ORG_CITY: CHAPEL HILL

ORG_NAME: UNIV OF NORTH CAROLINA CHAPEL HILL

ORG_STATE: NC

PHR: NARRATIVE Progression through the cell cycle is tightly controlled by changes in the abundance of hundreds of cellular proteins. Cells control protein abundance by regulating their degradation, and mis-regulation of this process causes human diseases, including cancer and neurological disorders. This proposal will address the enzymes and substrates involved, and their collective influence on proliferation and the integrity of our genetic material.

PI_NAMEs: EMANUELE, MICHAEL JAMES (contact)

PROJECT_TERMS: Address;Binding;Biochemical;Biological Assay;Cell Cycle;Cell Cycle Progression;Cell Cycle Proteins;Cell Cycle Regulation;Cells;Chromatin;Cryoelectron Microscopy;Cyclin-Dependent Kinase Inhibitor;Cyclin-Dependent Kinases;Cyclins;Cytoskeleton;Decision Making;Enzyme Kinetics;Enzymes;Eukaryota;Event;Exhibits;G2 Phase;Genetic Materials;Genetic Transcription;genome integrity;Goals;human disease;Kinetics;Maintenance;Malignant Neoplasms;Metabolism;Methods;Molecular;multicatalytic endopeptidase complex;Nervous System Disorder;Pathway interactions;Phase;Phosphotransferases;Play;PLK1 gene;Post-Translational Protein Processing;preference;Process;programs;Proliferating;protein degradation;Protein Dynamics;Proteins;Proteome;Proteomics;proteostasis;Regulation;Regulatory Pathway;Research;response;Role;Signal Transduction;Stress;Structure;System;Time;Ubiquitin;ubiquitin isopeptidase;ubiquitin-protein ligase;Ubiquitination

PROJECT_TITLE: Proteostasis signaling in cell cycle control


ADMINISTERING_IC: GM

ARRA_FUNDED: N

ED_INST_TYPE: SCHOOLS OF ARTS AND SCIENCES

FUNDING_MECHANISM: NON-SBIR/STTR RPGS

IC_NAME: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

ORG_CITY: ITHACA

ORG_COUNTRY: UNITED STATES

ORG_DEPT: CHEMISTRY

ORG_FIPS: US

ORG_NAME: CORNELL UNIVERSITY

ORG_STATE: NY

PHR: The proposed research is relevant to public health because the mechanisms identified will lead to the development of (bio)chemical strategies to manipulate Zn regulation in Gram-negative bacteria, which are related to many human pathogens. These strategies can be used to effect limitation of the essential micronutrient Zn, increase the toxicity of excess Zn, and thus restrict the growth of invading pathogens. Thus, the proposed research is relevant to the part of NIGMS's mission that pertains to laying the foundation for disease treatment and prevention.

PI_NAMEs: CHEN, PENG  (contact)

PROGRAM_OFFICER_NAME: ANSONG, CHARLES KWAKU

PROJECT_TERMS: antimicrobial;Bacteria;bacterial community;Bacterial Model;Behavior;Biochemical;Biological Models;Biophysics;Cell Communication;cell community;Cells;Cellular biology;cellular imaging;Chemicals;Collaborations;Development;Disease;disorder prevention;DNA;Engineering;Equipment;Escherichia coli;Foundations;Genetic Engineering;Goals;Gram-Negative Bacteria;Growth;Homeostasis;Human;human pathogen;imaging approach;imaging modality;Impairment;In Vitro;innovation;insight;International;Invaded;Knowledge;Location;Metals;microbial community;Microfluidics;Micronutrients;Mission;National Institute of General Medical Sciences;novel;optogenetics;parent project;pathogen;Pathway interactions;Physiological;Prevention;Preventive;Process;programs;Proteins;Public Health;Regulation;Repression;Research;single molecule;spatiotemporal;Structure;System;Therapeutic;Toxic effect;Transcriptional Regulation;Transition Elements;uptake

PROJECT_TITLE: Equipment supplement - Unusual mechanisms of metal regulation in bacteria: from single molecules to single cells to cell communities


NIH_SPENDING_CATS: Networking and Information Technology R&D (NITRD)

ORG_CITY: PHILADELPHIA

ORG_DEPT: BIOLOGY

ORG_NAME: TEMPLE UNIV OF THE COMMONWEALTH

ORG_STATE: PA

PHR: NARRATIVE We are requesting supplementary equipment purchase funds for the parent grant (GM151683, “Hypothesis Testing using Phylogenies for the 21st century”). The requested funds will be used to purchase an ARM Ampere Altra computing cluster with 1920 3GHz compute cores (15 x 128), a head node, and storage (quote included). The computational capacity afforded by this cluster will allow us to better execute the specific aims concerned with simulations, model validation, and complex model development. Second, we will provide a direct service to the broader research community by expanding the Datamonkey (datamonkey.org) server to run on the new cluster in addition to the older existing computing resources, expecting to realize >$120,000 of free compute (see research plan) per year for the worldwide research community.

PI_NAMEs: MUSE, SPENCER V.;NEKRUTENKO, ANTON ;POND, SERGEI L KOSAKOVSKY (contact)

PROGRAM_OFFICER_NAME: WANG, PEGGY

PROJECT_TITLE: Hypothesis Testing using Phylogenies for the 21st century (equipment supplement)


ADMINISTERING_IC: AG

IC_NAME: NATIONAL INSTITUTE ON AGING

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

ORG_CITY: SAINT LOUIS

ORG_DEPT: PSYCHOLOGY

ORG_NAME: WASHINGTON UNIVERSITY

ORG_STATE: MO

PHR: PROJECT NARRATIVE  Alzheimer’s Disease and Related Dementias (ADRD) is a substantial and rapidly-growing public health burden, with no available disease-modifying treatments. Well-being is an understudied but important protective factor against ADRD risk and progression, given that it has been associated with ADRD risk and is amenable to intervention. The planned research will examine multiple types of well-being as predictors of cognitive resilience to ADRD neuropathology as well as bidirectional associations between well-being and cognitive decline.

PI_NAMEs: WILLROTH, EMILY C (contact)

PROGRAM_OFFICER_NAME: HOROWITZ, TODD S

PROJECT_TERMS: Address;Adult;Aging;Agreement;Alzheimer's disease related dementia;Amyloid;Amyloid beta-Protein;Area;Autopsy;Award;Blood Vessels;Brain Pathology;Buffers;career;causal model;Cognitive;cognitive function;Collaborations;comorbidity;Data;Data Analyses;data analysis pipeline;Data Collection;Dementia;dementia risk;demographics;design;Diagnosis;Disease;Education;end of life;Environment;Epidemiologist;Etiology;experience;Health;Health behavior;hedonic;hippocampal sclerosis;Impaired cognition;improved;Individual;Intervention;Knowledge;Lewy Bodies;Lewy Body Disease;Life;life span;Link;longitudinal dataset;Longitudinal Studies;Measures;Medical;medical schools;Memory;Mentors;Mentorship;Modeling;negative affect;Neurobehavioral Manifestations;Neurofibrillary Tangles;neuropathology;older adult;Pathology;Pathway interactions;Personal Satisfaction;Personality;physical conditioning;Physiological Processes;Predictive Factor;prospective;protective factors;protein TDP-43;Psychologist;psychosocial;Public Health;religious order study;Research;Residual state;resilience;Risk Factors;Sampling;satisfaction;Scientist;Severities;skills;Social Sciences;Stress;Symptoms;tau aggregation;tau Proteins;Techniques;Testing;Training;trait;Well in self;Work

PROJECT_TITLE: Well-being as a Protective Factor against Cognitive Decline and Dementia Risk


ADMINISTERING_IC: AA

ED_INST_TYPE: SCHOOLS OF MEDICINE

IC_NAME: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Chronic Liver Disease and Cirrhosis;Clinical Research;Clinical Trials and Supportive Activities;Digestive Diseases;Liver Disease;Substance Misuse

ORG_CITY: INDIANAPOLIS

ORG_DEPT: INTERNAL MEDICINE/MEDICINE

ORG_NAME: INDIANA UNIVERSITY INDIANAPOLIS

ORG_STATE: IN

PHR: Project Narrative Alcoholic cirrhosis is being recognized as an emerging public health concern and one of the leading causes of mortality in the US. The current application seeks to determine the efficacy of S-adenosylmethionine in the treatment of alcoholic cirrhosis, Child class A and B, and its effect on the underlying mechanisms of alcohol- induced injury. We will also identify biomarkers that can predict response to treatment.

PI_NAMEs: GAO, BIN ;LIANGPUNSAKUL, SUTHAT  (contact);LU, SHELLY CHI-LOO

PROGRAM_OFFICER_NAME: MURRAY, GARY

PROJECT_TERMS: Abstinence;Alcohol abuse;Alcohol consumption;Alcohol-Induced Disorders;Alcoholic beverage heavy drinker;Alcoholic Liver Cirrhosis;Alcoholic Liver Diseases;Alcoholic steatohepatitis;Alcohols;Area;Biological;biomarker identification;Catalytic Domain;Cells;Child;Cirrhosis;Clinical Trials;Complex;Complication;COVID-19 pandemic;COVID-19 pandemic effects;CYP2E1 gene;Data;Diglycerides;dimer;Disease;Dose;double-blind placebo controlled trial;effective therapy;efficacy evaluation;endoplasmic reticulum stress;Endotoxemia;Endotoxins;Enrollment;Enzymes;extracellular vesicles;Fatty Acids;Fibrosis;Funding;Genes;Health;Hepatic;Human;Immune;immune activation;Immunologic Markers;improved;inclusion criteria;Indiana;Inflammation;Inflammatory;Injury;insight;Intestinal permeability;Knockout Mice;Lipopolysaccharides;Liver;Liver diseases;liver injury;Los Angeles;Macrophage;Malignant Neoplasms;Mammalian Cell;Mammals;Medical center;Messenger RNA;metabolic phenotype;metabolomics;Methionine;methionine adenosyltransferase;Mitochondrial DNA;Morbidity - disease rate;mortality;National Institute on Alcohol Abuse and Alcoholism;novel;novel strategies;Oral;Oral Administration;Oxidative Stress;Oxidative Stress Induction;pandemic disease;Participant;participant enrollment;particle;Pathogenesis;Pathologic;Pathway interactions;Patients;personalized medicine;Placebos;predicting response;primary endpoint;problem drinker;Process;Proteins;Public Health;Randomized;randomized placebo controlled study;Research;Research Activity;Research Design;Research Institute;response;Risk;Risk Factors;Role;S-Adenosylhomocysteine;S-Adenosylmethionine;Sample Size;Scientist;secondary endpoint;Secondary to;Series;Spain;Supplementation;survival outcome;Techniques;Time;treatment response;Triglycerides;United States;University Hospitals;Violence

PROJECT_TITLE: S-adenosylmethionine treatment in alcoholic cirrhosis


NIH_SPENDING_CATS: Genetics

ORG_CITY: Nashville

ORG_DEPT: BIOCHEMISTRY

ORG_NAME: VANDERBILT UNIVERSITY

ORG_STATE: TN

PHR: Narrative Faithful replication and maintenance of our genomes, which is vital to our survival, requires the action of complex multi-protein machinery that replicates our DNA and responds respond to aberrations in DNA that arise as a by-product of exposure to environmental toxins, sunlight, and even molecules produced naturally in cells. Defects in these protein machines lead to mutation and ultimately cancer and other diseases associated with genomic instabilities. Investigating the three-dimensional structure of the protein components of DNA replication and damage response machines and their interactions with each other and with the DNA will reveal intricate details of how replication and damage response occurs, what is defective in disease-associated mutant proteins, and open up new avenues for development of targeted therapies for patients suffering from maladies such as cancer that arise as a result of genomic instability.

PI_NAMEs: CHAZIN, WALTER J. (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: Address;Automobile Driving;Binding Proteins;Biochemical;biophysical properties;Biophysics;Cells;cofactor;Collaborations;Complex;Coupled;Cryoelectron Microscopy;daughter strand;Defect;Development;Disease;DNA;DNA Binding;DNA biosynthesis;DNA Damage;DNA polymerase alpha-primase;DNA Primase;DNA replication fork;Exposure to;Genome;Genomic Instability;Goals;insight;Knowledge;Lead;Length;Maintenance;Malignant Neoplasms;Modeling;Motor;Multiprotein Complexes;mutant;Mutation;Oxidation-Reduction;Pathway interactions;Patients;Play;Polymerase;Process;Property;Proteins;recruit;response;RNA chemical synthesis;Role;Signal Transduction;Single-Stranded DNA;structural biology;Structure;Sunlight;targeted treatment;Testing;three dimensional structure;Toxic Environmental Substances

PROJECT_TITLE: Integrative Structural Biology in DNA Replication and Damage Response


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Basic Behavioral and Social Science;Behavioral and Social Science;Brain Disorders;Neurosciences;Substance Misuse

ORG_CITY: Chicago

ORG_DEPT: PSYCHIATRY

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

ORG_STATE: IL

PHR: PROJECT NARRATIVE Chronic alcohol exposure produces tolerance to alcohol’s aversive properties, which functions to release the brake on drinking, contributing to difficulty controlling consumption. The neurobiological mechanisms underlying this effect are not well understood but likely include alterations in neural circuits involved in aversive signaling. The project proposed in the current application will examine the role of inputs from functionally distinct subregions of the medial prefrontal cortex to the rostromedial tegmental nucleus in driving chronic tolerance to alcohol’s aversive properties.

PI_NAMEs: GLOVER, ELIZABETH J (contact)

PROGRAM_OFFICER_NAME: POWELL, ELIZABETH

PROJECT_TERMS: alcohol abuse therapy;Alcohol consumption;alcohol exposure;alcohol response;alcohol reward;alcohol use disorder;Alcohols;Attenuated;Automobile Driving;Aversive Stimulus;avoidance behavior;Behavior;behavioral extinction;behavioral response;Brain;Calcium Signaling;Cell Nucleus;Cells;Chronic;Consumption;Data;Dendritic Spines;density;Dependence;design;Development;drinking;Electrophysiology (science);Equilibrium;Ethanol;experience;Experimental Designs;experimental study;Exposure to;Extinction;Feedback;Fiber;Fright;Health;Human;Impairment;in vivo;Individual;innovation;insight;Intoxication;Learning;Link;loss of function;Measures;Medial;Mediating;Midbrain structure;Morphology;neural circuit;neuroadaptation;neurobiological mechanism;neuromechanism;neuron loss;Neuronal Plasticity;Neurons;new therapeutic target;optogenetics;patch clamp;Photometry;Play;Prefrontal Cortex;Property;Public Health;Rattus;response;Rewards;Role;Signal Transduction;Slice;Stimulus;Synapses;Synaptic plasticity;Taste aversion;Testing;Viral;Work

PROJECT_TITLE: Neurobiological mechanisms underlying chronic tolerance to the aversive properties of ethanol

STUDY_SECTION: NAL

STUDY_SECTION_NAME: Neurotoxicology and Alcohol Study Section[NAL]


ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

PHR: PUBLIC HEALTH RELEVANCE CXCR3 plays a central role in inflammation and has established clinical relevance in diseases such as atherosclerosis, cancer and inflammatory bowel disease. We propose an innovative approach to study CXCR3 signaling to aid in the development of a novel drugs. Thus, the proposed research is relevant to the part of NIH’s mission to foster fundamental creative discoveries, innovative research strategies, and their applications as a basis for ultimately protecting and improving health.

PI_NAMEs: RAJAGOPAL, SUDARSHAN K (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: Adaptor Signaling Protein;Address;Agonist;Allosteric Regulation;antagonist;Atherosclerosis;beta-arrestin;Biological;cell motility;Cell Physiology;chemokine;chemokine receptor;Chemotaxis;clinically relevant;Clustered Regularly Interspaced Short Palindromic Repeats;Complex;Contact hypersensitivity;Creativeness;CXC chemokine receptor 3;CXCL9 gene;CXCR3 gene;Development;Disease;Drug Design;drug development;Drug Modelings;Drug Targeting;Endocytosis;Endosomes;FDA approved;Fostering;G-Protein-Coupled Receptors;Genetic Transcription;Goals;GTP-Binding Proteins;Health;Heterotrimeric GTP-Binding Proteins;Immediate-Early Genes;Immune;improved;In Vitro;in vivo;Inflammation;Inflammatory;Inflammatory Bowel Diseases;inflammatory modulation;Inflammatory Response;innovation;knock-down;Knowledge;Ligands;Location;Malignant Neoplasms;Mediating;Mission;Mitogen-Activated Protein Kinases;Modeling;Molecular Conformation;mouse model;mutant;Mutant Strains Mice;new therapeutic target;novel drug class;novel therapeutics;Output;Pattern;Pertussis Toxin;Phosphorylation;Play;prevent;public health relevance;receptor;Receptor Inhibition;receptor internalization;recruit;Regulation;Research;response;Role;Serum Response Element;Signal Pathway;Signal Transduction;skin disorder;small molecule;System;T cell regulation;T-Lymphocyte;targeted treatment;Testing;Therapeutic;United States National Institutes of Health;Work

PROJECT_TITLE: Biasing CXCR3 Signaling to Modulate the Inflammatory Response

STUDY_SECTION: MIST

STUDY_SECTION_NAME: Molecular and Integrative Signal Transduction Study Section[MIST]


ORG_CITY: BOSTON

ORG_NAME: BRIGHAM AND WOMEN'S HOSPITAL

ORG_STATE: MA

PHR: Project Narrative The tRNA cleavage pathway is an emerging mechanism of gene expression regulation based on the production of various tRNA-derived fragments. This mechanism is critical not only for survival under adverse conditions but also implicated in many human diseases such as cancer and neurodegenerative diseases. Here we propose to systematically characterize biogenesis, functions and molecular mechanisms of tRNA-derived molecules.

PI_NAMEs: IVANOV, PAVEL  (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Affect;Alanine-Specific tRNA;Amyotrophic Lateral Sclerosis;angiogenin;Anticodon;Apoptosis;Binding;Biogenesis;Biology;Cell Physiology;Cell Reprogramming;Cell Survival;Cells;Communities;Complex;Cysteine-Specific tRNA;Data;Employment;Ensure;Funding;Future;Gene Expression Regulation;human disease;innovation;Laboratories;Link;Malignant Neoplasms;Messenger RNA;Microscopy;Molecular;Molecular Biology;Mutation;Neurodegenerative Disorders;novel;Nucleotides;Nutrient;overexpression;Parkinson Disease;Pathway interactions;Patients;Play;Production;protein aminoacid sequence;Protein Biosynthesis;Resources;response;Ribonucleases;ribosome profiling;RNA;Role;Source;Stress;stress granule;Therapeutic;Transfer RNA;Translation Initiation;Translational Regulation;Translational Repression;Translations;Triplet Multiple Birth;Untranslated RNA;Work

PROJECT_TITLE: tRNA-derived stress-induced RNAs and translational control

STUDY_SECTION: MG

STUDY_SECTION_NAME: Molecular Genetics Study Section[MG]


ADMINISTERING_IC: OD

FUNDING_MECHANISM: OTHERS

IC_NAME: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome;Patient Safety;Precision Medicine

ORG_CITY: SEATTLE

ORG_NAME: UNIVERSITY OF WASHINGTON

ORG_STATE: WA

PI_NAMEs: EICHLER, EVAN ;EMPEY, PHILIP EARLE;JARVIK, GAIL PAIRITZ (contact);WEI, CHIA-LIN

PROGRAM_OFFICER_NAME: DUTKA, TARA

PROJECT_TERMS: All of Us Genome Center;All of Us Research Program;American;biobank;Board Certification;Businesses;Childhood;Classification;CLIA certified;Clinic;Clinical;clinically actionable;cost effective;Data;Disease;Environment;experience;Funding;Genes;genetic variant;Genetic Variation;Genome;Genomics;Genotype;Goals;Human Genetics;improved;Individual;innovation;Institutional Review Boards;International;Lead;Medical;Medical Genetics;medical schools;Mission;multiple omics;Participant;Pathogenicity;patient engagement;Patients;Pharmaceutical Preparations;Pharmacogenomics;Phase;Physician Executives;Population;Positioning Attribute;Prevalence;Principal Investigator;Process;Production;Reporting;Research;Research Personnel;Resources;Sampling;Technology;tool;United States;Update;Validation;Variant;whole genome;Work;working group

PROJECT_TITLE: Northwest Genomics Center for All of Us


ADMINISTERING_IC: FD

IC_NAME: FOOD AND DRUG ADMINISTRATION

PHR: PROJECT NARRATIVE The U.S. Food and Drug Administration (FDA), through its Office of Medical Policy (OMP), has sought to advance regulatory science, policy, and procedures to address a range of critical public health topics, including drug development, drug approval, bioresearch monitoring, human subject protection, and post market surveillance. The advancement of these critical public health needs requires collaboration with a broad range of stakeholders through convening activities that help advance scientific understanding of these topics, focus on key policy and procedural needs of evolving initiatives, and support or fulfill statutory commitments or requirements. The Robert J. Margolis, MD, Center for Health Policy at Duke University proposes to support the FDA in advancing its medical policy development through rigorous collaborative research and convening activities, building on Duke- Margolis and FDA’s decade-long track record of developing and delivering trusted, high-impact stakeholder engagement and research deliverables on priority regulatory and public health issues.

PI_NAMEs: HAMILTON LOPEZ, MARIANNE  (contact)

PROGRAM_OFFICER_NAME: LAUDA, MARK

PROJECT_TITLE: Convener and organizer of activities and engagements focused on the development of medical products and related processes, surveillance, and policies relevant to ongoing public health activities


NIH_SPENDING_CATS: Infectious Diseases

ORG_CITY: STONY BROOK

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

PHR: PROJECT NARRATIVE (taken from parent grant)  The fungal cell wall is the interface between the cell and its environment. In pathogenic fungi, proper function of the cell wall is important for survival in the host, and drugs targeting cell wall assembly are effective antifungal agents. The spores of baker's yeast Saccharomyces cerevisiae are not pathogenic but are surrounded by a complex coat, the spore wall, which includes many of the same components found in the walls of pathogenic fungi. We are using spore wall formation as a model system to unravel the biochemistry and genetics of fungal wall assembly. This application focuses on understanding how a conserved set of proteins localized on lipid droplets promote the formation of a specific structural feature in the cell wall.

PI_NAMEs: NEIMAN, AARON M (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: anti-fungal agents;Appearance;beta-Glucans;Biochemistry;Biological Models;Candida;Cell Physiology;Cell Wall;Cells;Chitosan;Complex;dityrosine;Drug Targeting;Encapsulated;Environment;environmental stressor;Enzymes;Equipment;fungal genetics;Genome;Grant;Haploidy;Immunocompromised Host;Individual;Infection;Lipids;Mannans;Meiosis;Mycoses;Organelles;parent grant;pathogen;pathogenic fungus;polyphenol;Polysaccharides;Proteins;Public Health;Regulation;Reproduction spores;Resistance;resistant strain;Saccharomyces cerevisiae;Saccharomycetales;Set protein;side effect;Stress;Triglycerides;Yeasts

PROJECT_TITLE: Equipment supplement for grant R01 GM072540  Assembly and Function of the Yeast Spore Wall.

STUDY_SECTION_NAME: Cell Structure and Function 1 Study Section[CSF1]


ADMINISTERING_IC: HL

ED_INST_TYPE: SCHOOLS OF PHARMACY

IC_NAME: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ORG_CITY: HOUSTON

ORG_DEPT: PHARMACOLOGY

ORG_NAME: UNIVERSITY OF HOUSTON

ORG_STATE: TX

PHR: PROJECT NARRATIVE Atherosclerosis-related cardiovascular diseases remain the leading cause of death in the US. We propose to define the protective roles and underlying mechanism of BAF60c-dependent metaboloepigenetic modulations in atherosclerosis. This will provide unique mechanistic insights on the metaboloepigenetic mechanism of atherogenesis and will set the basis to explore new targets for treatment.

PI_NAMEs: ZHAO, GUIZHEN  (contact)

PROGRAM_OFFICER_NAME: CHEN, JUE

PROJECT_TERMS: Abdominal Aortic Aneurysm;Address;Adoption;anaerobic glycolysis;Antibodies;Aorta;Apolipoprotein E;Apoptosis;Arterial Fatty Streak;atherogenesis;Atherosclerosis;atherosclerosis risk;BCL2 gene;Blood Vessels;Cardiovascular Diseases;cardiovascular disorder risk;Catalytic Domain;Cause of Death;cell behavior;Cell Separation;Cells;Cellular Metabolic Process;Cessation of life;Chimeric Proteins;ChIP-seq;Cholesterol;Chromatin;chromatin modification;Chromatin Remodeling Factor;Chromatin Structure;Chronic;Cleavage Under Targets and Release Using Nuclease;clinical practice;Co-Immunoprecipitations;cofactor;Complex;Coupled;Cues;Data;Disease;Energy Metabolism;environmental change;EP300 gene;Epigenetic Process;epigenetic regulation;epigenome;experimental study;Family;Family member;Fatty Acids;Female;Foam Cells;Functional disorder;Future;gain of function;Gene Expression;Genes;Genetic;Genetic Transcription;Global Change;Glucose;Homeostasis;Human;In Vitro;in vivo;Inflammation;inhibitor;insight;knock-down;Knock-in Mouse;Knock-out;Knockout Mice;Ligands;Link;Lipids;loss of function;Macrophage;male;Mass Spectrum Analysis;member;Metabolic;Metabolism;Modeling;Modification;Molecular;Mus;non-genetic;novel therapeutics;Nuclear Receptors;overexpression;Oxidative Stress;oxidized low density lipoprotein;Phenotype;Plasma;PPAR gamma;preservation;Reaction;Regulation;Research;Residual state;response;Risk Management;Role;selective expression;Serum Response Factor;Sex Differences;sexual dimorphism;side effect;Signal Transduction;single-cell RNA sequencing;SMARCA4 gene;Smooth Muscle Myocytes;Stimulus;Sucrose;Therapeutic;transcription factor;Transcriptional Activation;transcriptome sequencing;transcriptomics;Transgenic Mice;Transgenic Organisms;Vascular Smooth Muscle;western diet

PROJECT_TITLE: Metaboloepigenetics and Atherosclerosis

STUDY_SECTION: AVI

STUDY_SECTION_NAME: Atherosclerosis and Vascular Inflammation Study Section[AVI]


ADMINISTERING_IC: CA

ED_INST_TYPE: SCHOOLS OF NURSING

IC_NAME: NATIONAL CANCER INSTITUTE

ORG_CITY: NORFOLK

ORG_NAME: OLD DOMINION UNIVERSITY

ORG_STATE: VA

PHR: PROJECT NARRATIVE Prostate Cancer is a serious health crisis in the United States and remains the second leading cause of cancer-related male deaths despite implementation of new screening methods and therapeutic drugs for this disease. Glycosylation, involving the covalent attachment of carbohydrates onto proteins and lipids, is shown to impact their molecular stability, cellular localization, biological function and malignancy - but virtually nothing is known about the new field of glycosylated RNAs (glycoRNAs) or their role in human disease such as prostate cancer. Innovative/exploratory work described in this proposal employing a spectrum of human prostate cancer cell lines and an in vivo mouse model for prostate cancer will drastically improve our understanding of glycoRNA mechanisms involved during prostate tumor progression and lead to novel RNA-based biomarker and treatment strategies for lethal prostate cancer.

PI_NAMEs: KERSCHER, AURORA ESQUELA (contact)

PROGRAM_OFFICER_NAME: MCKEE, TAWNYA C

PROJECT_TERMS: advanced disease;angiogenesis;Animals;Apoptosis;Area;Azides;Benign;Biological;Biological Markers;Biological Process;biomarker development;Biotinylation;Cancer Biology;cancer biomarkers;Cancer Etiology;Cancer Patient;cancer prevention;cancer therapy;Carbohydrates;cell growth;Cell Line;Cell surface;Cells;Cellular Membrane;Cessation of life;Chemicals;Chemistry;Classification;Clinical;Colon;Comparative Study;Cultured Cells;curative treatments;Diagnosis;Disease;Disease Progression;Distant;Ensure;Enzymes;exosome;Extracellular Matrix;extracellular vesicles;Fractionation;Glycolipids;Glycoproteins;glycosylation;Golgi Apparatus;Health;Homeostasis;hormone sensitivity;Hormones;Human;human disease;Immune response;Immune System Diseases;Immunologic Surveillance;improved;in vivo;inhibitor;innovation;Inosine;insight;intercellular communication;Invaded;Knockout Mice;Label;Lectin;Link;Lipids;Liquid substance;male;Malignant - descriptor;Malignant neoplasm of prostate;Malignant Neoplasms;Mass Spectrum Analysis;Mediating;men;Metabolic;Methods;Modification;Molecular;Monitor;Morphologic artifacts;mouse model;Mus;Mutant Strains Mice;Neoplasm Metastasis;Non-Malignant;Northern Blotting;novel;Nucleic Acids;nucleocytoplasmic transport;Oncogenic;Organ;Pancreas;Pathology;Pathway interactions;patient stratification;Patient-Focused Outcomes;Patients;Pattern;Pharmaceutical Preparations;Play;Polysaccharides;Population;Post-Transcriptional RNA Processing;Post-Translational Protein Processing;posttranscriptional;Process;Prognosis;Prostate;prostate cancer cell;prostate cancer cell line;prostate cancer model;prostate cancer progression;Prostate Cancer therapy;Prostatic Intraepithelial Neoplasias;Prostatic Neoplasms;Protein Glycosylation;Proteins;Pseudouridine;Recurrent disease;response;RNA;Role;screening;Screening procedure;Sialic Acids;sialylation;Signal Transduction;Site;sugar;Survival Rate;survivorship;Tail;Testing;Therapeutic;Time;Tissues;tool;transcriptome sequencing;translational potential;treatment strategy;tumor growth;tumor progression;Tumor Suppressor Genes;tumorigenic;United States;Untranslated RNA;Uridine;virtual;Work

PROJECT_TITLE: Developing glycosylated RNAs as novel clinical targets for aggressive prostate cancer.


ADMINISTERING_IC: ES

IC_NAME: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

NIH_SPENDING_CATS: Cancer;Genetics

ORG_CITY: SAN ANTONIO

ORG_NAME: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER

PHR: NARRATIVE Homology-directed DNA repair (HDR) removes deleterious DNA lesions that are the result of exposure to environmental and chemotherapeutic agents, and defects therein lead to genomic instability, cancer, and other diseases. We will delineate the novel mechanisms by which the opposing actions of HDR factors and regulators help determine the timing and overall efficiency of HDR. Our findings will provide actionable information to identify predictive biomarkers of cancer drug response, and to help guide the development of targeted therapies to treat HDR-deficient cancers.

PI_NAMEs: SUNG, PATRICK  (contact)

PROGRAM_OFFICER_NAME: SHAUGHNESSY, DANIEL

PROJECT_TERMS: Amino Acids;Antineoplastic Agents;Attenuated;Award;BARD1 gene;Biochemical;Biochemistry;Biological;BRCA deficient;BRCA1 gene;cancer therapy;Cell Cycle;Cell Cycle Progression;Cell Death;Cells;Cellular biology;chemotherapeutic agent;Chromatin;Chromosomal Breaks;Chromosomes;combinatorial;Complex;Defect;Deoxyribonucleases;Development;Disease;DNA;DNA Binding;DNA biosynthesis;DNA Damage;DNA Double Strand Break;DNA lesion;DNA Repair;DNA Repair Pathway;DNA replication fork;Double Strand Break Repair;Drug resistance;endonuclease;Environment;Enzymes;Epigenetic Process;Excision;EXO1 gene;Exposure to;Failure;Filament;Foundations;Functional disorder;G1 Phase;G2 Phase;Genetic;Genomic Instability;Goals;Grant;helicase;Human;in vivo;inhibitor;insight;Lead;Length;Link;Malignant Neoplasms;Mediating;mutant;Neoplastic Cell Transformation;Nonhomologous DNA End Joining;novel;Outcome;p53-binding protein 1;Pathway interactions;Poly(ADP-ribose) Polymerase Inhibitor;Polymerase;predictive marker;Procedures;Process;protein complex;protein purification;Proteins;Rad51 recombinase;Reader;reconstitution;recruit;Regulation;repaired;Resected;Resistance;response;restoration;Ribose;S phase;Saccharomyces cerevisiae;Saccharomycetales;Single-Stranded DNA;spleen exonuclease;System;Tail;targeted cancer therapy;targeted treatment;Testing;Therapeutic;tool;treatment response;tumor;Tumor Suppressor Proteins

PROJECT_TITLE: MECHANISMS OF DNA DOUBLE-STRAND BREAK END RESECTION AND REPAIR PATHWAY CHOICE..


NIH_SPENDING_CATS: Infectious Diseases;Natural Products

ORG_CITY: BERKELEY

ORG_NAME: UNIVERSITY OF CALIFORNIA BERKELEY

ORG_STATE: CA

PHR: Narrative Dinuclear monooxygenases play essential roles in microbial metabolism and bioactive natural product formation. While many of these enzymes are thought to utilize di-iron cofactors to activate the strong carbon-hydrogen bonds of the cognate substrate, our group has recently characterized an enzyme that strictly requires formation of a mixed manganese/iron cofactor. To expand the context of this discovery and broadly understand uncharacterized monooxygenases present throughout biology, our investigation seeks to discover, characterize and understand an emergent family of manganese-dependent monooxygenases.

PI_NAMEs: RITTLE, JONATHAN D (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TERMS: Active Sites;Aerobic;Amidohydrolases;Amino Acid Motifs;Aminoisobutyric Acids;bioactive natural products;Biochemical Process;Bioinorganic Chemistry;Biological;Biology;Carbon;cofactor;Competence;Copper;Electron Transport;electronic structure;Endowment;Enzymatic Biochemistry;Enzymes;Family;geometric structure;Heme;Hydrogen Bonding;interest;Investigation;Ions;Iron;Kinetics;Manganese;member;Metabolism;metallicity;Metals;Methods;microbial;Mixed Function Oxygenases;Natural Products;Organism;oxidation;Oxidation-Reduction;Oxygenases;pathogen;photosystem II;Play;Protein Family;protein folding;Proteins;Reaction;Research;Rhodococcus;Role;spectroscopic survey;structural biology;Structure;Thermodynamics;Water

PROJECT_TITLE: Discovery and Characterization of Manganese-dependent Monooxygenases


ORG_CITY: LA JOLLA

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: PROJECT NARRATIVE The focus of this project is to understand the catalytic mechanism of the enzyme nitrogenase. Nitrogenase is the only biological agent that can reduce atmospheric dinitrogen into a bioavailable form (ammonia) and therefore has an immense global impact on human health and welfare through supporting the agricultural/nutritional needs of ~2 billion people. It is also a unique model enzyme that couples biological redox catalysis with ATP-dependent energy transduction processes, which are both central to cellular metabolism.

PI_NAMEs: TEZCAN, FAIK AKIF (contact)

PROJECT_TERMS: Active Sites;Agriculture;Ammonia;Atmosphere;ATP Hydrolysis;Binding;Biochemical;Biological;Biological Availability;Biological Models;Biological Products;Biophysics;Catalysis;Cell Physiology;Chemicals;Complex;Couples;Cryoelectron Microscopy;Development;enzyme mechanism;enzyme model;Enzymes;experimental study;Guanosine Triphosphate;Health;Human;Investigation;Maps;Metabolism;Methodology;Molecular Conformation;Nitrogen Fixation;Nitrogenase;Nucleotides;Nutritional;Oxidation-Reduction;Persons;Population;Process;programs;Protein Dynamics;Reaction;Research;Resolution;small molecule;welfare

PROJECT_TITLE: Mechanism of Energy Transduction and Substrate Activation in Biological Nitrogen Fixation


NIH_SPENDING_CATS: Nutrition

PHR: PROJECT NARRATIVE: Alterations in lipid metabolism and transport are linked to the onset and progression of various human diseases including cancer, diabetes, heart disease, and vision disorders. Our studies will contribute to understanding the molecular mechanisms for the action of enzymes and lipid transport proteins implicated in these processes.

PI_NAMEs: AIROLA, MICHAEL VIRGIL (contact)

PROGRAM_OFFICER_NAME: BARSKI, OLEG

PROJECT_TERMS: Anabolism;Binding;Biochemical;Biological;Biological Assay;Cardiovascular Diseases;Carrier Proteins;Cell membrane;cell motility;Cell Proliferation;Complex;Deuterium;Diabetes Mellitus;Diglycerides;Enzymes;extracellular;Fatty acid glycerol esters;Fatty Acids;Foundations;Funding;Goals;Heart Diseases;human disease;Hydrogen;Hydrolysis;improved;insight;insulin sensitivity;interest;Ions;Knowledge;Lecithin;Link;Lipid Biochemistry;lipid metabolism;lipid transfer protein;lipid transport;Lipids;lipine;Lipoproteins;Malignant Neoplasms;Mammalian Cell;Mass Spectrum Analysis;Mediating;Membrane;Metabolism;Molecular;Molecular Conformation;Molecular Mechanisms of Action;Nuclear Envelope;Obesity;pharmacologic;Phosphatidate Phosphatase;Phosphatidic Acid;Phosphatidylinositols;Phospholipase D;Phospholipids;Physiological;Play;Post-Translational Protein Processing;Process;Protein Dephosphorylation;protein function;Protein phosphatase;Proteins;receptor;Regulation;response;Role;Second Messenger Systems;Site;Stimulus;Structure;Substrate Specificity;therapeutic target;trafficking;Triglycerides;Vision Disorders;Work

PROJECT_TITLE: Structure and regulation of lipid metabolism and transport

STUDY_SECTION: MRAB

STUDY_SECTION_NAME: Maximizing Investigators’ Research Award B Study Section[MRAB]


ED_INST_TYPE: SCHOOLS OF PUBLIC HEALTH

NIH_SPENDING_CATS: Aging;Cardiovascular;Contraception/Reproduction;Genetics;Hypertension;Maternal Health;Maternal Morbidity and Mortality;Pregnancy;Prevention;Women's Health Research

ORG_CITY: BIRMINGHAM

ORG_DEPT: PUBLIC HEALTH & PREV MEDICINE

ORG_NAME: UNIVERSITY OF ALABAMA AT BIRMINGHAM

ORG_STATE: AL

PHR: NARRATIVE This project will explore if ambient heat exposure during the first trimester and/or accelerated epigenetic aging is associated with preeclampsia among pregnant individuals with chronic hypertension. It will add significantly to our understanding of environmental determinants of preeclampsia and if older biological age poses a risk for the development of preeclampsia. Considering the warming associated with climate change and the relationship between preeclampsia and the development of cardiovascular disease later in life, this work will contribute valuable evidence about how our changing environment may affect health for women across the adult lifespan.

PI_NAMEs: HIDALGO, BERTHA  (contact);TITA, ALAN THEVENET N.;TIWARI, HEMANT K.

PROGRAM_OFFICER_NAME: YAN, YE

PROJECT_TERMS: accelerated epigenetic aging;Acute;Address;Adult;advanced maternal age;Affect;Age;age related;Age Years;age-related disease;Ancillary Study;biological age;Cardiovascular Diseases;Cardiovascular system;Chronic;Chronology;Climate;climate change;Conceptions;Data;Data Set;design;Development;Diagnosis;Environment;Environmental Exposure;Environmental Risk Factor;Epidemiology;epigenetic aging;epigenetic marker;Epigenetic Process;epigenomics;Event;exhibitions;experience;Exposure to;fetal;Fetal Death;Fetal health;First Pregnancy Trimester;Future;geographic difference;Goals;Health;High temperature of physical object;Hypertension;Incidence;Individual;interest;Investigation;Kidney;Life;life span;Link;Maternal Health;Maternal Mortality;Mentors;Methods;Mothers;Outcome;parent grant;Parents;Participant;pathophysiology of preeclampsia;Pattern;Physiological;Play;poor health outcome;Pre-Eclampsia;Pregnancy;Pregnancy Complications;Pregnancy Outcome;pregnant;Proteinuria;Renal function;Research;Risk;Risk Factors;Role;Seasons;Site;System;Temperature;Testing;Training;United States;Women's Health;Work

PROJECT_TITLE: Epigenetic biomarkers of preeclampsia risk among mothers with chronic hypertension


NIH_SPENDING_CATS: Genetics;Infertility

ORG_CITY: NEW ORLEANS

ORG_NAME: TULANE UNIVERSITY OF LOUISIANA

ORG_STATE: LA

PHR: PROJECT NARRATIVE Transposons are mobile DNA elements that are ubiquitous in genomes of all animals, including humans. Overactive transposons are correlated with DNA damage and infertility, but it is unclear whether the transposons are playing a causative role in infertility. In this proposal, we will examine transposon activity in germ cells and experimentally block or activate transposition to assess the effects on genome integrity.

PI_NAMEs: HAN, JEFFREY S (contact)

PROGRAM_OFFICER_NAME: MACARTHUR, LINDA

PROJECT_TERMS: Aging;Alleles;Animals;Automobile Driving;Biochemical;Biogenesis;Biological;Biology;cell immortalization;Cell Line;Complex;Defect;Disease;DNA Damage;Elements;Endosomes;Family;Future;Genes;Genetic Screening;Genome;genome integrity;Germ Cells;Germ Lines;Germ-Line Mutation;Human;human male;human tissue;in vivo;Infertility;insight;Integration Host Factors;Knock-out;Knowledge;male;Male Infertility;Male Sterility;Malignant Neoplasms;mammalian genome;Mammals;Meiotic Prophase I;model organism;mouse genetics;mouse model;Mus;mutant;Mutate;Mutation;Nervous System Disorder;Nuclear;overexpression;Pathway interactions;Phenotype;piRNA;Play;Productivity;Regulation;Retrotransposition;Role;Small RNA;Sorting;tissue culture;trafficking;transposon/insertion element;Wild Type Mouse;Work;Yeasts

PROJECT_TITLE: In vivo biology of mammalian L1 retrotransposition - supplement 2024


ADMINISTERING_IC: NS

FUNDING_MECHANISM: OTHER RESEARCH-RELATED

IC_NAME: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

NIH_SPENDING_CATS: Charcot-Marie-Tooth Disease;Neurodegenerative;Neurosciences;Peripheral Neuropathy;Rare Diseases

ORG_CITY: COLUMBIA

ORG_DEPT: PHYSICAL MEDICINE & REHAB

ORG_NAME: UNIVERSITY OF MISSOURI-COLUMBIA

PHR: Project Narrative  Charcot-Marie-Tooth Disease Type 1A (CMT1A) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) are the most common dysmyelinating peripheral neuropathies. These diseases are caused by altered Peripheral Myelin Protein 22 (PMP22) gene dosage and an inadequate understanding on PMP22 protein function limits therapy development. The proposed research will expand knowledge of what PMP22 does in myelin, how it is regulated and when precise expression is required as a means to improve therapeutic potential of CMT1A and HNPP.

PI_NAMEs: MOSS, KATHRYN RENAE (contact)

PROGRAM_OFFICER_NAME: NUCKOLLS, GLEN H

PROJECT_TERMS: Acceleration;Adherens Junction;Adhesions;Affect;Aging;Award;Axon;biophysical properties;biophysical techniques;Biophysics;Canis familiaris;career;Career Transition Award;Cell Adhesion;Cell membrane;Cell model;Cells;Charcot-Marie-Tooth Disease;Complement;Complex;confocal imaging;Confocal Microscopy;Development;Disease;dosage;dysmyelination;Electrical Resistance;Electron Microscopy;Gene Dosage;Genes;Goals;Hereditary Motor and Sensory Neuropathy Type I;Hereditary neuropathy with liability to pressure palsies;Human;improved;inducible Cre;Inherited;Intercellular Junctions;Investigation;kidney epithelial cell;Knowledge;Label;MDCK cell;Membrane;Membrane Microdomains;Mentorship;Microscopy;Modeling;Modification;Molecular Neurobiology;Morphology;mouse model;mutant;Myelin;myelination;Nerve;Nerve Fibers;overexpression;palmitoylation;Pathogenesis;Peripheral;Peripheral Nerves;Peripheral Nervous System Diseases;Phase;Phenotype;PMP22 gene;Positioning Attribute;protein function;Regulation;Research;Research Personnel;Role;Schwann Cells;success;superresolution microscopy;System;Tamoxifen;Technical Expertise;Techniques;Therapeutic;therapeutically effective;therapy development;Tight Junctions;Training;Transfection;ultra high resolution;Vesicle;Work

PROJECT_TITLE: Function and Regulation of PMP22 in CMT1A and HNPP


NIH_SPENDING_CATS: Genetics;Human Genome

PHR: 8. PROJECT NARRATIVE Chromatin structure and organization profoundly influence gene expression which ultimately controls normal cell proliferation and cellular differentiation in humans. Mutations in genes functioning in chromatin assembly and remodeling are found associated with numerous human tumors. This grant is focused on understanding a unique type of chromatin structure and how this structure is used by the cell to influence genomic activities, such as gene expression. The outcome of this research could potentially lead to new targets for therapeutic intervention.

PI_NAMEs: LUK, EDWARD E (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Biochemical;Biological;Biological Process;Cell Differentiation process;Cell Proliferation;Cells;Chromatin;Chromatin Modeling;chromatin remodeling;Chromatin Structure;crosslink;Cryoelectron Microscopy;Data;Eukaryota;Eukaryotic Cell;Gene Expression;gene function;Gene Silencing;Genomics;Grant;Heterochromatin;Histone H4;Human;in vivo;insight;Methodology;Modification;mutant;Mutation;new therapeutic target;Normal Cell;Nucleoproteins;Nucleosomes;Outcomes Research;particle;Role;Structure;Techniques;telomere;Therapeutic Intervention;tumor;Variant;Yeasts

PROJECT_TITLE: Uncovering the biomolecular function of the R-octasome--a nucleosome-like particle with only H3 and H4 histones


ADMINISTERING_IC: DK

IC_NAME: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;Comparative Effectiveness Research;Health Disparities Research;Health Disparities and Racial or Ethnic Minority Health Research;Kidney Disease;Prevention;Racial and Ethnic Minority Health Research;Social Determinants of Health;Transplantation

ORG_CITY: Aurora

ORG_NAME: UNIVERSITY OF COLORADO DENVER

ORG_STATE: CO

PHR: PROJECT NARRATIVE The Latinx community bears a disproportionate burden of chronic kidney disease, and they are less likely to start recommended kidney replacement therapy, such as kidney transplant or home dialysis, compared to non- Latinx White individuals. Our funded parent grant (1U01DK137272-01) allows us to conduct a patient-level randomized controlled trial of NAVIGATE-Kidney, a multi-level, community health worker intervention for Latinx with kidney disease, that will reduce kidney health disparities. The proposed supplement responds to the NIH Office of Disease Prevention (ODP). The NIH ODP conducted a thoughtful review of our protocol and recommended we modify our study design to an individually randomized group treatment trial.

PI_NAMEs: CERVANTES, LILIA  (contact);MYASKOVSKY, LARISSA

PROGRAM_OFFICER_NAME: NORTON, JENNIFER MICHELLE

PROJECT_TERMS: American;arm;Arteriovenous fistula;arteriovenous graft;Caring;Catheters;Cessation of life;Chronic Kidney Failure;Clinical Trials;Colorado;Communities;community engaged research;Community Health Aides;Conflict (Psychology);Data;Dialysis procedure;Discrimination;disorder prevention;Dropout;effectiveness outcome;ethnic minority;Event;Face;Failure;Funding;Future;Gender;hazard;Health;health disparity;health equity;Hemodialysis;high risk;Hispanic Populations;Home;improved;Incentives;Individual;Infection;Intervention;Kidney;Kidney Diseases;Kidney Failure;Kidney Transplantation;Language;Latino;Latinx;Latinx population;Literature;Maintenance;Methods;Modeling;mortality risk;Nephrology;Outcome;parent grant;Participant;Patient-Focused Outcomes;Patients;payment;Peritoneal Dialysis;person centered;pilot test;Population;primary endpoint;primary outcome;Protocols documentation;racial minority;Randomized;Randomized, Controlled Trials;Recommendation;recruit;Renal Replacement Therapy;Research;Research Design;Research Methodology;Research Personnel;Risk;Sample Size;Schedule;Science;secondary outcome;Site;skills;Structural Racism;Testing;Time;treatment arm;treatment group;treatment trial;United States Centers for Medicare and Medicaid Services;United States National Institutes of Health;Venous;Visit;Work

PROJECT_TITLE: NAVIGATE-Kidney: Reducing Type 1 Error Rate by Modifying Methods to Individually Randomized Group Treatment Trial


PHR: NARRATIVE Although all cells have the same collection of genes, what makes them different is which genes are turned on and which are turned off. When genes are inappropriately expressed, cancer can sometimes occur, or the development of an organism can occur improperly. This proposal focuses on understanding links between different steps in turning on a gene, in particular, the relationship between destroying the ﬁnal protein product, making the protein product, and getting rid of intermediate products.

PI_NAMEs: RISSLAND, OLIVIA SELFRIDGE (contact)

PROJECT_TERMS: Area;Award;Biological;Biological Models;Biology;Cells;Codon Nucleotides;Collection;Development;Drosophila genus;Drosophila melanogaster;Embryo;Equipment;Excision;Gene Expression;Gene Expression Regulation;gene product;Genes;Human;Investigation;Lead;Link;Malignant Neoplasms;Mediating;Molecular;mRNA Decay;mRNA Translation;Organism;Output;Pathway interactions;Philosophy;Post-Transcriptional Regulation;posttranscriptional;Process;programs;Proteins;Reading;Regulation;Regulatory Pathway;Research;RNA-Binding Proteins;Role;Shapes;skills;System;Time;Translation Initiation;Translational Repression;Translations;Work

PROJECT_TITLE: Equipment Supplement 2R35GM128680: Exploring the connections between translation and mRNA decay

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


ADMINISTERING_IC: AT

IC_NAME: NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH

NIH_SPENDING_CATS: Biotechnology;Chronic Pain;Complementary and Integrative Health;Dietary Supplements;Natural Products;Neurodegenerative;Neurosciences;Nutrition;Pain Research;Peripheral Neuropathy

ORG_CITY: IRVINE

ORG_DEPT: PHYSIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA-IRVINE

PHR: PROJECT NARRATIVE This research addresses a specific unmet medical need, the absence of effective therapeutics for neuropathic pain (NeuP), a debilitating chronic pain syndrome that develops as a result of nerve injuries caused by trauma or disease and affects over 16 million Americans. This proposal seeks to optimize a novel fluorescent high- throughput screening (HTS) assay for identifying small molecule blockers of the voltage-gated proton channel (Hv1) from botanicals that reduce the release of inflammatory mediators by microglia and thereby relieve NeuP. The project will build on preliminary findings to optimize the HTS assay and identify lead compounds for devel- opment as drugs targeting Hv1; these agents will have a number of other potential uses because Hv1 is central not only to the development of NeuP but also contributes to tissue damage after ischemic stroke and spinal cord injury.

PI_NAMEs: GOLDSTEIN, STEVE A N;WU, LONG-JUN ;ZHAO, RUIMING  (contact)

PROGRAM_OFFICER_NAME: CHEN, WEN G

PROJECT_TERMS: Address;Affect;Affinity;American;Analgesics;Astrocytes;Attenuated;Automobile Driving;Biological Assay;Botanicals;Brain;Cells;Central Nervous System;channel blockers;Chronic pain syndrome;chronic painful condition;Clinical;cytokine;Data;design;Development;Disease;Drug Kinetics;Drug Targeting;efficacy evaluation;efficacy validation;Electrophysiology (science);Fluorescence;Goals;high throughput screening;Hour;Human;Immune;improved;In Vitro;in vivo;in vivo Model;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;inhibitor;innovation;intraperitoneal;Intrathecal Injections;Ischemic Stroke;Knockout Mice;Lavandula;Lead;Libraries;Link;link protein;marine;Mediating;Mediator;Medical;Medicinal Plants;Methods;Microglia;mouse model;Mus;Natural Compound;nerve injury;nerve transection;neuroinflammation;neuronal excitability;Neurotoxins;neutrophil;novel;novel therapeutics;operation;Opioid;Pain;pain relief;painful neuropathy;Patients;Peptides;Performance;Peripheral nerve injury;Pharmaceutical Preparations;pharmacologic;Pharmacology;Phase;Phytochemical;Plant Extracts;Plants;Production;Proteins;Protons;Public Health;Publications;Quality of life;Rapid screening;Reactive Oxygen Species;Reagent;real time monitoring;receptor;Recording of previous events;Refractory;Reporting;Research;Research Personnel;response;Risk;Role;Route;screening;side effect;small molecule;small molecule therapeutics;Specificity;Spinal Cord;Spinal cord injury;Spinal nerve structure;success;temporal measurement;Therapeutic;therapeutic target;therapeutically effective;Tissues;Traditional Medicine;Trauma;treatment effect;Validation;Variant;voltage;Work

PROJECT_TITLE: Identification of botanical hHv1 channel blockers as analgesics for neuropathic pain

STUDY_SECTION: NSD

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


ORG_CITY: Boulder

ORG_NAME: UNIVERSITY OF COLORADO

PHR: PROJECT NARRATIVE This equipment supplement application requests support to purchase a CytoFLEX S Analyzer, a next-generation flow cytometry analyzer for measuring multi-dimensional features of individual cells with increased speed, reliability, and reproducibility. The proposed purchase of this cutting-edge instrument will overcome current limitations in characterizing a novel class of unannotated proteins in regulated exocytosis.

PI_NAMEs: SHEN, JINGSHI  (contact)

PROGRAM_OFFICER_NAME: WAIRKAR, YOGESH PRABHAKAR

PROJECT_TERMS: Biochemical;Biological Process;Candidate Disease Gene;Cell Physiology;Cells;Clathrin;Clustered Regularly Interspaced Short Palindromic Repeats;Coupled;CRISPR screen;Cytosol;Dedications;Development;Dimensions;Disease;Endocytosis;enhancer-binding protein AP-2;Equipment;Exocytosis;Flow Cytometry;Genetic Screening;Genetic study;Glean;GLUT 4 protein;Goals;Homeostasis;human disease;Individual;insight;instrument;Insulin;Knowledge;Lead;Measures;Mediating;Membrane;Modeling;Molecular;Molecular Chaperones;next generation;novel;novel therapeutic intervention;Nutrient;Pathway interactions;Physiological;Proteins;Reproducibility;Request for Applications;Research;response;Signal Transduction;Speed;Stimulus;trafficking;Vesicle;Viral;Work

PROJECT_TITLE: Discovering protein networks underlying regulated exocytosis


ED_INST_TYPE: BIOMED ENGR/COL ENGR/ENGR STA

ORG_CITY: DAVIS

ORG_DEPT: BIOMEDICAL ENGINEERING

ORG_NAME: UNIVERSITY OF CALIFORNIA AT DAVIS

PHR: Project Narrative All cells in tissues and organs experience some degree of physical forces, but how cells react to such forces is not well defined. Using innovative techniques to detect protein associations, we will determine how physical forces change protein interactions surrounding cyto-keratins, a family of fibrous proteins required for maintaining the physical integrity of cells and tissues. This proposal aims to understand the molecular basis of the keratin network’s force-induced responses and reveal novel keratin functions that may contribute to how cancer cells break free from their primary tissues and metastasize to tissues elsewhere and identify targets for novel therapeutics.

PI_NAMEs: YAMADA, SOICHIRO  (contact)

PROJECT_TERMS: Actins;Biotin;cancer cell;candidate identification;cell behavior;cell motility;Cells;Cytokeratin;Cytokeratin filaments;Cytoskeleton;Environment;Epithelial Cells;Epithelium;experience;Extracellular Matrix;Family;Fiber;fibrous protein;Goals;In Situ;In Vitro;innovation;Intermediate Filament Proteins;Keratin;Label;Maintenance;mechanotransduction;Mediating;Molecular;Neoplasm Metastasis;new therapeutic target;novel;Organ;Physical Stimulation;Physiological;protein protein interaction;Proteins;Reaction;recruit;Regulation;response;Role;Techniques;Testing;Time;Tissues;Transcriptional Regulation;Tumor Promoters;Tumor Suppressor Proteins

PROJECT_TITLE: Molecular basis of force-sensing by the keratin network


ORG_CITY: PITTSBURGH

ORG_NAME: UNIVERSITY OF PITTSBURGH AT PITTSBURGH

PHR: Project Narrative We propose a novel immunotherapeutic approach to bolster the graft-versus-leukemia effect, addressing the urgent need for effective therapies for post-transplant relapse. In a multicenter phase 2 trial, we will evaluate the efficacy and safety of interferon-gamma and donor leukocyte infusion for patients with acute myeloid leukemia and myelodysplastic syndrome who have relapsed after allogeneic stem cell transplantation. The success of this trial could potentially, for the first time, establish a standard of care for patients with post-transplant relapse.

PI_NAMEs: ITO, SAWA  (contact);SHLOMCHIK, WARREN D

PROGRAM_OFFICER_NAME: SUN, HAIHAO

PROJECT_TITLE: Phase 2 Study of Interferon-Gamma and Donor Lymphocyte Infusion for the Treatment of Relapsed Myeloid Malignancies after Allogeneic Stem Cell Transplantation

STUDY_SECTION_NAME: Special Emphasis Panel[ZFD1 OC-S (01)]


ORG_CITY: ROCHESTER

ORG_NAME: UNIVERSITY OF ROCHESTER

PHR: Project Narrative Nearly all phenotypes, from height and weight to disease susceptibility, result from a complex interplay between genes and the environment. This project aims to illuminate basic rules acting to integrate environmental and genetic signals in the production of the phenotype. Thus, the proposed research is relevant to the part of NIH's mission that pertains to developing fundamental knowledge that will help to reduce the prevalence of human disease.

PI_NAMEs: BRISSON, JENNIFER A (contact)

PROGRAM_OFFICER_NAME: WELLS, MELISSA LYNN

PROJECT_TERMS: Address;Aphids;asexual;Bypass;Complex;Cues;Developmental Process;dimorphism;Disease;Disease susceptibility;Environment;Epigenetic Process;Evolution;Exhibits;experimental study;fascinate;Female;Follistatin;Genes;Genetic;Genetic Polymorphism;genomic locus;Health;Height;Horizontal Gene Transfer;Hormones;Human;human disease;innovation;insight;Knowledge;Life;male;Mission;Modeling;Molecular;Morphology;Nature;Organism;paralogous gene;Phenotype;Pisum sativum;Plants;Prevalence;Process;Production;programs;recruit;Research;Role;Signal Transduction;Testing;Textbooks;trait;United States National Institutes of Health;Variant;Weight;Wing;Women's study

PROJECT_TITLE: Molecular Mechanisms and Evolution of Phenotypic Plasticity


ADMINISTERING_IC: AI

IC_NAME: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

NIH_SPENDING_CATS: Behavioral and Social Science;Clinical Research;Clinical Trials and Supportive Activities;HIV/AIDS;Immunization;Infectious Diseases;Prevention;Vaccine Related;Vaccine Related - AIDS

ORG_CITY: BALTIMORE

ORG_NAME: JOHNS HOPKINS UNIVERSITY

ORG_STATE: MD

PHR: Project Narrative The Johns Hopkins University-Blantyre, Malawi Clinical Trials Unit (CTU) and its Clinical Research Site (CRS) in Blantyre, Malawi have the expertise, experience, infrastructure and commitment to contribute to the scientific agendas of four NIAID Clinical Research Networks. Over the past 30 years, including 13 years in the preivious and current CTU cycle, the CRS has strong relationships with the community, in order to educate stakeholders about the value of research and to share key findings from all studies. The CTU Principal Investigator is strongly supported by the host institution, the Johns Hopkins University, through its leadership and a wide array of research-related resources.

PI_NAMEs: JENNINGS, JACKY M;TAHA, TAHA E (contact)

PROGRAM_OFFICER_NAME: CASTILLO, BLANCA E

PROJECT_TERMS: Acquired Immunodeficiency Syndrome;Adolescent;Adult;Affect;Africa;Africa South of the Sahara;age group;AIDS prevention;Area;Basic Science;Behavior Therapy;Child;Childhood;Cities;Clinical;Clinical Management;Clinical Research;clinical research site;Clinical Trials;Clinical Trials Cooperative Group;Clinical Trials Network;Clinical Trials Unit;Collaborations;college;Communication;Communities;community collaboration;community engagement;Country;Data;data management;Development;Elements;Ensure;Epidemic;Ethics;Evaluation;experience;flexibility;Generations;Goals;Health;high standard;HIV;HIV Infections;HIV prevention trials network;HIV Seronegativity;HIV Seropositivity;HIV Vaccine Trials Network;HIV-1;HIV/AIDS;Individual;Information Technology;Infrastructure;Institution;International;Laboratories;Leadership;Malawi;Medicine;Mentors;Microbicide Trials Network;Modality;National Institute of Allergy and Infectious Disease;Occupational activity of managing finances;Office of Administrative Management;operation;Patient Self-Report;Persons;Pharmacy facility;Policies;Population;Prevalence;prevent;Prevention;Prevention Research;Preventive;Principal Investigator;programs;Prophylactic treatment;Protocols documentation;Regimen;Research;Research Infrastructure;Research Priority;research study;Resources;Risk;Role;Scientific Advances and Accomplishments;Site;social interventions;statistics;Structure;support network;Surveys;Testing;Therapeutic Clinical Trial;Training;treatment research;United States National Institutes of Health;Universities;Vaccine Research;vaccine trial;Vaccines;Viral Load result;Work

PROJECT_TITLE: The Johns Hopkins University-Blantyre Clinical Trials Unit


ORG_CITY: STANFORD

ORG_NAME: STANFORD UNIVERSITY

PHR: Project Narrative Ribosome quality control (RQC) monitors the fidelity of protein synthesis in real-time to ensure that genetic information is correctly decoded and defects in this process cause devastating human diseases. While basic mechanisms of RQC have been recently defined for cytosolic proteins, almost nothing is known about RQC for ribosomes at the endoplasmic reticulum (ER) that make the nearly one third of human proteins destined for the secretory pathway. The proposed research leverages innovative technologies to elucidate the RQC mechanism for proteins in the secretory pathway.

PI_NAMEs: KOPITO, RON R (contact)

PROGRAM_OFFICER_NAME: REDDY, MICHAEL K

PROJECT_TERMS: ATP phosphohydrolase;Binding;Biochemical;Biogenesis;Cells;Collaborations;Cytoplasm;Cytosol;Data;Defect;Disease;Dislocations;Dissection;Endoplasmic Reticulum;Endoplasmic Reticulum Degradation Pathway;Ensure;experimental study;Foundations;genetic information;Genome;Goals;Human;human disease;Impairment;In Vitro;innovative technologies;insight;Knowledge;Label;Lysine;Membrane;Membrane Proteins;Modification;Molecular;Monitor;multicatalytic endopeptidase complex;Organelles;Outcome;Pathway interactions;Peptides;Play;Process;Protein Biosynthesis;Proteins;proteostasis;proteotoxicity;Publishing;Quality Control;Reader;recruit;Recycling;Research;response;Ribosomal Proteins;Ribosomes;Role;Route;seal;secretory protein;segregation;Structure;System;Testing;Time;time use;Transfer RNA;Ubiquitin;Ubiquitin Like Proteins;ubiquitin-protein ligase;Work

PROJECT_TITLE: The role of UFMylation in ribosome quality control at the ER


NIH_SPENDING_CATS: Disability Research;Precision Medicine

ORG_CITY: ROCKVILLE

ORG_NAME: AMERICAN ASSN ON HEALTH AND DISABILITY

PHR: No PHR

PI_NAMEs: FORBER-PRATT, ANJALI J (contact)

PROGRAM_OFFICER_NAME: CROSBY, YONG RAY

PROJECT_TERMS: community engagement;disability

PROJECT_TITLE: Disability Community Engagement Partner Project


NIH_SPENDING_CATS: Alcoholism, Alcohol Use and Health;Genetics;Infectious Diseases;Stem Cell Research;Stem Cell Research - Nonembryonic - Non-Human;Substance Misuse

ORG_CITY: LEXINGTON

ORG_DEPT: MICROBIOLOGY/IMMUN/VIROLOGY

ORG_NAME: UNIVERSITY OF KENTUCKY

ORG_STATE: KY

PHR: PROJECT NARRATIVE/RELEVANCE Approximately 7% of alcohol users engage in chronic heavy drinking (CHD), which is associated with increased risk of bacterial and viral infections as well as decreased tissue repair ability. These observations suggest a failure of innate immune cells to perform their functions. The proposed research aims to identify CHD-mediated functional, transcriptomic, and epigenetic alterations in monocytes and their progenitors in the bone marrow, with the goal of better understanding the etiology of reduced immune fitness.

PI_NAMEs: MESSAOUDI, ILHEM  (contact)

PROGRAM_OFFICER_NAME: LIN, LI

PROJECT_TERMS: Abstinence;Address;Adverse event;alcohol availability;Alcohol consumption;alcohol effect;Alcoholic Liver Diseases;Alcohols;Animals;antimicrobial;Area;ATAC-seq;Bacterial Infections;Biological Assay;Biological Response Modifiers;Biology;Blood;Blood specimen;Bone Marrow;cancer type;Cardiovascular Diseases;Categories;Cell Line;Cells;Chromatin;Chronic;chronic alcohol ingestion;Chronic Disease;Communicable Diseases;comparison control;Complex;cytokine;Data;data integration;Defect;Development;Dose;drinking behavior;Environment;Epigenetic Process;epigenome;Ethanol;Etiology;Event;experimental study;Failure;Female;fitness;Gene Expression;Genetic Transcription;Goals;Health;Heavy Drinking;Hematopoietic;Hematopoietic stem cells;Heterogeneity;histone modification;Homeostasis;Host Defense;Housing;Human;Immune;immune activation;Immune Tolerance;Immunity;Immunocompetence;Immunologics;Immunology procedure;Impaired wound healing;improved;In Vitro;in vivo;in vivo Model;Individual;Infection;Inflammation Mediators;Inflammatory;Inflammatory Response;insight;Intercistronic Region;Intervention;Knowledge;Link;Macaca;Macaca mulatta;Macrophage;male;Mediating;Metabolic;Metabolism;migration;Modeling;monocyte;Myeloid Cells;Myeloid Progenitor Cells;Myelopoiesis;Natural Immunity;next generation sequencing;nonhuman primate;novel;Outcome;pathogen;Patients;Peripheral;peripheral blood;Peripheral Blood Mononuclear Cell;Phenotype;Physiology;Population;Postoperative Period;Predisposition;progenitor;programs;Promoter Regions;Reporting;Research;Respiratory Tract Infections;response;Risk;Sampling;Self Administration;single cell analysis;single-cell RNA sequencing;stem cells;Testing;therapy design;tissue repair;Tissues;transcriptome;transcriptomics;Virus Diseases;wound healing

PROJECT_TITLE: Impact of chronic alcohol consumption on the functional and epigenetic landscapes of monocytes and their progenitors


ORG_NAME: CARNEGIE-MELLON UNIVERSITY

PHR: Project Narrative Upstream Open Reading frames (uORFs) are important cis-regulatory elements that control mRNA translation and decay. Although the human genome encodes thousandsof uORFs, only a small number have been experimentally tested and many questions remain regarding their function and regulation. We propose to use novel high- throughput approaches to determine the functions of human uORFs, evaluate their importance in cellular stress responses, and investigate their potential regulation by RNA Binding Proteins.

PI_NAMEs: MCMANUS, CHARLES JOEL (contact)

PROGRAM_OFFICER_NAME: CZAPLINSKI, KEVIN

PROJECT_TERMS: Address;Binding Sites;Biological Assay;Cellular Stress;Cis-Acting Sequence;Computer Analysis;Computer Models;Disease;Funding;Gene Expression Regulation;Genes;Genetic Transcription;Genotype;Goals;Human;human disease;Human Genome;human tissue;Initiator Codon;innovation;Knowledge;Laboratories;Link;Modeling;mRNA Decay;mRNA Translation;Mutation;novel;Open Reading Frames;Phenotype;posttranscriptional;Primates;Production;Proteins;Regulation;Regulatory Element;Reporter;Research;RNA-Binding Proteins;Role;Systems Biology;Testing;tissue culture;tool;Trans-Activators;Transcription Process;Translations;Yeasts

PROJECT_TITLE: Regulation of mRNA translation by cis-acting sequences and trans-acting factors


NIH_SPENDING_CATS: Bioengineering;Clinical Research;Data Science;Health Services;Machine Learning and Artificial Intelligence;Patient Safety;Prevention

ORG_CITY: GAINESVILLE

ORG_NAME: UNIVERSITY OF FLORIDA

ORG_STATE: FL

PHR: Project Narrative We propose the purchase of a Leica Versa 200 slide scanner to provide a high throughput method of incorporating pathological images that will greatly improve our surgical outcome prediction tool. The proposed research is relevant to public health because it can result in enhanced perioperative care workflow and early intervention, ultimately improving patient outcomes and decreasing hospitalization costs. Thus, the proposed research is relevant to the part of NIH’s mission that pertains to advancing disease diagnosis through medical applications of new tools and technologies, as the proposed Explainable, Fair, Reproducible and Collaborative Surgical Artificial Intelligence: Integrating data, algorithms and clinical reasoning for surgical risk assessment (XAI- IDEALIST) advances computational methods to compute the risk of postoperative complications in real- time.

PI_NAMEs: BIHORAC, AZRA  (contact);RASHIDI, PARISA

PROGRAM_OFFICER_NAME: CHAO, CHIEN-CHUNG

PROJECT_TERMS: Adoption;advanced disease;Algorithms;American;Artificial Intelligence;artificial intelligence model;Artificial Intelligence platform;Benchmarking;Biopsy;Black Box;Clinical;clinical implementation;college;Complication;Computing Methodologies;Data;data integration;data modeling;Data Set;Diagnosis;digital;digital data;digital pathology;disease diagnosis;Early Intervention;Electronic Health Record;Environment;Equipment;explainable artificial intelligence;federated learning;Fees;Florida;Grant;high risk;Hospital Costs;Human;Image;Image-Guided Surgery;improved;Institution;Life;Maintenance;Medical;Medicine;Methods;Mission;Modeling;novel;operation;Operative Surgical Procedures;Pathologic;Pathology;pathology imaging;Patient-Focused Outcomes;Patients;Perioperative Care;Postoperative Complications;predictive tools;Privacy;Proliferating;prospective;Public Health;Reproducibility;Research;Resources;Risk;Risk Assessment;Scanning;Slide;surgery outcome;surgical risk;Technology;Time;tool;Training;United States;United States National Institutes of Health;Universities;Validation

PROJECT_TITLE: Explainable, Fair, Reproducible and Collaborative Surgical Artificial Intelligence: Integrating data, algorithms and clinical reasoning for surgical risk assessment (XAIIDEALIST)

STUDY_SECTION: CDMA

STUDY_SECTION_NAME: Clinical Data Management and Analysis Study Section[CDMA]


NIH_SPENDING_CATS: Chronic Liver Disease and Cirrhosis;Digestive Diseases;Hepatitis;Liver Disease

ORG_CITY: Chicago

ORG_NAME: UNIVERSITY OF ILLINOIS AT CHICAGO

PHR: Project narrative of parent grant - R01DK131038 Non-alcoholic fatty liver disease (NAFLD) is a burden on our healthcare system due to the lack of an efficient therapy. We will define how methionine metabolism is regulated by peroxisome proliferator-activated receptor g in hepatocytes to promote NAFLD. Our results will help to develop therapeutic approaches that improve the use of existing drugs to reverse efficiently this disease.

PI_NAMEs: CORDOBA-CHACON, JOSE  (contact)

PROGRAM_OFFICER_NAME: GARCIA, MARTHA

PROJECT_TERMS: Adipocytes;Adult;Anti-Inflammatory Agents;betaine-homocysteine methyltransferase;Caring;Cells;Cholesterol;chronic liver disease;clinical care;clinically relevant;Data;defined contribution;Dependovirus;Development;diabetogenic;Diet;Disease;Dose;Enzymes;expectation;experimental study;Extrahepatic;Fatty acid glycerol esters;FDA approved;fibrogenesis;Fibrosis;Fructose;Gene Expression;General Population;Health;Healthcare Systems;Hepatic;Hepatic Stellate Cell;Hepatic Tissue;Hepatocyte;Homocysteine;Human;improved;In Vitro;in vivo;Inflammation;innovation;Insulin Resistance;Knock-out;Label;Lecithin;Lipids;Liver;liver injury;Macrophage;Mediating;Messenger RNA;metabolomics;Methionine;Methionine Metabolism Pathway;methyl group;Methylation;Mus;non-alcoholic fatty liver disease;Non-Insulin-Dependent Diabetes Mellitus;nonalcoholic steatohepatitis;novel;Outcome;parent grant;Patients;Perfusion;Peroxisome Proliferator-Activated Receptors;Pharmaceutical Preparations;Pharmacological Treatment;Phosphatidylethanolamine N-Methyltransferase;PPAR gamma;Prevalence;Regulation;restoration;Testing;Therapeutic;Therapeutic Effect;Thiazolidinediones;Very low density lipoprotein

PROJECT_TITLE: PPARgamma-regulated mechanisms in hepatocytes that promote NAFLD


ORG_CITY: Columbus

ORG_DEPT: SURGERY

ORG_NAME: OHIO STATE UNIVERSITY

ORG_STATE: OH

PHR: PROJECT NARRATIVE Pulmonary hypertension affects the right ventricle of the heart, but there are no therapies targeted at this ventricle. The research in this proposal will contribute to fundamental knowledge of the right ventricle of the heart and have direct application towards the development of novel therapies for PH and other diseases affecting the right ventricle.

PI_NAMEs: GORR, MATTHEW WILLIAM (contact)

PROGRAM_OFFICER_NAME: XIAO, LEI

PROJECT_TERMS: Action Potentials;Affect;Animal Model;Biology;Calcium;Cardiac Myocytes;Data;Development;direct application;Disease;Failure;Fibrosis;Functional disorder;G-Protein-Coupled Receptors;heart dimension/size;Heart Ventricle;human subject;Knowledge;Molecular;Morbidity - disease rate;mortality;new therapeutic target;novel;novel therapeutics;Outcome;Patients;Pharmaceutical Preparations;pressure;Property;pulmonary arterial hypertension;Pulmonary Hypertension;Research;response;Right Ventricular Dysfunction;right ventricular failure;right ventricular remodeling;Right ventricular structure;Sarcomeres;Signal Transduction;targeted treatment;Testing;Therapeutic;therapeutic target;Transplantation;Work

PROJECT_TITLE: Right ventricle remodeling in pulmonary hypertension


NIH_SPENDING_CATS: Biomedical Imaging

ORG_NAME: NORTHWESTERN UNIVERSITY

PHR: Project Narrative Our program has assembled outstanding multidisciplinary teams devoted to understanding the roles played by transition metals in catalytic transformations central to human health and disease. The approaches to these problems incorporate a suite of advanced paramagnetic resonance techniques, many of which we have developed, augmented by kinetic and photophysical measurements. The essential biological and biochemical challenges we address include: radical reactions catalyzed by `Radical-SAM' enzymes, the most widespread metalloenzyme superfamily; enzymatic formation of bio-available nitrogen, on which over half the world's population depends; the role of Mn2+ in radiation resistance, including the resistance of human tumors, in aging, and in oocyte fertilization.

PI_NAMEs: HOFFMAN, BRIAN M (contact)

PROGRAM_OFFICER_NAME: SIMONOVIC, MILJAN

PROJECT_TITLE: Biological Transition Metals


ORG_DEPT: ANATOMY/CELL BIOLOGY

PHR: Project Narrative Function and regulatory mechanisms of the Wnt5a-Ror morphogenetic pathway PI: Ho Wnt5a-Ror signaling is an evolutionarily conserved developmental signaling pathway that controls cell and tissue morphogenesis. Genetic mutations that disrupt the pathway cause congenital birth defects. Our research aims to delineate the cell biological functions and regulatory mechanisms of the pathway and how these fundamental processes are perturbed in Wnt5a-Ror driven human diseases.

PI_NAMEs: HO, HSIN-YI HENRY (contact)

PROGRAM_OFFICER_NAME: XU, JIANHUA

PROJECT_TERMS: Actomyosin;Address;Administrative Supplement;Affinity;Affinity Chromatography;Anatomy;Automobile Driving;Behavior;Behavioral;beta catenin;Binding;Binding Proteins;Biochemical;Biological Assay;Biological Process;Biomechanics;Canis familiaris;cell behavior;Cell Culture System;Cell Extracts;cell motility;Cell surface;Cells;Cellular biology;Characteristics;Clinical;Column Chromatography;Complex;Congenital Abnormality;Congenital Disorders;Cytoplasm;Cytoskeleton;Cytosol;Defect;Deterioration;Development;Dimerization;Disease;disulfide bond;DNA Sequence Alteration;Dsh protein;Elements;Equipment;Exclusion;Exhibits;experimental study;Face;fast protein liquid chromatography;Funding;Genetic;Goals;Grant;Home;Human;human disease;Inherited;insight;instrument;interest;Ion Exchange;Knock-out;Ligands;Limb structure;Maintenance;Manufacturer;Mass Spectrum Analysis;Measurement;Mediating;medical schools;Molecular Sieve Chromatography;Morphogenesis;mutant;Mutation;National Institute of General Medical Sciences;novel;Pathogenesis;Pathogenicity;Pathway interactions;Patients;pharmacologic;Phenotype;Physiological;Policies;Portraits;Process;protein complex;protein function;Proteins;receptor;Regulation;Reporter;Research;Research Personnel;Resolution;Robinow syndrome;Role;Scaffolding Protein;Signal Pathway;Signal Transduction;Stress Fibers;Structure;System;three dimensional cell culture;Tissue Extracts;Tissues;Transducers;transmission process;United States National Institutes of Health;Vertebrates;WNT Signaling Pathway;WNT5A gene


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

ORG_CITY: STONY BROOK

ORG_NAME: STATE UNIVERSITY NEW YORK STONY BROOK

ORG_STATE: NY

PHR: Budget Justification Personnel: No additional personnel expenses are requested in this supplement Equipment: A Leica THUNDER Imager 3D Live Cell system including the DMi8 microscope and the Thunder 3D software and workstation. The Thunder 3D software provides computational clearing to remove out of focus light and provide high resolution images. The DMi8 microscope includes a multiline LED8 light source and filter cubes for 8 color imaging and rapid switching between wavelength acquisition, a motorized stage for 3D z- stack and multiple X-Y position image acquisition, a Leica K8 scientific CMOS camera for low light detection. No service contract is necessary for this microscope. The total cost of the microscope with software, filters, lenses, light source, and camera after a 5% discount is $169,060.20 (detailed in the accompanying quote). Unobligated balance statement: The unobligated balance of GM150290 will be below 25% at the end of the current year’s budget period.

PI_NAMEs: MARTIN, BENJAMIN L (contact)

PROJECT_TERMS: 3-Dimensional;Area;arm;Behavior;Biological;Biology;Biosensor;Budgets;Cell Cycle;Cell Differentiation process;Cell Maintenance;Cell model;cell motility;Cell Nucleus;cell type;Cells;Cellular biology;Collection;Color;Computer software;Computers;Contract Services;cost;Cyclin-Dependent Kinases;Cytoplasm;Data;Detection;Development;discount;Disease;Ectoderm;Embryo;Ensure;Equilibrium;Equipment;F-Actin;Family;Fluorescence;fluorophore;G1 Phase;G2 Phase;gastrulation;Gene Expression;Generations;genome-wide analysis;Germ Layers;high resolution imaging;Human Resources;Image;imager;improved;In Vitro;in vivo;insight;instrument;Invaded;lens;Light;Maintenance;Malignant Neoplasms;Mediating;Mesoderm;Methods;Microscope;Microscopy;microsystems;Molecular;Molecular Biology;Monitor;Morphogenesis;mosaic analysis;Motor;mRNA Expression;mutant;notochord;Output;Paraxial Mesoderm;parent grant;Pathway interactions;Performance;Phase;Photobleaching;Physiological;Play;Positioning Attribute;Postdoctoral Fellow;progenitor;ratiometric;Reaction;real-time images;Receptor Activation;Regulation;Reporter;Research;Resolution;Role;Sampling;Scanning;Services;Signal Pathway;Signal Transduction;Skeletal Muscle;Source;Specific qualifier value;Spinal Cord;Statistical Data Interpretation;Stem Cell Development;stem cells;System;TCF Transcription Factor;Techniques;Tissues;transcription factor;Transcriptional Regulation;Transgenic Organisms;Undifferentiated;Universities;vertebrate embryos;Visualization;WNT Signaling Pathway;Work;Zebrafish

PROJECT_TITLE: Molecular and Cell Biology of Neuromesodermal Progenitors


NIH_SPENDING_CATS: Pediatric

ORG_CITY: WALTHAM

ORG_DEPT: MISCELLANEOUS

ORG_NAME: BRANDEIS UNIVERSITY

PHR: Project Narrative Body symmetry is crucial for physiological posture and function. A prominent example of developmental failure in symmetry maintenance is fetal hemivertebrae, a rare congenital malformation that affects 5-10 in 10,000 births, resulting in spinal deformation such as scoliosis. This project will contribute to understanding the developmental origin of such body symmetry/asymmetry issues, and this improved understanding could lead, at term, to new medical treatments or preventive measures.

PI_NAMEs: TOUBOUL, JONATHAN DAVID (contact)

PROGRAM_OFFICER_NAME: NGUYEN, HAN

PROJECT_TERMS: Affect;Anatomy;Animals;Biological;Birth;Breathing;Buffers;Cilia;Congenital Abnormality;Coupled;Data;Data Analyses;Development;Diffusion;Embryo;Embryonic Development;Embryonic Structures;Exhibits;experimental study;Failure;fetal;Gene Expression;Genetic study;Image;Imaging Techniques;Impairment;improved;insight;Lead;Left;Liquid substance;Maintenance;mathematical model;Mediating;Medical;Modeling;Molecular;Movement;Mus;Paraxial Mesoderm;Phase;Physiological;Positioning Attribute;Posture;Preventive measure;Reaction;Research Design;rib bone structure;scoliosis;Segmentation Clock Pathway;Side;Signal Transduction;Signaling Molecule;simulation;Somites;somitogenesis;spatiotemporal;Specific qualifier value;Spinal;spine bone structure;System;Theoretical model;Tretinoin;Vertebrates;Wild Type Mouse

PROJECT_TITLE: Dynamical maintenance of left-right symmetry during vertebrate development


NIH_SPENDING_CATS: Bioengineering

ORG_CITY: MADISON

ORG_DEPT: ZOOLOGY

ORG_NAME: UNIVERSITY OF WISCONSIN-MADISON

ORG_STATE: WI

PHR: Project Narrative Understanding how cells attach to one another and move between one another is important for understanding many common birth defects, and many of the same processes that are tightly regulated in embryos are mis-regulated in cancer cells as they lose their connections to one another and invade the body. This supplement proposes to acquire a replacement, upgraded gel documentation to replace and upgrade a 30-year-old failing system to acquire images of nucleic acid (DNA, RNA) and protein gels relevant to all aspects of the parent award, which examines how actin – a protein essential for cell movements – works alongside proteins that regulate cell adhesiveness to build strong connections between cells and to help them avoid injury, and how signals regulate the actin machinery that allows cells to change position in the embryo.

PI_NAMEs: HARDIN, JEFFREY D (contact)

PROGRAM_OFFICER_NAME: RIGAS, MARC

PROJECT_TERMS: Actins;Actomyosin;Adherens Junction;Adhesiveness;alpha catenin;Area;Award;Binding;Biological Models;Biophysics;Cadherins;Caenorhabditis elegans;cancer cell;cell motility;Cell Shape;Cell surface;Cells;Complex;Computers;Congenital Abnormality;Custom;Cytoskeleton;Data;Data Set;DNA;Documentation;Embryo;Embryonic Development;Epithelial Cells;Epithelium;Event;F-Actin;Failure;Funding;Gel;Genetic;Goals;healing;Human;Human Development;human disease;Hybrids;Image;in vivo evaluation;Injury;insight;Intercalated Cell;Intercellular Junctions;Invaded;LIM Domain;Link;Malignant Neoplasms;Mechanics;mechanotransduction;Modeling;Modernization;Molecular Analysis;Morphogenesis;Motility;Movement;multidisciplinary;Nucleic Acids;Operating System;Organism;parent grant;parent project;polymerization;Polymers;Positioning Attribute;prevent;Process;protein protein interaction;Proteins;recruit;Regulation;Reproducibility;Resolution;rho GTP-Binding Proteins;RNA;Scanning;Security;Self-Injurious Behavior;Shapes;Signal Pathway;Signal Transduction;single molecule;System;Testing;Tissues;Work

PROJECT_TITLE: Regulation of dynamic actin networks during epithelial morphogenesis


ADMINISTERING_IC: TW

IC_NAME: FOGARTY INTERNATIONAL CENTER

NIH_SPENDING_CATS: Clinical Research;Dental, Oral, and Craniofacial Disease

ORG_CITY: BOSTON

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

PHR: Contact PD/PI: Fawzi, Wafaie W Project Narrative The HBNU Fogarty Global Health Training Program, a consortium of Harvard University, Boston University, Northwestern University and the University of New Mexico, proposes to continue to contribute to global health research capacity building and the use of research to improve the health outcomes related to priority health areas in low- and middle-income countries (LMICs) in partnership with 18 sites throughout Africa, Asia, and South America. The Program will recruit US and LMIC trainees to strengthen global health research networks and programs at academic institutions and ultimately help sustain global health research in the US and LMICs. Project Narrative Page 8

PI_NAMEs: FAWZI, WAFAIE W (contact);HAMER, DAVIDSON HOWES;HAWKINS, CLAUDIA A;PERKINS, DOUGLAS JAY

PROGRAM_OFFICER_NAME: KATZ, FLORA N

PROJECT_TERMS: Award;Biomedical Research;Boston;Cardiovascular Diseases;career;co-infection;Collaborations;Competence;Creativeness;Diabetes Mellitus;Discipline;Disease;E-learning;Education;Evaluation;experience;Fostering;Future;Future Generations;global health;HIV/AIDS;Individual;Institution;Interdisciplinary Study;International;Investments;low and middle-income countries;Malignant Neoplasms;Maternal and Child Health;medical schools;member;Mental Health;Mentors;Morbidity - disease rate;mortality;National Institute of Dental and Craniofacial Research;New Mexico;next generation;nutrition;Output;Peer Review;Persons;Postdoctoral Fellow;pre-doctoral;Principal Investigator;programs;Public Health Schools;Publications;Qualifying;Readiness;recruit;Research;research and development;Research Design;Research Methodology;Research Project Grants;Research Support;Research Training;Scientist;Site;Students;symposium;tool;Training;Training Programs;Underrepresented Populations;United States National Institutes of Health;Universities

PROJECT_TITLE: Launching Future Leaders in Global Health (LAUNCH) Research Training Program - Supplement for NIDCR

STUDY_SECTION_NAME: Special Emphasis Panel[ZRG1(58)-R]


ORG_CITY: MILWAUKEE

ORG_NAME: MEDICAL COLLEGE OF WISCONSIN

PHR: PROJECT NARRATIVE Dysregulation of GPCR signaling leads to several diseases, yet the molecular mechanisms remain poorly understood. The objective of this project is to elucidate the molecular mechanisms that govern GPCR signaling by canonical and non-canonical mechanisms. We expect to define novel paradigms of GPCR signaling with the hope of identifying new targets to modulate GPCR signaling for therapeutic development.

PI_NAMEs: MARCHESE, ADRIANO  (contact)

PROGRAM_OFFICER_NAME: LEWIS, MECHELLE MAYLEBEN

PROJECT_TERMS: A kinase anchoring protein;Address;Arrestins;Automobile Driving;Biochemical;Biological Assay;Biophysics;Cell Culture Techniques;Cessation of life;chemokine receptor;Confocal Microscopy;CXC Chemokines;Disease;drug discovery;Embryonic Development;Family;Fluorescence;G Protein-Coupled Receptor Signaling;G-Protein-Coupled Receptors;Goals;human disease;immune function;innovation;Knowledge;Label;Ligation;live cell imaging;Malignant Neoplasms;Modeling;Molecular;novel;Physiological Processes;Play;Prognosis;receptor;receptor binding;Receptor Signaling;reconstitution;Regulation;Research;Role;Signal Transduction;stem cells;structural determinants;Therapeutic;therapeutic development;Translating

PROJECT_TITLE: Regulation of chemokine receptor signaling

STUDY_SECTION: MRAC

STUDY_SECTION_NAME: Maximizing Investigators' Research Award C Study Section[MRAC]


ADMINISTERING_IC: DA

IC_NAME: NATIONAL INSTITUTE ON DRUG ABUSE

NIH_SPENDING_CATS: Brain Disorders;Cerebrovascular;Drug Abuse (NIDA only);Fentanyl Misuse and Addiction;HIV/AIDS;Infectious Diseases;Neurodegenerative;Neurosciences;Opioid Misuse and Addiction;Opioids;Stem Cell Research;Stem Cell Research - Induced Pluripotent Stem Cell;Stem Cell Research - Induced Pluripotent Stem Cell - Human;Substance Misuse

ORG_DEPT: PATHOLOGY

PHR: There has been a rapid increase in the use of synthetic opioids including among people living with HIV; however, the interactions of HIV and synthetic fentanyls are poorly understood. Furthermore, the blood-brain barrier (BBB) serves as a gatekeeper in regulating the delicate neuronal environment and its dysfunction is considered a hallmark of NeuroHIV. We propose to investigate how synthetic fentanyls alter important functions of the BBB (i.e. transport, immunological and physical barriers) and the implications on HIV neuroinflammation.

PI_NAMEs: ANDREWS, ALLISON MICHELLE (contact);HO, WENZHE ;POTULA, RAGHAVA

PROGRAM_OFFICER_NAME: BORGMANN, KATHLEEN RUTH

PROJECT_TERMS: 3-Dimensional;Acceleration;Acquired Immunodeficiency Syndrome;Address;Affect;antiretroviral therapy;Astrocytes;Binding;Biological Assay;biomaterial compatibility;Blood - brain barrier anatomy;Blood Vessels;blood-brain barrier function;blood-brain barrier permeabilization;Brain;brain cell;brain endothelial cell;Caring;Cell Adhesion Molecules;Cells;Chemicals;Classification;cohort;Complex;Cytoskeleton;Data;Development;Disease Outbreaks;drug action;drug market;drug of abuse;Drug Screening;Endothelium;Environment;Epidemic;Event;experimental study;Fentanyl;fentanyl analog;fentanyl exposure;fentanyl use;Floods;Functional disorder;Gatekeeping;Gene Expression;Genetic;HIV;HIV Infections;HIV-1;Homeostasis;Human;human induced pluripotent stem cells;illicit drug use;Illicit Drugs;Immune;immune cell infiltrate;Immunity;Immunologic Surveillance;Immunologics;Impairment;induced pluripotent stem cell;Infection;infection rate;Inflammatory;Inflammatory Response;Injecting drug user;Injections;innovation;insight;Investigation;Kinetics;Leukocytes;Life Cycle Stages;Link;Macrophage;manufacture;Microfluidics;Microglia;migration;Modeling;Molecular;monocyte;Natural Immunity;neuroAIDS;neuroinflammation;Neurologic Symptoms;Neurons;neuropathology;new outbreak;novel;Opioid;opioid epidemic;opioid misuse;Opioid Receptor;opioid user;overdose death;Pathogenesis;Pathologic;Pathway Analysis;Pathway interactions;Pericytes;Persons;Pharmaceutical Preparations;pharmacologic;Play;Policies;Publishing;Pump;receptor;Receptor Activation;Reporting;Research Support;response;Risk;Role;screening;Seminal;Signal Transduction;Structure;synthetic opioid;Testing;Tight Junctions;Tissue Engineering;tool;Toxicology;translational model;Up-Regulation;Urine;Viral;Viral reservoir;Virus

PROJECT_TITLE: Synthetic fentanyls adversely affect the blood-brain barrier and HIV replication in the context of neuroHIV


ORG_CITY: ATLANTA

ORG_DEPT: CHEMISTRY

ORG_NAME: EMORY UNIVERSITY

ORG_STATE: GA

PHR: Contact PD/PI: Dai, Mingji PROJECT NARRATIVE The proposed research aims to establish general and flexible synthetic approaches and methodologies to enable access of bioactive natural products and other medicinally important molecules, which are otherwise very difficult to acquire due to their scarcity, structural complexity, and high cost. This research will also open new avenues toward chemical libraries featuring structurally novel small molecules that incorporate the key structural elements of the selected natural molecules for anticancer, antimicrobial, and anti-neurodegenerative drug discovery. The strategies and methodologies developed in this research will significantly enrich the toolbox of both synthetic chemists and medicinal chemists. Project Narrative Page 7

PI_NAMEs: DAI, MINGJI  (contact)

PROGRAM_OFFICER_NAME: YANG, JIONG

PROJECT_TERMS: Alkaloids;anti-cancer;antimicrobial;bioactive natural products;Biological;Biology;cancer therapy;chemical synthesis;Collection;Communicable Diseases;Complex;cost;Development;drug discovery;Drug Industry;Drug resistance;Elements;Evaluation;flexibility;Goals;Health;Human;in vivo;innovation;Institution;Lead;lead optimization;Medicine;Methodology;Natural Products;Natural Selections;Nerve Degeneration;Nervous System Disorder;novel;novel lead compound;novel therapeutics;Organic Synthesis;Outcomes Research;Problem Solving;programs;rational design;Reaction;Research;research clinical testing;small molecule;small molecule libraries;Terpenes;Therapeutic;therapeutic development

PROJECT_TITLE: Synthesis and Study of Medicinally Important Molecules


ORG_CITY: SYRACUSE

ORG_NAME: UPSTATE MEDICAL UNIVERSITY

PHR: Bioactive immune-modulating nanodrug for sepsis treatment Project Narrative Sepsis, commonly caused by severe trauma and infection, results in dysregulated inflammation leading to tissue damage/organ failure, which unfortunately lacks effective pharmacological interventions in the clinic to improve patient survival. In recent years, my lab has developed a novel unique telodendrimer nanoplatform for both therapeutic delivery and versatile active immune modulation. In the next five years, my research program will focus on the development of the next generation of TD nanodrug for (1) active fine-tuned inflammation control against a broad spectrum of immune stimuli via pleiotropic mechanisms; (2) control of both hyperinflammation and immune suppression in sepsis by blocking cytokine storm and pyroptosis; and (3) delivery of vital antibiotics for simultaneous control of MDR infection and inflammation in sepsis.

PI_NAMEs: LUO, JUNTAO  (contact)

PROGRAM_OFFICER_NAME: ZHAO, XIAOLI

PROJECT_TERMS: Acute Respiratory Distress Syndrome;Anti-Inflammatory Agents;Antibiotics;Autoimmune Diseases;Cells;Cessation of life;Charge;chronic wound;Clinic;Clinical;Communication;Complex;Critical Illness;cytokine;cytokine release syndrome;design;Development;Disease;Dose;Encapsulated;Endotoxins;Gram-Negative Bacteria;Gram-Positive Bacteria;Hydrophobicity;Immune;Immune response;Immunologic Stimulation;immunomodulatory therapies;immunoregulation;Immunosuppression;improved;Infection;Infection Control;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Bowel Diseases;inhibitor;Injections;innovation;Intervention;Malignant Neoplasms;Molecular;mouse model;multimodality;Multiple Organ Failure;nanocarrier;nanodrug;nanomedicine;nanotechnology platform;nanotherapeutic;Nanotrap;Nature;next generation;novel;Organ failure;pathogen;Pathogenesis;Pathway interactions;Patients;Pattern;Perioperative;Pharmaceutical Preparations;pharmacologic;Plant Resins;prevent;programs;Publications;Reporting;Research;Resolution;Rheumatoid Arthritis;Risk;secondary infection;Sepsis;Series;Signal Transduction;Steroids;Stimulus;Structure;Systemic infection;Therapeutic;therapeutic target;Time;Tissues;TNF gene;Trauma;Traumatic injury


NIH_SPENDING_CATS: Genetics

ORG_CITY: LA JOLLA

ORG_DEPT: BIOLOGY

ORG_NAME: UNIVERSITY OF CALIFORNIA, SAN DIEGO

PHR: Project Narrative These studies will lead to a better understanding of gene regulation, and will therefore provide new insights into the molecular basis and potential treatment of human diseases, such as many forms of cancer, that involve defects in the proper control of gene expression.

PI_NAMEs: KADONAGA, JAMES T. (contact)

PROGRAM_OFFICER_NAME: CHOW, CHI-WING

PROJECT_TERMS: Affect;Animals;Area;Binding;Biological Phenomena;Biological Sciences;cancer prevention;Cell Nucleus;Cell Physiology;Chromatin;Chromatin Structure;Complex;Defect;DNA;DNA Damage;DNA Sequence;DNA Structure;Elements;Future;Gene Expression;Gene Expression Regulation;Genes;Genetic Materials;Genetic Transcription;Goals;Human;human disease;insight;interest;Knowledge;Malignant Neoplasms;Mediating;Molecular;Nucleosomes;Organism;Positioning Attribute;Process;programs;promoter;Reactive Oxygen Species;Regulation;Research;RNA Polymerase II;Signal Transduction;Site;Stretching;System;transcription factor;Transcription Initiation;Transcription Process;Transcriptional Regulation;Work

PROJECT_TITLE: Mechanisms of Eukaryotic Gene Regulation


NIH_SPENDING_CATS: Biotechnology;Genetics;Human Genome

ORG_CITY: NEW YORK

ORG_NAME: COLUMBIA UNIVERSITY HEALTH SCIENCES

PHR: Relevance to Public Health: Genome rewiring events, through translocations, deletions, and even massive chromosomal rearrangements, contribute to genome instability associated with many human diseases, including a significant portion of cancers and inherited or spontaneous diseases. Furthermore, many classes of noncoding RNAs participate in genome remodeling pathways or the maintenance of genome integrity, and their loss or dysfunction can increase the frequency of genome rearrangements, resulting in either deletion of tumor-suppressing genes, formation of chimeric genes, or over-expression of genes that promote tumor stability. The extreme degree of natural genome editing events in Oxytricha make it unparalleled as a model system to study genome stability, and similar mechanisms that may contribute to genome instability and cancer in humans.

PI_NAMEs: LANDWEBER, LAURA F (contact)

PROGRAM_OFFICER_NAME: VATAKIS, DIMITRIOS NIKOLAOS

PROJECT_TERMS: Address;Adenine;Architecture;Biochemistry;Biological Models;Biology;chimeric gene;Chromatin;Chromosomal Rearrangement;comparative genomics;Complex;Crying;Development;Disease;DNA;Eukaryota;Event;Evolution;Frequencies;Functional disorder;Gene Expression;Gene Rearrangement;Genes;Genetic;genetic architecture;Genome;genome editing;genome integrity;Genome Stability;Genomic Instability;Goals;Human;human disease;Inherited;insight;Knowledge;Maintenance;Malignant Neoplasms;Methylation;microbial;Molecular;Molecular Genetics;Organism;overexpression;Oxytricha;Pathway interactions;Process;Public Health;Research;RNA;RNA Editing;RNA Processing;RNA-Binding Proteins;Role;System;tool;Tumor Promotion;Tumor Suppressor Genes;Untranslated RNA;Variant

PROJECT_TITLE: Understanding Complex Genome Editing and RNA Biology in Oxytricha

STUDY_SECTION: MRAA

STUDY_SECTION_NAME: Maximizing Investigators? Research Award A Study Section[MRAA]


ORG_CITY: DURHAM

ORG_NAME: DUKE UNIVERSITY

ORG_STATE: NC

PHR: Project Narrative (Public Health Relevance Statement)  Protein glycosylation plays an important role in all kingdoms of life by regulating cellular responses to metabolic and environmental changes. Defects in protein glycosylation have been linked with abnormal plant development, parasitic virulence and viability, and a variety of human diseases, such as cancer, diabetes, and neurodegenerative diseases. Therefore, our proposed structural and functional studies of two distinct glycosyltransferases, SPY and SEC, and their opposing effects on key transcription regulators will reveal novel molecular insights into the genetic regulation by two distinct types of intracellular protein glycosylation: O- fucosylation and O-GlcNAcylation, with profound implications in agriculture and public health.

PI_NAMEs: SUN, TAI-PING ;ZHOU, PEI  (contact)

PROGRAM_OFFICER_NAME: BOND, MICHELLE RUEFFER

PROJECT_TERMS: Affect;Agriculture;Allosteric Regulation;Anabolism;Animals;Arabidopsis;Bacteria;Binding;Biochemical;Biological Assay;Biology;Cell Physiology;Cells;Complex;Cryoelectron Microscopy;Defect;Diabetes Mellitus;Disease;Environment;environmental change;Enzymes;Event;Family;Fucosyltransferase;gene conservation;Genes;Genetic;genetic analysis;Genetic Transcription;Gibberellins;glycosylation;glycosyltransferase;Growth;Guanosine Diphosphate Fucose;Health;Human;human disease;Individual;Insecta;insight;Knowledge;Length;Life;Link;link protein;Malignant Neoplasms;Mediating;Metabolic;Modification;Molecular;Molecular Conformation;mutant;Mutation;N-terminal;nanobodies;Neurodegenerative Disorders;novel;O-GlcNAc transferase;Organism;paralogous gene;Phenotype;Phytochrome;Plant Growth Regulators;plant growth/development;Plants;Play;Protein Glycosylation;Proteins;Proteome;Proteomics;Public Health;public health relevance;Regulation;Resistance;response;Role;Sequence Homology;Signal Pathway;Signal Transduction;Site-Directed Mutagenesis;Structure;Substrate Specificity;sugar;tool;transcription factor;Transcription Factor 3;Transcription Repressor;transcriptional reprogramming;UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase;Variant;Virulence

PROJECT_TITLE: Structural and Functional Analysis of Nucleocytoplasmic Protein O-Glycosyltransferases in Plants


NIH_SPENDING_CATS: Genetics;Hematology;Rare Diseases

ORG_CITY: LOS ANGELES

ORG_NAME: UNIVERSITY OF CALIFORNIA LOS ANGELES

PHR: Project Narrative The ends of telomeres, the DNA-protein complexes that cap our linear chromosomes, are maintained by telomerase that synthesizes the G-strand and CST–Polymeraseα-Primase that synthesizes the C-strand. Telomerase is a highly regulated determinant of aging, stem cell renewal, and tumorigenesis, and mutations in telomerase and telomere binding or associated proteins can lead to aplastic anemia, dyskeratosis congenita, pulmonary fibrosis, myelodysplastic syndromes, Coats plus syndrome, and other telomere biology disorders. We propose to use an integrative structural and molecular biology approach to investigate their mechanisms of action and regulation of telomere synthesis, which should reveal the structural basis of mutations leading to disease and for drug targeting.

PI_NAMEs: FEIGON, JULI  (contact)

PROJECT_TERMS: Affect;Aging;Aplastic Anemia;Binding;Biochemistry;Biology;Chromosomes;Coats plus syndrome;Complex;Cryoelectron Microscopy;Disease;DNA;DNA polymerase alpha-primase;DNA Primase;Drug Targeting;ds-DNA;Dyskeratosis Congenita;Dysmyelopoietic Syndromes;Goals;Health;Human;In Situ;Molecular Biology;Mutation;NMR Spectroscopy;Organism;particle;Polymerase;protein complex;Proteins;Pulmonary Fibrosis;recruit;Regulation;Research;RNA-Directed DNA Polymerase;stem cell division;structural biology;Structure;Telomerase;telomere;Tetrahymena;Tetrahymena thermophila;TNFRSF5 gene;tumorigenesis;Visualization

PROJECT_TITLE: Structural biology of telomerase and telomeres