcription Alteration;transcriptome sequencing;transposon sequencing;Treatment Failure;Tuberculosis;tuberculosis treatment;Variant

PROJECT_TITLE: Host-pathogen interactions and carbon processing in glycerol kinase deficient Mycobacterium tuberculosis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07A-B (20)]


ADMINISTERING_IC: NS

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

ORG_CITY: DURHAM

ORG_DEPT: NEUROLOGY

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project narrative: Currently there are no disease modifying therapies available for Parkinson's disease, in part because we still do not understand the exact biological mechanisms governing dopamine neuron susceptibility to death. Cell stress responses are implicated as one potential driver or contributor in Parkinson's disease. This proposal aims to elucidate the exact role of a specific stress response pathway throughout the course of disease to determine its role in Parkinson's pathophysiology, as well as, its potential as a therapeutic target.

PI_NAMEs: LOCKSHIN, ELANA  (contact)

PROGRAM_OFFICER_NAME: SARRAF, SHIREEN AKHAVAN

PROJECT_TERMS: Acceleration;advanced disease;Affect;Age;Aging;alpha synuclein;Apoptosis;Basal Cell;Behavioral;Biochemical Pathway;Biological;biological adaptation to stress;Brain;Buffers;Cell Death;Cell model;Cell Survival;Cells;Cellular Stress;Cessation of life;cholinergic;cholinergic neuron;Chronic;Collaborations;Corpus striatum structure;cytotoxic;Data;Disease;disease model;Disease Progression;dopaminergic neuron;Electrophysiology (science);endoplasmic reticulum stress;Exhibits;experimental study;Exposure to;Functional disorder;Future;Genes;Genetic;genetic approach;Goals;Health;Homeostasis;Human;Human Genetics;improved;Interneurons;Laboratories;Learning;Literature;Measures;Mediating;Messenger RNA;Methods;Midbrain structure;Mitochondria;Modeling;Modification;Motor disability;mouse model;Movement Disorders;Mus;Nerve Degeneration;Neurodegenerative Disorders;neuron loss;neuronal survival;Neurons;neuroregulation;novel;overexpression;Oxidopamine;Parkinson Disease;pars compacta;Pathogenesis;Pathologic;Pathology;Pathway interactions;perpetrators;Pharmaceutical Preparations;Phase;Phenotype;Population;Predisposition;PRKR gene;Property;protein aggregation;Protein Biosynthesis;Proteins;proteostasis;Recovery;Reporter;response;Risk Factors;Role;Runaway;sex;Signal Transduction;Stress;stress state;stressor;Study models;Substantia nigra structure;Techniques;Testing;Thapsigargin;Therapeutic;therapeutic target;transcription factor;transcriptome sequencing;Translations;Variant;Viral;Work

PROJECT_TITLE: The ISR pathway in Dopamine Neurons: Perpetrator or Protector in Parkinson's Disease

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F03C-N (20)]


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Autoimmune Disease;Biotechnology;Cancer;Cancer Genomics;Colorectal Cancer;Digestive Diseases;Genetics;Human Genome;Inflammatory Bowel Disease

ORG_CITY: CHARLESTON

ORG_DEPT: ANATOMY/CELL BIOLOGY

ORG_NAME: MEDICAL UNIVERSITY OF SOUTH CAROLINA

ORG_STATE: SC

PHR: PROJECT NARRATIVE Re-activation and integration of transposable elements (TEs) into a new genomic site can introduce mutations to regulatory or protein coding regions, which has been implicated in a variety of gastrointestinal (GI) diseases such as Crohn’s, colitis, Lynch syndrome, and cancer. However, the reasons for the increased activity of these elements in the GI epithelium still unclear. Our study has the potential to elucidate a previously underappreciated link between normal tissue architecture and transposon regulation, which may be critical for our understanding of the loss of epithelial integrity in GI diseases and could lead to the future development of novel therapeutics.

PI_NAMEs: RISNER, ALYSSA  (contact)

PROGRAM_OFFICER_NAME: DENSMORE, CHRISTINE L

PROJECT_TERMS: activation-induced cytidine deaminase;Adherens Junction;Adhesions;Apical;Architecture;Biological Assay;Biology;Cadherins;Cell Differentiation process;Cell Nucleus;Cell Polarity;Cell-Cell Adhesion;Cells;Clinical;Co-Immunoprecipitations;Code;Colitis;Colon;colon cancer patients;Colon Carcinoma;Colonic Diseases;Colorectal;Complex;CRISPR/Cas technology;Crohn's disease;Cytoplasm;Data;Development;Disease;DNA Damage;DNA Transposable Elements;DNA Transposons;Down-Regulation;E-Cadherin;Elements;Endoribonucleases;Epithelial Cells;Epithelium;experimental study;Future;Gastrointestinal Diseases;gastrointestinal epithelium;Gastrointestinal tract structure;Gene Silencing;Genome;genome integrity;Genomics;Germ Lines;Hereditary Nonpolyposis Colorectal Neoplasms;Homeostasis;Human;Human Genome;Immunoprecipitation;Inflammatory Bowel Diseases;innovation;knock-down;Knowledge;Lateral;Ligation;Link;Maintenance;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;metaplastic cell transformation;MicroRNAs;Molecular;monolayer;mRNA Expression;Mutagenesis;mutant;Mutation;Normal tissue morphology;novel;novel therapeutics;Open Reading Frames;Organoids;Pathway interactions;Patients;Phenotype;piRNA;Positioning Attribute;prevent;protein biomarkers;protein protein interaction;Proteins;recruit;Regulation;Research;Research Personnel;Retrotransposition;RNA;RNA Interference;Role;Site;skills;small hairpin RNA;Somatic Cell;Structural Protein;System;targeted treatment;Technical Expertise;Techniques;Testing;Tissue Sample;Tissues;tool;Training;Transcript;transcriptome sequencing;translational impact;transposon/insertion element;Virus Diseases

PROJECT_TITLE: Cadherin complexes recruit PIWIL2 to suppress transposons and maintain the normal epithelial phenotype

STUDY_SECTION_NAME: Special Emphasis Panel[ZDK1 GRB-7 (O1)]


ADMINISTERING_IC: GM

ED_INST_TYPE: UNIVERSITY-WIDE

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

NIH_SPENDING_CATS: Biotechnology;Genetics

ORG_CITY: FORT COLLINS

ORG_NAME: COLORADO STATE UNIVERSITY

ORG_STATE: CO

PHR: PROJECT NARRATIVE This proposal uses genetics and molecular biology tools to define the mechanisms directing local translation to plasma membranes. Impaired local translation in neurons and other cell types causes disease but studying mRNA localization in those contexts can be challenging. This project will achieve our long-term goal of understanding how local translation at membranes occurs by leveraging a tractable model system.

PI_NAMEs: TORRES, NALY  (contact)

PROGRAM_OFFICER_NAME: MCINTYRE, JEREMY COLIN

PROJECT_TERMS: Actins;Active Biological Transport;Address;Affect;Automobile Driving;Axon;Bioinformatics;Biological Models;Caenorhabditis elegans;Cell membrane;Cell Shape;cell type;Cells;Cellular Morphology;Co-Immunoprecipitations;Complement;Complex;Cytoplasm;Cytoskeleton;Diffusion;Disease;Embryo;Endoplasmic Reticulum;ERM protein;Event;experience;ezrin;Fluorescence Recovery After Photobleaching;Fluorescent in Situ Hybridization;Foundations;Gene Expression;Genetic;Goals;Health;Human;Human Cell Line;Image;Imaging Device;imaging system;Imaging Techniques;Immunofluorescence Immunologic;Impairment;Kinetics;Knowledge;Laboratory Finding;Learning;Link;Locales;malignant neurologic neoplasms;Mass Spectrum Analysis;Membrane;Messenger RNA;Methods;Microtubules;Modeling;moesin;Molecular Biology;Motor;N-terminal;Nervous System Disorder;Neurons;novel;Pathway interactions;Peptides;Permeability;Pharmaceutical Preparations;Pharmacotherapy;Phosphorylation;Process;Production;protein transport;Proteins;radixin protein;Recording of previous events;Reporter;Research;Research Design;Research Personnel;Ribosomes;RNA Interference;Rough endoplasmic reticulum;Scientist;secretory protein;single molecule;Site;Surveys;Techniques;technology development;Tertiary Protein Structure;Testing;Time;tool;trafficking;Training Programs;Translating;Translation Initiation;Translations;Visualization;Work

PROJECT_TITLE: Mechanisms Directing Translating Complexes to Plasma Membranes for Local Translation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-D (21)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Amyotrophic Lateral Sclerosis (ALS);Brain Disorders;Dementia;Neurodegenerative;Neurosciences;Prevention;Rare Diseases;Social Determinants of Health

ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE The environmental contribution to neurodegenerative diseases has been suggested from epidemiological studies, however, a comprehensive understanding of environmental agents that increase disease susceptibility remains a major unresolved question in the field. A toxicant screen coupled to high-content imaging has identified a set of environmental agents as putative triggers that drive TDP-43 dysfunction, a hallmark of neurodegeneration. This study will shed light on the identity, mode of action, perturbed signaling pathways, and the pathophysiological impact of these factors, with major implications towards disease prevention and mitigation strategies that alleviate cognitive and/or motor decline.

PI_NAMEs: COHEN, TODD JONATHAN (contact);PLANCHART, ANTONIO J.

PROGRAM_OFFICER_NAME: LI, TONG

PROJECT_TERMS: Address;Adult;Affect;Age;age related;age related neurodegeneration;Alanine;Alzheimer's Disease;Amino Acids;Amyotrophic Lateral Sclerosis;Automobile Driving;Behavioral;behavioral study;Biochemical;Brain Pathology;burden of illness;Cell Line;Chemicals;Cognitive;Computer Models;Coupled;Cyanobacterium;Cysteine;Data;Dementia;Development;Diet;Disease;Disease Progression;Disease susceptibility;disorder prevention;DNA-Binding Proteins;Dose;Electrophysiology (science);Environment;environmental agent;environmental chemical;Environmental Exposure;Environmental Impact;Environmental Risk Factor;Epidemiology;epidemiology study;Etiology;Event;exposed human population;Exposure to;frontotemporal lobar dementia amyotrophic lateral sclerosis;Functional disorder;Genetic;Genetic Models;Human;Image;in vivo;Induced pluripotent stem cell derived human neuron;innovation;insight;Libraries;Life Style;limbic-predominant age-related TDP-43 encephalopathy;Link;Measures;Mediating;Memory;Memory Loss;Metals;Microscopy;Modeling;Molecular Conformation;Motor;motor disorder;Mus;Nature;Nerve Degeneration;Neurodegenerative Disorders;neuron loss;Neuronal Dysfunction;Neurons;neuropathology;neurotoxic;Nuclear;Oxidative Stress;Parkinsonian Disorders;Pathogenesis;Pathology;Pathway interactions;Persons;Phenotype;Population;Predisposition;Prevalence;promoter;protein TDP-43;Proteomics;Publications;Reporter;Reporting;response;Risk;Risk Factors;screening;Signal Pathway;stem;Stress;Surveys;Synapses;TDP-43 aggregation;Therapeutic Intervention;Time;tool;Toxic Environmental Substances;toxicant;Toxicant exposure;toxicant screening;United States Environmental Protection Agency;Zebrafish

PROJECT_TITLE: Environmental risk factors linked to TDP-43 proteinopathies

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Clinical Research;Complementary and Integrative Health;Dietary Supplements;Digestive Diseases;Natural Products;Nutrition;Patient Safety

ORG_CITY: PULLMAN

ORG_NAME: WASHINGTON STATE UNIVERSITY

ORG_STATE: WA

PHR: PROJECT NARRATIVE Diclofenac is a widely used pain relief medicine, but its use has been associated with severe adverse events, including gastrointestinal ulcers, bleeding, and cardiotoxicity. This translational research project will investigate how genetic polymorphisms in an intestinal drug metabolizing enzyme, UGT2B17, and how the concomitant use of the popular natural product, curcumin, influence the large interindividual variation in the oral bioavailability of diclofenac. Results will provide critical information to both researchers and clinicians about the safe use of diclofenac with and without curcumin across populations to advance precision medicine.

PI_NAMEs: NAJI-TALAKAR, SIAVOSH  (contact)

PROGRAM_OFFICER_NAME: STILL, PATRICK COLBY

PROJECT_TERMS: Accounting;Adenocarcinoma Cell;Adult;African;African American population;Area;Arthritis;Australia;Biological Availability;Blood;Botanical dietary supplements;Cardiotoxicity;Caucasians;Cell Line;Cells;Chemicals;China;Chronic Disease;Clinical;Copy Number Polymorphism;Country;Curcumin;Cytochrome P450;Data;data modeling;Diclofenac;Dose;Drug Interactions;Drug Kinetics;drug metabolism;Drug Prescriptions;Drug usage;Elderly;Enterocytes;Enzyme Inhibitor Drugs;Enzymes;Europe;European;Exemestane;Exhibits;Exposure to;Female;Formulation;Frequencies;gastrointestinal;Gastrointestinal Diseases;Gene Deletion;Genes;Genetic Polymorphism;Genotype;Glucuronides;Glucuronosyltransferase;Hemorrhage;Herbal supplement;high risk;Human;improved;in silico;In Vitro;India;Individual;Inflammatory;inhibitor;insight;inter-individual variation;Intestines;Italy;Japanese;Japanese Population;Laboratories;Lead;Life;Liver;Liver diseases;male;Marketing;Mediating;Medicine;Metabolic Pathway;Metabolism;meter;Microsomes;Migraine;Modeling;National Center for Complementary and Integrative Health;Natural Product Drug;Natural Products;Nature;Non-Steroidal Anti-Inflammatory Agents;novel;Oral;Oral Administration;Pain;pain relief;Participant;patient population;Patients;Pediatrics;Pharmaceutical Preparations;Pharmacodynamics;pharmacokinetic model;physiologically based pharmacokinetics;Plasma;Population;precision medicine;Prevalence;Public Health;Recombinants;Regulation;Reporting;Research;Research Personnel;Research Project Grants;Risk;Rofecoxib;Role;Route;Russia;Safety;Sales;Sampling;Series;Serious Adverse Event;side effect;Spices;Testing;Time;Toxic effect;Training;Translational Research;Tumeric;Ulcer;Uridine;Urine;volunteer;Vorinostat;women versus men;Xenobiotics

PROJECT_TITLE: Effect of UGT2B17 deletion and curcumin inhibition on diclofenac PK

STUDY_SECTION_NAME: Special Emphasis Panel[ZAT1 AM (01)]


ADMINISTERING_IC: EY

IC_NAME: NATIONAL EYE INSTITUTE

NIH_SPENDING_CATS: Eye Disease and Disorders of Vision;Neurosciences

ORG_CITY: SYRACUSE

ORG_DEPT: OPHTHALMOLOGY

ORG_NAME: UPSTATE MEDICAL UNIVERSITY

ORG_STATE: NY

PHR: Project Narrative: This work seeks to understand the molecular mechanisms of rhodopsin transport into and along the photoreceptor cilium and its loading into new outer segment disc membranes. Retinal degeneration and blindness may be caused by improper breakdown of rhodopsin delivery to new discs in the outer segments of photoreceptor, the light detecting cells in our eyes. Understanding the mechanisms by which rhodopsin is properly delivered and packed into new disc membranes will help find new therapies to extend or restore vision in patients with genetic mutations that derail this process.

PI_NAMEs: CALVERT, PETER DEANE (contact)

PROGRAM_OFFICER_NAME: NEUHOLD, LISA

PROJECT_TERMS: 3-Dimensional;Affinity;Apical;apical membrane;Back;base;Binding;Blindness;Carrier Proteins;Cells;Cilia;Complement;Diffusion;dimer;Dimerization;DNA Sequence Alteration;Event;Eye;Fluorescence Microscopy;Frequencies;G-Protein-Coupled Receptors;Goals;Golgi Apparatus;Individual;Knock-out;Knowledge;Light;Location;Maintenance;Mammals;mathematical model;Membrane;Microscopy;Modeling;Molecular;Motor;mouse model;Movement;Mus;Nature;novel therapeutics;Opsin;particle;Patients;peripherin;photoreceptor disc;Photoreceptors;Process;Proteins;Resolution;Retinal Cone;Retinal Degeneration;Rhodopsin;Rod;Role;sight restoration;Site;Structure;Time;tissue fixing;Titrations;ultra high resolution;Vertebrate Photoreceptors;vesicle transport;Vision;Work

PROJECT_TITLE: Mechanisms of photoreceptor outer segment assembly

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


ED_INST_TYPE: SCHOOLS OF DENTISTRY/ORAL HYGN

ORG_CITY: MINNEAPOLIS

ORG_DEPT: DENTISTRY

ORG_NAME: UNIVERSITY OF MINNESOTA

ORG_STATE: MN

PHR: Relevance Narrative Deltaretroviruses are complex retroviruses, are associated with the development of lymphoid leukemias, and are notorious for being difficult to propagate in cell culture, which has prohibited rigorous analyses of virus replication, including the steps involved in retrovirus assembly. Deltaretroviruses have distinct immature and mature particle morphologies and utilize a distinct pathway for particle biogenesis. The studies proposed in this application will advance knowledge regarding the novel aspects of deltaretrovirus assembly, which will expand fundamental knowledge of retrovirus assembly and help reveal novel therapeutic targets for antiviral intervention.

PI_NAMEs: MANSKY, LOUIS M. (contact);MUELLER, JOACHIM D;ZHANG, WEI

PROGRAM_OFFICER_NAME: SAKALIAN, MICHAEL

PROJECT_TERMS: Address;Automobile Driving;Binding;Biogenesis;Biology;Bovine Leukemia Virus;Capsid;Cattle;Cell Culture Techniques;Cell membrane;Cells;Color;comparative;Complex;Cryoelectron Microscopy;Cytoplasm;Data;Deltaretrovirus;Development;experimental study;Fluorescence;Fluorescence Microscopy;gag Gene Products;Genes;HIV;HIV-1;Human;Human T-Cell Leukemia Viruses;Imaging technology;innovation;insight;Intervention;Investigation;Knowledge;Lymphoblastic Leukemia;Methods;Microscopy;molecular modeling;molecular site;Morphogenesis;Morphology;Nature;new therapeutic target;novel;Nucleocapsid;particle;Pathway interactions;Process;Property;reconstruction;recruit;Research;Resolution;Retroviridae;Retrovirology;Site;Site-Directed Mutagenesis;Spectrum Analysis;Structure;superresolution microscopy;System;Testing;tomography;Viral;viral transmission;Virion;Virus;Virus Assembly;Virus Replication

PROJECT_TITLE: Deltaretrovirus Morphology and Particle Assembly

STUDY_SECTION: MCV

STUDY_SECTION_NAME: Molecular and Cellular Biology of Virus Infection Study Section[MCV]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

IC_NAME: NATIONAL CANCER INSTITUTE

NIH_SPENDING_CATS: Cancer;Skin Cancer

ORG_CITY: Columbus

ORG_DEPT: GENETICS

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: NARRATIVE The most successful targeted therapies for RAS-driven cancers inhibit properties specific to the mutated RAS isoform or amino acid. However, little is known about the biochemical and functional differences among NRAS mutants, found commonly in melanoma, leukemia, thyroid, and colorectal cancers. This project will define the structural mechanisms that drive distinct functions among cancer-associated NRAS mutants, understand the impact of these differences on RAF inhibitor efficacy, and uncover new targets for cancer-specific drug discovery.

PI_NAMEs: LEW, RACHEL E. (contact)

PROGRAM_OFFICER_NAME: PURI, ANU

PROJECT_TERMS: Address;Affinity;Amino Acids;Automobile Driving;Binding;Biochemical;Biological Assay;Bioluminescence;Biosensor;BRAF gene;cancer initiation;Cancer Model;cancer type;Cell Proliferation;Cell Survival;Cells;clinical implementation;Clinical Trials;clinically relevant;Codon Nucleotides;Colorectal Cancer;Complement;Complex;conformer;Cysteine-Rich Domain;Data;design;Dimerization;Disease;drug discovery;drug sensitivity;Energy Transfer;Exhibits;experience;experimental study;extracellular;genomic locus;Growth Factor;Homo;Human;In Vitro;in vivo;Individual;inhibitor;Knowledge;KRAS2 gene;leukemia;Malignant neoplasm of thyroid;Malignant Neoplasms;MAP Kinase Gene;Measures;melanocyte;Melanoma;metaplastic cell transformation;Modeling;Molecular Conformation;molecular dynamics;Motility;mouse model;Mus;mutant;Mutate;Mutation;next generation;novel;novel therapeutic intervention;NRAS gene;Oncogenic;Pathway interactions;Pharmaceutical Preparations;preference;Property;Protein Isoforms;RAS driven cancer;RAS genes;Ras/Raf;Reporter;Research;Signal Pathway;Signal Transduction;Signal Transduction Pathway;structural biology;structural determinants;targeted treatment;Testing;therapeutic development;therapeutic target;Tipifarnib;Tissues;tumor;Variant;Western Blotting;Work

PROJECT_TITLE: Defining the biochemical properties and implications of NRAS mutant-specific BRAF interactions in melanoma

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09A-R (20)]


NIH_SPENDING_CATS: Cancer;Cancer Genomics;Digestive Diseases;Genetics;Human Genome;Pancreatic Cancer;Rare Diseases

ORG_CITY: NEW YORK

ORG_NAME: WEILL MEDICAL COLL OF CORNELL UNIV

PHR: PROJECT NARRATIVE Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent neoplastic disease of the pancreas, 15-20% of PDACs carry G12R mutations, but most preclinical animal models focus on the KrasG12D mutation, which reflects less than half of the KRAS mutations seen in human PDAC. My proposal represents a significant contribution to understanding the molecular underpinnings of disease initiation and progression of KrasG12R by testing the hypothesis that cell lineage and/or cooperating genetic events in the PI3K pathway impact the oncogenic potential of KrasG12R mutations in pancreas cancer. We anticipate that a better understanding of KrasG12R and related cellular and molecular processes will further elaborate on the KRAS heterogeneity found in PDAC, as well as provide avenues for the development of targeted therapeutics in patient populations with varying KRAS mutations.

PI_NAMEs: SISSO, WHITNEY JULIET (contact)

PROGRAM_OFFICER_NAME: ADAMS, GREGORY

PROJECT_TERMS: Acceleration;Acinar Cell;Address;Affect;Alleles;Amylases;Animal Model;ATAC-seq;Automobile Driving;base editing;Biological Assay;Cancer Etiology;Cell Line;Cell Lineage;cell type;Cells;Cessation of life;Chromatin;Clinical;Colon Carcinoma;Cre driver;CRISPR/Cas technology;Data;Development;Diagnosis;Disease;Disease Progression;driver mutation;Duct (organ) structure;Ductal Epithelial Cell;effective therapy;Epithelial Cells;Epithelium;Event;Foundations;Gene Expression;Genes;Genetic;genome editing;Heterogeneity;Histologic;Human;In Vitro;in vivo;in vivo Model;inducible Cre;KPC model;KRAS2 gene;KRASG12D;Lesion;live cell imaging;Malignant - descriptor;Malignant neoplasm of lung;Malignant neoplasm of pancreas;Malignant Neoplasms;Measures;Mediating;Mediator;MEKs;Metaplasia;Modeling;Molecular;Monitor;mouse model;Mus;mutant;Mutate;Mutation;Neoplasms;neoplastic;novel;Oncogenes;Oncogenic;organoid transplantation;Organoids;Pancreas;Pancreatic Adenocarcinoma;Pancreatic Diseases;Pancreatic Ductal Adenocarcinoma;pancreatic ductal adenocarcinoma cell;Pancreatic Intraepithelial Neoplasia;Pathway interactions;patient population;Patients;PI3K/AKT;PIK3CA gene;PIK3CG gene;Population;pre-clinical;Process;Prognosis;Proliferating;PTEN gene;Publishing;Role;Sampling;Signal Transduction;Stains;System;targeted treatment;Techniques;Technology;Testing;Time;TP53 gene;transcriptome;transcriptome sequencing;transcriptomics;Transplantation;treatment response;tumor;tumor initiation;tumor progression;tumorigenesis;unpublished works;Variant;Western Blotting;Work

PROJECT_TITLE: Understanding Kras Mutation Heterogeneity in PDAC


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

ORG_CITY: NEW HAVEN

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: YALE UNIVERSITY

ORG_STATE: CT

PHR: Project Narrative Intracellular bacterial pathogens remodel mammalian cell processes to replicate and cause disease. We propose to investigate how the intracellular pathogen Coxiella burnetii modulates the immune response to infection. This study will uncover fundamental details of the requirements for intracellular replication by bacterial pathogens and provide a possible therapeutic target for the treatment of these infections.

PI_NAMEs: DUNCAN-LOWEY, JEFFREY KARDAS (contact)

PROGRAM_OFFICER_NAME: PERDUE, SAMUEL S

PROJECT_TERMS: Acute;Address;antimicrobial;Binding;Biochemical;Biological Assay;C-terminal;career;Caspase;Cell Physiology;Cells;Chronic;chronic infection;Clinical Skills;clinical training;Communicable Diseases;Coxiella;Coxiella burnetii;Cysteine;cytokine;Cytoplasm;Development;Disease;Double-Stranded RNA;Engineering;Environment;experience;experimental study;Gene Expression;Gene Family;Genetic Epistasis;Genome;Goals;Human;Immune response;Immunoprecipitation;immunoregulation;improved;In Vitro;Infection;insight;Interferon Type I;Learning;Link;Luciferases;Lysosomes;Macrophage;Mammalian Cell;Maps;microbial;Modeling;Molecular;Molecular Target;Mutagenesis;mutant;N-terminal;pathogen;Pathogenesis;pathogenic bacteria;Pathway interactions;Patient Care;Peptide Hydrolases;permissiveness;Physicians;Preparation;Process;Productivity;programs;Proteins;Reporter;Research Personnel;RNA;RNA Binding;Role;Scientist;sensor;Signal Induction;Signal Transduction;skills;Specialist;Substrate Specificity;System;Testing;therapeutic target;Training;transcriptome sequencing;Ubiquitin;ubiquitin isopeptidase;Vacuole

PROJECT_TITLE: The role of a Coxiella burnetii effector protein that inhibits RIG-I signaling


NIH_SPENDING_CATS: Biotechnology

ORG_DEPT: CHEMISTRY

ORG_NAME: NEW YORK UNIVERSITY

PHR: Project Narrative Accessing a broad chemical space of small molecules, peptide structures, and carbohydrate analogues is crucial for drug discovery. The proposed research is highly relevant to public health as it aims to develop new synthetic methods for conducting late-stage functionalization and modification of pharmaceutically relevant molecules. By expanding the scope of available compounds and their functional groups, this research can pave the way for developing novel therapeutic agents with improved efficacy and fewer adverse effects, ultimately benefiting patients.

PI_NAMEs: DIAO, TIANNING  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: Address;Adverse effects;Alcohols;Amino Acids;Benchmarking;Biology;carbohydrate analog;Carbohydrates;Carbon;catalyst;Cells;Chemicals;Complex;Coupling;Cyclic Peptides;Cyclization;design;Development;drug development;drug discovery;electron donor;Electron Transport;Electrons;Exhibits;functional group;Head;hydroxyl group;improved;insight;Kinetics;Ligands;Ligation;Metabolic;Methods;Modification;Molecular Conformation;Nature;Nickel;novel;novel strategies;novel therapeutics;Patients;peptide analog;peptide structure;Peptide Synthesis;Peptides;Permeability;Pharmacologic Substance;phosphoramidite;Public Health;Reaction;Reagent;Research;Series;Site;small molecule;Specificity;Structure-Activity Relationship;Tail;Therapeutic Agents

PROJECT_TITLE: Late-Stage Modification of Biomolecules via Radical-Based Methods

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 MBBC-W (02)]


ORG_CITY: Los Angeles

ORG_DEPT: MISCELLANEOUS

ORG_NAME: UNIVERSITY OF SOUTHERN CALIFORNIA

PHR: PROJECT NARRATIVE Aging is associated with an accumulation of mitochondrial DNA mutations in human stem cells, neurons, cardiomyocytes and muscle fibers. It is thought that these mutations contribute to various age-related diseases, including Alzheimer’s disease, Parkinson’s disease, cancer and diabetes. In this application, we propose to clear these mutations from mammalian cells in an effort to prevent age-related pathology.

PI_NAMEs: SHEMTOV, SARAH JEAN (contact)

PROGRAM_OFFICER_NAME: FU, YI-PING

PROJECT_TERMS: Acceleration;Address;Age;age related;Age related pathologies;age-related disease;Aging;aging process;aging related;Alleles;Alzheimer's Disease;Autophagocytosis;Biological Assay;Brain;Cardiac Myocytes;Cell Aging;Cell Line;Cells;Child;Childhood;CRISPR/Cas technology;detection assay;Development;Diabetes Mellitus;dietary restriction;Disabling;Disease;DNA polymerase gamma;Enzymes;Epilepsy;Excision;experimental study;Freezing;Future;Generations;Genetic;Genetic Recombination;Genome;Goals;Heart;Human;human stem cells;Impairment;Inherited;insight;interest;Intervention;Intestines;Malignant Neoplasms;Mammalian Cell;Mitochondria;Mitochondrial DNA;mitochondrial DNA mutation;mitochondrial genome;Molecular;Molecular Biology;Monitor;Muscle Fibers;Muscle Weakness;Mutagenesis;mutant;Mutation;Mutation Detection;Neuromuscular Diseases;Neuronal Dysfunction;Neurons;normal aging;novel;Organism;Parkinson Disease;Pathogenicity;Play;Polymerase;Population;prevent;pro-aging;Process;Production;Protein Biosynthesis;protein function;Proteins;purge;Reactive Oxygen Species;Rejuvenation;Risk Factors;Role;sarcopenia;Skeletal Muscle;Skin;Societies;stem cells;Techniques;Testing;Therapeutic;therapy development;Time;Tissues;tool;treatment strategy

PROJECT_TITLE: Triggering the Selective Removal of Deleterious mtDNA Mutations from Mammalian Cells


ADMINISTERING_IC: NR

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL INSTITUTE OF NURSING RESEARCH

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Health Services;Prevention;Social Determinants of Health

ORG_CITY: ATLANTA

ORG_NAME: EMORY UNIVERSITY

PHR: PROJECT NARRATIVE Patients receiving dialysis experience multiple ongoing symptoms and diminished functional status along with frequent emergency department visits and hospital admissions, which contribute to lower quality of life and significant strain and costs on the healthcare system. This study will examine how symptom severity and functional status influence healthcare use over time in patients receiving dialysis and whether social vulnerability directly and/or indirectly influences those relationships. Information gained from this study will help to identify individuals whose healthcare use is most affected by symptoms and functional status, which can be used to develop screening tools and interventions to support these individuals while improving health outcomes and reducing burden to the healthcare system.

PI_NAMEs: NOORANI, NAZIYA P. (contact)

PROGRAM_OFFICER_NAME: KEHL, KAREN

PROJECT_TERMS: Acute;Address;Affect;Age;associated symptom;Behavioral Model;care providers;Censuses;Clinical;cognitive function;Communities;cost;County;Data;Data Set;Deterioration;Development;Dialysis procedure;Dimensions;disability;Electrolytes;Emergency department visit;emotional symptom;End stage renal failure;experience;Face;functional status;Future;General Population;Health;Health Care Costs;Health Food;Health Personnel;health service use;Health Services Accessibility;Healthcare;Healthcare Systems;high school degree;Hospitalization;Household;Housing;improved;Income;indexing;Individual;insight;Intervention;Kidney Transplantation;Knowledge;Language;life-sustaining therapy;Link;Liquid substance;longitudinal dataset;low socioeconomic status;Measures;Mediator;Medical Care Costs;Medicare;Mentors;Minority;multilevel analysis;neighborhood disadvantage;Neighborhoods;Neurobehavioral Manifestations;North Carolina;Nurses;Outcome;Outpatients;Patients;Persons;Pharmaceutical Preparations;Physical Function;physical symptom;Population;Quality of life;Race;racial minority;recruit;Research;Risk;Role;Scientist;Screening procedure;secondary analysis;Severities;skills;social health determinants;social influence;social vulnerability;Socioeconomic Status;Stress;Symptoms;theories;Time;Training;Transportation;transportation access;vulnerable community

PROJECT_TITLE: The Influence of Symptoms, Functional Status, and Social Vulnerability on Healthcare Use Among Patients Receiving Dialysis

STUDY_SECTION: NRRC

STUDY_SECTION_NAME: National Institute of Nursing Research Initial Review Group[NRRC (87)]


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

ORG_DEPT: BIOSTATISTICS & OTHER MATH SCI

PHR: Project Narrative Over 40% of American adults are obese and due to a lack of effective and affordable treatments for weight loss, the obesity epidemic remains a public health crisis. One hypothesis about the etiology of the obesity epidemic is that obesity is associated with increased reward sensitivity, coupled with increased impulsivity which drives excessive food intake. Here, we investigate how a ventral hippocampus to nucleus accumbens shell pathway regulates impulsive responding for palatable foods in order to provide basic science insight into the etiology of obesity.

PI_NAMEs: KLUG, MOLLY E (contact)

PROJECT_TERMS: Adult;adult obesity;American;Basic Science;Behavior;behavior test;Behavioral inhibition;Binge eating disorder;Body Weight decreased;Brain;Brain region;Calcium;Calcium Signaling;Classification;Communication;Coupled;Custom;Data;Deep Brain Stimulation;Desire for food;discounting;Dopamine Receptor;drug of abuse;Eating;Etiology;experimental study;Failure;Female;Fiber;Food;food consumption;Frequencies;Genetic;Hippocampus;improved;Impulsive Behavior;Impulsivity;In Situ Hybridization;in vivo;insight;Link;male;Measures;Medial;Mediating;motivated behavior;Motivation;neural;neural circuit;Neural Pathways;Neuroanatomy;Neurobiology;neurochemistry;Neurons;neuropsychiatric disorder;Nucleus Accumbens;Obesity;Obesity Epidemic;Opioid Receptor;Pathway interactions;Patients;Phenotype;Photometry;Pilot Projects;Play;preference;Prefrontal Cortex;premature;Process;Psychological reinforcement;Public Health;Rattus;receptor;Receptor Signaling;Regulation;Research;response;reward processing;Rewards;Role;Sex Differences;Signal Transduction;Site;Synapses;Synaptic Transmission;System;Testing;Virus;weight loss intervention;Work

PROJECT_TITLE: Neural circuits mediating food impulsive behavior

STUDY_SECTION: DDK

STUDY_SECTION_NAME: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]


NIH_SPENDING_CATS: Infectious Diseases;Malaria;Microbiome;Rare Diseases;Vector-Borne Diseases

PHR: PROJECT NARRATIVE Development of malaria parasites in the vector is intimately linked to mosquito nutrient assimilation and reproductive physiology. The proposed research will identify microbial regulators of egg formation and Plasmodium berghei development in Anopheles stephensi and define interactions between the gut microbiota and reproductive signaling that impact parasite maturation. This work will elucidate key host-microbiota- parasite interactions that may be exploited for reducing malaria transmission in the field.

PI_NAMEs: PHIPPS, BENJAMIN L (contact)

PROGRAM_OFFICER_NAME: COSTERO-SAINT DENIS, ADRIANA

PROJECT_TERMS: Acceleration;Adult;Adult women;Affect;Anopheles Genus;Beds;Blood;Blood-Borne Pathogens;Cessation of life;Clinical;Consumption;Culicidae;Deposition;Development;Digestion;Disease;egg;Egg Yolk Proteins;Environment;experimental study;feeding;Feeds;Female;Fertility;Gastrointestinal tract structure;Germ-Free;Gnotobiotic;Growth;gut microbes;gut microbiota;host microbiota;Human;human disease;Immunity;Incidence;Individual;Infection;Ingestion;innovation;Insecticide Resistance;Insecticides;insight;Insulin Receptor;insulin signaling;insulin-like peptide;knock-down;Life Cycle Stages;Link;Malaria;malaria infection;malaria mosquito;malaria transmission;Mediating;Microbe;microbial;microbial community;microbiota;microorganism;Modeling;Mosquito-borne infectious disease;Mus;Neuropeptides;normal microbiota;novel;novel strategies;Nutrient;Oocytes;parasite invasion;Parasites;pathogen;Persons;Physiological;Physiology;Plasmodium;Plasmodium berghei;Poison;Population;Predisposition;Process;Production;Protein Biosynthesis;Regulation;Reporting;reproductive;Reproductive Physiology;Research;Resources;response;Role;Signal Transduction;Techniques;Testing;Tissues;transmission process;vector;vector competence;Vertebrates;Work

PROJECT_TITLE: The impact of the mosquito gut microbiota on regulation of egg formation and malaria infection


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

NIH_SPENDING_CATS: Aging;Bioengineering;Biomedical Imaging;Biotechnology;Cancer;Nanotechnology;Regenerative Medicine;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Transplantation

ORG_DEPT: ENGINEERING (ALL TYPES)

ORG_NAME: GEORGIA INSTITUTE OF TECHNOLOGY

PHR: PROJECT NARRATIVE Stem cell therapy has the potential to restore degenerating tissues, but there are challenges in tracking the location and status of transplanted cells. This project aims to develop a non-invasive ultrasound-guided photoacoustic (US/PA) imaging approach for monitoring the location and differentiation of transplanted mesenchymal stem cells (MSCs) into tumorigenic cancer-associated fibroblasts (CAFs). The technology utilizes a versatile US/PA nanosensor to label and track MSCs in order to acquire information about their functional status and improve stem cell therapy outcomes for clinically relevant scenarios.

PI_NAMEs: JHUNJHUNWALA, ANAMIK  (contact)

PROGRAM_OFFICER_NAME: TSAP, LEONID V

PROJECT_TERMS: absorption;Acceleration;Adipose tissue;Aging;Anatomy;angiogenesis;Biological Assay;Biological Markers;Biological Process;biomaterial compatibility;Biopsy;Bone Marrow;Carcinoma;Cell Transplantation;Cells;chemokine;Clinical;clinical application;clinical translation;clinically relevant;Communication;Contrast Media;cost;Coupled;cytokine;cytotoxic;Degenerative Disorder;design;Detection;detection limit;directed differentiation;Disease;Dose;Engineering;Ethics;Event;Fibroblasts;Functional Imaging;functional improvement;functional status;Goals;high risk;histological stains;Histology;Human;Hydrophobicity;imaging approach;imaging capabilities;Imaging Device;imaging modality;Imaging Techniques;Immune;Immunosuppression;Implant;improved;In Vitro;in vivo;in vivo monitoring;Inflammation;Injections;injury and repair;Label;Location;LOXL2 gene;Lymphocyte;Maintenance;Malignant Neoplasms;Mass Spectrum Analysis;Measurable;Mediating;Mesenchymal Differentiation;Mesenchymal Stem Cell Transplantation;Mesenchymal Stem Cells;Mesenchyme;Methods;Modeling;Monitor;mouse model;nanoengineering;nanoGold;nanosensors;Nanosphere;Natural regeneration;Neoplasm Metastasis;neoplastic cell;non-invasive imaging;novel;Optics;Osteoporosis;Outcome;paracrine;Parkinson Disease;Peptides;Periodicity;Phenotype;photoacoustic imaging;plasmonics;Population;portability;potential biomarker;pre-clinical;preservation;Procedures;Proliferating;protein aminoacid sequence;real time monitoring;recruit;Regenerative Medicine;repaired;Reporting;Research Personnel;Resolution;response;restoration;Safety;sarcopenia;selective expression;Sensitivity and Specificity;sensor;serial imaging;Signal Transduction;Spinal cord damage;stem cell differentiation;stem cell fate;stem cell therapy;Stem cell transplant;stem cells;Stimulus;Surface;System;systemic inflammatory response;targeted biomarker;Techniques;Technology;Testing;Therapeutic;therapy outcome;Time;tissue degeneration;tissue regeneration;Tissues;tool;Translations;Transplantation;tumor;Tumor Escape;tumor growth;tumor microenvironment;Tumor Promotion;tumorigenesis;tumorigenic;Ultrasonography;ultrasound;Up-Regulation;uptake;Visualization

PROJECT_TITLE: In vivo Photoacoustic Monitoring of Stem Cell Differentiation to Cancer Associated Fibroblasts

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10C-D (20)]


ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Project Narrative Cardiac Ca2+ channels have a key role in excitation-contraction coupling and hormonal modulation of cardiac function. Dysregulation of basal activity and of hormonal modulation of Ca2+ channels is associated with major cardiovascular diseases, such as heart failure, hypertrophy and arrhythmias. By elucidating the mechanisms by which β-adrenergic signaling modulates heart function we seek to ultimately develop targeted and specific therapies for arrhythmias, heart failure, and other cardiovascular disorders.

PI_NAMEs: MARX, STEVEN O (contact);PITT, GEOFFREY S

PROGRAM_OFFICER_NAME: BALIJEPALLI, RAVI C

PROJECT_TERMS: Action Potentials;Acute;Adrenergic Agents;Adrenergic Agonists;Adrenergic beta-Agonists;Affinity;age effect;age related;Aging;Agonist;antagonist;Anti-Arrhythmia Agents;Arrhythmia;Attenuated;attenuation;Binding;Biological Markers;C-terminal;Ca(2+)-Transporting ATPase;Calcium Channel;Calsequestrin;Cardiac;Cardiac Myocytes;Cardiac Output;Cardiomyopathies;Cardiotoxicity;Cardiovascular Diseases;Catecholaminergic Polymorphic Ventricular Tachycardia;Catecholamines;Chronic;Collaborations;Compensation;Complex;Coupling;Cyclic AMP-Dependent Protein Kinases;DNA Sequence Alteration;exercise capacity;Exercise Tolerance;Exposure to;Fibrosis;fighting;Funding;Grant;GTP-Binding Proteins;Heart;Heart Contractilities;Heart Diseases;Heart failure;heart function;Heart Rate;heart rhythm;Hormonal;Hypertrophy;Hypoxia;Infiltration;inhibitor;Innovative Therapy;insight;Knock-in Mouse;Knock-out;Life;Macromolecular Complexes;Macrophage;Mediating;Membrane;Metabolism;Methodology;Methods;Mitochondria;Modeling;monocyte;mortality;Mus;Muscle Cells;mutant;Mutant Strains Mice;Mutate;Mutation;Myocardial;Myocardial dysfunction;myocardial injury;Necrosis;novel;novel therapeutics;old mice;Oxidative Stress;Pathologic;Patients;Pharmaceutical Preparations;Phosphorylation;Phosphorylation Site;Physiological;preservation;prevent;Probability;protein activation;Proteins;Proteomics;Regulation;response;Ryanodine Receptor Calcium Release Channel;Sarcolemma;Sarcoplasmic Reticulum;Serum;side effect;Signal Transduction;Stress cardiomyopathy;Sympathetic Nervous System;Syndrome;System;Testing;Time;Timothy syndrome;Transgenic Mice;voltage;Workload

PROJECT_TITLE: Phosphorylation-dependent regulation of calcium channels by macromolecular complexes

STUDY_SECTION: TDPS

STUDY_SECTION_NAME: Therapeutic Development and Preclinical Studies Study Section[TDPS]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

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

ORG_CITY: BOSTON

ORG_NAME: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH

ORG_STATE: MA

PHR: Project Narrative Though M. tuberculosis (Mtb) is under ongoing selection to adapt to the human host environment, the contribution of Mtb genetic variation to host disease is largely unexplored beyond antibiotic resistance. Using a library of Mtb clinical isolates, we designed a high-throughput RNA-sequencing pipeline to quantify gene expression variation in bacteria and link it to genetic change. Using this method, this study will characterize how evolution tunes the Mtb transcriptional regulatory network to create adaptive change and determine if and how evolution of the key virulence pathway, ESX-1, changes host response to infection.

PI_NAMEs: CULVINER, PETER H (contact)

PROGRAM_OFFICER_NAME: MENDEZ, SUSANA

PROJECT_TERMS: acid stress;adaptive immune response;Address;Aerosols;Affect;Alveolar Macrophages;Antibiotic Resistance;Automobile Driving;Bacillus;Bacteria;bacterial genetics;Bone Marrow;candidate identification;causal variant;Clinical;Code;cost;Critical Pathways;Cues;cytokine;Data;design;Disease;Disease Outcome;disease phenotype;ELF3 gene;Engineering;Environment;Environmental Risk Factor;Enzymes;Equation;Event;Evolution;Exposure to;Face;follow-up;Future;Gene Expression;Gene Expression Regulation;gene expression variation;Genes;Genetic;genetic regulatory protein;Genetic Transcription;genetic variant;Genetic Variation;genome sequencing;Genomics;Goals;Granuloma;Growth;Health;High-Throughput RNA Sequencing;Human;Hypoxia;Immune response;In Vitro;Infection;insight;Integration Host Factors;Intercistronic Region;Interferon Type I;Interferon-beta;Intervention;Laboratories;latent infection;Learning;Libraries;Life Cycle Stages;Link;M. tuberculosis genome;Macrophage;member;Metabolic;Metadata;Methods;Modeling;Molecular;mouse model;Mus;Mutation;Mycobacterium tuberculosis;Nucleic Acid Regulatory Sequences;Nutrient;Operon;Outcome;pathogen;Pathway interactions;Peru;Phagosomes;Phenotype;Phylogenetic Analysis;Population;pressure;prevent;Production;Productivity;programs;Proteins;Regulation;Regulatory Pathway;Regulon;response;Risk;Role;Route;success;therapy design;transcription regulatory network;Transcriptional Regulation;transcriptome;transcriptome sequencing;transcriptomics;Trees;Tuberculosis;uptake;validation studies;Variant;Vietnam;Virulence;virulence gene;whole genome;Work

PROJECT_TITLE: Dissecting virulence gene regulatory pathways in M. tuberculosis clinical isolates


NIH_SPENDING_CATS: Breast Cancer;Cancer;Clinical Research;Genetics;Natural Products;Women's Health Research

ORG_CITY: MADISON

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: NARRATIVE Only ~50% of patients benefit from the commonly used chemotherapy drug paclitaxel, but it has not been possible to predict which patients will respond. This project builds on preliminary evidence that pre-existing chromosomal instability (CIN) is a key determinant of paclitaxel response. Through clinical evaluation of this hypothesis, state-of-the-art measures of CIN, and consideration of an important modifier we recently identified called pole focusing, this project will provide the basic knowledge required to develop a predictive biomarker for paclitaxel and identify novel drug targets for sensitizing paclitaxel-resistant cancers.

PI_NAMEs: BURKARD, MARK E;WEAVER, BETH A (contact)

PROGRAM_OFFICER_NAME: VENKATACHALAM, SUNDARESAN

PROJECT_TERMS: Accounting;Affect;Aneuploid Cells;anti-cancer treatment;arm;Bayesian Analysis;Biological;Biological Markers;Biopsy;Breast Cancer Patient;Breast Cancer Treatment;Cancer Model;cancer subtypes;Cell Culture Techniques;Cell Death;Cell model;Cells;Cellular biology;chemotherapy;Chromosomal Instability;chromosome missegregation;Chromosome Segregation;Chromosomes;Clinical;Clinical Data;clinical efficacy;Clinical Trials;clinically relevant;cohort;Coupled;CRISPR screen;cytotoxicity;Data;daughter cell;Development;Disease;DNA sequencing;Dose;Dropout;Drug usage;effective therapy;Future;Genes;genetic signature;Goals;Human;improved;Incidence;inhibitor;insight;Knowledge;Laboratories;Maintenance;Malignant Breast Neoplasm;Malignant Neoplasms;Mammary Neoplasms;Measures;Metastatic breast cancer;Methods;Microtubules;Mitosis;Mitotic;Mitotic spindle;Modeling;Neoadjuvant Study;neoplastic cell;new therapeutic target;novel;Paclitaxel;Patients;Pharmaceutical Preparations;Poison;Population;pre-clinical;precision medicine;predictive marker;prevent;prospective;Radiology Specialty;refractory cancer;Research;research clinical testing;Resistance;resistance mechanism;response;Role;Sampling;sound;standard measure;standard of care;Techniques;Testing;Toxic effect;translational study;tumor;Tumor Suppression;Work

PROJECT_TITLE: Mechanisms of paclitaxel sensitivity and resistance

STUDY_SECTION: MCTA

STUDY_SECTION_NAME: Mechanisms of Cancer Therapeutics A Study Section[MCTA]


PHR: PROJECT NARRATIVE The opportunistic pathogens, Pseudomonas aeruginosa and Candida spp., are growing concerns in healthcare settings due to their increasing rates of antimicrobial resistance, and are commonly co-isolated from infections. The present study aims to develop two novel treatment strategies against such coinfections, ones using antimicrobial peptides and bacteriophages, viruses that selectively infect bacteria. Not only would such treatments provide alternative approaches to combating bacterial and fungal coinfections, but their development would provide a new pipeline for treatment of additional polymicrobial infections and site-specific delivery of drug compounds.

PI_NAMEs: LAM, CHARLTON  (contact)

PROGRAM_OFFICER_NAME: MOITRA, KAROBI

PROJECT_TERMS: Adopted;Adsorption;Alternative Therapies;alternative treatment;antagonist;Anti-Bacterial Agents;anti-microbial drug;anti-microbial peptide;antimicrobial;Antimicrobial Resistance;Bacteria;Bacterial Infections;bactericide;Bacteriophages;biofilm species;Biological Availability;Biomass;Body Fluids;Candida;Candida albicans;Candida auris;candida biofilm;Clinical;co-infection;combat;Combined Modality Therapy;Confocal Microscopy;CRISPR/Cas technology;delivery vehicle;Development;Dose;Drug Compounding;Drug Delivery Systems;drug resistant bacteria;drug resistant microorganism;Engineering;Exhibits;extracellular;Genetic;Genetic Engineering;Genome;Goals;health care settings;Host Defense;In Vitro;Infection;innovation;Label;Lung infections;Lytic;Lytic Phase;Lytic Virus;metabolic abnormality assessment;Methodology;Methods;Microbe;Microbial Biofilms;Multi-Drug Resistance;Mycoses;Nosocomial Infections;novel;novel strategies;opportunistic pathogen;Organism;pathogen;Peptides;Pharmaceutical Preparations;polymicrobial biofilm;Population;prevent;Production;Property;Pseudomonas;Pseudomonas aeruginosa;Research;Site;Stress;success;System;Testing;three dimensional structure;Toxic effect;transmission process;treatment response;treatment strategy;Virion;Virulence Factors;Virus;viscoelasticity;Wound Infection

PROJECT_TITLE: Development of novel bacteriophage-based therapies to combat Pseudomonas aeruginosa and Candida spp. dual-species biofilms.


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Basic Behavioral and Social Science;Behavioral and Social Science;Cancer;Clinical Research;Drug Abuse (NIDA only);Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Lung;Lung Cancer;Pediatric;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Substance Misuse;Substance Misuse Prevention;Tobacco;Tobacco Smoke and Health

ORG_CITY: RICHMOND

ORG_DEPT: PSYCHOLOGY

ORG_NAME: VIRGINIA COMMONWEALTH UNIVERSITY

ORG_STATE: VA

PHR: Project Narrative  Since the early onset of tobacco use among Latinx adolescents in the United States is a growing public health concern, a culturally-sensitive and ecological approach to understanding Latinx adolescent tobacco use and its influences is needed. This proposed project examines the longitudinal associations between (1) cultural values and adolescent tobacco use; (2) parental monitoring, family conflict, and adolescent tobacco use; and (3) caregiver-adolescent cultural value discrepancies, family conflict, and adolescent tobacco use over time using a mixed methods approach. The findings from this study will inform the present understanding of ecological factors that promote or prevent tobacco use among Latinx adolescents and thus, have critical implications for early intervention efforts.

PI_NAMEs: HERNANDEZ, CINDY MARIA (contact)

PROGRAM_OFFICER_NAME: ROMBERG, ALEXA RUTH

PROJECT_TERMS: Address;Adherence;Adolescent;adolescent substance use;Adult;Affect;Age;Area;Asthma;Attitude;authority;Buffers;California;career;Caregivers;Child Rearing;Chronic;Chronic Disease;Communication;Communities;community intervention;Conflict (Psychology);cultural values;Data;Data Analyses;Dependence;Disease;Early Intervention;early onset;Evidence based intervention;Family;family influence;Fellowship;Focus Groups;Goals;Grant;Growth;Health;health disparity;Heart Diseases;high risk;improved;innovation;Intervention;Knowledge;Latinx;Latinx population;Life;Link;Literature;Longitudinal Studies;Malignant Neoplasms;Manuscripts;Measures;Mentors;Methodology;Methods;Mexican;Modeling;National Institute of Drug Abuse;National Research Service Awards;neglect;non-cigarette tobacco product;parental monitoring;Participant;peer;Persons;Phase;Population;pre-doctoral;Prevalence;prevent;Prevention;Preventive care;protective factors;Public Health;Recovery;Reduce health disparities;Reporting;Research;Research Personnel;responsible research conduct;Risk;Role;Sampling;school district;skills;Social Identification;Social support;sociocultural determinant;Source;Statistical Methods;substance use;Substance Use Disorder;substance use prevention;Surveys;System;Teenagers;Time;time use;Tobacco;tobacco prevention;tobacco products;Tobacco use;Training;Translating;United States;Work;Writing;Youth

PROJECT_TITLE: Role of caregiver-adolescent interpersonal and cultural factors on Latinx adolescent tobacco use: A mixed-methods study

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F16-H (20)]


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

ORG_CITY: LOS ANGELES

ORG_NAME: CEDARS-SINAI MEDICAL CENTER

PHR: PROJECT NARRATIVE Colorectal cancer (CRC) metastasis is difficult to treat with any modern chemo- or immunotherapies, impacting CRC survival. IL27 cytokine regulates immune responses in CRC, including CRC metastasis in the liver. Here we will study microenvironmental and cell type specific mechanisms of IL27 signaling in CRC and test immunotherapies which are simultaneously aimed at neutralization of IL27 and activation of adaptive (CD8 T cells) or innate (macrophages) arms of anti-cancer immunity. 1

PI_NAMEs: GRIVENNIKOV, SERGEI I (contact)

PROGRAM_OFFICER_NAME: SNYDERWINE, ELIZABETH G

PROJECT_TERMS: Ablation;adaptive immunity;Advanced Malignant Neoplasm;Affect;Angiogenesis Inhibitors;Animals;anti-cancer;Anti-CD47;anti-CTLA4;Anti-Inflammatory Agents;anti-PD-1;anti-tumor immune response;arm;Autoimmune Diseases;Biological;Biological Testing;Biology;cancer cell;Cancer Etiology;Cancer Model;cancer survival;Cause of Death;CD47 gene;CD8-Positive T-Lymphocytes;CD8B1 gene;cell type;Cells;Chronic;colon cancer patients;Colorectal Cancer;colorectal cancer metastasis;cytokine;Cytokine Signaling;cytotoxic;Data;Development;Disease;effector T cell;Equilibrium;expectation;experience;experimental study;Family;Genetic;Genetic Models;Goals;Histologic;Human;IL6 gene;Image;Immune;immune checkpoint;Immune response;Immunity;Immunocompetent;Immunotherapeutic agent;Immunotherapy;in vivo;Inflammation;Inflammation Mediators;Inflammatory;Interleukin-12;Interleukins;Liver;liver development;Macrophage;Malignant neoplasm of liver;Malignant Neoplasms;Mediating;member;metastatic colorectal;Metastatic Neoplasm to the Liver;Methods;Microsatellite Repeats;Modality;Modeling;Modernization;Molecular;mortality;mouse model;Mus;Mutation;Myeloid Cells;Myeloid-derived suppressor cells;Natural Immunity;Neoplasm Metastasis;neutralizing antibody;novel;novel therapeutics;Organoids;Pathogenicity;Pathway interactions;Peritoneal;pharmacologic;pre-clinical;Pre-Clinical Model;Preventive;Production;Prognosis;programmed cell death protein 1;Property;receptor;Receptor Signaling;Refractory;Regulation;Regulatory T-Lymphocyte;reverse genetics;Role;Sampling;Scheme;Shapes;Signal Transduction;Specificity;T-Lymphocyte;targeted treatment;Testing;Therapeutic;tool;transcriptomics;tumor;tumor growth;Tumor Immunity;tumor microenvironment;tumor-immune system interactions;tumorigenesis;tumorigenic

PROJECT_TITLE: Cytokine-mediated regulation of immunity and microenvironment in colorectal cancer metastasis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 BTC-Q (80)]


NIH_SPENDING_CATS: Cancer;Genetics;Skin Cancer

ORG_CITY: CAMBRIDGE

ORG_NAME: BROAD INSTITUTE, INC.

PHR: PROJECT NARRATIVE Current standard of care targeted therapy options result in improved response rates and longer progression-free survival compared to traditional chemotherapy. However, the majority of responses to these treatment options are short-lived and limited by drug resistance. The main goal of this project is to establish a novel therapeutic strategy to exploit targeted therapy resistance for sensitization to the next therapeutic intervention.

PI_NAMEs: CHO, EUNICE  (contact)

PROGRAM_OFFICER_NAME: ODEH, HANA M

PROJECT_TERMS: Address;Automobile Driving;Bar Codes;BRAF gene;cancer cell;cancer therapy;cancer type;Cell Death Induction;Cell Line;Cell Survival;Cells;cellular engineering;chemotherapy;Clinical;Clonal Evolution;Clone Cells;combat;CRISPR screen;Dependence;Development;Drug resistance;drug withdrawal;efficacy evaluation;Frequencies;gain of function;Genes;Genetic;Genetic Markers;Goals;Immunotherapy;Impairment;improved;In complete remission;in vivo;inhibitor;Intervention;Knock-out;Malignant Neoplasms;MAP Kinase Gene;Mediating;Mediator;MEKs;Melanoma;Melanoma Cell;Melanoma patient;Modality;Modeling;Molecular;mutant;novel therapeutic intervention;novel therapeutics;Oncogenic;paralogous gene;Pathway interactions;patient response;PIK3CG gene;Population;Population Heterogeneity;Predisposition;Progression-Free Survivals;Resistance;Resistance development;resistance mechanism;response;Signal Pathway;Signal Transduction;standard of care;success;synergism;targeted treatment;Testing;Therapeutic;Therapeutic Intervention;Toxic effect;Treatment Protocols;treatment response;tumor;tumor eradication;tumor growth;tumor heterogeneity;Withdrawal;Work;Xenograft Model;Xenograft procedure

PROJECT_TITLE: Directed Clonal Evolution of Drug Resistant BRAF Mutant Melanoma for Cross-Sensitization to MAPK Hyperactivation

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09B-Z (20)]


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Asthma;Climate-Related Exposures and Conditions;Lung

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

PHR: PROJECT NARRATIVE Exposure to wildfire smoke is estimated to affect 25 million people in the US alone, with 33,000 deaths per year associated with wildfire smoke worldwide, largely due to pulmonary health effects. The proposed work seeks to understand the role of extracellular vesicles and the HIF-1α pathway in mediating wildfire health effects and susceptibility in the respiratory system using linked human in vitro and in vivo experimental approaches, with a focus on understanding increased susceptibility in asthmatic populations. The results of this work will help uncover mechanisms of wildfire smoke effects, ultimately contributing to efforts aimed at reducing wildfire- associated morbidity and mortality.

PI_NAMEs: HICKMAN, ELISE DANIELLE (contact)

PROGRAM_OFFICER_NAME: NADADUR, SRIKANTH

PROJECT_TERMS: Address;Affect;Air;airway epithelium;Asthma;asthma exacerbation;asthmatic;Attenuated;attenuation;Automobile Driving;Biological;Biological Markers;Biology;Biomass;biomass smoke;Cardiovascular Diseases;cell type;Cells;Cessation of life;Chemical Exposure;climate change;Clinical;Communication;Computing Methodologies;Data;design;Development;differential expression;Disease;disease phenotype;Disease susceptibility;epidemiology study;Epithelial Cells;Epithelium;Event;Exposure to;extracellular vesicles;Functional disorder;Goals;Health;Hospitalization;Human;human subject;Human Volunteers;hypoxia inducible factor 1;Hypoxia Pathway;Immune response;In Vitro;in vitro Model;in vivo;Individual;Inflammatory;inhibitor;innovation;insight;Link;Lung;lung health;Machine Learning;Measures;Mediating;Mediator;Medicine;Mentors;Methods;MicroRNAs;Molecular;Molecular Profiling;Morbidity - disease rate;mortality;Mus;novel;Outcome;Particulate Matter;Pathogenesis;Pathway interactions;Personal Satisfaction;Persons;Physical condensation;Play;Population;predictive modeling;Predisposition;Prevalence;Proteins;proteomic signature;Proteomics;Public Health;public health relevance;pulmonary function;Pulmonary Inflammation;Research;Research Personnel;Respiratory Disease;Respiratory System;response;Risk;Role;Sampling;Signal Transduction;Smoke;Specificity;Sputum;System;Testing;therapeutic target;Toxic effect;training opportunity;transcriptomics;United States;Vesicle;vesicular release;Wildfire;Work

PROJECT_TITLE: Mechanisms of wildfire smoke toxicity and susceptibility involving extracellular vesicles in humans

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F10A-K (20)]


NIH_SPENDING_CATS: Acquired Cognitive Impairment;Aging;Alzheimer's Disease;Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD);Brain Disorders;Cancer;Dementia;Hematology;Immunotherapy;Neurodegenerative;Neurosciences

ORG_NAME: NEW YORK UNIVERSITY SCHOOL OF MEDICINE

PHR: PROJECT NARRATIVE Cancer patients who develop brain metastasis are faced with particularly poor clinical outcomes, including severe neuropsychiatric symptomology and low survival rates. This project will investigate how amyloid beta, a protein classically associated with Alzheimer’s disease, can be targeted to amplify anti-tumor immunity in brain metastasis. This work will serve as a foundation for the development of novel immunotherapies specific to brain metastasis, improving outcomes for a patient population with largely unmet clinical needs.

PI_NAMEs: ESKOW, NICOLE MARIE (contact)

PROGRAM_OFFICER_NAME: BIAN, YANSONG

PROJECT_TERMS: Abeta synthesis;Acceleration;Affect;Alzheimer's Disease;Amyloid beta-Protein;Amyloid beta-Protein Precursor;anti-CTLA4;anti-PD-1;anti-tumor immune response;Apoptosis;Area;Astrocytosis;beta secretase;beta-site APP cleaving enzyme 1;Biology;Blood - brain barrier anatomy;Brain;brain shape;Cancer Biology;cancer cell;Cancer Patient;Cells;Cephalic;Cessation of life;Characteristics;chemotherapy;Clinical;clinical application;Clinical Sciences;clinical training;Clinical Trials;clinically relevant;Coculture Techniques;Combined Modality Therapy;Dedications;Development;Disease;Disease Progression;Educational Curriculum;Enzymes;Excision;experience;Fellowship;Fostering;Foundations;Genetic;Glioblastoma;Goals;Hematology;high school;Immune;immune cell infiltrate;Immune checkpoint inhibitor;immune function;Immune system;Immunocompetent;Immunocompromised Host;Immunofluorescence Immunologic;immunosuppressed;Immunosuppression;Immunotherapeutic agent;Immunotherapy;Impairment;improved;improved outcome;in vivo;Infiltration;Inflammatory;inhibitor;International;Investigation;ipilimumab;Laboratories;Local Therapy;Macrophage;Malignant Breast Neoplasm;Malignant neoplasm of lung;Malignant Neoplasms;Mediating;medical schools;meetings;Melanoma;Mentors;Mentorship;Metastatic malignant neoplasm to brain;Microglia;Modeling;Molecular;monocyte;Morbidity - disease rate;mortality;mouse model;Mus;Myelogenous;Neoplasm Metastasis;Neurocognitive Deficit;Neurodegenerative Disorders;neuropsychiatry;new therapeutic target;next generation;Nivolumab;novel;novel therapeutic intervention;Oncologist;Oncology;Operative Surgical Procedures;Outcome;Pathogenesis;Pathway interactions;patient population;Patient-Focused Outcomes;Patients;Phagocytes;Phagocytosis;Phagocytosis Inhibition;pharmacologic;Phenotype;Positioning Attribute;professor;programs;Proteins;Publishing;Radiation therapy;receptor;Reporting;Research;Resistance;response;Role;Signal Pathway;Signal Transduction;single-cell RNA sequencing;skills;Survival Rate;System;Systemic Therapy;T-Lymphocyte;Testing;therapeutic target;Training;Translational Research;translational scientist;tumor;Tumor Burden;Tumor Immunity;tumor immunology;tumor progression;Tumor Promotion;Tumor-associated macrophages;tumor-immune system interactions;undergraduate student;Work;Xenograft Model

PROJECT_TITLE: Targeting amyloid beta for myeloid reprogramming in brain metastasis

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F09C-Z (20)]


NIH_SPENDING_CATS: Cardiovascular;Clinical Research;Data Science;Heart Disease;Lung;Machine Learning and Artificial Intelligence;Networking and Information Technology R&D (NITRD);Precision Medicine;Prevention;Sleep Research

ORG_NAME: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

PHR: Project Narrative Our project aims to develop and validate parsimonious prediction models using machine learning to identify non-sleepy OSA individuals at risk for cardiovascular disease events and to accurately classify individuals who may benefit from continuous positive airway pressure therapy.

PI_NAMEs: NADKARNI, GIRISH NITIN;SHAH, NEOMI A (contact);SUAREZ-FARINAS, MAYTE

PROGRAM_OFFICER_NAME: ALFINI, ALFONSO JOSEPH

PROJECT_TERMS: acute coronary syndrome;Address;Adherence;Adult;Affect;Age;Area;atherosclerosis risk;Atrial Fibrillation;Big Data;Cardiovascular Diseases;cardiovascular disorder risk;cardiovascular risk factor;Cardiovascular system;Caring;Characteristics;Classification;Clinical;clinical decision-making;clinical practice;clinically relevant;cohort;Collaborations;Continuous Positive Airway Pressure;coronary calcium scoring;Data;Data Set;data-driven model;Databases;Drowsiness;Dyslipidemias;Effectiveness;Electronic Health Record;Ensure;Environment;ethnic diversity;Event;experience;follow-up;Goals;hazard;Health Care Costs;Health system;Heart failure;Heterogeneity;high risk;improved;Individual;Intervention;Machine Learning;machine learning method;Medicine;Modeling;multidisciplinary;multimodal data;multimodal learning;novel strategies;Obstructive Sleep Apnea;Outcome;patient population;Patient-Focused Outcomes;Patients;personalized approach;personalized medicine;personalized predictions;Physicians;Polysomnography;Population;precision medicine;Prediction of Response to Therapy;predictive modeling;predictive tools;Publications;randomized, clinical trials;Research;respiratory;Risk;Risk Assessment;risk prediction;Risk Reduction;risk stratification;Sample Size;Sampling;Severities;Sleep;Sleep Disorders;Subgroup;Techniques;Time;tool;Translations;treatment as usual;treatment effect;treatment optimization;treatment planning;United States National Institutes of Health;Validation;Work

PROJECT_TITLE: Application of Machine Learning to Identify Obstructive Sleep Apnea Subgroups at Risk for Atherosclerosis Progression and Cardiovascular Disease Events (OSA-GRANDE)

STUDY_SECTION: CRD

STUDY_SECTION_NAME: Cardiovascular and Respiratory Diseases Study Section[CRD]


ADMINISTERING_IC: HD

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

NIH_SPENDING_CATS: Bioengineering;Biotechnology;Breastfeeding, Lactation and Breast Milk;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Nutrition;Pediatric;Prevention

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

PHR: Project Narrative Human milk fat, which provides over 50% of an infant’s energy requirement during early lactation, has an optimized composition with respect to fatty acid chain length and regiospecific distribution. The fat ingredient of infant formula, which is typically derived from vegetable oil blends, does not match the structural diversity of human milk lipids with respect to chemical composition, and hence lacks some significant nutritional benefits of human milk fat. This project aims to provide a healthy and sustainable lipid source for infant formula by engineering an oleaginous green alga for human milk fat production through a synthetic biology approach that exploits the vast knowledge base of plant and algal lipid metabolism.

PI_NAMEs: LIN, YANG-TSUNG  (contact)

PROGRAM_OFFICER_NAME: ROSS, SHARON A

PROJECT_TERMS: absorption;Acyl Carrier Protein;Acyl Coenzyme A;Acyltransferase;Address;Algae;Biomass;bone health;Calcium;Calcium ion;Calories;Carrier Proteins;chelation;Chemicals;Chlamydomonas reinhardtii;Chloroplasts;Complex;Consumption;cost;Development;dietary;Digestion;Effectiveness;Energy-Generating Resources;Engineering;Environment;Enzymes;Epithelial Cells;Esterification;Esterified Fatty Acids;Esters;Exclusive Breastfeeding;Failure;Fat Substitutes;fatty acid biosynthesis;Fatty acid glycerol esters;Fatty Acids;Fatty-acid synthase;Feces;Friends;Gene Expression;Genetic;Genome;Glycerol;Goals;Green Algae;Human;Human Engineering;Human Milk;Immunization;improved;Individual;Infant;Infant formula;infant outcome;Institution;Intake;intestinal epithelium;knowledge base;Laboratories;Lactation;Length;Lipase;lipid metabolism;lipid structure;Lipids;lower income families;lysophosphatidic acid;Mass Fragmentography;Maternal Health;Medium chain fatty acid;metabolic engineering;Methods;milk fat;Modification;Monitor;Monoglycerides;Mothers;nutrition;Nutritional;Oils;Oleates;Oleic Acids;oleoyl-(acyl-carrier-protein) hydrolase;Organism;Output;palm oil;Palmitates;Palmitic Acids;Pancreas;Phosphatidic Acid;Plants;poor health outcome;Positioning Attribute;Post-Translational Protein Processing;Precipitation;Prevalence;prevent;Process;Production;Proteomics;Research;Role;rural area;Soaps;Source;Specificity;Structure;Substrate Specificity;Surveys;synthetic biology;System;tool;Training;Triglycerides;Variant;Vegetable Oils;Vertebral column;Western Blotting

PROJECT_TITLE: Synthetic Biology Approach in Engineered Algae for Improved Milk Fat Composition in Formula

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F04-S (20)]


ORG_CITY: SAN ANTONIO

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

ORG_STATE: TX

PHR: PROJECT NARRATIVE  APOBEC3B (A3B) is an innate immune enzyme that functions by catalyzing cytosine-to-uracil conversions in the genomes of DNA-based viruses. A3B is the only member of a larger 7-membered family of deaminases to localize constitutively to the nucleus. This project will contribute to our understanding of DNA virus restriction by identifying the molecular mechanism of A3B nuclear import, determining the impact of this process on multiple DNA viruses, and thereby delineating new targets for therapeutic intervention.

PI_NAMEs: AUERBACH, ASHLEY A (contact)

PROGRAM_OFFICER_NAME: GONDRE-LEWIS, TIMOTHY A

PROJECT_TERMS: Anti-viral Agents;antiviral immunity;Binding;Cell Culture Techniques;Cell Nucleus;Cercopithecidae;Chimera organism;Clustered Regularly Interspaced Short Palindromic Repeats;Cytoplasm;Cytosine;Deaminase;Defense Mechanisms;Development;DNA;DNA biosynthesis;DNA Viruses;Enzymes;Evolution;Exhibits;Family;Family member;Gatekeeping;Genome;Herpesviridae;Herpesviridae Infections;Human;human DNA;Human Herpesvirus 4;Image;Immune;Immunofluorescence Immunologic;in vivo;in vivo Model;Knock-out;Knowledge;Label;Macaca mulatta;Maps;Mass Spectrum Analysis;Measures;Mediating;member;Molecular;Molecular Biology;mouse model;mutant;Mutation;N-terminal;Natural Immunity;new therapeutic target;nonhuman primate;novel;Nuclear;Nuclear Import;Papillomavirus;pathogen;Play;Polyomavirus;Process;Protein Import;Proteins;Proteomics;Publications;Resolution;Ribonucleotide Reductase;Role;Scientist;Series;Single-Stranded DNA;Site;skills;Technology;Testing;Therapeutic Intervention;trafficking;Uracil;Viral;viral DNA;Viral Genome;Viral Physiology;virology;Virus;Virus Diseases;Virus Replication;virus testing

PROJECT_TITLE: Identifying a Critical Gatekeeper for DNA Virus Restriction

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


NIH_SPENDING_CATS: Cystic Fibrosis;Genetics;Lung;Orphan Drug;Rare Diseases

ORG_DEPT: PHYSIOLOGY

PHR: PROJECT NARRATIVE  Approximately 10% of people with cystic fibrosis (CF) are ineligible for new, life changing CFTR modulator therapy due to their specific CFTR variants, mainly due to mutations that cause premature termination codons (PTCs). CC-90009 is a thalidomide derivative drug that: 1) promotes ribosomal readthrough to rescue PTC- CFTR variants and 2) reduces epithelial sodium channel (ENaC) activity, and these two actions are both predicted to improve defective mucociliary transport in CF and other muco-obstructive lung diseases. Because reducing ENaC activity is a mutation-agnostic approach to treat CF, and because many other genetic diseases are caused by PTCs, this proposal will investigate the potentially broadly applicable mechanisms of action of CC-90009 and will test its efficacy in preclinical models of CF.

PI_NAMEs: BULIK-SULLIVAN, EMILY CLAIRE (contact)

PROGRAM_OFFICER_NAME: REYES, MADELYN

PROJECT_TERMS: Abbreviations;Acute Myelocytic Leukemia;Air;airway epithelium;Animal Model;Anions;Biomedical Research;biophysical properties;bronchial epithelium;career;Cells;Cellular biology;Climacteric;CRISPR/Cas technology;Cystic Fibrosis;cystic fibrosis mouse;Cystic Fibrosis Transmembrane Conductance Regulator;Dehydration;Disease;Epithelial Cells;epithelial Na+ channel;Epithelium;Equilibrium;Genes;Genetic Diseases;Height;Human;Hydration status;improved;improved outcome;In Vitro;in vivo evaluation;Inbred CFTR Mice;Individual;Inflammation;Inherited;innovation;Innovative Therapy;Investments;knock-down;Knowledge;Liquid substance;Lung;Lung infections;Measures;Medical;Mentors;Messenger RNA;Molecular;Morbidity - disease rate;mortality;mouse model;Mucociliary Clearance;Mucous body substance;mucus-associated lung diseases;Mus;mutant;Mutation;novel;novel therapeutics;Obstruction;Other Genetics;overexpression;Pathogenicity;Pathologic;Pathway interactions;Persons;Pharmaceutical Preparations;Phase I Clinical Trials;Phase Transition;Physicians;Positioning Attribute;pre-clinical;Pre-Clinical Model;premature;Proteins;Pulmonary Pathology;Regulator Genes;Research Technics;Resistance;respiratory;ribosome releasing factor;Ribosomes;S phase;Scientist;Services;small molecule;Surface;Symptoms;System;termination factor;Terminator Codon;Testing;Thalidomide;Therapeutic;therapeutic target;Tracheal Epithelium;Transgenic Organisms;translational physician;translational potential;translational therapeutics;Translations;ubiquitin-protein ligase;Ubiquitination;Variant;Water;Work

PROJECT_TITLE: Therapeutic potential of CC-90009 for cystic fibrosis


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

ORG_CITY: SEATTLE

ORG_NAME: FRED HUTCHINSON CANCER CENTER

PHR: Project Narrative Cells of complex tissues have specialized functions and identities to aid in the overall homeostasis of the tissue. However, the role chromatin modifications contribute to cell-type identity and function needs to be better understood. Using a sensitive chromatin profiling technique, I will characterize the genome-wide landscape of chromatin modifications and RNA Polymerase II in individual cell types based on a genetic marker or histone modification level to understand how chromatin varies from cell to cell and aid in cellular identity.

PI_NAMEs: LEICHTER, SARAH  (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Affect;Age;age effect;age related;Aging;Biological Models;Biological Process;Biology;Cell Count;Cell Differentiation process;cell injury;Cell Maintenance;Cell Physiology;Cell Separation;cell type;Cells;Chromatin;chromatin modification;Complex;Critical Pathways;Cytology;Development;Digestion;Disease;Drosophila genus;Drosophila melanogaster;Enteroendocrine Cell;Enzymes;Epigenetic Process;Fluorescence-Activated Cell Sorting;fly;Funding;Gene Expression Profile;Gene Expression Profiling;Gene Expression Regulation;Gene Silencing;genetic manipulation;Genetic Markers;Genetic Transcription;Genome;genome-wide;Histone H3;histone modification;Histones;Homeostasis;hormonal signals;Individual;insight;interest;Intestines;Investigation;knock-down;life span;Lysine;mammalian genome;Maps;Mediating;Methylation;Microbe;Mission;Mitotic;Modification;National Institute of General Medical Sciences;nutrient absorption;Organism;Pathway interactions;Pattern;Phenotype;Play;Polycomb;Population;Post-Translational Protein Processing;prevent;Process;progenitor;Proliferating;Research;RNA Polymerase II;Role;Source;stem;stem cell population;stem cells;Stimulus;System;Tail;Techniques;Tissues;uH2A

PROJECT_TITLE: Investigating the chromatin landscape of complex tissues through cell-type-specific patterns

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F05-Q (20)]


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

ORG_CITY: ANN ARBOR

ORG_NAME: UNIVERSITY OF MICHIGAN AT ANN ARBOR

ORG_STATE: MI

PHR: PROJECT NARRATIVE Diseases of ineffective erythropoiesis are characterized by dysfunctional progenitor cells that lead to decreased output of functional RBCs and, consequently, anemia. The emergence of effective metabolite therapies, such as L-glutamine for sickle cell disease, highlight the potential of metabolic inputs of erythropoiesis to develop targeted therapies. The goal of this proposal is to elucidate the mechanism by which redox balance through the malate-aspartate shuttle affects red blood cell development.

PI_NAMEs: POURMANDI, NARGES  (contact)

PROGRAM_OFFICER_NAME: PHILP, DEBORAH

PROJECT_TERMS: Affect;Amino Acids;Anemia;Aspartate;Aspartate Transaminase;Bone Marrow;Bone Marrow Cytometry;CD34 gene;Cells;Complete Blood Count;Cytoplasm;Cytosol;Data;Defect;Dependence;Development;Disease;Electron Transport;Enzymes;Equilibrium;Erythrocytes;Erythroid;Erythroid Cells;erythroid differentiation;Erythroid Progenitor Cells;Erythropoiesis;Exhibits;Failure;Generations;Genetic;genetic approach;Glutamine;Glycolysis;Goals;hematopoietic differentiation;hematopoietic stem cell self-renewal;Hematopoietic stem cells;Histology;Homeostasis;Human;In Vitro;in vitro Model;in vivo;ineffective therapies;insight;Knock-out;Knockout Mice;Lead;Literature;Maintenance;Malate-Aspartate Shuttle Pathway;Mass Spectrum Analysis;Megakaryocytes;Metabolic;Metabolic dysfunction;Metabolic Pathway;Metabolism;Mitochondria;Mitochondrial Aspartate Aminotransferase;Modeling;Molecular;mouse model;NADH;new therapeutic target;novel therapeutic intervention;Nucleotide Biosynthesis;Output;Oxidation-Reduction;Oxidative Phosphorylation;Oxidative Stress;peripheral blood;pharmacologic;Pharmacotherapy;Phenotype;Platelet Count measurement;Population;Process;Production;progenitor;Proliferating;Regulation;Role;Scheme;self-renewal;Sickle Cell Anemia;Spleen;stable isotope;stem cells;Stress;Supplementation;targeted treatment;Testing;Transfusion;Up-Regulation;Work

PROJECT_TITLE: Defining the metabolic regulation of erythropoiesis


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

ORG_CITY: COLLEGE STATION

ORG_DEPT: OTHER CLINICAL SCIENCES

ORG_NAME: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR

PHR: Project narrative Mycobacterium tuberculosis (Mtb) remains one of the most infectious and deadly pathogens worldwide. Key to Mtb virulence are membrane bound and secreted effector proteins that interact with host proteins to influence the host response to infection and promote Mtb survival. We predict that the uncharacterized effector protein Rv1075c is a nucleomodulin that interacts with the Set1 methyltransferase complex to modulate the type I interferon response and promote Mtb pathogenesis.

PI_NAMEs: COLEMAN, AJA  (contact)

PROJECT_TERMS: ASH2L gene;Automobile Driving;Bacterial Genes;bacterial genetics;Binding;Binding Proteins;Bioinformatics;Biological Assay;Cell Nucleus;Cells;ChIP-seq;chromatin remodeling;Co-Immunoprecipitations;Complex;cytokine;Cytosol;Data;Deposition;Development;Disease;disease model;Drug Design;Ectopic Expression;Epigenetic Process;Experimental Designs;Foundations;Future;Gene Expression;Genes;genetic approach;Genetic Transcription;histone methylation;histone methyltransferase;histone modification;Histones;Human;Immune;Immune response;Immunology;Immunoprecipitation;Infection;Inflammatory;Innate Immune Response;insight;Interferon Type I;Interferons;Knock-out;Knowledge;Learning;Link;Macrophage;Mammalian Genetics;Mass Spectrum Analysis;Measures;member;Membrane;Methyltransferase;Molecular Biology;mouse model;mRNA Precursor;mycobacterial;Mycobacterium Infections;Mycobacterium tuberculosis;Nature;novel;Nuclear;Nuclear Localization Signal;Nuclear RNA;Orthologous Gene;Outcome;pathogen;Pathogenesis;pathogenic bacteria;Pathogenicity;Pathway interactions;Phagosomes;Play;programs;promoter;Promoter Regions;Protein Secretion;Proteins;Proteomics;Regulation;response;RNA Processing;RNA Splicing;Role;Scientist;success;System;Technology;Testing;Time;trafficking;training opportunity;Transcription Elongation;Transcriptional Activation;Transcriptional Regulation;transcriptome sequencing;Tuberculosis;Virulence;Work

PROJECT_TITLE: The Mycobacterium tuberculosis secreted protein Rv1075c hijacks host histone methyltransferases to promote infection

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07A-B (20)]


PHR: Project Narrative Even simple pharmacological frameworks can be difficult to synthesize via traditional methods. Supramolecular catalysis offers unique opportunities for selectivity and reactivity in organic methodology. This proposal leverages the dual activation manifold permitted by coencapsulation to enable complementary regioselectivity, diasteroselectivity, and enantioselectivity in the synthesis of valuable drug-like precursors.

PI_NAMEs: TREACY, SEAN MICHAEL (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TITLE: Supramolecular Dual Substrate Activation: Synthetic Methods via Coencapsulation


NIH_SPENDING_CATS: Aging;Eye Disease and Disorders of Vision;Genetics;Macular Degeneration;Neurodegenerative;Neurosciences;Nutrition

ORG_CITY: IRVINE

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE The retinal pigment epithelium (RPE) is critical in preserving healthy vision, and degeneration of the RPE can lead to irreversible blindness. This project will investigate the basic biology of the RPE, its role in maintaining the health of the retina, and how essential processes are affected during aging. Understanding the molecular underpinnings of age- and disease-related changes in the RPE will inform the development of therapeutics to combat blinding diseases.

PI_NAMEs: TOM, EMILY  (contact)

PROGRAM_OFFICER_NAME: AGARWAL, NEERAJ

PROJECT_TERMS: 11 cis Retinal;Acids;Address;Affect;Age;Age Months;age related;age related changes;Age related macular degeneration;aged;Aging;aging biomarker;Anabolism;Biochemistry;Bioinformatics;Biological Assay;Biology;Biophysics;Blindness;California;Cell Communication;Cell Culture Techniques;Cell membrane;Cell Physiology;Cells;Cellular Membrane;chromophore;combat;Communication;CRISPR/Cas technology;Data;Deposition;design;Deterioration;Development;differential expression;Disease;Disease Progression;DNA Methylation;Docosahexaenoic Acids;Doctor of Philosophy;Drusen;Dryness;Elderly;Electroretinography;Enzymes;Epithelial Physiology;Epithelium;Exhibits;experimental study;Eye;fatty acid metabolism;Fluorescence;Fluorescence Microscopy;Functional disorder;Gene Expression;Gene Expression Profile;Genes;Goals;Health;High Pressure Liquid Chromatography;Histologic;Homeostasis;Hour;Human;Human body;human induced pluripotent stem cells;Impairment;improved;in vivo;Institution;Knock-out;Knowledge;Laboratory Finding;Light;Link;lipid metabolism;lipidome;lipidomics;Lipids;Measurement;Mediating;Medical;Membrane;Mentors;Mentorship;Metabolic;Molecular;Monitor;monolayer;Morphology;Mus;Mutant Strains Mice;Natural regeneration;Nonexudative age-related macular degeneration;novel strategies;Nucleic Acid Regulatory Sequences;Nutrient;Ocular Physiology;Outcome;Pathogenesis;Pathologic;Pathway interactions;Patients;Phagocytes;Phagocytosis;Photoreceptors;Phototransduction;Physiology;Play;Point Mutation;Polyunsaturated Fatty Acids;postmitotic;premature;preservation;Process;Production;Quantitative Reverse Transcriptase PCR;Recycling;Research;response;Retina;Retinal Degeneration;Retinoids;Role;Scientist;single-cell RNA sequencing;skills;social;Specialized Epithelial Cell;standard measure;Structure;Structure of retinal pigment epithelium;Supplementation;Technical Expertise;Testing;therapeutic development;Tissue-Specific Gene Expression;Tissues;Training;Training Programs;Treatment Cost;Universities;Very Long Chain Fatty Acid;Vision;Vision research;Visual;visual cycle;Visual disability;Western Blotting

PROJECT_TITLE: Role of ELOVL2 in age-related visual decline


ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative The microbiome is essential for immune health, but how microbes train the immune system through microbially-regulated molecules, such as serotonin, is unclear. This proposal explores how serotonin regulates intestinal immune tolerance; a pathway important for promoting commensalism and limiting inflammatory responses. Specifically, we will investigate how serotonin-inducing microbes and serotonin receptor 7 plays a role in regulating immunological tolerance in the colon.

PI_NAMEs: YU, LEWIS  (contact)

PROJECT_TERMS: Affect;Agonist;antagonist;Antigen Presentation;Bacteroides fragilis;Behavior;Biological Availability;Biological Process;Blood;Blood Platelets;Bone Marrow;Brain;CD4 Positive T Lymphocytes;Cell Communication;Cell Physiology;Cells;Chemicals;Chemotaxis;Chronic;Coculture Techniques;Colon;commensal bacteria;Complex;cytokine;Dendritic Cells;Development;Disease;dysbiosis;Eating;Enteral;Enterochromaffin Cells;Enteroendocrine Cell;Environment;Flow Cytometry;gastrointestinal function;Gastrointestinal tract structure;Gene Expression;Gene Expression Profile;genetic approach;gut microbes;gut microbiome;gut microbiota;Helper-Inducer T-Lymphocyte;Homeostasis;Hormones;host microbiome;host-microbe interactions;Human;Immune;immune function;immune health;Immune response;Immune system;Immune Tolerance;Immunofluorescence Immunologic;immunoregulation;In Vitro;Inflammatory;Inflammatory Response;intestinal homeostasis;Intestines;Lamina Propria;Macrophage;Maintenance;Mediating;member;Metabolism;Microbe;microbial;microbial colonization;microbial host;microbiome;microbiota;migration;Molecular;Moods;Motility;Mucous Membrane;Mus;Nervous System;neurotransmission;Neurotransmitters;novel;Oral;Pathway interactions;Physiological;Physiology;Polysaccharides;prevent;Process;Production;Property;Protein Isoforms;Regulation;Regulatory T-Lymphocyte;Reporting;Resolution;response;Role;Serotonergic System;Serotonin;serotonin 7 receptor;serotonin receptor;Signal Transduction;Sleep;Spatial Distribution;spatiotemporal;Supplementation;Symbiosis;T-Cell Activation;T-Cell Development;T-Lymphocyte;Testing;Tissue Stains;Training;transcriptome;transcriptome sequencing;Transgenic Mice;villin;Volatile Fatty Acids

PROJECT_TITLE: Identifying the role of serotonin receptor 7 in regulating intestinal immune tolerance

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1 F07B-G (20)]